Dietary Supplements
Herbal Medicine Gamma
Herbal Medicine Gamma - Linolenic Acid Boosts the Effectiveness of Herceptin in Cancer Cells
Translational Research Team at Evanston Northwestern Healthcare’s Research Institute Previously
Reported Effects of Olive Oil on Breast Cancer
11-02-05
EVANSTON, Ill., Nov 02, 2005 /PRNewswire via COMTEX/ — Gamma-linolenic acid (GLA), which is found in several plant oils and is used in herbal medicine, appears to be able to prevent resistance to the breast cancer drug Herceptin, according to a report in the Journal of the National Cancer Institute (JNCI).
Researchers at the Evanston Northwestern Healthcare (ENH) Research Institute examined the effect of GLA on the expression of the cancer gene Her-2/neu, and discovered that GLA kills cancer cells without affecting normal cells. Researchers treated cancer cells with GLA and discovered that GLA treatment substantially reduced Her-2/neu protein levels in breast, ovarian and gastrointestinal cancers.
Additionally, concurrent treatments of Her-2/neu overexpressing cancer cells with GLA and Herceptin led to synergistic increases in cell death and reduced growth and colony formation.
“The Her-2/neu oncogene plays a crucial role not only in the origin and progression of numerous types of human cancer but also in their responses to various treatments,” said Ruth Lupu, PhD, Director of Translational Breast Cancer Research at the ENH Research Institute.
“These findings reveal a valuable means by which an inexpensive herbal medicine might regulate cancer cell growth, metastasis, and sensitivity to chemo and endocrine therapies.”
Patients with cancer that exhibit high levels of Her-2/neu generally have a low survival rate. Treatments that target Her-2/neu in cancer cells, such as the drug Herceptin, have been shown to be useful.
However, fewer than 35 percent of patients with Her-2/neu-overexpressing metastatic breast cancer respond to Herceptin alone. Furthermore, the majority of patients who initially respond to Herceptin acquire resistance within one year.
So finding the mechanisms of resistance to Herceptin can help in the development of new compounds that might overcome resistance or have synergistic antitumor effects when given with Herceptin.
“In our tests, treating the cancer cell lines with both GLA and Herceptin led to a synergistic increase in cell death and reduced cancer cell growth,” said Dr. Lupu. “Although further studies are necessary before GLA can enter clinical trials, these findings may reveal a previously unrecognized way of influencing the poor outcome of Her-2/neu-positive cancer patients.”
“GLA’s inhibition of Her-2/neu works in a different manner from that of Herceptin,” said co-researcher Javier A. Menendez, PhD, research scientist Evanston Northwestern Research Institute. “While Herceptin attempts to neutralize thousands of Her-2/neu molecules commonly found in overexpressing cancer cells, GLA would be more efficient to reduce Her-2/neu levels by preventing the gene from copying itself.”
Lupu and Menendez were also the researchers who discovered that the oleic acid found in olive oil dramatically reduces the levels of a protein produced by the breast cancer gene Her-2/neu.
The latest study was supported by funding from the Susan G. Komen Breast Cancer Foundation and the federal government.
About Evanston Northwestern Healthcare
Located in Chicago’s northern suburbs, Evanston Northwestern Healthcare (ENH) is an integrated healthcare system that includes Evanston, Glenbrook and Highland Park Hospitals, ENH Medical Group (comprising 65 medical offices and facilities), ENH Home Services, ENH Research Institute and ENH Foundation. Through its affiliation with Northwestern University’s Feinberg School of Medicine, ENH supports extensive medical education and research. ENH is in the top nine percent of all institutions that receive funding from the National Institutes of Health; among multi-specialty independent research hospitals, it ranks 12th in the nation.
Effect of Gamma-Linolenic Acid on the Transcriptional activity of the Her- 2/neu (erbB-2) oncogene, Journal of the National Cancer Institute, Vol. 97, No. 21, November 2, 2005, p. 1611-1615.
SOURCE Evanston Northwestern Healthcare
Herbal Medicine Gamma - Linolenic Acid Boosts the Effectiveness of Herceptin in Cancer Cells
Translational Research Team at Evanston Northwestern Healthcare’s Research Institute Previously
Reported Effects of Olive Oil on Breast Cancer
11-02-05
EVANSTON, Ill., Nov 02, 2005 /PRNewswire via COMTEX/ — Gamma-linolenic acid (GLA), which is found in several plant oils and is used in herbal medicine, appears to be able to prevent resistance to the breast cancer drug Herceptin, according to a report in the Journal of the National Cancer Institute (JNCI).
Researchers at the Evanston Northwestern Healthcare (ENH) Research Institute examined the effect of GLA on the expression of the cancer gene Her-2/neu, and discovered that GLA kills cancer cells without affecting normal cells. Researchers treated cancer cells with GLA and discovered that GLA treatment substantially reduced Her-2/neu protein levels in breast, ovarian and gastrointestinal cancers.
Additionally, concurrent treatments of Her-2/neu overexpressing cancer cells with GLA and Herceptin led to synergistic increases in cell death and reduced growth and colony formation.
“The Her-2/neu oncogene plays a crucial role not only in the origin and progression of numerous types of human cancer but also in their responses to various treatments,” said Ruth Lupu, PhD, Director of Translational Breast Cancer Research at the ENH Research Institute.
“These findings reveal a valuable means by which an inexpensive herbal medicine might regulate cancer cell growth, metastasis, and sensitivity to chemo and endocrine therapies.”
Patients with cancer that exhibit high levels of Her-2/neu generally have a low survival rate. Treatments that target Her-2/neu in cancer cells, such as the drug Herceptin, have been shown to be useful.
However, fewer than 35 percent of patients with Her-2/neu-overexpressing metastatic breast cancer respond to Herceptin alone. Furthermore, the majority of patients who initially respond to Herceptin acquire resistance within one year.
So finding the mechanisms of resistance to Herceptin can help in the development of new compounds that might overcome resistance or have synergistic antitumor effects when given with Herceptin.
“In our tests, treating the cancer cell lines with both GLA and Herceptin led to a synergistic increase in cell death and reduced cancer cell growth,” said Dr. Lupu. “Although further studies are necessary before GLA can enter clinical trials, these findings may reveal a previously unrecognized way of influencing the poor outcome of Her-2/neu-positive cancer patients.”
“GLA’s inhibition of Her-2/neu works in a different manner from that of Herceptin,” said co-researcher Javier A. Menendez, PhD, research scientist Evanston Northwestern Research Institute. “While Herceptin attempts to neutralize thousands of Her-2/neu molecules commonly found in overexpressing cancer cells, GLA would be more efficient to reduce Her-2/neu levels by preventing the gene from copying itself.”
Lupu and Menendez were also the researchers who discovered that the oleic acid found in olive oil dramatically reduces the levels of a protein produced by the breast cancer gene Her-2/neu.
The latest study was supported by funding from the Susan G. Komen Breast Cancer Foundation and the federal government.
About Evanston Northwestern Healthcare
Located in Chicago’s northern suburbs, Evanston Northwestern Healthcare (ENH) is an integrated healthcare system that includes Evanston, Glenbrook and Highland Park Hospitals, ENH Medical Group (comprising 65 medical offices and facilities), ENH Home Services, ENH Research Institute and ENH Foundation. Through its affiliation with Northwestern University’s Feinberg School of Medicine, ENH supports extensive medical education and research. ENH is in the top nine percent of all institutions that receive funding from the National Institutes of Health; among multi-specialty independent research hospitals, it ranks 12th in the nation.
Effect of Gamma-Linolenic Acid on the Transcriptional activity of the Her- 2/neu (erbB-2) oncogene, Journal of the National Cancer Institute, Vol. 97, No. 21, November 2, 2005, p. 1611-1615.
SOURCE Evanston Northwestern Healthcare
Kolaviron
Kolaviron/Natural Bioflavonoid (Garcinia kola seeds (rat study)
Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural biflavonoid of Garcinia kola seeds.
Farombi, E O 1; Adepoju, B F 1; Ola-Davies, O E 2; Emerole, G O 1
Abstract:
The chemopreventive effects of kolaviron, a natural antioxidant biflavonoid from the seeds of Garcinia kola, on aflatoxin B1 (AFB1)-induced genotoxicity and hepatic oxidative damage was investigated in rats.
Kolaviron administered orally at a dose of 200 mg/kg once a day for the first 2 weeks and then 100 mg/kg twice a day for the last 4 weeks of AFB1 (2 mg/kg, single dose, intraperitoneal) treatment reduced the AFB1-increased activities of aspartate amino transferase (AST), alanine amino transferase (ALT) and gamma glutamyltransferase ([gamma]-GT) by 62%, 56% and 72% respectively.
Malondialdehyde (MDA) formation and lipid hydroperoxide (LHP) accumulation were observed in the livers of AFB1- treated rats. Kolaviron significantly reduced the AFB1-induced MDA and LHP formation. Vitamins C and E were protective in reducing the increase in the activities of AST, ALT and [gamma]-GT as well as lipid peroxidation caused by AFB1 (P
Administration of rats with kolaviron alone resulted in significant elevation in the activities of glutathione S-transferase, uridyl glucuronosyl transferase and NADH:quinone oxidoreductase by 2.45-, 1.62- and 1.38-folds respectively.
In addition, kolaviron attenuated the AFB1-mediated decrease in the activities of these enzymes (P0.05). Co-treatment of rats intraperitoneally with kolaviron (500 mg/kg) 30 min before and 30 min after AFB1 (1 mg/kg) administration inhibited the induction of MNPCEs by AFB1 (P
While vitamin C was effective in reducing AFB1-induced MNPCEs formation, vitamin E did not elicit any antigenotoxic response. These results indicate kolaviron as effective chemo preventive agent against AFB1-induced genotoxicity and hepatic oxidative stress.
Thus kolaviron may qualify for clinical trial in combating the menace of aflatoxicosis in endemic areas of aflatoxin contamination of foods.
European Journal of Cancer Prevention. 14(3):207-214, June 2005.
J Basic Clin Physiol Pharmacol, 2016 Jun 1;27(4):363-70. doi: 10.1515/jbcpp-2015-0075.
Antinociceptive and Anti-Inflammatory Potentials of Kolaviron: Mechanisms of Action
Samuel A Onasanwo,Rume A Rotu PMID:26812784 DOI:10.1515/jbcpp-2015-0075
Abstract
Background: Major attention has been on dietary and medicinal phytochemicals that inhibit or reverse abnormal conditions caused by nociceptive and inflammatory stimuli. Garcinia kola (Guttiferae) seed, known as "bitter kola", plays an important role in African ethno-medicine and traditional hospitality like in the treatment of inflammation, colds, bronchitis, bacterial, and viral infections. A number of useful phytochemicals have been isolated from the seed, and the most prominent of them is kolaviron (Garcinia bioflavonoid), which has been suggested to have antinociceptive and anti-inflammatory potentials. The aim of this experiment is to explore the mechanisms of action of the antinociceptive and anti-inflammatory potentials of kolaviron.
Methods: The probable mechanisms of action of kolaviron were assessed by using naloxone, prazosin, and atropine to investigate the involvement of adrenergic, opioidergic, and cholinergic systems, respectively, using tail flick, the acetic acid-induced writhing, formalin-induced paw licking, and carrageenan-induced paw edema models. Also, hematoxylin and eosin (H&E) staining was used to analyze the level of inflammation.
Results: In the acetic acid-induced writhing test in mice, pretreatment with naloxone, prazosin, and atropine significantly reversed the antinociception effects of kolaviron (200 mg/kg) when compared with control and kolaviron groups. In the formalin-induced paw licking test in mice, there was a significant decrease on the antinociceptive effects of kolaviron in the late phase when compared with the control, while the pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine did not have any significant decrease when compared with the kolaviron group. In the tail flick latency assay in rats, pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine; however, did not have any significant increase when compared with the control and kolaviron groups. The result of the study also shows a highly significant inhibition of paw edema in the carrageenan-induced receiving kolaviron when compared with the vehicle carrageenan-induced groups. Histological staining also showed that kolaviron significantly reduced the infiltration of inflammatory cells in the paw tissues.
Conclusions: Kolaviron possesses antinociceptive and anti-inflammatory activity, both centrally and peripherally, which justifies its folkloric use to relieve pain and inflammation. It may be exerting its effects through mechanisms that involve opioidergic and adrenergic systems, and may not involve the cholinergic system.
Kolaviron/Natural Bioflavonoid (Garcinia kola seeds (rat study)
Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural biflavonoid of Garcinia kola seeds.
Farombi, E O 1; Adepoju, B F 1; Ola-Davies, O E 2; Emerole, G O 1
Abstract:
The chemopreventive effects of kolaviron, a natural antioxidant biflavonoid from the seeds of Garcinia kola, on aflatoxin B1 (AFB1)-induced genotoxicity and hepatic oxidative damage was investigated in rats.
Kolaviron administered orally at a dose of 200 mg/kg once a day for the first 2 weeks and then 100 mg/kg twice a day for the last 4 weeks of AFB1 (2 mg/kg, single dose, intraperitoneal) treatment reduced the AFB1-increased activities of aspartate amino transferase (AST), alanine amino transferase (ALT) and gamma glutamyltransferase ([gamma]-GT) by 62%, 56% and 72% respectively.
Malondialdehyde (MDA) formation and lipid hydroperoxide (LHP) accumulation were observed in the livers of AFB1- treated rats. Kolaviron significantly reduced the AFB1-induced MDA and LHP formation. Vitamins C and E were protective in reducing the increase in the activities of AST, ALT and [gamma]-GT as well as lipid peroxidation caused by AFB1 (P
Administration of rats with kolaviron alone resulted in significant elevation in the activities of glutathione S-transferase, uridyl glucuronosyl transferase and NADH:quinone oxidoreductase by 2.45-, 1.62- and 1.38-folds respectively.
In addition, kolaviron attenuated the AFB1-mediated decrease in the activities of these enzymes (P0.05). Co-treatment of rats intraperitoneally with kolaviron (500 mg/kg) 30 min before and 30 min after AFB1 (1 mg/kg) administration inhibited the induction of MNPCEs by AFB1 (P
While vitamin C was effective in reducing AFB1-induced MNPCEs formation, vitamin E did not elicit any antigenotoxic response. These results indicate kolaviron as effective chemo preventive agent against AFB1-induced genotoxicity and hepatic oxidative stress.
Thus kolaviron may qualify for clinical trial in combating the menace of aflatoxicosis in endemic areas of aflatoxin contamination of foods.
European Journal of Cancer Prevention. 14(3):207-214, June 2005.
J Basic Clin Physiol Pharmacol, 2016 Jun 1;27(4):363-70. doi: 10.1515/jbcpp-2015-0075.
Antinociceptive and Anti-Inflammatory Potentials of Kolaviron: Mechanisms of Action
Samuel A Onasanwo,Rume A Rotu PMID:26812784 DOI:10.1515/jbcpp-2015-0075
Abstract
Background: Major attention has been on dietary and medicinal phytochemicals that inhibit or reverse abnormal conditions caused by nociceptive and inflammatory stimuli. Garcinia kola (Guttiferae) seed, known as "bitter kola", plays an important role in African ethno-medicine and traditional hospitality like in the treatment of inflammation, colds, bronchitis, bacterial, and viral infections. A number of useful phytochemicals have been isolated from the seed, and the most prominent of them is kolaviron (Garcinia bioflavonoid), which has been suggested to have antinociceptive and anti-inflammatory potentials. The aim of this experiment is to explore the mechanisms of action of the antinociceptive and anti-inflammatory potentials of kolaviron.
Methods: The probable mechanisms of action of kolaviron were assessed by using naloxone, prazosin, and atropine to investigate the involvement of adrenergic, opioidergic, and cholinergic systems, respectively, using tail flick, the acetic acid-induced writhing, formalin-induced paw licking, and carrageenan-induced paw edema models. Also, hematoxylin and eosin (H&E) staining was used to analyze the level of inflammation.
Results: In the acetic acid-induced writhing test in mice, pretreatment with naloxone, prazosin, and atropine significantly reversed the antinociception effects of kolaviron (200 mg/kg) when compared with control and kolaviron groups. In the formalin-induced paw licking test in mice, there was a significant decrease on the antinociceptive effects of kolaviron in the late phase when compared with the control, while the pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine did not have any significant decrease when compared with the kolaviron group. In the tail flick latency assay in rats, pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine; however, did not have any significant increase when compared with the control and kolaviron groups. The result of the study also shows a highly significant inhibition of paw edema in the carrageenan-induced receiving kolaviron when compared with the vehicle carrageenan-induced groups. Histological staining also showed that kolaviron significantly reduced the infiltration of inflammatory cells in the paw tissues.
Conclusions: Kolaviron possesses antinociceptive and anti-inflammatory activity, both centrally and peripherally, which justifies its folkloric use to relieve pain and inflammation. It may be exerting its effects through mechanisms that involve opioidergic and adrenergic systems, and may not involve the cholinergic system.
L Glutamine
From the September 1999 edition of Life Extension Foundation Magazine:
Although glutamine is heavily used by all rapidly dividing cells, it has been shown to prolong survival by slowing down carbolic wasting (cachexia). Ann’s NOTE: This is what Hydrazine Sulfate does too. Glutamine is beneficial to the depleted immune system and can help preserve the intestinal function. Clinical use and animal studies have “suggested” that glutamine can be given to cancer patients “without stimulating tumor growth or metastasis.” Patients should consult their physicians before beginning use.
Rats given glutamine and implanted with breast cancer showed 40% less tumor growth than the control group. Natural killer cells showed 2.5 times greater activity (see MGN-3). Additionally inflammatory prostaglandins decreased. Those substances have shown an ability to fuel tumor growth.
Glutamine can be used as adjuvant therapy with methotrexaste (a chemotherapy). It acts to lower the toxicity while augmenting its effectiveness against inflammatory breast cancer (considered a hard-to-treat type of breast cancer). The authors of this study stated that “No toxicity of oral glutamine was detected (and) no patient showed ANY sign of chemotherapy-related toxicity”. Ann’s emphasis added. Glutamine was used in conjunction with methotrexate at .5g/kg/day.
Glutamine is also essential for learning and short and long-term memory.
Some relevant studies: “Effect of glutamine on tumor and host growth” by Bartlett, DL et al AnnSurgOncol 1995;2:71-6
“Glutamine suppresses PGE2 synthesis and breast cancer growth” by Klimberg VS et al JSurgRes 1996;63″293-7
“Effect of glutamine on methotrexate efficacy and toxicity” by Rubio IT et al AnnSurg 1998;227:772-8
“Glutamine supplementation in catabolic patients” by Sacks, GS AnnPharmacother 1999;33:348-54
Int J Mol Sci, 16 (9), 22830-55 2015 Sep 22
Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach Lian Chen 1, Hengmin Cui 2 3 PMID:26402672 PMCID:PMC4613338 DOI:10.3390/ijms160922830
Abstract
Glutamine metabolism has been proved to be dysregulated in many cancer cells, and is essential for proliferation of most cancer cells, which makes glutamine an appealing target for cancer therapy. In order to be well used by cells, glutamine must be transported to cells by specific transporters and converted to glutamate by glutaminase. There are currently several drugs that target glutaminase under development or clinical trials. Also, glutamine metabolism restriction has been proved to be effective in inhibiting tumor growth both in vivo and vitro through inducing apoptosis, growth arrest and/or autophagy. Here, we review recent researches about glutamine metabolism in cancer, and cell death induced by targeting glutamine, and their potential roles in cancer therapy.
From the September 1999 edition of Life Extension Foundation Magazine:
Although glutamine is heavily used by all rapidly dividing cells, it has been shown to prolong survival by slowing down carbolic wasting (cachexia). Ann’s NOTE: This is what Hydrazine Sulfate does too. Glutamine is beneficial to the depleted immune system and can help preserve the intestinal function. Clinical use and animal studies have “suggested” that glutamine can be given to cancer patients “without stimulating tumor growth or metastasis.” Patients should consult their physicians before beginning use.
Rats given glutamine and implanted with breast cancer showed 40% less tumor growth than the control group. Natural killer cells showed 2.5 times greater activity (see MGN-3). Additionally inflammatory prostaglandins decreased. Those substances have shown an ability to fuel tumor growth.
Glutamine can be used as adjuvant therapy with methotrexaste (a chemotherapy). It acts to lower the toxicity while augmenting its effectiveness against inflammatory breast cancer (considered a hard-to-treat type of breast cancer). The authors of this study stated that “No toxicity of oral glutamine was detected (and) no patient showed ANY sign of chemotherapy-related toxicity”. Ann’s emphasis added. Glutamine was used in conjunction with methotrexate at .5g/kg/day.
Glutamine is also essential for learning and short and long-term memory.
Some relevant studies: “Effect of glutamine on tumor and host growth” by Bartlett, DL et al AnnSurgOncol 1995;2:71-6
“Glutamine suppresses PGE2 synthesis and breast cancer growth” by Klimberg VS et al JSurgRes 1996;63″293-7
“Effect of glutamine on methotrexate efficacy and toxicity” by Rubio IT et al AnnSurg 1998;227:772-8
“Glutamine supplementation in catabolic patients” by Sacks, GS AnnPharmacother 1999;33:348-54
Int J Mol Sci, 16 (9), 22830-55 2015 Sep 22
Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach Lian Chen 1, Hengmin Cui 2 3 PMID:26402672 PMCID:PMC4613338 DOI:10.3390/ijms160922830
Abstract
Glutamine metabolism has been proved to be dysregulated in many cancer cells, and is essential for proliferation of most cancer cells, which makes glutamine an appealing target for cancer therapy. In order to be well used by cells, glutamine must be transported to cells by specific transporters and converted to glutamate by glutaminase. There are currently several drugs that target glutaminase under development or clinical trials. Also, glutamine metabolism restriction has been proved to be effective in inhibiting tumor growth both in vivo and vitro through inducing apoptosis, growth arrest and/or autophagy. Here, we review recent researches about glutamine metabolism in cancer, and cell death induced by targeting glutamine, and their potential roles in cancer therapy.
L_Carnitine
L-Carnitine & Epirubicin (Cardiomyopathy)
Supplementation with l-carnitine does not reduce the efficacy of epirubicin treatment in breast cancer cells
Christie E. Delaneya, Sean P. Hopkinsb and Christina L. Addisona, ,
aCentre for Cancer Therapeutics, Ottawa Health Research Institute, 501 Smyth Road, 3rd Floor TOHRCC, Box 926, Ottawa, Ont., Canada K1H 8L6b Department of Pharmacy, The Ottawa Hospital Regional Cancer Centre, Ottawa, Ont., Canada K1H 8L6
Abstract
One of the cornerstones of therapy for invasive breast cancer includes the use of anthracyclines. Epirubicin, a stereoisomer of doxorubicin, is one of the commonly used anthracyclines.
Anthracyclines while effective therapy for breast cancer, have their own unique toxicities, such as cardiomyopathy. l- Carnitine, a quarternary ammonium compound synthesized from methionine and lysine, is required for oxidative metabolism in mitochondria.
Cardiac function is closely linked with oxidative metabolism whereby l-carnitine is an essential cofactor. A hypothesis is being investigated to determine if supplementation with carnitine in breast cancer patients treated with epirubicin will reduce the development of cardiac toxicity.
We determined whether addition of l-carnitine altered the tumor cytotoxic effects of epirubicin using a number of in vitro cell viability assays in different breast cancer cell lines including BT549, MDA-MB-435, NCI-ADR-RES, MCF7 and T47D.
Additionally we investigated the ability of cells to respond to l-carnitine following analysis of the expression of carnitine metabolic enzymes by RT-PCR. We determined that supplementation with l-carnitine had no effect on the ability of epirubicin to kill a variety of breast cancer cell lines.
Additionally, no differences in the induction of apoptosis by epirubicin were observed. Furthermore, all cell lines examined expressed proteins required for carnitine uptake and use. Our data suggest that supplementation with l-carnitine does not impair the ability of epirubicin to kill breast cancer cells.
These results suggest that supplementation with l-carnitine in patients undergoing epirubicin treatment could be safely used to reduce associated cardiotoxicities without fear that the efficacy of chemotherapy is jeopardized.
Abbreviations: CPT-1, carnitine palmitoyltransferase-1; CRAT, carnitine acetyltransferase; DMEM, Dulbecco s modified essential media; FBS, fetal bovine serum; FEC100, 500 mg/m2 5-fluorouracil, 100 mg/m2 epirubicin, 500 mg/m2 cyclophosphamide; MMLV, Moloney Murine leukemia virus; MTT, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; OCTN2, carnitine/organic cation transporter; PARP, poly ADP-ribose polymerase; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; PMSF, phenylmethylsulfonyl fluoride; RT-PCR, reverse transcriptase polymerase chain reaction; SDS, sodium dodecyl sulfate
Cancer Letters in press, March 2007
doi:10.1016/j.canlet.2006.12.027
L-Carnitine & Epirubicin (Cardiomyopathy)
Supplementation with l-carnitine does not reduce the efficacy of epirubicin treatment in breast cancer cells
Christie E. Delaneya, Sean P. Hopkinsb and Christina L. Addisona, ,
aCentre for Cancer Therapeutics, Ottawa Health Research Institute, 501 Smyth Road, 3rd Floor TOHRCC, Box 926, Ottawa, Ont., Canada K1H 8L6b Department of Pharmacy, The Ottawa Hospital Regional Cancer Centre, Ottawa, Ont., Canada K1H 8L6
Abstract
One of the cornerstones of therapy for invasive breast cancer includes the use of anthracyclines. Epirubicin, a stereoisomer of doxorubicin, is one of the commonly used anthracyclines.
Anthracyclines while effective therapy for breast cancer, have their own unique toxicities, such as cardiomyopathy. l- Carnitine, a quarternary ammonium compound synthesized from methionine and lysine, is required for oxidative metabolism in mitochondria.
Cardiac function is closely linked with oxidative metabolism whereby l-carnitine is an essential cofactor. A hypothesis is being investigated to determine if supplementation with carnitine in breast cancer patients treated with epirubicin will reduce the development of cardiac toxicity.
We determined whether addition of l-carnitine altered the tumor cytotoxic effects of epirubicin using a number of in vitro cell viability assays in different breast cancer cell lines including BT549, MDA-MB-435, NCI-ADR-RES, MCF7 and T47D.
Additionally we investigated the ability of cells to respond to l-carnitine following analysis of the expression of carnitine metabolic enzymes by RT-PCR. We determined that supplementation with l-carnitine had no effect on the ability of epirubicin to kill a variety of breast cancer cell lines.
Additionally, no differences in the induction of apoptosis by epirubicin were observed. Furthermore, all cell lines examined expressed proteins required for carnitine uptake and use. Our data suggest that supplementation with l-carnitine does not impair the ability of epirubicin to kill breast cancer cells.
These results suggest that supplementation with l-carnitine in patients undergoing epirubicin treatment could be safely used to reduce associated cardiotoxicities without fear that the efficacy of chemotherapy is jeopardized.
Abbreviations: CPT-1, carnitine palmitoyltransferase-1; CRAT, carnitine acetyltransferase; DMEM, Dulbecco s modified essential media; FBS, fetal bovine serum; FEC100, 500 mg/m2 5-fluorouracil, 100 mg/m2 epirubicin, 500 mg/m2 cyclophosphamide; MMLV, Moloney Murine leukemia virus; MTT, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; OCTN2, carnitine/organic cation transporter; PARP, poly ADP-ribose polymerase; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; PMSF, phenylmethylsulfonyl fluoride; RT-PCR, reverse transcriptase polymerase chain reaction; SDS, sodium dodecyl sulfate
Cancer Letters in press, March 2007
doi:10.1016/j.canlet.2006.12.027
Lack of Marine Omega
Lack of Marine Omega-3 Increases Breast Cancer Risk
Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study.
Gago-Dominguez M, Yuan JM, Sun CL, Lee HP, Yu MC.
USC/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441
Eastlake Avenue, Los Angeles, CA 90089-9181, USA. mgago@usc.edu
We investigated the effects of individual fatty acids on breast cancer in a prospective study of 35,298 Singapore Chinese women aged 45-74 years, who were enrolled during April 1993 to December 1998 (The Singapore Chinese Health Study).
At recruitment, each study subject was administered, in-person, a validated, semiquantitative food frequency questionnaire consisting of 165 food and beverage items. As of December 31, 2000, 314 incident cases of breast cancer had occurred.
We used the Cox regression methods to examine individual fatty acids in relation to breast cancer risk, with adjustment for age at baseline interview, year of interview, dialect group, level of education, daily alcohol drinking, number of live births, age when menstrual periods became regular, and family history of breast cancer.
Consumption of saturated, monounsaturated or polyunsaturated fat overall was unrelated to risk. On the other hand, high levels of dietary n-3 fatty acids from fish/shellfish (marine n-3 fatty acids) were significantly associated with reduced risk.
Relative to the lowest quartile of intake, individuals in the higher three quartiles exhibited a 26% reduction in risk (relative risk (RR)=0.74, 95% confidence interval (CI)=0.58, 0.94)); RRs were similar across the top three quartiles of intake (0.75, 0.75, 0.72, respectively).
Overall, there was no association between n-6 fatty acids and breast cancer risk. However, among subjects who consumed low levels of marine n-3 fatty acids (lowest quartile of intake), a statistically significant increase in risk was observed in individuals belonging to the highest vs the lowest quartile of n-6 fatty acid consumption (RR=1.87, 95% CI=1.06-3.27); the corresponding RR for advanced breast cancer was 2.45 (95% CI=1.20-4.97, P for trend=0.01).
To our knowledge, these are the first prospective findings linking the intake of marine n-3 fatty acids to breast cancer protection. Br J Cancer. 2003 Nov 3; 89(9): 1686-92.
Breast Cancer Res . 2015 May 4;17(1):62. doi: 10.1186/s13058-015-0571-6.
Omega-3 Fatty Acids for Breast Cancer Prevention and Survivorship
Carol J Fabian, Bruce F Kimler , Stephen D Hursting PMID:25936773 PMCID:PMC4418048 DOI:10.1186/s13058-015-0571-6
Abstract
Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case- control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship.
Nutr Hosp. 2018 Sep 7;35(Spec No6):64-69. doi: 10.20960/nh.2291.
[Bioactive Food Compounds as Adjuvants to Breast Cancer Treatment: Vitamin D and omega-3]
Laura M Bermejo , Carmen Gómez-Candela, Sergio Dahdouh, Bricia López-Plaza
Affiliations expand PMID:30351165 DOI: 10.20960/nh.2291
Abstract
Introduction: breast cancer (BC) is the most commonly diagnosed tumor in women and it continues to be the leading cause of cancer death in women. Quality of life decreases significantly during treatment and in the survivors. There is growing evidence linking the intake of certain foods, or their bioactive compounds, with better prognosis of the disease or improvements in physiological parameters that can increase BC patients' quality of life. But there are hardly any reviews to clarify the scientific evidence.
Objectives: gathering and summarizing the available evidence on the effectiveness of the dietary compounds use as coadjuvants for BC treatment.
Method: literature search using Pubmed to identify and analyze bioactive compounds as coadjvants for BC treatment.
Results: all tested compounds showed antitumor effects in vitro. Vvitamin D decrease risk of bone fracture, and marine lipids may reduce bone resorption and inflammation.
Conclusion: there are bioactive compounds with potential to improve the quality of life of women with BC. Vitamin D a marine lipids provide a solid quality scientific evidence. Despite this, more controlled clinical trials are required to establish a direct link between the use of these compounds and the tumor progression or patient survival.
Lack of Marine Omega-3 Increases Breast Cancer Risk
Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study.
Gago-Dominguez M, Yuan JM, Sun CL, Lee HP, Yu MC.
USC/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441
Eastlake Avenue, Los Angeles, CA 90089-9181, USA. mgago@usc.edu
We investigated the effects of individual fatty acids on breast cancer in a prospective study of 35,298 Singapore Chinese women aged 45-74 years, who were enrolled during April 1993 to December 1998 (The Singapore Chinese Health Study).
At recruitment, each study subject was administered, in-person, a validated, semiquantitative food frequency questionnaire consisting of 165 food and beverage items. As of December 31, 2000, 314 incident cases of breast cancer had occurred.
We used the Cox regression methods to examine individual fatty acids in relation to breast cancer risk, with adjustment for age at baseline interview, year of interview, dialect group, level of education, daily alcohol drinking, number of live births, age when menstrual periods became regular, and family history of breast cancer.
Consumption of saturated, monounsaturated or polyunsaturated fat overall was unrelated to risk. On the other hand, high levels of dietary n-3 fatty acids from fish/shellfish (marine n-3 fatty acids) were significantly associated with reduced risk.
Relative to the lowest quartile of intake, individuals in the higher three quartiles exhibited a 26% reduction in risk (relative risk (RR)=0.74, 95% confidence interval (CI)=0.58, 0.94)); RRs were similar across the top three quartiles of intake (0.75, 0.75, 0.72, respectively).
Overall, there was no association between n-6 fatty acids and breast cancer risk. However, among subjects who consumed low levels of marine n-3 fatty acids (lowest quartile of intake), a statistically significant increase in risk was observed in individuals belonging to the highest vs the lowest quartile of n-6 fatty acid consumption (RR=1.87, 95% CI=1.06-3.27); the corresponding RR for advanced breast cancer was 2.45 (95% CI=1.20-4.97, P for trend=0.01).
To our knowledge, these are the first prospective findings linking the intake of marine n-3 fatty acids to breast cancer protection. Br J Cancer. 2003 Nov 3; 89(9): 1686-92.
Breast Cancer Res . 2015 May 4;17(1):62. doi: 10.1186/s13058-015-0571-6.
Omega-3 Fatty Acids for Breast Cancer Prevention and Survivorship
Carol J Fabian, Bruce F Kimler , Stephen D Hursting PMID:25936773 PMCID:PMC4418048 DOI:10.1186/s13058-015-0571-6
Abstract
Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case- control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship.
Nutr Hosp. 2018 Sep 7;35(Spec No6):64-69. doi: 10.20960/nh.2291.
[Bioactive Food Compounds as Adjuvants to Breast Cancer Treatment: Vitamin D and omega-3]
Laura M Bermejo , Carmen Gómez-Candela, Sergio Dahdouh, Bricia López-Plaza
Affiliations expand PMID:30351165 DOI: 10.20960/nh.2291
Abstract
Introduction: breast cancer (BC) is the most commonly diagnosed tumor in women and it continues to be the leading cause of cancer death in women. Quality of life decreases significantly during treatment and in the survivors. There is growing evidence linking the intake of certain foods, or their bioactive compounds, with better prognosis of the disease or improvements in physiological parameters that can increase BC patients' quality of life. But there are hardly any reviews to clarify the scientific evidence.
Objectives: gathering and summarizing the available evidence on the effectiveness of the dietary compounds use as coadjuvants for BC treatment.
Method: literature search using Pubmed to identify and analyze bioactive compounds as coadjvants for BC treatment.
Results: all tested compounds showed antitumor effects in vitro. Vvitamin D decrease risk of bone fracture, and marine lipids may reduce bone resorption and inflammation.
Conclusion: there are bioactive compounds with potential to improve the quality of life of women with BC. Vitamin D a marine lipids provide a solid quality scientific evidence. Despite this, more controlled clinical trials are required to establish a direct link between the use of these compounds and the tumor progression or patient survival.
Lactobacillus Species Cytotoxic
Lactobacillus Species Cytotoxic: Human Bladder Ca Cells
Lactobacillus Species is More Cytotoxic to Human Bladder Cancer Cells Than Mycobacterium Bovis (Bacillus Calmette-guerin)
SHIH WEE SEOW; JUWITA NORASMARA BTE RAHMAT; AMEER ALI KANAKKAPPILLAI MOHAMED; RATHA MAHENDRAN; YUAN KUN LEE; BOON HUAT BAY
ABSTRACT
Purpose:
We determined if Lactobacillus species has growth inhibitory effects in human bladder cancer cell lines and how this effect compares with the known effects of Mycobacterium bovis, that is bacillus Calmette-Guerin (BCG).
Materials and Methods:
The growth of MGH and RT112 cells were determined by cell counts after 24, 48 and 72 hours of exposure to L. casei strain Shirota (Yakult, Singapore) or L. rhamnosus strain GG (National Collection of Industrial and Marine Bacteria, Ltd., Aberdeen, Scotland) (1 × 107 and 1 × 108 cfu) or BCG (1 × 107 cfu) in the presence and absence of streptomycin. Annexin-V was used to monitor the presence of pre-apoptotic cells.
Results:
L. rhamnosus GG inhibited MGH proliferation and it was cytotoxic to RT112 cells (p
Cytotoxic activity was not found in Lactobacilli culture supernates but it was induced in the presence of mammalian cells. L. rhamnosus GG induced apoptosis in RT112 but not in MGH cells. No apoptotic cells were detected after treatment with L. casei Shirota.
Conclusions:
Lactobacillus species induced cytotoxic effects in bladder cancer cells. Unlike BCG, it requires bacterial protein synthesis. Like BCG, L. casei Shirota induces cell death primarily via necrosis.
The cytoxicity of these lactobacilli in bladder cancer cells raises the possibility of using this species of bacteria as intravesical agents for treating bladder cancer.
The Journal of Urology 2002; 168(5):2236-2239
Anticancer Drugs
2016 Apr;27(4):269-77.
doi: 10.1097/CAD.0000000000000337.
Spontaneous Regression of Tumour and the Role of Microbial Infection--Possibilitiesfor Cancer Treatment
Petra Kucerova, Monika Cervinkova PMID:26813865 PMCID:PMC4777220 DOI:10.1097/CAD.0000000000000337
Abstract:
This review deals with the role of microorganisms in spontaneous regression of a tumour. Spontaneous cancer regression is a phenomenon that has been described for many centuries. One of the most well known methods of inducing spontaneous regression of cancer is the application of Coley's toxin (heat-killed Streptococcus pyogenes and Serratia marcescens), which has been used for the successful treatment of sarcomas, carcinomas, lymphomas, myelomas and melanomas. In clinical practice, the use of Bacillus Calmette-Guérin vaccine for the treatment of superficial urinary bladder cancer is the most common instance of the application of microorganisms for the treatment of cancer. This review provides further information on other tested bacteria-- Clostridium spp., Bifidobacterium spp., Lactobacillus spp. and Salmonella spp.--in this field of study. Among new age methods, bactofection, alternative gene therapy, combination bacteriolytic therapy and bacteria-directed enzyme prodrug therapy are some of the potential cancer treatment modalities that use microorganisms. We have also provided information about the interconnection among microorganisms, immune system response, and the possible mechanisms involved in the spontaneous regression of tumours.
Int J Cancer. 2019 May 1;144(9):2099-2108. doi: 10.1002/ijc.31959. Epub 2018 Dec 3.
Fermented Dairy Foods Intake and Risk of Cancer
Kui Zhang 1, Hao Dai 1, Weibo Liang 1, Lin Zhang 1, Zhenhua Deng 1 PMID: 30374967
DOI: 10.1002/ijc.31959
Abstract: Fermented dairy foods are known to be nutrient-rich and probiotic content, which gather optimism due to their potential in prevention and management of cancer. We searched the PubMed, Embase and CNKI databases for all available studies through July 2018 on the association between fermented dairy foods intake and cancer risk. The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to assess the association using a random-effect meta-analysis. Finally, 61 studies met the inclusion criteria for our study, with 1,962,774 participants and 38,358 cancer cases. Overall, statistical evidence of significantly decreased cancer risk was found to be associated with fermented dairy foods intake (OR = 0.86, 95% CI = 0.80-0.92) in cohort studies. Yogurt consumption was significantly with decreased cancer risk in the overall comparison (OR = 0.87, 95% CI = 0.80-0.95) and in the cohort studies (OR = 0.81, 95% CI = 0.74-0.88). In terms of subgroup analyses by cancer type, fermented dairy foods intake significantly decreased bladder cancer, colorectal cancer and esophageal cancer risk. In stratified analyses, significantly decreased colorectal cancer risk was found to be associated with cheese intake. Yogurt consumption was significantly decreased [in] bladder cancer and colorectal cancer risk. Our meta-analysis indicated that fermented dairy foods intake was associated with an overall decrease in cancer risk.
Lactobacillus Species Cytotoxic: Human Bladder Ca Cells
Lactobacillus Species is More Cytotoxic to Human Bladder Cancer Cells Than Mycobacterium Bovis (Bacillus Calmette-guerin)
SHIH WEE SEOW; JUWITA NORASMARA BTE RAHMAT; AMEER ALI KANAKKAPPILLAI MOHAMED; RATHA MAHENDRAN; YUAN KUN LEE; BOON HUAT BAY
ABSTRACT
Purpose:
We determined if Lactobacillus species has growth inhibitory effects in human bladder cancer cell lines and how this effect compares with the known effects of Mycobacterium bovis, that is bacillus Calmette-Guerin (BCG).
Materials and Methods:
The growth of MGH and RT112 cells were determined by cell counts after 24, 48 and 72 hours of exposure to L. casei strain Shirota (Yakult, Singapore) or L. rhamnosus strain GG (National Collection of Industrial and Marine Bacteria, Ltd., Aberdeen, Scotland) (1 × 107 and 1 × 108 cfu) or BCG (1 × 107 cfu) in the presence and absence of streptomycin. Annexin-V was used to monitor the presence of pre-apoptotic cells.
Results:
L. rhamnosus GG inhibited MGH proliferation and it was cytotoxic to RT112 cells (p
Cytotoxic activity was not found in Lactobacilli culture supernates but it was induced in the presence of mammalian cells. L. rhamnosus GG induced apoptosis in RT112 but not in MGH cells. No apoptotic cells were detected after treatment with L. casei Shirota.
Conclusions:
Lactobacillus species induced cytotoxic effects in bladder cancer cells. Unlike BCG, it requires bacterial protein synthesis. Like BCG, L. casei Shirota induces cell death primarily via necrosis.
The cytoxicity of these lactobacilli in bladder cancer cells raises the possibility of using this species of bacteria as intravesical agents for treating bladder cancer.
The Journal of Urology 2002; 168(5):2236-2239
Anticancer Drugs
2016 Apr;27(4):269-77.
doi: 10.1097/CAD.0000000000000337.
Spontaneous Regression of Tumour and the Role of Microbial Infection--Possibilitiesfor Cancer Treatment
Petra Kucerova, Monika Cervinkova PMID:26813865 PMCID:PMC4777220 DOI:10.1097/CAD.0000000000000337
Abstract:
This review deals with the role of microorganisms in spontaneous regression of a tumour. Spontaneous cancer regression is a phenomenon that has been described for many centuries. One of the most well known methods of inducing spontaneous regression of cancer is the application of Coley's toxin (heat-killed Streptococcus pyogenes and Serratia marcescens), which has been used for the successful treatment of sarcomas, carcinomas, lymphomas, myelomas and melanomas. In clinical practice, the use of Bacillus Calmette-Guérin vaccine for the treatment of superficial urinary bladder cancer is the most common instance of the application of microorganisms for the treatment of cancer. This review provides further information on other tested bacteria-- Clostridium spp., Bifidobacterium spp., Lactobacillus spp. and Salmonella spp.--in this field of study. Among new age methods, bactofection, alternative gene therapy, combination bacteriolytic therapy and bacteria-directed enzyme prodrug therapy are some of the potential cancer treatment modalities that use microorganisms. We have also provided information about the interconnection among microorganisms, immune system response, and the possible mechanisms involved in the spontaneous regression of tumours.
Int J Cancer. 2019 May 1;144(9):2099-2108. doi: 10.1002/ijc.31959. Epub 2018 Dec 3.
Fermented Dairy Foods Intake and Risk of Cancer
Kui Zhang 1, Hao Dai 1, Weibo Liang 1, Lin Zhang 1, Zhenhua Deng 1 PMID: 30374967
DOI: 10.1002/ijc.31959
Abstract: Fermented dairy foods are known to be nutrient-rich and probiotic content, which gather optimism due to their potential in prevention and management of cancer. We searched the PubMed, Embase and CNKI databases for all available studies through July 2018 on the association between fermented dairy foods intake and cancer risk. The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to assess the association using a random-effect meta-analysis. Finally, 61 studies met the inclusion criteria for our study, with 1,962,774 participants and 38,358 cancer cases. Overall, statistical evidence of significantly decreased cancer risk was found to be associated with fermented dairy foods intake (OR = 0.86, 95% CI = 0.80-0.92) in cohort studies. Yogurt consumption was significantly with decreased cancer risk in the overall comparison (OR = 0.87, 95% CI = 0.80-0.95) and in the cohort studies (OR = 0.81, 95% CI = 0.74-0.88). In terms of subgroup analyses by cancer type, fermented dairy foods intake significantly decreased bladder cancer, colorectal cancer and esophageal cancer risk. In stratified analyses, significantly decreased colorectal cancer risk was found to be associated with cheese intake. Yogurt consumption was significantly decreased [in] bladder cancer and colorectal cancer risk. Our meta-analysis indicated that fermented dairy foods intake was associated with an overall decrease in cancer risk.
Life Ext Fndn on Selenium
Selenium
Don’t count on the new media or popular health publications to keep you fully informed about new medical findings. An article published in the December 25, 1996, issue of the Journal of the American Medical Association (JAMA) showed that 200 mcg of supplemental selenium a day reduced overall cancer mortality by 50% in humans compared to a placebo group not receiving supplemental selenium. This 9-year study, published in the American Medical Association’s scientific journal (JAMA), demonstrated that a low-cost mineral supplement could cut the risk of dying from cancer in half.
In the prior week’s issue of JAMA (December 18, 1996), an article was published indicating that folic acid could substantially reduce cardiovascular disease risk. The selenium cancer study received some media attention, but the folic acid cardiovascular study did not. The fact is that the news media have not been consistent in reporting on studies that substantiate the disease-preventing role of dietary supplements, even when these studies appear in the most prestigious medical journals in the world.
One of the most compelling reports that high-potency supplements extend lifespan in humans was published in the August 1996 issue of the American Journal of Clinical Nutrition. This study involved 11,178 elderly people, who participated in a trial to establish the effects of vitamin supplements on mortality. This study showed that the use of vitamin E reduced the risk of death from all causes by 34%. Effects were strongest for coronary artery disease, where vitamin E resulted in a 63% reduction in death from heart attack. In addition, the use of vitamin E resulted in a 59% reduction in cancer mortality. When the effects of vitamin C and E were combined, overall mortality was reduced by 42% (compared to 34% for vitamin E alone). These results are the most significant evidence yet presented about the value of vitamin supplementation, yet the media failed to report on it.
If you are healthy now, and want to stay that way, the Life Extension Foundation has designed protocols that incorporate the best-documented disease-preventing nutrients and hormones.
Ann’s NOTE: Lest you think the idea of dietary supplements are new, this article was written in 1999. Life Extension Foundation was among the very first resources I found when seeking alternatives to conventional medicine.
Selenium
Don’t count on the new media or popular health publications to keep you fully informed about new medical findings. An article published in the December 25, 1996, issue of the Journal of the American Medical Association (JAMA) showed that 200 mcg of supplemental selenium a day reduced overall cancer mortality by 50% in humans compared to a placebo group not receiving supplemental selenium. This 9-year study, published in the American Medical Association’s scientific journal (JAMA), demonstrated that a low-cost mineral supplement could cut the risk of dying from cancer in half.
In the prior week’s issue of JAMA (December 18, 1996), an article was published indicating that folic acid could substantially reduce cardiovascular disease risk. The selenium cancer study received some media attention, but the folic acid cardiovascular study did not. The fact is that the news media have not been consistent in reporting on studies that substantiate the disease-preventing role of dietary supplements, even when these studies appear in the most prestigious medical journals in the world.
One of the most compelling reports that high-potency supplements extend lifespan in humans was published in the August 1996 issue of the American Journal of Clinical Nutrition. This study involved 11,178 elderly people, who participated in a trial to establish the effects of vitamin supplements on mortality. This study showed that the use of vitamin E reduced the risk of death from all causes by 34%. Effects were strongest for coronary artery disease, where vitamin E resulted in a 63% reduction in death from heart attack. In addition, the use of vitamin E resulted in a 59% reduction in cancer mortality. When the effects of vitamin C and E were combined, overall mortality was reduced by 42% (compared to 34% for vitamin E alone). These results are the most significant evidence yet presented about the value of vitamin supplementation, yet the media failed to report on it.
If you are healthy now, and want to stay that way, the Life Extension Foundation has designed protocols that incorporate the best-documented disease-preventing nutrients and hormones.
Ann’s NOTE: Lest you think the idea of dietary supplements are new, this article was written in 1999. Life Extension Foundation was among the very first resources I found when seeking alternatives to conventional medicine.
Linoleic Acid Lowers Risk for Prostate Ca
In middle-aged men, a relatively high dietary intake of linoleic acid may help lower the risk of prostate cancer and other cancers, according to a Finnish cohort study.
The researchers say these findings hint that recommendations to substitute dietary linoleic acid for saturated fat to prevent cardiovascular disease may have the added benefit of protecting against cancers.
“Dietary and serum fatty acid composition has been implicated in the pathogenesis of prostate and other cancers, but findings have been conflicting,” Dr. David E. Laaksonen from the University of Kuopio and colleagues explain in the September 1st International Journal of Cancer.
“Cohort studies reporting serum fatty acid composition are lacking.”
The investigators studied the association between dietary fatty acid composition assessed by food diary and serum and incident prostate cancer or “any” cancer in 2,002 middle-aged men free of cancer at baseline and during the first 4 years of follow up.
During 12.6 years of follow up, 46 men developed prostate cancer and 151 any cancer.
Data analysis showed that men with serum linoleic acid, n-6 fatty acids, and polyunsaturated fatty acids (PUFAs) in the upper tertile were “less than one-third” as likely to develop prostate cancer during follow up as those with levels in the lowest tertile.
The association held after adjustment for socioeconomic status, physical activity, obesity, and insulin concentrations.
Dietary linoleic acid intake obtained from 4-day food records also “tended to be inversely associated with incident prostate cancer,” with an age-adjusted relative risk of 0.55 for the upper vs the lower tertile.
The team also found “similar but weaker” associations with any cancer.
Dr. Laaksonen and colleagues conclude, “Substitution of linoleic acid for saturated fat in middle-aged men consuming a high saturated-fat diet may decrease the risk of prostate and other cancers,” although they acknowledge that other nutrients associated with vegetable fats may be responsible for the protective effect.
Int J Cancer 2004;111:444-450.
Thanks to Reuters Health
In middle-aged men, a relatively high dietary intake of linoleic acid may help lower the risk of prostate cancer and other cancers, according to a Finnish cohort study.
The researchers say these findings hint that recommendations to substitute dietary linoleic acid for saturated fat to prevent cardiovascular disease may have the added benefit of protecting against cancers.
“Dietary and serum fatty acid composition has been implicated in the pathogenesis of prostate and other cancers, but findings have been conflicting,” Dr. David E. Laaksonen from the University of Kuopio and colleagues explain in the September 1st International Journal of Cancer.
“Cohort studies reporting serum fatty acid composition are lacking.”
The investigators studied the association between dietary fatty acid composition assessed by food diary and serum and incident prostate cancer or “any” cancer in 2,002 middle-aged men free of cancer at baseline and during the first 4 years of follow up.
During 12.6 years of follow up, 46 men developed prostate cancer and 151 any cancer.
Data analysis showed that men with serum linoleic acid, n-6 fatty acids, and polyunsaturated fatty acids (PUFAs) in the upper tertile were “less than one-third” as likely to develop prostate cancer during follow up as those with levels in the lowest tertile.
The association held after adjustment for socioeconomic status, physical activity, obesity, and insulin concentrations.
Dietary linoleic acid intake obtained from 4-day food records also “tended to be inversely associated with incident prostate cancer,” with an age-adjusted relative risk of 0.55 for the upper vs the lower tertile.
The team also found “similar but weaker” associations with any cancer.
Dr. Laaksonen and colleagues conclude, “Substitution of linoleic acid for saturated fat in middle-aged men consuming a high saturated-fat diet may decrease the risk of prostate and other cancers,” although they acknowledge that other nutrients associated with vegetable fats may be responsible for the protective effect.
Int J Cancer 2004;111:444-450.
Thanks to Reuters Health
Liposomal vit E Formulated
Liposomal Formulated-dl-alpha Tocopherol :Mammary Tumor
#C164 Liposomal Formulated dl-alpha-Tocopherol Acetate Administered by Aerosol or Gavage Reduce Syngeneic Mouse Mammary Tumor Burden and Metastasis.
Weiping Yu, Li Jia, Bob G. Sanders, Kimberly Kline, Univ. of Texas, Austin, TX.
Synthetic vitamin E, dl-alpha-tocopherol, and its derivative dl-alpha-tocopherol acetate, commonly used as dietary supplements, are ineffective in preventing tumor cell growth in culture, and show inconsistent results when used as chemopreventive agents in chemically-induced mammary cancer in rats.
In this paper, we compare the antitumor properties of liposomal formulations of these two forms of vitamin E to alpha-TEA, a novel vitamin E analog with established anti-cancer properties in vitro, and in vivo (Kawson, K.A., et al. Mol. Cancer Therap. 2:437-44, 2003).
In comparison to alpha-TEA, the two synthetic vitamin E forms are ineffective in preventing growth of human breast cancer cells or Balb/c 66cl-4-GFP mammary cancer cells in vitro.
However, liposomal formulated dl-alpha-tocopherol and dl-alpha-tocoperol acetate administered by aerosol or orally by gavage to Balb/c mice transplanted with 66cl-4-GFP tumor cells significantly inhibited tumor burden and lung and lymph node metastasis in a manner similar to alpha-TEA.
Liposomal formulated dl-alpha-tocopherol or dl-alpha-tocopherol acetate delivered by aerosol or gavatge reduced tumor volume by 65 and 33% and by 56 and 38%, respectively.
Visible lung metastases were reduced by 82 and 46% when dl-alpha-tocopherol and dl-alpha-tocopherol acetate were administered by aerosol and 100 and 57% when administered by gavage.
Liposomal formulated dl-alpha-tocopherol acetate administered by gavage reduced lung micrometastases by 77 and 70% and reduced lymph nod metastases by 64% and 57%, respectively.
Immunohistological analyses of tumor sections from dl-alpha-tocopherol or dl-alpha-tocopherol acetate treated mice each showed a 53% reduction of expression of endothelial antigen CD31, an indicator of small capillaries in primary tumor tissue.
alpha-TEA showed a 60% reduction of CD31 staining.
Analyses of tumor sections from dl-alpha-tocopherol and dl-alpha-tocopherol acetate gavage treated mice by TUNEL for apoptosis and Ki-67 staining for cell proliferation showed 387 and 32% enhanced apoptosis and 39 and 25% reduction in Ki-67, respectively.
Tumor sections from alpha-TEA treated mice showed 44% increase in apoptosis and 39% decrease in cell proliferation. Based on these data, we conclude that dl-alpha-tocopherol and dl-alpha-tocopherol acetate inhibition of tumor growth is similar to alpha-TEA.
In contrast to dl-alpha-tocopherol and dl-alpha-tocopherol acetate, RRR-alpha-tocopherol, a naturally occurring form of tocopherol, shows little to no anti-tumor activity in the 66cl-4-GFP tumor model when formulated in liposomes and administered by aerosol or gavage.
Since the dl-form of vitamin E is composed of 8 stereoisomers with RRR-alpha-tocopherol representing 1/8 of the forms, these data suggest that dl-alpha-tocopherol stereoisomers other than RRR-alpha-tocopherol are involved in the antitumor activity of these two compounds.
Supported by CA59739 and the Foundations for Research.
Frontiers in Cancer Prevention Research, 2203
AACR
Liposomal Formulated-dl-alpha Tocopherol :Mammary Tumor
#C164 Liposomal Formulated dl-alpha-Tocopherol Acetate Administered by Aerosol or Gavage Reduce Syngeneic Mouse Mammary Tumor Burden and Metastasis.
Weiping Yu, Li Jia, Bob G. Sanders, Kimberly Kline, Univ. of Texas, Austin, TX.
Synthetic vitamin E, dl-alpha-tocopherol, and its derivative dl-alpha-tocopherol acetate, commonly used as dietary supplements, are ineffective in preventing tumor cell growth in culture, and show inconsistent results when used as chemopreventive agents in chemically-induced mammary cancer in rats.
In this paper, we compare the antitumor properties of liposomal formulations of these two forms of vitamin E to alpha-TEA, a novel vitamin E analog with established anti-cancer properties in vitro, and in vivo (Kawson, K.A., et al. Mol. Cancer Therap. 2:437-44, 2003).
In comparison to alpha-TEA, the two synthetic vitamin E forms are ineffective in preventing growth of human breast cancer cells or Balb/c 66cl-4-GFP mammary cancer cells in vitro.
However, liposomal formulated dl-alpha-tocopherol and dl-alpha-tocoperol acetate administered by aerosol or orally by gavage to Balb/c mice transplanted with 66cl-4-GFP tumor cells significantly inhibited tumor burden and lung and lymph node metastasis in a manner similar to alpha-TEA.
Liposomal formulated dl-alpha-tocopherol or dl-alpha-tocopherol acetate delivered by aerosol or gavatge reduced tumor volume by 65 and 33% and by 56 and 38%, respectively.
Visible lung metastases were reduced by 82 and 46% when dl-alpha-tocopherol and dl-alpha-tocopherol acetate were administered by aerosol and 100 and 57% when administered by gavage.
Liposomal formulated dl-alpha-tocopherol acetate administered by gavage reduced lung micrometastases by 77 and 70% and reduced lymph nod metastases by 64% and 57%, respectively.
Immunohistological analyses of tumor sections from dl-alpha-tocopherol or dl-alpha-tocopherol acetate treated mice each showed a 53% reduction of expression of endothelial antigen CD31, an indicator of small capillaries in primary tumor tissue.
alpha-TEA showed a 60% reduction of CD31 staining.
Analyses of tumor sections from dl-alpha-tocopherol and dl-alpha-tocopherol acetate gavage treated mice by TUNEL for apoptosis and Ki-67 staining for cell proliferation showed 387 and 32% enhanced apoptosis and 39 and 25% reduction in Ki-67, respectively.
Tumor sections from alpha-TEA treated mice showed 44% increase in apoptosis and 39% decrease in cell proliferation. Based on these data, we conclude that dl-alpha-tocopherol and dl-alpha-tocopherol acetate inhibition of tumor growth is similar to alpha-TEA.
In contrast to dl-alpha-tocopherol and dl-alpha-tocopherol acetate, RRR-alpha-tocopherol, a naturally occurring form of tocopherol, shows little to no anti-tumor activity in the 66cl-4-GFP tumor model when formulated in liposomes and administered by aerosol or gavage.
Since the dl-form of vitamin E is composed of 8 stereoisomers with RRR-alpha-tocopherol representing 1/8 of the forms, these data suggest that dl-alpha-tocopherol stereoisomers other than RRR-alpha-tocopherol are involved in the antitumor activity of these two compounds.
Supported by CA59739 and the Foundations for Research.
Frontiers in Cancer Prevention Research, 2203
AACR
Lycopene and Chemotherapy
Lycopene and Chemotherapy Toxicity Kazim Sahin 1, Nurhan Sahin, Omer Kucuk
PMID: 20924974 DOI: 10.1080/01635581.2010.509838
Abstract
Antineoplastic agents induce the production of free radicals and other reactive oxygen species (ROS) in biological systems. Cytotoxic effects of antineoplastic drugs depend on rapid proliferation of cancer cells. Oxidative stress occurring during chemotherapy may potentially interfere with these effects through reducing the rate of cell proliferation. ROS may also contribute to side effects that occur with chemotherapeutic agents such as doxorubicin-induced cardiotoxicity, cisplatin-induced nephrotoxicity, and bleomycin- induced pulmonary fibrosis. Lycopene is a major carotenoid present in tomatoes, and it is a potent antioxidant that may provide protection against cellular damage caused by ROS. Lycopene may reduce or prevent the side effects of chemotherapy due to its antioxidant and anti-inflammatory properties. This review focuses on the protective effects of lycopene against antineoplastic agent induced toxicity.
Lycopene and Chemotherapy Toxicity Kazim Sahin 1, Nurhan Sahin, Omer Kucuk
PMID: 20924974 DOI: 10.1080/01635581.2010.509838
Abstract
Antineoplastic agents induce the production of free radicals and other reactive oxygen species (ROS) in biological systems. Cytotoxic effects of antineoplastic drugs depend on rapid proliferation of cancer cells. Oxidative stress occurring during chemotherapy may potentially interfere with these effects through reducing the rate of cell proliferation. ROS may also contribute to side effects that occur with chemotherapeutic agents such as doxorubicin-induced cardiotoxicity, cisplatin-induced nephrotoxicity, and bleomycin- induced pulmonary fibrosis. Lycopene is a major carotenoid present in tomatoes, and it is a potent antioxidant that may provide protection against cellular damage caused by ROS. Lycopene may reduce or prevent the side effects of chemotherapy due to its antioxidant and anti-inflammatory properties. This review focuses on the protective effects of lycopene against antineoplastic agent induced toxicity.
Micronutrients Predict Risk of Bca
Micronutrients Predict Risk of Bca
Serum Levels of Micronutrients, Antioxidants and Total Antioxidant Status Predict Risk of Breast Cancer in a Case Control Study.
Ching S, Ingram D, Hahnel R, Beilby J, Rossi EDepartment of Clinical Biochemistry, PathCentre, Nedlands, Western Australia, 6009, Breast Centre, Sir Charles Gairdner Hospital and. Centre for Molecular Immunology and Instrumentation, University of Western Australia, QE II Medical Centre, Nedlands, Western Australia, 6009.
We performed a case control study to assess the association between serum micronutrient and antioxidant levels and the risk of breast cancer. Newly diagnosed breast cancer cases were recruited before any treatment and matched with controls randomly selected from the electoral roll. Blood samples were collected from 153 breast cancer cases and 151 controls. Serum samples were analyzed for retinol, alpha-tocopherol, lycopene, alpha- and beta-carotene by HPLC, and total antioxidant status by the Trolox-equivalent antioxidant assay. Serum albumin, bilirubin and uric acid levels were also determined.
After adjustment for age at menarche, parity, dietary fat and alcohol intake, we observed the following reductions in odds ratios for breast cancer risk comparing the highest with the lowest quartiles: 0.47 [95% confidence interval (CI) 0.24, 0.91] for Beta-carotene; 0.53 (CI 0.28, 1.01) for retinol; 0.50 (CI 0.26, 0.97) for bilirubin and 0.47 (CI 0.24, 0.94) for total antioxidant status.
We conclude that increased serum levels of beta-carotene, retinol, bilirubin and total antioxidant status are associated with reductions in breast cancer risk.
J Nutr 2002 Feb;132(2):303-306
PMID: 11823595
Oncol Rep, 24 (4), 815-28 Oct 2010
Nutrition in Oncology: The Case of Micronutrients (Review) Alexander Ströhle, Kurt Zänker, Andreas Hahn PMID:20811659 DOI:10.3892/or.2010.815
Abstract
In the course of cancer disease, many oncological patients develop tumor-associated malnutrition characterized by an insufficient supply of macro- and micronutrients. The inadequate nutritional status and the cancer anorexia-cachexia syndrome related to it are clinically relevant, as the response to antineoplastic measures, such as radiation and chemotherapy, is diminished, their side effects aggravated and the patient's quality of life and prognosis negatively affected. Therefore, the supportive nutrition care of oncological patients is of central importance. In this context, vitamins, minerals and long-chain omega -3 fatty acids are becoming more and more relevant in oncology although the benefit of such supplements is discussed controversially. Starting from a description of the enteropathogenesis and the pathophysiological consequences of cancer-associated malnutrition, the present study provides an overview of the importance of micronutrients for oncological patients. In the case of reduced food intake and/or inappropriate food choice the use of a multi-vitamin- multimineral supplement administered in physiological doses, i.e. nutrient quantities approximately corresponding to the recommended daily allowances, can be generally recommended. However, to enhance postoperative wound healing, it seems that cancer patients require higher amounts of micronutrients than healthy individuals. Because vitamin D deficiency is highly prevalent in oncological patients, improvement of vitamin D status is of special interest.
Micronutrients Predict Risk of Bca
Serum Levels of Micronutrients, Antioxidants and Total Antioxidant Status Predict Risk of Breast Cancer in a Case Control Study.
Ching S, Ingram D, Hahnel R, Beilby J, Rossi EDepartment of Clinical Biochemistry, PathCentre, Nedlands, Western Australia, 6009, Breast Centre, Sir Charles Gairdner Hospital and. Centre for Molecular Immunology and Instrumentation, University of Western Australia, QE II Medical Centre, Nedlands, Western Australia, 6009.
We performed a case control study to assess the association between serum micronutrient and antioxidant levels and the risk of breast cancer. Newly diagnosed breast cancer cases were recruited before any treatment and matched with controls randomly selected from the electoral roll. Blood samples were collected from 153 breast cancer cases and 151 controls. Serum samples were analyzed for retinol, alpha-tocopherol, lycopene, alpha- and beta-carotene by HPLC, and total antioxidant status by the Trolox-equivalent antioxidant assay. Serum albumin, bilirubin and uric acid levels were also determined.
After adjustment for age at menarche, parity, dietary fat and alcohol intake, we observed the following reductions in odds ratios for breast cancer risk comparing the highest with the lowest quartiles: 0.47 [95% confidence interval (CI) 0.24, 0.91] for Beta-carotene; 0.53 (CI 0.28, 1.01) for retinol; 0.50 (CI 0.26, 0.97) for bilirubin and 0.47 (CI 0.24, 0.94) for total antioxidant status.
We conclude that increased serum levels of beta-carotene, retinol, bilirubin and total antioxidant status are associated with reductions in breast cancer risk.
J Nutr 2002 Feb;132(2):303-306
PMID: 11823595
Oncol Rep, 24 (4), 815-28 Oct 2010
Nutrition in Oncology: The Case of Micronutrients (Review) Alexander Ströhle, Kurt Zänker, Andreas Hahn PMID:20811659 DOI:10.3892/or.2010.815
Abstract
In the course of cancer disease, many oncological patients develop tumor-associated malnutrition characterized by an insufficient supply of macro- and micronutrients. The inadequate nutritional status and the cancer anorexia-cachexia syndrome related to it are clinically relevant, as the response to antineoplastic measures, such as radiation and chemotherapy, is diminished, their side effects aggravated and the patient's quality of life and prognosis negatively affected. Therefore, the supportive nutrition care of oncological patients is of central importance. In this context, vitamins, minerals and long-chain omega -3 fatty acids are becoming more and more relevant in oncology although the benefit of such supplements is discussed controversially. Starting from a description of the enteropathogenesis and the pathophysiological consequences of cancer-associated malnutrition, the present study provides an overview of the importance of micronutrients for oncological patients. In the case of reduced food intake and/or inappropriate food choice the use of a multi-vitamin- multimineral supplement administered in physiological doses, i.e. nutrient quantities approximately corresponding to the recommended daily allowances, can be generally recommended. However, to enhance postoperative wound healing, it seems that cancer patients require higher amounts of micronutrients than healthy individuals. Because vitamin D deficiency is highly prevalent in oncological patients, improvement of vitamin D status is of special interest.
RAND CORPORATION UNFAIRLY SMEARS FISH OIL PILLS
RAND CORPORATION UNFAIRLY SMEARS FISH OIL PILLS; CALL FOR WITHDRAWAL OF BOGUS STUDY
Following an analysis of 38 previously published studies involving the dietary consumption of omega-3 fish oil and the incidence of cancer, Rand Corporation investigators falsely conclude that omega-3 fish oil pills are of useless value in preventing cancer, when no fish oil pills were used in any of the assessed studies.
The flaw in the widely publicized Rand study, published in the January 25, 2006 issue of the Journal of the American Medical Association, apparently escaped scrutiny by peer reviewers at the journal. Journal editors have been asked to withdraw the study.
The stated claims of the study, to assess omega-3 fatty acid-containing dietary supplements (that) have appeared on the market claiming to protect against the development of a variety of conditions including cancer and the actual study itself, which analyzed 38 articles with a description of effects of consumption of omega-3 fatty acids on tumor incidence, all which were dietary intake studies, mistakenly concluded that dietary supplementation with omega-3 fatty acids is unlikely to reduce the risk of cancer.
Commercially produced omega-3 fish oil supplements differ from fresh fish in that they do not contain detectable amounts of mercury. [Archives Pathology Laboratory Medicine 127: 1603-05, 2003; 129: 74-77, 2005]
The mercury content of fresh fish is believed to negate some of the health benefits of omega-3 oils.[Arteriosclerosis Thrombosis Vascular Biology 25: 228-33, 2005]
Mercury is known to stimulate the growth of cancer cells. [Environmental Toxicology 20: 32-44, 2005; Endocrinology 144: 2425-36, 2003] For example, exposure to mercury from industrial pollution in Japan increased the risk for leukemia (cancer of the blood) by 8 times. [Journal Epidemiology 6: 134-38, 1996]
Furthermore, fish oil may not significantly reduce the risk for cancer, but may reduce cancer mortality rates. In one study, fish consumption only protected against later stages of cancer, not the initiation of cancer. [European Journal Cancer Prevention 4: 329-32, 1995]
Omega-3 oils appear to protect against metastasis (spread of cancer to other organs), which is the primary cause of death among cancer patients. [In Vivo 8: 371-74, 1994]
It is widely known that most senior-aged males harbor cancer cells in their prostate glands, but an autopsy of 61 deceased male Eskimo (Inuit) men, who are known to consume high amounts of omega-3 fish oil, found only 1 case of the invasive mortal-type of prostate cancer. [Cancer Epidemiology Biomarkers Prevention 12: 926-27, 2003]
Omega-3 oils are also known to prolong survival among individuals who have developed cancer. [Cancer 82: 395-402, 1998] Omega-3 fish oils have also been shown to improve the efficacy of anti-cancer drugs. [Journal Nutrition 134:3427S-3430S, 2004]
Recently a remarkable report was published in the Journal of Nutrition & Cancer which cited the case of a 78-year old male with a malignant form of cancer (fibrous histiocytoma), with tumor masses in both lungs, who declined conventional chemotherapy and elected to solely consume omega-3 oils (15,000 milligrams/day) as treatment.
A remarkably slow and steady decrease in the size and number of tumors was carefully documented by his doctors. The man experienced no side effects and remains symptom-free from cancer. [Nutrition & Cancer 52: 121-29, 2005]
Source: Bill Sardi, Knowledge of Health, Inc., 1/06
Response to: Press Release: Journal Am. Med. Assn. (JAMA. 2006;295:403-415) Consumption of Omega-3 Fatty Acids Unlikely to Reduce Cancer Risk
Ann’s NOTE: It is well known that Parsley. Cilantro and/or Dandelion leaves can help the body DETOX heavy metals including mercury. Isn’t it interesting that fish is so often garnished with parsley?
RAND CORPORATION UNFAIRLY SMEARS FISH OIL PILLS; CALL FOR WITHDRAWAL OF BOGUS STUDY
Following an analysis of 38 previously published studies involving the dietary consumption of omega-3 fish oil and the incidence of cancer, Rand Corporation investigators falsely conclude that omega-3 fish oil pills are of useless value in preventing cancer, when no fish oil pills were used in any of the assessed studies.
The flaw in the widely publicized Rand study, published in the January 25, 2006 issue of the Journal of the American Medical Association, apparently escaped scrutiny by peer reviewers at the journal. Journal editors have been asked to withdraw the study.
The stated claims of the study, to assess omega-3 fatty acid-containing dietary supplements (that) have appeared on the market claiming to protect against the development of a variety of conditions including cancer and the actual study itself, which analyzed 38 articles with a description of effects of consumption of omega-3 fatty acids on tumor incidence, all which were dietary intake studies, mistakenly concluded that dietary supplementation with omega-3 fatty acids is unlikely to reduce the risk of cancer.
Commercially produced omega-3 fish oil supplements differ from fresh fish in that they do not contain detectable amounts of mercury. [Archives Pathology Laboratory Medicine 127: 1603-05, 2003; 129: 74-77, 2005]
The mercury content of fresh fish is believed to negate some of the health benefits of omega-3 oils.[Arteriosclerosis Thrombosis Vascular Biology 25: 228-33, 2005]
Mercury is known to stimulate the growth of cancer cells. [Environmental Toxicology 20: 32-44, 2005; Endocrinology 144: 2425-36, 2003] For example, exposure to mercury from industrial pollution in Japan increased the risk for leukemia (cancer of the blood) by 8 times. [Journal Epidemiology 6: 134-38, 1996]
Furthermore, fish oil may not significantly reduce the risk for cancer, but may reduce cancer mortality rates. In one study, fish consumption only protected against later stages of cancer, not the initiation of cancer. [European Journal Cancer Prevention 4: 329-32, 1995]
Omega-3 oils appear to protect against metastasis (spread of cancer to other organs), which is the primary cause of death among cancer patients. [In Vivo 8: 371-74, 1994]
It is widely known that most senior-aged males harbor cancer cells in their prostate glands, but an autopsy of 61 deceased male Eskimo (Inuit) men, who are known to consume high amounts of omega-3 fish oil, found only 1 case of the invasive mortal-type of prostate cancer. [Cancer Epidemiology Biomarkers Prevention 12: 926-27, 2003]
Omega-3 oils are also known to prolong survival among individuals who have developed cancer. [Cancer 82: 395-402, 1998] Omega-3 fish oils have also been shown to improve the efficacy of anti-cancer drugs. [Journal Nutrition 134:3427S-3430S, 2004]
Recently a remarkable report was published in the Journal of Nutrition & Cancer which cited the case of a 78-year old male with a malignant form of cancer (fibrous histiocytoma), with tumor masses in both lungs, who declined conventional chemotherapy and elected to solely consume omega-3 oils (15,000 milligrams/day) as treatment.
A remarkably slow and steady decrease in the size and number of tumors was carefully documented by his doctors. The man experienced no side effects and remains symptom-free from cancer. [Nutrition & Cancer 52: 121-29, 2005]
Source: Bill Sardi, Knowledge of Health, Inc., 1/06
Response to: Press Release: Journal Am. Med. Assn. (JAMA. 2006;295:403-415) Consumption of Omega-3 Fatty Acids Unlikely to Reduce Cancer Risk
Ann’s NOTE: It is well known that Parsley. Cilantro and/or Dandelion leaves can help the body DETOX heavy metals including mercury. Isn’t it interesting that fish is so often garnished with parsley?
Resveratrol articles
Resveratrol-induced apoptotic death in human U251 glioma cells
Hao Jiang1,4,5, Lijie Zhang1,4, Jarret Kuo1,4, Kelly Kuo1, Subhash C. Gautam2, Laurent Groc1, Alba I. Rodriguez1,4, David Koubi1, Tangella Jackson Hunter1, George B. Corcoran6, Michael D. Seidman3,4 and Robert A. Levine1,4,5,6
1 William T. Gossett Neurology Laboratories, Departments of 2 Surgery and 3 Otolaryngology Research, and 4 Complementary and Integrative Medicine Program, Henry Ford Health System; 5 John D. Dingell VA Medical Center; and 6 Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan
Requests for reprints: Robert A. Levine, William T. Gossett Neurology Laboratories, Henry Ford Health System, One Ford Place, Detroit, MI 48202. Phone: 313-874-3771; Fax: 313-874-3770. E-mail: bob- levine@earthlink.net
Resveratrol (trans-3,4′,5-trihydroxystilbene) is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Resveratrol has antiinflammatory and antioxidant properties, and also has potent anticancer properties.
Human glioma U251 cells were used to understand the molecular mechanisms by which resveratrol acts as an anticancer agent, since glioma is a particularly difficult cancer to treat and eradicate.
Our data show that resveratrol induces dose- and time-dependent death of U251 cells, as measured by lactate dehydrogenase release and internucleosomal DNA fragmentation assays. Resveratrol induces activation of caspase-3 and increases the cleavage of the downstream caspase substrate, poly(ADP-ribose) polymerase.
Resveratrol-induced DNA fragmentation can be completely blocked by either a general caspase inhibitor (Z-VAD-FMK) or a selective caspase-3 inhibitor (Z-DEVD-FMK), but not by a selective caspase-1 inhibitor. Resveratrol induces cytochrome c release from mitochondria to the cytoplasm and activation of caspase-9.
Resveratrol also increases expression of proapoptotic Bax and its translocation to the mitochondria. Resveratrol inhibits U251 proliferation, as measured by MTS assay [3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], and induces G0/G1 growth arrest, as determined by flow cytometry.
The cyclin-dependent kinase inhibitor, olomoucine, prevents cell cycle progression and resveratrol-induced apoptosis.
These results suggest that multiple signaling pathways may underlie the apoptotic death of U251 glioma induced by resveratrol, which warrants further exploration as an anticancer agent in human glioma.
Mol Cancer Ther. 2005;4:554-561
Ann’s NOTE: You can find more information on resveratrol by going to the Studies section (left side of any page), then Nutrition area or SEARCH on our site.
Abstract
Owing to their antimicrobial, antioxidant, and anti-inflammatory activity, grapes (Vitis vinifera L.) are the archetypal paradigms of fruits used not only for nutritional purposes, but also for exclusive therapeutics. Grapes are a prominent and promising source of phytochemicals, especially resveratrol, a phytoalexin antioxidant found in red grapes which has both chemo preventive and therapeutic effects against various ailments. Resveratrol's role in reducing different human cancers, including breast, cervical, uterine, blood, kidney, liver, eye, bladder, thyroid, esophageal, prostate, brain, lung, skin, gastric, colon, head and neck, bone, ovarian, and cervical, has been reviewed. This review covers the literature that deals with the anti-cancer mechanism of resveratrol with special reference to antioxidant potential. Furthermore, this article summarizes the literature pertaining to resveratrol as an anti-cancer agent.
Crit Rev Food Sci Nutri, 58 (9), 1428-1447 2018 Jun 13
Resveratrol as an Anti-Cancer Agent: A Review Abdur Rauf 1, Muhammad Imran 2, Masood Sadiq Butt 3, Muhammad Nadeem 4, Dennis G Peters 5, Mohammad S Mubarak 6
____________________________________________________________________________________________________
Besides chemo preventive effects, resveratrol appears to exhibit therapeutic effects against cancer. Limited data in humans have revealed that resveratrol is pharmacologically quite safe. Currently, structural analogues of resveratrol with improved bioavailability are being pursued as potential therapeutic agents for cancer.
Anticancer Res , 24 (5A), 2783-840 Sep-Oct 2004 Role of Resveratrol in Prevention and Therapy of Cancer: Preclinical and Clinical Studies
Resveratrol-induced apoptotic death in human U251 glioma cells
Hao Jiang1,4,5, Lijie Zhang1,4, Jarret Kuo1,4, Kelly Kuo1, Subhash C. Gautam2, Laurent Groc1, Alba I. Rodriguez1,4, David Koubi1, Tangella Jackson Hunter1, George B. Corcoran6, Michael D. Seidman3,4 and Robert A. Levine1,4,5,6
1 William T. Gossett Neurology Laboratories, Departments of 2 Surgery and 3 Otolaryngology Research, and 4 Complementary and Integrative Medicine Program, Henry Ford Health System; 5 John D. Dingell VA Medical Center; and 6 Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan
Requests for reprints: Robert A. Levine, William T. Gossett Neurology Laboratories, Henry Ford Health System, One Ford Place, Detroit, MI 48202. Phone: 313-874-3771; Fax: 313-874-3770. E-mail: bob- levine@earthlink.net
Resveratrol (trans-3,4′,5-trihydroxystilbene) is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Resveratrol has antiinflammatory and antioxidant properties, and also has potent anticancer properties.
Human glioma U251 cells were used to understand the molecular mechanisms by which resveratrol acts as an anticancer agent, since glioma is a particularly difficult cancer to treat and eradicate.
Our data show that resveratrol induces dose- and time-dependent death of U251 cells, as measured by lactate dehydrogenase release and internucleosomal DNA fragmentation assays. Resveratrol induces activation of caspase-3 and increases the cleavage of the downstream caspase substrate, poly(ADP-ribose) polymerase.
Resveratrol-induced DNA fragmentation can be completely blocked by either a general caspase inhibitor (Z-VAD-FMK) or a selective caspase-3 inhibitor (Z-DEVD-FMK), but not by a selective caspase-1 inhibitor. Resveratrol induces cytochrome c release from mitochondria to the cytoplasm and activation of caspase-9.
Resveratrol also increases expression of proapoptotic Bax and its translocation to the mitochondria. Resveratrol inhibits U251 proliferation, as measured by MTS assay [3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], and induces G0/G1 growth arrest, as determined by flow cytometry.
The cyclin-dependent kinase inhibitor, olomoucine, prevents cell cycle progression and resveratrol-induced apoptosis.
These results suggest that multiple signaling pathways may underlie the apoptotic death of U251 glioma induced by resveratrol, which warrants further exploration as an anticancer agent in human glioma.
Mol Cancer Ther. 2005;4:554-561
Ann’s NOTE: You can find more information on resveratrol by going to the Studies section (left side of any page), then Nutrition area or SEARCH on our site.
Abstract
Owing to their antimicrobial, antioxidant, and anti-inflammatory activity, grapes (Vitis vinifera L.) are the archetypal paradigms of fruits used not only for nutritional purposes, but also for exclusive therapeutics. Grapes are a prominent and promising source of phytochemicals, especially resveratrol, a phytoalexin antioxidant found in red grapes which has both chemo preventive and therapeutic effects against various ailments. Resveratrol's role in reducing different human cancers, including breast, cervical, uterine, blood, kidney, liver, eye, bladder, thyroid, esophageal, prostate, brain, lung, skin, gastric, colon, head and neck, bone, ovarian, and cervical, has been reviewed. This review covers the literature that deals with the anti-cancer mechanism of resveratrol with special reference to antioxidant potential. Furthermore, this article summarizes the literature pertaining to resveratrol as an anti-cancer agent.
Crit Rev Food Sci Nutri, 58 (9), 1428-1447 2018 Jun 13
Resveratrol as an Anti-Cancer Agent: A Review Abdur Rauf 1, Muhammad Imran 2, Masood Sadiq Butt 3, Muhammad Nadeem 4, Dennis G Peters 5, Mohammad S Mubarak 6
____________________________________________________________________________________________________
Besides chemo preventive effects, resveratrol appears to exhibit therapeutic effects against cancer. Limited data in humans have revealed that resveratrol is pharmacologically quite safe. Currently, structural analogues of resveratrol with improved bioavailability are being pursued as potential therapeutic agents for cancer.
Anticancer Res , 24 (5A), 2783-840 Sep-Oct 2004 Role of Resveratrol in Prevention and Therapy of Cancer: Preclinical and Clinical Studies
Resveratrol 2005
Resveratrol-induced apoptotic death in human U251 glioma cells
Hao Jiang1,4,5, Lijie Zhang1,4, Jarret Kuo1,4, Kelly Kuo1, Subhash C. Gautam2, Laurent Groc1, Alba I. Rodriguez1,4, David Koubi1, Tangella Jackson Hunter1, George B. Corcoran6, Michael D. Seidman3,4 and Robert A. Levine1,4,5,6
1 William T. Gossett Neurology Laboratories, Departments of 2 Surgery and 3 Otolaryngology Research, and4 Complementary and Integrative Medicine Program, Henry Ford Health System; 5 John D. Dingell VA Medical Center; and 6 Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan
Requests for reprints: Robert A. Levine, William T. Gossett Neurology Laboratories, Henry Ford Health System, One Ford Place, Detroit, MI 48202. Phone: 313-874-3771; Fax: 313-874-3770. E-mail: bob-levine@earthlink.net
Resveratrol (trans-3,4′,5-trihydroxystilbene) is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Resveratrol has antiinflammatory and antioxidant properties, and also has potent anticancer properties.
Human glioma U251 cells were used to understand the molecular mechanisms by which resveratrol acts as an anticancer agent, since glioma is a particularly difficult cancer to treat and eradicate.
Our data show that resveratrol induces dose- and time-dependent death of U251 cells, as measured by lactate dehydrogenase release and internucleosomal DNA fragmentation assays. Resveratrol induces activation of caspase-3 and increases the cleavage of the downstream caspase substrate, poly(ADP-ribose) polymerase.
Resveratrol-induced DNA fragmentation can be completely blocked by either a general caspase inhibitor (Z-VAD-FMK) or a selective caspase-3 inhibitor (Z-DEVD-FMK), but not by a selective caspase-1 inhibitor. Resveratrol induces cytochrome c release from mitochondria to the cytoplasm and activation of caspase-9.
Resveratrol also increases expression of proapoptotic Bax and its translocation to the mitochondria. Resveratrol inhibits U251 proliferation, as measured by MTS assay [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], and induces G0/G1 growth arrest, as determined by flow cytometry.
The cyclin-dependent kinase inhibitor, olomoucine, prevents cell cycle progression and resveratrol-induced apoptosis.
These results suggest that multiple signaling pathways may underlie the apoptotic death of U251 glioma induced by resveratrol, which warrants further exploration as an anticancer agent in human glioma.
Mol Cancer Ther. 2005;4:554-561
Ann’s NOTE: You can find more information on resveratrol by going to the Studies section (left side of any page), then Nutrition area or SEARCH on our site.
Abstract
Owing to their antimicrobial, antioxidant, and anti-inflammatory activity, grapes (Vitis vinifera L.) are the archetypal paradigms of fruits used not only for nutritional purposes, but also for exclusive therapeutics. Grapes are a prominent and promising source of phytochemicals, especially resveratrol, a phytoalexin antioxidant found in red grapes which has both chemopreventive and therapeutic effects against various ailments. Resveratrol's role in reducing different human cancers, including breast, cervical, uterine, blood, kidney, liver, eye, bladder, thyroid, esophageal, prostate, brain, lung, skin, gastric, colon, head and neck, bone, ovarian, and cervical, has been reviewed. This review covers the literature that deals with the anti-cancer mechanism of resveratrol with special reference to antioxidant potential. Furthermore, this article summarizes the literature pertaining to resveratrol as an anti-cancer agent.
Crit Rev Food Sci Nutri, 58 (9), 1428-1447 2018 Jun 13
Resveratrol as an Anti-Cancer Agent: A Review Abdur Rauf 1, Muhammad Imran 2, Masood Sadiq Butt 3, Muhammad Nadeem 4, Dennis G Peters 5, Mohammad S Mubarak 6
____________________________________________________________________________________________________
Besides chemopreventive effects, resveratrol appears to exhibit therapeutic effects against cancer. Limited data in humans have revealed that resveratrol is pharmacologically quite safe. Currently, structural analogues of resveratrol with improved bioavailability are being pursued as potential therapeutic agents for cancer.
Anticancer Res , 24 (5A), 2783-840 Sep-Oct 2004 Role of Resveratrol in Prevention and Therapy of Cancer: Preclinical and Clinical Studies
Resveratrol-induced apoptotic death in human U251 glioma cells
Hao Jiang1,4,5, Lijie Zhang1,4, Jarret Kuo1,4, Kelly Kuo1, Subhash C. Gautam2, Laurent Groc1, Alba I. Rodriguez1,4, David Koubi1, Tangella Jackson Hunter1, George B. Corcoran6, Michael D. Seidman3,4 and Robert A. Levine1,4,5,6
1 William T. Gossett Neurology Laboratories, Departments of 2 Surgery and 3 Otolaryngology Research, and4 Complementary and Integrative Medicine Program, Henry Ford Health System; 5 John D. Dingell VA Medical Center; and 6 Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan
Requests for reprints: Robert A. Levine, William T. Gossett Neurology Laboratories, Henry Ford Health System, One Ford Place, Detroit, MI 48202. Phone: 313-874-3771; Fax: 313-874-3770. E-mail: bob-levine@earthlink.net
Resveratrol (trans-3,4′,5-trihydroxystilbene) is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Resveratrol has antiinflammatory and antioxidant properties, and also has potent anticancer properties.
Human glioma U251 cells were used to understand the molecular mechanisms by which resveratrol acts as an anticancer agent, since glioma is a particularly difficult cancer to treat and eradicate.
Our data show that resveratrol induces dose- and time-dependent death of U251 cells, as measured by lactate dehydrogenase release and internucleosomal DNA fragmentation assays. Resveratrol induces activation of caspase-3 and increases the cleavage of the downstream caspase substrate, poly(ADP-ribose) polymerase.
Resveratrol-induced DNA fragmentation can be completely blocked by either a general caspase inhibitor (Z-VAD-FMK) or a selective caspase-3 inhibitor (Z-DEVD-FMK), but not by a selective caspase-1 inhibitor. Resveratrol induces cytochrome c release from mitochondria to the cytoplasm and activation of caspase-9.
Resveratrol also increases expression of proapoptotic Bax and its translocation to the mitochondria. Resveratrol inhibits U251 proliferation, as measured by MTS assay [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], and induces G0/G1 growth arrest, as determined by flow cytometry.
The cyclin-dependent kinase inhibitor, olomoucine, prevents cell cycle progression and resveratrol-induced apoptosis.
These results suggest that multiple signaling pathways may underlie the apoptotic death of U251 glioma induced by resveratrol, which warrants further exploration as an anticancer agent in human glioma.
Mol Cancer Ther. 2005;4:554-561
Ann’s NOTE: You can find more information on resveratrol by going to the Studies section (left side of any page), then Nutrition area or SEARCH on our site.
Abstract
Owing to their antimicrobial, antioxidant, and anti-inflammatory activity, grapes (Vitis vinifera L.) are the archetypal paradigms of fruits used not only for nutritional purposes, but also for exclusive therapeutics. Grapes are a prominent and promising source of phytochemicals, especially resveratrol, a phytoalexin antioxidant found in red grapes which has both chemopreventive and therapeutic effects against various ailments. Resveratrol's role in reducing different human cancers, including breast, cervical, uterine, blood, kidney, liver, eye, bladder, thyroid, esophageal, prostate, brain, lung, skin, gastric, colon, head and neck, bone, ovarian, and cervical, has been reviewed. This review covers the literature that deals with the anti-cancer mechanism of resveratrol with special reference to antioxidant potential. Furthermore, this article summarizes the literature pertaining to resveratrol as an anti-cancer agent.
Crit Rev Food Sci Nutri, 58 (9), 1428-1447 2018 Jun 13
Resveratrol as an Anti-Cancer Agent: A Review Abdur Rauf 1, Muhammad Imran 2, Masood Sadiq Butt 3, Muhammad Nadeem 4, Dennis G Peters 5, Mohammad S Mubarak 6
____________________________________________________________________________________________________
Besides chemopreventive effects, resveratrol appears to exhibit therapeutic effects against cancer. Limited data in humans have revealed that resveratrol is pharmacologically quite safe. Currently, structural analogues of resveratrol with improved bioavailability are being pursued as potential therapeutic agents for cancer.
Anticancer Res , 24 (5A), 2783-840 Sep-Oct 2004 Role of Resveratrol in Prevention and Therapy of Cancer: Preclinical and Clinical Studies
Supplements Colorectal
Supplements: Talk to Your Doctor: Colon Cancer
Colorectal cancer
Identifying and eradicating the causative factors responsible for the development of colorectal cancer is of the utmost importance to those individuals who are at high-risk for developing the disease and to those who have been diagnosed with colorectal cancer.
These factors include diet, lifestyle, exercise, tobacco and alcohol use, parity, hormone use, energy intake, and nonsteroidal anti-inflammatory drug (NSAID) use.
The following is a summary of what an individual with colorectal cancer (either colon cancer or rectal cancer) should consider and discuss with their physician, as an adjuvant approach to conventional colorectal cancer therapy:
Cimetidine, 800 mg each night for 12 continuous months.
Curcumin, 10,800 mg, in divided doses of four 900-mg capsules 3 times a day.
Lightly caffeinated green tea extract, 5,250 mg in divided doses of five 350-mg capsules 3 times daily with meals. If caffeine interferes with sleep, take decaffeinated capsules in the evening. Each capsule should contain at least 100 mg of epigallocatechin gallate (EGCG).
Se-methylselenocysteine, 200-400 mcg daily in divided doses.
Fish oil, 8 capsules of a supplement called Mega EPA supply 3200 mg of EPA and 2400 mg of DHA.
Vitamin E succinate, 800-1200 IU daily.
Gamma E Tocopherol/Tocotrienols, 200 mg daily.
Vitamin D3, 4000-6000 IU, taken daily on an empty stomach with monthly blood testing to monitor for toxicity. Reduce dosage at 6 months.
Water-soluble vitamin A, 100,000-300,000 IU daily, with monthly blood testing to monitor for toxicity. Reduce dosage at 6 months (refer to Appendix A: Vitamin A Precautions).
Modified citrus pectin, 15 grams daily in 3 divided doses.
Whey protein concentrate isolate, 10-20 grams three times daily.
Resveratrol, 20 mg daily.
Vitamin C, 4000-12,000 mg in divided doses throughout the day.
CoQ10, 100-300 mg daily.
Life Extension Mix, 3 tablets 3 times daily. (Patients with advanced colon cancer may want to avoid Life Extension Mix and other multivitamins since they all contain folic acid.
While folic acid may be the most effective nutrient to prevent colon cancer, in advanced stages, or in combination with certain chemotherapy drugs, folic acid may be detrimental because it may facilitate hypermethylation in colon cancer cells.)
Supplements: Talk to Your Doctor: Colon Cancer
Colorectal cancer
Identifying and eradicating the causative factors responsible for the development of colorectal cancer is of the utmost importance to those individuals who are at high-risk for developing the disease and to those who have been diagnosed with colorectal cancer.
These factors include diet, lifestyle, exercise, tobacco and alcohol use, parity, hormone use, energy intake, and nonsteroidal anti-inflammatory drug (NSAID) use.
The following is a summary of what an individual with colorectal cancer (either colon cancer or rectal cancer) should consider and discuss with their physician, as an adjuvant approach to conventional colorectal cancer therapy:
Cimetidine, 800 mg each night for 12 continuous months.
Curcumin, 10,800 mg, in divided doses of four 900-mg capsules 3 times a day.
Lightly caffeinated green tea extract, 5,250 mg in divided doses of five 350-mg capsules 3 times daily with meals. If caffeine interferes with sleep, take decaffeinated capsules in the evening. Each capsule should contain at least 100 mg of epigallocatechin gallate (EGCG).
Se-methylselenocysteine, 200-400 mcg daily in divided doses.
Fish oil, 8 capsules of a supplement called Mega EPA supply 3200 mg of EPA and 2400 mg of DHA.
Vitamin E succinate, 800-1200 IU daily.
Gamma E Tocopherol/Tocotrienols, 200 mg daily.
Vitamin D3, 4000-6000 IU, taken daily on an empty stomach with monthly blood testing to monitor for toxicity. Reduce dosage at 6 months.
Water-soluble vitamin A, 100,000-300,000 IU daily, with monthly blood testing to monitor for toxicity. Reduce dosage at 6 months (refer to Appendix A: Vitamin A Precautions).
Modified citrus pectin, 15 grams daily in 3 divided doses.
Whey protein concentrate isolate, 10-20 grams three times daily.
Resveratrol, 20 mg daily.
Vitamin C, 4000-12,000 mg in divided doses throughout the day.
CoQ10, 100-300 mg daily.
Life Extension Mix, 3 tablets 3 times daily. (Patients with advanced colon cancer may want to avoid Life Extension Mix and other multivitamins since they all contain folic acid.
While folic acid may be the most effective nutrient to prevent colon cancer, in advanced stages, or in combination with certain chemotherapy drugs, folic acid may be detrimental because it may facilitate hypermethylation in colon cancer cells.)
The kava kava scare
Another false herbal scare arose over kava kava, the South Pacific Island herb that helps to overcome mild cases of depression.
Pharmaceutical companies in Europe were selling kava kava and reported, without adequate substantiation, that there were reports of liver toxicity in less than 100 people and withdrew the herb (a drug in Europe) from distribution in 2002.
US sales of kava kava were then about $34 million a year. The American Herbal Products Association was put on the defensive to prove a long-used herbal extract was safe when there were only specious reports of liver toxicity from Europe.
Then the US Food & Drug Administration destroyed US sales of kava kava by issuing a warning of a ‘potential’ hazard and asked health professionals to report any cases of liver toxicity associated with this herb.
(For comparison, the US Poison Control Centers report that acetaminophen (Tylenol) causes 70,000 reported cases of liver toxicity annually which results in 70-100 deaths per year.)
Only a handful of adverse reports were submitted to the FDA by US physicians. None panned out to be of concern.
But consumers taking kava kava for anxiety and depression were getting more anxious and depressed every time they heard another negative news reports about kava.
Dr. Donald Waller, a toxicologist and professor at the University of Illinois, reviewed the reported cases of liver toxicity associated with the use of kava kava and concluded there was no clear evidence that the liver damage reported in the US and Europe was caused by the consumption of kava.
Other researchers also could not find a link between kava and the reported cases of liver toxicity. [Planta Med. 2004 Mar; 70: 193-6]
In many of these cases the kava patients were also taking prescription drugs that are known to be toxic to the liver.
But the May 2004 issue of Consumer Reports still listed kava among its list of Dangerous Supplements Still at Large.
Dr. Marvin Lipman, Consumer Reports chief medical advisor said: Given the weight of the evidence against Kava, we would urge everyone to avoid its use.”
In March of 2004 Canadian researchers were horrified that health food stores were still recommending kava kava to their customers. [J Gen Intern Med. 2004 Mar; 19: 269-72]
“There was no clear evidence that the liver damage reported in the US and Europe was caused by the consumption of kava.” –Dr. Donald Waller, toxicologist
Among Hawaiian farmers, sales of kava kava raw material dropped by 87% in just one year. [Hawaii Dept. of Agriculture] Thousands of jobs were wiped out. An efficacious anti-anxiety herb was cast into question, and most consumers didnt suspect that there were competing commercial interests behind this whole fiasco. 7/04
Integr Med Res. 2019 Jun;8(2):123-128. doi: 10.1016/j.imr.2019.04.007. Epub 2019 Apr 20.
A Naturalistic Study of Herbal Medicine for Self-Reported Depression and/or Anxiety a Protocol
David Casteleijn 1, Amie Steel 1, Diana Bowman 1, Romy Lauche 2, Jon Wardle 1 PMID: 31193603
PMCID: PMC6536771
Abstract
Background: Mental health conditions including anxiety and depression account for around 8% of the global disease burden. Anxiety and depression often coexist and impose a high individual and social burden. Patients with mental and behavioural conditions may be at increased risk of co-morbidities and are often high health-care utilisers. Herbal medicine is estimated to be used by up to 80% of the worlds population, and by 22% of Australian women seeking care for depression. The holistic and tailored treatment approach offered by practitioners of herbal medicine is difficult to capture in randomised controlled trials and as such there is a paucity of research demonstrating the outcomes of real-life practice. This project aims to address this gap with a whole practice, observational model.
Methods/design: The study will employ a naturalistic observational design. Two-hundred patient participants will be recruited to be treated by 15 clinician participants from different naturopathic clinics. The observed changes in anxiety and depression symptoms of patients will be documented across three consultations using validated patient-reported outcome measures (SF-36, DASS-21, GHQ-28 and POMS-2).
Conclusion: Clinical studies investigating the efficacy of individualised herbal medicine treatment as prescribed by a naturopath are rare. Our study attempts to fill this gap with a longitudinal observation of individualised care as practiced by naturopaths in Australia; to offer valuable insights into the effectiveness of individualised herbal medicine practice and provide contextualisation of data currently focused on individual herbal medicines in specific conditions.Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616000010493.
Kava feeding in rats does not cause liver injury nor enhance galactosamine-induced hepatitis
Robert A. DiSilvestro, a, Wenyi Zhanga and David J. DiSilvestroa aHuman Nutrition, The Ohio State University, 345 Campbell Hall, 1787 Neil Avenue, Columbus, OH 43210-1295, United States
Abstract
Kava, like a number of herbals, has been associated with causing liver damage based on limited evidence. In contrast, the present study found that in rats, 3 mo feedings of two types of kava extracts (an acetone extract and an ethanol extract of the Samoan kava cultivar Ava Laau) at three different doses (31.25, 62.5 and 133 mg/kg diet) produced no liver injury based on serum markers of liver damage (sorbitol dehydrogenase activities, bile acid concentrations, and â-glucuronidase activities) and serum lipid peroxide readings.
In fact, for some measurements and some kava doses, the injury marker readings were below control values.
Moreover, for these same parameters, kava feeding did not enhance the effects of the hepatotoxin galacatosamine (500 mg/kg ip); some kava doses even showed modest protection against liver injury. Liver histology analysis showed no signs of kava causing or enhancing liver injury.
Thus, this study does not support the concept that kava produces or aggravates liver injury.
Food and Chemical Toxicology
Volume 45, Issue 7, July 2007, Pages 1293-1300
doi:10.1016/j.fct.2007.01.015
Author Ann FonfaCategorie
Another false herbal scare arose over kava kava, the South Pacific Island herb that helps to overcome mild cases of depression.
Pharmaceutical companies in Europe were selling kava kava and reported, without adequate substantiation, that there were reports of liver toxicity in less than 100 people and withdrew the herb (a drug in Europe) from distribution in 2002.
US sales of kava kava were then about $34 million a year. The American Herbal Products Association was put on the defensive to prove a long-used herbal extract was safe when there were only specious reports of liver toxicity from Europe.
Then the US Food & Drug Administration destroyed US sales of kava kava by issuing a warning of a ‘potential’ hazard and asked health professionals to report any cases of liver toxicity associated with this herb.
(For comparison, the US Poison Control Centers report that acetaminophen (Tylenol) causes 70,000 reported cases of liver toxicity annually which results in 70-100 deaths per year.)
Only a handful of adverse reports were submitted to the FDA by US physicians. None panned out to be of concern.
But consumers taking kava kava for anxiety and depression were getting more anxious and depressed every time they heard another negative news reports about kava.
Dr. Donald Waller, a toxicologist and professor at the University of Illinois, reviewed the reported cases of liver toxicity associated with the use of kava kava and concluded there was no clear evidence that the liver damage reported in the US and Europe was caused by the consumption of kava.
Other researchers also could not find a link between kava and the reported cases of liver toxicity. [Planta Med. 2004 Mar; 70: 193-6]
In many of these cases the kava patients were also taking prescription drugs that are known to be toxic to the liver.
But the May 2004 issue of Consumer Reports still listed kava among its list of Dangerous Supplements Still at Large.
Dr. Marvin Lipman, Consumer Reports chief medical advisor said: Given the weight of the evidence against Kava, we would urge everyone to avoid its use.”
In March of 2004 Canadian researchers were horrified that health food stores were still recommending kava kava to their customers. [J Gen Intern Med. 2004 Mar; 19: 269-72]
“There was no clear evidence that the liver damage reported in the US and Europe was caused by the consumption of kava.” –Dr. Donald Waller, toxicologist
Among Hawaiian farmers, sales of kava kava raw material dropped by 87% in just one year. [Hawaii Dept. of Agriculture] Thousands of jobs were wiped out. An efficacious anti-anxiety herb was cast into question, and most consumers didnt suspect that there were competing commercial interests behind this whole fiasco. 7/04
Integr Med Res. 2019 Jun;8(2):123-128. doi: 10.1016/j.imr.2019.04.007. Epub 2019 Apr 20.
A Naturalistic Study of Herbal Medicine for Self-Reported Depression and/or Anxiety a Protocol
David Casteleijn 1, Amie Steel 1, Diana Bowman 1, Romy Lauche 2, Jon Wardle 1 PMID: 31193603
PMCID: PMC6536771
Abstract
Background: Mental health conditions including anxiety and depression account for around 8% of the global disease burden. Anxiety and depression often coexist and impose a high individual and social burden. Patients with mental and behavioural conditions may be at increased risk of co-morbidities and are often high health-care utilisers. Herbal medicine is estimated to be used by up to 80% of the worlds population, and by 22% of Australian women seeking care for depression. The holistic and tailored treatment approach offered by practitioners of herbal medicine is difficult to capture in randomised controlled trials and as such there is a paucity of research demonstrating the outcomes of real-life practice. This project aims to address this gap with a whole practice, observational model.
Methods/design: The study will employ a naturalistic observational design. Two-hundred patient participants will be recruited to be treated by 15 clinician participants from different naturopathic clinics. The observed changes in anxiety and depression symptoms of patients will be documented across three consultations using validated patient-reported outcome measures (SF-36, DASS-21, GHQ-28 and POMS-2).
Conclusion: Clinical studies investigating the efficacy of individualised herbal medicine treatment as prescribed by a naturopath are rare. Our study attempts to fill this gap with a longitudinal observation of individualised care as practiced by naturopaths in Australia; to offer valuable insights into the effectiveness of individualised herbal medicine practice and provide contextualisation of data currently focused on individual herbal medicines in specific conditions.Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616000010493.
Kava feeding in rats does not cause liver injury nor enhance galactosamine-induced hepatitis
Robert A. DiSilvestro, a, Wenyi Zhanga and David J. DiSilvestroa aHuman Nutrition, The Ohio State University, 345 Campbell Hall, 1787 Neil Avenue, Columbus, OH 43210-1295, United States
Abstract
Kava, like a number of herbals, has been associated with causing liver damage based on limited evidence. In contrast, the present study found that in rats, 3 mo feedings of two types of kava extracts (an acetone extract and an ethanol extract of the Samoan kava cultivar Ava Laau) at three different doses (31.25, 62.5 and 133 mg/kg diet) produced no liver injury based on serum markers of liver damage (sorbitol dehydrogenase activities, bile acid concentrations, and â-glucuronidase activities) and serum lipid peroxide readings.
In fact, for some measurements and some kava doses, the injury marker readings were below control values.
Moreover, for these same parameters, kava feeding did not enhance the effects of the hepatotoxin galacatosamine (500 mg/kg ip); some kava doses even showed modest protection against liver injury. Liver histology analysis showed no signs of kava causing or enhancing liver injury.
Thus, this study does not support the concept that kava produces or aggravates liver injury.
Food and Chemical Toxicology
Volume 45, Issue 7, July 2007, Pages 1293-1300
doi:10.1016/j.fct.2007.01.015
Author Ann FonfaCategorie
Tocotrienols: The Promising Analogues of Vitamin E for Cancer Therapeutics Bethsebie Lalduhsaki Sailo 1, Kishore Banik 1, Ganesan Padmavathi 1, Monisha Javadi 1, Devivasha Bordoloi 1, Ajaikumar B Kunnumakkara 2 PMID: 29496592 DOI: 10.1016/j.phrs.2018.02.017 Pharmacol Res. 2018 Apr;130:259-272.Epub 2018 Feb 27.
Abstract
Despite the significant advancements in the diagnosis and treatment of cancer, it still remains one of the most fatal diseases in the world due to the lack of sensitive diagnosis methods and effective drugs. Therefore, discovering novel therapies that are safe, efficacious and affordable are required for the better management of this disease. Tocotrienols, analogues of vitamin E have gained increased attention due to their safety and efficacy. Extensive research over the past several years has strongly indicated that tocotrienols can efficiently prevent/inhibit the growth of different cancers such as cancers of blood, brain, breast, cervical, colon, liver, lung, pancreas, prostate, skin, stomach etc. This is mainly accredited to their ability to modulate various molecular targets involved in cancer cell proliferation, survival, invasion, angiogenesis, and metastasis such as NF-κB, STAT3, Akt/mTOR, etc. In addition, increasing lines of evidence has shown that tocotrienols can sensitize cancer cells to chemotherapeutic agents such as celecoxib, doxorubicin, erlotinib, gefitinib, gemcitabine, paclitaxel, statin etc. Moreover, several clinical trials have confirmed the safety and tolerability of tocotrienols in humans. This review summarizes the potential of tocotrienols for the prevention and treatment of different cancers based on the available in vitro, in vivo and clinical studies.
Abstract
Despite the significant advancements in the diagnosis and treatment of cancer, it still remains one of the most fatal diseases in the world due to the lack of sensitive diagnosis methods and effective drugs. Therefore, discovering novel therapies that are safe, efficacious and affordable are required for the better management of this disease. Tocotrienols, analogues of vitamin E have gained increased attention due to their safety and efficacy. Extensive research over the past several years has strongly indicated that tocotrienols can efficiently prevent/inhibit the growth of different cancers such as cancers of blood, brain, breast, cervical, colon, liver, lung, pancreas, prostate, skin, stomach etc. This is mainly accredited to their ability to modulate various molecular targets involved in cancer cell proliferation, survival, invasion, angiogenesis, and metastasis such as NF-κB, STAT3, Akt/mTOR, etc. In addition, increasing lines of evidence has shown that tocotrienols can sensitize cancer cells to chemotherapeutic agents such as celecoxib, doxorubicin, erlotinib, gefitinib, gemcitabine, paclitaxel, statin etc. Moreover, several clinical trials have confirmed the safety and tolerability of tocotrienols in humans. This review summarizes the potential of tocotrienols for the prevention and treatment of different cancers based on the available in vitro, in vivo and clinical studies.
Vit C Proline and Green Tea
Ann’s NOTE: In 2005 this animal study was published. Thereafter studies were published in cell cultures (see below), 2006 and 2016
In Vivo Antitumor Effect of Ascorbic Acid, Lysine, Proline, and Green Tea Extract on Human Colon Cancer Cell HCT 116 Xenografts in Nude Mice: Evaluation of Tumor Growth and Immunohistochemistry
M.W. Roomi, V.Ivanov, T.Kalinovsky, A. Niedzwiecki, M.Rath
Colorectal cancer is the second most deadly cancer in the United States. When diagnosed early, current treatments bring a limited success; however once metastasis occurs, radiation and chemotherapy are generally ineffective.
Structural changes in the ECM are necessary for cell migration during tissue remodeling. MMPs, VEGF, Ki 67 (proliferative protein), and constituents of ECM, such as fibronectin, play a critical role in angiogenesis and are thus crucial in neoplastic invasion and metastasis.
Based on antitumor properties of certain nutrients, we investigated the effect of a diet containing lysine, proline, arginine, ascorbic acid, and green tea extract on the growth of tumors induced by implanting human colon HCT 116 cancer cells in athymic nude mice and the expression of MMPs, VEGF, Ki 67 and fibronectin in these tumors, as well as the production of mucin (by PAS staining).
After one-week of isolation, 5-6 week old athymic male nude mice (n=12) were inoculated with 3×106 colon cancer HCT 116 cells. After injection, the mice were randomly divided into two groups; group A was fed a regular diet and group B was fed a regular diet supplemented with 0.5% of the nutrient mixture.
Four weeks later, the mice were sacrificed, and their tumors were excised, weighed, and processed for histology.
Results showed that the nutrient mixture (NM) inhibited the growth and reduced the size of tumors in nude mice. Furthermore, histological evaluation revealed increased mitotic index, MMP-9 and VEGF secretion and reduced basement membrane in the control group tissues.
Nutrient supplementation strongly suppressed the growth of tumors without any adverse effects in nude mice, suggesting the nutrient combination has potential as an anticancer agent.
Histological studies supported these findings by showing inhibition of MMP-9 and VEGF secretion and mitotic index – critical parameters for cancer control and prevention.
Oncology Reports, 2005, 12 (3), 421-425.
Med Oncol. 2006;23(3):411-7. doi: 10.1385/mo:23:3:411.
Effect of Ascorbic Acid, Lysine, Proline, and Green Tea Extract on Human Osteosarcoma Cell Line MNNG-HOS Xenografts in Nude Mice: Evaluation of Tumor Growth and Immunohistochemistry
“Results demonstrate that the nutrient mixture of lysine, proline, arginine, ascorbic acid, and green tea extract tested strongly suppressed the growth of tumors without adverse effects in nude mice, suggesting potential as an anticancer agent.”
Oncol Rep. 2006 Nov;16(5):943-7.
Anticancer Effect of Lysine, Proline, Arginine, Ascorbic Acid and Green Tea Extract on Human Renal Adenocarcinoma Line 786-0
“Our results support a potential role for the nutrient mixture tested in the treatment of renal cell carcinoma, by inhibition of MMP-2 and MMP-9 secretion and invasion.”
Int J Urol. 2006 Apr;13(4):415-9. doi: 10.1111/j.1442-2042.2006.01309.x.
Antitumor Effect of Ascorbic Acid, Lysine, Proline, Arginine, and Green Tea Extract on Bladder Cancer Cell Line T-24
“Conclusion: Our results suggest that our nutrient mixture is an excellent candidate for therapeutic use in the treatment of bladder cancer, by inhibiting critical steps in cancer development and spread, such as MMP secretion and invasion.
Ann’s NOTE: In 2005 this animal study was published. Thereafter studies were published in cell cultures (see below), 2006 and 2016
In Vivo Antitumor Effect of Ascorbic Acid, Lysine, Proline, and Green Tea Extract on Human Colon Cancer Cell HCT 116 Xenografts in Nude Mice: Evaluation of Tumor Growth and Immunohistochemistry
M.W. Roomi, V.Ivanov, T.Kalinovsky, A. Niedzwiecki, M.Rath
Colorectal cancer is the second most deadly cancer in the United States. When diagnosed early, current treatments bring a limited success; however once metastasis occurs, radiation and chemotherapy are generally ineffective.
Structural changes in the ECM are necessary for cell migration during tissue remodeling. MMPs, VEGF, Ki 67 (proliferative protein), and constituents of ECM, such as fibronectin, play a critical role in angiogenesis and are thus crucial in neoplastic invasion and metastasis.
Based on antitumor properties of certain nutrients, we investigated the effect of a diet containing lysine, proline, arginine, ascorbic acid, and green tea extract on the growth of tumors induced by implanting human colon HCT 116 cancer cells in athymic nude mice and the expression of MMPs, VEGF, Ki 67 and fibronectin in these tumors, as well as the production of mucin (by PAS staining).
After one-week of isolation, 5-6 week old athymic male nude mice (n=12) were inoculated with 3×106 colon cancer HCT 116 cells. After injection, the mice were randomly divided into two groups; group A was fed a regular diet and group B was fed a regular diet supplemented with 0.5% of the nutrient mixture.
Four weeks later, the mice were sacrificed, and their tumors were excised, weighed, and processed for histology.
Results showed that the nutrient mixture (NM) inhibited the growth and reduced the size of tumors in nude mice. Furthermore, histological evaluation revealed increased mitotic index, MMP-9 and VEGF secretion and reduced basement membrane in the control group tissues.
Nutrient supplementation strongly suppressed the growth of tumors without any adverse effects in nude mice, suggesting the nutrient combination has potential as an anticancer agent.
Histological studies supported these findings by showing inhibition of MMP-9 and VEGF secretion and mitotic index – critical parameters for cancer control and prevention.
Oncology Reports, 2005, 12 (3), 421-425.
Med Oncol. 2006;23(3):411-7. doi: 10.1385/mo:23:3:411.
Effect of Ascorbic Acid, Lysine, Proline, and Green Tea Extract on Human Osteosarcoma Cell Line MNNG-HOS Xenografts in Nude Mice: Evaluation of Tumor Growth and Immunohistochemistry
“Results demonstrate that the nutrient mixture of lysine, proline, arginine, ascorbic acid, and green tea extract tested strongly suppressed the growth of tumors without adverse effects in nude mice, suggesting potential as an anticancer agent.”
Oncol Rep. 2006 Nov;16(5):943-7.
Anticancer Effect of Lysine, Proline, Arginine, Ascorbic Acid and Green Tea Extract on Human Renal Adenocarcinoma Line 786-0
“Our results support a potential role for the nutrient mixture tested in the treatment of renal cell carcinoma, by inhibition of MMP-2 and MMP-9 secretion and invasion.”
Int J Urol. 2006 Apr;13(4):415-9. doi: 10.1111/j.1442-2042.2006.01309.x.
Antitumor Effect of Ascorbic Acid, Lysine, Proline, Arginine, and Green Tea Extract on Bladder Cancer Cell Line T-24
“Conclusion: Our results suggest that our nutrient mixture is an excellent candidate for therapeutic use in the treatment of bladder cancer, by inhibiting critical steps in cancer development and spread, such as MMP secretion and invasion.
Vitamin C
Read Linus Pauling’s complete 1968 paper on megavitamin therapy at
A 1974 Pauling megavitamin paper is posted at
Linus Pauling and colleagues believe that vitamin C and the amino acid lysine may prevent and cure atherosclerosis.
The Vitamin C Foundation is a great source of megavitamin information:
Read Linus Pauling’s complete 1968 paper on megavitamin therapy at
- http://www.orthomed.org/pauling2.htm
A 1974 Pauling megavitamin paper is posted at
- http://www.orthomed.org/pauling.htm
Linus Pauling and colleagues believe that vitamin C and the amino acid lysine may prevent and cure atherosclerosis.
- http://www.internetwks.com/pauling/
The Vitamin C Foundation is a great source of megavitamin information:
- http://www.vitamincfoundation.org/ , as are the following sites:
- http://www.internetwks.com/pauling/hoffer.html
- http://bookman.com.au/vitamins/vitc.html
- http://www.fightingcancer.com/vitaminc.htm
- http://www.achievement.org/autodoc/page/pau0int-1 (be sure to read the interview)
Vitamins and HERBS during Chemo
DO HERBS, VITAMINS, AND ANTIOXIDANTS ADVERSELY AFFECT CANCER THERAPIES?
preliminary report by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon
For more than 30 years now, Chinese herbs and materials derived from the herbs, such as long chain polysaccharides, have been used as adjunct therapies for cancer patients.
This modern application was first developed clinically in China and Japan during the 1970s and was relayed to the rest of the world in 1983 through an international conference in Beijing which was followed up by press reports in English and other languages (see: Physiological responses to immunologically active polysaccharides).
The Institute for Traditional Medicine (ITM) made an effort to alert practitioners of Chinese medicine in the U.S. to this promising role for Chinese herbs immediately after that conference, with updated information provided as available over the years. The utilization of Chinese roots, leaves, and fruits (e.g., astragalus, gynostemma, ligustrum, and lycium), and several mushrooms (e.g., coriolus, ganoderma, cordyceps, and lentinus) for cancer patients is now a routine procedure when these patients visit acupuncturists, naturopathic physicians, and others offering adjunctive cancer health care.
Within the past couple of years, however, an increasing number of patients have been told by their oncologists to avoid herbs, and to more generally avoid supplements (such as vitamins), or, even more broadly, simply avoid anything with antioxidant potential while they are undergoing cancer therapies.
The admonition itself is difficult to interpret, since all foods contain antioxidants and vitamins, and they also contain most of the other substances offered in dietary supplements. Most fruits, vegetables, beans, and nuts differ only slightly from herbs. A more specific recommendation is needed.
But first, the question arises: why are doctors giving these instructions? What kind of information is being released to the public?
I have attempted to trace back the origins of the restrictions imposed by some oncologists, and it seems that the primary instigator of the concern was Dr. David Golde at the Memorial Sloan-Kettering Cancer Center, even though he was not the first to raise the matter (but within a few months of being first).
The main issue he raised was the use of high doses of vitamin C, a therapy that has nothing directly to do with herbs. Herbs usually have little or no vitamin C; still, vitamin C is commonly prescribed or recommended as a supplement by practitioners involved in natural healing.
In a June 19, 2000 report of WebMD Medical News, the use of high doses of vitamin C to prevent heart disease, cancer, and other disorders, was called into question, and Dr. Golde’s research and comments were relayed (1, 2):
The first of two recent studies that called this notion [of taking high doses of vitamin C as a disease preventive] into question was carried out by David Golde, MD, physician-in-chief at Memorial Sloan-Kettering Cancer Center in New York City, and described at an American Cancer Society meeting in March 2000.
Golde and his colleagues transplanted human cancer cells into mice, injected the mice with vitamin C, and then measured the amount of the vitamin in the cells. They found that cancer cells seem to soak up large amounts of vitamin C by converting it into a form that’s easier to absorb. The results, Golde says, raise the possibility that cancer cells may use vitamin C to shield themselves against radiation and chemotherapy.
The second study, performed by James Dwyer, Ph.D., an epidemiologist at the University of Southern California, caused an even bigger stir. Dwyer told an American Heart Association meeting in March 2000 that middle-aged men who took 500 milligrams of vitamin C supplements daily showed a rapid narrowing of their carotid arteries, which supply blood to the brain.
The studies sound alarming, but experts warn against making too much of them. While Golde says that cancer patients shouldn’t take large doses of the vitamin, other researchers say it’s far too early to make that recommendation.
There’s no evidence yet that C actually shields cancer cells from treatment, says Mark Levine, MD, an endocrinologist and Vitamin C expert at the National Institutes of Health. The cancers tested in Golde’s research, he says, may simply have grown from tissues that normally take in large amounts of the vitamin.
As for the heart disease finding, Dwyer himself cautioned that it is preliminary. The study lasted only 18 months and included just 573 men. And Robert Jacob, Ph.D., a research chemist with the U.S. Department of Agriculture, points out that previous studies suggested just the opposite-that vitamin C reduces the narrowing of carotid arteries.
From these very modest beginnings in Spring of 2000, the worry about antioxidants and cancer therapies grew, despite several warnings about the interpretation of data, such as those mentioned in the above analysis, and almost everyone who wished to provide a basis for the antioxidant and vitamin worry seemed to harken back to Dr. Golde’s very preliminary research.
A pharmacist, John Russo, Jr., wrote the following to caution his readers about the possible interaction of antioxidants with brachytherapy (radiation therapy where the radiation source is placed inside the body) for prostate cancer (3):
How might an antioxidant adversely affect brachytherapy?
The precise role that the antioxidant, vitamin C, plays in tumors is not known, but recent studies have shown possible interactions between dietary antioxidants and cancer treatment.
We know that vitamin C is a powerful antioxidant. It consumes free radicals, the toxic substances in the body that can be generated by chemotherapy agents to destroy cancer cells. “It is possible,” according to Dr. David Golde, Physician-in-Chief at Memorial Sloan-Kettering Cancer Center, “that taking large amounts of vitamin C could interfere with the effects of chemotherapy or even radiation therapy.” These therapies often kill cells, in part, by using oxidative mechanisms.
It’s conceivable then, that vitamin C might make cancer treatment less effective, and it is reasonable that cancer patients undergoing chemotherapy avoid taking large amounts of this vitamin.”
Building on past research
Earlier research by Dr. Golde and his colleagues established that specific glucose transporter molecules carry vitamin C into cells. This occurs once vitamin C, which is used by cells in the form of ascorbic acid, is converted into dehydroascorbic acid and transported into the cell. Once inside, the vitamin is converted back to ascorbic acid.
Applying this information to patient care
According to David Agus, an oncologist at Memorial Sloan-Kettering Cancer Center, we now know that tumors acquire and retain large amounts of vitamin C. And their nutritional needs appear to be similar to healthy cells that take in large amounts of the vitamin.”
However, what cancer cells do with the vitamin C after it is absorbed is not known. This will have to be determined before guidelines for the complementary use of antioxidants during chemotherapy and radiation become established.
Furthermore, research from University of Tubingen, School of Medicine in Germany suggests caution in applying this knowledge to all antioxidants in all types of malignancies. Examination of the modulation of drug-induced cytotoxicity and clonogenic cell death of glioma cells by three structurally unrelated antioxidants revealed that these antioxidants inhibit acute cytotoxicity and clonogenic cell death induced by cisplatin.
However, they had little effect on the toxicity of other cancer drugs including BCNU, doxorubicin, vincristine, cytarabine, or camptothecin.
In the discussion of brachytherapy, the pharmacist carries the implications over to chemotherapy agents, but mistakenly states that these function by producing free radicals. In general, this is not the case, and only applies to radiation (see explanation of mechanism, Appendix).
The research cited here about an inhibition of cisplatin therapy by antioxidants (but, notably, no effect of the tested antioxidants on several other chemotherapy drugs) was published in 1998 (4), and did not produce much interest at the time, nor has a follow-up report been published to date (end of 2002).
Glioma cells (a type of brain cancer) are normally resistant to the effects of chemotherapy, and the authors were examining factors influencing this already poor response. They determined, in their study, that cisplatin did not rely on free-radical formation to damage glioma cells, so antioxidant activity working directly against cisplatin effects was not an issue.
Rather, the substances tested in this in vitro study appeared to function by some other unknown mechanism.
By contrast, another platin drug, oxaliplatin, was used in a double-blind, placebo controlled clinical trial along with administration of the antioxidant glutathione (GSH; see Figure 1).
The authors concluded (5): “This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.”
This is an important finding, because it had been proposed that cancer cells could become resistant to platin drugs (e.g., cisplatin and carboplatin;) due to changes in the cancer cell membrane, where the resistance may be caused by the binding of platinum to intracellular thiols, such as glutathione.
This possibility, based on in vitro studies, implies that the interaction between platinum and GSH could prevent the active compounds from reaching the DNA nucleus. It is unclear at this point, whether administering glutathione can be recommended (as is often done by proponents of its protective effects), but this substance does not appear to have any direct interference with oxaliplatin when used clinically based on the recent clinical trial.
In vitro studies indicate that high intracellular glutathione levels protect cancer cells from the effects of chemotherapy, but this may not carry over to the clinical situation.
A related concern about chemotherapy drug resistance has been raised about using antioxidants with cyclophosphamide, a particularly toxic anticancer drug. When the literature was reviewed, it was found that, if anything, the substances were beneficial for patients on cyclophosphamide therapy. Here is the interaction caution about this drug as relayed in Healthnotes (6-10):
Interactions with Dietary Supplements
Antioxidants
Cyclophosphamide requires activation by the liver through a process called oxidation. In theory, antioxidant nutrients (vitamin A, vitamin E, beta-carotene and others) might interfere with the activation of cyclophosphamide.
There is no published research linking antioxidant vitamins to reduced cyclophosphamide effectiveness in cancer treatment.
In a study of mice with vitamin A deficiency, vitamin A supplementation enhanced the anticancer action of cyclophosphamide. Another animal research report indicated that vitamin C may increase the effectiveness of cyclophosphamide without producing new side effects.
Preliminary human research found that adding antioxidants (beta-carotene, vitamin A, and vitamin E) to cyclophosphamide therapy increased the survival of people with small-cell lung cancer treated with cyclophosphamide.
It is too early to know if adding antioxidants to cyclophosphamide for cancer treatment is better than cyclophosphamide alone. Vitamin A can be toxic in high amounts.
Intravenous injections of the antioxidant, glutathione, may protect the bladder from damage caused by cyclophosphamide.
Preliminary evidence suggests, but cannot confirm, a protective action of glutathione in the bladders of people on cyclophosphamide therapy. There is no evidence that glutathione taken by mouth has the same benefits.
As reported here, when laboratory animal and clinical evaluation is the basis for the information, the potential benefits of antioxidants appear. One could say that there has been some backlash at the anti-antioxidant stance promoted by those who quote Dr. Golde and extend his vitamin C research to imply that all antioxidants are problematic for cancer patients.
At the Rush Presbyterian St. Luke’s Medical Center, the suggestion that vitamin E might inhibit radiation effects was discounted. A press report stated (11):
Vitamin E Does Not Protect Cancer Cells Against Radiation
New York. 15 January 2000 (posted 19 March, 2001). Cancer patients who take vitamin E are probably not hindering the desired effects of radiation, according to a laboratory study done by radiation oncologists at Rush-Presbyterian-St. Luke’s Medical Center in Chicago.
Researchers at Rush were concerned that patients who take vitamin E may be inadvertently providing protection for the cancer cells that are the target of radiation therapy. Radiation damage is one form of oxidation, and vitamin E’s antioxidant properties presumably extend to cancer cells.
To determine if this were true, Rush researchers, led by Dr. Ed Blazek, director of radiation biology in the Rush department of radiation oncology, grew cells originating from human breast and prostate tumors in nutrient solutions containing several concentrations of vitamin E. The cells were then irradiated with the same daily doses used for patients.
The Rush team found that the tested concentrations of vitamin E did not interfere with the desired killing of cancer cells by radiation. An important limitation of this study, however, is that the level of vitamin E taken up by the cancer cells in laboratory culture has not yet been measured, and might be smaller than the level taken up by cells of a tumor in the patient’s body. If so, it is still possible that vitamin E might worsen treatment outcomes.
Although no undesirable protection of cancer cells was found, the researchers issued a caution to those taking vitamin E and other alternative therapies. “Any drug that is taken during cancer radiotherapy or chemotherapy should be tested to prove that it does not protect the tumor cells, defeating the intended effect of the treatment,” Blazek said.
Natural extensions of this work would include the addition of the drug pentoxifylline to vitamin E, since this combination has been reported to partially reverse radiation damage to normal tissue, the testing of vitamin C for radioprotection, and the testing of both vitamins E and C for protection from representative cancer chemotherapy drugs.
This research, performed by Drs. Alex Perez and Katherine Baker together with Dr. Blazek, was presented at the annual meeting of the Radiological Society of North America in Chicago.
Then, in a follow-up report from the same hospital, this time including vitamin C (12, 13):
Vitamins C and E Fight Side Effects of Pelvic Radiation for Cancer
March 20, 2001. A small study of 20 men and women suffering from chronic radiation proctitis has shown that daily vitamins E and C substantially reduced or eliminated their symptoms. Proctitis has traditionally been treated with anti-inflammatory agents, without satisfactory results.
Radiation therapy is one treatment option for men with localized prostate cancer and for women with cervix and endometrial cancers. Radiation therapy is effective in killing cancer cells. But the therapy damages also any normal, non-cancerous cells within range of the beam.
Complications are especially common in patients who are treated with older equipment. New, 3D conformal, Intensity Modulated or Proton beam equipment (available in the USA and some other countries) targets the beam much more precisely. Higher doses can be given to tumor with less damage to bladder and rectum.
Most patients take vitamins-does this interfere with killing cancer cells?
Even under the best conditions patients want to do everything possible to protect themselves from radiotherapy side effects. Many patients who undergo cancer treatments take vitamins and supplements. Until recently, oncologists seldom asked patients about this.
Doctors still have almost no evidence on which to advice cancer patients about common supplements. But a previous, laboratory study by radiation oncologists at Rush-Presbyterian-St. Luke’s Medical Center found that “Cancer patients who take vitamin E are probably not hindering the desired effects of radiation.”
Dr. Keith Bruninga, gastroenterologist at Rush-Presbyterian-St. Luke’s has now looked to see how much protection vitamins E and C actually offer patients irradiated for prostate, cervical or endometrial cancer. The effect of the vitamins in the treatment of chronic radiation proctitis had not been studied before, Dr. Bruninga said.
In normal bowel and rectal tissues exposed to radiation for cancer in the pelvis, oxygen radicals form and patients experience the symptoms of proctitis, he said. The condition starts with swollen, inflamed tissue, and it increases with dose. The symptoms, which may include diarrhea, pain, bleeding and incontinence, usually clear up within a few weeks of the last radiation treatment.
However, the symptoms do not clear up in 10-20 percent of patients. Some patients develop symptoms months or years after the initial radiation exposure.
“Our study showed that we can harness the potent antioxidant properties of the vitamins to repair cell damage and bring relief to many people who suffer from the persistent, lifestyle-altering symptoms of chronic radiation proctitis,” Dr. Bruninga says in a paper published in the April issue of The American Journal of Gastroenterology.
Oxygen free radicals form from cells that have been injured. Oxygen free radicals are highly active molecules that react with cells by changing or damaging their structure. The formation of the oxygen free radicals increases the amount of injury to the cells and results in a chronic condition as blood flow to the cells is decreased.
Vitamin E is a potent antioxidant that can react with damaging oxygen free radicals. Vitamin C in combination with E increases the effects of vitamin E. The researchers believe that the antioxidant treatment regimen using the vitamins counteracts and can prevent oxygen free radical injury and increase blood flow to the injured cells of patients with chronic radiation proctitis.
Patients in the study, ten men and ten women with chronic radiation proctitis, took one 400 IU vitamin E tablet along with one 500 mg vitamin C tablet three times each day for eight consecutive weeks. Patients purchased the vitamins themselves at the store of their choice.
Each patient in the study rated their symptoms in terms of severity and frequency before and after treatment with the vitamins using a questionnaire developed by the researchers.
The impact of the symptoms on the lifestyle of the patients was also assessed using a questionnaire. Ten of the patients were assessed again after one year to determine if their initial responses were sustained.
The assessments showed a significant improvement in bleeding, diarrhea and urgency after taking the vitamins. Patients with rectal pain did not improve significantly. Thirteen patients reported an improvement in their lifestyle including seven whom reported a complete return to normal.
All of the ten patients who were assessed after one year reported a sustained improvement in their symptoms while continuing to take the vitamins.
The Rush physicians believe that the actual incidence of the ailment is greater than the estimated 10-20 percent of radiation patients. They feel that many patients, relieved and grateful that their cancers are remission, are embarrassed to tell their physicians about the symptoms of radiation proctitis.
Currently, the Rush physicians are seeking additional individuals with chronic radiation proctitis to conduct a larger, double-blinded study of the effectiveness of antioxidants in the treatment of the illness.
“If our continued research shows that the antioxidant regimen is successful in treatment of this illness, we plan to investigate its use to prevent chronic radiation proctitis,” said Dr. Bruninga.
Results of the study appear in April 2002 issue of The American Journal of Gastroenterology.
THE ALTERNATIVE: AVOIDING EVEN NORMAL LEVELS OF ANTIOXIDANT INTAKE
One of the early complaints about vitamins and chemotherapy was this one, described just four months before Dr. Golde made his comments at an American Cancer Society Meeting, summarized by a report on prostate cancer (13):
Vitamins and Chemotherapy
Although the antioxidant vitamins A, C, and E help repair damaged cells, it is probably not a good idea to take large amounts during radiation treatment. One object of chemotherapy is to damage cancer cells. Antioxidants, however, appear to counteract the process, according to Dr. Rudolph Salganik’s report to the annual meeting of the American Society for Cell Biology (December 1999).
He pointed out that “Almost all anticancer drugs kill cancer cells by way of apoptosis, and antioxidants like vitamin A and vitamin E dramatically reduce apoptosis in cancer cells.” Patients should therefore avoid taking any more than a normal amount of these vitamins during chemotherapy treatment.
This sounds like reasonable advice-just don’t add to normal intake-but Dr. Salganik’s own suggestion went further: indicating that an antioxidant-depleted diet could improve cancer therapies. The study referred to above was reported on as follows (14):
Study: avoiding vitamins A, E might improve cancer therapy
By David Williamson, UNC-CH News Services
CHAPEL HILL-Vitamins A and E, which normally boost human health in numerous ways, also appear to keep cancer cells from dying through the natural protective process scientists call apoptosis, new University of North Carolina at Chapel Hill research shows.
As a result, giving patients those vitamins may prevent cancer cells from self-destructing and work against cancer therapy, scientists say.
Researchers at UNC-CH’s schools of public health and medicine presented their findings Monday (Dec. 13) during a news conference at the American Society for Cell Biology’s annual meeting in Washington, D.C. Drs. Rudolph Salganik, research professor of nutrition, and Terry Van Dyke, professor of biochemistry and biophysics, directed the studies.
“We believe this work is important because it may make cancer treatments more effective,” Salganik said. “It suggests that cancer patients, especially those undergoing chemotherapy or radiation therapy, may do better on an antioxidant-depleted diet.”
The scientist and his colleagues study reactive oxygen species (ROS), which play a central role in the series of signals that allow cells to kill bacteria and viruses, destroy toxins and trigger the apoptotic “suicide” of defective cells such as cancer, he said. Antioxidants, such as vitamins A and E, protect normal cells from the damaging effects of ROS but apparently also can prevent the targeted apoptotic death of cancer cells that threaten humans and other mammals, the new work suggests.
Other researchers involved were Drs. Craig D. Albright, research assistant professor of nutrition; and Steven H. Zeisel, professor of nutrition and pediatrics and chair of nutrition.
The UNC-CH experiments involved putting mice that were predisposed to developing brain tumors on specially modified diets that were either supplemented with standard amounts of antioxidants or were antioxidant deficient for four months. Researchers then carefully monitored the rodents’ health and their brain tumors, if any, to see how the animals fared on the different diets.
Mice receiving extra vitamins A and E showed no benefit in either the size or incidence of brain tumors, Salganik said. They also had relatively short lives.
“Interestingly and more importantly, in animals that received antioxidant-depleted diets, brain tumors were significantly reduced in size because of induction of oxidant stress due to what are commonly called free radicals in the brain tumors,” Albright said. “Higher levels of cell death was restricted only to the brain tumors, while normal tissues were not affected by depletion of antioxidants in the mouse diets.”
In mice getting low levels of vitamins A and E, no negative effects were seen in normal cells, but about 19 percent of tumor cells showed evidence of apoptosis. In those ingesting normal quantities of antioxidant vitamins, only about 3 percent of tumor cells were apoptotic.
The group’s findings may explain two previous clinical studies showing that heavy smokers who ate a diet high in beta-carotene antioxidants had significantly higher rates of lung cancer, Salganik said.
“These new studies raise important issues regarding the advisability of ingesting high levels of antioxidants as a potential anti-cancer benefit,” Albright said. “Clearly, more studies are needed at the clinical level in human populations to address the real value of antioxidant supplements or antioxidant depletion in people at risk of developing cancer.”
Salganik said he hoped clinical studies would begin within a year or two. Van Dyke is a member of the UNC Lineberger Comprehensive Cancer Center.
Up to this point, no clinical study results along these lines have been reported.
The suggestion of starving antioxidants, however, runs contrary to most of the information currently available. The study referred to above, involving heavy smokers and beta-carotene intake has already been the subject of considerable controversy and it appears there were unique factors in this population of heavy smokers in Finland that were studied.
Findings to the contrary are common. For example, in a recent evaluation of the risks of lung cancer in relation to various carotenoids ingested. The conclusion was (15):
Lower risks of lung cancer were observed for the highest versus the lowest quintiles of lycopene (28%), lutein/zeaxanthin (17%), beta-cryptoxanthin (15%), total carotenoids (16%), serum beta-carotene (19%), and serum retinol (27%). These findings suggest that high fruit and vegetable consumption, particularly a diet rich in carotenoids, tomatoes, and tomato-based products, may reduce the risk of lung cancer.
SHOULD HERBS BE WORRISOME ADJUNCTS TO CANCER THERAPIES?
There is only one herb that has been implicated in a potential adverse effect on chemotherapy, and its effect has nothing to do with antioxidant activity of the herb. This one herb has been implicated in lowering the dose of a wide range of drugs because it strongly activates the drug-metabolizing enzyme cytochrome P450 CYP3A4.
This is St. John’s wort (16), which was commonly used for treating depression during the 1990s, but has since become little used due to the concerns for drug interactions (as well as some question about its efficacy). No other herb has been identified as a potential inhibitor of chemotherapy drugs.
Although many herbs have some antioxidant potential, their influence over oxidative reactions is low due to the low dosage commonly employed. Unlike vitamin C, which is presented as a pure or nearly pure compound in dietary supplements, herbs contain little vitamin C (in relation to Dr. Golde’s concern) and low levels of antioxidant substances. Further they contain little, if any, of the substances that appeared to inhibit cisplatin cytotoxicity in cultured glioma cells.
There are no pharmacology or clinical studies showing problems with herbs other than St. John’s wort in relation to chemotherapy or radiation therapy. By contrast, the widespread use of herbs and herb extracts to minimize cancer therapy side effects in the Orient is accompanied by extensive favorable reports.
REASONABLE PHYSICIAN’S ADVICE
Cautions that can reasonably be forwarded by physicians are these:
The use of herbs and dietary supplements, including vitamins and antioxidants, as adjuncts to modern cancer therapies, is an area of ongoing research and, at this time, little is known about the clinical effects.
Concerns have been raised about use of antioxidants, mainly high doses of vitamin C and high doses of glutathione, based on laboratory experiments suggesting that these substances might impair the full effect of cancer therapies.
Clinical studies have not yet revealed any adverse effects, but the concern persists on a theoretical basis, backed up by the laboratory reports; there are also laboratory and clinical reports that suggest that vitamin C and glutathione have positive effects in relation to cancer therapies.
There is a wide range of recommendations for patient actions based on interpretations of the data available so far. These range from recommendations to administer herbs, vitamins, and other supplements to reduce the adverse effects of cancer therapies without impairing the benefits of the cancer therapies, to maintaining normal healthy dietary recommendations without adding anything, to specifically avoiding antioxidant substances, including those that are normally present in a healthy diet.
Most medical experts agree that one should not pursue high doses of nutritional supplements or herbs because not enough is known about their potential impact on cancer therapies; their purported benefits may not be confirmed, while there could be risks.
However, the only substances for which a strong caution has been repeated are St. John’s wort, which may lower the dose of chemotherapy drugs in the body (no impact on radiation therapy is expected), high doses of vitamin C, which might have some protective effect for cancer cells during the therapy, and the antioxidant glutathione, which if taken continuously in large dose might aid cancer cell drug resistance.
In making these comments, physicians should recognize that a wide range of therapies are offered to patients and that the meaning of “high dose” or “continuous use” may vary.
For example, physicians should recognize that some proponents of high dose vitamin C therapy recommend huge doses of the vitamin specifically for purported anti-cancer effects. The amounts involved are difficult to consume in one day (e.g., orally consumed up to bowel tolerance, which is typically in the range of 6-12 grams per day). Indeed, some have recommended a continuous vitamin C intravenous drip (8 hours a day) to try inhibiting cancers that are resistant to standard medical therapies (this is after chemotherapy has been suspended).
Such huge doses of vitamin C are unproven for effectiveness and could conceivably reduce the impact of concurrent cancer therapies by a number of mechanisms because very high blood levels are attained.
However, most nutritional supplements that involve high doses of vitamin C provide less than 2 grams of the vitamin each day, usually spread over 2 to 3 doses. Blood levels do not rise very much by oral administration, as the vitamin is absorbed gradually and excreted within hours.
There is no evidence that these amounts of oral vitamin C would be harmful for cancer patients. Most proponents of nutritional supplementation, relying upon extensive reports on vitamin C, currently recommend doses of 500-1,500 mg/day. Patients could be cautioned to limit their intake of this particular vitamin to no more than that range.
It is important to note that if cancer cells have a mechanism for absorbing large amounts of vitamin C, and if this is helpful to the growth of cancer cells or to protect against anti-cancer therapies, the amount of vitamin C available in the body normally (baseline of about 60 micromoles/liter) should be sufficient to satisfy the cancer’s appetite for it.
Aside from the projected problems with high-dose vitamin C (Dr. Golde did not show inhibition of cancer therapies, only high uptake of vitamin C by cancer cells), there simply is no evidence that other antioxidants (except possibly glutathione), nutritional supplements, or herbs (except St John’s wort) inhibit cancer therapies or worsen overall outcomes.
To the contrary, they appear to improve outcomes. In the case of St. John’s wort, this herb was not proposed as either a treatment for cancer nor a treatment for cancer therapy side effects; rather, it has been used incidentally in the treatment of depression.
Thus, no herbs intentionally used as adjuncts to cancer therapy have been implicated in adverse effects clinically.
Even in the case of glutathione, there is reason to believe this substance is not problematic in clinical practice. A concern was raised earlier about supplementation with glutamine, an amino acid that is used to produce glutathione in the body and which is considered a “glutathione-sparing” agent: as glutamine levels increase, glutathione levels are maintained at high levels.
Several studies have indicated that glutamine might be a valuable aid to cancer patients, recommended to prevent neuropathy from high dose chemotherapy, to protect the heart from damage due to doxorubicin therapy, and to protect the bowel from damage due to radiation or chemotherapy, but the concern was raised that it would also benefit cancer cells. The studies conducted to date do not support a negative effect for glutamine in relation to cancer.
To the contrary, glutamine appears to improve the retention of the chemotherapy drug methotrexate by tumor cells. In one report on this subject, it was concluded that: “These data suggest that oral glutamine supplementation will enhance the selectivity of antitumor drugs by protecting normal tissues from and possibly sensitizing tumor cells to chemotherapy treatment-related injury.” The mechanism of action was proposed to be the increase in cellular glutathione related to elevated glutamine levels (18).
Dr. VS Klimberg, of the Department of Pharmacology, University of Arkansas, has been a leading researcher in the use of glutamine as a protective agent for cancer patients and has reported widely on its effects. Glutamine and glutathione are currently recommended by many who advocate the use of adjunctive cancer therapies.
Physicians who wish to approach the issue with the most conservative viewpoint could caution patients about extreme therapies, with multiple high dose antioxidants, but cannot with any clinical evidence argue against moderate use of herbs, vitamins, or antioxidants.
In fact, the evidence, limited as it may be, is that moderate use of antioxidants is a reasonable approach for patients who are concerned about chemotherapy side effects.
In a recent review of the subject, Kedar Presad and colleagues at the Center for Vitamin and Cancer Research, Department of Radiology, Health Sciences Center, University of Colorado, described the differing views and, as a summary, they pointed out (19):
Radiation therapy is one of the major treatment modalities in the management of human cancer. While impressive progress like more accurate dosimetry and more precise methods of radiation targeting to tumor tissue has been made, the value of radiation therapy in tumor control may have reached a plateau.
At present, two opposing hypotheses regarding the use of antioxidants during radiation therapy have been proposed.
One hypothesis states that supplementation with high doses of multiple micronutrients including high dose dietary antioxidants (vitamins C and E, and carotenoids) may improve the efficacy of radiation therapy by increasing tumor response and decreasing some of its toxicity on normal cells.
The other hypothesis suggests that antioxidants (dietary or endogenously made) should not be used during radiation therapy, because they would protect cancer cells against radiation damage.
Each of these hypotheses is based on different conceptual frameworks that are derived from results obtained from specific experimental designs, and thus, each may be correct within its parameters.
The question arises whether any of these concepts and experimental designs can be used during radiation therapy to improve the management of human cancer by this modality.
Based on the review of literature, the authors concluded that vitamin C, vitamin E, carotene, and other antioxidants could be useful as a safe adjunct to radiation therapy. Matt Brignall, of the Seattle Cancer Treatment and Wellness Center, where adjunctive therapies are emphasized, also pointed to the evidence supporting the benefit of antioxidants during cancer therapy, saying (20):
Critics of the concurrent use of antioxidants and chemotherapy often point to the lack of clinical trials in humans.
Previous preliminary clinical trials, however, have concluded that the antioxidants ginkgo (Ginkgo biloba), melatonin, coenzyme Q10, and N-acetylcysteine did not appreciably reduce the effect of cancer therapies.
Pharmaceutical antioxidants, such as amifostine and mesna, have also been extensively studied in conjunction with chemotherapy and radiation, and have not appeared to cause a negative interaction.
Many prominent cancer scientists believe that the dietary and pharmaceutical antioxidants prevent some of the worst side effects of cancer treatments.
Further, a common antioxidant now recommended to cancer patients is green tea, which contains an amino acid (theanine) that appears to help retain doxorubicin and other chemotherapy drugs within cancer cells (21).
Thus, while it can be reasonable for physicians to offer some limited cautions about use of herbs, vitamins, and antioxidants, they must also be careful not to warn people away from potentially usefully adjunct therapies.
December 2002
REFERENCES
Leslie M, Vitamin C: How much do you really need?, WebMDHealth, June 19, 2000.
Cancer tumors shown to consume large amounts of vitamin C. Researchers are cautious about cancer patients taking vitamin C supplements. Memorial Sloan-Kettering Cancer Center, 1999. http://www.mskcc.org/mskcc/html/1166.cfm.
Russo J, Potential interaction between antioxidants and cancer treatment, http://www.medcomres.com/articles/antioxidants_cancer.htm.
Roller A, Weller M, Antioxidants specifically inhibit cisplatin cytotoxicity of human malignant glioma cells, Anticancer Research 1998; 18(6A): 4493-4497.
Cascinu S, et al., Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind placebo-controlled trial, Journal of Clinical Oncology 2002; 20(16): 3478-3483.
Health Notes, 2000 Healthnotes, Inc.: http://www.hollandandbarrett.com/Drug/Cyclophosphamide.htm.
Ghosh J, Das S, Role of vitamin A in prevention and treatment of sarcoma 180 in mice, Chemotherapy 1987; 33: 211-8.
Taper HS, de Gerlache J, Lans M, Roberfroid M, Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment, International Journal of Cancer 1987; 40: 575-9.
Jaakkola K, Lahteenmaki P, Laakso J, et al., Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer, Anticancer Research 1992; 12: 599-606.
Nobile MT, Vidili MG, Benasso M, et al., A preliminary clinical study of cyclophosphamide with reduced glutathione as uroprotector, Tumori 1989; 75: 257-8.
Rush Presbyterian St. Luke’s Medical Center, Vitamin E does not protect cancer cells against radiation, January 15, 2000, PSA Rising Magazine, http://psa-rising.com/medicalpike/ebr/andvitEC031901.shtml.
Rush Presbyterian St. Luke’s Medical Center, Vitamins C and E does fight side effects of pelvic radiation for cancer, March 20, 2001, PSA Rising Magazine http://psa-rising.com/medicalpike/ebr/vitE-C-proctitis031901.shtml.
Dykes B, Hypertext Guide to Prostate Cancer, Chemotherapy: vitamins and chemotherapy, 2001, http://www.hypertext.org/ENGLISH/ADVANCED.html.
Williamson D, Study: Avoiding vitamins A, E might improve cancer therapy, University of North Carolina News Services, December 13, 1999, http://www.unc.edu/news/newsserv/research/dec99/salganik121399.htm.
Holick CN, et al., Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the alpha-tocopherol, beta-carotene cohort study, American Journal of Epidemiology 2002; 156(6): 536-547.
Mathijssen RH, Effects of St. John’s wort on irinotecan metabolism, Journal of the National Cancer Institute 2002; 94(16): 1187-1188.
Levine M, et al., Criteria and recommendations for vitamin C intake, Journal of the American Medical Association 1999; 281:1415-1423.
Rouse K, Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism, Annals of Surgery 1995; 221(4): 420-426.
Prasad KN, et al., Pros and cons of antioxidant use during radiation therapy, Cancer Treatment Reviews 2002 28(2): 79-91.
Brignall M, Is it safe to use antioxidant supplements with chemotherapy?, Healthnotes Newswire, October 10, 2002.
Sadzuka Y, et al., Enhancement of the activity of doxorubicin by inhibition of glutamate transporter, Toxicology Letters 2001; 123(2-3): 159-67.
APPENDIX 1. BASIC UNDERSTANDING OF THE CANCER THERAPIES
The precise mechanisms of cancer therapies are not fully worked out, though considerable information is available. The following is an overview, based on the author’s understanding, indicating the potential role of herbs, vitamins, and antioxidants in preventing side effects of cancer therapies without impairing anticancer treatment.
Radiation
Standard external radiation therapy pinpoints a beam of intensely energetic photons (x-rays, gamma-rays or beta-rays) to a tumor site (see Figure 4). The radiation dose at the focal point is lethal to the cells. Some of the radiation directly breaks up cellular DNA and other components in the target area; it is estimated that about one-third of the damage is direct destruction of critical molecules, leading to inability of the cell to reproduce or to prompt cell death. The primary damage to the tumor, however, comes from generation of a huge number of free radicals that interact with cellular components and disrupt them. These free radicals are mostly generated from water, because it is the most abundant substance in the cells. Because of the beam intensity at the focal point, no amount of antioxidant activity from orally ingested supplements is likely to be able to save these cells.
External radiation therapy is usually administered over an extended period, with several treatments spaced out with many days interval between. The reason that the whole task is not performed with one treatment is that the collateral damage from the radiation would be so severe as to threaten the patient’s survival. As it is, when the beam enters the body on its way to the tumor site and exits beyond the tumor, and spreads a bit on either side of the target, the collateral damage is notable and can be extreme. The skin becomes burned and delicate internal organs can become severely damaged and almost unusable. For example, radiation to the throat area can make swallowing virtually impossible; abdominal radiation can cause intestinal ulceration that doesn’t heal for months if at all. Still, these off-target tissues are able to repair somewhat between the treatments thanks to the more limited damage at these sites compared to at the tumor itself. As the distance from the beam’s focal point increases, there is greater chance to protect the cells with antioxidants that are able to handle the small number of free radicals that are generated.
There are other types of radiation therapy, including brachytherapy, in which radioactive material is inserted into the tumor (as commonly employed for prostate cancer): the radiation spreads out around radioactive “seeds” and kills all cells in the surrounding area, with reduced damage the greater the distance from the radiation source. There are now proton and neutron beams that have a higher proportion of damage caused by direct strikes at DNA and other cellular components, with less reliance on free radical generation.
It is a desired outcome that the collateral damage from all radiation techniques be minimized, which is a potential valuable role for antioxidants. The chances of antioxidants protecting the tumor cells are minimal; there is simply too much radiation at the target. Failures of radiation therapy are mostly attributable to metastasis of the cancer cells (before radiation begins) rather than failure of the radiation to destroy every cancer cell at the target tumor site. No amount of antioxidant therapy nor the reverse-complete avoidance of antioxidant therapy during radiotherapy-will have an impact on this metastasis that has occurred before radiation therapy. Metastatic cells can not be detected by current means and may not reveal themselves for months or even years, which is why cancer therapies are not considered a true success until 5 years pass without sign of new tumor growth, usually at a different site.
One cannot know for certain what effect-good or bad-antioxidants will have on the effects of radiation therapy, without extensive clinical testing that may take years. The concept that tumor cells can be protected is largely based on the assumption that antioxidants are extremely efficient. They would have to clean up the reactive oxygen species as fast as they are produced. Yet, the very large amount of antioxidant research conducted over the past decade clearly shows that these substances have limited impact for several diseases. Where they were thought to have the potential to treat diseases, they have not been very successful, and where they are thought to prevent diseases, they appear effective so long as the exposure to the antioxidants is for years and years, having a continuous mild impact. Antioxidants can be expected to provide some aid to cells unintentionally caught in the periphery of radiation therapy, but, even there, complete protection is not expected due to limited effects.
Chemotherapy
As with radiation therapy, chemotherapy is administered over an extended period, often (though not always), with a duration of several days or weeks between treatments. As with radiation therapy, the task cannot be accomplished all at once, because a lethal chemotherapy dose for the entire tumor would also be lethal for the patient. In fact, one of the key measures of the patient’s ability to continue chemotherapy is recovery of the white blood cell count that has been impaired by the drug therapy (this does not apply to some of the new immune based and genetic therapies). Chemotherapy is usually not as focused as radiation therapy on the tumor, and affects the entire body (commonly causing hair loss, distress of the gastro-intestinal system, white blood cell depletion, and fatigue). An adjunctive treatment that protects non-target cells (normal cells) might also protect cancer cells. However, as occurs with radiation therapy, there is a difference between the intensity of the drug action on cancer cells and on other cells, such as bone marrow cells. Otherwise, once the cancer was destroyed successfully, the bone marrow would also be destroyed (which is, in fact, one of the radical chemotherapy approaches, but not the first line treatment). Chemotherapy drugs are selected for clinical use on the basis that they have a more potent action on cancer cells than on other cells. Thus, after the cancer is destroyed, hair grows back, digestion returns to normal, and the immune system functions fully once again. Protection that helps the bone marrow does not necessarily have the potency to protect the cancer cells. Failure of chemotherapy is often the result of the presence of some resting cells, usually cells outside the active tumor mass, that do not respond to chemotherapy drugs. The drugs usually interact with replicating DNA and might miss such individual metastatic cells that are quiescent.
Polysaccharides from herbs have been used for protecting the bone marrow in cancer patients undergoing chemotherapy in China, Japan, and other countries for many years. The clinical study reports indicate improved outcomes (better survival) in patients who utilize this adjunct therapy. It can be argued that the study methodology is inadequate to support the improved survival, and it can be argued that the valid outcomes might be clinically insignificant, so that there is little or no interest in pursing this approach here. But, there is no evidence that bone marrow protection leads to negative effects in terms of tumor destruction or survival rates.
A positive role for antioxidants in the case of chemotherapy drugs is protection against a variety of undesired secondary effects, particularly neuropathy and cardiac damage. The chemotherapy drugs do not function as oxidants, but, rather, influence the cellular DNA and RNA (see Figures 5-6). Except in one in vitro study cited above for glioma cells that are normally resistant to chemotherapy, there is no evidence that antioxidants worsen the outcome of cancer chemotherapies. To the contrary, there is some evidence of protection for secondary effects. Dr. Golde’s in vitro research on vitamin C did not show that this substance impaired cancer therapies, only that cancer cells seem to “soak up” the vitamin. His results may not translate to an impairment of the effects of radiation therapy or chemotherapy.
The essential factor in both radiation therapy and chemotherapy is the specificity of the treatment for cancer cells. Antioxidants, herbs, and other kinds of natural supplements are being applied to protect cells that are unintentionally damaged by cancer therapy where the damage is substantially less severe than that caused to the cancer cells. The ability to provide protection for non-target cells without interfering with the damage to cancer cells is based largely on the differential. One may expect that where a cancer therapy is equally lethal to target and non-target cells, that a therapy protective of the non-target cells might also be protective of the target cells. Despite the apparent protection offered by antioxidants and herbs to non-target cells, their abilities to provide that protection are limited. Patients still experience side effects; they are only reduced in intensity. The ability of these same substances to protect target cells is far less, which explains why there hasn’t been a sudden failure of cancer therapies during the past decade when millions of people have turned to routine use of supplements with vitamin C, vitamin E, and other antioxidants.
From: preliminary report by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon http://www.itmonline.org/
We posted this 6/03
DO HERBS, VITAMINS, AND ANTIOXIDANTS ADVERSELY AFFECT CANCER THERAPIES?
preliminary report by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon
For more than 30 years now, Chinese herbs and materials derived from the herbs, such as long chain polysaccharides, have been used as adjunct therapies for cancer patients.
This modern application was first developed clinically in China and Japan during the 1970s and was relayed to the rest of the world in 1983 through an international conference in Beijing which was followed up by press reports in English and other languages (see: Physiological responses to immunologically active polysaccharides).
The Institute for Traditional Medicine (ITM) made an effort to alert practitioners of Chinese medicine in the U.S. to this promising role for Chinese herbs immediately after that conference, with updated information provided as available over the years. The utilization of Chinese roots, leaves, and fruits (e.g., astragalus, gynostemma, ligustrum, and lycium), and several mushrooms (e.g., coriolus, ganoderma, cordyceps, and lentinus) for cancer patients is now a routine procedure when these patients visit acupuncturists, naturopathic physicians, and others offering adjunctive cancer health care.
Within the past couple of years, however, an increasing number of patients have been told by their oncologists to avoid herbs, and to more generally avoid supplements (such as vitamins), or, even more broadly, simply avoid anything with antioxidant potential while they are undergoing cancer therapies.
The admonition itself is difficult to interpret, since all foods contain antioxidants and vitamins, and they also contain most of the other substances offered in dietary supplements. Most fruits, vegetables, beans, and nuts differ only slightly from herbs. A more specific recommendation is needed.
But first, the question arises: why are doctors giving these instructions? What kind of information is being released to the public?
I have attempted to trace back the origins of the restrictions imposed by some oncologists, and it seems that the primary instigator of the concern was Dr. David Golde at the Memorial Sloan-Kettering Cancer Center, even though he was not the first to raise the matter (but within a few months of being first).
The main issue he raised was the use of high doses of vitamin C, a therapy that has nothing directly to do with herbs. Herbs usually have little or no vitamin C; still, vitamin C is commonly prescribed or recommended as a supplement by practitioners involved in natural healing.
In a June 19, 2000 report of WebMD Medical News, the use of high doses of vitamin C to prevent heart disease, cancer, and other disorders, was called into question, and Dr. Golde’s research and comments were relayed (1, 2):
The first of two recent studies that called this notion [of taking high doses of vitamin C as a disease preventive] into question was carried out by David Golde, MD, physician-in-chief at Memorial Sloan-Kettering Cancer Center in New York City, and described at an American Cancer Society meeting in March 2000.
Golde and his colleagues transplanted human cancer cells into mice, injected the mice with vitamin C, and then measured the amount of the vitamin in the cells. They found that cancer cells seem to soak up large amounts of vitamin C by converting it into a form that’s easier to absorb. The results, Golde says, raise the possibility that cancer cells may use vitamin C to shield themselves against radiation and chemotherapy.
The second study, performed by James Dwyer, Ph.D., an epidemiologist at the University of Southern California, caused an even bigger stir. Dwyer told an American Heart Association meeting in March 2000 that middle-aged men who took 500 milligrams of vitamin C supplements daily showed a rapid narrowing of their carotid arteries, which supply blood to the brain.
The studies sound alarming, but experts warn against making too much of them. While Golde says that cancer patients shouldn’t take large doses of the vitamin, other researchers say it’s far too early to make that recommendation.
There’s no evidence yet that C actually shields cancer cells from treatment, says Mark Levine, MD, an endocrinologist and Vitamin C expert at the National Institutes of Health. The cancers tested in Golde’s research, he says, may simply have grown from tissues that normally take in large amounts of the vitamin.
As for the heart disease finding, Dwyer himself cautioned that it is preliminary. The study lasted only 18 months and included just 573 men. And Robert Jacob, Ph.D., a research chemist with the U.S. Department of Agriculture, points out that previous studies suggested just the opposite-that vitamin C reduces the narrowing of carotid arteries.
From these very modest beginnings in Spring of 2000, the worry about antioxidants and cancer therapies grew, despite several warnings about the interpretation of data, such as those mentioned in the above analysis, and almost everyone who wished to provide a basis for the antioxidant and vitamin worry seemed to harken back to Dr. Golde’s very preliminary research.
A pharmacist, John Russo, Jr., wrote the following to caution his readers about the possible interaction of antioxidants with brachytherapy (radiation therapy where the radiation source is placed inside the body) for prostate cancer (3):
How might an antioxidant adversely affect brachytherapy?
The precise role that the antioxidant, vitamin C, plays in tumors is not known, but recent studies have shown possible interactions between dietary antioxidants and cancer treatment.
We know that vitamin C is a powerful antioxidant. It consumes free radicals, the toxic substances in the body that can be generated by chemotherapy agents to destroy cancer cells. “It is possible,” according to Dr. David Golde, Physician-in-Chief at Memorial Sloan-Kettering Cancer Center, “that taking large amounts of vitamin C could interfere with the effects of chemotherapy or even radiation therapy.” These therapies often kill cells, in part, by using oxidative mechanisms.
It’s conceivable then, that vitamin C might make cancer treatment less effective, and it is reasonable that cancer patients undergoing chemotherapy avoid taking large amounts of this vitamin.”
Building on past research
Earlier research by Dr. Golde and his colleagues established that specific glucose transporter molecules carry vitamin C into cells. This occurs once vitamin C, which is used by cells in the form of ascorbic acid, is converted into dehydroascorbic acid and transported into the cell. Once inside, the vitamin is converted back to ascorbic acid.
Applying this information to patient care
According to David Agus, an oncologist at Memorial Sloan-Kettering Cancer Center, we now know that tumors acquire and retain large amounts of vitamin C. And their nutritional needs appear to be similar to healthy cells that take in large amounts of the vitamin.”
However, what cancer cells do with the vitamin C after it is absorbed is not known. This will have to be determined before guidelines for the complementary use of antioxidants during chemotherapy and radiation become established.
Furthermore, research from University of Tubingen, School of Medicine in Germany suggests caution in applying this knowledge to all antioxidants in all types of malignancies. Examination of the modulation of drug-induced cytotoxicity and clonogenic cell death of glioma cells by three structurally unrelated antioxidants revealed that these antioxidants inhibit acute cytotoxicity and clonogenic cell death induced by cisplatin.
However, they had little effect on the toxicity of other cancer drugs including BCNU, doxorubicin, vincristine, cytarabine, or camptothecin.
In the discussion of brachytherapy, the pharmacist carries the implications over to chemotherapy agents, but mistakenly states that these function by producing free radicals. In general, this is not the case, and only applies to radiation (see explanation of mechanism, Appendix).
The research cited here about an inhibition of cisplatin therapy by antioxidants (but, notably, no effect of the tested antioxidants on several other chemotherapy drugs) was published in 1998 (4), and did not produce much interest at the time, nor has a follow-up report been published to date (end of 2002).
Glioma cells (a type of brain cancer) are normally resistant to the effects of chemotherapy, and the authors were examining factors influencing this already poor response. They determined, in their study, that cisplatin did not rely on free-radical formation to damage glioma cells, so antioxidant activity working directly against cisplatin effects was not an issue.
Rather, the substances tested in this in vitro study appeared to function by some other unknown mechanism.
By contrast, another platin drug, oxaliplatin, was used in a double-blind, placebo controlled clinical trial along with administration of the antioxidant glutathione (GSH; see Figure 1).
The authors concluded (5): “This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.”
This is an important finding, because it had been proposed that cancer cells could become resistant to platin drugs (e.g., cisplatin and carboplatin;) due to changes in the cancer cell membrane, where the resistance may be caused by the binding of platinum to intracellular thiols, such as glutathione.
This possibility, based on in vitro studies, implies that the interaction between platinum and GSH could prevent the active compounds from reaching the DNA nucleus. It is unclear at this point, whether administering glutathione can be recommended (as is often done by proponents of its protective effects), but this substance does not appear to have any direct interference with oxaliplatin when used clinically based on the recent clinical trial.
In vitro studies indicate that high intracellular glutathione levels protect cancer cells from the effects of chemotherapy, but this may not carry over to the clinical situation.
A related concern about chemotherapy drug resistance has been raised about using antioxidants with cyclophosphamide, a particularly toxic anticancer drug. When the literature was reviewed, it was found that, if anything, the substances were beneficial for patients on cyclophosphamide therapy. Here is the interaction caution about this drug as relayed in Healthnotes (6-10):
Interactions with Dietary Supplements
Antioxidants
Cyclophosphamide requires activation by the liver through a process called oxidation. In theory, antioxidant nutrients (vitamin A, vitamin E, beta-carotene and others) might interfere with the activation of cyclophosphamide.
There is no published research linking antioxidant vitamins to reduced cyclophosphamide effectiveness in cancer treatment.
In a study of mice with vitamin A deficiency, vitamin A supplementation enhanced the anticancer action of cyclophosphamide. Another animal research report indicated that vitamin C may increase the effectiveness of cyclophosphamide without producing new side effects.
Preliminary human research found that adding antioxidants (beta-carotene, vitamin A, and vitamin E) to cyclophosphamide therapy increased the survival of people with small-cell lung cancer treated with cyclophosphamide.
It is too early to know if adding antioxidants to cyclophosphamide for cancer treatment is better than cyclophosphamide alone. Vitamin A can be toxic in high amounts.
Intravenous injections of the antioxidant, glutathione, may protect the bladder from damage caused by cyclophosphamide.
Preliminary evidence suggests, but cannot confirm, a protective action of glutathione in the bladders of people on cyclophosphamide therapy. There is no evidence that glutathione taken by mouth has the same benefits.
As reported here, when laboratory animal and clinical evaluation is the basis for the information, the potential benefits of antioxidants appear. One could say that there has been some backlash at the anti-antioxidant stance promoted by those who quote Dr. Golde and extend his vitamin C research to imply that all antioxidants are problematic for cancer patients.
At the Rush Presbyterian St. Luke’s Medical Center, the suggestion that vitamin E might inhibit radiation effects was discounted. A press report stated (11):
Vitamin E Does Not Protect Cancer Cells Against Radiation
New York. 15 January 2000 (posted 19 March, 2001). Cancer patients who take vitamin E are probably not hindering the desired effects of radiation, according to a laboratory study done by radiation oncologists at Rush-Presbyterian-St. Luke’s Medical Center in Chicago.
Researchers at Rush were concerned that patients who take vitamin E may be inadvertently providing protection for the cancer cells that are the target of radiation therapy. Radiation damage is one form of oxidation, and vitamin E’s antioxidant properties presumably extend to cancer cells.
To determine if this were true, Rush researchers, led by Dr. Ed Blazek, director of radiation biology in the Rush department of radiation oncology, grew cells originating from human breast and prostate tumors in nutrient solutions containing several concentrations of vitamin E. The cells were then irradiated with the same daily doses used for patients.
The Rush team found that the tested concentrations of vitamin E did not interfere with the desired killing of cancer cells by radiation. An important limitation of this study, however, is that the level of vitamin E taken up by the cancer cells in laboratory culture has not yet been measured, and might be smaller than the level taken up by cells of a tumor in the patient’s body. If so, it is still possible that vitamin E might worsen treatment outcomes.
Although no undesirable protection of cancer cells was found, the researchers issued a caution to those taking vitamin E and other alternative therapies. “Any drug that is taken during cancer radiotherapy or chemotherapy should be tested to prove that it does not protect the tumor cells, defeating the intended effect of the treatment,” Blazek said.
Natural extensions of this work would include the addition of the drug pentoxifylline to vitamin E, since this combination has been reported to partially reverse radiation damage to normal tissue, the testing of vitamin C for radioprotection, and the testing of both vitamins E and C for protection from representative cancer chemotherapy drugs.
This research, performed by Drs. Alex Perez and Katherine Baker together with Dr. Blazek, was presented at the annual meeting of the Radiological Society of North America in Chicago.
Then, in a follow-up report from the same hospital, this time including vitamin C (12, 13):
Vitamins C and E Fight Side Effects of Pelvic Radiation for Cancer
March 20, 2001. A small study of 20 men and women suffering from chronic radiation proctitis has shown that daily vitamins E and C substantially reduced or eliminated their symptoms. Proctitis has traditionally been treated with anti-inflammatory agents, without satisfactory results.
Radiation therapy is one treatment option for men with localized prostate cancer and for women with cervix and endometrial cancers. Radiation therapy is effective in killing cancer cells. But the therapy damages also any normal, non-cancerous cells within range of the beam.
Complications are especially common in patients who are treated with older equipment. New, 3D conformal, Intensity Modulated or Proton beam equipment (available in the USA and some other countries) targets the beam much more precisely. Higher doses can be given to tumor with less damage to bladder and rectum.
Most patients take vitamins-does this interfere with killing cancer cells?
Even under the best conditions patients want to do everything possible to protect themselves from radiotherapy side effects. Many patients who undergo cancer treatments take vitamins and supplements. Until recently, oncologists seldom asked patients about this.
Doctors still have almost no evidence on which to advice cancer patients about common supplements. But a previous, laboratory study by radiation oncologists at Rush-Presbyterian-St. Luke’s Medical Center found that “Cancer patients who take vitamin E are probably not hindering the desired effects of radiation.”
Dr. Keith Bruninga, gastroenterologist at Rush-Presbyterian-St. Luke’s has now looked to see how much protection vitamins E and C actually offer patients irradiated for prostate, cervical or endometrial cancer. The effect of the vitamins in the treatment of chronic radiation proctitis had not been studied before, Dr. Bruninga said.
In normal bowel and rectal tissues exposed to radiation for cancer in the pelvis, oxygen radicals form and patients experience the symptoms of proctitis, he said. The condition starts with swollen, inflamed tissue, and it increases with dose. The symptoms, which may include diarrhea, pain, bleeding and incontinence, usually clear up within a few weeks of the last radiation treatment.
However, the symptoms do not clear up in 10-20 percent of patients. Some patients develop symptoms months or years after the initial radiation exposure.
“Our study showed that we can harness the potent antioxidant properties of the vitamins to repair cell damage and bring relief to many people who suffer from the persistent, lifestyle-altering symptoms of chronic radiation proctitis,” Dr. Bruninga says in a paper published in the April issue of The American Journal of Gastroenterology.
Oxygen free radicals form from cells that have been injured. Oxygen free radicals are highly active molecules that react with cells by changing or damaging their structure. The formation of the oxygen free radicals increases the amount of injury to the cells and results in a chronic condition as blood flow to the cells is decreased.
Vitamin E is a potent antioxidant that can react with damaging oxygen free radicals. Vitamin C in combination with E increases the effects of vitamin E. The researchers believe that the antioxidant treatment regimen using the vitamins counteracts and can prevent oxygen free radical injury and increase blood flow to the injured cells of patients with chronic radiation proctitis.
Patients in the study, ten men and ten women with chronic radiation proctitis, took one 400 IU vitamin E tablet along with one 500 mg vitamin C tablet three times each day for eight consecutive weeks. Patients purchased the vitamins themselves at the store of their choice.
Each patient in the study rated their symptoms in terms of severity and frequency before and after treatment with the vitamins using a questionnaire developed by the researchers.
The impact of the symptoms on the lifestyle of the patients was also assessed using a questionnaire. Ten of the patients were assessed again after one year to determine if their initial responses were sustained.
The assessments showed a significant improvement in bleeding, diarrhea and urgency after taking the vitamins. Patients with rectal pain did not improve significantly. Thirteen patients reported an improvement in their lifestyle including seven whom reported a complete return to normal.
All of the ten patients who were assessed after one year reported a sustained improvement in their symptoms while continuing to take the vitamins.
The Rush physicians believe that the actual incidence of the ailment is greater than the estimated 10-20 percent of radiation patients. They feel that many patients, relieved and grateful that their cancers are remission, are embarrassed to tell their physicians about the symptoms of radiation proctitis.
Currently, the Rush physicians are seeking additional individuals with chronic radiation proctitis to conduct a larger, double-blinded study of the effectiveness of antioxidants in the treatment of the illness.
“If our continued research shows that the antioxidant regimen is successful in treatment of this illness, we plan to investigate its use to prevent chronic radiation proctitis,” said Dr. Bruninga.
Results of the study appear in April 2002 issue of The American Journal of Gastroenterology.
THE ALTERNATIVE: AVOIDING EVEN NORMAL LEVELS OF ANTIOXIDANT INTAKE
One of the early complaints about vitamins and chemotherapy was this one, described just four months before Dr. Golde made his comments at an American Cancer Society Meeting, summarized by a report on prostate cancer (13):
Vitamins and Chemotherapy
Although the antioxidant vitamins A, C, and E help repair damaged cells, it is probably not a good idea to take large amounts during radiation treatment. One object of chemotherapy is to damage cancer cells. Antioxidants, however, appear to counteract the process, according to Dr. Rudolph Salganik’s report to the annual meeting of the American Society for Cell Biology (December 1999).
He pointed out that “Almost all anticancer drugs kill cancer cells by way of apoptosis, and antioxidants like vitamin A and vitamin E dramatically reduce apoptosis in cancer cells.” Patients should therefore avoid taking any more than a normal amount of these vitamins during chemotherapy treatment.
This sounds like reasonable advice-just don’t add to normal intake-but Dr. Salganik’s own suggestion went further: indicating that an antioxidant-depleted diet could improve cancer therapies. The study referred to above was reported on as follows (14):
Study: avoiding vitamins A, E might improve cancer therapy
By David Williamson, UNC-CH News Services
CHAPEL HILL-Vitamins A and E, which normally boost human health in numerous ways, also appear to keep cancer cells from dying through the natural protective process scientists call apoptosis, new University of North Carolina at Chapel Hill research shows.
As a result, giving patients those vitamins may prevent cancer cells from self-destructing and work against cancer therapy, scientists say.
Researchers at UNC-CH’s schools of public health and medicine presented their findings Monday (Dec. 13) during a news conference at the American Society for Cell Biology’s annual meeting in Washington, D.C. Drs. Rudolph Salganik, research professor of nutrition, and Terry Van Dyke, professor of biochemistry and biophysics, directed the studies.
“We believe this work is important because it may make cancer treatments more effective,” Salganik said. “It suggests that cancer patients, especially those undergoing chemotherapy or radiation therapy, may do better on an antioxidant-depleted diet.”
The scientist and his colleagues study reactive oxygen species (ROS), which play a central role in the series of signals that allow cells to kill bacteria and viruses, destroy toxins and trigger the apoptotic “suicide” of defective cells such as cancer, he said. Antioxidants, such as vitamins A and E, protect normal cells from the damaging effects of ROS but apparently also can prevent the targeted apoptotic death of cancer cells that threaten humans and other mammals, the new work suggests.
Other researchers involved were Drs. Craig D. Albright, research assistant professor of nutrition; and Steven H. Zeisel, professor of nutrition and pediatrics and chair of nutrition.
The UNC-CH experiments involved putting mice that were predisposed to developing brain tumors on specially modified diets that were either supplemented with standard amounts of antioxidants or were antioxidant deficient for four months. Researchers then carefully monitored the rodents’ health and their brain tumors, if any, to see how the animals fared on the different diets.
Mice receiving extra vitamins A and E showed no benefit in either the size or incidence of brain tumors, Salganik said. They also had relatively short lives.
“Interestingly and more importantly, in animals that received antioxidant-depleted diets, brain tumors were significantly reduced in size because of induction of oxidant stress due to what are commonly called free radicals in the brain tumors,” Albright said. “Higher levels of cell death was restricted only to the brain tumors, while normal tissues were not affected by depletion of antioxidants in the mouse diets.”
In mice getting low levels of vitamins A and E, no negative effects were seen in normal cells, but about 19 percent of tumor cells showed evidence of apoptosis. In those ingesting normal quantities of antioxidant vitamins, only about 3 percent of tumor cells were apoptotic.
The group’s findings may explain two previous clinical studies showing that heavy smokers who ate a diet high in beta-carotene antioxidants had significantly higher rates of lung cancer, Salganik said.
“These new studies raise important issues regarding the advisability of ingesting high levels of antioxidants as a potential anti-cancer benefit,” Albright said. “Clearly, more studies are needed at the clinical level in human populations to address the real value of antioxidant supplements or antioxidant depletion in people at risk of developing cancer.”
Salganik said he hoped clinical studies would begin within a year or two. Van Dyke is a member of the UNC Lineberger Comprehensive Cancer Center.
Up to this point, no clinical study results along these lines have been reported.
The suggestion of starving antioxidants, however, runs contrary to most of the information currently available. The study referred to above, involving heavy smokers and beta-carotene intake has already been the subject of considerable controversy and it appears there were unique factors in this population of heavy smokers in Finland that were studied.
Findings to the contrary are common. For example, in a recent evaluation of the risks of lung cancer in relation to various carotenoids ingested. The conclusion was (15):
Lower risks of lung cancer were observed for the highest versus the lowest quintiles of lycopene (28%), lutein/zeaxanthin (17%), beta-cryptoxanthin (15%), total carotenoids (16%), serum beta-carotene (19%), and serum retinol (27%). These findings suggest that high fruit and vegetable consumption, particularly a diet rich in carotenoids, tomatoes, and tomato-based products, may reduce the risk of lung cancer.
SHOULD HERBS BE WORRISOME ADJUNCTS TO CANCER THERAPIES?
There is only one herb that has been implicated in a potential adverse effect on chemotherapy, and its effect has nothing to do with antioxidant activity of the herb. This one herb has been implicated in lowering the dose of a wide range of drugs because it strongly activates the drug-metabolizing enzyme cytochrome P450 CYP3A4.
This is St. John’s wort (16), which was commonly used for treating depression during the 1990s, but has since become little used due to the concerns for drug interactions (as well as some question about its efficacy). No other herb has been identified as a potential inhibitor of chemotherapy drugs.
Although many herbs have some antioxidant potential, their influence over oxidative reactions is low due to the low dosage commonly employed. Unlike vitamin C, which is presented as a pure or nearly pure compound in dietary supplements, herbs contain little vitamin C (in relation to Dr. Golde’s concern) and low levels of antioxidant substances. Further they contain little, if any, of the substances that appeared to inhibit cisplatin cytotoxicity in cultured glioma cells.
There are no pharmacology or clinical studies showing problems with herbs other than St. John’s wort in relation to chemotherapy or radiation therapy. By contrast, the widespread use of herbs and herb extracts to minimize cancer therapy side effects in the Orient is accompanied by extensive favorable reports.
REASONABLE PHYSICIAN’S ADVICE
Cautions that can reasonably be forwarded by physicians are these:
The use of herbs and dietary supplements, including vitamins and antioxidants, as adjuncts to modern cancer therapies, is an area of ongoing research and, at this time, little is known about the clinical effects.
Concerns have been raised about use of antioxidants, mainly high doses of vitamin C and high doses of glutathione, based on laboratory experiments suggesting that these substances might impair the full effect of cancer therapies.
Clinical studies have not yet revealed any adverse effects, but the concern persists on a theoretical basis, backed up by the laboratory reports; there are also laboratory and clinical reports that suggest that vitamin C and glutathione have positive effects in relation to cancer therapies.
There is a wide range of recommendations for patient actions based on interpretations of the data available so far. These range from recommendations to administer herbs, vitamins, and other supplements to reduce the adverse effects of cancer therapies without impairing the benefits of the cancer therapies, to maintaining normal healthy dietary recommendations without adding anything, to specifically avoiding antioxidant substances, including those that are normally present in a healthy diet.
Most medical experts agree that one should not pursue high doses of nutritional supplements or herbs because not enough is known about their potential impact on cancer therapies; their purported benefits may not be confirmed, while there could be risks.
However, the only substances for which a strong caution has been repeated are St. John’s wort, which may lower the dose of chemotherapy drugs in the body (no impact on radiation therapy is expected), high doses of vitamin C, which might have some protective effect for cancer cells during the therapy, and the antioxidant glutathione, which if taken continuously in large dose might aid cancer cell drug resistance.
In making these comments, physicians should recognize that a wide range of therapies are offered to patients and that the meaning of “high dose” or “continuous use” may vary.
For example, physicians should recognize that some proponents of high dose vitamin C therapy recommend huge doses of the vitamin specifically for purported anti-cancer effects. The amounts involved are difficult to consume in one day (e.g., orally consumed up to bowel tolerance, which is typically in the range of 6-12 grams per day). Indeed, some have recommended a continuous vitamin C intravenous drip (8 hours a day) to try inhibiting cancers that are resistant to standard medical therapies (this is after chemotherapy has been suspended).
Such huge doses of vitamin C are unproven for effectiveness and could conceivably reduce the impact of concurrent cancer therapies by a number of mechanisms because very high blood levels are attained.
However, most nutritional supplements that involve high doses of vitamin C provide less than 2 grams of the vitamin each day, usually spread over 2 to 3 doses. Blood levels do not rise very much by oral administration, as the vitamin is absorbed gradually and excreted within hours.
There is no evidence that these amounts of oral vitamin C would be harmful for cancer patients. Most proponents of nutritional supplementation, relying upon extensive reports on vitamin C, currently recommend doses of 500-1,500 mg/day. Patients could be cautioned to limit their intake of this particular vitamin to no more than that range.
It is important to note that if cancer cells have a mechanism for absorbing large amounts of vitamin C, and if this is helpful to the growth of cancer cells or to protect against anti-cancer therapies, the amount of vitamin C available in the body normally (baseline of about 60 micromoles/liter) should be sufficient to satisfy the cancer’s appetite for it.
Aside from the projected problems with high-dose vitamin C (Dr. Golde did not show inhibition of cancer therapies, only high uptake of vitamin C by cancer cells), there simply is no evidence that other antioxidants (except possibly glutathione), nutritional supplements, or herbs (except St John’s wort) inhibit cancer therapies or worsen overall outcomes.
To the contrary, they appear to improve outcomes. In the case of St. John’s wort, this herb was not proposed as either a treatment for cancer nor a treatment for cancer therapy side effects; rather, it has been used incidentally in the treatment of depression.
Thus, no herbs intentionally used as adjuncts to cancer therapy have been implicated in adverse effects clinically.
Even in the case of glutathione, there is reason to believe this substance is not problematic in clinical practice. A concern was raised earlier about supplementation with glutamine, an amino acid that is used to produce glutathione in the body and which is considered a “glutathione-sparing” agent: as glutamine levels increase, glutathione levels are maintained at high levels.
Several studies have indicated that glutamine might be a valuable aid to cancer patients, recommended to prevent neuropathy from high dose chemotherapy, to protect the heart from damage due to doxorubicin therapy, and to protect the bowel from damage due to radiation or chemotherapy, but the concern was raised that it would also benefit cancer cells. The studies conducted to date do not support a negative effect for glutamine in relation to cancer.
To the contrary, glutamine appears to improve the retention of the chemotherapy drug methotrexate by tumor cells. In one report on this subject, it was concluded that: “These data suggest that oral glutamine supplementation will enhance the selectivity of antitumor drugs by protecting normal tissues from and possibly sensitizing tumor cells to chemotherapy treatment-related injury.” The mechanism of action was proposed to be the increase in cellular glutathione related to elevated glutamine levels (18).
Dr. VS Klimberg, of the Department of Pharmacology, University of Arkansas, has been a leading researcher in the use of glutamine as a protective agent for cancer patients and has reported widely on its effects. Glutamine and glutathione are currently recommended by many who advocate the use of adjunctive cancer therapies.
Physicians who wish to approach the issue with the most conservative viewpoint could caution patients about extreme therapies, with multiple high dose antioxidants, but cannot with any clinical evidence argue against moderate use of herbs, vitamins, or antioxidants.
In fact, the evidence, limited as it may be, is that moderate use of antioxidants is a reasonable approach for patients who are concerned about chemotherapy side effects.
In a recent review of the subject, Kedar Presad and colleagues at the Center for Vitamin and Cancer Research, Department of Radiology, Health Sciences Center, University of Colorado, described the differing views and, as a summary, they pointed out (19):
Radiation therapy is one of the major treatment modalities in the management of human cancer. While impressive progress like more accurate dosimetry and more precise methods of radiation targeting to tumor tissue has been made, the value of radiation therapy in tumor control may have reached a plateau.
At present, two opposing hypotheses regarding the use of antioxidants during radiation therapy have been proposed.
One hypothesis states that supplementation with high doses of multiple micronutrients including high dose dietary antioxidants (vitamins C and E, and carotenoids) may improve the efficacy of radiation therapy by increasing tumor response and decreasing some of its toxicity on normal cells.
The other hypothesis suggests that antioxidants (dietary or endogenously made) should not be used during radiation therapy, because they would protect cancer cells against radiation damage.
Each of these hypotheses is based on different conceptual frameworks that are derived from results obtained from specific experimental designs, and thus, each may be correct within its parameters.
The question arises whether any of these concepts and experimental designs can be used during radiation therapy to improve the management of human cancer by this modality.
Based on the review of literature, the authors concluded that vitamin C, vitamin E, carotene, and other antioxidants could be useful as a safe adjunct to radiation therapy. Matt Brignall, of the Seattle Cancer Treatment and Wellness Center, where adjunctive therapies are emphasized, also pointed to the evidence supporting the benefit of antioxidants during cancer therapy, saying (20):
Critics of the concurrent use of antioxidants and chemotherapy often point to the lack of clinical trials in humans.
Previous preliminary clinical trials, however, have concluded that the antioxidants ginkgo (Ginkgo biloba), melatonin, coenzyme Q10, and N-acetylcysteine did not appreciably reduce the effect of cancer therapies.
Pharmaceutical antioxidants, such as amifostine and mesna, have also been extensively studied in conjunction with chemotherapy and radiation, and have not appeared to cause a negative interaction.
Many prominent cancer scientists believe that the dietary and pharmaceutical antioxidants prevent some of the worst side effects of cancer treatments.
Further, a common antioxidant now recommended to cancer patients is green tea, which contains an amino acid (theanine) that appears to help retain doxorubicin and other chemotherapy drugs within cancer cells (21).
Thus, while it can be reasonable for physicians to offer some limited cautions about use of herbs, vitamins, and antioxidants, they must also be careful not to warn people away from potentially usefully adjunct therapies.
December 2002
REFERENCES
Leslie M, Vitamin C: How much do you really need?, WebMDHealth, June 19, 2000.
Cancer tumors shown to consume large amounts of vitamin C. Researchers are cautious about cancer patients taking vitamin C supplements. Memorial Sloan-Kettering Cancer Center, 1999. http://www.mskcc.org/mskcc/html/1166.cfm.
Russo J, Potential interaction between antioxidants and cancer treatment, http://www.medcomres.com/articles/antioxidants_cancer.htm.
Roller A, Weller M, Antioxidants specifically inhibit cisplatin cytotoxicity of human malignant glioma cells, Anticancer Research 1998; 18(6A): 4493-4497.
Cascinu S, et al., Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind placebo-controlled trial, Journal of Clinical Oncology 2002; 20(16): 3478-3483.
Health Notes, 2000 Healthnotes, Inc.: http://www.hollandandbarrett.com/Drug/Cyclophosphamide.htm.
Ghosh J, Das S, Role of vitamin A in prevention and treatment of sarcoma 180 in mice, Chemotherapy 1987; 33: 211-8.
Taper HS, de Gerlache J, Lans M, Roberfroid M, Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment, International Journal of Cancer 1987; 40: 575-9.
Jaakkola K, Lahteenmaki P, Laakso J, et al., Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer, Anticancer Research 1992; 12: 599-606.
Nobile MT, Vidili MG, Benasso M, et al., A preliminary clinical study of cyclophosphamide with reduced glutathione as uroprotector, Tumori 1989; 75: 257-8.
Rush Presbyterian St. Luke’s Medical Center, Vitamin E does not protect cancer cells against radiation, January 15, 2000, PSA Rising Magazine, http://psa-rising.com/medicalpike/ebr/andvitEC031901.shtml.
Rush Presbyterian St. Luke’s Medical Center, Vitamins C and E does fight side effects of pelvic radiation for cancer, March 20, 2001, PSA Rising Magazine http://psa-rising.com/medicalpike/ebr/vitE-C-proctitis031901.shtml.
Dykes B, Hypertext Guide to Prostate Cancer, Chemotherapy: vitamins and chemotherapy, 2001, http://www.hypertext.org/ENGLISH/ADVANCED.html.
Williamson D, Study: Avoiding vitamins A, E might improve cancer therapy, University of North Carolina News Services, December 13, 1999, http://www.unc.edu/news/newsserv/research/dec99/salganik121399.htm.
Holick CN, et al., Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the alpha-tocopherol, beta-carotene cohort study, American Journal of Epidemiology 2002; 156(6): 536-547.
Mathijssen RH, Effects of St. John’s wort on irinotecan metabolism, Journal of the National Cancer Institute 2002; 94(16): 1187-1188.
Levine M, et al., Criteria and recommendations for vitamin C intake, Journal of the American Medical Association 1999; 281:1415-1423.
Rouse K, Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism, Annals of Surgery 1995; 221(4): 420-426.
Prasad KN, et al., Pros and cons of antioxidant use during radiation therapy, Cancer Treatment Reviews 2002 28(2): 79-91.
Brignall M, Is it safe to use antioxidant supplements with chemotherapy?, Healthnotes Newswire, October 10, 2002.
Sadzuka Y, et al., Enhancement of the activity of doxorubicin by inhibition of glutamate transporter, Toxicology Letters 2001; 123(2-3): 159-67.
APPENDIX 1. BASIC UNDERSTANDING OF THE CANCER THERAPIES
The precise mechanisms of cancer therapies are not fully worked out, though considerable information is available. The following is an overview, based on the author’s understanding, indicating the potential role of herbs, vitamins, and antioxidants in preventing side effects of cancer therapies without impairing anticancer treatment.
Radiation
Standard external radiation therapy pinpoints a beam of intensely energetic photons (x-rays, gamma-rays or beta-rays) to a tumor site (see Figure 4). The radiation dose at the focal point is lethal to the cells. Some of the radiation directly breaks up cellular DNA and other components in the target area; it is estimated that about one-third of the damage is direct destruction of critical molecules, leading to inability of the cell to reproduce or to prompt cell death. The primary damage to the tumor, however, comes from generation of a huge number of free radicals that interact with cellular components and disrupt them. These free radicals are mostly generated from water, because it is the most abundant substance in the cells. Because of the beam intensity at the focal point, no amount of antioxidant activity from orally ingested supplements is likely to be able to save these cells.
External radiation therapy is usually administered over an extended period, with several treatments spaced out with many days interval between. The reason that the whole task is not performed with one treatment is that the collateral damage from the radiation would be so severe as to threaten the patient’s survival. As it is, when the beam enters the body on its way to the tumor site and exits beyond the tumor, and spreads a bit on either side of the target, the collateral damage is notable and can be extreme. The skin becomes burned and delicate internal organs can become severely damaged and almost unusable. For example, radiation to the throat area can make swallowing virtually impossible; abdominal radiation can cause intestinal ulceration that doesn’t heal for months if at all. Still, these off-target tissues are able to repair somewhat between the treatments thanks to the more limited damage at these sites compared to at the tumor itself. As the distance from the beam’s focal point increases, there is greater chance to protect the cells with antioxidants that are able to handle the small number of free radicals that are generated.
There are other types of radiation therapy, including brachytherapy, in which radioactive material is inserted into the tumor (as commonly employed for prostate cancer): the radiation spreads out around radioactive “seeds” and kills all cells in the surrounding area, with reduced damage the greater the distance from the radiation source. There are now proton and neutron beams that have a higher proportion of damage caused by direct strikes at DNA and other cellular components, with less reliance on free radical generation.
It is a desired outcome that the collateral damage from all radiation techniques be minimized, which is a potential valuable role for antioxidants. The chances of antioxidants protecting the tumor cells are minimal; there is simply too much radiation at the target. Failures of radiation therapy are mostly attributable to metastasis of the cancer cells (before radiation begins) rather than failure of the radiation to destroy every cancer cell at the target tumor site. No amount of antioxidant therapy nor the reverse-complete avoidance of antioxidant therapy during radiotherapy-will have an impact on this metastasis that has occurred before radiation therapy. Metastatic cells can not be detected by current means and may not reveal themselves for months or even years, which is why cancer therapies are not considered a true success until 5 years pass without sign of new tumor growth, usually at a different site.
One cannot know for certain what effect-good or bad-antioxidants will have on the effects of radiation therapy, without extensive clinical testing that may take years. The concept that tumor cells can be protected is largely based on the assumption that antioxidants are extremely efficient. They would have to clean up the reactive oxygen species as fast as they are produced. Yet, the very large amount of antioxidant research conducted over the past decade clearly shows that these substances have limited impact for several diseases. Where they were thought to have the potential to treat diseases, they have not been very successful, and where they are thought to prevent diseases, they appear effective so long as the exposure to the antioxidants is for years and years, having a continuous mild impact. Antioxidants can be expected to provide some aid to cells unintentionally caught in the periphery of radiation therapy, but, even there, complete protection is not expected due to limited effects.
Chemotherapy
As with radiation therapy, chemotherapy is administered over an extended period, often (though not always), with a duration of several days or weeks between treatments. As with radiation therapy, the task cannot be accomplished all at once, because a lethal chemotherapy dose for the entire tumor would also be lethal for the patient. In fact, one of the key measures of the patient’s ability to continue chemotherapy is recovery of the white blood cell count that has been impaired by the drug therapy (this does not apply to some of the new immune based and genetic therapies). Chemotherapy is usually not as focused as radiation therapy on the tumor, and affects the entire body (commonly causing hair loss, distress of the gastro-intestinal system, white blood cell depletion, and fatigue). An adjunctive treatment that protects non-target cells (normal cells) might also protect cancer cells. However, as occurs with radiation therapy, there is a difference between the intensity of the drug action on cancer cells and on other cells, such as bone marrow cells. Otherwise, once the cancer was destroyed successfully, the bone marrow would also be destroyed (which is, in fact, one of the radical chemotherapy approaches, but not the first line treatment). Chemotherapy drugs are selected for clinical use on the basis that they have a more potent action on cancer cells than on other cells. Thus, after the cancer is destroyed, hair grows back, digestion returns to normal, and the immune system functions fully once again. Protection that helps the bone marrow does not necessarily have the potency to protect the cancer cells. Failure of chemotherapy is often the result of the presence of some resting cells, usually cells outside the active tumor mass, that do not respond to chemotherapy drugs. The drugs usually interact with replicating DNA and might miss such individual metastatic cells that are quiescent.
Polysaccharides from herbs have been used for protecting the bone marrow in cancer patients undergoing chemotherapy in China, Japan, and other countries for many years. The clinical study reports indicate improved outcomes (better survival) in patients who utilize this adjunct therapy. It can be argued that the study methodology is inadequate to support the improved survival, and it can be argued that the valid outcomes might be clinically insignificant, so that there is little or no interest in pursing this approach here. But, there is no evidence that bone marrow protection leads to negative effects in terms of tumor destruction or survival rates.
A positive role for antioxidants in the case of chemotherapy drugs is protection against a variety of undesired secondary effects, particularly neuropathy and cardiac damage. The chemotherapy drugs do not function as oxidants, but, rather, influence the cellular DNA and RNA (see Figures 5-6). Except in one in vitro study cited above for glioma cells that are normally resistant to chemotherapy, there is no evidence that antioxidants worsen the outcome of cancer chemotherapies. To the contrary, there is some evidence of protection for secondary effects. Dr. Golde’s in vitro research on vitamin C did not show that this substance impaired cancer therapies, only that cancer cells seem to “soak up” the vitamin. His results may not translate to an impairment of the effects of radiation therapy or chemotherapy.
The essential factor in both radiation therapy and chemotherapy is the specificity of the treatment for cancer cells. Antioxidants, herbs, and other kinds of natural supplements are being applied to protect cells that are unintentionally damaged by cancer therapy where the damage is substantially less severe than that caused to the cancer cells. The ability to provide protection for non-target cells without interfering with the damage to cancer cells is based largely on the differential. One may expect that where a cancer therapy is equally lethal to target and non-target cells, that a therapy protective of the non-target cells might also be protective of the target cells. Despite the apparent protection offered by antioxidants and herbs to non-target cells, their abilities to provide that protection are limited. Patients still experience side effects; they are only reduced in intensity. The ability of these same substances to protect target cells is far less, which explains why there hasn’t been a sudden failure of cancer therapies during the past decade when millions of people have turned to routine use of supplements with vitamin C, vitamin E, and other antioxidants.
From: preliminary report by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon http://www.itmonline.org/
We posted this 6/03