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Vitamins and Chemotherapy, Do They Mix?

by Jeffrey Dach MD

Occasionally a relative or a friend will ask my opinion about taking vitamins along with chemotherapy. The usual scenario is they are starting a course of chemotherapy and the oncologist has ordered them to stop the vitamins because of possible interferance with the chemo.

Perhaps my friend wants to continue the vitamins because he feels that the vitamins and added nutrition would help to fortify against the toxicity of the chemo drugs and improve chances of surviving not only the malignancy but also the toxic chemo. Perhaps they are looking for someone to tell them it’s OK to continue with the vitamins against the oncologists wishes. Perhaps they are looking for another opinion from someone who has researched the medical literature and says that vitamins are not only OK to take, they are recommended during chemotherapy.

First of all, let me state that I would not knowingly interfere with a doctor-patient relationship. If a doctor advises a patient to follow a treatment plan, then as a general rule, that is between them.  Having said that, doctors disagree all the time and have been known to give conflicting advice.  So for anyone reading this, I would advise discussing this issue with your own physician and following the advice of your personal physician in the matter.

Getting back to my friend, it was not necessary for me to even reply because this question has been asked, researched and answered by other high powered docters many times over.   Here are the conclusions of a few other knowledgable doctors:

Dr. Block reviewed 19 trials and found that antioxidants reduced toxic side effects, and increased survival without reducing efficacy of the chemotherapy.  He concluded.” None of the trials reported evidence of significant decreases in efficacy from antioxidant supplementation during chemotherapy. Many of the studies indicated that antioxidant supplementation resulted in either increased survival times, increased tumor responses, or both, as well as fewer toxicities than controls” (6)(7)

Dr Prasad reviewed 71 scientific papers, found no evidence that antioxidants interfered with the therapeutic effect of chemotherapy and, on the contrary, suggest the hypothesis that it would increase the efficacy.(3)

Dr Prasad concluded, “Antioxidants such as retinoids, vitamin E, vitamin C and carotenoids inhibit the growth of cancer cells. These antioxidants individually, and in combination, enhance the effects of chemotherapeutic agents. Antioxidants individually protect normal cells against some of the toxicities produced by these therapeutic agents. Therefore, the fear of oncologists and radiation therapists that these antioxidants may protect cancer cells against free radicals that are generated by these agents is unfounded. (4)

Again, the conclusion is that antioxidants increase the killing effectiveness of chemotherapy, while increasing patient survival:  “Since the 1970s, 280 peer-reviewed in vitro and in vivo studies, including 50 human studies involving 8,521 patients, 5,081 of whom were given nutrients, have consistently shown that non-prescription antioxidants and other nutrients do not interfere with therapeutic modalities for cancer.   Furthermore, they enhance the killing of therapeutic modalities for cancer, decrease their side effects, and protect normal tissue.In 15 human studies, 3,738 patients who took non-prescription antioxidants and other nutrients actually had increased survival.” (5)

Here is another article of intererest: ANTIOXIDANTS AND OTHER NUTRIENTS DO NOT INTERFERE WITH CHEMOTHERAPY OR RADIATION THERAPY AND CAN INCREASE KILL AND INCREASE SURVIVAL, (5) by Charles B. Simone II, MD; Nicole L. Simone, MD; Victoria Simone, RN; Charles B. Simone, MD (5)

Links to the above article:  Part one , and part two .

“The fear of oncologists and radiation therapists that antioxidants may protect cancer cells against free radicals that are generated by these agents is unfounded.”  quoted Abram Hoffer (1)

Three Interactions to Look Out For and Avoid:

“(1) flavonoids with tamoxifen, (2) NAC with doxorubicin, and (3) beta-carotene with 5- fluorouracil” (8)

What about Folate and Methotrexate?

The vitamin, Folate, is needed for DNA synthesis.  Folate serves as a 1-carbon donor for synthesis of purines and thymidine as well as in the remethylation cycle of homocysteine to methionine.  Methotrexate is specially an anti-folate drug.  It blocks the conversion of inactive Di-Hydrofolate to the active form of Tetrahydofolate.  Therefore supplementing with folate would seem counteractive to the action of methotrexate.  However, folate is present as a vitamin fortification in cereals and flours, and in many foods, so it is not practical to avoid dietary sources of folate.  However, food sources of folate do not appear to be adequate to counteract methotrexate related toxicity and treatment related deaths.

Toxicity of Methotrexate Reduced with Folate Supplementation

Nutritional supplementation with folate and folinic acid has been advocated in the oncology literature to avoid methotrexate related deaths while preserving anticancer activity.  Dr Calvert writes in Seminars of Oncology 2002, “A policy of nutritional supplementation (with folate) was introduced and led to a marked reduction in toxicity and the abolition of treatment-related deaths with apparent preservation of anticancer activity.(13)

Rescuing the Patient from Folate Deficiency

To counteract the toxicity of methotrexate, folinic acid (lecovorin) is used as the more active form of folate.  It is common practice for patients receiving methotrexate for autoimmune diseases such as rheumatoid arthritis to be given folate supplements along with the methotrexate to protect from folate deficiency.  Studies show that the additional folate does not reduce clinical efficacy of the methotrexate.(11)(12)

Disclaimer: None of the above is to be considered as medical advice.  The reader is advised to consult their personal physician and follow their advice concerning the above issues.

Jeffrey Dach MD
4700 Sheridan, Suite T.
Hollywood, Fla 33021
954-983-1443
www.drdach.com
www.jeffreydach.com
www.truemedmd.com

References:

(1) http://www.tldp.com/issue/11_00/hoffer.htm
High Doses of Antioxidants Including Vitamin C Do Not Decrease the Efficacy of Chemotherapy by Abram Hoffer, M.D., Ph.D.   Reprinted with permission of the author and the Townsend Letter for Doctors and Patients, 911 Tyler Street, Pt. Townsend WA 98368; (360) 385-6021 

(2) http://orthomolecular.org/resources/omns/v04n12.shtml
IF CHEMOTHERAPY DOESN’T WORK, DON’T BLAME VITAMIN C
(Orthomolecular Medicine News Service, October 7, 2008

(3) http://www.jacn.org/cgi/reprint/18/1/13.pdf
Prasad KN, Kumar A, Kochupillai V & Cole WC.
High Doses of Multiple Antioxidant Vitamins: Essential Ingredients in Improving the Efficacy of Standard Cancer Therapy. Journal American College of Nutrition 18:13-25, 1999.

(4) http://www.hopeforcancer.com/research/Prasad_Multiple_Dietary_Antioxidants.pdf
Prasad KN, Cole WC & Prasad JE.
Multiple Antioxidant Vitamins as an Adjunct to Standard and Experimental Cancer Therapies. Z.Onkol/J. of Oncol 31:1201-1078, 1999.

(5) Part one Click Here:
http://www.jpsupplement.com/Antioxidants&ChemoPart1.pdf

Part two Click Here:
http://www.alternative-therapies.com/at/web_pdfs/simone.pdf

ANTIOXIDANTS AND OTHER NUTRIENTS DO NOT INTERFERE WITH CHEMOTHERAPY OR RADIATION THERAPY AND CAN INCREASE KILL AND INCREASE SURVIVAL, PART 1 and 2 Charles B. Simone II, MD; Nicole L. Simone, MD; Victoria Simone, RN; Charles B. Simone, MD

(6) http://www.ncbi.nlm.nih.gov/pubmed/18623084
Int J Cancer. 2008 Sep 15;123(6):1227-39.

Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C.

Much debate has focused on whether antioxidants interfere with the efficacy of cancer chemotherapy. The objective of this study is to systematically review the randomized, controlled clinical trial evidence evaluating the effects of concurrent use of antioxidants with chemotherapy on toxic side effects.

We performed a search of literature from 1966-October 2007 using MEDLINE, Cochrane, CinAhl, AMED, AltHealthWatch and EMBASE databases. Randomized, controlled clinical trials reporting antioxidant-based mitigation of chemotherapy toxicity were included in the final tally. Searches were performed following a standardized protocol for systematic reviews. Only 33 of 965 articles considered, including 2,446 subjects, met the inclusion criteria. Antioxidants evaluated were: glutathione (11), melatonin (7), vitamin A (1), an antioxidant mixture (2), N-acetylcysteine (2), vitamin E (5), selenium (2), L-carnitine (1), Co-Q10 (1) and ellagic acid (1).

The majority (24) of the 33 studies included reported evidence of decreased toxicities from the concurrent use of antioxidants with chemotherapy. Nine studies reported no difference in toxicities between the 2 groups. Only 1 study (vitamin A) reported a significant increase in toxicity in the antioxidant group. Five studies reported the antioxidant group completed more full doses of chemotherapy or had less-dose reduction than control groups. Statistical power and poor study quality were concerns with some studies.

This review provides the first systematically reviewed evidence that antioxidant supplementation during chemotherapy holds potential for reducing dose-limiting toxicities. However, well-designed studies evaluating larger populations of patients given specific antioxidants defined by dose and schedule relative to chemotherapy are warranted. 

(7) http://www.ncbi.nlm.nih.gov/pubmed/17367938

Cancer Treat Rev. 2007 Aug;33(5):407-18. Epub 2007 Mar 23. Links
Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials. Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C.

PURPOSE: Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. Some have argued that antioxidants scavenge the reactive oxygen species integral to the activity of certain chemotherapy drugs, thereby diminishing treatment efficacy. Others suggest antioxidants may mitigate toxicity and thus allow for uninterrupted treatment schedules and a reduced need for lowering chemotherapy doses. The objective of this study is to systematically review the literature in order to compile results from randomized trials that evaluate concurrent use of antioxidants with chemotherapy.

DESIGN: MEDLINE, Cochrane, CinAhl, AMED, AltHealthWatch and EMBASE databases were searched. Only randomized, controlled clinical trials that reported survival and/or tumor response were included in the final tally. The literature searches were performed in duplicate following a standardized protocol. No meta-analysis was performed due to heterogeneity of tumor types and treatment protocols used in trials that met the inclusion criteria.

RESULTS: Of 845 articles considered, 19 trials met the inclusion criteria. Antioxidants evaluated were: glutathione (7), melatonin (4), vitamin A (2), an antioxidant mixture (2), vitamin C (1), N-acetylcysteine (1), vitamin E (1) and ellagic acid (1). Subjects of most studies had advanced or relapsed disease.

CONCLUSION: None of the trials reported evidence of significant decreases in efficacy from antioxidant supplementation during chemotherapy. Many of the studies indicated that antioxidant supplementation resulted in either increased survival times, increased tumor responses, or both, as well as fewer toxicities than controls; however, lack of adequate statistical power was a consistent limitation. Large, well-designed studies of antioxidant supplementation concurrent with chemotherapy are warranted.

(8) http://www.thorne.com/media/antioxidants_cancer_part1.pdf
Antioxidants in Cancer Therapy; Their Actions and Interactions With Oncologic Therapies Davis W. Lamson, MS, ND and Matthew S. Brignall, ND Alternative Medicine Reviews, 1999;4(5):304-329

Conclusion: Frequently, the effects of using antioxidants concurrent with chemotherapy and radiation are synergistic. Except for three specific interactions outlined above (flavonoids with tamoxifen, NAC with doxorubicin, and beta-carotene with 5-
fluorouracil),
there is no evidence to date showing that natural antioxidants interfere with conventional cancer therapeutics in vivo. Studies have shown patients treated with antioxidants, with or without chemotherapy and radiation, have many benefits. Patients have been noted to tolerate standard treatment better, experience less weight loss, have a better quality of life, and most importantly, live longer than patients receiving no supplements. It is time to research the role of these agents in conventional oncologic treatment, rather than dismiss them as a class based on theoretical concerns.

(9) http://www.naturalissues.com/?p=6
Fallacies Abound: Do natural treatments interfere with traditional chemotherapy and radiation?  The joke, of course, is that the same oncologists who pontificate on the dangers of natural treatments also prescribe amifostine and dexrazoxane, 2 prescription antioxidants generally used during chemo and radiation treatments.

(10) http://en.wikipedia.org/wiki/Folic_acid#cite_note-Oldref_53-50
Folic acid, wikipedia

(11) http://www.ncbi.nlm.nih.gov/pubmed/93611641
Rheum Dis Clin North Am. 1997 Nov;23(4):969-80.
The use of folates concomitantly with low-dose pulse methotrexate.Shiroky JB.

(12) http://www.ncbi.nlm.nih.gov/pubmed/7978695
Ann Intern Med. 1994 Dec 1;121(11):833-41.
Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Morgan SL, 

CONCLUSIONS: Folic acid, an inexpensive vitamin, is safe in a broad range of doses and protects patients with rheumatoid arthritis who are taking methotrexate from toxicity while preserving the efficacy of methotrexate.

(13) http://www.ncbi.nlm.nih.gov/pubmed/12023786
Semin Oncol. 2002 Apr;29(2 Suppl 5):3-7. Folate status and the safety profile of antifolates. Calvert H.

Throughout the history of cancer chemotherapy, the control of drug-related toxicity has been a major concern. Antifolates such as methotrexate also have a reputation for sporadic and unpredictable toxicity. Pretreatment levels of plasma or red cell folate have not been found to be useful in predicting which patients will develop toxicity. During the phase II development of pemetrexed, the plasma levels of homocysteine and methylmalonic acid were studied as sensitive surrogate markers for folate and vitamin B(12) status, respectively. These were found to be strongly correlated with the subsequent development of serious drug-related toxicities (myelosuppression, diarrhea, mucosal toxicity, and infection), suggesting that toxicity was related to relative folate deficiency in some cancer patients. A policy of nutritional supplementation was introduced and led to a marked reduction in toxicity and the abolition of treatment-related deaths with apparent preservation of anticancer activity.

http://www.ncbi.nlm.nih.gov/pubmed/12571807

Semin Oncol. 2002 Dec;29(6 Suppl 18):24-9. Links
Pemetrexed safety and dosing strategy.Niyikiza C, Hanauske AR, Rusthoven JJ, Calvert AH, Allen R, Paoletti P, Bunn PA Jr.Eli Lilly and Company, Indianapolis, IN 46285, USA.

Pemetrexed is a novel antifolate/antimetabolite that inhibits several folate-dependent enzymes, including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide transformylase. As a class, antifolates have been associated with sporadic severe myelosuppression with gastrointestinal toxicity. Although infrequent, a combination of such toxicities carries a high risk of potentially life-threatening complications. Severe toxicity from pemetrexed-based therapy has become more predictable using the vitamin deficiency marker homocysteine and, to a lesser extent, methylmalonic acid. Evidence now suggests that reducing total plasma homocysteine levels by supplementation with folic acid and vitamin B(12) leads to a better safety profile for pemetrexed, while not adversely affecting its efficacy.

Link to this article:
http://jeffreydach.com/2008/12/09/vitamins-and-chemotherapy-do-they-mix-by-jeffrey-dach-md.aspx

Jeffrey Dach MD
4700 Sheridan Suite T
Hollywood Fl 33021
954-983-1443
www.jeffreydach.com
www.drdach.com
www.naturalmedicine101.com
www.truemedmd.com

Disclaimer click here: http://www.drdach.com/wst_page20.html

The reader is advised to discuss the comments on these pages with
his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question,  I am NOT creating a physician — patient relationship.
Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.
Link to this article:

(c) 2008 Jeffrey Dach MD All Rights Reserved
This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

Link to this article:
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