Antioxidants in Cancer Therapy-Review of Literature

August 2008

Parenteral treatment with vitamin C can reduce the growth of aggressive tumor xenografts in mice, according to a report in the August 4th Early Edition of the Proceedings of the National Academy of Sciences.

Although vitamin C is typically thought of as an antioxidant, Dr. Mark Levine and colleagues show in the new study that it can also act as a prooxidant. The results also indicate that at pharmacologic levels, the essential nutrient elicits hydrogen peroxide-dependent cytotoxicity only toward cancer cells, leaving normal cells unscathed.

Testing in mice with glioblastoma xenografts showed that a single parenteral dose of vitamin C leads to free radical formation in tumor interstitial fluids, but not in the blood, Dr. Levine, from National Institutes of Health in Bethesda, Maryland, and co-authors found.

Daily treatment with vitamin C significantly slowed the growth of glioblastoma, ovarian cancer, and pancreatic cancer in mice.

To gauge the therapeutic potential of vitamin C, the researchers administered the nutrient intravenously to humans and found that concentrations corresponding to the efficacious levels in mice were, in fact, achievable.

Despite these encouraging results, the authors note that "use of pharmacologic ascorbate as a single agent was not curative." Still, they believe that it could be used in combination with other therapies to increase the efficacy against prognostically poor malignancies, such as those examined in the study.

Reuters Health, August 2008

U. S. Department of Health and Human Services U. S. Food and Drug Administration Center for Food Safety and Applied Nutrition Office of Nutritional Products, Labeling and Dietary Supplements

April 1, 2003

Letter Regarding Dietary Supplement Health Claim for Antioxidant Vitamins and Risk of Certain Cancers

Jonathan W. Emord Emord and Associates, P.C. Suite 600 1050 17th Street, N.W. Washington, D.C. 20036

Dear Mr. Emord:

This letter is a follow-up to the Food and Drug Administration's February 11, 2003, letter, pursuant to the opinion and order issued December 26, 2002, by the U.S. District for the District of Columbia in Whitaker, et al. v. Thompson, et al., Civil No. 01-1539, and your response dated February 13, 2003.

As you know, the United States withdrew its notice of appeal in this matter on March 28. The purpose of this letter is to formalize the contingent understanding we reached in mid-February.

In its opinion and order, the Court instructed FDA to draft one or more "short, succinct, and accurate disclaimers" for the health claim: "Consumption of antioxidant vitamins may reduce the risk of certain kinds of cancer." Slip Op. at 37; see Order at 1-2.

As we explained in our February 11 letter, FDA considered the two disclaimers suggested by the Court, as well as a number of others, and concluded the following three alternative disclaimers best meet the criteria specified in the Court's decision:

Some scientific evidence suggests that consumption of antioxidant vitamins may reduce the risk of certain forms of cancer.

However, FDA has determined that this evidence is limited and not conclusive.

Some scientific evidence suggests that consumption of antioxidant vitamins may reduce the risk of certain forms of cancer.

However, FDA does not endorse this claim because this evidence is limited and not conclusive.

FDA has determined that although some scientific evidence suggests that consumption of antioxidant vitamins may reduce the risk of certain forms of cancer, this evidence is limited and not conclusive.

Your February 13 letter indicated that your clients accept these disclaimers, and that the various petitioners in this matter wish to have the option of using any of three disclaimers on their products with the antioxidant vitamin claim.

FDA intends to exercise its enforcement discretion with respect to antioxidant vitamin dietary supplements containing vitamin E and/or vitamin C when:

(1) one of the above disclaimers is placed immediately adjacent to and directly beneath the antioxidant vitamin claim, with no intervening material, in the same size, typeface, and contrast as the claim itself;

(2) the supplement does not recommend or suggest in its labeling, or under ordinary conditions of use, a daily intake exceeding the Tolerable Upper Intake Level established by the Institute of Medicine (IOM) of 2000 mg per day for vitamin C and 1000 mg per day for vitamin E (see May 4, 2001, letter at 4-6 and references cited therein).

Antioxidant vitamin supplements bearing the claim and one of the disclaimers are still required to meet all applicable statutory and regulatory requirements under the Federal Food, Drug, and Cosmetic Act, including the applicable requirements for health claims.


Christine L. Taylor, Ph.D. Director Office of Nutritional Products, Labeling and Dietary Supplements Center for Food Safety and Applied Nutrition

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Antioxidants in Cancer Therapy; Their Actions and Interactions With Oncologic Therapies

Davis W. Lamson, MS, ND and Matthew S. Brignall, ND


There is a concern that antioxidants might reduce oxidizing free radicals created by radiotherapy and some forms of chemotherapy, and thereby decrease the effectiveness of the therapy. The question has arisen whether concurrent administration of oral antioxidants is contraindicated during cancer therapeutics.

Evidence reviewed here demonstrates exogenous antioxidants alone produce beneficial effects in various cancers, and except for a few specific cases, animal and human studies demonstrate no reduction of efficacy of chemotherapy or radiation when given with antioxidants. In fact, considerable data exists showing increased effectiveness of many cancer therapeutic agents, as well as a decrease in adverse effects, when given concurrently with antioxidants.

Alternative Medicine Reviews, 1999;4(5):304-329

Review: Antioxidants do NOT Interfere w/Chemo or RTx

Altern Ther Health Med, Jan-Feb, 2007

Antioxidants and Radiation Therapy (RTx)
Ralph Moss on Chemo/RTx and Antioxidants
Antioxidant Supplementation on Chemotherapeutic Efficacy:systematic review

Cancer Treatment Reviews, 8/07

Introduction and Conflicting Views

Antioxidant Use in Cancer Therapy

Vitamin A (Retinoids) and Carotenoids
Vitamin C
Overview of Cancer Therapeutic Agents
Vitamin E
Co Q10
NAC and Glutathione
Combining Antioxidants
Current Attitudes & New Approaches
Conclusions - Antioxidants in Cancer Therapy
Antioxidant Supplementations in Men Reduces Incidence CA

JAMA,11/04 Archives of Internal Medicine


180 studies examined

Use of Antioxidants & Cytotoxic Treatments

Ralph Moss Talk, July, 2001

Cancer (Adjuvant) Therapy
Mega-Dose Vitamins/Minerals in Treatment
Chemo & Supplements:Adriamycin/Vit E/Fish Oil
Antioxidants enhance cytotoxicity of chemotherapy:Colorectal Ca
Dietary Antioxidants & Chemotherapy

Nutrition and Cancer 37(1):1-18, 2000

Dietary Antioxidants- Conclusions from an Overview
Dietary Antioxidants in Swedish Women
Serum Cartotenoids/Breast Cancer
Chemotherapy w Antioxidants
Vitamin supplementation Reduced Toxicity Pemetrexed/Vit Bs
Antioxidants Resolve Rtx Adverse Effects

Am J Gastroenterol, 2001

Review of Italian Studies on Veg/Fruit/Antioxidants

Eur J of Nutritoin, 2001

Multiple Antioxidants Improve Efficacy

Paper was published and presented at NOAT, 2000 (See Meeting Summaries)

Systemic Screening of Total Antioxidants in Dietary Plants

J. Nutr. 132:461-471, 2002

High Oxidation/Low Antioxidant Levels...

Cancer, 6/02 Plus direct communication with the author

Herbs, Vitamins & Antioxidants w/Cancer Treatments:TCM

Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine

Garlic (Allium sativum) & Pharmacokinetics of Docetaxel

Clin Cancer Res, 8/06

Article References

Alternative Medicine Reviews, 1999;4(5):304-329.

Molec targets of dietary agents 4 prvntn & thrpy of cancer.

Biochem Pharmacol, 5/06

High Doses Antioxidants Do NOT decrease Chemo Efficacy

Letter by Dr. Abram Hoffer (part I)

Supplemental antioxidants during chemo &radiation therapy?

J Natl Cancer Inst, June 2008

LETTERS about supplemental antioxidant use during treatment

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