Glutathione (GSH) and Whey Protein in Cancer

Copyright © 2002 1Whey2Health
Reproduction Prohibited

► How do Glutathione and whey protein help in Cancer?

► News Reports of Glutathione, Whey Protein in Cancer

► Scientific Research on Cancer and Glutathione and whey protein

► Cancer Clinical Trials with Glutathione and whey protein

► Books on Glutathione (GSH), Antioxidants and Cancer

► Cancer Links

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How do Glutathione and whey protein help in Cancer Prevention, Treatment?

The anti-cancer effect of glutathione and whey proteins is well documented in the medical literature, but their exact mechanism of action is not clear.

Undenatured whey protein is known to be effective in the case of cancer as stated in the medical patents and clinical trials. Here are some of the documented cancer-fighting effects of un-denatured whey protein.

► Antioxidant Effect of Glutathione

Veteran medical writer Dr. Ralph Moss believes that -- contrary to popular medical bias -- antioxidants and other dietary supplements should play a part in almost every cancer patient's treatment.

Glutathione is the body's master antioxidant. When liver glutathione levels rise, the liver is able to more effectively detoxify the body. Un-denatured whey protein optimizes serum and liver glutathione levels.

New research suggests that whey may play a role in helping prevent prostate cancer. When Ohio State University food scientists treated human prostate cells in the lab with whey protein, cellular levels of the antioxidant glutathione increased. Cancer researchers suspect that the accumulation of free radicals plays a role in the development of prostate cancer.

In the current study, the Ohio State scientists found that treating prostate cells with whey protein elevated glutathione levels in the cells by up to 64 percent. ".. whey proteins are rich in cysteine, an amino acid that increases glutathione in the prostate," Kent said.

"...cysteine is the amino acid that helps create healthy glutathione levels in the prostate, and glutathione helps keep free radicals under control." The study appears in a recent issue of the journal Toxicology in Vitro. (1)

In studies published in the Dec. 3, 2001, EMBO (European Molecular Biology Organization) Journal, scientists at the Salk Institute for Biological Studies in San Diego have pinpointed the biological chain of events that caused wasting in mice, then identified the same process in liver tissue from cancer patients.

They described the steps by which tumor necrosis factor (TNF) alpha, an immune-system protein, prevents the production of albumin. Low levels of albumin, a critical protein made in the liver, is a keynote of wasting.

The researchers found that one way of stopping the downward spiral caused by TNF- alpha was to treat TNF-alpha-enhanced mice with vitamin E and other antioxidants. "If we block oxidative stress, we normalize everything," explained Dr. Chojkier.

According to Dr. Chojkier, a gastroenterologist and liver specialist, antioxidants such as vitamin E might halt wasting in humans if these supplements were delivered in very high amounts-or even better, if they were targeted to the liver. "One solution will be to find a liver-specific antioxidant," he said.** (2)

**NOTE: Glutathione is the most important liver-specific antioxidant. It also acts to reconstitute vitamins C and E after they have been oxidized, and therefore plays a determinant role in their function.

► Anti-cancer effect of Lactalbumin & Whey components

In research conducted by C. Svanborg et al, lactalbumin was associated with apoptosis (or the programmed death) of breast cancer cells. (3)

Glutathione and lactalbumin have been associated with the strengthening of healthy cells and (paradoxically) the weakening of cancerous cells.

In one study, when different groups of rats were given a powerful carcinogen, those fed whey protein concentrate showed fewer tumors and reduced tumor masses (4).

In another published study, rats fed a whey protein-based diet had a decrease in their risk of developing colon tumors (5).

Whey appears to inhibit the growth of breast cancer cells at low concentrations. In one clinical study, when cancer patients were fed whey protein concentrate at 30 grams a day, some patients' tumors showed a regression (6).

A wide-ranging Australian research program using laboratory animals has shown that whey proteins protect against colon cancer and possibly skin cancer. (7)

Dietary lactoferrin, a component of whey protein, has been shown to prevent colon, esophagus, lung, and bladder cancer and prevent the spread (metastasis) of cancer. (8,9,10)

In a recent study, high serum levels of cysteine were linked to a lower risk of breast cancer. Women with the highest cysteine levels were 56% less likely to develop breast cancer than those with the lowest levels.

Regardless of other known risk factors, as cysteine levels rose, breast cancer risk fell. However, the beneficial effects of a high cysteine level appeared to be strongest in lean women. (11,12)

In a new paper published in the Anticancer Research Journal, the role of the cysteine-GSH antioxidant cellular system in the prevention and treatment of various types of malignancies was reviewed. (13)

It states that besides increasing intra-cellular synthesis of glutathione, cysteine itself - or a natural cysteine donor, such as a Whey Protein Concentrate (WPC) - may exert a direct antitumor effect in two different ways:

1.Cysteine can inhibit tumors by directly increasing cellular thiol levels. Thiols are sulfur-containing compounds that are an essential component of the glutathione antioxidant system. Depletion of thiol levels may be related to a fall in antioxidant levels in the progression of cancers. (14)

2. Cysteine can inhibit the formation of new blood vessels (neoangiogenesis) that feed tumor tissue and promote tumor growth and spread.(15)

► Selective depletion of glutathione in cancer cells

The research using whey protein concentrate has led researchers to a discovery regarding the relationships between cancerous cells, whey protein concentrate, and glutathione.

It was found that cancer cells and normal cells will respond differently to nutrients and drugs that affect glutathione status.

It is not known why but cancerous cells seem to have a higher level of glutathione than your healthy cells. This of course makes the cancer cells stronger than your healthy cells.

By taking undenatured whey protein, a person raises the level of glutathione in the healthy cells thus making them stronger.

And when you raise the glutathione levels in the cancer cells, they actually peak out and then shut off (by a mechanism called "feedback inhibition") causing a reduction of glutathione and thus weakening these cells.

Whey protein concentrate selectively depletes cancer cells of their glutathione, thus making them more susceptible to such cancer treatments as radiation and chemotherapy

Hence, although whey protein beneficially increases glutathione within healthy cells, it actually reduces glutathione concentration within cancer cells, making them more vulnerable to chemotherapy. (16, 17)

► Improved response to chemotherapy

Low glutathione levels are commonly found among those undergoing cancer chemotherapy.

There is abundant evidence that GSH plays a major role in tumor cell resistance against radiation therapy and chemotherapy - such as with DNA alkylators (e.g., cisplatin, melphalan, etc.) and redox cycling (e.g., doxorubicin) drugs. (18, 19, 20)

In many cases, cancer cell resistance to therapy with these agents is correlated with abnormally elevated levels of GSH. Previous studies have suggested that glutathione (GSH) can reduce the toxicities of cisplatin (CDDP) chemotherapy. (16)

The concentration of glutathione in tumor cells is higher than that in the normal cells that surround the tumor. This difference in glutathione status between normal cells and cancer cells is believed to be an important factor in the resistance of cancer cells to chemotherapy.

Studies have shown that cancer cells subjected to whey proteins are depleted of their glutathione and their growth was inhibited, while normal cells had an increase in glutathione and increased cellular growth. These effects were not seen with other proteins. (16, 17)

Not surprisingly, the researchers concluded, "Selective depletion of tumor glutathione may, in fact, render cancer cells more vulnerable to the action of chemotherapy and eventually protect normal tissue against the deleterious effects of chemotherapy."

Glutathione supplementation has been scientifically demonstrated to decrease cancerous cells' resistance to chemotherapeutic drugs, while protecting healthy cells.

By optimizing glutathione levels, you have strengthened your healthy cells and weakened your cancer cells. This would theoretically allow a patient to respond better to chemotherapy with less side effects.

There have been considerations that because glutathione enhances hepatic detoxification, chemotherapy may be rendered less effective.

"Many patients are treated with surgery, radiation, and chemotherapy, and they are often told by their doctors to avoid taking their antioxidant supplements during treatment. They are given the impression that such supplements may interfere with their treatment.

But so far, the evidence all points to a protective effect of the supplements, no matter what other treatments are administered.

In addition, the supplements appear to reduce the sometimes devastating side effects of the treatments, such as nausea, diarrhea, hair loss, and profound fatigue. (21)

This reference also quotes from one study of lung cancer patients, in which "those given high dose antioxidants and other nutrients survived far longer than would be expected, and it worked best in those who started the supplements at the earliest opportunity. They also tolerated their other treatments better than those without supplements."

In another study of patients with bladder cancer, "the recurrence rate was cut in half if they were given supplements, and the average survival time was doubled." (21)

Note: Consult your healthcare provider to find out whether anti-oxidants are compatible with your chemo regimen

► Whey protein in cancer cachexia (catabolic wasting, weight loss)

It is estimated that one half of all cancer patients experience catabolic wasting, with a higher occurrence seen in cases of malignancies of the lung, pancreas, and gastrointestinal tract.

Catabolic wasting or cachexia is a clinical wasting syndrome that is characterized by unintended and progressive weight loss, weakness, and low body fat and muscle. Catabolic wasting is a symptom that diminishes the quality of life, worsens the underlying condition, and is a major cause of death.

Cachexia is caused by a metabolic state in which a "breaking down" rather than a "building up" occurs in bodily tissues no matter how much nutritional intake occurs. Additionally, whether a patient receives nutrition orally or intravenously makes no difference. The patient simply cannot gain weight, so eating more is not an answer.

Clinicians are currently treating cancer-related catabolic wasting with a variety of interventions, including nutritional supplementation, administration of cytokine inhibitors, steroids, hormones, cannabinoids, and thalidomide.

Scientists have examined the impact of whey protein concentrate on preventing or treating catabolic wasting, immune dysfunction, and cancer.

A study involving HIV-positive men fed whey protein concentrate found dramatic increases in glutathione levels, with most men reaching their ideal body weight (22).

Whey protein has the highest biological value rating of any protein (which is why it is used by body-builders to build muscle mass). When the biological value is high, that means protein is absorbed, used, and retained better in the body.

High biological values also are associated with tissue sparing. Thus, whey protein concentrate can be beneficial for people with wasting catabolic diseases.

► Whey protein - A"SUPER-FOOD" for Cancer patients

At the 84th Annual Meeting of the American Dietetic Association in Philadelphia, PA, Dr. Keith Block from the Block Medical Center in Chicago, IL. Dr. Block reviewed the seven key components of integrative care for cancer patients, which are Attitude, Medicine, Nutrition, Supplements, Physical Care, Stress Care and Alternatives.

In regards to nutrition, Dr. Block stated that whey protein is considered to be a “Super Food” for cancer patients.

David Grotto, R.D. and spokesperson for the American Dietetic Association, commented, “whey protein is an essential dietary element in aiding cancer patients in their quest for optimal nutrition.”

Dr. Block and Mr. Grotto are not alone in recommending whey protein to cancer patients. A new book by Dr. Michael Murray titled “How To Treat and Prevent Cancer with Natural Medicine” recommends 40-60 grams of whey protein per day for cancer patients.

Cancer patients have a significant need for perfectly balanced protein. A high quality un-denatured whey protein isolate formula, provides the patient with a perfectly balanced protein without the added burden of saturated fat solids or lactose associated with other protein sources.

Undenatured whey protein supplies a concentrated form of easily digestible, high efficiency protein, without the need to consume large volumes of food.

A number of clinics have observed that patients rendered anemic due to chemotherapy and radiation appear to also have robust recovery of their hemoglobin and hematocrit when fed adequate levels of nondenatured whey protein isolates.

► Improved Immune Function

Natural Killer (NK) cells are the "hit men" of the immune system, and are directly responsible for attacking and destroying virus-infected and cancerous cells. NK cells may become glutathione-depleted over time, and immune response weakens.

Studies have shown that a combination of nutraceuticals, including undenatured whey protein, can raise NK cell function and TNF-alpha alpha activity and result in improved clinical outcomes in patients with late stage cancer. (23, 24)

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References:

1. Eat your whey: It may protect against prostate cancer
   Press release from Ohio State University ; 28 May, 2003
2. Scientists Find Key To ‘Wasting Syndrome’ Seen In Cancer, AIDS
   UCSD Health Sciences Communications
3. HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects
   Svanborg C, Agerstam H, Aronson A, Bjerkvig R, Duringer C, Fischer W, Gustafsson L, Hallgren O, Leijonhuvud I, Linse S, Mossberg AK, Nilsson H, Pettersson J, Svensson M. [Adv Cancer Res. 2003;88:1-29. ]
4. Dairy proteins protect against dimethylhydrazine-induced intestinal cancers in rats
   McIntosh GH, Regester GO, Le Leu RK, Royle PJ, Smithers GW. [J Nutr. 1995 Apr;125(4):809-16.]
5. Dietary whey protein protects against azoxymethane-induced colon tumors in male rats
   Hakkak R, Korourian S, Ronis MJ, Johnston JM, Badger TM. [Cancer Epidemiol Biomarkers Prev. 2001 May;10(5):555-8.]
6. The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I-II clinical study
   Kennedy RS, Konok GP, Bounous G, Baruchel S, Lee TD. [Anticancer Res. 1995 Nov-Dec;15(6B):2643-9.]
7. Whey proteins reduce cancer risk
   CSIRO Australia
8. Milk and dairy products in cancer prevention: focus on bovine lactoferrin
   Tsuda H, Sekine K, Ushida Y, Kuhara T, Takasuka N, Iigo M, Han BS, Moore MA. [Mutat Res 2000 Apr;462(2-3):227-33]
9. Cancer prevention by bovine lactoferrin and underlying mechanisms--a review of experimental and clinical studies
   Tsuda H, Sekine K, Fujita K, Ligo M. [Biochem Cell Biol. 2002;80(1):131-6.]
10. Prevention of colon carcinogenesis and carcinoma metastasis by orally administered bovine lactoferrin in animals
    Tsuda H, Sekine K, Takasuka N, Toriyama-Baba H, Iigo M. [Biofactors 2000;12(1-4):83-8]
11. AACR: High Cysteine Levels Linked to Lower Rates of Breast Cancer
12. A Prospective Study of Plasma Cysteine and Risk of Breast Cancer.
    Abstract LB-3; Zhang et al, Presented at the American Association for Cancer Research 2003 Annual Meeting, Orlando, FL
13. The Antioxidant System (Review) (pdf)
    G. BOUNOUS, S. SUKKAR, J.H. MOLSON [Anticancer Research Volume: 23 Year: 2003 Issue: 2B]
14. Antioxidant action via p53-mediated apoptosis
    Liu M, Pelling JC, Ju J, Chu E, Brash DE. [Cancer Res. 1998 Apr 15;58(8):1723-9.]
15. The role of the thiol N-acetylcysteine in the prevention of tumor invasion and angiogenesis
    Morini M, Cai T, Aluigi MG, Noonan DM, Masiello L, De Flora S, D'Agostini F, Albini A, Fassina G. [Int J Biol Markers. 1999 Oct-Dec;14(4):268-71.]
16. The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I-II clinical study
    Kennedy RS, Konok GP, Bounous G, Baruchel S, Lee TD. [Anticancer Res. 1995 Nov-Dec;15(6B):2643-9.]
17. In vitro selective modulation of cellular glutathione by a humanized native milk protein isolate in normal cells and rat mammary carcinoma model
    Baruchel S, Viau G. [Anticancer Res. 1996 May-Jun;16(3A):1095-9.]
18. Glutathione Synthase (GSH) Inhibitors and Cancer Therapy
19. Mechanism of action, metabolism and toxicity of buthionine sulfoximine and its higher homologs, potent inhibitors of glutathione biosynthesis
    Griffith OW. Journal of Biological Chemistry. 257:13704-13712, 1982.
20. Inhibition of metabolic drug inactivation: modulation of drug activity and toxicity by perturbation of glutathione metabolism. in Synergism and Antagonism in Chemotherapy
    Griffith OW. Friedman HS. (Chou TC. and Rideout DC. eds.) Academic Press, New York pp. 245-284 (1991).
21. Supplements Against Cancer
    Dr. Michael Janson; Healthy Living™ Vol. 4 Number 12 - December, 2002
22. Whey proteins as a food supplement in HIV-seropositive individuals
    Bounous G, Baruchel S, Falutz J, Gold P. [Clin Invest Med. 1993 Jun;16(3):204-9.]
23. Nutritional therapy of chronic hepatitis by whey protein (non-heated)
    Watanabe A, et. al [J Med. 2000;31(5-6):283-302.]
24. Increased tumor necrosis factor alpha (TNF-alpha) and natural killer cell (NK) function using an integrative approach in late stage cancers
    See D, Mason S, Roshan R. [Immunol Invest. 2002 May;31(2):137-53.]

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