Whey Protein

Notes from Researchers

Whey proteins in cancer prevention
Bounous G, Batist G, Gold P. Montreal General Hospital, McGill University, Quebec, Canada

Epidemiological and experimental studies suggest that dietary milk products may exert an inhibitory effect on the development of several types of tumors. Some recent experiments in rodents indicate that the antitumor activity of the dairy products is in the protein fraction and more specifically in the whey protein component of milk. We and others have demonstrated that whey protein diets result in increased glutathione (GSH) concentration in a number of tissues, and that some of the beneficial effects of whey protein intake are abrogated by inhibition of GSH synthesis. Whey protein is particularly rich in substrates for GSH synthesis. We suggest that whey protein may be exerting its effect on carcinogenesis by enhancing GSH concentration.
Publication Types: PMID: 2025891 [PubMed - indexed for MEDLINE]

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

Glutathione (GSH) concentration is high in most tumour cells and this may be an important factor in resistance to chemotherapy. Previous in-vitro and animal experiments have shown a differential response of tumour versus normal cells to various cysteine delivery systems. More specifically, an in-vitro assay showed that at concentrations that induce GSH synthesis in normal human cells, a specially prepared whey protein concentrate, Immunocal, caused GSH depletion and inhibition of proliferation in human breast cancer cells. On the basis of this information five patients with metastatic carcinoma of the breast, one of the pancreas and one of the liver were fed 30 grams of this whey protein concentrate daily for six months. In six patients the blood lymphocyte GSH levels were substantially above normal at the outset, reflecting high tumour GSH levels. Two patients (#1, #3) exhibited signs of tumour regression, normalization of haemoglobin and peripheral lymphocyte counts and a sustained drop of lymphocyte GSH levels towards normal. Two patients (#2, #7) showed stabilisation of the tumour, increased haemoglobin levels. In three patients (#4, #5, #6,) the disease progressed with a trend toward higher lymphocyte GSH levels. These results indicate that whey protein concentrate might deplete tumour cells of GSH and render them more vulnerable to chemotherapy.
Publication Types: Case Reports / Clinical Trial / PMID: 8669840 [PubMed - indexed for MEDLINE]

Whey protein isolate increases glutathione levels in human prostate epithelial cells
K. D. Kent, J. A. Bomser, and W. J. Harper. [Annual Meeting and Food Expo - Anaheim, California, Session 73, Dairy Foods: Probiotics and bioactive components in milk]

Prostate cancer is the second leading cause of cancer death among American men. Studies suggest that dietary whey proteins may reduce the risk for cancer by increasing cellular levels of the antioxidant glutathione. Whey proteins are rich in cysteine, the hypothesized rate-limiting amino acid for glutathione synthesis. Supplementation with whey protein isolate may represent a means to increase glutathione synthesis within the prostate. The objective of this study was to determine the effect of whey protein isolate supplementation on glutathione levels in human prostate epithelial cells (RWPE-1).... an increase in available cysteine is responsible for the elevation of glutathione within the prostate epithelial cells.... hydrolyzed whey protein isolate can significantly increase glutathione levels within the prostate epithelium. This represents a potential mechanism by which whey protein isolate can provide protection against the development of prostate cancer.

What is whey protein and why is it essential to your health?

The simple answer is that it is something everyone should be taking on a regular basis. It contains properties that help repair DNA and RNA, regulates blood sugar and brain chemicals, produces antioxidants, improves liver and red blood cell production, binds and safely removes heavy metals, builds and retains muscles, enhances iron absorption and fights infections.

"Studies on whey demonstrate it's an even better protein supplement than previously thought. Although whey protein's health benefits have only recently been elucidated, the use of whey protein for medicinal purposes has been prescribed since the time of Hippocrates. In fact, there are two ancient proverbs from the Italian city of Florence that say, "If you want to live a healthy and active life, drink whey," and, "If everyone were raised on whey, doctors would be bankrupt."

"We've chronicled the extensive research showing the many potential health benefits of whey protein concentrate. The majority of that research was done in the 1980s and early 1990s, and was extremely persuasive. Scientists have continued their research on whey proteins with even more impressive results. What follows is some of the more current, interesting and useful research on whey proteins:

Whey and Cancer

Additional studies have been done on animals regarding cancer-causing chemicals to see what effects whey protein concentrate would have on cancer prevention or treatment. Scientists fed rats various proteins and then subjected them to the powerful carcinogen dimethylhydrazine.

As with the previous research, the rats fed whey protein concentrate showed fewer tumors and a reduced pooled area of tumors (tumor mass index). The researchers found whey protein offered "considerable protection to the host" over that of other proteins, including soy.

Even more exciting, in vivo research on cancer and whey showed whey protein concentrate inhibited the growth of breast cancer cells at low concentrations (Baruchel S. and Vaiu G., Anti Cancer Research, 1996). Finally, and most importantly, a fairly recent clinical study with cancer patients showed a regression in some patient's tumors when fed whey protein concentrate at 30 grams per day.

Whey and Glutathione

This new research using whey protein concentrate led researchers to an amazing discovery regarding the relationship between cancerous cells, glutathione (GSH) and whey protein concentrate. It was found that whey protein concentrate selectively depletes cancer cells of their glutathione, thus making them more susceptible to cancer treatments such as radiation and chemotherapy.

It has been found that cancer cells and normal cells will respond differently to nutrients and drugs that affect glutathione status. What is most interesting to note is the fact that the concentration of glutathione in tumor cells is higher than that of the normal cells that surround it. This difference in glutathione status between normal cells and cancer cells is believed to be an important factor in cancer cells' resistance to chemotherapy.

As the researchers put it, "Tumor cell GSH concentration may be among the determinants of the cytotoxicity [poisonous to cells] of many chemotherapeutic agents and of radiation, and an increase in GSH concentration appears to be at least one of the mechanisms of acquired drug resistance to chemotherapy.

They further state, "It is well-known that rapid GSH synthesis in tumor cells is associated with high rates of cellular proliferation. Depletion of tumor GSH in vivo decreases the rate of cellular proliferation and inhibits cancer growth."

The problem is, it's difficult to reduce glutathione sufficiently in tumor cells without placing healthy tissue at risk and putting the cancer patient in a worse condition. What is needed is a compound that can selectively deplete the cancer cells of their glutathione, while increasing, or at least maintaining, the levels of glutathione in healthy cells.

This is exactly what whey protein appears to do. In this new research it was found that cancer cells subjected to whey proteins were depleted of their glutathione, and their growth was inhibited, while normal cells had an increase in GSH and increased cellular growth.

These effects were not seen with other proteins. Not surprisingly, the researchers concluded, "Selective depletion of tumor GSH may in fact render cancer cells more vulnerable to the action of chemotherapy and eventually protect normal tissue against the deleterious effects of chemotherapy." The exact mechanism by which whey protein achieves this is not fully understood, but it appears that it interferes with the normal feedback mechanism and regulation of glutathione in cancer cells.

It is known that glutathione production is negatively inhibited by its own synthesis. Being that baseline glutathione levels in cancer cells are higher than that of normal cells, it is probably easier to reach the level of negative-feedback inhibition in the cancer cells' glutathione levels than in the normal cells' glutathione levels.

Whey and LDL Cholesterol

The positive health benefits of whey protein concentrate does not end with its effects on immunity and cancer prevention and treatment. Whey protein concentrate also was found to be a potent inhibitor of oxidized low density lipoprotein cholesterol. Current research suggests that the conversion of LDL to oxidized LDL is the trigger that leads to atherogenesis... the formation of the plaque and lesions associated with atherosclerosis.

Therefore, any substance that prevents the oxidation of LDL is thought to be anti-atherogenic. Though animal-based proteins have traditionally been implicated as being pro-atherogenic, whey proteins appear to be an exception to the rule. whey protein is made up of several minor and major fractions, such as beta-lactoglobulin, alpha-lactalbumin, albumin, lactoferrin and immunoglobulin. It was discovered that the minor constituent responsible for the ability of whey protein concentrate to prevent the oxidation of LDL appears to be the lactoferrin fraction of the protein.

Lactoferrin In Whey

When the lactoferrin was removed from the protein, the ability of the whey-protein concentrate to prevent LDL oxidation was greatly reduced, leading the researchers to speculate, "Our results suggest that LF (lactoferrin) is the main factor responsible for the inhibitory effect of whey protein (on LDL) and it may function synergistically together with other factors in the whey protein, for example, alpha-lactalbumin.

Another study using rats examined the effects of whey protein concentrate and casein on cholesterol and the risk factors of heart disease. Though casein (another milk-based protein commonly used in research) is known to raise cholesterol in humans and animals, whey protein has the opposite effect, leading the researchers to note, "At the high dietary protein level [300 gram per kilogram of feed] , whey protein significantly lowered plasma and liver cholesterol and also plasma triacylglycerols."

The cholesterol-lowering effects of whey protein concentrate in this study also was associated with a reduction in LDL cholesterol. Most interesting was the fact that this effect on cholesterol was not seen when the animals were fed amino acid mixtures that simulated whey protein, so it is clear that there are properties within the whey that have these effects beyond that of its amino acid profile.

Whey and Bone Growth

Finally, whey protein appears to play a direct role in bone growth. Researchers found that rats fed whey protein concentrate showed increased bone strength and bone protein such as collagen. This discovery led researches to test whether or not whey protein directly stimulated osteoblast (bone cell) growth in vitro.

Whey protein was found to stimulate, dose dependently, total protein synthesis, DNA content, and increased hydroxyproline contents of bone cells.

It should be noted that not all whey protein concentrates are created equal. Processing whey protein to remove the lactose and fats without losing its biological activity takes special care by the manufacturer. The protein must be processed under low temperature and low acid conditions so as not to "denature" the protein. Maintaining the natural state of the protein is essential to its biological activity. These research findings, combined with the previous decade of study on whey protein, should convince anyone that whey protein concentrate is truly the life-extension protein.

Higher Glutathione Levels and Whey

A decade-and-a-half of findings on the benefits of whey protein are far-reaching.

Previous Studies Include The Following:

Whey protein concentrate dramatically raises glutathione levels. Glutathione is an essential water-soluble antioxidant in the body that protects cells and serves as a primary detoxifier of harmful compounds such as peroxides, heavy metals, carcinogens and other toxins.

Glutathione also is intimately tied to immunity, and reduced glutathione levels have been associated with disease such as AIDS, atherosclerosis, Alzheimer's disease and Parkinson's disease, to name only a few. In fact, glutathione levels appear to be one way of modulating immunity.

Whey protein concentrate was found to consistently raise this extremely important immune stimulating antioxidant beyond that of any protein studied (including soy) to higher than normal levels in multiple animal studies.

A small pilot study with HIV-positive men who were fed whey protein concentrate found dramatic increases in glutathione levels of all the study participants, with two out of three men reaching their ideal body weight.

In fact, there have been several U.S. and international patents granted for the treatment of AIDS and improving immunity with whey protein concentrates.Whey protein improves immune function and fights infections. Animals fed whey protein concentrate consistently showed dramatic enhancement of both the humoral and cellular immune response to a variety of immune challenges, such as salmonella, streptococcus pneumonia 9 and extreme cancer-causing chemicals. This effect on immunity was not seen with other proteins.

Whey protein concentrate fights cancer!

Whey Protein Isolate

Protein is the building block of life. Essential to a balanced diet and strong muscles, both serious athletes and serious life extensionists use protein to enhance their health and performance.

Because so much evidence supports the benefits of whey as a fitness, strength and health enhancer, there should be every effort made to find the best. And it is whey protein that is increasingly coming to the public's attention as one of the most comprehensive forms of protein available.

In fact, in many aspects, whey protein, which is often mixed into a delicious shake, is even superior to soy.

Whey protein is a potent ally to the general immune system. The protein in whey has been shown to dramatically raise glutathione levels, which is an essential water-soluble antioxidant that protects cells and serves to neutralize toxins such as peroxides, heavy metals, carcinogens, and many others. In animal studies, whey protein concentrate consistently raised glutathione levels beyond those of any other protein studied, including soy (Bounous G. and Gold P., Clin. Invest. Med. 1991).

In fact, glutathione is so necessary to a healthy immune system that it appears immunity itself can be modulated by glutathione levels (Rosanne K., Fidelus and Min Fu Tsan. Cellular Immunology, 1986). Sufferers of diseases such as AIDS, atherosclerosis, Alzheimer's and Parkinson's often exhibit reduced glutathione levels; however, a small pilot study of HIV-positive men who ate whey protein found dramatic increases in glutathione levels, with two out of the three men reaching an ideal weight (Bounous G., Baruchel S., Faiutz J., Gold P., Clin. Invest. Med. 1992).

In its ability to enhance the immune system, whey protein also fights infections. Animals fed whey protein showed increased response from both the humoral and cellular immune systems to a variety of challenges, such as salmonella and streptococcus pneumonia (Bounous G., Konshavn P., Gold P. Clin. Invest. Med. 1988). Again, this effect was not seen with other proteins.

Perhaps the most exciting potential of whey protein is its ability to fight cancer. In vitro research has shown that the growth of breast cancer cells is strongly inhibited when exposed to low concentrations of whey protein (Baruchel S. and Vaiu G., Anti Cancer Research 1996).

Another recent clinical study showed a regression in some cancerous tumors when patients were administered 30 grams per day of whey protein powder (Kennedy R.S., Konok G.P., Bounous G., Baruchel S., Lee T.D., Anti Cancer Research 1995). Likewise, animals fed whey protein before being subjected to dimethylhydrazine (DMH), a strong cancer-causing agent, mounted a much more vigorous immune response than animals fed any other type of protein. More importantly, any resulting tumors were smaller and far fewer in number in the animals fed whey protein (Bounous G., Clin. Invest. Med. 1988).

This study was confirmed by additional research showing that rats subjected to DMH and fed whey protein showed fewer tumors and a reduced pooled area of tumors. The researchers concluded that whey protein offered "considerable protection to the host," compared with other proteins, including soy (McIntosh G.H., et al. Journal of Nutrition 1995).

It is interesting to note that the concentration of glutathione in tumor cells is often much higher than in surrounding normal cells, meaning that cancer cells will respond differently to nutrients and drugs that alter glutathione status. This discrepancy in glutathione status between normal cells and cancer cells also makes it harder to kill cancer cells with chemotherapy. Because the surrounding cells have lower levels of glutathione to begin with, anything that further suppresses glutathione puts normal healthy cells in danger long before cancer cells are affected.

Instead, cancer patients need a compound that can target cancer cells and deplete only their glutathione. Whey protein appears to be just such a compound. When introduced in studies, cancer cells responded to whey protein by losing glutathione, while normal cells actually increased in glutathione and cellular growth (Baruchel S. and Vaiu G., Anti Cancer Research 1996). No other protein reported the same effect. Even the mechanism by which whey protein acts is not fully understood. It appears that whey protein interferes with the cancer cells' ability to regulate glutathione.

Whey protein is effective because of its abnormally high biological value, which is a measure of the nitrogen retained for growth or maintenance, expressed as a percentage of the nitrogen absorbed (Renner E., 1983). Whey, with the highest biological value of any protein, is absorbed, utilized and retained in the body better than other proteins. This has caused athletes to make whey protein concentrate a best-seller. In fact, one recent pilot study found whey protein isolate corrected the immune suppression often seen in athletes suffering from over-training syndrome (C.M. Colker, D. Kalman, W.D. Brink, and L.G. Maharam. Med. Sci. in Sports in Exercise 1998).

And proteins with a high biological value are more tissue-sparing, making whey protein concentrate a good choice for people suffering from wasting diseases such as AIDS, cancer, and/or aging-related muscle losses.

In addition, some animal research suggests whey can prevent atherogenesis by preventing LDL cholesterol from oxidizing (M.Kajikawa et al. Biochemica et Biophysica Acta 1994). A complementary study found that whey may reduce LDL levels as well as triglycerides (Zhang X. and Beynen A.C. Brit. J. of Nutri. 1993). Whey also appears to have a direct in vitro effect on bone cell growth. It was found to stimulate protein synthesis, DNA content, and increased hydroxyproline contents of bone cells (Takada Y., Aoe S., Kumegawa M., Biochemical Research Communications 1996).

Coupled with the observation that animals fed whey protein powder had stronger bones, researchers concluded, "These findings suggest that whey protein contains active components that can activate osteoblast cell proliferation and differentiation. Also these active components can probably permeate or be absorbed by the intestines. We propose the possibility that the active component in the whey protein plays an important role in bone formation by activating osteoblasts."

Finally, whey is a highly complex protein that is made up of many sub-fractions, including beta-lactoglobulin, immuno-globulins, bovine serum albumin (BSA), lactoperoxidases, lysozyme, lactoferrin and others. Each of these subfractions has its own unique biological properties and benefits.

Even a brief discussion of lactoferrin, for instance, illustrates the many positive effects of this one sub-fraction. Lactoferrin is found in tiny amounts in the human body, yet appears to be a first-line immune system defense. It binds to iron so strongly that it inhibits the growth of iron-dependent bacteria (Oram, J., Reiter, B. Biochem. Biophys. Acta, 1968), and can block the growth of many pathogenic bacteria and yeast (Bellamy W. et al., J. Appl. Bacteriol. 1992). Its antimicrobial action may even improve antibiotics (Ellison, R.T., Infect. and Immun. 1988).

In the digestive tract, lactoferrin may help by stimulating intestinal cell growth (Hagiwara, T., et al., Biosci. Biotech. Biochem. 1995), and enhancing the growth of "good" intestinal microflora (Petschow, B., et al., Pediat. Res. 1991). A strong antioxidant, lactoferrin has positive immunomodulatory effects and scavenges free iron, which prevents uncontrolled iron-based free radical reactions (Eugine. P. et al., 1993) and protects certain cells from lipid peroxidation (Gutteridge et al., 1981).

It would be wise to incorporate whey protein into a supplement program just to receive the benefits of lactoferrin. But when these positive influences are combined with whey protein's many other strengths, including helping the immune system and fighting cancer, it should become a valuable element of any program.

Fighting Cancer With Whey
By Will Brink

Recent studies on whey demonstrate it's an even better protein supplement than previously thought.

Although whey protein's health benefits have only recently been elucidated, the use of whey protein for medicinal purposes has been prescribed since the time of Hippocrates. In fact, there are two ancient proverbs from the Italian city of Florence that say, "If you want to live a healthy and active life, drink whey," and, "If everyone were raised on whey, doctors would be bankrupt."

In previous issues, we've chronicled the extensive research showing the many potential health benefits of whey protein concentrate. The majority of that research was done in the 1980s and early 1990s, and was extremely persuasive (see sidebar story). Recently, scientists have continued their research on whey proteins with even more impressive results. What follows is some of the more current, interesting and useful research on whey proteins.

Whey and Cancer

Additional studies have been done on animals regarding cancer-causing chemicals to see what effects whey protein concentrate would have on cancer prevention or treatment. Scientists fed rats various proteins and then subjected them to the powerful carcinogen dimethylhydrazine.

As with the previous research, the rats fed whey protein concentrate showed fewer tumors and a reduced pooled area of tumors (tumor mass index). The researchers found whey protein offered "considerable protection to the host" over that of other proteins, including soy.

McIntosh G.H., et al., Journal of Nutrition, 1995)

Even more exciting, in vivo research on cancer and whey showed whey protein concentrate inhibited the growth of breast cancer cells at low concentrations (Baruchel S. and Vaiu G., Anti Cancer Research, 1996). Finally, and most importantly, a fairly recent clinical study with cancer patients showed a regression in some patient's tumors when fed whey protein concentrate at 30 grams per day. (Kennedy R.S., Konok G.P., Bounous G., Baruchel S., Lee T.D., Anti Cancer Research, 1995).

Whey and Glutathione

This new research using whey protein concentrate led researchers to an amazing discovery regarding the relationship between cancerous cells, glutathione (GSH) and whey protein concentrate. It was found that whey protein concentrate selectively depletes cancer cells of their glutathione, thus making them more susceptible to cancer treatments such as radiation and chemotherapy.

It has been found that cancer cells and normal cells will respond differently to nutrients and drugs that affect glutathione status. What is most interesting to note is the fact that the concentration of glutathione in tumor cells is higher than that of the normal cells that surround it. This difference in glutathione status between normal cells and cancer cells is believed to be an important factor in cancer cells' resistance to chemotherapy.

As the researchers put it, "Tumor cell GSH concentration may be among the determinants of the cytotoxicity [poisonous to cells] of many chemotherapeutic agents and of radiation, and an increase in GSH concentration appears to be at least one of the mechanisms of acquired drug resistance to chemotherapy."

They further state, "It is well-known that rapid GSH synthesis in tumor cells is associated with high rates of cellular proliferation. Depletion of tumor GSH in vivo decreases the rate of cellular proliferation and inhibits cancer growth."

The problem is, it's difficult to reduce glutathione sufficiently in tumor cells without placing healthy tissue at risk and putting the cancer patient in a worse condition. What is needed is a compound that can selectively deplete the cancer cells of their glutathione, while increasing, or at least maintaining, the levels of glutathione in healthy cells.

This is exactly what whey protein appears to do. In this new research it was found that cancer cells subjected to whey proteins were depleted of their glutathione, and their growth was inhibited, while normal cells had an increase in GSH and increased cellular growth.

These effects were not seen with other proteins. Not surprisingly, the researchers concluded, "Selective depletion of tumor GSH may in fact render cancer cells more vulnerable to the action of chemotherapy and eventually protect normal tissue against the deleterious effects of chemotherapy." The exact mechanism by which whey protein achieves this is not fully understood, but it appears that it interferes with the normal feedback mechanism and regulation of glutathione in cancer cells.

It is known that glutathione production is negatively inhibited by its own synthesis. Being that baseline glutathione levels in cancer cells are higher than that of normal cells, it is probably easier to reach the level of negative-feedback inhibition in the cancer cells' glutathione levels than in the normal cells' glutathione levels.

Whey and LDL Cholesterol

The positive health benefits of whey protein concentrate does not end with its effects on immunity and cancer prevention and treatment. Whey protein concentrate also was found to be a potent inhibitor of oxidized low density lipoprotein cholesterol. Current research suggests that the conversion of LDL to oxidized LDL is the trigger that leads to atherogenesis...the formation of the plaque and lesions associated with atherosclerosis.

Therefore, any substance that prevents the oxidation of LDL is thought to be anti-atherogenic. Though animal-based proteins have traditionally been implicated as being pro-atherogenic, whey proteins appear to be an exception to the rule. whey protein is made up of several minor and major fractions, such as beta-lactoglobulin, alpha-lactalbumin, albumin, lactoferrin and immunoglobulin. It was discovered that the minor constituent responsible for the ability of whey protein concentrate to prevent the oxidation of LDL appears to be the lactoferrin fraction of the protein. (M. Kajikawa et al. Biochemica et Biophysica Acta, 1994).

Lactoferrin in Whey

When the lactoferrin was removed from the protein, the ability of the whey-protein concentrate to prevent LDL oxidation was greatly reduced, leading the researchers to speculate, "Our results suggest that LF (lactoferrin) is the main factor responsible for the inhibitory effect of whey protein (on LDL) and it may function synergistically together with other factors in the whey protein, for example, alpha-lactalbumin."

Another study using rats examined the effects of whey protein concentrate and casein on cholesterol and the risk factors of heart disease. Though casein (another milk-based protein commonly used in research) is known to raise cholesterol in humans and animals, whey protein has the opposite effect, leading the researchers to note, "At the high dietary protein level [300 gram per kilogram of feed] , whey protein significantly lowered plasma and liver cholesterol and also plasma triacylglycerols." (Zhang X. and Beynen A.C. Brit. J. of Nutri., 1993).

The cholesterol-lowering effects of whey protein concentrate in this study also was associated with a reduction in LDL cholesterol. Most interesting was the fact that this effect on cholesterol was not seen when the animals were fed amino acid mixtures that simulated whey protein, so it is clear that there are properties within the whey that have these effects beyond that of its amino acid profile.

Whey and Bone Growth

Finally, whey protein appears to play a direct role in bone growth. Researchers found that rats fed whey protein concentrate showed increased bone strength and bone protein such as collagen. This discovery led researches to test whether or not whey protein directly stimulated osteoblast (bone cell) growth in vitro.

Whey protein was found to stimulate, dose dependently, total protein synthesis, DNA content, and increased hydroxyproline contents of bone cells. (Takada Y., Aoe S., Kumegawa M., Biochemical Research Communications, 1996).

It should be noted that not all whey protein concentrates are created equal. Processing whey protein to remove the lactose and fats without losing its biological activity takes special care by the manufacturer. The protein must be processed under low temperature and low acid conditions so as not to "denature" the protein. Maintaining the natural state of the protein is essential to its biological activity.

These research findings, combined with the previous decade of study on whey protein, should convince anyone that whey protein concentrate is truly the life-extension protein.

Higher Glutathione Levels and Whey:

A decade-and-a-half of findings on the benefits of whey protein are far-reaching. Previous studies include the following:

• Whey protein concentrate dramatically raises glutathione levels. Glutathione is an essential water-soluble antioxidant in the body that protects cells and serves as a primary detoxifier of harmful compounds such as peroxides, heavy metals, carcinogens and other toxins.
• Glutathione also is intimately tied to immunity, and reduced glutathione levels have been associated with disease such as AIDS, atherosclerosis, Alzheimer's disease and Parkinson's disease, to name only a few. In fact, glutathione levels appear to be one way of modulating immunity. (RosanneK., Fidelus and Min Fu Tsan. Cellular Immunology, 1986).
• Whey protein concentrate was found to consistently raise this extremely important immune stimulating antioxidant beyond that of any protein studied (including soy) to higher than normal levels in multiple animal studies. (Bounous G. and Gold P., Clin. Invest. Med. 1991).
• A small pilot study with HIV-positive men who were fed whey protein concentrate found dramatic increases in glutathione levels of all the study participants, with two out of three men reaching their ideal body weight. (Bounous G., Baruchel S., Faiutz J., Gold P., Clin. Invest. Med. 1992).
• In fact, there have been several U.S. and international patents granted for the treatment of AIDS and improving immunity with whey protein concentrates.
• Whey protein improves immune function and fights infections. Animals fed whey protein concentrate consistently showed dramatic enhancement of both the humoral and cellular immune response to a variety of immune challenges, such as salmonella, streptococcus pneumonia (Bounous G., Konshavn P., Gold P., Clin. Invest. Med. 1988) and extreme cancer-causing chemicals. This effect on immunity was not seen with other proteins.

The Benefits of Whey (Abstracts from Published Papers)

Whey protein as cancer treatment adjuvant, antibiotic, and anti-aging agent

Whey and Chemotherapy

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. In: Anticancer Res (1996 May-Jun)16(3A):1095-9

We report the in vitro selective inhibitory activity of a humanized whey protein concentrate Immunocal on growth of mammary carcinoma cells and Jurkat T cells in comparison to normal peripheral blood mononuclear cells. We relate this inhibitory activity to a selective depletion of intracellular glutathione synthesis. The use of humanized whey protein concentrate as a food supplementation may have direct implication in clinical trial with adjuvant chemotherapy.

Whey and Diseases of Aging

The influence of dietary whey protein on tissue glutathione and the diseases of aging

Bounous G Gervais F Amer V Batist G Gold P. In: Clin Invest Med (1989 Dec) 12(6):343-9

This study compared the effects of a whey-rich diet (20 g/100 g diet), with that of Purina mouse chow or casein-rich diet (20 g/100 g diet), on the liver and heart glutathione content and on the survival of old male C57BL/6NIA mice.

The study was performed during a limited observation period of 6.3 months. In mice fed the whey protein-rich diet between 17 months and 20 months of age, the heart tissue and liver tissue glutathione content were enhanced significantly above the corresponding values of the casein diet-fed and Purina-fed mice.

Mice fed the whey protein diet at the onset of senescence at 84 weeks exhibited increased longevity as compared to mice fed Purina mouse chow over the 6.3-month observation period extending from the age of 21 months (corresponding to a human age of 55 years) to 26-27 months of age (corresponding to a human age of 80 years), during which time 55% mortality was observed. The corresponding mean survival time of mice fed the defined casein diet is almost identical to that of Purina-fed controls.

Body weight curves were similar in all three dietary groups. Hence a whey protein diet appears to enhance the liver and heart glutathione concentration in aging mice and to increase longevity over a 6.3-month observation period.

Whey and Cholesterol Concentrations

Lowering effect of dietary milk-whey protein v. casein on plasma and liver cholesterol concentrations in rats

Zhang X Beynen AC. In: Br J Nutr (1993 Jul) 70(1):139-46

The effect of dietary whey protein versus casein on plasma and liver cholesterol concentrations was investigated in female, weanling rats. Balanced, purified diets containing either whey protein or casein, or the amino acid mixtures simulating these proteins, were used.

The high-cholesterol diets (10 grams of cholesterol per kg feed) had either 150 or 300 grams protein or amino acids/kg feed. The diets were given for 3 weeks. At the low dietary protein level, whey protein versus casein did not affect plasma total cholesterol, but lowered the concentration of liver cholesterol.

At the high dietary-protein level, whey protein significantly lowered plasma and liver cholesterol and also plasma triacylglycerols. The hypocholesterolemic effect of whey protein was associated with a decrease in very-low-density-lipoprotein cholesterol.

At the high dietary protein concentration, whey protein reduced the fecal excretion of bile acids when compared with casein. The effects of intact whey protein versus casein were not reproduced by the amino acid mixtures simulating these proteins. It is suggested tentatively that the cholesterol-lowering effect of whey protein in rats is caused by inhibition of hepatic cholesterol synthesis.

Lactoferrin's Antibacterial Synergy

Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferring

Ellison RT 3d Giehl TJ LaForce FM. In: Infect Immun (1988 Nov) 56(11):2774-81

We hypothesized that the iron-binding proteins could affect the gram-negative outer membrane in a manner similar to that of the chelator EDTA. The ability of lactoferrin and transferrin to release radiolabeled lipo polysaccharide (LPS) from a UDP- galactose epimerase deficient Escherichia coli mutant and from wild-type Salmonella typhimurium strains was tested. Initial studies in barbital-acetate buffer showed that EDTA and lactoferrin cause significant release of LPS from all three strains. Further studies found that LPS release was blocked by iron saturation of lactoferrin, occurred between pH 6 and 7.5, was comparable for bacterial concentrations from 10(4) to 10(7) CFU/ml, and increased with increasing lactoferrin concentrations. Studies using Hanks balanced salt solution lacking calcium and magnesium showed that transferrin also could cause LPS release. Additionally, both lactoferrin and transferrin increased the antibacterial effect of a subinhibitory concentration of rifampin, a drug excluded by the bacterial outer membrane. This work demonstrates that these iron-binding proteins damage the gram-negative outer membrane and alter bacterial outer membrane permeability.

Antibacterial Activity of Lactoferrin

Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment

Yamauchi K Tomita M Giehl TJ Ellison RT 3d. In: Infect Immun (1993 Feb) 61(2):719-28

Recent work has indicated that in addition to binding iron, human lactoferrin damages the outer membrane of gram-negative bacteria. In this study, we determined whether bovine lactoferrin and a pepsin- derived bovine lactoferrin peptide (lactoferricin) fragment have similar activities. We found that both 20 microM bovine lactoferrin and 20 microM lactoferricin release intrinsically labeled [3H]lipopolysaccharide ([3H]LPS) from three bacterial strains, Escherichia coli CL99 1-2, Salmonella typhimurium SL696, and Salmonella montevideo SL5222. Under most conditions, more LPS is released by the peptide fragment than by whole bovine lactoferrin. In the presence of either lactoferrin or lactoferricin there is increased killing of E. coli CL99 1-2 by lysozyme. Like human lactoferrin, bovine lactoferrin and lactoferricin have the ability to bind to free intrinsically labeled [3H]LPS molecules. In addition to these effects, whereas bovine lactoferrin was at most bacteriostatic, lactoferricin demonstrated consistent bactericidal activity against gram-negative bacteria. This bactericidal effect is modulated by the cations Ca2+, Mg2+, and F3+ but is independent of the osmolarity of the medium. Transmission electron microscopy of bacterial cells exposed to lactoferricin show the immediate development of electron-dense "membrane blisters." These experiments offer evidence that bovine lactoferrin and lactoferricin damage the outer membrane of gram-negative bacteria. Moreover, the peptide fragment lactoferricin has direct bactericidal activity. As lactoferrin is exposed to proteolytic factors in vivo which could cleave the lactoferricin fragment, the effects of this peptide are of both mechanistic and physiologic relevance.

Whey's Antibacterial Spectrum

Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin

Bellamy W Takase M Wakabayashi H Kawase K Tomita M. In: J Appl Bacteriol (1992 Dec) 73(6):472-9

A physiologically diverse range of Gram-positive and Gram-negative bacteria was found to be susceptible to inhibition and inactivation by lactoferricin B, a peptide produced by gastric pepsin digestion of bovine lactoferrin. The list of susceptible organisms includes Escherichia coli, Salmonella enteritidis, Klebsiella pneumoniae, Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa, Campylobacter jejuni, Staphylococcus aureus, Streptococcus mutans, Corynebacterium diphtheriae, Listeria monocytogenes and Clostridium perfringens. Concentrations of lactoferricin B required to cause complete inhibition of growth varied within the range of 0.3 to 150 micrograms/ml, depending on the strain and the culture medium used. The peptide showed activity against E. coli O111 over the range of pH 5.5 to 7.5 and was most effective under slightly alkaline conditions. Its antibacterial effectiveness was reduced in the presence of Na+, K+, Mg2+ or Ca2+ ions, or in the presence of various buffer salts. Lactoferricin B was lethal, causing a rapid loss of colony-forming capability in most of the species tested. Pseudomonas fluorescens, Enterococcus faecalis and Bifidobacterium bifidum strains were highly resistant to this peptide.