Wellwisdom Whey Proteins Versus Other Whey Proteins
Bovine Serum Albumin, alpha-lactalbumin and beta-lactoglobulins
Whey Protein Facts and Application, Dr. Lawrence Sosna
Whey Protein Quality As Compared to Other Available Proteins
What is Whey? a report by: David Marshall, Jr., O.D., Ph.D.
Soy Vs. Whey, Carlon M. Colker, M.D.
What is Lactoferrin?
Lactoferrin is an iron-binding and iron-modulating protein found in bovine milk and even more prevalent in our whey protein concentrate. Lactoferrin resides in the chemical family called cytokines. This family of chemicals coordinates the body's cellular immune defensive response that protects us from most infections, tumors and cancers. They also boost the activity of T-cells and stimulate production of immunoglobulins. Without these cytokines our immune system suffers and reacts by creating an over-active immune response. It is our body's first defense, protecting orifices such as the eyes, mouth and nose from bacterial infection.
Lactoferrin and Iron Modulation
Lactoferrin is a very important bioactive molecule which can provide iron to those cells in need, and limit it to those in excess, thus maintaining an iron homeostasis within the body.
Iron deficiency is a fairly common disorder, affecting billions of people a year. The result of iron deficiency can lead to extreme anemia, characterized by fatigue, lethargy, heart palpitations, and shortness of breath. The role of iron in a well functioning body and immune system is well documented and pretty much agreed upon across the board. Common sufferers of iron deficiency include (but are not limited to) women, children, vegetarians, and many studies conclude, high endurance athletes. The body does not easily assimilate iron (or lactoferrin) in a denatured state (highly processed) which is how it is presented in many bovine dietary supplements. With these supplements, high amounts are required for any benefit to arise. Our Proserum® whey protein concentrate is an non-denatured whey protein supplement that is minimally processed to maintain the bioavailability of the lactoferrin.
On the flip side excess iron is a risk as well, although not as common. Some complications associated with this disorder are: bacterial infections, diarrhea, gastrointestinal disorders and even iron-toxicity. A lot of these complications arise from the body's ingestion of unbound iron. Iron that is bound to lactoferrin is much easier to absorb and utilize, and is not lost through human excretions or through other organisms in the body. Iron not bound in the body is a catalyst for the production of free radicals, which have a negative effect on the body's biology. Lactoferrin is an important part of the body's natural defense system. Studies show that it inhibits the binding of pathogens like H. pylori and E. coli to the intestinal wall. Many micro-organisms need iron for growth and by limiting the levels of free iron, lactoferrin can actually inhibit bacterial growth. The pathogens cellular structure loses its integrity because of the iron deprivation and necrosis ensues.
The first major entrance of lactoferrin on the health scene was prompted by a paper written by an AIDS researcher discussing the importance of lactoferrin as a regulator of the immune response in people with AIDS. Recent studies have shown that lactoferrin can also inhibit the growth of the HIV virus.
There have been many other studies proving lactoferrin to be a very beneficial substance. The antibacterial properties have been documented very well. A study by the Institute of Public Health in Tokyo, Japan showed that E. coli 0157:H7 can falter under influence of the antimicrobial effects of bovine lactoferrin. Another well documented study by the National Cancer Institute in Tokyo, Japan concluded that bovine lactoferrin inhibits the Hepatitis C infection in human cells. This is of major importance because Hepatitis C has been found to be the main causative factor in chronic viral hepatitis. Lactoferrin seems to inhibit the absorption of the viral particle to the human cell by binding to the cell receptor site or to the virus.
Lactoferrin has a broad range of benefits, with new discoveries being made daily. It enhances and modulates immune system function and provides many iron-enhancing and modulating benefits. It has also been said to act as an immunostimulator in the digestive system, as well as an inhibitor of the growth of many unhealthy micro-organisms in the digestive tract. Lactoferrin regulates the immune response of the body in many differing ways. It inhibits many viruses from thriving in the body and is a very important component in immune-therapy. Our Vital Whey ® and ImmunoPro® products provide an excellent source of non-denatured lactoferrin in its most biologically available state.
Immunoglobulins (IgG) are proteins that are present in bovine whey protein. One of their functions is as a transporter of antibodies against harmful microorganisms like viruses, bacteria and other foreign invaders. IgG has been used to treat diseases such as multiple sclerosis, rheumatoid arthritis, hepatitis A, anemia, Chronic Fatigue Syndrome, and chickenpox, among others. IgG are essential elements to maintain a humans immunity from detrimental microorganisms and toxins. This substance is transferred from mother to child inside the womb to protect him/her from the introduction of pathogens in the outside world. This way the child is born with a passive immunity. IgG work together and separately to battle antigens. They circulate in the blood and lymphatic systems, and also reside in the mucous membranes to act as a barrier against invaders.
These immunoglobulins are of a critical importance because many bacteria's become more resistant to antibiotics every day. These bacteria infect our food supply and there are more viruses created at a faster rate than the vaccines used to battle them, science is constantly having to catch up. More and more diseases are being linked to bacterial infection, including peptic ulcers and heart disease.The claim of a link between bacterial infection and heart disorders have very strong evidence to support them(1). ImmunoPro®, with its high amounts of IgG, plays a major role as a supplier of these key protein fractions.
How The Body Utilizes IgG
Our body's first line of immune defense to unhealthy organisms is the intestinal tract(2). The IgG has been found to resist break down by the digestive enzymes within the digestive tract (due to the glycoproteins and trypsin inhibitors), therefore the IgG enters the intestinal wall fully intact where they defend the lining against invading organisms, and prevent the absorption of foreign proteins. The IgG is a factor in increasing the immune system activity level. This substance is important in stabilizing and restoring a damaged intestinal tract so it can function once again at its optimum capacity for nutrient absorption and utilization.
The antibodies derived from bovine milk have many of the mothers milk IgG characteristics and may be active against the same diseases in humans. Immunoglobulins consist of four polypeptide chains with two of the same heavy chains linked by covalent and non-covalent bridges. The light and heavy chains both have areas with constant amino acids and with a variable region. This variable region is where the antibody meets the antigen (foreign molecule). The bovine milk antigens are resistant to the peptic digestion process, which is good for those of us using an non-denatured whey protein abundant in IgG proteins(3).
1. G. Bauriedel, et al.Chlamydia pnuemoniae in coronary plagues. Increased detection with acute coronary syndrome. Dtsch Med Wochenssch 124(13) (April 1, 1999): 37-80; FL Visseren, et al. Atherosclerosis as an infectious disease. Ned Tijdschr Geneeskdl 143(6) (Feb 6, 1999): 291-95; J. Danesch, et al. Is helicobacter pylori a factor in atherosclerosis? J Clin Microbiol 37(5) )May, 1999): 1651; Dp Strachan, et al., Relation of Chlamydia pnuemonia serology to mortality and incidence of ischaemic over 13 years in the caerphilly prospective heart disease study. Br Med J 318(7190) (April 17, 1999): 1035-39; Norman Watner, The Salt lake Tribune June 1, 1996.
2. Guyton AC. Protein Metabolism. In: Textbook of Medical Psyiology 8th edition. Philadephia (PA): WB Saunders; 1991.
3. Watson DL. Immunologic functions of the mammary gland and its secretion - Comparative review. Aust J Biol Sci 1980; 33:402-422
How do Vital Whey® and ImmunoPro® compare to other whey proteins?
Proserum® is the most potent native whey protein available:
The vast majority of whey is from grain-fed cows, which has been shown to be of inferior quality to grass-fed cows. Grass-fed cows have 2 to 4 times the amount of omega 3 fatty acids, and is also a rich source of CLA (Conjugated Linoleic Acid). When cows are allowed to graze on fresh pastures alone their milk contains 3 to 5 times more CLA than products from cows fed grain. Proserum whey protein is derived from cows that graze year-round on chemical and pesticide-free natural pastures.
Proserum® utilizes a proprietary filtration and drying method that involves a minimal amount of processing. The result is a microbial safe product that exceeds all standards and makes it the optimum nutrition whey protein powder. We DO NOT use cross-flow filtration, microfiltration, isolate filtration, hydrolyzation or ion exchange because these methods denature (damage) the original protein components. After use of these commercial methods, the damaged proteins are then filtered out and what remains is a narrow range of "undenatured" proteins that have survived the whey manufacturing process. Additionally the vital protein-bound fats have been removed. Some of these whey protein products are then referred to as undenatured/cold processed. It is not possible to undenature or restore the full biological activity of a protein after it has been damaged.
When considering a whey product it is best to ask for a lab analysis of the whey showing actual percentages of components present from the distributor/manufacturer. You should not receive a range of percentages as that denotes it is not from an actual test. Test results on our products are from an independent lab that performs SDS PAGE Gel method testing.
Proserum® contains the Glutathione precursor, covalent bonded Cysteine, which makes it the optimum whey protein. Additionally, it contains the full range and highest levels of the most important protein components: Lactoferrin, Immunoglobulins, Serum Albumin, Active Peptides and Growth Factors making it the optimum nutrition protein powder to support proper immune function.
Vital Whey® and ImmunoPro® whey proteins contain naturally occurring Cysteine. It is the optimal component for the intracellular production of Glutathione (GSH). Cysteine is very scarce in our modern diet and therefore Glutathione production is limited and deficiency is prevalent. If Cysteine undergoes prolonged heating or processing, as seen with most conventional dairy and dairy by-products do, it is denatured and converted to Cystine. Cystine is the form that is found in high-end whey proteins isolates, as they are all heavily processed to raise their protein content. Vital Whey® and ImmunoPro® are unique as they are minimally processed native whey products and retain naturally occurring Cysteine in its original form.
An important note on the synthesized free form amino acid L-cysteine. It can have adverse effects in supplemental doses with sensitive individuals or those who have any heavy metal accumulation.
Regarding Whey Protein Concentrate: The Journal Immunology reports: The bioactivity occurs through the ability of the protein concentrate to help replenish Glutathione levels via continuous dietary provision of Glutathione precursors, especially Cysteine, during lymphocyte proliferation, thus supporting an optimal immune response. This process seems to not only increase intercellular levels of Glutathione and precursors at the time of ingestion, but also builds up stores of these substances within the cells which lasts for a substantial post-ingestion time interval.” Fidelus RK, Tsan MF. GSH and lymphocyte activation: a function of aging and autoimmune disease. Immunology 61: 503-508, 1987
*** Analysis of protein as determined by an independent laboratory using the SDS PAGE Gel method. This is the industry accepted method to determine the actual biological activity of a milk protein.
|Bovine serum albumin enhances pregastric lipases, promoting more efficient newborn digestion, and it also binds fatty acids in the body. More importantly, it also contains an appreciable amount of cysteine, which is the molecular precursor to glutathione.
Alpha-lactalbumin is the subunit of lactose synthesis the enzyme which catalyzes the addition of galactose to glucose to create lactose*. It is possible this may aid in infant digestion of milk. It also contains cysteine, though not in as great a ratio as bovine serum albumin.
Beta-lactoglobulin is involved with the transfer of passive immunity and the binding of retinol and fatty acids. This binding allows for the efficient uptake of fats by the cells.
The presence of beta-lactoglobulin and alpha-lactalbumin protein in milk is a major cause for allergic reaction in humans. Subsequently, those with true milk allergies to milk protein should not ingest these milk proteins and should caution their use in any form. Lactose intolerance is not a factor in this allergic response. Typically lactose intolerance presents itself as diarrhea from the excess consumption of lactose (this can vary from individual to individual). ImmunoPro® contains low levels of lactose and this is well below the tolerance level for most people.
Our Body's Master Antioxidant and Best Kept Secret
Glutathione is the body's own natural antioxidant. Antioxidants neutralize free radical activity in the body, and are vitally important for the function of a healthy immune system.
GSH is depleted by oxidative stress, which usually occurs by illness, infection, trauma, medication or surgery.
"Antioxidants are well documented to play vital roles in health maintenance and disease prevention. GSH is our cell's own major antioxidant. Why not use what is natural?"(1)
Glutathione (GSH) is a tripeptide composed of the amino acids Cysteine, Glutamine, and Glycine. These molecules are found in a larger ratio in non-denatured whey protein compared with any other proteins ingested by humans. Both Cysteine and Glutamine are principle players in the coordinated T-cell response of macrophages and lymphocytes(2).
GSH is naturally found in all the cells of mammals. It provides the principal intracellular defense against oxidative stresses. GSH levels decrease with an insufficient nutrient intake, non-denatured protein specifically. Cysteine in the combined molecule of Glutamine and Cysteine (glutamylcysteine dipeptidesU) is the rate limiting step for GSH production. The natural conformation of the proteins is essential for producing intracellular Glutathione. Therefore the consumption of proteins that are low in Cysteine limit GSH production and availability.
True non-denatured Whey Protein Concentrate is the optimal nature prescribed precursor (required for the production) of Glutathione (GSH). It contains non-denatured Cysteine and Glutamine, the amino acids required for intracellular GSH production. It naturally contains the full range of proteins that enhance immune function including the protein bound fats that, in whey protein isolates, have been removed.
There are many whey proteins to choose from. The critical factors are: How was the whey produced? What are the actual amounts of the important proteins measured by independent lab analysis? These questions are addressed in our FAQ Page and throughout our website.
For more research details see Whey Protein Report, Glutathione by: David Marshall Jr.,O.D., Ph.D.
Glutathione "....since it is this protein more than any other that has been thought to provide a protective function for a number of organ systems, including the crystalline lens of the eye, the retina, prostate gland, and the immune system."(3)
Non-denatured Whey Protein is acknowledged by the medical establishment as a dietary supplement that supports immune function and detoxification. It is now listed in the Physicians Desk Reference (PDR).
Immune Depressed individuals have lower GSH levels when fighting disease. Lymphocytes, cells vital for your immune response, depend on GSH for their proper function and replication. Immunology 61: 503-508 1987. Cellular depletion of Glutathione has been implicated as a causative, or contributory factor in many pathologies including Parkinson's, Alzheimer's, cataracts, arteriosclerosis, cystic fibrosis, malnutrition, aging, AIDS and cancer (Bounous et al., 1991). In addition, Glutathione is essential in supporting the immune system, including natural killer cells (Droege et al., 1997) and in the maintenance of T-lymphocytes (Gutman, 1998).
GSH plays a role in eliminating many carcinogens as well as maintaining immune function towards providing stronger anti-tumor defenses.Cancer Letters 57: 91-94 1991
It is known that as we age, there is a precipitous drop in GSH levels. Lower Glutathione levels are implicated in many diseases associated with aging, including Cataracts, Alzheimer's disease, Parkinson's, arteriosclerosis and others. Journal of Clinical Epidemiology 47: 1021-28 1994
Strong muscular activity generates oxyradicals leading to muscle fatigue and poorer performance. GSH neutralizes these radicals. Whey proteins promote muscular development. Sports Medicine 21; 213 - 238, 1996. Recent research indicates that propensities toward many degenerative diseases and aging itself are related to the capacity of the cell to robustly recover from oxidative insult. The capacity of a cell to recover from such insult can be determined by measuring the intracellular stores of Glutathione. (Noelle et al., 1981)
Antioxidants are well documented to play vital roles in health maintenance and disease prevention. GSH is our cell's own major antioxidant. Why not use what is natural? Biochemical Pharmacology 47:2113-2123 1994
Low GSH has been demonstrated in neurodegenerative diseases such as MS (Multiple Sclerosis), ALS (Lou Gehrig's Disease), Alzheimer's, and Parkinson's, among others. The Lancel 344: 796-798 1994
Toxins, Pollution, Radiation
GSH detoxifies many pollutants, carcinogens and poisons, including many in fuel exhaust and cigarette smoke. It retards damage from radiation such as seen with loss of the ozone. Annual Review of Biochemistry 52 : 711-780 1983. The liver is the main detoxification organ of the body. In the liver we find very high concentrations of GSH, as it is a major factor in numerous biochemical detoxification pathways. Numerous studies have demonstrated that patients with compromised liver function due to alcohol abuse have significant reduction of GSH in the liver. (Lamestro, 1995)
Low Glutathione levels with poor survival in AIDS patients. Much literature has been written demonstrating the role of enhancing GSH levels in AIDS. Proc. National Acad. Science USA 94: 2967-72 1997
1. Biochemical Pharmacology 47:2113-2123 1994
2. Droege W, Holm E. Role of cysteine and glutathione HIV-wasting and other diseases associated with muscle wasting and immunoglobulin function. FASEB J 1997; 11:10771089
3. WHEY PROTEIN REPORT,Current Concepts on Whey Protein Usage, Prepared for The Cleveland Eye Clinic,by: David Marshall, Jr., O.D., Ph.D., Consult
Whey protein is considered a very safe supplement for most people when used appropriately. You will want to check with your doctor if you are currently taking any medications to make sure there will not be any adverse reactions with the whey protein. Whey protein side-effects would most likely be caused if you have a true milk allergy (not lactose intolerance), in which case you should avoid any product containing milk. Our Proserum® contains 1g of lactose per 10g serving (which is considered below intolerance levels), and less than 1 percent non-denatured casein.
Dr. Lawrence Sosna
The word Protein means “first substance”. Our first protein food was found in our mother’s milk. Milk is the only food designed specifically to optimally sustain the life of a mammal. In fact, the root word for nutrition means to suckle. As a species, we would not have survived if not for the nutrition and protection mother’s milk offers.
Whey is one of the two protein groups found in milk. It is a liquid complex consisting of a wide range of proteins. The other protein group is casein, which curds are made from and then processed into cheese.
Whey is an original complete protein food and is considered number one for building and regenerating our bodies and maintaining a strong immune system. Our entire metabolic process relies on the intake of complete protein. We cycle proteins into amino acids constantly.
Even Hippocrates, the Greek physician of the 5th century B.C., the “father of medicine”, knew the benefits of whey protein. He stated that the body has an inner adaptive or healing power, and that to strengthen this healing power, he prescribed serum (liquid whey) to his patients. It was true non-denatured, native whey. It provided full biological activity and numerous health benefits. All commercial whey proteins available now are derived from extensively processed milk and incomparable to the vitality in that 2500 year-old prescription.
It is appropriate to review some important definitions of terms used:
Native Protein: The naturally occurring conformation of a protein. Unaltered by heat, chemicals, enzyme action or processing. (Native is the same structure and proportion as in the original substance.)
Denatured: To cause the tertiary structure of (a protein) to unfold, as with heat, alkali, or acid, so that some of its original properties, especially its biological activity, are diminished or eliminated. (It means damaged.)
Undenatured: To undamage. (A term that is used without discretion in the industry and is misleading. It is not possible for a protein to be undenatured.)
Non-denatured: The same structure and proportion as in the original substance with full biological activity. (Never damaged.)
Presently, the various commercial methods of processing whey do not improve or even maintain the fragile immune modulating and regenerative components or the biological activity that was originally in the milk. Most are overly processed and damaged during the manufacturing process.
There are three commercial production methods, which comprise the majority of available whey proteins. They are isolates (the most popular), ion-exchange and hydrolyzed forms. They are all ultra-filtered, cross-flow filtered or micro-filtered via elaborate patented methods developed by large dairies. The milk used in these three methods undergoes major processing that involves high heat (often multiple times) and drastic acidification of the whey to produce curds for manufacturing cheese. These steps denature (damage) the proteins. What is then required is extensive filtration to remove the many denatured proteins in order to produce the highest percentage of protein. Unfortunately the fragile vital protein components (immunoglobulins, lactoferring, serum albumin, etc), which determine the biological activity of the protein, are not retained. The terms undenatured and cold-processed are prevalent with these commercial products, but once a protein is denatured it is not possible to undenature it.
The key point in regard to the quality and effectiveness of whey is that the full range of biological activity and proportion of the protein components be preserved in their original native form as nature provided. Only whey that is minimally processed and maintained can achieve that goal. Additionally, the health of the milking cows and quality of the milk is the foundation of this type of product.
Non-denatured whey protein has the highest biological value of any protein. It is a complete protein, unlike soy, and provides all the essential amino acids in the correct balance. The five major active proteins of whey are lactoferrin, immunoglobulins, bovine serum albumin, alpha-lactalbumin and beta-lactoglobulin. There are many whey products available; therefore it is highly advisable to have in writing from the manufacturer, the treatment of the cows and the processing the milk undergoes.
Covalent Bonded Cysteine (the non-denatured form), is the critical amino acid required for the all-important intracellular production of the antioxidant glutathione (GSH). Glutathione is our body’s master antioxidant and is responsible for numerous defense and repair functions and is an effective anti-aging substance. Glutathione is best utilized when we produce it internally. Cysteine is very scarce in our modern diet and therefore glutathione production is limited and deficiency is prevalent. If cysteine undergoes extreme heating or processing, as most commercial whey products do, it is denatured and converted to cystine. Covalent-bonded cysteine, active peptides, anabolic growth factors and enzymes are also present in non-denatured whey protein.
The public is now becoming more aware of the value of quality protein and is choosing whey protein for many good reasons. Whey protein benefits are numerous, and can yield a wide range of immune-enhancing properties. It also has the ability to act as an antioxidant, antihypertensive, anti-tumor, antiviral and antibacterial. A number of clinical trials have successfully been performed using whey as an antimicrobial agent and in the treatment of cancer, HIV, hepatitis B & C, cardiovascular disease and osteoporosis. It has a major role in red blood cell production, support in chemotherapy treatment, safe binding and detoxification of heavy metals, wound healing, growth of new muscle, weight regulation and the support of numerous immune functions. It is used by populations that have Chronic Fatigue Syndrome (CFS), Fibromyalgia, Hepatitis, Cancer, HIV/AIDS, Respiratory disease, cognitive disorder from nutritional compromise and for any sports performance improvement.
Dr. Lawrence Sosna
Dr. Lawrence Sosna Graduated first in his class from the Fairfield College of Myopractics and Naturopathic Medicine. He is a N.D. and has a PhD in Myology with an emphasis in Orthomolecular Biochemistry. He strictly practices Integrative Medicine - his research field being cellular regeneration, Anti-Aging and bio-identical comprehensive hormone replacement therapy. Dr. Sosna lectures on these topics at symposiums all over the world.
Copyright © January 2005
Whey Protein Facts and Applications
Bonang G, Monintja HE, Sujudi, van der Waaij D. Influence of breastmilk on the development of resistance to intestinal colonization in infants born at the Atma Jaya Hospital, Jakarta. Scand J Infect Dis 2000;32:189-196.
Bounous G. Whey Protein concentrate and glutathione modulation in cancer treatment, Anticancer Res. 2000;20:4785-92
Bounous G, Kongshavn PA. Influence of dietary proteins on the immune system of mice. J Nutr 1982;112:1747-1755.
Bounous G, Gervais F, Amer V, et al. The influence of dietary whey protein on tissue glutathione and the diseases of aging. Clin Invest Med 1989;12:343-349.
Bowen J, Noakes M, Clifton P. Whey Protein and body fat loss. Asia Pac J Clinical Nut. 2003; 12:S9
Crinnion WJ. Environmental medicine, part 2 – health effects of and protection from ubiquitous airborne solvent exposure. Altern Med Rev 2000;5:133-143.
Guimont C, Marchall E, Girardet JM, Linden G. Biologically active factors in bovine milk and dairy byproducts: influence on cell culture. Crit Rev Food Sci Nutr 1997;37:393-410.
Ha E, Zemel MB. Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people (review). J Nutr Biochem 2003;14:251-258.
Hakkak R, Korourian S, Ronis MJ, et al. Dietary whey protein protects against azoxymethane-induced colon tumors in male rats. Cancer Epidemiol Biomarkers Prev 2001;10:555-558.
Jones EM, Smart A, Bloomberg G, et al. Lactoferricin, a new antimicrobial peptide. J Appl Bacteriol 1994;77:208-214.
Kawase M, Hashimoto H, Hosoda M, et al. Effect of administration of fermented milk containing whey protein concentrate to rats and healthy men on serum lipids and blood pressure. J Dairy Sci 2000;83:255-263.
Kennedy RS, Konok GP, Bounous G, et al. The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I-II clinical trial study. Anticancer Res 1995;15:2643-2649.
Kimball SR, Jefferson LS. Control of protein synthesis by amino acid availability. Curr Opin Clin Nutr Metab Care 2002;5:63-67.
Lands LC, Grey VL, Smountas AA. Effect of supplementation with a cysteine donor on muscular performance. J Appl Physiol 1999;87:1381-1385.
Laursen I, Briand P, Lykkesfeldt AE. Serum albumin as a modulator on growth of the human breast cancer cell line MCF-7. Anticancer Res 1990;10:343-351.
Levay PF, Viljoen M. Lactoferrin: a general review. Haematologica 1995;80:252-267.
Markus CR, Olivier B, de Haan EH. Whey protein rich in alpha-lactalbumin increases the ratio of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stress-vulnerable subjects. Am J Clin Nutr 2002;75:1051-1056.
Marshall David Jr., O.D., Ph.D. WHEY PROTEIN REPORT - Review of Various Whey Protein. Current Concepts on Whey Protein Usage.
Micke P, Beeh KM, Buhl R. Effects of longterm supplementation with whey proteins on plasma glutathione levels of HIV-infected patients. Eur J Nutr 2002;41:12-18.
Sawatzki G, Rich IN. Lactoferrin stimulates colony stimulating factor production in vitro and in vivo. Blood Cells 1989;15:371-385.
Smithers GW, McIntosh GH, Regester GO, et al. Anti-cancer effects of dietary whey proteins. Proceedings of the Second International Whey Conference 1998;9804:306-309.
Shah NP. Effects of milk-derived bioactives: an overview. Br J Nutr 2000;84:S3-S10. Sundberg J, Ersson B, Lonnerdal B, Oskarsson A. Protein binding of mercury in milk and plasma from mice and man – a comparison between methylmercury and inorganic mercury. Toxicology 1999;137:169-184.
Takada Y, Aoe S, Kumegawa M. Whey protein stimulated the proliferation and differentiation of osteoblastic MC3T3-E1 cells. Biochem Biophys Res Commun 1996;223:445-449.
Tsuda H, Sekine K, Ushida Y, et al. Milk and dairy products in cancer prevention: focus on bovine lactoferrin. Mutat Res 2000;462:227-233.
Watanabe A, Okada K, Shimizu Y, et al. Nutritional therapy of chronic hepatitis by whey protein (non-heated). J Med 2000;31:283-302.
Walzem RL, Dillard CJ, German JB. Whey components: millennia of evolution create functionalities for mammalian nutrition: what we know and what we may be overlooking. Crit Rev Food Sci Nutr 2002;42:353-375.
Yamamura J, Aoe S, Toba Y, et al. Milk basic protein (MBP) increases radial bone mineral density in healthy adult women. Biosci Biotechnol Biochem 2002;66:702-704.
The quality of dietary proteins is a vital factor in determining what proteins are the most valuable in terms of how the body assimilates and utilizes the protein as a resource.
To test these ratios in a protein source we begin with an amino acid analysis, a nitrogen analysis, and then we proceed to the biologic testing. Measuring changes in the protein of the body is a well accepted evaluative analysis used to determine protein quality, measured as Biologic Value (BV). This involves the measurement of nitrogen intake from the protein and the output of nitrogen in the feces and urine. BV is therefore a measurement of the nitrogen absorbed and utilized by the body.
Biologic Value (BV) of Dietary Proteins(1)
As this table shows, the animal proteins are high in BV, and are therefore complete proteins(2). While vegetable proteins are much more incomplete and retain a lower BV rating, due as well to their lower digestibility(1). With a mixture of these vegetable proteins the effect of a complete protein can be produced when eaten in sufficient quantity, but this requires a great deal more total protein to satisfy these requirements.
Whey Protein Concentrates
The benefits (as shown above) of using a whey protein concentrate (WPC) is great according to the BV of this protein source. It fulfills the body's amino acid intake beyond any other source of protein listed above, as well as being a very versatile dietary food. Our Proserum® native whey protein concentrate contains all of the essential amino acids for the body as well as providing cysteine and glutamine. These amino acids are precursors and are necessary for the production of glutathione, a vital free radical neutralizer in the body.
WPC is defined as a whey protein concentrate containing approximately 80% protein. Proserum® is a WPC.
1. Renner E. Milk Protein. In: Milk and Dairy Products in Human Nutrition. Munich: Volkswirtschaftlicher Verlag, 1983
2. Mahan LK, Escott-Stump S. Proteins. In: Krauses Food Nutrition and Diet Therapy, 9th edition, Philidelphia: WB Saunders; 1996
WHEY PROTEIN REPORT
Current Concepts on Whey Protein Usage, Prepared for The Cleveland Eye Clinic
by: David Marshall, Jr., O.D., Ph.D., Consult
A. What is WHEY?
Whey is a by-product of cheese manufacture resulting from drainage of liquid from the curd(1). It contains lactose, protein, ash, and lipids. The protein concentration at this stage of processing is about 67 protein. Whey proteins can be fractioned and concentrated via a process called micro-filtration to yield whey protein concentrates (WPC). The protein concentration can be as high as ~ 95% protein after the removal of the fats and lactose. WPC's are an excellent source of nutrition and are high in lactalbumin, minerals, and vitamins. It possesses a number of functional advantages such as solubility, high water retention, foaming and gelation(1). As a result of these qualities, whey protein concentrates (WPC) have been used in a wide range of food products such as the formulation of dairy foods, egg white replacement, beverages, surimi and comminuted meat products (1).
In response to the efficacy of whey consumption, Karen Collins, M.S., R.D., a registered dietician from the American Institute for Cancer Research, states that whey is a safe and healthy ingredient in foods since levels of pesticides and hormones are not concentrated in whey (2).
Whey protein concentrates are of particular interest to the practitioner due to their wide-range and near full-blend of essential and non-essential amino acids, which are commonly referred to as the building blocks of life. Linked amino acids combine to form proteins. These protein comprise nearly every tissue and organ in the body, therefore any supplementation of the diet with proteins may be beneficial to injury repair, metabolism, and general health.
B. Whey Manufacturing
The importance of whey products has gained prominence within the last 5 years. Asia is the leading exporter of whey produce, exporting an estimated 15,680,683 kg in 1992 and 16,184,519 kg in 1995. This represents~ 60% of all worldwide exports. The leading importer of whey is North America, which in 1995 brought in an estimated 26,444.593 kg . This amount represents a 5 fold increase in imported product over a four year span and nearly 90% of all worldwide imports of whey(3).
Commonly whey is prepared from cheese products such as cheddar cheese. In accordance with the Ohio State University method(11), whey is prepared from milk using lactic acid culture and rennet as a coagulant. The milk is HTST (High Temperature Short Time) pasteurized (163° F, 30 seconds) and held overnight at 40°C then warmed to 30° C and inoculated with 1.5% cheese starter. After incubation for 30 minutes, 38.7 ml rennet extract is diluted with cold water and added to 50 gallons of milk with stirring. Twenty-five minutes later curd is cut and cooked by gradual warming to 38-40°. Cover a thirty minute time interval while the temperature is maintained for 1.5 hours. The whey is then drained through a stainless steel screen and separated at 55° C.
Whey Protein is produced by ultrafiltration at 45° C after addition of 20 g of citric acid with the pH adjusted to 3. After ultrafiltration to 1/5 the original volume, the retentate is diafiltered with addition of 20 g citric acid at pH 3. The concentrated whey is warmed to 40°C and spray dried to, provide whey protein concentrates. This WPC (protein 79.9% and calcium 0.136%) is then used to prepare laboratory scale samples and the WPC solutions are freeze dried(3). Additional micro-filtration techniques may be added to increase the protein yield to ~95%.
Many whey products are then put through an ion-exchange process to remove fat and lactose. In this procedure the cold-filtered protein concentrate is put through a static electrical charge which separates undesirable fractions from the WPC. However, there is a price to pay for this process. The immunoglobulin fraction is greatly reduced(4). The end product is a whey protein isolate that is relatively fat, lactose, and sugar-free product possessing a high amino acid (protein) concentration.
In addition to the before-mentioned procedures, some manufacturers hydrolyze their WPC to produce di-, tri-, oligo-, and polypeptide (long and short-chain amino acids). It also provides for a variety of amino acids, with special emphasis on the branched-chained amino acids (L-leucine, L-isoleucine, and L-valine), in addition to important amino acids such as L-cystine and glutamine, all of which are essential for wound healing, immunity, and cellular nitrogen retention.
note: Hydrolyzing breaks apart peptide bonds. The ion-exchange and hydrolyzing process used on whey protein permanently modifies the native structure. The protein is denatured and the biological activity is ended.
Current Concepts of Whey Usage
A. Nutritional Value
The real nutritional value of WPC's lies in their abundance of amino acids. For example the typical WPC contains up to 18 amino acids, which nearly represents the full blend(57).
Alanine, arginine, and aspartic acid are three common amino acids found in numerous whey proteins. Alanine aid in the metabolism of glucose, whereas arginine causes retardation of tumors and assists in the release of growth hormones and the maintenance of a healthy immune system. It also provides an environment for an increase in muscle mass and body fat reduction, in addition to being an essential ingredient of protein synthesis.
Aspartic acid increases stamina, therefore it is good for fatigue. It also aids in RNA/DNA synthesis.
Cysteine/cystine are perhaps two of the more important amino acids found in WPC. They are helpful in detoxifying toxins and are precursors to the body's most potent antioxidant, glutathione. They promote the burning of fat and are useful in the treatment of rheumatoid arthritis and bronchitis. Due to the possible toxic effects of cysteine at high levels it is not a recommended supplement.
Glutamic acid and glutamine are essential to nervous tissue function. Glutamic acid is a neurotransmitter for retinal neurons and is commonly referred to as "brain fuel" since the brain converts it to a compound that regulates brain cell activity. It is also a precursor to glutathione. Glutamine is important to cellular nitrogen retention and is important in alcoholism, mental ability, impotence and maintaining a healthy digestive tract.
Glutathione, a potent antioxidant, is important for the safe metabolism of the hydrogen peroxide free radical. It helps protect against radiation and oxidative damage and is the body's best defense against the formation of cataracts, age-related macular degeneration (ARMD), cancer, and immunity. This important protein will be discussed in detail later in text.
The essential amino acids are well represented in most WPC's. They can't be manufactured by the body and therefore must be obtained through dietary consumption. They consist of the branched-chained amino acids, lysine, phenylalanine, methionine, and tryptophan. The three branched-chained amino acids are leucine, isoleucine, and valine. They are essential to tissue growth and repair, and promote the healing of bones, skin, and muscle. They also regulate blood sugar levels, so they must be taken in a balance to insure proper regulation.
Phenylalanine is often used to treat depression. It is a precursor to the neurotransmitter, norepinephrine and aids in memory. It should be avoided by phenylketonurics (PKU)
Lysine, methionine and tryptophan are also found in many WPC's. Lysine is an essential building block for all protein and helps to maintain proper nitrogen balance.
The body uses methionine to derive the brain food, choline. It also aids in digestion, as well as serving as a fat burner. It can interact with other substances to detoxify harmful agents, and is essential for the production of cysteine and taurine.
L-Tryptophan acts as a sleep aid, as demonstrated by the drowsy feeling we sometimes experience after Thanksgiving dinner (turkey meat has a relatively high amount of tryptophan.). It is also necessary for the production of niacin and is used by the body to make the neurotransmitter, serotonin.
The rational for using WPC's to attain this dietary level of nutrition is that 25 grams of powder provides approximately 20 grams of amino acids. To achieve this level of nutrition taking tablets or soft gels would require taking 48 to 60 units per day, which would be difficult and expensive.
A large number of weightlifters and bodybuilders use WPC's during their training regimen. They sometimes utilize a three step process which consists of stacking, "cycling", and "cutting". The initial stage, stacking involves taking two or more compounds at one time to maximize results. They may take WPC and or creatine or chromium. This is then followed by cycling, in which large doses of a supplement is used to change the level of body fat. Some will use 10 or more one ounce WPC servings a day. This should be approached with caution since large doses of protein consumption may present challenges to the liver. The final stage, cutting, involves maximizing the muscle bundles for visualization. This is the point in which the bodybuilder aspires to achieve that "cut up" appearance.
It is important to consult a physician before attempting any of these extreme methods.
C. Clinical Implications
1. Wound Healing
Australian researchers claim that whey extract could become a standard treatment for chronic wounds, especially ulcerations from diabetes and hypertension. Initial experiments using a whey extract containing a number of natural growth factors excelled at spurring cells to grow thus prompting this essential step in the body's normal repair of injuries(32). The compound also encouraged rapid wound healing in rats and pigs(32).
Scientists working on a joint government-industry project at the Cooperative Research Center for Tissue Growth and Repair in Adelaide, Australia have patented a process for mitogenic bovine whey extract which is unique as a naturally-derived cocktail of growth factors in which 1000 L of milk yields 30 grams of extract. When the extract is mixed with a collagen gel and applied to wounds it enhanced the healing of surgical incisions.
These observations have their origin in the fact that whey protein contains high levels of amino acids which may be important to wound healing. These amino acid include arginine, glycine, and particularly the branch-chained amino acids (BCAA) leucine, isoleucine and valine, which are essential to promote healing of bones, skin, and muscle tissues. Another amio acid, proline, aids in the production of collagen, heals cartilage and strengthens joints, tendons and cardiac muscle.
In order to understand the mechanisms beneficial biochemical interactions and possible whey protein potential health benefits of WPC, a brief biochemical review of the protein Glutathione is required, since it is this protein more than any other that has been thought to provide a protective function for a number of organ systems, including the crystalline lens of the eye, the retina, prostate gland, and the immune system.
a. Glutathione Synthesis
For the body to produce Glutathione (GSH) six building blocks are required: L-glutamate, L-cysteine, L-glycine, magnesium, potassium, and 5' ATP. Two enzymes are also required and they are L-gamma-glutamyl-cysteine synthetase (equation 1) and glutathione synthetase (equation 2) and the reaction proceeds in the following manner:
(1) L-glutamate + L-cysteine + ATP--------->
L-gamma -glutamylcysteine + ADP + P
(2) L-gamma-glutamylcysteine + L-glycine +ATP----------->
L-gamma-glutamylcysteinylglycine +ADP + P
L-cysteine is the rate limiting substrate in this reaction12 , while the rate controlling enzyme for the reaction is L-gamma -glutamylcysteine synthetase(5) .
b. Scavenger Pathways
The 2 major functions of glutathione are to detoxify hydrogen peroxide (H2O2) and other organoperoxidases (free radicals) and to defend against oxidation within cells via the Glutathione Redux Cycle, or more commonly referred to as the Scavenger Pathways(6,7).
Glutathione plays it's role of "scavenger" through out the body. The role of scavenger is primarily accomplished through glutathione peroxidase (GSH px). The peroxidase interacts with the H2O(2) to reduce it to harmless water, thus limiting it electron stealing capacity. This is illustrated in the following equation:
(2) 2-glutathione-SH +ROOH ------>
glutathione disulfide + ROH + H2O
The disulfide is then reduced with the co-enzyme NADPH in the prescene of the enzyme Glutathione Reductase to yield the original glutathione compound.
(3) glutathione reductase +NADPH + H+ ----------->
2-glutathione-SH + NADP -
Many theories of aging and disease are based upon the interaction of the formation of free-radicals and the subsequent reduction in glutathione levels which allows for an accumulation of free-radicals to remain within a cell and organ or organ system. Free-radicals that remain within cells may cause cell damage, DNA damage and may even cause cell death, cancer transformation or loss of cell immunity to viral or bacterial infection.
3. Ocular Ramifications
To fully appreciate the manner in which supplementation with WPC may be beneficial to maintenance of ocular tissues, let us look at the processes of cataractogenesis and oxidative insult to the retina.
1. Mechanisms of cataractogenesis
The exact mechanism of cataract formation follows a strict ordered sequence. Initially, in the pre-cataractous state, a cascade of early cataract-related changes occurs resulting in an oxidative insult to the cell membrane and to the amino acids methionine and cysteine (17-20). This can be caused by x-rays, photochemical insult, hyperbaric oxygen levels 18 and other causes. The remaining cascade of events then proceeds in the following manner: (a) unfolding of protein structures, which exposes the protein thiols making them available for further oxidation, (b) di-sulphide linked aggregate formation, and (c) a decrease in enzymatic activity (glutathione peroxidase) which protects and repairs damage (17,18,20). It is at this stage that the cataract truly begins to develop accompanied by a change in the lens Redux ratio, decreased ATP levels, and a change in cation permeability which induces an influx of H2O (water) within the cell membrane(17-20).
The site of initial damage according to Spector(18) occurs in the lens epithelium. The causative agent at this point is thought to be primarily the hydrogen peroxide radical, which in the absence of glutathione, may now accumulate unopposed. These free-radicals which are defined as molecules with an one or more unpaired electrons in their outer orbit, which attempt to stabilize their charge by stealing an electron from the outer shell of a stable neighboring molecule setting off a chain-reaction sequence(6), causes DNA damage to the lens epithelium cells(21). Examination of lens epithelial cells at the time of cataract surgery usually reveals an ongoing pattern of programmed cell death (apoptosis)(18) which may be documented by evaluation of lens chromatin fragmentation(21) .
In the case of experimentally UV-induced cataracts, exposure to the UV radiation generated hydrogen peroxide, superoxide and DNA damage(21,31). The consequences of this action is to degrade the lens crystalline, decrease transmembrane voltage, reduce glutathione stores(24), decrease enzyme activity, and increase in prostaglandin production(25). It is interesting to note that no significant change in the non-protein thiols occurred until 85% of the lens epithelium cells were already dead(21).
2. Cataractogenesis and Glutathione
The major role of glutathione in the crystalline lens of the eye is to provide lens clarity via maintenance of the limiting anterior epithelial cell layer and to correct and/or halt oxidative damage to the lens(5). Arnold was perhaps the first investigator to discover the presence of glutathione in the lens, and it is now clearly evident that the highest concentration of glutathione is found in the lens epithelium(6) , which has a 5X greater concentration than in the second most glutathione rich site, the lens cortex. The nuclear region of the lens is primarily devoid of GSH(5,6).
It is well is established that lenticular glutathione levels decrease with age (5,6,8) ranging from a concentration of 3.5 umol/g at age 20 and decreasing to 1.8 umol/g at age 65. It is inferred that it is this age related reduction in GSH which is in part responsible for cataract formation in the elderly. In fact, Reis was the first to note the lack of GSH in cataractous lenses(5). In addition, a number of substances which inhibit GSH synthesis, such as Buthionine Sulfoximine(16) produce cataracts in experimental conditions. It is interesting to note that glutathione levels are unchanged in some reversible forms of cataracts, such as those induced after the administration of diquat(5). Reduced GSH levels is a precipitating factor age-related cataract formation(7). To further illustrate this point, researchers at Alcon Laboratories have used aldose reductase inhibitors to halt the progression of certain cataracts(13). The importance in this finding is that aldose reductase acts competitively to reduce levels of GSH and its inhibition allowed GSH levels to remain high.
As mentioned previously, glutathione and it's enzyme, glutathione peroxidase has great importance in regards to the elimination of free-radicals within the lens. Recent reports indicate that glutathione metabolizes chronic low levels of free-radical production26 typical of normal metabolism and the most potent anti-oxidant in the lens system. This point is illustrated by the inability of other enzymes, such as catalase to limit lens damage caused by hyperbaric oxygen(27) and H202(28,29).
Glutathione is essential for the maintenance of tissue ascorbate (Vitamin C) and alpha-tocopherol (vitamin E) levels (30) according to Mrtensson. He found that as GSH levels decreased, a corresponding decrease in ascorbic acid and vitamin E followed, which led to systematic mitochondrial death, which in turn leads to a cessation of cellular metabolism(31).
The regional distribution of glutathione in different cataracts is of interest. Pau (et al 9) found that in primary nuclear and supranuclear cataracts, there was only a slight decrease in GSH levels relative to the subcapsular and (20) nuclear, implying a different mechanism for various cataract types and possibly a different mode of non-surgical intervention.
Experimental data has shown that supplying the lens with additional glutathione, particularly in the form of the peroxidase increases delays cataract development and may even prevent cataract development(23). This may be accomplished my enriching the aqueous with the glutathione precursor amino acids or glutathione directly(10) . Glutathione in conjunction with vitamin E added as a supplement to a galactose diet did halt opacification of cortical cataracts in the animal model15. Further evidence for GSH infiltration into the lens comes from the identification of glutathione transporters in the lens epithelium(11). Taking glutathione orally has not been shown to raise tissue levels of glutathione. Taking WPC which contains high levels of cystine, the rate-limiting substitute for the production of glutathione, may be helpful for the prevention of cataracts.
b. Macular degeneration
It is widely accepted that lipid peroxidation plays a major role in retinal light damage(58). The vertebrae retina is known to contain relatively high levels of antioxidants and anti-oxidant enzymes(59). Among these are three members of the glutathione system, glutathione peroxidase, reductase, and transferase. The others are catalase and superoxide dismutase (60). When levels of these antioxidants begin to decrease with increasing age(59, 60) , retinal changes associated with macular degeneration begin to develop. This is particularly true for glutathione peroxidase and catalase(59, 60) .
The method oxidative damage occurs is due to light or heat damage and then coupled with the age-related reduction in GSH(px) and catalase allows for the propagation and accumulation of the free radicals, making the retina susceptible to further damage(60).
Stone and Dratz (61) found evidence of glutathione-dependent enzymes in the outer segments of rats and suggest that since these membranes are rich in polyunsaturated fatty acids, they are susceptible to free-radical induced peroxidation. Therefore when RPE disruption occurs with early ARMD, which limits the amount of phagocytosis occurring, coupled with the age-related reductions in antioxidant activity, adverse retinal changes are manifested and may proceed unchallenged.
It may therefore be possible to replenish or revitalize the antioxidant activity of the retina by dietary supplementation primarily with a glutathione or precursor to halt the progressive lipid peroxidation occurring during ARMD.
Primarily the process of enhancing the immune response is accomplished through the replenishment of glutathione (GSH). It has been theorized that the ability of lymphocytes (CD4 cells) to correct oxidative damage is determined by their capacity to regenerate intracellular stores glutathione which allows them to respond vigorously to a wide variety of antigens(33).
In 1981, researchers discovered that mice fed a non-denatured whey protein concentrate exhibited a marked increase in antibody production in response to T-cell dependent antigens(36). Numerous experiments in subsequent years have confirmed this early observation (37,38,39,40,41,42,43,44). Thus, enhanced immunity against colds and hepatitis and most dramatically pneumococcal infection(42) could be accomplished through dietary supplementation with whey protein concentrates (WPC's).
An interesting peripheral observation was that the immuno sustaining effect of the protein mixture found in whey was unrelated to its nutritional efficiency and as a result of this phenomenon this unique property was defined as the bioactivity of the product(33).
This bioactivity occurs through the ability of the protein concentrate to help replenish glutathione levels via continuous dietary provision of glutathione precursors, especially cysteine, during lymphocyte proliferation, thus supporting an optimal immune response. This process seems to not only increase intercellular levels of GSH or GSH precursors at the time of ingestion, but also builds up stores of these substances within the cells which lasts for a substantial post-ingestion time interval(33).
The proposed bioactivity is dependent upon three bioactive proteins contained in whey, serum albumin, lactoferrin and alpha lactalbumin. These proteins contain a high number of cysteine/cystine residues, an important GSH precursor. Serum albumin contains 17 cysteine/cystine residues/ 66,000 MW molecule and 6 glutamylcysteine dipeptides(39). Lactoferrin contains 17 cysteine/cystine residues/ 77,000 MW molecule and four gluatmylcysteine dipeptides, while alpha-lactalbumin contains 4 residues per 14,000 Mw molecules (39). It is these residues which are primarily responsible for replenishment of GSH stores.
Two major theories of oncology both implicate GSH as a putative protective factor due to its dual role as a antioxidant and detoxifying agent. Free radical accumulation is thought to be a major factor in tumor formation (45). In fact at least twelve carcinogens have been identified that are detoxified by GSH conjugation. These are: aflaxotoxin B1, N-acetyl-2-aminofluorene, benzanthracene, benzopyrene, benzidine, dimethyl-hydrazine, 1-nitropyrine dimethylnitrosamine, ethylmethane sulfonate, N-methyl-4-aminobenzene, 7-methylbenzanthracene and 3-methyl-cholanthracene (46,47,48).
Further evidence supporting the anti-tumor forming capacity of whey protein is illustrated by a University of Wisconsin study in which hormones known as androgens are responsible for depleting GSH levels in the prostate. This relatively GSH-free environment is thought to promote prostate carcino-genesis in men (49). This condition can be reversed in vitro by increasing colonial levels of GSH via continuous whey protein supplementation.
e. Diseases of Aging
As in carcinogenesis, free-radical accumulation has been implicated in producing a variety of diseases associated with aging (50).These maladies result from the toxic accumulation of these materials due to the absence or reduced levels of GSH. Diseases such as Alzheimer's (51), Parkinson's 52, and arteriosclerosis53 all appear to be preceded or associated with cellular organ or organ system reductions in GSH. Therefore much speculation has arisen regarding the potential benefits supplementation with whey protein may provide in these cases. If results obtained from other organ system studies are of any indication results could be promising.
f. HIV and AIDS
The mechanism by which whey protein concentrate yields an enhanced immune response has already been discussed. Recently this knowledge has been applied to the treatment of HIV infected individuals. Staal (et al 34) reported that HIV-infected individuals have lower GSH concentrations in their blood lymphocytes, while Herzenberg (et al 35) found that the more glutathione patients carry in their CD4 helper T-cells, the cells primarily targeted by the HIV virus, the greater the chance of increased longevity exists.
More recent claims have stated that supplementation with whey protein concentrates (WPC's) may help AIDS patients maintain body weight and in some cases limit wasting syndrome. In a pilot study WPC's were given to a population consisting of 14 AIDS infected children (ages 8 months-15 years) in an attempt to limit determine the efficacy of daily oral dietary ingestion of whey proteins. They found no toxic side effects and an average weight gain of 3.2 - 18% from their entrance weight(54).
A. Robert Neurath M.D. and his colleagues at the Laboratory of Biochemical Urology at Lindsley F. Kimball Research Institute of the New York Blood Centers has reported that a modified version of protein extracted from whey blocked the aids virus from infecting cells in vitro(55). In their National Institutes of Health sponsored study the scientists modified beta- lactoglobulin to produce a substance referred to as B69. They reported that B69 latched onto a protein structure called CD4 on the surface of cells which kept the aids virus from using this site as an entryway into the cell.
Newarth further hypothesized that if additional results with B69 were promising, the compound may be formulated into a cream or foam that could be dispensed within condoms to limit the transmission of the virus.
Dr. Jefferey Laurance, an AIDS researcher at Cornell Medical College, however, urges caution regarding B69 developments. He states that HIV can infect some cells , including rectal and vaginal cells, without using the CD4 site as an entryway.
In summary, animal studies have yielded promising reports regarding prolonged life spans of infected animals in the laboratory, while theoretical data(56) and initial clinical observations in humans have produced evidence that dietary supplementation with WPC's can provide definite benefits to the HIV infected individual. Further research, however, is warranted in this area.
1 Choi, MJ. and Mangino, M.. The Effect of Pre-heating Conditions on the Gelation of Whey Proteins. Preliminary Report. Preprint. pgs 1-11, 1997.
2 Collins, K.. Is Whey Good for You? How do Cooking Oils Differ? Medical Tribune News Service, 1997.
3 Exports and Imports of Whey products. Statistics, Canada, Dairy Section, AAFC, 1997.
4 1 Nutrition, Frequently Asked Questions.AST Research Communique, 1997.
5 Rathburn, WB. Glutathione in Ocular Tissues. 469-510.
6 Rathburn, WB. Gutathione Metabolism int the Mammalian Ocular Lens. 194-206.
7 Reddy, VN. Glutathione and its Function in the Lens - An Overview. Exp Eye Res.50:771-778, 1990.
8 Hockwin, O. and Korte, I.Role of Glutathione in the Aging Process of the Lens. 207-214.
9 Pau, H., Graf, P., and Sies, H.Glutathione Levels in Human Lens: Regional Distribution in Different Forms of Cataract. Exp Eye Res 45: 17-20, 1990.
10 Harding, JJ. Free and Protein-Bound Glutathione in Normal and Cataractous Human Lenses. Biochem J. 117, 957-960, 1970.
11 Kannan, R., Yi, JR., Tang, D., Zlokovic, BV., Kaplowitz, N.. Identifcation of a Novel, Sodium-Dependent, Reduced Glutathione Transporter in the Rat Lens Epithelium. Invest Ophthalmol. Vis Sci 37:11: 2269-2275, 1996.
12 Rathburn, WB., and Murray, DL. Age-related Cysteine Uptake as Rate-limiting in Glutathione Synthesis and Glutathione Half-life in the Cultured Human Lens. Exp Eye Res. 53: 205-212, 1991.
13 Lou, MF., Dickerson Jr., JE., Garadi, R., and York Jr., BM.Glutathione Depletion in the Lens of Galactosemic and Diabetic Rats. Exp Eye Res 38:517-530, 1988.
14 Spector, A., Wang GM., and Wang, RR..Photochemically Induced Cataracts in Rat Lenses can be Prevented by AL-3823A, a Glutatthione Peroxidase Mimic. Proc. Natl. Acad. Sci. USA 90: 7485-7489, 1993.
15 Creighton, MO., and Trevithick, JR..Cortical Cataract Formation Prevented byVitamin E and Glutathione. Exp Eye Res. 29: 689-693, 1979.
16 Maitra, I., Serbinova, E., Trishler, H., and Packer, L.. Alpha-lipoic acid Prevents Buthionine Sulfoximide-induced Cataract Formation in Newborn Rats. Free Radical Biology and Medicine 18:4: 823-829, 1995.
17 Spector, A. Oxidation and Cataract.Symposium Paper. 1984 Human Cataract Formation. Ciba Foundation Symposium 106, 48-64, 1984.
18 Spector, A., Wang, GM., Wang, RR., Li, WC., and Kuszak, JR.. A Brief PhotochemicallyInduced Oxidative Insult Causes Irreversible Lens Damage and Cataract I. Transparency and Epithelial Cell Layer. Exp Eye Res. 60: 471-481, 1995.
19 Spector, A., Wang, GW., Wang, RR., Li, WC., and Kleiman, NJ.. A Brief Photchemically Induced Oxidative Insult Causes Irreversible Lens Damage and Cataract II. Mechanism of Action. Exp Eye Res. 60: 483- 493, 1995.
20 Spector, A.. The Search for a Solution to Senile Cataracts Proctor Lecture. Invest Oph. and Vis Sci. 25: 130-146, 1984.
21 Li, WC., and Spector, A.. Lens Epithelial Cell Apoptosis is an Early Event in the Development of UVB-induced Cataract. Free Radical Biology and Medicine 20:3: 310-311, 1996.
22 Li, WC., Wang, GM., Wang, RR., and Spector, A.. The Redox Active Components of H2O2 and N-Acetyl-L-Cysteine Regulate Expression of c-jun and c-fos in Lens Systems. Eye Exp Res. 59:179-190, 1994.
23 Spector, A., Wang, GM., Wang, RR., Garner, WH., Moll, H.. The Prevention of Cataract Caused by Oxidative Stress in Cultured Rat Lenses. I H2O2 and Photochemically Induced Cataract. Curr Eye Res. 12:2: 163-179, 1993.
24 Hightower, KR., McCready, JP.. Mechanism Involved in Cataract Development FollowingNear-ultraviolet radiation of Cultured Lenses. Curr. Eye Res. 11:679-689, 1992.
25 Andley, UP.,, Herbet, JS., Morrison, AR., Reddan, JR, Pentland, AP.. Mechanism of Lens Epithelial Cell Proliferation by Enhanced Protaglandin Synthesis after UVB Exposure. Invest. Ophthalmol. Vis. Sci. 35 : 374-381, 1994
26 Tumminia, SJ., Chambers, C., Qin, C., Zigler Jr., S., and Russell, P. Curr Eye Res. 15: 845-851, 1996.
27 Giblin, FJ., Schrimscher, L., Chakrapani, B., and Reddy, VN.. Exposure of Rabbit Lens to hyperbaric Oxygen in Vitro: Regional Effects on GSH Level. Invest Ophthalmol. Vis. sci. 26:8: 1312-1319, 1988.
28 Giblin, FJ., Reddan, Jr., Schrimscher, L., Dziedic, DC., and Reddy, VN.. The Relative Roles of the Glutathione Redox Cycle and Catalase in Detoxification of H2O2 by Cultured Rabbit Lens Epithelial Cells.. Exp Eye Res. 51: 795-804, 1990.
29 Garland, D.. Role of Site-specific, Metal-catalyzedOxidation in Lens Aging and Cataract: A Hypothesis. Exp Eye Res. 50: 677-682, 1990.
30 Mrtenssson, J., and Meister, A.. Gluathione Deficiency Decreases Tissue Aswcorbate Levels in Newborn Rats: Ascorbate Spares Glutathione and Protects. Proc. Natl. Acad. Sci. USA 88:4656-46460, 1991.
31 Varma, SD., Kumar, S., and Richards, RD.. Light-induced Damage to Ocular Lens Cation Pump: Prevention by Vitamin C..Proc. Natl. Acad. Sci. USA 76: 3504-3506, 1979.
32 Daily InScight.. A Better Whey to Heal?. Academic Press, 1997.
33 Fidelus, RK., Tsan, MF.. Glutathione and Lymphocyte Activation: A Function of Aging and Auto-immune Disease. Immunology 61: 503-508, 1987.
34 Staal, FJT., Roederer, M., Israelski, DM., Bubp, J.. Intracellular Glutathione levels in T cell Subsets Decreases in HIV-infected individuals. AIDS Res and Hum Retroviruses 8: 305-311, 1992.
35 Herzenberg, L., De Rosa, S., Dubs, G., Roederer, M.. Glutathione Deficiency is Associated with Impaired survival in HIV Disease. Proc Natl Acad Sci USA 94: 1967-1972, 1997.
36 Bounous, G., Stevenson, MM., Konshavn, PAL.. Influence of Dietary Lactalbumin Hydrolsate on the Immune System of Mice and Resistance to Salmonellosis. J. Infect. Dis. 144: 282, 1981.
37 Bounous, G., Kongshavn, PAL.. Influence of Dietary Proteins on the Immune System of Mice. J. Nutr. 112: 1747-1755, 1982.
38 Bounous, G., Letourneau, L., Kongshavn, PAL.. Influence of Dietary Protein Type on the Immune System of Mice. J. Nutr. 113: 1415-1421, 1983.
38 Bounous, G., Kongshavn, PAL.. Differential effect of Dietary Protein Type on the B-cell and T-cell Immune Response in Mice. J. Nutr. 115: 1403-1408, 1985.
40 Bounous, G.,Shenouda, N., Kongshavn, PAL., Osmond, DG.. Mechanism of Altered B-cell Response induced by Changes in Dietary Protein Type in Mice. J. Nutr. 115: 1409-1417, 1985.
41 Bounous, G., Kongshavn, PAL., Gold, P.. The Immunoenhancing Property of Dietary whey Protein Concentrate. Clin. Invest. Med. 11: 271-278, 1988.
42 Bounous, G., Kongshavn, PAL.. Influence of Protein Type in Nutritionally Adequate Diets on the Development of Immunity. In: Friedman, M. ed. Absorption and Utilization of Amino Acids. Boca Raton, Florida: CRC Press. 2: 219-223, 1989.
43 Parker, N., Goodrum, KJ.. A Comparison of Casein, Lactalbumin, and Soy Protein Effect on the Immune Response to a T-dependent antigen. Nutrit. Res. 10: 781-792, 1990.
44 Hirai, R., Nakai, S., Kikuishi, H, Kawai, K.. Evalaution of the Immunological Enhancement Activities of Immunocal. Otsuka Pharmaceutical Co. Cellular Technolgy Insitiute, 1990.
45 Ritchie, JP.. The Role Glutathione in Aging and Cancer. Exp Gerontol 27: 615-626, 1992.
46 Newberne, PM, Bulter, WH.. Acute and Chronic Effects of Aflatoxin B1 on the Liver of Domestic and Laboratory Animal: A Review. Cancer Res 29: 236-250, 1969.
47 Meerman, JHN., Beland, FA., Ketterer, B., Srai, SKF.. Indentification of Glutathione Conjugates Formed from N-hydroxy-2-acetylaminofluorene in the Rat. Chem Biol Interact 39: 149-168, 1982.
48 Boyland, E., Sims, P.. The Metabolism of Benz(a)anthrracene and Dibenz (a,h)anthracene and Their 5,6 di-hydro Derivatives by Rat Liver Homogenates. Biochem J. 97:7-16, 1965.
49 Waterfall, JF., Sims, P.. Epoxy Derivatives of Aromatic Polycyclic Hydrocarbons. The Properties and Metabolism of EpoxidesRelated to Benzo(a) pyrene and to 7-8 and 9-dihydrobenzo(a)pyrene. Biochem J. 128: 265-277, 1972.
50 Blumberg, JB., Meydani, SN.. Role of Dietary Antioxidants in Aging. In: Nutrition and Aging. Hutchinson, MG., Munro, HN. (Eds.) New York: Academic Press, 85-97, 1986.
51 Jeandel, C., Nicholas, MB., dubois, F., Nabey-Belleville, F.. Lipid Peroxidation and Free Radical Scavengers in Alzheimer's Disease. Gerontology 35: 275-282, 1989.
52 Ebadi, M., Srinvasan, SK., Baxi, MD.. Oxidative Stress and Antioxidant Therapy in Parkinson's Disease. Proc Neurobiol 48: 1-19, 1996.
53 Kuzuya, M., Naito, M., Funaki, C., Hayahi, T.. Protective Role of Intracellular Glutathione Against Oxidized Low Density Lipoprotein in Cultured Endothelial Cells. Biochem Biophys Res Commun 163: 1466-1472, 1989.
54 CTN Trial Results. Whey protein Supplementation. Whey Protein Supplementation in HIV-infected Children: A Pilot Study. 1997
55 The Associated Press News Release. Whey Eyed as AIDS Blocker. The Associated Press, New York, New York, 1995.
56 Noelle, RJ., Lawrence, DA.. Determination of Glutathione in Lymphocytes and Possible Association of Redox state and Proliferative Capacity of Lymphocytes. Biochem J. 198: 571-579, 1981.
57 Balch, JF., Balch, PA.. Presciption for Nutritional Healing. Avery Publishing Group, Garden City Park, New York, 27-31, 1990.
58 Taylor, A., Jaques, PF.. Oxidation and Aging: Impact on Vision. In: Sies, H., Erdman, J., Williams, G. (Eds.) Proceedings International Conference on Antioxidants. Princeton, New Jersey, Univ. Press, 1992.
59 Newsome, DA., Miceli, MV., Liles, MR.. Antioxidants in the Retinal Pigment Epithelium. In: Prog Retinal Eye Res. 13: 101-123, 1994.
60 Dovrat, A., and Gershon, D.. Rat Lens Superoxide Dismutase and Glucose-6-phophate dehyrogenase: Studies on the Catalytic Activity and the Fate of Enzyme Antigen as a Function of Age. Exp Eye Res. 33: 651-655, 1981.
61 Stone, WL., and Dratz, EA.. Selenium and Non-selenium Glutathione Peroxidase Activities in Selected Ocular and Non-Ocular Rat Tissues. Exp Eye Res. 35: 405-412, 1982.
62 Rathbun, W.B., Holleschau, A.M., Cohen, J.F., Nagasawa, H.T. Prevention of Acetominophen and Naphthalene - Induced Cataract and Glutathorne Loss by CySSME. Invest Ophthalmol. 37:5: 923-9, 1996.
Proteins Duke it Out for Prominence,
but Only One is a True Champion
Carlon M. Colker, M.D.
Although debated for years, it is now not merely a widely held belief, but an accepted fact, that athletes and people who exercise need more protein than sedentary non-exercising individuals.1-9 But as protein has gained in popularity and finally assumed its rightful place as king of the macronutrients, a new war has begun. The battlefield has been drawn, pitting all available sources of protein against each other in an all-out brawl to see which rules. In the words of Apollo Creed- when he was set to face the Italian Stallion- "Sounds like a damn monster movie!" Of course, if you've been paying attention to the media, you know that two top contenders have emerged.
Hold the fort down fight fans, and let's get ready to rumble! In the blue corner, a lower quality protein weighing in without all the essential amino acids, a debatable cardio-protective effect, and a known and worrisome phytoestrogen content soy protein. In the red corner, the highest quality and biologics value protein, weighing in with all the essential amino acids, immune enhancing powers, and offering greater cancer protection than soy - whey protein!
Sounds like a mismatch to me. Of all the protein sources out there, you might wonder why these two have emerged as top dogs. The answer is that whey protein is in contention as a result of a wellspring of supporting research and scientific fact. Soy protein, on the other hand, has emerged for honors simply because of clever exaggerations of flimsy studies, as well as misleading propaganda driven by a powerful and profit oriented soy lobby.
Sorry soy enthusiasts, if I've touched a sore spot. But let's examine this issue further and include the important basic differences, as well as some of the latest research on both these proteins.
The Big Lie
First of all, I'm tired of hearing all this garbage about soy being a complete protein (meaning it contains all the essential amino acids our bodies can't synthesize from other sources and must instead directly consume). Don't let anyone shove this lie down your throat. Soy protein is not a complete protein because it lacks the amino acid methionine. This is a non-debatable scientific fact.
Whey protein, on the other hand, lacks no essential amino acids. As a result, it has a much higher biological value in terms of similarity to our own human protein. Whey protein beats soy protein hands down in this category simply because whey protein needs no fortification or additive to make it complete. It is complete in its natural form.
Perhaps the greatest coup for soy fans of late was approval by the FDA for soy-containing products to be listed as able to reduce the risk of heart disease This government seal of approval was not only premature, but also potentially dangerous. There was, and still is, no solid scientific research to back such cavalier support by our government. I wonder how a government steeped in the practice of forcing products to be thoroughly researched and tested before claims can be made, would do something so reckless.
The fact is, soy has no more impressive research to support such broad-based government support than that which supports whey protein in the area of heart health. The research supporting soy as cardio-protective is almost completely epidemiological and observational across broad spectrums of the population. In fact, as far as whey protein is concerned, nearly a decade ago the Chinese demonstrated the cholesterol and plasma lipid lowering ability of whey protein.10 But this, along with piles of subsequent research, hasn't motivated the government to give whey protein the same whorish kiss it gave soy.
Much Ado About Estrogen
I think what's really going on starts with the soy lobbyists. Soy is big business. Nearly a million metric tons have come into this country this past year alone; nearly $500 million worth of soy products moved off supermarket shelves just last year.11 When big bucks are on the line, lobbyists find the motivation to aggressively seduce government.
A lot of support for soy being heart healthy stems from soy enthusiasts focusing on the estrogenic effect of soy. Soy contains genistein and other phytoestrogens that are hormonally akin to estrogen. Unfortunately, it now appears these folks have jumped the gun. A landmark study in the Journal of the American Medical Association looked at estrogen therapy and the prevention of heart disease.
The study showed that over four years, estrogen treatment did not reduce the rate of heart disease in postmenopausal women. In fact, it increased the rate of blood clots and gallbladder disease! The conclusion of this comprehensive study of nearly 3,000 subjects sent a clear message to physicians that, while it might help bone density and lessen the chance of hip fractures, estrogen therapy does not protect the heart. Thus, it should not be given for preventing heart disease. "Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD (coronary heart disease) events, we do not recommend starting this treatment for the purpose of secondary prevention of CHD."12
Thus, those taking soy as an estrogen analog for protection against heart disease have been woefully misled by the propaganda. In fact, as the research clearly shows, the road of estrogenic substances is filled with perils., Why the soy supporters and the FDA have ignored this, is beyond, my comprehension. I should highlight here that, unlike soy protein, whey protein has no phytoestrogen content. And, while the exact mechanism remains unclear, the cardioprotective effect, if any, probably has more to do with a powerful antioxidant effect that benefits the entire body, not just the heart.
There are other problems with exposure to estrogens and estrogen-like substances, namely cancer. Somehow soy got labeled a cancer preventive! The absurdity of this flawed logic makes me laugh; the potential health ramifications of the misinformation make me cry.
Receptor Site Skirmish
The theory behind soy as a cancer preventive stems from the fact that the phytoestrogens in soy protein, although estrogen-like in function, are weaker receptor stimulators than the estrogens in our bodies. When this weaker estrogen is put in the body, it competes with the body's own estrogens for receptor sites. A temporary "blocking" effect is exerted because these estrogen-like compounds don't stimulate the receptor to the same degree as actual estrogens. This is the mechanism of action of tamoxifin, a chemotherapy agent many soy supporters say soy protein is akin to.
The problem with this theory: While an estrogen-like substance might have a weaker stimulatory property on one area of receptors in the body, it may be stimulatory to the same degree as true estrogen at other receptor sites. It's for this reason drugs with more estrogen site specificity are currently being developed. New drugs like raloxifene appear to have estrogen site selectivity so that, for the postmenopausal female, the risk of osteoporosis is reduced without stimulating uterine or breast cancer.13
So, while phytoestrogens in soy might be weaker estrogens at some sites in the body and thus help prevent cancer spurred by the body's own unopposed estrogens, it has no receptor site specificity, and thus may actually stimulate cancer, in other areas of the body.14
In fact, in recent discussions with prominent cancer specialists and colleagues at the world renowned Memorial Sloan Kettering Cancer Center in New York, the subject of soy protein came up. All three specialists I spoke with are telling successfully treated breast cancer survivors to avoid soy. Of even greater interest was that they maintained this recommendation even for those individuals whose cancer was deemed "non-estrogen dependent" (i.e., estrogen receptor negative). They said they did this "just to be on the safe side."
But, thankfully, the public is getting hip. In a recent New York Times article, prominent physician researchers called our attention to the potential perils of soy. Dr. Margo Woods at tufts University School of Medicine, Dr. Gregory Burke at Wake Forest University School of Medicine, Dr. William Helferich at the University of Illinois, and even the FDA's own research biologist at the National Center for toxicological Research, have all voiced very serious concerns."
My recommendation would be to examine your family history carefully. If you have a history of cancer (especially breast), consider soy a danger.
But if it's cancer prevention you're interested in, without playing Russian roulette with the phytoestrogens found in soy, take a good look at whey protein. More than a decade ago, whey protein demonstrated an ability to prevent cancer and tumor growth.15
The current thought is, in much the way whey protein may be cardio-protective, the key mechanism of action has to do with whey's unique ability to bolster the immune system by increasing intracellular antioxidant power.
We have all heard of vitamins E and C and their antioxidant ability in the bloodstream. But, a far more powerful and target-specific antioxidant exists within each living cell called gamma-L-glutamyl-L-cysteinyl-glycine, more easily referred to as GSH (Glutathione). This powerful antioxidant exerts its action within the cell. In fact, it cannot only be synthesized inside the cell from smaller molecules since there is no efficient transport mechanism to get GSH from the blood stream into the cells.
The key building block for GSH is an amino acid called cysteine. When two molecules of cysteine are coupled and then linked by a disulfide bond, the result is a molecule called cystine. This cystine molecule is not only stable, but travels easily through the body and into each living cell. Once in the cell, it's broken down into cysteine molecules; and used to form GSH.
Because of whey protein's unmatched biological value, bioavailability, impressive solubility, level of absorption, and high percentage content of cystine residues and branch chain amino acids (23 percent), it's the superior form of protein supplementation for athletes.16 Though moderate exercise has been shown to improve immunity, intense exercise has been shown to reduce GSH levels, which are associated with immunosuppression.17 This negative effect on immunity is directly related to the intensity and duration of the physical activity and immune status of the athlete. Over the past decade it has been shown that whey protein possesses immune enhancing properties that can help the athlete recover and avoid over training syndrome.18
Unlike soy protein, which is profoundly deficient in these and other sulfur-containing amino acids whey protein (in particular, the concentrate form) contains an abundance of highly biologically active cystine residues, thus making it a powerful immuno-modulator against cancer, toxins, infections, or any other bodily insult.19
In support of the notion of whey being protective, against cancer, a recent study published by the American Association for Cancer Research compared whey Protein to soy protein and casein (a low order milk protein). The article concluded that "Whey appears to be at least twice as effective as soy in reducing both tumor incidence and multiplicity."20 This staggering news has profound ramifications with respect to choosing between soy protein and whey protein.
Furthermore, the same "cysteine donor" effect unique to whey and not found in soy, that seems to be at work in preventing cancer, has recently been shown to enhance muscular performance and decrease muscular fatigue. Another recent study concluded that prolonged supplementation with a product designed to augment antioxidant defenses resulted in improved volitional performance."21 Remember, this characteristic is unique to whey and something soy simply cannot achieve because it is not a cysteine donor.
Going back to the issue of soy containing phytoestrogens, the problem may be worse for men than for women.
The research indicates that these phytoestrogens are not as weak and harmless as soy enthusiasts would lead you to believe. In fact, when genistein (the main phytoestrogen in soy) Was given to mice in doses similar to those contained in an average soy-based diet, in only nine days testosterone concentration was dramatically reduced. The reduction seemed to stem from a decrease in production of luteinizing hormone, secreted by the anterior pituitary gland.22 In fact, several other animal studies clearly indicate the rather frightening feminizing effect of unopposed estrogen stimulation in the form of dietary phytoestrogens.23,24
My own fight card says soy loses yet another round. Stick with whey, unless of course you want to get in touch with your feminine side.
Moreover, another recent, study by Dr. Stephen Liu of UCLA Medical Center, demonstrated the influence of estrogen on weakening ligaments and thus increasing the probability of injury. This would explain why women are up to six times as likely as men to suffer an anterior cruciate ligament tear.25 Although this research is somewhat controversial and preliminary, it warrants careful examination. As with the concerns over soy protein negatively influencing thyroid function in children, don't discard these possible early indicators of what could become a serious health issue as the soy juggernaut rolls on unopposed.
As we near the end of the final round, know that the research continues to mount supporting whey as the protein of choice and, unless used carefully only in select cases as a medicinal food, soy is far inferior and dangerously problematic. In this head-to-head battle, soy protein is simply outclassed by whey. But since the Don Kings of the soy industry are showing no signs of letting up on the pro-soy hype, something tells me this mismatch is destined for a rematch.
1. Brouns F. et al. Metabolic changes induced by sustained exhaustive cycling and diet manipulation. lnt J Sports Med. 10(Suppl.1):S49-S62,1989.
2. Dolny D.G. et al. Effect of ambient temperature on protein utilization during prolonged exercise. J Appl Physiol.64:550-555, 1988.
3. Lemon P. Effects of exercise on dietary protein requirements. Int ,J Sports Nutr. 8:426-447 1988
4. Lemon P. Do athletes need more protein and amino acids? lnt J Sport Ntrtr. 5(Suppl):S39-S61, 1995
5. Lemon P. Effects of exercise on protein and amino acid metabolism. Mod Sci Sports Exerc. 13:141-149,1961.
6. Lemon P. et al. Protein requirements and muscle mass/strength changes during intensive training novice bodybuilders. J Appl Physiol. 73:767-775, 1992.
7. Meredith C.N. et al. Dietery protein requirements and protein metabolism in endurance-trained men. J Appl Physiol. 66:2850-2856, 1989.
8. Tamopoisky M.A. et al. Evaluation of protein requirements strength trained athletes. J Appl Physiol. 73:1986-1995, 1992.
9. Tarnopolsky MA at al. Influence of protein Intake and training status on nitrogen balance and lean body mass. J Appl Physiol. 64:187-193,1988.
10. Zhang X. et al. Whey proteins, effect on plasma and triacylglyerols. Brit J Nutr. 1993.
11. Burros M. Doubts cloud rosy news on soy. The Science Times The New York Times Jan. 26, 2000.
12. Hulley S. et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA. 1998;280:605-612.
13. Cummings S.R. et al. The effect of raloxifene on risk of breast, cancer in postmenopausal women. JAMA. 1999;281:2189-2197.
14. Willet W. at al. Postmenopausal estrogens- Opposed, unopposed, or none of the above. JAMA. 2000;283:534-535.
15. Bounos G. Whey protein and cancer. Clin Invest Med..1998.
16. Satterman W. Whey protein for athletes. Dtsh Milchwirsch. 1986; 37(33):1010- 1012.
17. Nowsholme EA. Biochemical mechanisms to explain immunosuppression in well-trained and overtrained athletes. Int J Sports Med 1994;15(3):sl42-47.
18. Colker C., Kalman D., Brink W., Antonio J. Immune status of elite athletes, Role of whey protein concentrate. Med Sci Sports Exerc 1998;30(5):a95.
19. Bounos G. The story behind a health-promoting product-patented milk serum (whey) protein concentrate. lmmunotec Clinical Foundations. 1998.
20. Hakkak R. et al. Diets containing whey proteins Or soy protein isolate protect against 7,12-dimethylbenz(a)anthracene-induced mammary tumors in female rats. Canc Epid Bio Prev. 2000;9:113-117.
21. Lands LC. Effect of supplementation with a cysteine donor on muscular performance. J Appl Physiol. 1999;87(4):1381-1385.
22. Strauss E. et al. Genistein exerts estrogen-like effects in the male mouse reproductive tract. Mol Cell Endocrinol. 1988;25.144(1-2):83-93.
23. Casanova M. et al. Developmental effects of dietary phytoestrogens in Sprague-Dawley rats and interactions of genistsin and diadzein with rat estrogen receptors alpha and beta in vitro. Toxicol Sci. 1999;51(2):236-244.
24. Kumi-Diaka J. et al. Cytotoxic potential of the phytochemical genistein isoflavone and certain environmental chemical compounds on testicular cells. Biol Cell. 1999;91(7)-515-523.
25. Female hormones blamed for knee injury; The NewYork Pbst, Jan. 29, 2000.
CFS Radio Program February 28th, 1999 Roger G. Mazlen, M.D. Host With Dr. Paul Cheney, M. D., Ph.D.
Dr. Mazlen: We are really honored today to have a very eminent guest with us today, Dr. Paul Cheney. Dr. Cheney is the founder/director of the Cheney Clinic which is located on Bald Head Island in North Carolina. He's also prominent from the early beginning of research into Chronic Fatigue Syndrome or CFIDS. He's a board certified internist. He additionally trained for two years in tumor immunology at the CDC and then became Chief of Medicine at the Mount Home Air force Base Hospital in Montana. Of course, from there there's a long history of research and involvement and prominence in the field of research into Chronic Fatigue Syndrome, so I'm going ask Paul to tell us a little bit about how that started. Paul, welcome to the show and we'd like to hear from you now.
Dr. Cheney: Yes, thank you, Roger. My introduction to this illness was as a practicing internist on the north shore of Lake Tahoe in 1985 when in the spring of that year we began to see an increasing, actually, an accelerating number of patients, peaking in the summer of '85 and then decelerating quickly by the fall of '85, producing about 200 cases in that small area of the California/Nevada line and the Sierra Nevada Mountains. Initially we thought there was some sort of flu-like illness among our patients who were previously quite healthy but over time they would not resolve the symptomatology and evolved slowly over time a triad of symptoms, characterized by debilitating fatigue, increasing cognitive disturbances affecting their ability to function cognitively, and then incredible pain, particularly muscle pain but also other kinds of accelerated pain. And that was the triad that we saw and these patients would not get well. And so we invited both the CDC and later Dr. Komaroff, then chief of medicine at Harvard who'd been seeing a large number of cases in Boston to come out and help us research this epidemic culminating in a publication in the Annals of Internal Medicine at about 1991 describing what we saw in that time.
Dr. Mazlen: Well, of course, it's history and most of the patients with Chronic Fatigue Syndrome are well aware of your work and Peterson and others in this area and we commend you for those early efforts, but you've gone a long way since. You've been very much involved nationally in the area of research into Chronic Fatigue Syndrome. You had mentioned to me a new concept as to what the disease is as it develops, when we had spoken prior to the show, maybe you would just like to go into that a little bit.
Dr. Cheney: Yes, the syndrome we call Chronic Fatigue Syndrome probably belongs to a larger subset of disorders known as post-infectious or post-viral syndromes, at least in a hefty subset of patients, perhaps 60-70% who were perfectly healthy until one day they come down a flu-like or mono-like illness and aren't the same thereafter. There's a smaller subset that have more insidious onset and they represent a different type of illness, but the majority of patients appear to be a post-infectious or post-viral syndrome. In that regard, there's another syndrome known as Reye's Syndrome, which evolves typically in children, although it can hit adults as well, who come down with a viral illness, sometimes the flu, sometimes chicken pox, and are resolving the acute viral syndrome and then take a dramatic turn for the worse almost at the moment they're getting better from the viral syndrome and the disease we call Reye's is characterized by disturbed liver function in the aftermath of the viral infection, that then produces a severe toxicity that affects the central nervous system and frequently death ensues. And Chronic Fatigue Syndrome might be viewed as a sort of slowly developing Reye's Syndrome in that they come down with a viral syndrome and then they emerge from that with a disorder in liver function and detoxification at the cellular level, we think involving glutathione but also other pathways, and that results in a progressive toxification systemically, particularly from the portal circulation similar to Reye's and then a hit to the central nervous system, probably a zenobiotic toxicity to the deep brain structures that gives us the emerging picture of debilitating fatigue, cognitive disturbances, hypothalamic-pituitary-adrenal axis disturbances and severe pain. So, it's sort of like a post-infectious slowly developing Reye's Syndrome as an analogy to another more acute illness we call Reye's Syndrome.
Dr. Mazlen: Now, also, there's a connection here which you make me aware of to the 37 kilodalton variant of the RNase L and I want you to do on and talk about that.
Dr. Cheney: Right, well, that's a really intriguing issue because no one really fully understands why liver detoxification fails in Reye's Syndrome, but in Chronic Fatigue Syndrome there was discovered some years ago by Dr. Robert Suhadolnik that a very significant up regulation in an enzymatic pathway known as the 2-5A RNase L pathway was highly activated in Chronic Fatigue Syndrome. This particular pathway, although a potent antiviral pathway inhibiting viral protein synthesis and therefore viral replication, also inhibits human protein synthesis and enzyme production and could easily be the cause of this liver detox and cellular detox failure in this disorder that sets off this compounded set of problems. Dr. Suhadolnik, a few years after discovering this pathway was highly activated then discovered it was aberrantly activated with evidence of a low molecular weight, 37 kDA protein, kDA simply that as kilodalton, the size of the protein. The normal RNase L is 80 kilodaltons. This low molecular weight is only 37, slightly less than half the size. This could particular enzyme is extraordinarily active, over 6 times more active than normal RNase L and it resists proteolytic degradation and therefore lasts longer in the body and it can really cream protein synthesis and enzyme production and cellular function and from that human function.
Dr. Mazlen: Apparently, it also uses up some of the precursors for glutathione production, is that correct?
Dr. Cheney: Well, it certainly is a rapid cycling enzyme system that consumes ATP by the bucket load, kind of a black hole for ATP, as it were. So, it's a consumer of energy, but most importantly, it impairs enzymatic production in virtually every enzyme in the body. It has a huge, huge effect on human function.
Dr. Mazlen: So, this is one of the cornerstones, but on the other hand, it's only been found in about 30-40% of Chronic Fatigue Syndrome cases.
Dr. Cheney: Correct. That was kind of an interesting discovery because we were hopeful that it might be true marker for this disease, but it was not to be present in a large subset, but it was primarily present in the first 5 years of illness and at about 5 years or so, plus or minus, it begins to down regulate, such that by the 8th to 12th year of illness there's virtually no 37 kDA left, yet the patients do not necessarily recover, although we think their illness shifts or changes as this 37 kDa down regulates.
Dr. Mazlen: I want to ask you, Paul, if you can talk a little bit about your current research in Chronic Fatigue Syndrome?
Dr. Cheney: Yes, of course we have a number of projects. One is of course collaborating with Dr. Suhadolnik regarding the 37 kDa protein and it's meaning in this disorder, but a recent effort at this clinic has been--actually it's the culmination of several years of looking at defects in detoxification pathways, in particular the glutathione system which appears to be particularly impaired in this syndrome and we tried treating this in a variety of ways, first, obviously with oral therapy with reduced l-glutathione and injectable glutathione and in a few cases with precursors to glutathione such as n-acetylcysteine and although we were seeing modest benefits, particularly pressure headaches, with reduced l-glutathione, we were not getting a huge clinical benefit overall and the glutathione system remained impaired as measured by endpoint markers such as liver peroxides in the urine. So we began to look out at other approaches that might work better and we became aware of a weakly hydrolyzed whey protein concentrate, marketed as Immunocal™ (he is now using ImmunoPro®) but in fact a whey protein concentrate that's weakly hydrolyzed and that appears to be important in it's effectiveness. We read about this product and were interested in its potential for improving the glutathione system and from there wondering if it would help this disease. So, we launched a program about 6 months ago testing the efficacy of this in CFIDS and we are, at this point, analyzing the data and pleasantly surprised at what we're seeing.
Dr. Mazlen: So, you're getting some positive results then?
Dr. Cheney: Yes, we are and we do think, however, there's a subset of patients that appear not to respond to this product. There's a larger subset that appears to respond clinically. Some interesting and unexpected results were seen in the study but overall I think it was a positive clinical response and other interesting facets of this product making us a lot more interested and perhaps more aggressive in treating this glutathione defect with these kinds of products.
Dr. Mazlen: Now, this is a small study so I presume that you feel at this point it warrant expansion into larger trials. I think so.
Dr. Cheney: We only have 7 patients which isn't a large number, but there was a very consistent response in several areas suggesting that 7 is almost enough to make some observations about it, but I think from a scientific standpoint we'll need more studies and larger numbers.
Dr. Mazlen: Well, it's exciting because anything that's helps this population of people who reign from moderate to severely ill or totally disabled is certainly a welcome advent to the therapeutic armamentarium for us, primary care physicians and researchers. I want to take one quick call on the line from Jeeney, then we'll go on with other things. Jeeney, welcome to the show. Do you have a quick question?
Jeeney: My question today is about ampligen. I've been hearing so many mixed reviews. After you had your study and the people stopped taking the ampligen, what was that result?
Dr. Cheney: Well, there are several things I think that are important to note about ampligen. First, of all, there's no doubt in my mind as I've seen it in clinical practice that this drug is bioactive in this syndrome. That is it can help people sometimes substantially. However, it does not help everyone. And it may be that the reason--there may be a couple of different reasons--one reason may be that no everyone has activation of this RNase L pathway which ampligen appears to be very potent at regulating, in CFIDS at least, downregulating. If that pathway is not activated, then ampligen may not be very rational or even effective. Ampligen also has potent antiviral properties as well and I think some of these patients may not have a significant viral activation state which may be another reason why it doesn't work in everyone. The other parallel issue for ampligen is that it appears that the longer that you take it, if you are responding to it, the better the outcome and in the initial study in 1991-92 we essentially only treated for 6 months in most cases, a year at most and that may have been a relative under treatment and so when you're under treated with ampligen, even if you're a responder you tend to degrade very quickly when you stop and conversely, when the drug is treated for longer periods of time a better clinical therapeutic plateau is reached, there appears to be some stability at maintaining a plateau once the drug is stopped. So, I think it's kind of uncertain in my own mind exactly what will happen when you stop this drug. My sense is that if it's stopped prematurely, one will end up pretty much back where you were. If it's maintained over a longer period of time, there's a much better chance of stability. If you are a responder, the chances of a response, all comers, appears to be 2 chances in 3 and that might be raised a little bit if one targets a subset of patients, specifically ones that are within the first 5 years of their illness who have abrupt onset and who may have activation of this RNase L pathway.
Dr. Mazlen: You mentioned earlier, briefly to me, not on the show, but privately, that there's a significant incidence of chlamydia pneumoniae found in CFIDS patients. Can you comment further on that?
Dr. Cheney: Yes, of course this syndrome has sort of a long history of viral and, more recently, non-viral microbial activation reported as associated with this disorder. For the listening audience, it's important to distinguish between association of an organism versus causality, and that's a thing critically important in this syndrome. This syndrome may represent an immune activation state and with the disordered glutathione system which can create a sort of biological terrain in which microorganisms that lay dormant in our bodies almost back from childhood can activate and then other organisms that we may catch during our lives, and these organisms are not typically active, but are kept in a dormant state by our immune systems indicates that in CFS the conditions are ripe at times for the reactivation of these dormant and latent organisms. One of these organisms which is ubiquitous in the population but typically not active is chlamydia pneumoniae, which has been reported as active in a large percentage of these cases.
Dr. Mazlen: Well, that's a significant addition because they still have trouble with a lot of infectious disease specialists in dealing with Chronic Fatigue Syndrome. Many of them don't feel it has anything significant if they just show a positive Epstein Barr viral capsid antibody, IgG, etc. I want you, Paul, to give me your email address for the audience.
Caroline: I actually have two. One is that College Pharmacy is selling a generic Immunocal and I wanted to know whether Dr. Cheney thinks that is as good or if he's familiar with it and the second is that if you have the test for the RNase L marker for ampligen and you don't have that activated pathway, are you definitely not a good candidate for ampligen?
Dr. Cheney: Very good questions. Regarding generic type products of a whey protein concentrate, we do know from the patent application involving Immunocal™ that in comparison with the typical whey protein concentrates, the Immunocal™ product is far superior in it's ability to improve glutathione status. With regard to other generic products that might be available however, I can't comment. I haven't looked at them. Theoretically, in my view it would be possible to make a generic that would work, I just don't know if a particular generic will work and that would have to be looked at carefully. With regard to RNase L itself, if it's not activated doesn't exclude, in my opinion, a response to ampligen, but rather reduces the chance somewhat, I don't know how much, but I think there are people that definitely responded to ampligen to did not have activation of this pathway because ampligen may do more than just modulate this enzyme pathway. It has other effects.
* Dr. Paul Cheney M.D. is currently using ImmunoPro® with the patients in his clinic.
February 1999: (Transcription)
. . . immune-activation states can also induce the activation of endogenous microbes in the presence of Glutathione deficiency. And that might explain why in this immune-activation state that we call Chronic Fatigue Syndrome you see a lot of endogenous viral activation such as EBV, CMV, HHV6, mycoplasma incognitus, chlamydia pneumonia, candida, and on and on and on. You see the activation of this microbial ecology, and why is this happening? It could be that it happens because cytokines in excess stimulate these organisms, especially in the presence of glutathione deficiency. The converse is true, however. In the presence of good glutathione levels, it's very difficult for that to happen
. . . . Conclusions from all of this are: Glutathione has potent anti-viral properties--if you raise the glutathione level you can stop the replication of most any, at least, intracellular pathogen. Chronic fatigue syndrome patients are glutathione deficient. Glutathione deficiency itself has a potent pro-viral effect. That is, not only does (high?) glutathione levels tend to act as an anti-viral, but glutathione deficiency produces a pro-viral effect. It can actually augment viral replication. Augment it from the case of toxins, toxins could augment viral replication and also cytokines themselves. So immune-activation states would itself augment these things.
. . . I'm trying to set the stage for how important it is to address this glutathione defect. It could be THE major issue in this illness. Maybe not so much in the beginning, but over time become the major issue. Because we're dealing with a sub-group of people who have cellular detox failure and all that that causes. Because if you have cell detox failure, you become a canary to your environment. . . . If you get a glutathione defect, then you become vulnerable to your own cell toxicity, specifically the portal circulation.
We found out that when you give oral reduced glutathione, it helps a little bit in some people, especially these pressure toxic headaches they get. But when you keep raising the dose, they actually get sick again, and it was never a very impressive response. When we tried NAC we saw some evidence of toxicity. In the use of NAC--I'm concerned about high-dose NAC in this disease. I think it may be toxic. We tried other methods to affect glutathione. Nothing seemed to be working.
Then we got wind of non-denatured whey protein, lightly denatured to preserve the peptide action of this milk protein. It's concentrated to about 90 percent protein and it's very, very lightly denatured. In fact, the more lightly they denature it, the better the action appears to be. And the more they denature it, the less active it appears to be. In fact, if you denature it completely, down to its constituent amino acids, it really doesn't work well at all. People who normally have milk protein allergy seem to tolerate this, by and large. Not 100 percent, but by and large.
This is the data from a six-month study. There were eight people entered into the study, seven of them completed the study. We got data on seven of them. One dropped out at three months for a reason involved with the design of the study. (Note from Carol: the patient dropped out when the study protocol randomly required half of the participants to drop to one packet (10 grams) a day at the halfway point. He was improving so much on two packets a day that he refused to drop back, so he quit the study.) The first three months of the study we treated with two packets a day, and then the second three months, half were randomized to two packets a day and half were randomized to one packet a day. We wanted to see if you could tell a difference clinically or by other means between one packet a day versus two packets a day.
We did this because there was some indication that the more you treat with this, the higher the dose, the better the effect. When you look at the group that goes from two packs a day to one pack a day, you can see this nice dip where they started going back up (in their urine lipid peroxides). Suggesting that one pack a day doesn't work very well. (He's referring to a slide of a chart here, I think.)
By the way, you can extend this--there are people, I've discovered since the study was done, that do really well on three packs a day and not very well at all on two. (Note from Carol: Cheney told me in October that he has patients on 4, 5, and even 6 packets a day!!!) So clearly there is a dose response issue. Two packs a day would probably be my recommended starting dose, but I wouldn't hesitate to go up if it seemed like it wasn't working.
This is the exciting stuff. We wanted to see not only if this product improved glutathione functionality, which it did, but we also wanted to see if it knocked out micro-organisms, like the PNS article said it would. Chlamydia pneumonia is an intracellular pathogen. It's a common cause of hospital-acquired pneumonia. It ubiquitously infects the population, but seems to activate under certain conditions. And if it activates, some of the clinical conditions of this organism are chronic sinusitis, pharyngitis, and laryngitis. But it also gets into the central nervous system.
In a study published by a neurologist out of Vanderbilt showed that chlyamdia pneumoniae may be a very important pathogen in multiple sclerosis. Indeed, data they shared with me recently (and this is coming to publication soon) showed that 80 percent of the cerebral spinal fluid of MS patients is actively infected with this organism. Versus 15 percent of other neurological diseases that are not MS. In a journal-published article on neurology, aggressive treatment for chlyamdia pneumoniae rapidly reversed an acute exacerbation of multiple sclerosis.
So we measured IgM levels for this pathogen at Vanderbilt. Most laboratory measurements of this organism are not very good, so this is a research grade assessment, and probably may not generalize to the run-of-the-mill types of tests that you might get in your local labs. But IgM elevations of 1 to 1600 (?) dilutions is evident of significant active infection with this organism. Six months later, it just wiped it out. IgM just fell to normal levels. It didn't really matter whether you were taking one pack a day or two packs a day. Just wiped it out. Makes you wonder what this might do for MS. Think about that.
We also looked at mycoplasma fermentans and mycoplasma penetrans. Both of these pathogens have been linked to Gulf War Syndrome. They've been linked to chronic fatigue syndrome. Again, they may be a relatively ubiquitous mycoplasma species, intracellular, and can cause a variety of problems when active. Again, by PCR done in Irvine, California. We were able to show that this product also wiped out mycoplasma incognitus and penetrans.
Then we looked at HHV6. It was a little mixed here. We tested three people.
By the way, this study was designed to do some microbial testing on everybody, but not everything on everybody. The patients were allowed to pick and choose depending on what we had in their chart before. We weren't able to do everything on everybody because they were paying for this.
We did HHV6 rapid culture testing, which is a technique developed by a company in Wisconsin. This particular culture technique uses an intermediate (captures fiberglass?) cell line, so that you are positive only if you are really infected, so it reduces false positives to zero. That is, under these conditions, all normal people are negative. You have to do that because HHV, both A and B strains, are relatively ubiquitous. Under these conditions, we had two positives and one negative at beginning of the study. The person on two packs a day went to zero culture (negative); the person on one pack a day stayed positive. The person that was negative stayed negative. Suggesting that maybe this isn't as good against viruses as it is against bacteria, but at two packs a day it might be good against viruses. Again, the numbers (of participants) are small.
But to me, the satisfaction of this is tremendous because I'm always faced in this disease population--well, are they sick from EBV? or are they sick from HHV6? or are they sick from mycoplasma incognitus? or are they sick from c pneumoniae? And the [traditional] treatment for mycoplasma and c pneumoniae is 18 months of triple drug antibiotic therapy. And if we're wrong on this issue, we've wiped out their gut flora and leave them a gut ecology cripple for the rest of their lives. So now what we have is a nice way to address almost any microorganism that happens to be there. Just as the PNS article suggested.