Whey protein is a mixture of globular proteins isolated from whey, the liquid material created as a by-product of cheese production. Some preclinical studies in rodents have suggested that whey protein may possess anti-inflammatory or anti-cancer properties. The effects of whey protein on human health are of great interest and are currently being investigated as a way of reducing disease risk, as well as a possible supplementary treatment for several diseases.
Whey protein is commonly marketed and ingested as a dietary supplement, and various health claims have been attributed to it in the alternative medicine community. Although whey proteins are responsible for some milk allergies, the major allergens in milk are the caseins.
Whey is left over when milk is coagulated during the process of cheese production, and contains everything that is soluble from milk. It is a 5% solution of lactose in water, with some minerals and lactalbumin. The fat is removed and then processed for human foods. Processing can be done by simple drying, or the protein content can be increased by removing lipids and other non-protein materials. For example, spray drying after membrane filtration separates the proteins from whey.
Whey can be denatured by heat. High heat (such as the sustained high temperatures above 72 °C associated with the pasteurization process) denatures whey proteins. While native whey protein does not aggregate upon renneting or acidification of milk, denaturing the whey protein triggers hydrophobic interactions with other proteins, and the formation of a protein gel. Heat-denatured whey can still cause allergies in some people.
Whey protein is the collection of globular proteins isolated from whey, a by-product of cheese manufactured from cow's milk. The protein in cow's milk is 20% whey protein and 80% casein protein, whereas the protein in human milk is 60% whey and 40% casein. The protein fraction in whey constitutes approximately 10% of the total dry solids in whey. This protein is typically a mixture of beta-lactoglobulin (~65%), alpha-lactalbumin (~25%), bovine serum albumin (~8%)(see also serum albumin), and immunoglobulins. These are soluble in their native forms, independent of pH.
Being a by-product of the cheese making process, and likelihood of animal rennet use, whey protein as well as casein products may not be suitable for consumption by lacto-vegetarians or observers of kosher dietary laws. There are, however, specialty producers of vegetarian-approved whey protein products produced using non-animal "rennet" (enzymes). These products are often also labeled as kosher and halal approved.
- Concentrates have typically a low (but still significant) level of fat and cholesterol but, in general, compared to the other forms of whey protein, have higher levels of bioactive compounds, and carbohydrates in the form of lactose — they are 29%–89% protein by weight.
- Isolates are processed to remove the fat, and lactose, but are usually lower in bioactivated compounds as well — they are 90%+ protein by weight. Like whey protein concentrates, whey protein isolates are mild to slightly milky in taste.
- Hydrolysates are whey proteins that are predigested and partially hydrolyzed for the purpose of easier metabolizing, but their cost is generally higher. Highly hydrolysed whey may be less allergenic than other forms of whey.
Whey protein and muscle building
The effects of whey protein supplementation on muscle growth in response to resistance training are debatable. One study demonstrated some increase in lean body mass and strength in men supplementing whey protein vs. no supplementation, while another study found greater increases in strength in a group supplementing whey compared to another group supplementing casein, which could be evidence of whey protein's superior amino acid profile. However, other research exists that show little to no benefit of whey protein supplementation. The authors of one study concluded that "young adults who supplement with protein during a structured resistance training program experience minimal beneficial effects in lean tissue mass and strength,", although it did not control for other sources of protein in the participant's diets. The timing of protein supplement ingestion may not have any significant effects on strength, power, or body-composition. A study of elderly men found supplementation with whey protein after exercise improved muscle protein synthesis and erectile disfunction.
Scientific evidence has shown that proteins high in essential amino acids (EAA), branched chain amino acids (BCAA), and particularly leucine (Leu) are associated with increased muscle protein synthesis, weight loss, body fat loss, and decreased plasma insulin and triglyceride pro-file.  Whey protein and leucine are beneficial for stimulation of acute muscle protein synthesis in older adults. 
The use of whey protein as a source of amino acids and its effect on reducing the risks of diseases such as heart disease, cancer and diabetes is the focus of ongoing research. Whey is an abundant source of branched-chain amino acids (BCAAs), which are used to stimulate protein synthesis. In particular, leucine plays a key role in initiating the transcription of protein synthesis. When leucine is ingested in high amounts, such as with whey protein supplementation, there is greater stimulation of protein synthesis, which may speed recovery and adaptation to stress (exercise).
Whey protein contains the amino acid cysteine, which can be used to make glutathione. However, this amino acid is not essential for the synthesis of glutathione, and some studies have suggested that the amount of cysteine in the diet may have little effect on glutathione synthesis. However, another study suggested that large amounts of whey protein can increase cellular glutathione levels. Glutathione is an antioxidant that defends the body against free radical damage and some toxins, and studies in animals have suggested that milk proteins might reduce the risk of cancer.
Aflatoxin, an extremely potent carcinogen and major cause of mitochondria damage (thereby having the potential to negatively affect all bodily processes including skeletal muscles), has been shown to be inhibited by whey protein and ginseng extract. However, the amount of aflatoxin within whey protein itself, was shown to be reflected by the amount in the unprocessed milk used to make it.
Some people experience severe digestive issues following consumption of whey protein powder. These may include gas, bloating, cramps, tiredness, weakness, fatigue, headaches, and irritability. One of the possible causes is lactose intolerance after they ingest whey concentrate. Undigested protein in the colon will undergo bacterial fermentation which leads to the production of, among other things, gas and fatty acids.
- Hakkak R, Korourian S, Ronis MJ, Johnston JM, Badger TM (May 2001). "Dietary whey protein protects against azoxymethane-induced colon tumors in male rats". Cancer Epidemiol. Biomarkers Prev. 10 (5): 555–8. PMID 11352868.
- Xiao R, Carter JA, Linz AL, Ferguson M, Badger TM, Simmen FA (September 2006). "Dietary whey protein lowers serum C-peptide concentration and duodenal SREBP-1c mRNA abundance, and reduces occurrence of duodenal tumors and colon aberrant crypt foci in azoxymethane-treated male rats". J. Nutr. Biochem. 17 (9): 626–34. doi:10.1016/j.jnutbio.2005.11.008. PMID 16504496.
- Krissansen GW (December 2007). "Emerging health properties of whey proteins and their clinical implications". J Am Coll Nutr 26 (6): 713S–23S. PMID 18187438.
- Marshall, K (2004). "Therapeutic applications of whey protein". Alternative Medicine Review 9 (2): 136–156. PMID 15253675.
- Wal JM (November 2004). "Bovine milk allergenicity". Ann. Allergy Asthma Immunol. 93 (5 Suppl 3): S2–11. doi:10.1016/S1081-1206(10)61726-7. PMID 15562868.
- Burks W, Helm R, Stanley S, Bannon GA (June 2001). "Food allergens". Curr Opin Allergy Clin Immunol 1 (3): 243–8. PMID 11964696.
- "Whey." The Encyclopædia Britannica. 15th ed. 1994
- Foegeding, EA; Davis, JP; Doucet, D; McGuffey, MK (2002). "Advances in modifying and understanding whey protein functionality". Trends in Food Science & Technology 13 (5): 151–9. doi:10.1016/S0924-2244(02)00111-5.
- Tunick MH (2008). "Whey Protein Production and Utilization." (abstract). In Onwulata CI, Huth PJ. Whey processing, functionality and health benefits. Ames, Iowa: Blackwell Publishing; IFT Press. pp. 1–13.
- Lee YH (November 1992). "Food-processing approaches to altering allergenic potential of milk-based formula.". J. Pediatr. 121 (5 Pt 2): S47–50. doi:10.1016/S0022-3476(05)81406-4. PMID 1447634.
- Jay R. Hoffman and Michael J. Falvo (2004). "Protein - Which is best?". Journal of Sports Science and Medicine (3): 118–130.
- Luhovyy BL, Akhavan T, Anderson GH (2007). "Whey proteins in the regulation of food intake and satiety". Journal of the American College of Nutrition 26 (6): 704S–712S. PMID 18187437.
- Haug A, Høstmark AT, Harstad OM, A; Høstmark, AT; Harstad, OM (25 September 2007). "Bovine milk in human nutrition – a review". Lipids Health Dis 6: 25. doi:10.1186/1476-511X-6-25. PMC 2039733. PMID 17894873.
- Burke, Darren G. "The Effect of Whey Protein Supplementation With and Without Creatine Monohydrate Combined With Resistance Training on Lean Tissue Mass and Muscle Strength". International Journal of Sport Nutrition and Exercise Metabolism. Human Kinetics Publishers, Inc. Retrieved 2012-04-04.
- Cribb, Paul J.; Andrew D. Williams, Michael F. Carey, Alan Hayes. "The Effect of Whey Isolate and Resistance Training on Strength, Body Composition, and Plasma Glutamine". International Journal of Sport Nutrition and Exercise Metabolism. Human Kinetics, Inc. Retrieved 2012-04-04.
- Candow, DG; Burke, NC; Smith-Palmer, T; Burke, DG (2006). "Effect of whey and soy protein supplementation combined with resistance training in young adults". International journal of sport nutrition and exercise metabolism 16 (3): 233–44. PMID 16948480.
- Hoffman, JR; Ratamess, NA; Tranchina, CP; Rashti, SL; Kang, J; Faigenbaum, AD (2009). "Effect of protein-supplement timing on strength, power, and body composition changes in resistance-trained men". International journal of sport nutrition and exercise metabolism 19 (2): 172–85. PMID 19478342.
- Yang, Y; Breen, L; Burd, NA; Hector, AJ; Churchward-Venne, TA; Josse, AR; Tarnopolsky, MA; Phillips, SM (Feb 7, 2012). "Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men.". The British journal of nutrition 108 (10): 1–9. doi:10.1017/S0007114511007422. PMID 22313809.
- Etzel, M.R.. “Manufacture and use of dairy protein fractions.” J. Nutr. 134:996S-1002S.
- Luiking, Yvette C., et al. "Postprandial Muscle Protein Synthesis Is Higher After A High Whey Protein, Leucine-Enriched Supplement Than After A Dairy-Like Product In Healthy Older People: A Randomized Controlled Trial." Nutrition Journal 13.1 (2014): 1-26. Academic Search Premier. Web. 10 Apr. 2014.
- Rieu I, Balage M, Sornet C, et al. (April 2007). "Increased availability of leucine with leucine-rich whey proteins improves postprandial muscle protein synthesis in aging rats". Nutrition 23 (4): 323–31. doi:10.1016/j.nut.2006.12.013. PMID 17367997.
- Kimball Scott; Jefferson, LS (2006). "Signaling Pathways and Molecular Mechanisms through which Branched-Chain Amino Acids Mediate Translational Control of Protein Synthesis". The Journal of Nutrition 136 (1): 227S–31S. PMID 16365087.
- Fujita, Dreyer, Drummon, Glynn, cadenas, Et Al. (2007). "Nutrient signalling in the regulation of human muscle protein synthesis". The Journal of physiology 582 (Pt 2): 813–23. doi:10.1113/jphysiol.2007.134593. PMC 2075348. PMID 17478528.
- Ha E, Zemel MB (May 2003). "Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people (review)". J. Nutr. Biochem. 14 (5): 251–8. doi:10.1016/S0955-2863(03)00030-5. PMID 12832028.
- Layman D.K., Evans E., Baum J.I., Seyler J., Erickson D.J., Boileau R.A. (2005). "Dietary protein and exercise have additive effects on body composition during weight loss in adult women". J. Nutr 135: 1903–1910.
- Courtney-Martin G, Rafii M, Wykes LJ, Ball RO, Pencharz PB (November 2008). "Methionine-adequate cysteine-free diet does not limit erythrocyte glutathione synthesis in young healthy adult men". J. Nutr. 138 (11): 2172–8. doi:10.3945/jn.108.093302. PMID 18936215.
- Zavorsky, Kubow, Grey, Riverin, Lands (2007). "An open-label dose-response study of lymphocyte glutathione levels in healthy men and women receiving pressurized whey protein isolate supplements". International Journal of Food Sciences and Nutrition 58 (6): 429–36. doi:10.1080/09637480701253581. PMID 17710587.
- P.W. Parodi. "A Role for Milk Proteins and their Peptides in Cancer Prevention". Current Pharmaceutical Design 13 (8): 813–828. ISSN 1873-4286.
- "Digestive Problems Commonly Associated With Whey Protein". Livestrong.Com. Retrieved 2013-02-07.
- Does 100% whey protein make you have bad gas?, Livestrong.com
- Le Leu, R. K.; Brown, I. L.; Hu, Y.; Morita, T.; Esterman, A.; Young, G. P. (2006). "Effect of dietary resistant starch and protein on colonic fermentation and intestinal tumourigenesis in rats". Carcinogenesis 28 (2): 240–5. doi:10.1093/carcin/bgl245. PMID 17166881.
- Whey protein resources, National Dairy Council
- Whey Protein Healthnotes, University of California, San Diego
- Whey Protein Facts, Whey Protein Institute
- What does science say about whey protein and muscle building?, European Food Safety Authority on whey protein claims