Scientific Backgrounders

Whey Protein

The purpose of this backgrounder is to present a summary of current scientific data and research regarding the use of whey protein as a food or dietary ingredient or dietary supplement. It is intended for educational use only and is not intended to be used as third-party literature.

Whey is the milk component remaining after the removal of casein, as by curdling. It contains about 17% of the total protein in milk. The proteins in whey and their percentage of the total whey protein are: beta(β)-lactoglobulin (58%), alpha(α)-lactalbumin (13%), immunoglobulins (12%), serum albumin (6%) and proteose-peptides (12%) (1C). Whey protein is a complete protein; it contains all of the essential amino acids. Whey protein has one of the highest protein digestibility-corrected amino acid scores (PDCAAS; a measure of protein bioavailability) and is more rapidly digested than other proteins, increases protein synthesis faster, and is therefore believed to be appropriate for post-exercise (2A, 3A). Total whey protein is usually purified using acid hydrolysis, heat, ion-exchange methodology or a combination of these methods. Concentration of these proteins in total whey protein may vary based on the chosen purification technique.

Performance and Exercise Effects
Research suggests that muscle synthesis is modulated by extracellular amino acid concentration, not intracellular, thus dietary ingestion of amino acids is critical for muscle building (anabolism) (4A). Active persons ingest supplemental protein primarily to promote muscle strength, function and possibly size (5A^). The determinants of individual need are dependent on individual activity regimen and habitual nutrient intake (6A^). Whey protein supplements have been utilized in sports products based largely on the high content (~26%) of branched chain amino acids (BCAA's), believed to stimulate protein synthesis and muscle building (anabolism) (7A^). Recent studies support ingestion of 20-25g of whey (or casein) either before or after resistance exercise led to muscle protein synthesis (8A^, 9A). Whey contains an abundance of the amino acid leucine, significant for protein metabolism and as a key signal in the initiation of muscle protein synthesis. The amino acid composition of whey is very similar to that of human skeletal muscle, providing almost all of the amino acids in approximate proportion to their ratios in muscle, which may be beneficial in terms of rapidly providing substrates for protein synthesis. Calcium is one of the primary minerals low in the diets of athletes- especially female athletes. (10A, 11A) Major mineral components present in whey proteins include the monovalent sodium, potassium and chloride ions as well as the more reactive calcium, magnesium and phosphate ions, which may benefit restoration of depleted mineral concentrations. A recent animal study demonstrated a diet rich in whey protein increased liver and skeletal muscle glycogen in exercise trained rats, which indicated the potential to enhance performance in strength-endurance activities (12A).

Other effects
While whey is used primarily for sports performance and exercise benefits, research on whey has shown other potential benefits. The science has shown whey demonstrates modest activity as an immune enhancer, antioxidant, antihypertensive, anti-tumor, anti-microbial and hypolipidemic agent (13B). Whey is believed to exert a number of these effects primarily through its high content of the sulfur-containing amino acid cysteine, an essential component of the antioxidant glutathione (13B). A patented whey protein concentrate was shown to increase immune response in mice (14A^) and provide cysteine for glutathione production during the immune response, potentially of interest toward inhibiting carcinogenesis (15A^, 16A^). Other studies demonstrate dietary whey protein advances cell differentiation and genetic expression of anti-carcinogenic factors in rats (17A, 18A). Another study demonstrated cytotoxic enhancement of baicalein, a potential chemotherapeutic agent, by inducing more apoptosis using a patented whey concentrate than baicalein alone (19A^). A major component of whey, α-lactalbumin, has also been shown to be capable of undergoing structural changes to induce apoptosis (programmed cell death) in a cancer cell line, under conditions similar to the stomach (20A). Whey α-lactalbumin is rich in tryptophan content. Tryptophan is used by the body to make the neurotransmitter serotonin. A supplement of alpha-lactalbumin enriched whey protein was shown to increase the ratio of plasma tryptophan to other large neutral amino acids and improve the cognitive ability (evaluated by memory tests) of high stress-vulnerable individuals. The cognitive ability of low stress-vulnerable individuals was not affected (21A^). Whey protein also contains lactoferrin, an iron-binding glycoprotein with potential bacteriostatic, bacteriocidal and antifungal activities (13B). Lactoferrin is only present in small quantities (<1%) in whey protein. Lactoperoxidase, an enzyme found in whey, possesses antibacterial and antiviral activities (22A). In a few clinical studies the use of antibiotics plus whey components has provided better results than antibiotic use alone (13B).

Other animal studies have suggested that whey proteins have potential beneficial effects in maintaining cardiovascular health. Peptides derived from a fermented whey product or a whey concentrate demonstrated anti-hypertensive activity in spontaneously hypertensive rats (23A^, 24A). Fermented milk with added whey concentrate was shown to lower serum cholesterol levels in rats and was used in a study with 20 healthy adult men. The human subjects were given 200 mL of the fermented milk-whey mixture two times a day for 8 weeks. After 8 weeks the HDL-cholesterol levels were significantly higher and triglyceride and systolic blood pressure were lower in the fermented milk-whey group compared to the placebo group (non-fermented milk alone) (25A^).


Some benefits of whey protein have been demonstrated in clinical study with as little as 20 grams per day. For persons engaged in resistance training (e.g. weight training) a commonly used amount is between 25-75 grams of whey protein per day. (26A, 27A, 28A). Most clinical research has used similar amounts of whey protein. Studies that have directly assessed the protein needs of such individuals, including athletes, have determined that total protein needs, from all sources, should be 1.7-2 grams per 2.2 pounds body weight, with additional intakes being excessive and offering no additional benefit (6A^)

No specific studies of whey safety were found. As a component of milk, whey has a long history of human use. Allergies or lactose sensitivity can be safety factors for individuals depending on the whey preparation used. Recent advances in purification techniques have afforded lactose-free whey products which would reduce the risk of adverse reactions for these individuals.

By furnishing this backgrounder, the Natural Products Association does not provide any opinion as to:

  • The safety of any product containing this ingredient;
  • The efficacy of any product containing this ingredient;
  • The use of any specific brand of product; or
  • The level of substantiation for either the safety or efficacy of any such product.

Neither this backgrounder nor any portion of this backgrounder may be used in advertising or promotional materials. In addition, this backgrounder does not constitute, and is not to be used as, "third party literature" as that term is used in connection with section 5 of the Dietary Supplement Health and Education Act (DSHEA).

As with any health-related product, consumers should discuss the use of any products with a health care practitioner


1C Ohio State University, Food Science 822.

2A Boirie, Y, et al. Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci USA. 94:14930-14935, 1997

3A FAO/WHO: Report of the Joint FAO/WHO Expert Consultation on Protein Quality Evaluation. Rome: Food and Agriculture Organization of the United Nations, 1990.

4A Bohé, J. et al., Human muscle protein synthesis is modulated by extracellular, not intramuscular amino acid availability: a dose-response study. J Physiol 552, 315-324 (2003).

5A^ Wolfe, RR. Protein supplements and exercise. Am J Clin Nutr 72, 551S-7S (2000).

6A^ Tipton, KD. & Wolfe RR. Protein and amino acids for athletes. J Sports Sci 22, 65-79 (2004)

7A^ 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. 42, 353-72 (2002)

8A^ Tipton, KD et al. Ingestion of casein and whey proteins result in muscle anabolism after resistance exercise. Med Sci Sports Exerc 36, 2073-81 (2004)

9A Hulmi, JJ et al. Protein ingestion prior to strength exercise affects blood hormones and metabolism. Med Sci Sports Exerc 37, 1990-97 (2005)

10A Haymes EM & Clarkson PM. Minerals and trace minerals. In: Berning JR, Steen SN, eds. Nutrition for Sport and Exercise. Gaithersburg, Md: Aspen Publishers, 1998, pp. 77107.

11A Manore MM. Nutritional needs of the female athlete. In: Wheeler KB, Lombardo JA, eds. Clinics in Sports Medicine: Nutritional Aspects of Exercise. Philadelphia, Pa: WB Saunders Company; 549563, 1999.

12A Morifuji M et al., Dietary whey protein increases liver and skeletal muscle glycogen levels in exercise-trained rats. Br J Nutr. 93, 439-45 (2005).

13B Marshall, K. Therapeutic applications of whey protein. Alt Med Rev 9, 136-156 (2004)

14A^ Bounous, G et al. The immunoenhancing property of dietary whey protein concentrate. Clin Invest Med 11, 271-8 (1988)

15A^ Bounous, G. Whey protein concentrate (WPC) and glutathione modulation in cancer treatment. Anticancer Res 20, 4785-92 (2000)

16A^ Bounous, G & Molson, JH. The antioxidant system. Anticancer Res 23, 411-5 (2003)

17A Xiao, R et al. Dietary exposure to soy or whey proteins alters colonic global gene expression profiled during rat colon tumorigenesis. Mol Cancer 11, 1 (2005)

18A Eason, RR et al., Dietary exposure to whey proteins alters rat mammary gland proliferation, apoptosis, and gene expression during postnatal development. J Nutr. 134, 3370-7 (2004)

19A^ Tsai, WY et al. Enhancing effect of patented whey protein isolate (Immunocal) on cytotoxicity of an anticancer drug. Nutr Cancer 38, 200-8 (2000).

20A Svensson, M et al. Conversion of alpha-lactalbumin to a protein inducing apoptosis. Proc Natl Acad Sci USA 97, 4221-6 (2000)

21A^ Markus, CR et al. Whey proteins rich in alpha-lactalbumin increase 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 75, 1051-6 (2002)

22A FitzGerald, RJ & H Meisel. Lactokinins: whey protein-derived ACE inihibitory peptides. Nahrung 43, 165-7 (1999)

23A^ Yamamoto, N et al. Purification and characterization of an anti-hypertensive peptide from a yogurt-like product fermented by Lactobacillus helveticus CPN4. J Dairy Sci 82, 1388-93 (1999)

24A Murakami, M et al. Structural analysis of a new anti-hypertensive peptide (beta-lactosin B) isolated from a commercial whey product. J Dairy Sci 87, 1967-74 (2004)

25A^ Kawase, 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 83, 255-63 (2000).

26A Brown EC, et al., Soy versus whey protein bars: Effects on exercise training impact on lean body mass and antioxidant status. Nutrition Journal 2004, 3:22 (2004).

27A Demling RH & DeSanti L., Effect of a Hypocaloric Diet, Increased Protein Intake and Resistance Training on Lean Mass Gains and Fat Mass Loss in Overweight Police Officers. Ann Nutr Metab;44:2129 (2000)

28A Middleton et al., Whole blood and mononuclear cell glutathione response to dietary whey protein supplementation in sedentary and trained male human subjects. Int J Food Sci Nutr, 55, 131-141 (2004).

A reference: research article or editorial comment in peer-reviewed journal B reference: letters to the editor, professional personal communications, meeting/conference abstracts (NOT usually peer reviewed), and pending reviewed publications C reference: lay/trade press publications, interviews, patents and Web site material (NOT peer-reviewed) This hierarchy shows the relative reliability and scrutiny of the science in the references cited. In general, articles in peer-reviewed journals are subjected to critical evaluation by disinterested scientists before acceptance for publication. A backgrounder with few A references, or a preponderance of B and C references, will usually indicate a substance with little critically reviewed scientific research to support its use and/or safety.