Whey Protein:

A Functional Food

Carol Bayford, BSc (Hons) Nutritional Therapy

Introduction

Whey protein, with its high protein quality score and high percentage of BCAAs
(branched chain amino acids), has long been popular in the exercise industry as a
muscle-building supplement. However, research suggests it may have far wider
applications as a functional food in the management of conditions such as cancer,
hepatitis B, HIV, cardiovascular disease, osteoporosis and even chronic stress.

Whey Protein Production

Whey protein is extracted from whey, the liquid material created as a by-product of cheese
production. Advances in processing technology have resulted in a number of different finished whey
products with varying nutritional profiles. These are summarised in Table 1 which is has been
1
extracted from K. Marshalls Therapeutic Applications of Whey Protein .
Table 1: Commercially Available Whey Proteins
Product Description

Protein Concentration

Whey Protein Isolate

Whey Protein Concentrate

90-95%

Hydrolysed Whey Protein

Variable
Hydrolysis used to
cleave peptide bonds,
creating smaller peptide
fractions
Reduces allergic
potential compared with
non-hydrolysed

Undenatured Whey Concentrate

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May range from 25-89%

Most commonly available
as 80%

Variable
Usually ranges from 2589%
Processed to preserve
native protein
structures: typically has

Fat, Lactose, Mineral

Content
Negligible
Some fat / lactose /
minerals which decrease
as protein concentration
increases
Varies with protein
concentration

Some fat / lactose /

minerals which decrease
as protein concentration
increases

Spring 2010

Whey Protein A functional food

Carol Bayford
higher amounts of
immunoglobulins and
lactoferrin

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Whey Protein A functional food

Carol Bayford

Biological Components
Amino Acid Content

Whey is made up of a number of proteins including beta-lactoglobulin, alpha-lactalbumin, bovine

serum albumin (BSA) and glycomacropeptide (GMP). Collectively, these contain a full spectrum of
amino acids including the BCAAs leucine, isoleucine and valine. BCAAs are required for tissue growth
1.
and repair and leucine in particular plays a key role in the translation-initiation of protein synthesis
The sulphur-containing amino acids cysteine and methionine are also found in high concentrations in
whey protein, contributing to enhanced immune function through intracellular conversion to
1
glutathione . Interestingly, GMP although a source of BCAAs lacks the aromatic amino acids
phenylalanine, tryptophan and tyrosine. This makes it a viable protein option for individuals with
PKU (Phenylketonuria).

Lactoferrin

2,3

Lactoferrin is a non-haem iron-binding glycoprotein with antimicrobial and antioxidant effects .

Comprising a single polypeptide chain with two binding sites for ferric ions, whey lactoferrin appears
to exert its effects by regulating iron absorption.4
Immunoglobulins

Immunoglobulins form a significant 10-15% of total whey proteins derived from bovine milk and of
1,5
these, IgG has been found at concentrations of 0.6-0.9 mg/ml . According to the results of an in vitro

study, bovine IgG at concentrations as low as 0.3mg/ml suppressed synthesis of human IgG, IgA and
IgM by up to 98%. Based on these findings, the study concluded that bovine milk has the potential to
modulate immune response in humans5. Other studies have demonstrated that raw milk from nonimmunised cows contains specific antibodies to E. coli, Salmonella enteriditis, S. typhimurium,
Shigella flexerni and human rotovirus.6,7
Lactoperoxidase

Lactoperoxidase is the most abundant enzyme in whey and has been shown to have anti-bacterial
effects across a range of species. Its effects are linked to its ability to reduce hydrogen peroxide,
1,8
catalysing peroxidation of thiocyanate and certain halides (including iodine and bromium) .
Lactoperoxidase appears to have the qualities of a stable preservative as it is not inactivated during
1
the pasteurisation process.

Mechanism of Action

Wheys antioxidant and detoxifying activity is most likely linked to its contribution to the synthesis of
glutathione (GSH). Cysteine (which contains an antioxidant thiol group) combines with glycine and
1
glutamate to form GSH . GSH is the major endogenous antioxidant produced by cells, providing
protection for RNA, DNA and proteins via its redox cycling from GSH (the reduced form) to GSSH
9
(the oxidised form) . Through direct conjugation, GSH detoxifies a host of both endogenous and
exogenous toxins including toxic metals, petroleum distillates, lipid peroxides, bilirubin and
9
prostaglandins.
Lactoferrins antioxidant and antimicrobial effects have already been touched on briefly. Due to its
ability to chelate iron, organisms requiring this metal to replicate would seem to be particularly
vulnerable to lactoferrins effects. Lactoferrin also demonstrates an ability to stimulate immune
1,10
responses involving natural killer (NK) cells, neutrophils and macrophage cytotoxicity .
Furthermore, a mouse study concluded that lactoferrin acts as an anti-inflammatory by regulating
11
levels of tumour necrosis factor (TNF) and interleukin 6 (IL-6).
The protein beta-lactoglobulin contains anti-hypertensive peptides which act as significant
12
angiotensin 1 converting enzyme (ACE) inhibitors . Cholesterol-lowering effects have also been noted
1
as a result of changes in micellar cholesterol solubility in the intestine.

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Whey Protein A functional food

Carol Bayford

Absorption

Whey proteins are considered to be fast proteins in that they reach the jejunum quickly after entering
the gastrointestinal tract. Once in the small intestine (SI), whey undergoes slow hydrolysis which
1
encourages greater absorption over the length of the SI . This superior absorption makes whey an
ideal optional source of vital protein for those with compromised GI function, such as ileostomy
1
patients . It is speculated that cancer patients undergoing chemotherapy may also benefit, as anti13
cancer therapies influence nutrient intake and absorption.

Clinical Indications
Cancer

A number of animal studies have examined wheys anticancer potential, believed to derive largely
1
from the antioxidant, detoxifying and immune enhancing effects of GSH and lactoferrin. In the
14
presence of lactoferrin, colon cancer induced in rats showed reduced tumour expression while
15
metastasis of primary tumours in mice was inhibited . Results of an in vitro study have also been
encouraging, demonstrating inhibition of growth in human breast cancer cells when treated with the
16
protein BSA.
A small number of clinical trials have been undertaken, proposing that high levels of GSH in tumour
1
cells confer resistance to chemotherapeutic agents . Of these, one study of 5 patients produced
17
conflicting results, highlighting the need for larger trials . In another, 20 patients with stage IV
malignancies were treated daily with 40g whey in combination with supplements such as ascorbic acid
and a multi-vitamin/mineral formulation18. Six months later the 16 survivors demonstrated increased
levels of NK cell function, GSH, haemoglobin and haematocrit. Unfortunately the study did not
include a comparison with whey alone.
Whey may also have a role to play as part of an integrated approach which combines nutrition,
exercise and hormonal support to counteract the muscle-wasting frequently associated with cancer.
Professor Vickie Baracos explores the feasibility of using this sports medicine model in her article
19
New Approaches in Reversing Cancer-related Weight Loss . She highlights that this combination
has already been adopted by researchers exploring muscle wasting in other groups: the elderly,
patients with wasting syndromes associated with AIDS and COPD (chronic obstructive pulmonary
disease).

Hepatitis B

Although an initial in vitro study found that bovine lactoferrin prevented hepatitis C virus (HCV) in a
20
human hepatocyte line , subsequent trials have proved inconclusive. However, results for hepatitis B
virus (HBV) have been more positive, particularly an open study on 8 patients taking 12g of whey
daily. Subjects demonstrated improved liver function markers, decreased serum lipid peroxidase
21
levels and increased IL-2 and NK activity.

Human Immunodeficiency Virus (HIV)

Individuals with HIV commonly have low levels of GSH . Several studies have sought to address this
by testing the effect of whey protein on the GSH levels of HIV-positive subjects. In one instance, 18
participants were randomised to receive daily doses of 45g whey protein from two different products
22
over a six month period . Only one of the products significantly elevated GSH levels (Protectamin,
manufactured by Fresenius Kabi, Germany), a result that may be related to production at differing
isolation temperatures and non-comparable amino acid profiles.

Cardiovascular Disease

According to the results of a number of studies, milk intake and milk products can lower blood
1
pressure and reduce the risk of hypertension . In one particular eight week trial, 20 healthy men were

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Whey Protein A functional food

Carol Bayford

given a combination of fermented milk and whey protein concentrate to establish whether serum
23
lipids and blood pressure would be affected . The placebo group received only unfermented milk.
After eight weeks, the fermented milk group demonstrated comparatively higher HDLs, lower
triglycerides and reduced systolic blood pressure. The effect of whey alone was not studied.

Osteoporosis

Milk basic protein (MBP) is a component of whey which demonstrates the ability to not only suppress
1
bone resorption, but also to stimulate proliferation and differentiation of osteoblastic cells . MBP
contains largely lactoferrin and lactoperoxidase. Animal studies suggest that lactoferrin may be the
key active component, mediating its effects through two main pathways: LRP1 (a low-density
lipoprotein receptor-related protein which endocytoses lactoferrin into the cytoplasm of primary
24
osteoblasts) and p42/44 MAPK (which stimulates osteoblast activity) . A number of clinical trials
support MBPs positive effects in both men and women, the latter ranging in age from young to post25, 26,27
menopausal
. Daily doses of MBP 40mg (equivalent to 400-800 mL of milk) appear to be
sufficient to produce significantly increased bone mineral density and reduced bone resorption.

Stress Adaptation

Whey enriched with the protein alpha-lactalbumin has been shown to improve cognitive performance
28,29
and mood in stress-vulnerable subjects
. Alpha-lactalbumin is particularly high in tryptophan and
the authors propose that this acts as a substrate to increase serotonin levels which may be vulnerable
to depletion by chronic stress. After the studies, subjects all showed higher ratios of plasma TrpLNAA (the ratio of plasma tryptophan to the sum of the other large neutral amino acids), believed to
be an indirect indication of brain serotonin function.

Gastrointestinal Support

Whey is used as a gastrointestinal supporter by health professions such as Nutritional Therapy

Practitioners. Its mucosa-protective effects are well-proven by several animal studies and are likely to
1
be associated with its GSH-stimulating properties . In addition to its role in GSH synthesis, the amino
acid glutamate may play a further role when it is converted to glutamine, an amino acid utilised as a
30,31
fuel by intestinal mucosa

Choosing the Right Whey Product

Given the variety of different whey products available, it is possible to select products for specific
clinical indications. For athletes or those looking for a highly-absorbable, low allergenicity protein
source, hydrolysed whey with its readily available di- and tri-peptides - may be a good option. For
the immune-compromised or microbe-challenged, undenatured wheys high levels of lactoferrin and
immunoglobulins may be helpful.

Comparison of Whey with Pea and Soy Protein Powders

Despite no serious adverse reactions to whey powders having been reported, they may not be suitable
1
for those with frank milk allergies . That said, it is worth noting that casein which is not a
component of whey - is often the culprit for dairy-sensitive individuals. Although most whey proteins
are processed to remove all but trace amounts of lactose, for the lactose-intolerant, a de-lactosed whey
may be a more sensible option. Prior to using therapeutic quantities, a challenge test with a small
1
amount of the proposed whey product would certainly be advisable for those with dairy sensitivities.
Non-dairy protein powders are an alternative for individuals with dairy issues, including vegans.
Table 2 below compares the amino acid profile of specific whey, pea and soy protein powders and
highlights possible clinical indications for each.
Table 2: Comparison of Whey, Pea and Soy Protein Powders
Amino Acids

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Whey32

Pea33

Soy34

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Whey Protein A functional food

(*=Essential)

Alanine
Arginine
Aspartic Acid
Cysteine
Glutamic Acid
Glycine
Histidine
Isoleucine (BCAA)*
Leucine (BCAA)*
Lysine*
Methionine*
Phenylalanine*
Proline
Serine
Threonine*
Tryptophan*
Tyrosine
Valine (BCAA)*

(Metagenics Perfect
Protein microfiltered isolate)
g/100g
4.00
1.43
8.78
1.83
13.57
1.43
1.30
4.70
8.09
6.87
1.74
2.30
4.26
3.52
5.35
1.43
2.35
4.48
A comprehensive
functional food which
supplies key proteins such
as lactoferrin and
immunoglobulins in
addition to amino acids.

Carol Bayford
(Kirkman Pea Protein
Powder)
g/100g
5.04
8.71
12.43
0.76
13.74
4.64
2.52
5.59
8.44
6.82
1.31
6.13
5.29
4.80
4.34
1.06
3.12
5.27
Ideal for vegetarians
and/or individuals with
sensitivity issues.

(NutraBio Soy Protein

Isolate)
g/100g
3.80
6.70
10.20
1.10
16.80
3.70
2.30
4.30
7.20
5.60
1.10
4.60
4.50
4.60
3.30
1.20
3.30
4.40
Suitable for vegetarians
and those with sensitivity
issues, although soy may
be a problem for some. A
source of isoflavones
which may have possible
positive effects on heart
disease, menopausal
symptoms, osteoporosis
and breast/prostate
cancers

The relatively high levels of arginine in both pea and

soy protein powders may stimulate the onset of
Herpes simplex in susceptible individuals, as this
35
amino acid is essential for replication of the virus

Conclusion

Whey protein is a complex functional food which reflects its wide range of potential therapeutic
applications. The variety of available products allows for a tailored clinical approach although caution
is advised if dairy sensitivity is suspected. In these cases, non-dairy options such as pea or soy protein
powders may be viable alternatives.
About the Author
Carol Murrell is a qualified nutritional therapist who trained at the Centre for Nutrition &
Lifestyle Management (CNELM) in Wokingham. A keen runner and cyclist, her areas of
special interest include sports nutrition from a nutritional therapy perspective, womens
health and cancer care. She is also a qualified NLP (Neuro Linguistic Programming)
practitioner and uses these powerful techniques to help individuals effect change in their
lives. Carol is a Professional Member of the South African Association of Nutritional

The Nutrition Practitioner

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Whey Protein A functional food

Carol Bayford

References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.

13.
14.
15.
16.
17.
18.

19.
20.
21.
22.
23.

24.
25.

Marshall, K., 2004. Therapeutic Applications of Whey. Alternative Medicine Review, 9 (2): 136-156
Caccavo, D., 2002. Review: Antimicrobial and immunoregulatory functions of lactoferrin and its potential
therapeutic application. Journal of Endotoxin Research, 8 (6): 403-417
Gutteridge, J.M.C, Paterson, S.K., Segal, A.W. et al., 1981. Inhibition of lipid peroxidation by the iron-binding
protein lactoferrin. Biochem J., 199 (1): 259-261
Nemet, K., Simonovits, I., 1985. The biological role of lactoferrin. Haematologica (Budap)., 18 (1): 3-12
Kulczycki, A., Macdermott, R.P., 1985. Bovine IgG and Human Immune responses: Con A-Induced Mitogenesis of
Human Mononuclear Cells is Suppressed by Bovine IgG. Int.l Arch. Allergy and Immunology, 77 (1-2) : 255-258
Losso, J.N., Dhar, J., Kummer, A. et al., 1993. Detection of antibody specificity of raw bovine and human milk to
bacterial lipopolysaccharides using PCFIA. Food and Agricultural Immunology, 5 (4): 231-239
Yolken, R.H., Losonsky, G.A., Vonderfecht, S. et al., 1985. Antibody to human rotovirus in cows milk. The New
England Journal of Medicine, 312 (10): 605-610
Bjorck, L., 1978. Antibacterial effect of the lactoperoxidase system on psychrophic bacteria in milk. Journal of
Dairy Research, 45: (109-118)
Bland, J.S., Costarella, L., Levin, B. et al. (2004). Clinical Nutrition A Functional Approach. 2nd ed. Gig
Harbour: The Institute for Functional Medicine
Gahr, M., Speer, C.P., Damerau, B. et al., 1991. Influence of lactoferrin on the function of human
polymorphonuclear leukocytes and monocytes. Journal of Leukocyte Biology, 49(5): 427-433
Machnicki, M., Zimecki, M., Zagulski, T., 1993. Lactoferrin regulates the release of tumour necrosis factor alpha
and interleukin 6 in vivo. Int J Exp Pathol., 74(5): 433-439
Pihlanto-Leppala, A., Koskinen, P., Piilola, K. et al., 2000. Angiotensin 1-converting enzyme inhibitory properties
of whey protein digests : concentration and characterisation of active peptides. Journal of Dairy Research, 67: 5364
Lindsey, A.M., 2005. Cancer cachexia: Effects of the disease and its treatment. Nutrition and Cancer, 2 (1): 19-29
Kazunori, S., Watanabe, E., Nakamura, J. et al., 1997. Inhibition of Azoxymethane-initiated Colon Tumour by
Bovine Lactoferrin Administration in F344 Rats. Cancer Science, 88 (6): 523-526
Yoo, Y.C., Watanabe, S., Watanabe, R., et al., 1998. Bovine lactoferrin and Lactoferricin inhibit tumour metastasis
in mice. Adv Exp Med Biol., 443: 285-91
Laursen, I., Briand, P., Lykkesfeldt, A.E., 1990. Serum albumin as a modulator on growth of the human breast
cancer cell line, MCF-7. Anticancer Res., 10 (2A): 343-51
Kennedy, R.S., Konok, G., Bounous, G., et al., 1995. The Use of Whey Protein Concentrate in the Treatment of
Patients with Metastatic Carcinoma : A Phase I-III Clinical Study. Anticancer Res., 15: 2643-2650
See, D., Mason, S., Roshan, R., 2002. Increased Tumour Necrosis Factor Alpha (TNT-) And Natural Killer Cell
(NK) Function Using An Integrative Approach In Late Stage Cancers. Immunological Investigations, 31 (2): 137153
Baracos, V.E., 2004. New Approaches in Reversing Cancer-related Weight Loss. Oncology Issues, 9 (2): 5-10
Ikeda, M., Sugiyama, K., Tanaka, T. et al., 1998. Lactoferrin Markedly Inhibits Hepatitis C Virus Infection in
Cultured Human Hepatocytes. Biochemical and Biophysical Research Communication, 245 (2): 549-553
Watanabe, A., Okada, K., Shimizu, Y. et al., 2000. Nutritional therapy of chronic hepatitis by whey protein (nonheated). J Med., 31 (5-6): 283-302
Micke, P., Beeh, K.M., Buhl, R., 2002. Effects of long-term supplementation with whey proteins on plasma
glutathione levels of HIV-infected patients. European Journal of Nutrition, 41 (1): 12-18
Kawase, M., Hashimoto, H., Hosoda, M. et al., 2000. Effect of Administration of Fermented Milk Containing Whey
Protein Concentrate to Rats and Healthy Men on Serum Lipids and Blood Pressure. Journal of Dairy Science,83 (2):
255-263
Naot, D., Grey, A., Reid, I.R. ert al., 2005. Lactoferrin a Novel Bone Growth Factor. Clin Med Res., 3 (2): 93101
Toba, Y., Takada, Y., Matsuoka, Y. et al., 2001. Milk Basic Protein Promotes Bone Formation and Suppresses
Bone Resorption in Healthy Adult Men. Bioscience, Biotechnology and Biochemistry, 65 (6): 1353-1357

The Nutrition Practitioner

Spring 2010

Whey Protein A functional food

26.
27.
28.

29.

30.
31.
32.
33.
34.
35.

Carol Bayford

Uenishi, K., Ishida, H., Toba, Y. et al., 2007. Effect of milk basic protein on bone metabolism in healthy young
women. Osteoporosis International, 18 (3): 385-390
Aoe, S., Koyama, T., Toba, Y. et al., 2005. A controlled trial of the effect of milk basic protein (MBP)
supplementation on bone metabolism in healthy menopausal women, 16 (12): 2123-2128
Markus, C., R., Olivier, B., de Haan, E., 2002. Whey protein rich in alpha-lactalbumin increases the ratio of plasma
tryptophan to the sum of the other large neural amino acids and improves cognitive performance in stress-vulnerable
subjects. American Journal of Clinical Nutrition, 75 (6): 1051-1056
Markus, C.,R., Olivier, B., Panhuysen, G.E.M. et al., 2000. The bovine protein alpha-lactalbumin increases the
plasma ratio of tryptophan to the other large neural amino acids, and in vulnerable subjects raises brain serotonin
activity, reduces cortisol concentration and improves mood under stress. American Journal of Clinical Nutrition, 71
(6): 1536-1544
Braverman, E.R. (1987). The Healing Nutrients Within. 3rd Ed. Laguna Beach: Basic Health Publications, Inc.
ODwyer, T., 1989. Maintenance of Small Bowel Mucosa with Glutamine-Enriched Parenteral Nutrition. Journal
of Parenteral and Enteral Nutrition, 13 (6): 579-585
Metagenics Practitioner Range Catalogue
Kirkman. Pea Protein Powder. Available from: www.kirkmanlabs.com/ViewProduct [Accessed 9 March 2010]
NutraBio.com. Soy Protein Isolate (Supro). Available from : www.nutrabio.com/Products [Accessed 28 March
2010]
Becker, Y., Olshevsky, U., Levitt, J., 1967. The Role of Arginine in the Replication of Herpes Simplex Virus. J
Gen Virol., 1: 471-478

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