|If you've got brawn and brain you will realize that whey is much more than a potent muscle builder.|
If you've read almost all ~2,000 SuppVersity articles, you will even know about the GLUT4 and thus glucose uptake promoting effects isoleucine containing dipeptides in whey protein hyrolysates, but I guess that some of the other benefits whey protein owes to its complex mixture of proteins and peptides are going to be news for you.
In their latest paper in the Austin Journal of Nutrition and Food Science Rie Tsutsumi and Yasuo M. Tsutsumi provide a concise overview of the biological effects of a range of peptides and proteins in whey protein. The latter include...
Amino acid composition of whey, casein and breast milk - whey excells in terms of pro-anabolic BCAAs (McDonough. 1974)
- whey protein has the highest biological value (indicative of the most balanced EAA profile) of all dairy proteins (the biological value is the ratio of the amount of nitrogen that is consumed to the amount of nitrogen that is absorbed, and this value is 74 for soy protein, 71 for casein, and 104 for whey protein)
- whey protein has the highest protein efficacy ratio, i.e. the body weight increase associated with an intake of 1 g protein is 3.0 (vs. 2.0 for soy protein and 2.5 for casein protein)
- b-lactoglobulin binds retinol (vitamin A) and promotes uptake of retinol via gut; by a similar mechanism it may also facilitate the uptake of long-chain fatty acids
- a-lactoalbumin kills tumour cells (in vitro) and exerts anti-bacterial effects in the upper respiratory systems; it has also been shown to have protective effects on gastric mucosa.
- serum albumin binds and carries fatty acids and bile pigment
- immuno-globulin G involves with bactericidal (anti-bacterial) effects with complements and prevents bacteria from adhering to tissues; neutralizes toxins and viruses
- immuno-globulin A inhibits growth of various bacteria by condensing them; prevents bacteria from adhering to the surface of mucosa; neutralizes toxins produced by viruses and bacteria.
- immuno-globulin M has the same effects as IgG, but its bioactivity is stronger
- lactoperoxidase catalyzes the reaction of producing cyanogen ion with strong bactericidal power from cyanic ion and hydrogen peroxide in the body
- lysozyme kills bacteria by destroying cell walls
"Cysteine, which contains an antioxidant thiol group, combines with glycine and glutamate to form GSH. GSH is the major endogenous antioxidant produced by cells, providing production for RNA, DNA, and proteins via its redox cycling from the reduced form, GSH, to the oxidized form, GSSH. Though direct conjugation, GSH detoxifies a host of endogenous and exogenous toxins including toxic metals, petroleum distillates, lipid peroxides, bilirubin, and prostaglandins." (Tsutsumi. 2014)The antioxidant and antimicrobial effects of lactoferrin have already been mentioned above. In addition, lactoferrin demonstrates an ability to stimulate immune responses involving natural killer cells, neutrophils, and macrophage cytotoxicity. Furthermore, a mouse study concluded that lactoferrin acts as an anti-inflammatory by regulating the levels of tumor necrosis factor and interleukin-6.
"Owing to its ability to chelate iron, organisms requiring iron for replication appear to be particularly vulnerable to the effects of lactoferrin. The protein beta-lactoglobulin contains anti-hypertensive peptides, which lower blood pressure as significantly as angiotensin converting enzyme (ACE) inhibitors. Cholesterol-lowering effects have also been noted as a result of changes in micellar cholesterol solubility in the intestine." (Tsutsumi. 2014)Moreover, the formation of peptides through the hydrolysis of whey proteins in your tummy is a rather novel, but very interesting effect that may well contribute to the beneficial health effects of whey proteins. In fact, whey peptide is one of the major peptides that inhibit ACE (FitzGerald. 2004), which induces blood-pressure regulating effects.
It is very likely that peptides are also responsible for many of the metabolic benefits
Pal et al. demonstrated a decrease in fasting plasma concentrations of triacylglycerols after long-term whey protein intake (12 weeks) in overweight and obese individuals (Pal. 2010a,b,c). And while the mechanisms behind the effects of whey protein on triacylglycerols are not understood, Mortensen et al. proposed that a meal containing whey might have resulted in reduced production of chylomicrons and accelerated chylomicron clearance resulting from the stimulation of lipoprotein lipase by whey.
|Figure 2: Changes in insulin and HOMA-IR (insulin resistance) insulin response to 12 weeks on 27g of whey vs. casein (vs. control) in overweight / obese subjects (Pal. 2010b)|
Pal et al. are obviously not the only ones, who observed significant beneficial effects on glucose management in response to the ingestion of whey protein supplements. As Tsutsumi & Tsutsumi point out "[t]he majority of these studies reported that whey protein intake decreases blood glucose and insulin levels" (Tsutsumi. 2014)
Whey a source of bioactive anti-diabetic, pro-satiety peptides?
The latter is interesting, because we know that in type II diabetics, whey protein will increase not decrease the insulin response. I that, the acute effects of whey protein on postprandial blood glucose are comparable to sulfonylureas and other insulin secretagogues used for the pharmaceutical management of hyperglycemia in type 2 diabetes. A benefit that is probably related to bioactive peptides and amino acids that are generated during gastrointestinal digestion and enhance the release of several hormones (including insulin) which are able to reduce the food intake and increased satiety (e.g. cholecystokinin, peptide YY, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1)). How exactly this works is still being researched, but both, ...
Figure 3: Effects of 48 g casein (full circles) or whey (open squares) on GLP-1 (Hall. 2003)
- a mechanism that involves BCAAs, specifically leucine, which activates the mTOR signaling pathway and protein synthesis leading to elevated hormone expression and secretion and increased thermogenesis
I won't bore you with the muscle building effects of whey: You just have to click here to see previous articles on whey protein, if you actually feel you need to know more about the muscle-building prowess of whey protein.If whey protein helps prevent or even cure diabesity it will also help to prevent a hell lot of the side effects of being an overweight type II diabetic. And still, researchers believe that there may be a more direct link than diabesity prevention to the following health benefits of whey protein that are listed in Tsutsumi & Tsutsumi's latest review (the following bulletpoints are in large parts direct quotes from Tsutsumi. 2014):
- cancer -- A number of animal studies have examined the anti-cancer potential of whey, believed to be primarily associated with the antioxidizing, detoxifying, and immune-enhancing effects of GSH and lactoferrin.
A few clinical trials have been undertaken, proposing that high levels of GSH in tumor cells confer resistance to chemotherapeutic agents. One of these studies showed that 20 patients with stage IV malignancies were treated daily with 40 g whey in combination with supplements such as ascorbic acid and a multi-vitamin/mineral formulation (See. 2002). The 16 survivors demonstrated increased levels of natural killer cell function, GSH, hemoglobin, and hematocrit 6 months later. An aggressive combination of immunoactive nutraceuticals was effective in significantly increasing natural killer function, other immune parameters, and plasma hemoglobin in patients with late stage cancers.
- hepatitis B & C -- The results of trials for the hepatitis B virus have been positive, particularly those from an open study that included 8 patients administered 12 g non-heated whey/day. The patients demonstrated improved liver function markers, decreased serum lipid peroxidase levels, and increased interleukin-2 and natural killer cell activity (Watanabe. 1999)
Regarding hepatitis C, several trials have proved inconclusive, although an initial in vitro study found that bovine lactoferrin prevented the hepatitis C virus in a human hepatocyte line (Ikeda. 1998)
Figure 4: Next to reductions in blood pressure, whey induced reductions in blood lipids are a likely mechanism behind the reduced CVD risk with whey (illustration from Pal. 2013)
- hypertension --Various investigators have hypothesized that certain bioactive peptides formed through the hydrolysis of food proteins have the ability to inhibit ACE, and this subject has been comprehensively reviewed in a number of studies. In general, it has been claimed that a diet rich in foods containing anti-hypertensive peptides is effective for the prevention and treatment of hypertension. ACE-inhibitory peptides may be obtained from precursor food proteins via enzymatic hydrolysis, the use of viable or lysed microorganisms, or specific proteases.
However, studies relating to whey peptides with ACE inhibitory activities are more limited; this may be due to the rigid structure of beta-lactoglobulin, which makes it particularly resistant to digestive enzymes.
- osteoporosis -- Milk basic protein (MBP) is a component of whey that demonstrates the ability to not only suppress bone resorption but also stimulate proliferation and differentiation of osteoblastic cells (Marshall. 2004).
The role of calcium intake in determining bone mineral mass is well recognized to be the most critical nutritional factor to achieve optimal peak bone mass; milk protein is also important for preventing osteoporosis. A number of clinical trials support milk protein’s positive effects in both men and women, the latter ranging in age from young to postmenopausal. Daily doses of 40 mg MBP (equivalent to 400–800 mL milk) appear to be sufficient to significantly increase bone mineral density and reduce bone resorption.
Recently, de Moura et al. evaluated the effects of whey protein intake on the expression of heat shock protein HSP70 (de Moura. 2013). HSP70 confers cellular tolerance against stressors, and there was a greater increase in the HSP70 expression in the soleus, gastrocnemius, and lungs of the whey protein hydrolysate-fed rats than in the casein-fed rats.
- de Moura, Carolina Soares, et al. "Whey protein hydrolysate enhances the exercise-induced heat shock protein (HSP70) response in rats." Food chemistry 136.3 (2013): 1350-1357.
- FitzGerald, Richard J., Brian A. Murray, and Daniel J. Walsh. "Hypotensive peptides from milk proteins." The Journal of Nutrition 134.4 (2004): 980S-988S.
- Hall, W. L., et al. "Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion, and appetite." British Journal of Nutrition 89.02 (2003): 239-248.
- Havea, Palatasa, Harjinder Singh, and Lawrence K. Creamer. "Characterization of heat-induced aggregates of β-lactoglobulin, α-lactalbumin and bovine serum albumin in a whey protein concentrate environment." Journal of Dairy Research 68.03 (2001): 483-497.
- Ikeda, Masanori, et al. "Lactoferrin markedly inhibits hepatitis C virus infection in cultured human hepatocytes." Biochemical and biophysical research communications 245.2 (1998): 549-553.
- Markus, C. Rob, Berend Olivier, and Edward HF de Haan. "Whey protein rich in α-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." The American journal of clinical nutrition 75.6 (2002): 1051-1056.
- Marshall, Keri N. D. "Therapeutic applications of whey protein." Alternative Medicine Review 9.2 (2004): 136-156.
- Pal, Sebely, and Vanessa Ellis. "The chronic effects of whey proteins on blood pressure, vascular function, and inflammatory markers in overweight individuals." Obesity 18.7 (2010a): 1354-1359.
- Pal, Sebely, Vanessa Ellis, and Satvinder Dhaliwal. "Effects of whey protein isolate on body composition, lipids, insulin and glucose in overweight and obese individuals." British journal of nutrition 104.05 (2010b): 716-723.
- Pal, Sebely, Vanessa Ellis, and Suleen Ho. "Acute effects of whey protein isolate on cardiovascular risk factors in overweight, post-menopausal women." Atherosclerosis 212.1 (2010c): 339-344.
- Pal, Sebely, and Simone Radavelli‐Bagatini. "The effects of whey protein on cardiometabolic risk factors." Obesity Reviews 14.4 (2013): 324-343.
- See D, Mason S, Roshan R. "Increased tumor necrosis factor alpha (TNFalpha) and natural killer cell (NK) function using an integrative approach in late stage cancers." Immunol Invest 21 (2002):137-153.
- Smithers, Geoffrey W. "Whey and whey proteins—from ‘gutter-to-gold’." International Dairy Journal 18.7 (2008): 695-704.
- Tsutsumi, R., and Y. M. Tsutsumi. "Peptides and proteins in whey and their benefits for human health." Austin J Nutri Food Sci 1.1 (2014): 9.
- Watanabe, Akiharu, et al. "Nutritional therapy of chronic hepatitis by whey protein (non-heated)." Journal of medicine 31.5-6 (1999): 283-302.