Milk, a Glucose Uptake Promoter That's More Than the Sum of Its Parts. Plus: HICA & HMB in Yogurt. How Much EAA in Your Protein? Raw Milk Does not Cure Lactose Intolerance

Milk is one of the few foods that are advertized by celebrities that could actually be good for you (photo from the "Got Milk" campaign)

I hope you are not fed up with milk and dairy, yet, because today's SuppVersity short news have a ton of it. What exactly?

Well, after taking a closer look at the surprisingly high amount of HICA and the comparatively small amount of HMB in yogurt and reviewing the EAA content of six common protein sources, we are going to delve deeper into the latest evidence that shows that milk is much more than the sum of its parts, i.e. milk protein, lactose and fat and conclude on a note on another widely known Internet myth that says that people with lactose intolerance could drink raw milk without a problem.

You can learn more about dairy at the SuppVersity

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Lactulose For Your Gut & Overall Health

Is There a "Fat Advantage" for Dairy Lovers

Dairy, Diabetes, Estrogen, IGF-1, Cancer & More

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  Figure 1: Amount of HICA & HMB (in µg/L) in commercial whole milk and yogurt (Ehling. 2014)

  Significant amounts of HMB and specifically HICA in yogurt. We all know that yogurt is among the dairy products with the most evidence of significant health benefits. That yogurt could be a decent muscle builder, on the other hand, would be news.
  
  With ~5 mg of β-hydroxy-β-methylbutyric acid (HMB) and up to 12.5 mg of α-hydroxyisocaproic acid (HICA) yogurt would have what it takes if the values of HMB and HICA Stefan Ehling and Todime M. Reddy measured in regular yogurt were on a per gram, not a per liter basis (Ehling. 2014).
• How much EAA in my protein? Since I have been repeatedly questioned about the essential amino acid content in whey, milk, soy, and egg protein. I have published Table 1 which originally appeared in a 2010 study by Hulmi et al. on Facebook, already.

  

  Table 1: Approximate amino acid composition of popular protein powders (Hulmi. 2010)

  For those of you who are missing out on the daily 12+ SuppVersity Facebook News, because they haven't liked www.facebook.com/SuppVersity, yet. I will now publish it again - as a reference source, if you will.
• Milk a glucose uptake promoter that's more than the sum of its parts. In view of the fact that we have already two dairy related news in today's SuppVersity article, I decided to have another "milky news" in today's SuppVersity short news item. One all the milk-drinkers among the SuppVersity readers will cherish.
  
  Recently, Shirin Panahi and colleagues from the University of Toronto, the Mount Saint Vincent University and the University of Guelph published the results of a randomized, cross-over study that was conducted to prove / disprove the hypothesis that

  "[T]hat regulation of postprandial glycemia after milk consumption occurs through both insulin and insulin-independent actions due to interactions among its macronutrient components and energy content. The objective was to compare the effects of isovolumetric (500ml) beverages of whole milk (3.25% M.F.), each of its macronutrient components (protein, lactose and fat) and their combination (a simulated milk beverage) on postprandial glycemia, glucoregulatory and gastrointestinal hormones and gastric emptying in healthy young men" (Panahi. 2014).

  In the course of the study, the 12 young, male subjects consumed beverages containing 500 ml of whole milk (3.25% M.F.) (control), a simulated milk beverage based on milk macronutrients or milk protein (16g), lactose (24g) and milk fat (16g) in isolation.

  

  Table 2: Nutritional composition of the test meals | ^a Composition of each beverage as provided by
  the manufacturer; ^b amounts given are per 500ml serving. Paracetamol (1.5g), vanilla extract (1.2ml)
  and sucralose (0.02g) were added to all beverages (Panahi. 2014).

  What the researchers found was that both the whole and simulated milk had similar beneficial effects on blood glucose rise after their "meal" (drink), but as it turned out the simulated milk resulted in a significantly higher (41%) glucagon-like peptide-1 (GLP-1) production and lower (43%) ghrelin areas under the curve (AUC) than whole milk (P=.01 and P=.04, respectively).

  

  Figure 2: Glucose, insulin, c-peptite, rate of insulin secretion, GLP-1, PYY, CKK
  and ghrelin levels after the test "meals" expressed relative to the sum of the effects
  of the same amount of milk protein, lactose and fat (Panahi. 2014)

  Now, all that would hardly be newsworthy (at least not for regular SuppVersity readers, if the two samples, i.e. both the whole and simulated milk, didn't lower the glucose (P=.0005) levels more than predicted by the sum of AUCs for their components (see Figure 2)!

  "Adjusted for energy content, milks produced lower glucose and hormone responses than predicted from the sum of their components. The effect of protein/kcal on the AUCs was higher than fat/kcal for insulin, C-peptide, insulin secretion rate, GLP-1, CCK and paracetamol (P < .0001), but similar to lactose except for CCK and paracetamol, which were lower. The response in PYY and ghrelin was similar per unit of energy for each macronutrient" (Panahi. 2014).

  In other words: Milk is way more than the sum of it's parts. In that, the "regulation of postprandial glycemia after milk consumption occurs through both insulin and insulin-independent actions due to interactions among its macronutrient components and energy content to achieve lower postprandial glycemia than predicted from the sum of its components" (Panahi. 2014).

If you haven't read it, already, take a look at my rebuttal to the latest assault on milk | read more

Bottom line: Quite the "milky" short news, right? Well, I guess it may be worth topping off all these good news about dairy products with a bad one. The common "Internet wisdom" that raw milk could offset the problems of people with lactose intolerance is a myth.

According to a 2014 paper by Sarah Mummah et al. who tested this myth in 16 adults with self-reported lactose intolerance and lactose malabsorption confirmed by hydrogen (H2) breath testing, "raw milk fail[s] to reduce lactose malabsorption or lactose intolerance symptoms compared with pasteurized milk among adults positive for lactose malabsorption." (Mummah. 2014) The "raw milk can be consumed by anyone" anecdote does thus belong to the realms of scientifically unwarranted die-hard bro-science | Comment on Facebook!

References:

• Ehling, Stefan, and Todime M. Reddy. "Investigation of the Presence of β-Hydroxy-β-methylbutyric Acid and α-Hydroxyisocaproic Acid in Bovine Whole Milk and Fermented Dairy Products by a Validated Liquid Chromatography–Mass Spectrometry Method." Journal of agricultural and food chemistry 62.7 (2014): 1506-1511.
• Hulmi, Juha J., Christopher M. Lockwood, and Jeffrey R. Stout. "Review Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein." (2010).
• Mummah, Sarah, et al. "Effect of Raw Milk on Lactose Intolerance: A Randomized Controlled Pilot Study." The Annals of Family Medicine 12.2 (2014): 134-141. 
• Panahi, Shirin, et al. "Mechanism of action of whole milk and its components on glycemic control in healthy young men." The Journal of nutritional biochemistry (2014).

True or False: α-Hydroxy-Isocaproic Acid aka HICA is a Potent Anti-Catabolic, Just Like the Shiny Ads Say

Even Arnold benefited from α-hydroxy-isocaproic acid aka HICA - the HICA his body produced and the HICA he got from his diet, whenever he ate cheese and other fermented foods.

You know that I am not the kind of person who likes to tell others what to do. After reading my summary of the contemporary research on α-hydroxy-isocaproic acid aka HICA, you should yet be able to decide whether it's worth a try or not.

If you take a look at the pertinent databases you will realize that there are more patents than papers on α-hydroxy-isocaproic acid - usually, this is a good indicator we are dealing with another industry scam, but in contrast to the many funky forms of creatine, α-hydroxy-isocaproic acid does actually have a handful of studies to back up that it does... or I should say "that it could" help you getting big and buffed.

If I had to chose between HMB and HICA, I would choose HMB... or better stick to whey!

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That being said, it may be worth taking a look at what α-hydroxy-isocaproic acid actually is. Just like HMB which is about to make a comeback in liquid form, these days, HICA is a metabolite of the mTOR and thus protein synthesis triggering branch-chained amino acid leucine. It is also known as "leucic acid" or "DL-2-hydroxy-4-methylvaleric acid" and is formed by α-hydroxylaction from leucine. It's one of the end-products of leucine metabolism in muscle and connective tissue (Walser. 1978). It's usual concentration in our blood is about 0.2560.02 mmol/L - that's ~100x less than the amount of α-keto-isocaproic acid (KIC), the corresponding keto acid of leucine of which you'll find more than 21 mmol per liter in your blood.

Figure 1: Relative changes in lean mass (%) during 4 weeks of intense soccer training on 1.5g/day HICA (Mero. 2010)

Cheese, wine, soy sauce, etc. - the recently celebrated fermented foods, they all contain HICA, which appears to be the anti-catabolic counterpart to leucine. While the latter is a potent promoter of protein synthesis, the former appears to make sure that the work of its predecessor leucine is not lost.

It is thus no wonder that the promising results of a 2010 study by Mero et al. were recorded during an intensive and thus potentially catabolic training period in soccer athletes. In contrast to the placebo group, where only one individual gained a significant amount of lean mass, while 4 lost muscle, the subjects who had been consuming 1.5g/day of α-hydroxy-isocaproic acid gained 300g of lean mass, on average, in the course of the 4-week study.

That's not much and it was not fat free (ca. 150g of fat), but the data in Figure 1 shows that this is a difference between minimal muscle loss and gain... and I guess most athletes would prefer a marginal muscle gain over a marginal loss of lean mass.

HICA, a potent anti-catabolic? I don't think so!

The notion that HICA is, above all, a muscle loss inhibitor appears questionable, if we take a look at the results Charles H. Lang, Hugues Magne, Elizabeth Offord and Denis Breuille presented at a 2013 FASEB meeting. In the abstract to their presentation they cite the results of a rodent study in the course of which the rodents were immobilized for two full weeks. The consequence, an increase in the expression of catabolic hormones and a profound loss of muscle mass was identical in both the HICA and placebo supplemented groups, but in spite of the fact that "αHICA did not alter the immobilization-induced increase in proteasome activity and atrogene expression", the muscle mass had returned to control values only in αHICA-fed rats after 14 days.

No performance enhancing effects: In spite of the increase in muscle size (or should I say absence of a decrease?) Mero et al. didn't record any performance enhancing effects of HICA in their study w/ professional soccer players. Minimal muscle gain, yes. Reduced DOMS, yes, even that. Increased performance? No. As the authors point out, the study period (4 weeks) may have been to short. That's correct, but if you take another look at the data in Figure 1 you would still expect to see marginal differences, at least, right?

The fast recovery in the HICA group was associated with increased muscle protein synthesis and higher levels of the "protein synthesis pump initiator proteins" S6K1 and 4EBP1 in the previously immobilized muscle. The results Lang et. al. have not yet published in a full paper (at least I couldn't find it) put a huge questionmark behind the long-heralded hypothesis that HICA supplementation would slow muscle loss and puts it in line with its cousin HMB and its precursor leucine as a purported pro-anabolic muscle builder.

Figure 2: Gastrocnemius weight (rel. to control) immediately before and 14-days after the immobilization (Lang. 2013).

The data from the corresponding full paper the authors published a couple of month later in the American Journal of Physiology - Endocrinology and Metabolism you see in Figure 2 are even more impressive, though. According to this rodent data HICA is a more potent muscle (re-)builder than leucine; and, importantly, neither of the two does what the industry keeps promising: prevent muscle catabolism in response to disuse.

Bottom line: A confirmation of Lang's results in humans and/or a resistance training scenario like the one Wilson et al. did for the free acid form of HMB recently ("Breakthrough HMB Research: Additional(!) 10% Reduction in Body Fat, 5% Higher Lean Mass + 2x Higher Strength Gains After 12W of Heavy Lifting in Trained Individuals" | read more) are yet still missing. Aside from the previously cited soccer player study by Mero et al. we do have...

• a paper by Chow & Walser (1975) who report that leucine and its α-hydroxy analog (HICA) promote muscle growth equally effective, although replacement of leucine with HICA reduced food intake and increased the volume of urine and its nitrogen concentration
• a study by Woods & Goldman (1979) who report that HICA can be used as a leucine replacement in the diet without reducing food intake or growth of the animals

...and thus not enough arguments for me to spend money on currently hilariously overpriced α-hydroxy-isocaproic acid, but I am running a non-profit blog, so if you are making big money with a website or whatever else and want to give it a try - there is no evidence that HICA may harm anything but your purse.

Reference:

• Chow K., and Walser M. "Effects of substitution of methionine, leucine, phenylalanine, or valine by their alpha-hydroxy analogs in the diet of rats." J Nutr 1975;105(3):372 8
• Lang, Charles H., et al. "Chronic α-hydroxyisocaproic acid treatment improves muscle recovery after immobilization-induced atrophy." American Journal of Physiology-Endocrinology and Metabolism 305.3 (2013): E416-E428.
• Mero, Antti A., et al. "Effects of alfa-hydroxy-isocaproic acid on body composition, DOMS and performance in athletes." Journal of the International Society of Sports Nutrition 7.1 (2010): 1.
• Walser, Mackenzie. "Therapeutic compositions comprising alpha-hydroxy analogs of essential amino acids and their administration to humans for promotion of protein synthesis and suppression of urea formation." U.S. Patent No. 4,100,160. 11 Jul. 1978.
• Woods M., and Goldman P. "Replacement of L-Phenylalanine and Leucine by a-Hydroxy analogues in the diets of germ-free rats." J Nutr 1979;709:738 43.