Strengthless Gains: HMB+Arginine+Lysine Build Muscle. Strength Gains Require Vitamin D Levels >30mg/mL

Image 1: I wonder, why
gerontologists don't use
plain BCAAs - too convenient?

If, as I hope, you are a regular visitor of the SuppVersity, you know that in this day and age of vitamin-D3-loving, I am an outspoken skeptic, as far as the "magic" of supplementing with the undreestimated bone-building vitamin is concerned. That being said, I am all the more happy that after thousands of worthless epidemiological studies, scientists eventually begin to conduct well-controlled clinical trials, which provide factual information instead of dodgy hypothesis on the complex mechanisms by which our vitamin D status modulates a number of metabolic processes which reach far beyond the health of our bones.

Did you know that the most recent studies on the effects of vitamin D on weightloss (Soares. 2011) and type 2 diabetes (Mitri. 2011) conclude that "[c]urrent evidence from RCTs [randomized controlled studies] did not consistently support the contention that calcium and vitamin D accelerated weight or fat loss in obesity" and that, in the majority of hitherto published, well-powered studies "no effect of vitamin D supplementation on glycemic outcomes" was seen "among participants with normal glucose tolerance at baseline and in three small underpowered (n=32–62) trials of patients with established type 2 diabetes". The obvious discrepancy between the euphoria, or I should say, hype the unreliable epidemiological trials brought about and the disillusioning results of real science, which will always go beyond mere observation, should remind you of the ease with which you can design or (mis-)interpret epidemiological studies in order to prove whatever hypothesis you want - I do not have to remind you of the "fat lies" related to the detrimental effects of saturated fats on heart health, do I?

But let's get back to the topic at hand - strengthless muscle growth. In a year-long double-blinded, controlled study (Fuller. 2011) John C. Fuller, Jr. and his colleagues from Iowa State University and the Vanderbilt University Medical Center provided 39 elderly women and 38 elderly men (age 76+/-1.6 years) with an amino acid supplement which contained either a blend of HMB + Arginine + Lysine (2.0 g CaHMB, 5.0 g arginine, and 1.5 g lysine) or an isocaloric non-essential amino acid placebo (alanine 5.6 g, glutamic acid 0.9 g, glycine 3.1 g, serine 2.2 g). The supplement, of which the heavier participants (>65kg) consumed 1.5x the amount of their lighter age-mates, was to be taken each day, with breakfast. Based on previous research by Vukovich (2001) and Flakoll (2004), Fuller et al. hypothesized that the intake of the HMB-containing amino acid blend would result in statistically significant gains in both strength and size of the muscles of their elderly participants.

In fact, HMB has been shown to stimulate protein synthesis and reverse its inhibition by lowering proteolysis-inducing factor, lipopolysaccharide, tumor necrosis factor α, and angiotensin II via an upregulation of the mTOR / p70S6k pathway. By attenuating the activation of caspases-3 and -8, HMB supplementation may also decrease the formation of reactive oxygen species and the activation of the ubiquitin-proteosome degradation pathway. If you asked me, however, you would probably see the very same benefits from supplementing with HMB's way cheaper precursor leucine - keep that in mind before you waste your money on a hardly palatable amino acid derivative your body will synthesize on its own, if you just provide the right substrate, i.e. l-leucine from BCAAs, EAAs or just plain whey protein.

In view of the fact that in a previous study by the same group (Baier. 2009) an identical amino acid supplement had failed to elicit  significant strength increases in a similar subject group, and based on previous findings by various scientists on the detrimental effects of full-blown vitamin D deficiency (<15ng/mL 25OHD3) on muscle strength, Fuller et al. speculated that there could be a synergy (which does not equal "vitamin D builds strength) or interdependence between the provision of the leucine metabolite HMB, the vitamin D status of a person and the ensuing improvements in muscle size and strength.

Figure 1: Relative changes in lean body mass in 77 elderly subjects after one year on a HMB+Arginine+Lysine supplement (calculated based on data from Fuller. 2011)

The results of their study (cf. figures 1-2) suggest that 'adequate' vitamin D levels (25OH-D3 > 30ng) are not required for the HMG + Arginine + Lysine amino acid mixture to work its muscle building magic on elderly subjects.

Figure 2: Increase in total leg strength [in ft-lbs] as measured by the sum of knee extension and flexion at 60 and 120 degrees/s in 77 elderly subjects after one year on a HMB+Arginine+Lysine supplement (data adapted from Fuller. 2011)

Yet, in subjects with 25OH-D3 levels <30ng was this increase in muscle mass also accompanied by strength gains, which were approximately 4x higher than in the unsupplemented control group (cf. figure 2).

Vitamin D and muscular strength in the elderly: Bischoff-Ferrari et al. (2004) found continued improvements in lower extremity function up to 40ng 25OH-vitD3/mL, a level well above what has been previously thought necessary for maximum benefit. Although this does not sound much, clinical trials such as the one Andres Ernesto Carillo conducted as part of his dissertation (Carillo. 2010) show that supplementation with 4.000 IU VitD3, which is way beyond what conservative physicians would deem tolerable, raised vitamin D in 23 previously deficient individuals (25OHD levels = 19.3ng/ml; age 26.1 +/- 4.7yrs) levels by no more than + 2.7ng/mL over control.

A word of caution before you ramp up your supplemental vitamin D intake to a bottle a day: Although this was a "double-blind controlled" trial, the controlled parameter was not vitamin D supplementation, but the HMB+Arginine+Lysine mixture the elderly subjects received - as far as the vitamin D status was concerned, the study was merely observational. That being said, the study may have higher significance than the unreliable epidemiological guesswork, you will hear about in the news almost daily, it does not allow, however, any (not even preliminary) conclusions regarding the potential effect supplemental vitamin D would have had on the outcome of the study. If the low vitamin D level was just corollary to or caused by some other underlying conditions, for example, it would be very unlikely that even 100.000IU of vitamin D would have had a significant effect on the muscular performance of the subjects.