More Muscles For Old Chaps, Less Fat for Baby Boomers: The Age Specific Anabolic Anti-Obesity Effect of HMB

Image 1: Nutrition, exercise and most importantly the right mindset will always be the foundation of leading a long, strong and healthy life - irrespective of how many supplements you take - you cannot out-supplement a bad diet, laziness and a lack of motivation and determination.

The hype was, as usual, huge, when back in the day Beta-Hydroxy-Beta-Methl-Butyrate (HMB), marketed as the natural alternative to Deca (Nandrolone; update: thx to anonymous for the heads-up that it was not just Anavar, as I original thought ;-), hit the market. What was yet even bigger than the hype, though, was the disappointment of customers who felt ripped off; and that not without reason, because the early HMB supplements were not only touted to be as effective as the previously mentioned anabolic steroid, they were also sold at similarly high prices and low doses, of which every scientists could easily have told you that the one thing that would grow were the purses of the manufacturers.When the marketing bubble eventually burst, the (at that time) pretty expensive and incredibly disgustingly tasting (no way you put a working amount of that stuff into a tasty pre- or postworkout amount without ruining the taste!) supplement disappeared from the market, literally overnight. Today, HMB is, if at all, sold as a standalone in 250mg-500mg capsule form or 250-1,000g pouches from bulk suppliers and leads an overall miserable existence being perceived as a probably useful, but simply unnecessary metabolite of the contemporary "natural Deca", leucine.

HMB - More than expensive leucine for old folks!?

The astonishing results of a recently published study from Jacob M Wilson's lab at the Department of Nutrition, Food and Exercise Sciences at The Florida State University in Tallahassee do yet suggest that at least the best-agers among the SuppVersity students, beta-hydroxy-beta-methl-butyrate could derive  undeniable advantages from the almost forgotten leucine metabolite (5% of a normal dietary leucine intake from food sources are metabolized into HMB; cf. Van Koevering et al.1993, according to Wilson. 2012). In what was allegedly "only another rodent study" (before you start complaining, please acknowledge that as long as you don't have your rodents "work out", those studies usually elicit pretty accurate results), the scientists enriched the diets of twelve young (44 wk.), 6 middle-aged (60 wk.), 10 old (86 wk.), and 5 very old (102 wk.) male rats with ~500mg/kg body weight HMB per day, which, using the standard conversion chart (cf. "Ask Dr. Andro: What Are Human Equivalent Doses "), yields a human equivalent of ~81mg/kg or 6.5g for a person who weighs 80kg.

Figure 1: Changes in body composition (left) and strength (right) during 16-week transition from young to middle age and old to very old age with and without supplementation in male Fisher rats (data adapted from Wilson. 2012)

As the data in figure 1 clearly shows this supplementation protocol (16 weeks, transition from young to middle aged and from old to very old) did not only prevent the decline in muscle strength, it had also pretty profound effects on the body composition of the aging animals. In case of the very old rodents, those effects were so profound (-56% body fat!) that it is questionable whether they were actually able to eat or rather metabolize enough food (food intake was not different) to accommodate for the +10% increase in lean mass.

HMB shuts down atrophic and ramps up myogenic factors, but why does it burn fat?

The late, but profound increase in lean mass in the very old animals (102wk) was brought about by a totally blunted increase in the "catabolic" Atrogin-1 signaling, the expression of which is so characteristic of aging skeletal muscle, and (and this is actually surprising) an increase of the "anabolic" myogenin expression that yielded myogenin levels which exceed those of the young (44 week) control group by +40%!

Although these changes in Atrogin-1 and myogenin expression can explain the anti-sarcopenic (=working against the age-induced decline in muscle mass) effects of HMB and would even suggest tat it is a very useful "muscle builder" in the elderly population, where similar amounts of leucine (7.5g) have hitherto not yielded not the desired results (Verhoeven. 2009), they do not explain the unquestionably profound effect on the total fat mass of the animals, which reached statistical significance during both, the transition from young to a middle age (HMB body fat change not significant vs. +49% body fat mass in control) and the transition from the old to the very old age (HMB body fat -56%, control -8% n.s.) and of which Wilson et al. say (Wilson. 2012):

To date, the underlying mechanisms that HMB exerts its effects on adipose remain to be elucidated. It may be that HMB directly increases oxidative capacity in myofibers, as exposure of cultured myotubes to the leucine metabolite increased palmitate oxidation by 30%.

If the latter, i.e. the increase in palmitate oxidation transfers to human studies, Skelton et al. observed in their in-vitro studies (Skelton. 1994, according to Wilson. 2012), was dose dependent, I would be interested to see studies on the effect of twice the amount of the 3.0g/day HMB per day that did already produce greater increases in lean and decreases in fat mass over the course of a four week resistance training program in a twelve-year-old study in young (Panton. 2000), as well as an eleven-year-old study in 70-year old individuals (Vukovic. 2001), in younger and older trainees, and sedentary individuals.

Something to think about

Also, what if HMB was in fact one of the rare cases, where "more" actually yields "more". I mean, wouldn't it be remotely possible that our body's ability to convert leucine to HMB is not just rate limited, but that the rate decreases with age (this would explain why leucine works much better in younger folks) and saturates, when a certain concentration of HMB is achieved (if that was the case even the 5% conversion could be questionable, because you could have an upper limit of say 500mg, which would be 5% of 10g leucine and just 1% of 50g)? The latter would mean that you could not produce more than x grams of HMB total per day and would imply that the "old natural Deca" could in fact turn out to be superior to the "new natural Deca" for trainees (and maybe even non-trainees) from all age groups - as long as the dosage was appropriate, i.e. beyond what your body would produce from dietary leucine.

References:

1. Panton LB, Rathmacher JA, Baier S, Nissen S. Nutritional supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (hmb) during resistance training.Nutrition 2000,16(9):734-739.
2. Skelton DA, Greig CA, Davies JM, Young A. Strength, power and related functional ability of healthy people aged 65-89 years. Age Ageing 1994, 23(5):371-377
3. Van Koevering M, Gill DR, Smith RA, Owens F, Nissen S, Ball R. Effect of β-hydroxy-β-methyl butyrate on the health and performance of shipping-stressed calves.Oklahoma State Univ Res Rep; 1993, 312-331.
4. Vukovich MD, Stubbs NB, Bohlken RM. Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. J Nutr. 2001 Jul;131(7):2049-52.
5. Wilson JM, Grant SC, Lee SR, Masad IS, Park YM, Henning PC, Stout JR, Loenneke JP, Arjmandi BH, Panton LB, Kim JS. Beta-hydroxy-beta-methyl-butyrate blunts negative age-related changes in body composition, functionality and myofiber dimensions in rats. J Int Soc Sports Nutr. 2012 Apr 18;9(1):18.

Sunlight, L-Tryptophan & Vitamin B6 With Breakfast Increase Serotonin and Wakefulness During the Day and Melatonin and Restful Sleep at Night

Image 1: For these kids the high tryptophan + B6 breakfast would be useless unless they already got their 10min+ of direct sun exposure this morning

A recently published study that was conducted by a team of international researchers led by Miyo Nakade from the Gakuen University in Nagoya, Japan (Nakade. 2012), concludes that sunlight exposure and vitamin B6 and l-tryptophan intake with breakfast could be profound modulators of circadian rhytmicity in young children (N=816, age = 2-6 years). The results the researchers published in the latest issue of the Journal of Physiological Anthropology clearly suggest that the increased production of serotonin from l-tryptophan and the vitamin B6 metabolite pyridoxal 5’-phosphate (also known as PLP or p5p) exerts beneficial effects on the morningness-eveningness (M-E) score - a measure for the natural and highly desirable difference in wakefulness in the morning and sleepiness in the evening, the disturbance of which is among the emerging correlates of metabolic diseases, such as diabetes, obesity and abnormal lipid metabolism.

[C]hildren showed a tendency to be more morning-typed if they ate breakfast with
a high estimated Trp content. This study also confirmed a similar trend with estimated Vi-B6
content. Among essential amino acids, the Trp content in food is quite small, and thus it is
necessary to make a special effort to consume a sufficient amount in one’s diet.

That those foods with specifically high tryptophan content are, as so often, eggs, meats, and fish is something I probably don't have to tell you - just as I don't have to tell you that soybeans, and other soy products, which also contain significant amounts of tryptophan should not constitute a major part of your diet; regardless of whether you are a man or a woman.

Sunlight must not be hidden behind curtains or seen just through the windows your car

Interestingly, all the vitamin B6 and tryptophan in the world appears to be of little use, if you get too little sun-exposure (Rosenthal. 1997). And, now listen up!, they can become disturbed when you sleep with black out curtains and use an alarm clock to wake you up (Harada. 2003) - in how far these effects are mitigated, or even reversed (i.e. using black-out curtains = beneficial) in people who would otherwise be constantly exposed to unnatural light-exposure (e.g. a street lantern right before your window) would require further investigation, though.

Figure 1: Distribution of early birds (low M-E score on the x-axes) and late risers (high M-E score) among the study population (data calculated based on Nakade. 2012).

Anyways, as you can see in figure 1 the effect of the curtains was statistically significant, but not as pronounced as the scientists' emphasis in their report would have it. There are tendencies for more morning types (lower M-E scores) in the children sleeping without blackout curtains, yes. And there are no real evening types in the children sleeping without blackout curtains, but the broad majority falls into the same 18-23 M-E score range on the 7-28 early bird to long sleeper scale Nakade et al. employed.

Vitamin B6 and inflammation: Although this is only indirectly related to the topic of circadian rythmicity and wake-sleep patterns, it is quite intriguing that vitamin B6 is still touted as an anti-inflammatory agent. And though even very recent population based studies confirm that there is in fact an inverse relation of low plasma vitamin B6 and its active metabolite pyridoxal-5-phosphate (PLP) are inversely associated with the "overall inflammation" score in the US population (Sakakeeny. 2012), another recent study by Ulvik et al. clearly suggests that these associations are corollary, at best (Ulvik. 2012). In their trial, the results of which have been published in the May issue of the American Journal of Clinical Nutrition, Ulvik et al. administered 40 mg pyridoxine hydrochloride per day to patients with stable angina pectoris. Contrary to their expectations, this practice did neither replete the low vitamin B6 levels, nor sooth the inflammation. On the contrary, the rapidly metabolized vitamin B6 appeared to preserve or even increased the expression of inflammatory markers.

What's good in the morning won't hurt at night

With tryptophan being a serotonine precursor and vitamin B6 a necessary co-factor in its synthesis, it may come as a surprise that both, and the sunlight induced serotonin synthesis boost can boost "morningness" and make you more alert. After all, you will probably have read on the label of various dietary supplements that tryptophan is supposed to make you sleepy, right? What those labels don't tell you is that the exposure to sunlight and not the shear availability of precursors and co-factors, let alone the position of the hands on your clock modulate its destiny. And determine whether the tryptophan will get you going, as it obviously does in the children with the highest breakfast intake of tryptophan and vitamin B6 (cf. figure 2), or helps you fall and stay asleep at night.

Figure 2: M-E index relative to group mean in high / low tryptophan & vitamin B6 breakfast intake groups (data calculated based on Nakade. 2012)

That both is possible and obviously works quite fine, is thus the main message of this study, the results of which Nakade et al. interpret as direct evidence for the potential usefulness of

[...] a higher Trp and Vi-B6 intake [to] promote the synthesis of serotonin via light stimulation in the morning and have a natural sleep-inducing effect when converted to melatonin at night [and thus] help prevent a phase delay in young children’s circadian clocks and promote their morningness against the effects of the 24-h commercialization of society.

Against the background, that similar improvements have been observed in 35 middle-aged/elderly (aged 55-75 year) volunteers who consumed a tryptophan enriched  (+30mg per serving) cereal at breakfast and dinner for three weeks by Bravo et al. (Bravo. 2012). And since there is no effect without "side effects", I guess I better mention that the Spanish researchers also observed significant increases in

Table 1: Tryptophan content of various foods (in g per 100g, 2nd column), ordered by tryptophan per protein content (3rd column; data based on Wikipedia)

• sleeping time,
• sleep efficiency, and
• immobile time

as well as concomitant decreases in

• sleep latency (almost 25%!),
• wake bouts,
• total activity, and
• sleep fragmentation index

If you take into consideration that their subjects' total antioxidant capacity levels and mood improved, as well and that the treatment elicited a -50% decrease in state anxiety and a significant drop on Beck's Depression Inventory Index, both of which returned to their initial value, when the treatment was seized, it should be obvious that you better make get out in the sun, immediately after you made the right food choices (and no, I am not talking about tryptophan-enriched breakfast cerals, here) at breakfast and watch the sunset after dinner ;-)

References:

1. Bravo R, Matito S, Cubero J, Paredes SD, Franco L, Rivero M, Rodríguez AB, Barriga C. Tryptophan-enriched cereal intake improves nocturnal sleep, melatonin, serotonin, and total antioxidant capacity levels and mood in elderly humans. Age (Dordr). 2012 May 24.
2. Harada T, Matsumura A, Takeuchi H: Effects of the usage of a blacked-out curtain on the sleep-wake rhythm of Japanese University students. Sleep Biol Rhythms 2003, 1:179–181
3. Nakade M, Takeuchi H, Taniwaki N, Noji T, Harada T. An integrated effect of protein intake at breakfast and morning exposure to sunlight on the circadian typology in Japanese infants aged 2-6 years. J Physiol Anthropol. 2009 Sep;28(5):239-45. 
4. Nakade M, et al. Can breakfast Tryptophan and Vitamin B6 intake and morning exposure to
   sunlight promote morning-typology in young children aged 2-6 years? Journal of Physiological Anthropology 2012, 31:11
5. Sakakeeny L, Roubenoff R, Obin M, Fontes JD, Benjamin EJ, Bujanover Y, Jacques  PF, Selhub J. Plasma Pyridoxal-5-Phosphate Is Inversely Associated with Systemic Markers of Inflammation in a Population of U.S. Adults. J Nutr. 2012 May 23.
6. Rosenthal N, Schwartz P, Tumer E, Nalm S, Matthews J, Hardin T, Barnett R, Wehr T:
   The psychobiology of SAD and the mechanism of action of light therapy. Biol Psychiatry
   1997, 42:57S.
7. Ulvik A, Midttun O, Ringdal Pedersen E, Nygård O, Ueland PM. Association of plasma B-6 vitamers with systemic markers of inflammation before and after pyridoxine treatment in patients with stable angina pectoris. Am J Clin Nutr. 2012 May;95(5):1072-8. 
8. Wikipedia contributors. Tryptophan. Wikipedia, The Free Encyclopedia; 2012 May 26, 00:42 UTC [cited 2012 May 27]