Betaine For Strength, Size & Endurance Gains: 2.5g/Day For 6 Weeks Does the Trick - Even in Advanced Trainees

If you feel like a shadow of yourself, betaine may help - specifically with  metabolically demanding workouts.

"Six-weeks of betaine supplementation improved body composition, arm size, bench press work capacity, attenuated the rise in urinary HCTL, and tended to improve power (p = .07) but not strength." (Cholewa. 2013) That's not just the conclusion to the latest paper Jason Cholewa et al. have just published in every supplement junkie's favorite scientific journal (do I have to mention it's the one of the International Society of Sports Supplementation, ISSN?), it's also exciting news on trimethylglycine and further evidence that it has the potential to queue up in the short line of effective dietary supplements you may spend money on without having a guilty conscience.

6 Weeks + 2.5g/day = Increased mass, volume and strength gains

The routine the researchers had their 23 experienced recreationally strength trained males (weight: 86.8 ± 9.1 kg; training experience: 4.8 ± 2.3 months; BF%: 16.9 ± 8%) between the ages of 18 and 35 follow was clustered into three microcycles (figure 1)

Figure 1: Overview of the training schedule sets, reps and rest times (Cholewa. 2013)

Obviously a pretty solid training program that was (no surprise) able to increase muscle size, strength and strength endurance irrespective of whether the subjects received

• When do you take betaine? After checking back with the author, I can now tell you that the betaine can be taken at any time point and that you may want to have it with a meal to avoid stressing your gastrointestinal system.
  2 x 1.25g placebo capsules, or
• 2 x 1.25g betaine capsules

The dosage was chosen because it's safe (9-12g/day = safe; ), effectively elevated plasma betaine levels (2.5-5g; ) and did already produce strength and performance gains in previous studies (Hoffman. 2009; Lee. 2010; Trepanowski. 2011).

Figure 2: Pre / Post bench press volume (left) and muscle cross section (right; Cholewa. 2013)

What is somewhat surprising, at least in my humble opinion, though, is the greater increase in bench press volume (figure 2, left) in the first microcycle and the "comeback" of the placebo group afterwards. Considering the fact that this parameter did not improve in previous studies at all, and comparing the workload on the chest day during the different microcycles, the researchers managed a reasonable explanation for this observation:

"Advanced Trainees Benefit from Increased Training Volume! Greater & Steadier Strength Gains with 8 Sets of Squats. Plus: Over 6 Weeks, 1 Set and 4 Sets Equally (In-)Effective." | read more

"Given improved work capacity with higher volume resistance training prescriptions, and the lack of improvement during micro-cycle 2 which imposed less of a metabolic demand (4 sets of 4–6 repetitions with 3 min rest), it is likely that betaine poses the most ergogenic potential in resistance training exercise protocolsthat impose higher metabolic demands.

Betaine is actively taken up by skeletal muscle during periods of stress, and may be ergogenic as an osmolyte by protecting sensitive metabolic pathways against cellular hypertonicity such as protein turnover, amino acid and ammonia metabolism, pH regulation, and gene expression. Specifically, betaine maintains cellular hydration to protect myosin ATPase and myosin heavy chain proteins against denaturation by urea. Moreover, the affinity of troponin for Ca 2+ , and thus force production, is negatively affected by reductions in protein hydration." (Cholewa. 2013)

Or put simply: The more metabolically challenging (~high volume) the workout the greater the chances you will benefit from taking betaine aka trimethylglycine (not be confused with betaine HCL, the digestive aid).

"Body recomposition" in trained athletes is what could betaine make a huge success

Against that background it seems only logical that the back squat work capacity improved nearly twofold compared to placebo during microcycle 3 (4 sets of 4–6 repetitions with 3 min rest; data not shown). You could even argue that the increases in muscle cross-sectional area (CSA) with betaine may occur only in the arms, because biceps and triceps are hammered directly and indirectly and thus at a relatively higher volume than the legs.

Figure 3: Changes in body composition in betaine & placebo group (Cholewa. 2013)

Eventually, the volume increase, or rather the improved handling of the metabolically demanding workouts, could also explain the highly desirable body recomposition effects we see in the betaine group. Less metabolic waste cluttering around = improved effects on body composition...? Well, the HCTL levels and changes in homocysteine the scientists measured would not support this notion. However,

Betaine content (in mg/100g) in some common food items (read more)

"[...] betaine supplementation may have impacted body composition via other mechanisms. Betaine has been shown to elevate plasma GH and IGF-1, and increase Akt phosphorylation in human skeletal muscle (Apicella. 2012). In mice betaine improves insulin sensitivity by restoring activation of IRS1 and the subsequent phosphorylation of PI3K/Akt by 50-100% in a concentration-dependent manner (Jakubowski. 2009). Thus, it is possible that by elevating anabolic hormones and enhancing downstream cellular signaling, betaine may have improved muscle protein synthesis, thus leading to an increase in lean mass." (Cholewa. 2013)

An alternative explanation Cholewa et al. present pertains to the osmo-regulatory effects of betaine, which may have lead to a "cellular swelling without an appreciable increase in myofibril protein accretion" (Cholewa. 2013). Obviously, these are not the gains you are looking for, but in view of the fact that Keller et al, were able to show that this correlates with decreases in proteolysis it would at least minimize the amount of protein that's getting lost from the musculature right after you "pumped" it into it (Keller. 2003).

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What do eggs and homocysteine have in common? None of them causes heart disease. Eating eggs nay even prevent it by modulating the lipoprotein profile and cholesterol efflux (read more)

Bottom line: The study at hand adds more and, above all, highly relevant (human study, advanced trainees) evidence that betaine (2.5g/day in two servings) could make a valuable addition to the supplementation regimen of fitness models, physique competitors and bodybuilders, alike.

With its long-proven ability to reduce homocysteine levels () it has also been implicated as an agent that may prevent heart disease... unfortunately,  this assumption is based on the hypothesis that homocysteine plays a causative role in the development of heart disease and neither this nor the beneficial effects of choline & betaine on CVD are proven facts (Folsom. 1998; HCS. 2002; Olthof. 2005).

References:

• Apicella JM, Lee EC, Bailey BL, Saenz C, Anderson JM, Craig SA, Kraemer WJ, Volek JS, Maresh CM. Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise. Eur J Appl Physiol. 2013 Mar;113(3):793-802.  
• Cholewa JM, Wyszczelska-Rokiel M, Glowacki R, Jakubowski H, Matthews T, Wood R, Craig SA, Paolone V. Effects of betaine on body composition, performance, and homocysteine thiolactone. J Int Soc Sports Nutr. 2013 Aug 22;10(1):39. [Epub ahead of print].
• Folsom AR, Nieto FJ, McGovern PG, Tsai MY, Malinow MR, Eckfeldt JH, Hess DL, Davis CE. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 1998 Jul 21;98(3):204-10.
• Hoffman JR, Ratamess NA, Kang J, Rashti SL, Faigenbaum AD: Effect of betaine supplementation on power performance and fatigue. J Int Soc Sports Nutr. 2009, 6:7.
• Homocysteine Studies Collaboration (HCS). Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002 Oct 23-30;288(16):2015-22.
• Jakubowski H. The pathophysiological hypothesis of homocysteine thiolactone-mediated vascular disease. J Physiol Pharmacol. 2008 Dec;59 Suppl 9:155-67. Review.
• Lee EC, Maresh CM, Kraemer WJ, Yamamoto LM, Hatfield DL, Bailey BL, Armstrong LE, Volek JS, McDermott BP, Craig SA: Ergogenic effects of betaine supplementation on strength and power performance. J Int Soc Sports Nutr. 2010, 7:27.
• Keller U, Szinnai G, Bilz S, Berneis K. Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health. Eur J Clin Nutr. 2003 Dec;57 Suppl 2:S69-74.
• Olthof MR, Verhoef P. Effects of betaine intake on plasma homocysteine concentrations and consequences for health. Curr Drug Metab. 2005 Feb;6(1):15-22.
• Trepanowski JF, Farney TM, McCarthy CG, Schilling BK, Craig SA, Bloomer RJ: The effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation and associated biochemical parameters in resistance trained men. J Strength Cond Res. 2011, 25:3461–3471.

Nasty Insights into the Yo-Yo-Effect: Lower Body Fat Sticks and From Fit2Fat There's no Easy Way Back! Plus: Why It's Easier to Get 6-Pack Abs Than Striated Glutes & Hams.

Image 1: The person in the middle was probably once morbidly obese. How I know? Lower body adipose tissue sticks.

After yesterday's first installment of "On Short Notice", which by the way appears to have pleased most of you (thanks for the feedback, everyone!), we are going back to an in-depth analysis of another cherry-picked study, today. Don't worry, though, I believe even those who are more into the "rumpy pumpy" news will like this one. After all, it could provide some more insights into why your upper body and lower body don't match each other and - what's even more important it puts another emphasis on the primer to never ever let yourself go for too long.

The fat you gain today, will not be gone tomorrow!

In the scientific version of "from fit2fat2fit" (click here to watch the ABC report on the "experiment"), Prachi Singh and his colleagues from the Mayo Clinic in Rochester, UK, fed 23 volunteers (15 men and 8 women; BMI 23.6 6kg/m², mean age 30y), who were sedentary, but normal-weight and free of chronic disease, standardized diets with a macronutrient composition of 20% protein, 40% carbs and 40% fat. In addition each of the participants, who were weighed at least 5x per week had to eat 1-3 of the following snacks

• ice-cream shake (402 kcal),
• chocolate bars (a king-size Snickers bar, 510 kcal), or
• an energy drink (Boost Plus, 360 kcal/8 oz)

in order to gain ~5% of body weight within the initial 8-week weight gain phase. By dropping the extra snacks, dietary counseling from and an increase in overall activity the participants had shed those extra pounds in a subsequent 8-week weight loss phase, again - and, somewhat to my surprise, this did actually work quite well, as the data in figure 1 goes to show you:

Figure 1: Body composition and fat depot weight at baseline and after weight gain and loss (based on Singh. 2012)

But despite the fact that it looks as if they were more or less exactly back to baseline a more detailed statistical analysis of the data revealed that only the total body weight, total fat mass and total fat free mass of the subjects (figure 1, left) , as well as their visceral and upper body subcutaneous (UBSQ) fat loss showed statistically significant correlations with the initial weight gain (p < 0.0001, p =0.001, respectively), or as a non-scientist would say it: Only for the aforementioned parameters everything was in fact back to baseline - the lower body fat gains, on the other hand stuck.

Figure 2: Correlation of changes in lower-body fat mass and femoral fat cell size (men: squares, women: circles; Singh. 2012)

Is lower body fat not a female problem? No, according to the study at hand which was however not not adequately powered to provide any definitive answers to this question, there were "no sex differences in fat distributions during weight gain and weight loss" (Singth. 2012). And while the actual actual data in figure 2 (taken directly from the original study) does confirm that, there is still a non-negligible difference in the total amount of body fat gained and lost, which reminds me of a previous post of mine on "Busting the 3,500kcal = 1lbs Weight Loss Myth! Plus: Women Need More, Men Less Than the Rule Predicts", it only confirms the scientists observation.

Due to the limited number of subjects and relative scarce data Singh et al. can only speculate about the exact underlying reasons for this phenomenon, stating that it is most likely related to the "differential triglyceride storage capacity or lipolysis rates of lower- and upper-body adipocytes". An assumption that does appear very likely, though, also because the reverse, i.e. the increased ability to rapidly store meal triglycerides of upper body fat cells (Marin. 1990; Jenson. 2003) and their overall increased susceptibility to to lipolytic stimuli (e.g. your average caffeine based lipolytic "fat burner") had been established in previous studies already (Gui. 1997; Martin. 1991; Nielsen. 2004).

Faster in faster out ain't the whole explanation, though.

Image 2: You can ask any bodybuilder, a six-pack is easier to get than striated glutes & hamstrings. And the difference between upper - and lower body fat storage could well explain this phenomenon!

Unfortunately, Singh et al.'s study does also suggest that the "faster in - faster out" mechanism is not the only physical / physiological reason for the persistence of lower body fat... when I come to think about it, you may yet well argue that it is in the end the reason that another phenomenon takes place. One, the scientists had observed in a previous study, already (Tchoukalova. 2010), namely that "UBSQ [upper body subcutaneous] and lower-body subcutaneous fat respond differently at the cellular level to accommodate increased energy storage" (Singh. 2012). While the former simply increases in size, the latter "reproduces", or to say it in medical terms:

• upper body subcutaneous fat mass increases (mainly) by cellular hypertrophy
• lower body subcutaneous fat mass increases (mainly) by cellular hyperplasia

You have encountered this difference in the "Intermittent Thoughts on Building Muscle" already (specifically in "Intermittent Thoughts on Building Muscle: The Skeletal Muscle Hypertrophy 101 - Part 1: What is Hypertrophy?") and may remember that it is essentially not much different from inflating a given number of balloons (hypertropy) vs. adding more balloons until the few large or the many small balloons eventually occupy the same total volume or, in this case, the fat depots (=sum of many small or few large fat cells) can hold the same amount of triglycerides.

Hypertophy vs. hyperplasia - the latter sticks!

In fact previous research suggests that as soon as the storage ability of the individual fat cells is exceeded, hyperplasia becomes the predominant way to increase the bodies fat storage capacities (usually this is also when the overflowing existing adipose tissue stores begin to "burn down" the house by releasing copious amounts of inflammatory cytokines; cf. Skurk. 2007). Consequently,

[a]fter weight loss, obese people have smaller adipocytes than do people with a similar percentage of body fat and stable weight [though] it is unknown whether those obese adults had more adipocytes before they became obese [...] evidence has suggested that postobese adults have a larger number of fat cells, which could be a long-term consequence of adult weight gain on adipose tissue cellularity. (Singh 2012)

And in fact, these changes in "adipose tissue cellularity" became obvious in the study at hand after no more than 8 weeks of weight gain and loss - life long body fat accumulation or weight gain in the double digit range may not even be necessary...

Limitations of the study: Taken on it's own the Singh study does yet fail to prove the hypothesis that weight gain is associated with increases in fat cell number while weight loss is not, simply because the scientists did take biopsies only at the end of the study - in my eyes a major design flaw, irrespective of the fact, whether the data they would have elucidated would have been "statistically non-significant", as they point out. I did therefore decide against plotting the respective data on adipocyte size and number because without appropriate knowledge of where the subjects were coming from it is worthless anyway.

In this context, it is also noteworthy that the amount of leptin that's released by a given fat cell appears to (non-linearly!) increase with it's size. Against that background the "adipocyte abundance" (many now almost empty fat cells with a very low leptin secretion) in formerly obese subjects could even explain why most of them are having a very hard time to keep the weight off, let alone shed those pounds that still cover their abs, buttocks, etc. After all, on the individual cell level, their body fat stores are in fact almost empty - regardless of the fact that these people still carry 20+ more pounds of body fat on their frame than someone who has not gotten obese in the first place.

Bottom line: NEVER go from fit2fat!

Video 1 (click here to watch): Don't do the "Drew Manning" - making money and becoming famous with being fat is not going to work out another time - after all, Ozzy has already had it on the show... well, maybe if you used Ozzy's Rasberry product (see previous post) to shed the weight again ;-)

Unless Spalding et al. are right and obese individuals must have developed their entire compliment of adipocytes before reaching adulthood (Spalding. 2008; studies such as Löfgren et al. suggest the exact difference, by the way) the results of this study do thus suggest that you better not do the Drew Manning (see video 1) - after all, your chances to cause a similar media stir like Drew (who by the way appears to be a nice guy), are invited by Dr. Oz and make it into the main news on almost all global television channels are close to zero. And with the profoundly reduced leptin expression, from your emptied fat cells you are going to have a very hard time to get rid of any of those new fat cells which may have formed while you were bulking (regardless of whether they are sitting in your upper or lower body), because an abundance of circulating leptin appears to be the crucial signal for your body to send those nasty storage cells into the fat cell nirvana (Della-Fera. 2001).

There are studies that suggest that supplements like CLA could help accelerate this process (Tsuboyama-Kasaoka. 2000). Unfortunately, the data comes from rodent studies, many human trials on the other hand did not elicit any beneficial results, in parts certainly due to lower dosages, which are however a safety measure to prevent side effects such as the profound insulin resistance and hyperinsulinemia Tsuboyma-Kasoaka et al. observed in their study. It appears only logical that the latter would be a direct consequence of the combination of triglyceride release profoundly reduced leptin levels in response to the sudden death of the fat cells, which was in fact so pronounced that the scientists do speak of "lipodystrophy", a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue.

In the end, the only feasible option left appears - once again - to turn your life inside out and wait until the pendulum will have swung back into the right direction.

References:

1. Della-Fera MA, Qian H, Baile CA. Adipocyte apoptosis in the regulation of body fat mass by leptin. Diabetes Obes Metab. 2001 Oct;3(5):299-310.
2. Dilzer A, Park Y. Implication of conjugated linoleic acid (CLA) in human health. Crit Rev Food Sci Nutr. 2012;52(6):488-513.
3. Guo Z, Johnson CM, Jensen MD. Regional lipolytic responses to isoproterenol in women. Am J Physiol 1997;273:E108–12.
4. Jensen MD, Sarr MG, Dumesic DA, Southorn PA, Levine JA. Regional uptake of meal fatty acids in humans. Am J Physiol Endocrinol Metab 2003;285:E1282–8.
5. Löfgren P, Andersson I, Adolfsson B, Leijonhufvud B, Hertel K, Hoffstedt J, Arner P. Long-term prospective and controlled studies demonstrate adipose tissue hypercellularity and relative leptin deficiency in the postobese state. J Clin Endocrinol Metab 2005;90:6207–13.
6. Marin P, Rebuffe-Scrive M, Bjorntorp P. Uptake of triglyceride fatty acids in adipose tissue in vivo in man. Eur J Clin Invest 1990;20:158–65.
7. Martin ML, Jensen MD. Effects of body fat distribution on regional lipolysis in obesity. J Clin Invest 1991;88:609–13.
8. Nielsen S, Guo ZK, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. J Clin Invest 2004;113:1582–8.
9. Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007
10. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T, et al. Dynamics of fat cell turnover in humans. Nature 2008;453:783–7
11. Tchoukalova YD, Votruba SB, Tchkonia T, Giorgadze N, Kirkland JL, Jensen MD. Regional differences in cellular mechanisms of adipose tissue gain with overfeeding. Proc Natl Acad Sci USA 2010;107: 18226–31.
12. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes. 2000 Sep;49(9):1534-42.