New dietary supplements enter the fitness space all the time, but they rarely pan out and make the jump from promising to reliably effective. While betaine, also known as trimethylglycine, is anything but new, it has yet to become a household name in the world of fitness-oriented supplements, and research investigating its effects on human performance and body composition is finally beginning to accumulate. While much of my recent writing has been on some of the “tried and true” staples in the typical strength or physique athlete’s supplement drawer, such as creatine and caffeine, betaine is a lesser-known ingredient that warrants further exploration.
As I alluded to previously, betaine might seem relatively novel to us, but it’s far from new. It has been used for several decades in the livestock industry, for the purpose of increasing meat yield and reducing fat storage in a range of animals including cattle, pigs, and chickens. In terms of human research, I’m aware of studies going back at least as far as 1952, when a group of researchers reported that a treatment containing betaine and guanidinoacetate improved a number of outcomes related to strength and fatigue in patients with polio. Betaine was originally identified as a nutritional component of sugar beets (hence the name beet-aine), but is found in a variety of foods including spinach, wheat products, shrimp, and other grains and seafood. The human diet typically includes 0.1-0.4g/day of betaine intake, whereas most of the literature investigating performance and body composition outcomes in humans uses a dose of around 2.5g/day. This article will review what betaine does in the body and discuss studies evaluating the effects of betaine supplementation on body composition and performance. If you’re more of an auditory learner and want to hear more about betaine, we’ve previously discussed it on the podcast on two different occasions, but this article will go into quite a bit more detail.
Mechanisms of Action
You might recall that we’ve discussed beetroot juice – another beet-derived dietary supplement – in a previous Stronger By Science article. While performance is primarily affected by the nitrate content of beetroot juice (with some minor assistance from antioxidants), the mechanisms by which betaine could affect body composition and performance are quite different. In a recent meta-analysis, Gao et al laid out the potential mechanisms by which betaine could specifically influence fat loss or hypertrophy, which are as follows:
- By influencing a bunch of pathways and enzymes associated with fat metabolism (such as PPAR-⍺, SREBP-1c, acetyl-CoA carboxylase, and fatty acid synthase), betaine could promote lipolysis (breaking down triglycerides and releasing fatty acids from fat cells) and reduce lipogenesis (the synthesis and storage of new triglycerides).
- By reducing the expression of lipoprotein lipase, betaine could reduce the amount of triglyceride that fat cells take up from the blood.
- By increasing the mitochondrial content of white fat cells, it could turn them more “beige” in terms of their metabolic characteristics, thereby enhancing thermogenesis and lipolysis.
- By increasing the transmethylation (conversion) of homocysteine to methionine, betaine may increase lipolysis as a result of lower homocysteine levels.
- By altering levels of growth hormone, insulin-like growth factor 1 (IGF-1), and homocysteine thiolactone, betaine may promote protein synthesis via the insulin/IGF-1 pathway.
When it comes to potential mechanisms for performance enhancement, those have been effectively outlined by Ismaeel. As a methyl donor, betaine could potentially enhance endogenous synthesis of creatine and carnitine, in addition to sparing dietary methionine and choline. It’s also osmolytic, meaning it increases cellular hydration and can protect cells (and maintain cellular function) in response to a variety of physiological stressors. There’s also some evidence to suggest that betaine may increase nitric oxide levels (check out this article for a detailed description of why that would matter). Finally, as noted previously, betaine may have some positive effects on fatty acid metabolism, and may also favorably affect hypertrophy via effects on the insulin/IGF-1 pathway of muscle protein synthesis. If these effects on the insulin/IGF-1 pathway actually pan out to result in increased net muscle accretion over time, that’d be a great thing for long-term strength development and hypertrophy.
It’s very possible that some people reading this article might have supplemented with betaine before, without actually realizing it. Betaine has found its way into some commercial multi-ingredient pre-workout blends, but it’s rarely the “headliner” that gets featured in enormous font in the center of the advertisement. One such formula was recently tested in a 4-week study by Schwarz and colleagues. In the study, 16 recreationally trained men were randomly assigned to receive a pre-workout supplement (n = 8) or placebo (n = 8) throughout the duration of a supervised, periodized, 4-week training program designed to promote strength and hypertrophy. The supplement group experienced significantly larger increases in body weight (3.19kg versus 0.44kg; Figure 1), lean body mass (3.15kg versus 0.89kg), and squat 1RM (23.9kg versus 14.2kg; Figure 2), and a notably larger (but not quite statistically significant) increase in bench press 1RM (10.5kg versus 4.6kg).
I know a lot of people were a bit shocked when this paper was first making the rounds and they saw those numbers, but there are a couple important things to keep in mind. First, mean values from small samples tend to be pretty sensitive to extreme cases, so a couple of really positive responses can yield a large average effect, just as a couple of really negative responses can drag a mean down (and since there was a two-fold difference in mean bench press strength gains that wasn’t statistically significant, that suggests substantial heterogeneity; thus, the presence of a few extreme responders isn’t unlikely). Second, we have to keep in mind that this was a multi-ingredient formula. In addition to 2.4g of betaine, it also contained creatine, caffeine, citrulline malate, and several other potentially ergogenic ingredients. As such, body mass and lean body mass could have been acutely inflated due to the osmolytic properties of creatine and betaine, and the strength effects were likely related to contributions from multiple ergogenic ingredients (especially creatine). So, we know that there are plausible mechanisms by which betaine could reduce fat mass, increase muscle mass, and enhance performance, and this pre-workout paper was at least a promising sign. However, given the multi-ingredient nature of the formulation, it’s virtually impossible to speculate about the independent contribution that betaine made to the results. So, let’s dive into some of the literature looking at betaine’s independent effects on body composition and performance.
Effects on body composition
In a recent meta-analysis, Gao et al summarized the results of the few placebo-controlled human trials to date that have evaluated the effects of betaine on various measures related to adiposity, including body weight, BMI, waist circumference, fat mass, and body-fat percentage. Six total studies were included in the review; each study ranged from 10 days to 24 weeks in duration, with betaine doses ranging from 2.0g/day to 9.9g/day. However, it’s important to note that six studies were included because they reported at least one of the relevant measures of adiposity, not all of the relevant measures; so, the analysis for each specific outcome contains data from fewer than six studies.
Only two studies reported waist circumference values, and body weight and BMI have some inherent limitations when we try to use them as proxies for changes in fat mass. I think the effects reported for body-fat percentage and total fat mass are most directly relevant to the Stronger By Science audience, so I will restrict my focus to those two outcomes. Four studies reported changes in fat mass (Figure 3); the least favorable result was a 0.7kg fat gain for betaine in comparison to placebo, while the most favorable result was a 3.20kg loss of fat favoring betaine. The result of the pooled analysis including all four studies was a 2.25kg fat loss favoring betaine in comparison to placebo. The same four studies were the only studies reporting changes in body-fat percentage (Figure 4); the least favorable result was an increase of 0.3 body-fat percentage points in comparison to placebo, while the most favorable result was a decrease of 3.4 percentage points in comparison to placebo. The pooled analysis indicated that betaine supplementation resulted in a 2.44 point reduction in body-fat percentage compared to placebo.
Overall, this very preliminary meta-analysis would suggest that betaine could have some promising effects pertaining to fat loss. However, it’s important to note that this is a remarkably small body of literature, so these findings absolutely cannot be viewed as firm conclusions. In addition, the most favorable results were from studies by Cholewa et al in 2013 and 2018; these studies contributed over 70% of the weighting for the fat mass and body-fat percentage analyses, meaning that the findings of this meta-analysis were largely driven by only two studies. A notable difference between Cholewa’s studies and the other two studies is that Cholewa’s studies included a structured, supervised resistance training program throughout the supplementation period, while the other two studies had no exercise component. That might be a good sign for the Stronger By Science readership, as it would tentatively suggest that betaine’s fat loss effects are more likely to be observed in individuals that are actively engaged in resistance exercise.
Speaking of resistance training, the Cholewa studies also allow us to assess betaine’s potential impact on hypertrophy. In the 2013 study, resistance-trained men completed two, 3-week microcycles that included two weekly upper-body training sessions and two weekly lower-body training sessions. The researchers assessed body composition via skinfold measurements, and also assessed arm and thigh cross-sectional area using a method that involves combining the results from skinfold thickness measurements and limb circumference measurements, which seems to estimate muscle size reasonably well compared to CT scans. Results indicated that the betaine group experienced significantly larger increases in lean body mass (Figure 5) and arm cross-sectional area (Figure 6), but not thigh cross-sectional area. Of course, as you can see in the figures, the betaine group began the study with lower values for lean body mass and arm cross-sectional area, so you could justifiably suggest that the betaine group was simply “catching up” to the placebo group.
In Cholewa et al’s 2018 study, untrained women completed two, 4-week mesocycles including two weekly lower-body sessions and one weekly upper-body session. In this study, body composition was measured via air displacement plethysmography (BodPod), and rectus femoris muscle thickness was measured via ultrasound. In this study, gains in fat-free mass and rectus femoris thickness were not significantly different between the betaine and placebo groups. The mean change and 95% confidence interval [lower boundary, upper boundary] for fat-free mass was +2.9 [1.31, 4.56] kg for the betaine group and +1.9 [1.33, 2.52] kg for the placebo group. For rectus femoris thickness, changes were +0.14 [0.08, 0.19] mm for the betaine group and +0.14 [0.09, 0.18] mm for the placebo group. The hypertrophy results from this study with female subjects aren’t quite as promising as those reported in the prior study with male subjects by the same research group. It’s possible that men receive a larger benefit from betaine supplementation than women, as estrogen can increase the activity of an enzyme that breaks down betaine, which might explain why women appear to have lower plasma levels of betaine than men. However, these two studies also had different timelines, implemented different training programs, utilized different methods for body composition measurements, and recruited samples with different training statuses (resistance trained men versus untrained women). Due to the multifaceted differences between these studies, we can’t conclusively determine why the results were somewhat divergent until future studies shed more light on the topic.
Overall, there are a couple of promising studies suggesting that betaine could potentially facilitate reductions in fat mass and increases in muscle mass. There’s nowhere near enough evidence to draw anything resembling a confident conclusion, but there’s definitely enough to warrant some optimism when it comes to betaine’s effects on body composition. However, before deciding whether or not betaine might be worth a try, a review of the performance literature is also warranted.
Effects on performance
The body composition effects of betaine supplementation seem somewhat promising, but a big percentage of the Stronger By Science readership is more closely focused on performance goals, mostly related to strength and power. While there isn’t an enormous body of betaine literature evaluating performance effects, Ismaeel wrote a 2017 review summarizing most of the literature available. The review included seven total studies investigating the effects of betaine supplementation on strength or power outcomes; dosing was very consistent among the studies, with all studies using 2.0-2.5g/day of betaine, but the duration of supplementation periods varied considerably. The longest study in the review implemented a supplementation period that was six weeks long, but the remaining studies involved 15 days of supplementation or fewer, with the shortest supplementation period lasting only 7 days. A fairly unique characteristic of this literature is that there are minimal studies conducted with truly untrained samples, with six of the seven studies featuring a resistance-trained sample. One of the studies contained a mixed-sex sample (males and females combined), while the other six sampled males exclusively.
When it comes to the results of these studies, a surface-level evaluation of strength and power outcomes doesn’t incite a great deal of optimism or excitement. A few studies have reported statistically significant performance improvements of some kind, while several others have reported generally underwhelming results. Lee et al was one of the studies reporting a performance improvement; 12 resistance-trained males completed the 14-day supplementation intervention with 2.5/day of betaine using a crossover design (so, each subject did a 14-day supplementation phase, as well as a 14-day placebo phase). During each arm of the study, participants completed two standardized workouts that were designed to help participants maintain their typical fitness level. Supplementation resulted in significantly larger increases in isometric bench press force and bench press throw power in comparison to placebo, and a significant increase from pre-testing to post-testing was observed for vertical jump power and isometric squat force within the betaine group. However, values for vertical jump power and isometric squat force following betaine supplementation were not significantly different than placebo values, and supplementation did not cause significant increases in jump squat power or the number of bench press or squat repetitions to failure with 85% of 1RM. So, betaine supplementation may have had beneficial effects on performance, but you have to tilt your head and squint just right; this study certainly wasn’t an unambiguous win for betaine.
Pryor et al also reported a statistically significant performance benefit from betaine supplementation. In this study, 16 resistance-trained people (9 males, 7 females) completed a crossover trial consisting of two, 7-day supplementation periods (2.5g/day betaine or placebo). The study did not include a strength outcome, but assessed power output on a cycling sprint test consisting of four, 12-second sprints against a resistance equal to 5.5% of the participant’s body mass, with 2.5 minutes of rest between sprints. Compared to the placebo condition, betaine supplementation resulted in higher average and maximum peak power values, along with higher average and maximum mean power values. Hoffman et al published two studies included in the review by Ismaeel; in the first, betaine did not significantly improve bench press repetitions to fatigue (Figure 7), nor did it improve performance in a variety of power assessments, including vertical jump power, bench press throw power, and a cycling sprint test. The results indicated that betaine did improve squat repetitions to fatigue, with the betaine group cranking out an extra five reps or so after 1-2 weeks of supplementation, although this difference was statistically significant at mid-testing (1 week) but not at post-testing (2 weeks) (Figure 8). One of the two studies by Cholewa et al reported an improvement in vertical jump performance that was not statistically significant, but had a low enough p-value to garner some degree of attention (p = 0.07). Of course, “increased attention” simply suggests that we take a closer look, not that we conclude “close enough, let’s go with it.” In this study, betaine failed to significantly increase bench press 1RM or squat 1RM, and had inconsistent effects on training volume. So, it’s hard to walk away from that study with the conclusion that betaine meaningfully improved strength and power adaptations in response to the resistance training program that was implemented.
While a few studies have reported improvements for select performance outcomes following betaine supplementation, multiple studies in the review by Ismaeel reported no statistically significant performance effects. For example, del Favero et al did not find statistically significant benefits of betaine supplementation for squat or bench press strength or power outcomes. In a second study by Hoffman et al, betaine did not significantly enhance peak eccentric or concentric force during isokinetic chest presses. Trepanowski et al evaluated the effects of betaine on bench press power, bench press isometric force, leg press isometric force, vertical jump height, and chest press reps to fatigue. The authors found no statistically significant improvements attributable to betaine supplementation, although some very liberal post hoc testing suggested that betaine may have slightly improved the total number of repetitions completed during a chest press test consisting of 10 sets to failure using a 50% 1RM load. Finally, Cholewa’s study with female subjects was published after Ismaeel’s review came out, so it obviously wasn’t included. While Cholewa et al found that betaine might have had a slight benefit favoring increased training volume (p = 0.056, slightly above the threshold value of 0.05), betaine did not significantly improve squat 1RM, bench press 1RM, or vertical jump performance.
Overall, betaine’s effects on strength and power performance have been inconsistent in the research literature to date. There are certainly some instances in which select performance outcomes have improved, but it’s difficult to say that there’s a clear pattern in which betaine reliably improves strength, power, or muscular endurance. One notable consideration to keep in mind is the duration of these studies; of the seven studies included in Ismaeel’s review, six involved supplementation periods of 15 days or less. If betaine does, in fact, promote hypertrophy, that would specifically bode well for long-term strength and power outcomes, measured over a time course in which meaningful hypertrophy could realistically occur. As such, this body of literature seems to suggest that short-term betaine supplementation (generally in the 2-6 weeks range) has unreliable effects on strength, power, and muscular endurance, although some positive findings have been reported. In addition, this is a pretty small body of literature, so future studies will almost certainly help us develop a more nuanced understanding of the inconsistent results that have been reported thus far.
Finally, I will note that adding betaine to pig feed (typically in concentrations around 0.1-0.2% of feed) has resulted in some pretty favorable effects on the accretion of lean mass, and I can’t imagine that folks in the livestock industry like to mess around with thoughtlessly adding expensive additives to their feed. Greg did some rough calculations suggesting that the typical supplementation strategy used for pigs would equate to a human dose of around 3-6g/day; given that the literature evaluating strength and hypertrophy outcomes has almost exclusively studied doses of 2.0-2.5g/day, we can’t necessarily reject the possibility that higher doses might yield more favorable effects on lean mass and, by extension, long-term strength development. It has been estimated that daily betaine doses around 12g (the range provided was 9-15g) should be safe for human consumption, and one of the weight loss trials included in the meta-analysis by Gao et al provided 9.9g/day of betaine to prediabetic subjects with obesity. This dose resulted in some modestly negative effects on blood lipids (and modestly positive effects on a couple of measures related to glycemic control), but no notable adverse events occurred. So, it’s possible that higher doses could potentially be safe, well-tolerated, and more efficacious, but that suggestion would be totally speculative and require more research to confirm or refute it. If one were to experiment with some higher dosages, it’d probably be prudent to keep an eye out for potential increases in total cholesterol and triglyceride levels.
Conclusions and Applications
When it comes to strength, power, and hypertrophy outcomes, I tend to view supplements in a series of “tiers.” The top tier consists only of creatine, as it stands alone as the most effective and most rigorously studied supplement on the market. The second tier consists of supplements that either have a smaller magnitude of effect, a smaller body of evidence supporting their efficacy, or a more limited set of scenarios or circumstances in which they work. Examples of second-tier supplements would include things like caffeine, dietary nitrate, citrulline malate, whey protein, and beta-alanine. I haven’t seen quite enough evidence to warrant placing betaine on this second tier, but from my perspective, a few more positive studies would probably bump it up to that level.
Based on the research available, betaine supplementation might be worth a shot if it fits your budget and you’re interested in testing the waters, especially if you’re primarily focused on body composition goals or prioritizing hypertrophy. It might also be interesting to try out if you’ve got a photoshoot or physique competition coming up, as its osmolytic properties could potentially make your muscles look a bit more full. In terms of dosing, 2.5g/day is used most commonly in the research reporting positive outcomes for strength, power, and body composition, and I’d give it a solid 6-8 weeks before assessing its impact. Of course, you don’t necessarily need to supplement in order to achieve a betaine intake up in the 2-3g/day range. Per 100g serving, you can find a pretty substantial amount of betaine in wheat bran (1339mg), wheat germ (1241mg), spinach (600-645mg), beets (114-297mg), pretzels (237mg), shrimp (219mg), and wheat bread (201mg), in addition to a variety of other wheat products and shellfish. If you’re looking for ideas, a nice smoothie with frozen beets, frozen spinach, and a little bit of wheat germ would be a good option, and the earthy flavor of beets is pleasantly complemented by some milk (dairy or non-dairy), peanut butter, and chocolate protein powder. Of course, supplementation can be a bit more convenient, and there are multiple commercially available betaine supplements on the market, which are either labeled as “betaine” or “trimethylgycine” (but make sure it’s not betaine hydrochloride [HCl] – that’s another supplement entirely). I wouldn’t expect any life-changing results from increasing betaine intake, but there’s at least some research suggesting that it might be worth a shot for lifters that are trying to squeeze every last drop of progress out of their training and supplementation.
Disclaimer: Eric Trexler is not a medical doctor or a dietitian. Speak to a qualified healthcare professional before making any changes to your diet or exercise habits.