Effects of betaine on performance and body composition: a review of recent findings and potential mechanisms

Betaine is a methyl derivative of glycine first isolated from sugar beets. Betaine consumed from food sources and through dietary supplements presents similar bioavailability and is metabolized to di-methylglycine and sarcosine in the liver. The ergogenic and clinical effects of betaine have been investigated with doses ranging from 500 to 9,000 mg/day. Some studies using animal models and human subjects suggest that betaine supplementation could promote adiposity reductions and/or lean mass gains. Moreover, previous investigations report positive effects of betaine on sports performance in both endurance- and resistance-type exercise, despite some conflicting results. The mechanisms underlying these effects are poorly understood, but could involve the stimulation of lipolysis and inhibition of lipogenesis via gene expression and subsequent activity of lipolytic-/lipogenic-related proteins, stimulation of autocrine/endocrine IGF-1 release and insulin receptor signaling pathways, stimulation of growth hormone secretion, increased creatine synthesis, increases in protein synthesis via intracellular hyper-hydration, as well as exerting psychological effects such as attenuating sensations of fatigue. However, the exact mechanisms behind betaine action and the long-term effects of supplementation on humans remain to be elucidated. This review aims to describe evidence for the use of betaine as an ergogenic and esthetic aid, and discuss the potential mechanisms underlying these effects.

Cholewa, J.M., L. Guimaraes-Ferreira, and N.E. Zanchi, Effects of betaine on performance and body composition: a review of recent findings and potential mechanisms. Amino Acids, 2014

Betaine supplementation improved body composition, arm size, bench press work capacity, attenuated the rise in urinary HCTL, and tended to improve power but not strength

BACKGROUND: This study investigated the effects of long term betaine supplementation on body composition, performance, and homocysteine thiolactone (HCTL) in experienced strength trained men. METHODS: Twenty-three subjects were matched for training experience (4.8 +/- 2.3 years) and body fat percentage (BF%: 16.9 +/- 8.0%), randomly assigned to either a placebo (PL; n = 12) or betaine group (BET; n = 11; 2.5 g/day), and completed a 6 week periodized training program consisting of 3 two-week micro-cycles. Bench press and back squat training volumes were recorded and changes in training volume were assessed at each micro-cycle. Fasting urine was collected at baseline (BL), weeks 2, 4 and 6, and assayed for HCTL. Subjects were tested prior to and following 6 weeks of treatment. Arm and thigh cross sectional area (CSA) was estimated via girth and skin fold measurements. Body density was estimated via skin fold calipers and used to estimate BF%, fat mass (FM), and lean body mass (LBM). Performance was assessed via vertical jump (VJ), bench press 1 RM (BP), and back squat 1 RM (BS).
RESULTS: Arm CSA increased significantly (p < .05) in BET but not PL. No differences existed between group and time for changes in thigh CSA. Back squat training volume increased significantly (p < .05) for both groups throughout training. Bench press training volume was significantly (p < .05) improved for BET compared to PL at microcycles one and three. Body composition (BF%, FM, LBM) improved significantly (p < .05) in BET but not PL. No differences were found in performance variables (BP, BS, VJ) between groups, except there was a trend (p = .07) for increased VJ power in BET versus PL. A significant interaction (p < .05) existed for HCTL, with increases from BL to week 2 in PL, but not BET. Additionally, HCTL remained elevated at week 4 in PL, but not BET.
CONCLUSION: 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, J.M., et al., Effects of betaine on body composition, performance, and homocysteine thiolactone. J Int Soc Sports Nutr, 2013. 10(1): p. 39

Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance

We aimed to investigate the role of betaine supplementation on muscle phosphorylcreatine (PCr) content and strength performance in untrained subjects. Additionally, we compared the ergogenic and physiological responses to betaine versus creatine supplementation. Finally, we also tested the possible additive effects of creatine and betaine supplementation. This was a double-blind, randomized, placebo-controlled study. Subjects were assigned to receive betaine (BET; 2 g/day), creatine (CR; 20 g/day), betaine plus creatine (BET + CR; 2 + 20 g/day, respectively) or placebo (PL). At baseline and after 10 days of supplementation, we assessed muscle strength and power, muscle PCr content, and body composition. The CR and BET + CR groups presented greater increase in muscle PCr content than PL (p = 0.004 and p = 0.006, respectively). PCr content was comparable between BET versus PL (p = 0.78) and CR versus BET + CR (p = 0.99). CR and BET + CR presented greater muscle power output than PL in the squat exercise following supplementation (p = 0.003 and p = 0.041, respectively). Similarly, bench press average power was significantly greater for the CR-supplemented groups. CR and BET + CR groups also showed significant pre- to post-test increase in 1-RM squat and bench press (CR: p = 0.027 and p < 0.0001; BET + CR: p = 0.03 and p < 0.0001 for upper- and lower-body assessments, respectively) No significant differences for 1-RM strength and power were observed between BET versus PL and CR versus BET + CR. Body composition did not differ between the groups. In conclusion, we reported that betaine supplementation does not augment muscle PCr content. Furthermore, we showed that betaine supplementation combined or not with creatine supplementation does not affect strength and power performance in untrained subjects.

Del Favero, S., et al., Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids, 2012. 42(6): p. 2299-2305

Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation

BACKGROUND: Betaine (BET) is a component of many foods, including spinach and wheat. It is an essential osmolyte and a source of methyl groups. Recent studies have hypothesized that BET might play a role in athletic performance. However, BET effects on skeletal muscle differentiation and hypertrophy are still poorly understood.
METHODS: We examined BET action on neo myotubes maturation and on differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR array, Western blot and immunofluorescence analysis to study the BET effects on morphological features of C2C12 and on signaling pathways involved in muscle differentiation and hypertrophy.
RESULTS: We performed a dose--response study, establishing that 10 mM BET was the dose able to stimulate morphological changes and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to identify the expression profile of genes encoding proteins involved in IGF-1 pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R) expression. Western blot and immunofluorescence analysis, performed in neo myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of Myosin Heavy Chain (MyHC) and neo myotubes length.In addition, we investigated BET role on myoblasts proliferation and differentiation. During proliferation, BET did not modify C2C12 proliferative rate, but promoted myogenic induction, enhancing MyoD protein content and cellular elongation. During differentiation, BET caused an increase of muscle-specific markers and IGF-1 R protein levels. CONCLUSIONS: Our findings provide the first evidence that BET could promote muscle fibers differentiation and increase myotubes size by IGF-1 pathway activation, suggesting that BET might represent a possible new drug/integrator strategy, not only in sport performance but also in clinical conditions characterized by muscle function impairment.

Senesi, P., et al., Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation. J Transl Med, 2013. 11(1): p. 174

Betaine supplementation reduced subjective measures of fatigue to an exercise protocol

Effect of 15 days of betaine ingestion on concentric and eccentric force outputs during isokinetic exercise. J Strength Cond Res 25(8): 2235-2241, 2011—The purpose of this study was to examine the efficacy of 15 days of betaine supplementation on peak concentric (CON) and eccentric (ECC) force during isokinetic exercise in active college-aged men. Eleven men volunteered for this study (21.7 ± 5.1 years; height: 178.5 ± 6.4 cm; body mass: 79.8 ± 10.3 kg). Subjects were randomly assigned to either a supplement (BET) or placebo (PL) group. Supplementation occurred for 15 days. Subjects reported to the Human Performance Laboratory on 5 occasions during this period, separated by 72 hours, for a testing and exercise session on an isokinetic chest press device. After each exercise protocol, subjects rated their fatigue and muscle soreness on a 15-cm visual analog scale. Subjects then consumed no daily BET for 4 weeks but maintained familiarity with the exercise device once per week. After the washout period, subjects resumed the BET protocol using the opposite drink and repeated the same 15-day protocol. No differences were noted in maximum CON force output between pre (335.9 ± 78.3 and 321.6 ± 63.6 N) and post (330.3 ± 74.8 and 330.2 ± 71.6 N) workouts in both BET and PL, respectively. In addition, no differences were noted in maximum ECC force output between pre (352.0 ± 90.6 and 324.4 ± 85.2 N) and post (353.2 ± 98.2 and 366.9 ± 128.5 N) workouts in BET and PL, respectively. No differences in subjective measures of soreness and fatigue were seen, but a significant reduction in Δ fatigue was observed in BET compared to PL. In conclusion, 15 days of betaine supplementation did not increase peak CON or ECC force outputs during an isokinetic chest press but did appear to reduce subjective measures of fatigue to the exercise protocol.

Hoffman, J.R., et al., Effect of 15 Days of Betaine Ingestion on Concentric and Eccentric Force Outputs During Isokinetic Exercise. The Journal of Strength & Conditioning Research, 2011. 25(8): p. 2235-2241.

Betaine ingestion improves cycling sprint power in recreationally active males and females

ABSTRACT: Purpose To examine the effect of betaine supplementation on cycling sprint performance. METHODS: Sixteen recreationally active subjects (7 females and 9 males) completed three sprint tests, each consisting of four 12 sec efforts against a resistance equal to 5.5% of body weight; efforts were separated by 2.5 min of cycling at zero resistance. Test one established baseline; test two and three were preceded by seven days of daily consumption of 591 ml of a carbohydrate-electrolyte beverage as a placebo or a carbohydrate-electrolyte beverage containing 0.42% betaine (approximately 2.5 grams of betaine a day); half the beverage was consumed in the morning and the other half in the afternoon. We used a double blind random order cross-over design; there was a 3 wk washout between trials two and three. Average and maximum peak and mean power were analyzed with one-way repeated measures ANOVA and, where indicated, a Student Newman-Keuls.
RESULTS: Compared to baseline, betaine ingestion increased average peak power (6.4%; p < 0.001), maximum peak power (5.7%; p < 0.001), average mean power (5.4%; p = 0.004), and maximum mean power (4.4%; p = 0.004) for all subjects combined. Compared to placebo, betaine ingestion significantly increased average peak power (3.4%; p = 0.026), maximum peak power max (3.8%; p = 0.007), average mean power (3.3%; p = 0.034), and maximum mean power (3.5%; p = 0.011) for all subjects combined. There were no differences between the placebo and baseline trials.
CONCLUSIONS: One week of betaine ingestion improved cycling sprint power in recreationally active males and females.

Pryor, J.L., S.A. Craig, and T. Swensen, Effect of betaine supplementation on cycling sprint performance. J Int Soc Sports Nutr, 2012. 9(1): p. 12-18.

Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise

Our aim was to examine the effect of betaine supplementation on selected circulating hormonal measures and Akt muscle signaling proteins after an acute exercise session. Twelve trained men (age 19.7 +/- 1.23 years) underwent 2 weeks of supplementation with either betaine (B) (1.25 g BID) or placebo (P). Following a 2-week washout period, subjects underwent supplementation with the other treatment (B or P). Before and after each 2-week period, subjects performed an acute exercise session (AES). Circulating GH, IGF-1, cortisol, and insulin were measured. Vastus lateralis samples were analyzed for signaling proteins (Akt, p70 S6k, AMPK). B (vs. P) supplementation approached a significant increase in GH (mean +/- SD (Area under the curve, AUC), B: 40.72 +/- 6.14, P: 38.28 +/- 5.54, p = 0.060) and significantly increased IGF-1 (mean +/- SD (AUC), B: 106.19 +/- 13.45, P: 95.10 +/- 14.23, p = 0.010), but significantly decreased cortisol (mean +/- SD (AUC), B: 1,079.18 +/- 110.02, P: 1,228.53 +/- 130.32, p = 0.007). There was no difference in insulin (AUC). B increased resting Total muscle Akt (p = 0.003). B potentiated phosphorylation (relative to P) of Akt (Ser(473)) and p70 S6 k (Thr(389)) (p = 0.016 and p = 0.005, respectively). Phosphorylation of AMPK (Thr(172)) decreased during both treatments (both p = 0.001). Betaine (vs. placebo) supplementation enhanced both the anabolic endocrine profile and the corresponding anabolic signaling environment, suggesting increased protein synthesis.
Apicella, J.M., et al., Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise. Eur J Appl Physiol, 2013. 113(3): p. 793-802

The effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation and associated biochemical parameters in resistance trained men

We examined the effects of chronic betaine supplementation on exercise performance and associated parameters in resistance trained men. Men were randomly assigned in a double-blind manner using a crossover design to consume betaine (2.5 g of betaine mixed in 500 ml of Gatorade(R)) or a placebo (500 ml of Gatorade(R)) for 14 days, with a 21-day washout period. Before and after each treatment period, tests of lower- and upper-body muscular power and isometric force were conducted, including a test of upper-body muscular endurance (10 sets of bench press exercise to failure). Muscle tissue oxygen saturation (StO2) during the bench press protocol was measured via near infrared spectroscopy. Blood samples were collected before and after the exercise test protocol for analysis of lactate, nitrate/nitrite (NOx), and malondialdehyde (MDA). When analyzed using a repeated measures analysis of variance, no significant differences were noted between conditions for exercise performance variables (p > 0.05). However, an increase in total repetitions (p = 0.01) and total volume load (p = 0.02) in the 10-set bench press protocol was noted with betaine supplementation (paired t-tests), with values increasing approximately 6.5% from preintervention to postintervention. Although not of statistical significance (p = 0.14), postexercise blood lactate increased to a lesser extent with betaine supplementation (210%) compared with placebo administration (270%). NOx was lower postintervention as compared with preintervention (p = 0.06), and MDA was relatively unchanged. The decrease in StO2 during the bench press protocol was greater with betaine vs. placebo (p = 0.01), possibly suggesting enhanced muscle oxygen consumption. These findings indicate that betaine supplementation results in a moderate increase in total repetitions and volume load in the bench press exercise, without favorably impacting other performance measures.

Trepanowski, J.F., et al., 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(12): p. 3461-71.

Betaine supplementation improved cycling sprint power

This study examined the effect of betaine on cycling sprint performance.

Sixteen untrained subjects (7 females and 9 males) completed three sprint tests, each consisting of four 12 sec efforts against 5.5% of body weight as resistance; efforts were separated by 2.5 min of cycling at zero resistance. Test one established baseline; test two and three were preceded by daily consumption of 591 ml of a carbohydrate-electrolyte beverage as a placebo or a carbohydrate-electrolyte beverage containing 0.42% betaine. A double blind random order crossover design and a three-week washout between trials were used. Average and maximum peak and mean power were analyzed with one-way repeated measures ANOVA and, where indicated, a Student Newman–Keuls; α was set at 0.05.

Compared to baseline, betaine ingestion increased average peak power (6.4%, p < 0.001), max peak power (5.7%, p < 0.001), average mean power (5.4%, p = 0.004), and max mean power (4.4%, p = 0.004) for all subjects combined. Compared to placebo, betaine ingestion significantly increased average peak power (3.4%, p = 0.026), max peak power max (3.8%, p = 0.007), average mean power (3.3%, p = 0.034), and max mean power (3.5%, p = 0.011) for all subjects combined. There were no differences between the placebo and baseline trials.

One week of betaine ingestion improved cycling sprint power in untrained males and females.

Czapla R, Swensen T, and Craig SAS. Effect of betaine on cycling sprint power. Journal of the International Society of Sports Nutrition. 2010;7(Suppl 1):P23

Ergogenic effects of betaine on strength and power

Twelve men completed two 14-day experimental trials separated by a 14-day washout period, in a balanced, randomized, double-blind, repeated measures, crossover design. Prior to and following 14 days of twice daily betaine (B) or placebo (P) supplementation, subjects completed two consecutive days (D1 and D2) of a standardized high intensity strength/power resistance exercise challenge (REC). Performance included bench, squat, and jump tests.

Following 14-days of B supplementation, D1 and D2 bench throw power and isometric bench press force were increased during REC compared to pre-supplementation values and corresponding P values. Compared to pre-supplementation, vertical jump power and isometric squat force increased on D1 and D2 following B supplementation. However, there were no differences in jump squat power or the number of bench press or squat repetitions.

Therefore, B supplementation increased power, force and maintenance of these measures in selected performance measures, and these were more apparent in the smaller upper-body muscle groups.

Lee et al (2010). "Ergogenic effects of betaine supplementation on strength and power performance." Journal of the International Society of Sports Nutrition 7(1): 27.

Muscle endurance and quality of repetitions

This study examined the efficacy of 15 days of betaine supplementation on muscle endurance, power performance and rate of fatigue in active college-aged men. Male subjects (24) were randomly assigned to one of two groups; the first consumed betaine daily (2.5 g/d), and the second consumed a placebo. Subjects were tested prior to the onset of supplementation (T1) and 7 (T2) and 14 days (T3) following supplementation. Subjects were tested over a 2-day period for:

- vertical jump power (VJP)
- bench press throw (BPT) power
- number of squat repetitions at 75% 1-RM (peak and mean power)
- number of bench press repetitions at 75% 1-RM (peak and mean power)
- two 30-sec Wingate anaerobic power tests (WAnT) (Day 2)

There were no differences in power assessment (VJP, BPT, WAnT) between the groups, or in the repetitions performed to exhaustion or in the number of repetitions performed at 90% of both peak and mean power between the groups in the bench press exercise.

However, the number of repetitions performed in the squat exercise for BET was significantly greater (p < 0.05) than that seen for PL at T2. The number of repetitions performed at 90% or greater of peak power in the squat exercise was significantly greater for BET at both T2 and T3 than PL. It was concluded that either 1 or 2 weeks of betaine supplementation in active, college males improved muscle endurance of the squat exercise, and increased the quality of repetitions performed.

Hoffman et al (2009). "Effect of Betaine Supplementation on Power Performance and Fatigue." Journal of the International Society of Sports Nutrition 6(1): 7.

Strength and Power

Maresh et al (2007). "The Effects of Betaine Supplementation on Strength and Power Performance" Med Sci Sports Exerc 39(5 Suppl): S101.

This study found that ingestion of betaine over 2 weeks led to increased power, force and maintenance as measured in:

- vertical jump power
- isometric squat force
- isometric bench press
- bench throw power

There were no differences in bench press repetitions, number of squat repetitions, and jump squat power.

Athletic Performance in the Heat

Armstrong et al (2008). "Influence of betaine consumption on strenuous running and sprinting in a hot environment." J Strength Cond Res 22(3): 851-60.

Investigators found a trend towards longer sprint time until exhaustion when betaine was present in either a sports beverage or in flavored water compared to placebo.

Papers 2004-7:

Millard-Stafford et al (2005). "Fluid replacement in the heat - effects of betaine." Med Sci Sports Exerc 37(5): S28.

Betaine and Muscle

This paper helps explain the positive effects seen on muscle by betaine.

Ortiz-Costa et al (2008) "Betaine protects urea-induced denaturation of myosin subfragment-1."

Myosin belongs to a family of motor proteins that transform the chemical energy of ATP into mechanical work.

Urea, a waste-product of protein metabolism, can increase due to exercise. Urea alters the structure of skeletal muscle myosin subfragment-1 (the catalytic domain), thereby inhibiting ATPase activity and reducing energy production.

Betaine, acting as a 'counteracting' osmolyte, was able to protect against these changes in structure, thereby preserving the enzyme’s catalytic activity.

Papers 2003-7:

Brigotti et al (2003). "Effects of osmolarity, ions and compatible osmolytes on cell-free protein synthesis." Biochem. J. 369(2): 369-374.