BJSM reviews: A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance—Part 16
- M Manore1,
- R Meeusen2,
- B Roelands3,
- S Moran4,
- A D Popple5,
- M J Naylor6,
- L M Burke4,
- S J Stear7,
- L M Castell8
- 1Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, Oregon, USA
- 2Department Human Physiology and Sports Medicine, Vrije Universiteit Brussel, Brussel, Belgium
- 3Vrieje Universiteit Brussel, Brussels, Belgium
- 4Australian Institute of Sport, Canberra, Australia
- 5English Institute of Sport, Loughborough, UK
- 6English Institute of Sport, Twickenham, UK
- 7Performance Influencers Limited, London, UK
- 8University of Oxford, Oxford, UK
- Correspondence to Dr L M Castell, University of Oxford, Green Templeton College, Oxford OX2 6HG, UK;
- Accepted 8 November 2010
Part 16 looks at folate, an important vitamin required in cell division and formation of proteins in the body, and at three supplement ingredients primarily used by body builders: γ-aminobutyric acid (GABA), γ-oryzanol and γ-hydroxybutyrate (GHB). GABA, a major inhibitory neurotransmitter in the brain, became a popular supplement with bodybuilders in the early 1980s after a study showed it increased plasma growth hormone (GH) levels in man. γ-Oryzanol, a mixture of a plant sterol and ferulic acid ester, also marketed to body builders and strength training athletes, was used in hopes of boosting strength, increasing muscle gain, reducing body fat, speeding recovery and reducing postexercise soreness. GHB, a short-chain 4-carbon fatty acid found in the brain, has also been promoted as a nutritional supplement alleging enhanced muscle growth, better sleep quality and improved sexual performance.
M M Manore
Adequate folate intake is important for athletes and active individuals because of its role in red blood cell (RBC) production and tissue repair and maintenance.1 Folate plays a significant part in cell division, especially in tissues with rapid turnover such as RBCs. Folate deficiency leads to anaemia, caused by failure of the red cell precursors to develop into functional RBCs. The result is abnormally large RBCs that cannot effectively transport oxygen or remove carbon dioxide.
For many countries, the recommended dietary allowance (RDA) for folate is 400 µg/day for individuals aged >19 years.2 Folate is found in many foods but is especially high in leafy green vegetables, nuts, legumes and liver. The bioavailability of folate in food is ∼50%,2 but reduced by prolonged cooking. Many foods, such as breakfast cereals, are fortified with synthetic folic acid (∼50–100% of the RDA for folate), which is highly bioavailable (∼85%). Some countries have also made fortification of folic acid in enriched breads, flours and other grain products compulsory. Thus, our diets contain a mixture of food folate and synthetic folic acid with differing levels of bioavailability. Overall, the diets of active males appear to be adequate in folate as long as energy intake is adequate.1 Conversely, the apparent intake of dietary folate is consistently below recommendations for active females,1 3,–,6 which can be due to energy restriction for weight loss and/or under-reporting of food intake in food records. However, in female marathon runners, although folate supplementation (5 g/day for 10 weeks in conjunction with iron) improved blood folate levels, there was no effect on performance.7
R Meeusen and B Roelands
GABA is synthesised through the decarboxylation of glutamate by the enzyme glutamatic acid decarboxylase. Glutamate is the main excitatory neurotransmitter, and GABA is the major inhibitory neurotransmitter in the mature brain. GABA acts primarily by activating Cl− channels called GABAA receptors, and by eliciting metabotropic G-protein mediated responses by GABAB receptors.8 9 GABA is considered to act as a natural tranquiliser and antiepileptic agent in the brain.
GABAA receptors are the site of action of benzodiazepines, barbiturates and anaesthetics10 and known to mediate sedation. GABAB agonists may be useful for the treatment of pain and drug dependence.8 Baclofen, the first synthetic GABAB receptor agonist, is used clinically for the treatment of spasticity and skeletal muscle rigidity.11 GABAB antagonists on the other hand have shown antidepressant and cognition-enhancing effects.8 12
Baclofen, in rats, has been shown to prolong time to fatigue, possibly because of a boost in glycogen owing to the effect of interleukin 6 release in the muscle.13 Recently it was shown that GABA ingestion at rest increases immunoreactive GH (irGH) and immunofunctional GH (ifGH) secretion, which may enhance the skeletal muscle response to resistance training. Moreover, when GABA ingestion was combined with exercise, concentrations of irGH and ifGH rose even higher.14 Although some effects have been found, specifically for the response to resistance training, much more research regarding the effects of GABAergic manipulations on exercise performance is needed to elucidate the role of GABA.
γ-Oryzanol and ferulic acid
γ-Oryzanol, a mixture of a plant sterol and ferulic acid ester first isolated from rice bran oil in the early 1950s, has since been found to be in the lipid fraction of many other plants, and can be identified in various vegetable oils and products. The phytosterol base, structurally similar to cholesterol, has been promoted as having cholesterol-lowering and testosterone-enhancing activities, but these have not been substantiated in humans. Like other plant sterols, γ-oryzanol is poorly absorbed from the gastrointestinal tract. However, ferulic acid is well absorbed and has been proposed to be the active agent in γ-oryzanol, with activities including antioxidant properties.15 16 As a result, ferulic acid has been isolated and marketed as a separate supplement.
Despite a lack of evidence or consistent explanation of mechanisms underpinning claimed benefits, γ-oryzanol and ferulic acid have been marketed to, and used by, body builders and strength-training athletes in the hope of boosting strength, increasing muscle gain, reducing body fat, speeding recovery and reducing postexercise soreness. These supplements also claim to promote endorphin release. Only three studies, of which only one was published in a peer-reviewed publication, have tested these supplement claims on athletic performance.
A double-blind, placebo-controlled study of 22 recreationally weight-trained male college students involved a 9-week resistance exercise training protocol, combined with a daily intake of 500 mg of γ-oryzanol or placebo. Improvements in muscle strength and vertical jump power, increased body mass and decreased skinfold thickness were observed in both groups.16 A significant decrease in resting testosterone and cortisol concentrations was also observed at the end of the testing period in both groups, with no other alterations in hormone, lipid or blood parameters. These findings support the benefits of a training programme but do not find additional benefits from γ-oryzanol ingestion in terms of functional gains or alterations of various hormone concentrations.
An abstract describes a double-blind crossover study of six highly trained male distance runners who were supplemented with either placebo or 50 mg of ferulate daily for 3 weeks. Although workouts increased blood concentrations of cortisol, testosterone and β-endorphins, there were no differences in the response between ferulate and placebo trials, with the exception of an increase in postexercise β-endorphin concentrations during some sessions in the final week of intensified training.17 A further study reported in abstract form describes a multicentre double-blind, placebo-controlled trial in which weight lifters received either a placebo or ferulate treatment (15 mg twice daily) for 8 weeks. Using small numbers of participants, the authors reported a significant increase in body weight and shoulder press strength in the supplemented group (n=6) compared with the placebo group (n=4), but no differences in leg and chest strength.18
In summary, the effects of supplementation with γ-oryzanol and ferulic acid on athletic performance have not been well studied, and there is no current evidence to support their use in sport.
GHB and γ-butyrolactone
A D Popple and M J Naylor
GHB is a short-chain 4-carbon fatty acid found endogenously in the brain, mainly in the hypothalamus and basal ganglia, in the form of γ-hydroxybutyric acid. GHB has several precursors, including γ-butyrolactone, which are metabolised into GHB upon ingestion through various pathways. Concurrently, GHB is transformed into the inhibitory neurotransmitter GABA, with preference for the GABAb receptor.
The precise mechanism of action of GHB remains unclear. Its properties indicate a role in the brain as a neurotransmitter or neuromodulator.19 Additional research has shown it could influence serotonergic and dopaminergic activity, both directly and indirectly through interaction with other systems (eg, GABAb receptors).20 Primary effects include lowered inhibition, induced feelings of euphoria and increased libido. GHB was identified and synthesised more than 40 years ago as a central nervous system depressant: it has been used as an anaesthetic adjuvant and to improve sleep patterns.
Links to athletic performance came from a study proposing that GHB administration increased GH release.21 The drug was then marketed as a nutritional supplement alleging enhanced muscle growth, better sleep quality and improved sexual performance.
Simultaneously, GHB became popular during the 1980s with body builders due to the potential anabolic and performance-enhancing properties. These benefits have never been proven in athletic populations but, interestingly, a recent study that examined the effects of GHB on sleep and sleep-related GH release found that low-dose supplementation (2.5–3.5 g/day) caused a twofold increase in GH secretion during sleep.22 An exact mechanism was not identified, but it was suggested that GHB augments GH release by inducing deeper phases of sleep.
GHB and its precursors are not typically present in the diet, but can be found in flavouring agents. It is typically taken as a liquid or powder, and dosages range hugely from 12.5–100 mg/kg/day. It is rapidly absorbed and metabolised, and effects occur almost instantaneously. After a single dose (12.5–50 mg/kg), maximal plasma concentrations are reached after approximately 30–40 min, and its elimination half-life ranges from 30–50 min.23 24
Side effects include drowsiness, alcohol-like inebriation, dizziness and induction of sleep. Overdose can cause coma, respiratory depression and death. Frequent and prolonged use has resulted in increased tolerance, and dependence.25 Currently, no available evidence supports the use of GHB in the athletic population.
Female athletes routinely have lower levels of folate than recommended: however, in those whose levels have been raised by supplementation, no effect on performance has been observed. The succinct mini-reviews demonstrate the paucity of research on GABA, γ-oryzanol and ferulic acid, GHB supplementation in athletes and the lack of credible performance effects in athletes despite their popularity among body builders. For all four supplements, the overall message is again that there is insufficient evidence at the time of publication to warrant use of any of these supplements for performance, except where folate is required to correct a deficiency. Furthermore, athletes are cautioned against the high risk of inadvertent contamination and positive doping results from using GABA, GHB, γ-oryzanol and ferulic acid supplements.
LB, LC and SJ edited this series.
Competing interests None.
Provenance and peer review Not commissioned; not externally peer reviewed.