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Glycerol, guarana and the weight-loss agent, hydroxycut, occupy part 19; glycine will appear in part 20. The ubiquitous product, glycerol, is used both orally, for example, as an emulsifier in ice cream and topically, for example, as glycerine in hand cream. In the area of sports nutrition, glycerol plays a role in improving hydration status, as described in detail below. Guarana has been used for centuries as a stimulant in South America, due to its high caffeine content; it also contains xanthine alkaloids, such as theobromine and theophylline, which enhance the effects of caffeine. Further information on caffeine and sports performance can be found in part 6 of this series.1 Unlike glycerol and guarana, hydroxycut is an example of a multi-ingredient supplement with a proprietary formulation that presents special challenges when assessing safety and efficacy, including uncertainty as to which ‘active’ ingredients may provide the desired effects and frequent formulation changes.
L M Burke
Glycerol is a 3-carbon sugar alcohol that provides the backbone of triglycerides and is naturally found in foods as a component of dietary fats. However, its various physical and chemical properties are valuable in food technology: glycerol is added to manufactured foods and drinks as an emulsifier, humectant, sweetener, filler and thickener. Its viscosity also makes it useful as a component of lotions and creams, explaining its common availability for purchase in purified form under the name of glycerine. Although it has been suggested as a gluconeogenic precursor that could provide a substrate for exercise, the ingestion of glycerol by athletes is best known for its role as an osmolyte. When ingested or released following lipolysis, glycerol contributes to the osmotic pressure of body fluids until it is slowly metabolised. When consumed simultaneously with a substantial volume of fluid, there is a temporary retention of this fluid and expansion of body fluid compartments. Effective protocols for glycerol hyperhydration are 1–1.5 g/kg glycerol with an intake of 25–35 ml/kg of fluid.2 Such a protocol typically achieves a fluid expansion or retention of approximately 600–1000 ml above a fluid bolus alone by a reduction in urinary volume. Several challenging situations commonly arise in sport in which athletes have made use of these strategies to promote better hydration status. These include hyperhydration before exercise in hot environments where a large fluid deficit will otherwise accumulate, and reduction of diuresis associated with aggressive rehydration (eg, following weight-making practices in sport or after dehydrating exercise).2 General guidelines for fluid intake in exercise typically discount the value of hyperhydration or fluid overloading strategies.3 Indeed, there are occasional side-effects of glycerol use including nausea, gut discomfort and headaches from increased intracranial pressure.2 4 However, more focused reviews of glycerol hyperhydration in specific situations in sport, including a meta-analysis of glycerol hyperhydration before exercise in hot environments, have reported evidence of enhanced fluid balance and endurance performance compared with the intake of large volumes of water alone or no hyperhydration.2 4 There has been less focus, but some support, for the addition of glycerol to rehydration beverages to promote the rapid reversal of dehydration and assist the performance of subsequent exercise.2 Indeed, there anecdotal reports that some athletes add glycerol to rehydration beverages for practical reasons; for example, to reduce overnight diuresis and its interruption to sleep patterns when completing dehydrating exercise sessions late in the day. The apparent contradictions in the literature may be due to the specificity of the situations in which glycerol hyper/re-hydration is beneficial. The major problem related to the use of glycerol by athletes, however, arises because of recent changes to antidoping codes. The 2011 World Anti-Doping Agency (WADA) list of substances prohibited at all times includes the category of Diuretics and other Masking agents (Section 5). Plasma expanders further qualified in this section are: “eg, glycerol, intravenous administration of albumin, dextran, hydroxethyl starch and mannitol” (http://www.wada-ama.org). How the normal dietary intake of glycerol is distinguished from specific intake to aid fluid balance is unclear.
S J Stear
Guarana (Paullinia cupana), a climbing plant in the maple family, native to the Amazon basin and especially common in Brazil, contains a high amount of guaranine, a chemical substance with the same characteristics as caffeine. Guaranine, a synonym for caffeine, is defined only as the caffeine chemical in guarana and is identical to the caffeine chemical derived from other sources (eg, coffee, tea, maté).
Guarana features large leaves, clusters of flowers, and a fruit similar in size to the coffee bean. As a dietary supplement, guarana is a useful caffeine source with guarana seeds containing approximately twice the amount of caffeine (2–4.5%) compared with 1–2% for coffee beans.5 Table 1 contains a partial listing of some of the main chemicals found in guarana seeds.
Table 1 illustrates that guarana, alongside other natural sources of caffeine, also contains varying mixtures of other xanthine alkaloids such as theobromine and theophylline. Guarana is generally recognised as an acceptable ingredient and can be found in drinks, ‘energy’ shots, herbal teas or capsules.
Consequently, guarana is best known for its stimulatory properties, providing similar benefits to caffeine, such as reducing fatigue, increasing alertness, and as an ergogenic aid in the athletic arena.1 6 The maximal ergogenic benefits of caffeine and guarana can be seen at small to moderate caffeine doses (2–3 mg/kg). Theoretically, it is possible to overdose on caffeine or guarana, with the fatal dose being estimated at a single dose of 10 g pure caffeine/guaranine.
A Lobb, M Ellison
Hydroxycut is a combination weight-loss supplement whose active ingredients include Cissus quadrangularis (CQ) (part 9)13 and caffeine (part 6).1 There are several subformulations containing various combinations of other botanical ingredients, including extracts of goji (Lycium barbarum), acerola (Malpighia glabra), wild mint (Mentha longifolia) and pomegranate (Punica granatum). As currently formulated, we could find no published studies assessing the product's safety and efficacy for weight loss in any population. The botanical ingredients lack evidence of efficacy for weight loss in high quality randomised trials in any population, and the safety of individual ingredients in humans, and potential interactions, are largely unknown. Some of these botanical agents may have a significant polyphenol/antioxidant component, which may be beneficial during hard training and weight loss. However, these ingredients will be covered elsewhere in this series. A previous formulation of hydroxycut was withdrawn from the market after being associated with 23 cases of hepatotoxicity and one death.7 8 The suspected hepatotoxic ingredients included hydroxycitric acid (HCA) extracted from the garcinia cambogia fruit, chromium, and Camellia sinensis (green tea).9 These ingredients have been removed from the current formulation, although HCA continues to be available in other products, both alone and in combination with chromium and Camellia sinensis. Small, short-duration pilot studies have reported that 8 weeks of HCA supplementation resulted in statistically significant weight loss compared with placebo.10
In hydroxycut's current formulation, HCA has been replaced with CQ (chromium and Camellia sinensis have also been removed). Small, short-duration pilot studies of CQ have reported that 10 weeks of supplementation resulted in statistically significant weight loss compared with placebo.11 12 When taken as directed, the supplement provides 200 mg of caffeine per dose, with two doses suggested per day. In athletes, modest caffeine supplementation has been found to be an ergogenic aid that positively affects exercise capacity and performance; potential side-effects include irritability, tremor and an increase in heart rate.1 As is the case with many weight-loss supplements, hydroxycut contains potentially powerful pharmacoactive ingredients, but has never undergone high quality study to assess its safety and efficacy. To date the few published trials of CQ (and HCA) effectiveness in non-athletes have methodological weaknesses including short duration and small size. For both HCA and CQ, many published positive studies are funded by supplement manufacturers yet lack standard conflict of interest declarations.7
Furthermore, as a product that receives minimal regulatory oversight or postmarket surveillance,7 14 there is an increased risk of issues with purity or potency (that the supplement contains what it claims, and that there are no unlisted ingredients), and the true scale of any safety risk is not clear. Because of the lack of good evidence of safety and efficacy, herbal weight-loss products are avoided by most performance nutrition practitioners in elite sport. Athletes seeking to lose weight should instead aim for an energy deficit of 500–1000 kcal/day through diet and/or training.
There are clearly unwanted effects with the use of all the supplements discussed in this part of our series. Glycerol has been used to assist athletes in weight-making practices in sport or after dehydrating exercise; by contrast, hydroxycut may have been used by athletes trying to achieve weight loss. However, as a plasma expander, glycerol has recently (2011) come under the jurisdiction of WADA, and it is difficult to ascertain the current ramifications for its role in aiding fluid balance. Guarana seeds have approximately twice as much caffeine as coffee beans. Nevertheless, it does not appear to be compulsory to state on nutritional advice labels that guarana contains caffeine, despite its high levels. It is sometimes included in products that already contain a large amount of caffeine. Athletes thus need to be aware of the possible effects of high caffeine, such as tremors, irritability and increased heart rate. Caffeine is also included in hydroxycut. While weight loss products such as hydroxycut are claimed to have pharmacological effects, they are not required to meet the same degree of regulatory scrutiny as pharmaceutical agents before going to market, are heavily advertised, and are widely available on the internet and in retail outlets. It bears repeating that all athletes are strongly advised to seek advice from a qualified, professional nutritionist before deciding to take a supplement: this advice is particularly appropriate to part 19.
Competing interests None.
Provenance and peer review Commissioned; not externally peer reviewed.