Br J Sports Med 46:689-690 doi:10.1136/bjsports-2012-091314
  • Nutritional supplement series

A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance–Part 34

  1. L M Castell7
  1. 1Department of Kinesiology, Iowa State University, Ames, Iowa, USA
  2. 2Hammersley & Partners Medical Practice, Oxford, UK
  3. 3Department of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
  4. 4Biology Department, Drake University, Des Moines, Iowa, USA
  5. 5Australian Institute of Sport, Canberra, Australia
  6. 6Performance Influencers Limited, London, UK
  7. 7Green Templeton College, University of Oxford, Oxford, UK
  1. Correspondence to L M Castell, Green Templeton College, University of Oxford, Oxford OX2 6HG, UK; lindy.castell{at}
  • Received 23 April 2012
  • Accepted 23 April 2012

Introductory remarks

Part 34 is dominated by a review of prohormones, or more specifically, testosterone prohormones, which cause concern in sports nutrition related to their direct use or inadvertent intake as contaminants in other supplements. When taken specifically for their alleged effects as testosterone alternatives, they may give rise to health problems while failing to achieve the claimed benefits of enhanced strength and muscle mass. Prohormones are a Prohibited Substance on the World Anti-Doping Agency (WADA) list and, even in minute concentrations (as occurs in contaminated supplements) these products can lead to a positive doping outcome. This part also contains brief summaries of ribose and smilax, two supplements which have not lived up to any claims related to benefits to athletic performance.


D S King, R Baskerville

The term prohormone strictly refers to a post-translational peptide that is cleaved by convertases into a variety of bioactive hormones .In the supplement context, prohormones refer to androgenic precursors which, when ingested, become enzymatically activated to testosterone derivatives. An understanding of the biochemical pathways emphasises the similarity between testosterone and its precursors.

Users see prohormones as a natural means to improve muscle strength, body composition and general well-being with fewer side effects than testosterone or synthetic androgenic steroids and a more practical (capsule) form of intake. The marketing strategy of commercial websites is to promote prohormones as ‘legal alternatives’ to testosterone with similar anabolic effects. Of course, many consumers are unaware that these prohormones are included on the WADA list of prohibited substances as well as being illegal for sale or importation in many countries. Prohormones have another concerning role in sports nutrition as contaminants in other sports supplements which account for a large proportion of inadvertent doping offences.

From cholesterol, pregnenolone is produced which converts to testosterone via dihydroepiandosterone (DHEA). The path via DHEA produces androstenedione (DIONE) and androstenediol (DIOL) which convert to testosterone. Importantly, however, these precursors can also be converted to the oestrogens, which may cause effects such as gynaecomastia and liver dysfunction. To counteract this effect, some users of prohormones alternate between 1 month on and 2 months off,allowing restoration of intrinsic function within each ‘cycle’. Users also often ‘stack’ differing prohormones of differing oestrogenicity within each cycle, and take N-acetyl cysteine to prevent liver dysfunction. In addition, selective oestrogen receptor modulators or aromatase inhibitors are taken to mitigate oestrogenic effects, and androgenic herbal compounds taken to reduce the ‘low’ period between cycles.

Despite these sophisticated multidrug regimens and marketing claims, research fails to demonstrate any anabolic or ergogenic effects of taking DHEA, DIONE or DIOL, and confirms the risk of adverse side effects for DIONE and DIOL. For example Broeder et al1 gave 200 mg/day DIONE or DIOL to middle-aged men over a 12-week resistance training programme, and showed a significant 16% increase in testosterone levels after 1 month of use which had returned to prestudy levels by 12 weeks. DIOL did not significantly increase blood testosterone levels. The major fate of the ingested DIONE and DIOL appears to be aromatisation, since blood oestrogen levels were increased by∼63%. There was no enhancement in muscle strength during resistance training above placebo but, conversely, an 11% increase in the LDL-Cholesterol/HDL-Cholesterol lipid ratio, corresponding to a significant increase in the cardiovascular disease risk. Twelve weeks of supplementation reduced blood luteinising hormone levels, which may serve to decrease inherent testicular and adrenal testosterone production.

The last major literature review, by Brown et al,2 confirmed the findings that DIONE, DIOL and DHEA do not augment muscle size and strength gains observed from resistance training alone, and that use of DIONE and DIOL may predispose users to serious health risks. UK Legislation in this field comes under Schedule 4 of the Misuse of Drugs Act 1971, and the current list of 54 ‘class C’ substances includes both prohormones and anabolic steroids and closes a loophole in recognition of their biochemical similarity. However, in contrast to US law, personal use is not yet criminalised under the act, although supply or production without a licence carries a maximum sentence of 14 years. This legal framework augments the ban by sports which adopt the WADA antidoping code.


Y Hellsten

ATP is the only directly usable source of energy for muscle contraction. At high-exercise intensities, the rate of ATP utilisation can exceed that of its regeneration from other energy sources and ATP levels in the muscle cells decrease. Most degraded ATP remains within the muscle as inosine monophosphate (IMP) which, after exercise, is used for resynthesis of ATP. However, a fraction of the IMP is degraded and lost from the muscle as purines. If intense exercise sessions are repeated, there may be an accumulated loss of ATP through the release of purines, whereby ATP stores in the muscle cells are reduced. The ATP lost from muscle may be replenished by de novo synthesis and D-ribose availability may be limiting for ATP de novo synthesis.

Experimental studies have shown that ribose supplementation does not lower the loss in nucleotides with repeated intense exercise bouts but allows for a faster recovery of ATP levels within 72 h after termination of exercise training, most likely due to an improved rate of de novo ATP synthesis.3 However, despite a higher level of ATP after ribose supplementation, the study showed no effect on intense intermittent exercise performance.3 Accordingly, other studies examining the effect of ribose on performance during intense intermittent exercise4,,7 and rowing8 have not been able to demonstrate improved performance in humans. Ribose dosages up to ∼40 g/day, at times divided in 2–3 supplementations per day have been examined. There are no known adverse effects of ribose but reports on long-time use are lacking. It is concluded that, although ribose supplementation appears to improve the rate of de novo synthesis of ATP in muscle, existing scientific evidence do not support the use of ribose as an ergogenic aid in young, healthy individuals.

Royal Jelly

L M Castell

Royal jelly is secreted by worker bees to feed young larvae to produce a queen bee: it contains a source of amino acids, fatty acids, carbohydrate and B-vitamins, and has long been used as a dietary supplement in complementary medicine. Little, however, is known about it in the context of exercise. Chupin et al9 used sublingual doses of royal jelly, apparently combined with other components, on athletes undergoing rehabilitation in Irkutsk. It was not possible to deduce which components might have been responsible for the apparent improvements observed in the athletes' general well-being. Kamakura et al10 reported a possible beneficial effect of fresh royal jelly (it degrades in storage) in mice, on recovery from swimming to exhaustion. No other studies on royal jelly per se in exercise have been found, and there is little or no evidence to suggest that it might be of use to athletes. Furthermore, royal jelly can cause allergic reactions.

Smilax (sarsaparilla)

D S Senchina

The plant genus Smilax includes several hundred species from the lily order that are distributed globally and commonly known as greenbriar or sarsaparilla (also spelled ‘zarzaparilla’ and often pronounced ‘sasparilla’). Belowground parts (rhizomes and roots) and bark from these plants are used in many traditional cultures to produce root beer, food or various herbal medicines. Smilax supplements are often produced from Smilax medica, Smilax officinalis and Smilax regelii belowground parts via extraction, and are rich in a category of plant sterols called saponins including sarsasapogenin (sarsapogenin), smilagenin (a derivative of sapogenin), sitosterol and stigmasterol. Bodybuilders consume Smilax supplements for their purported anabolic effects,11 mistakenly perceiving sarsaparilla sterols as prohormonal compounds that can be converted into testosterone by the human body and subsequently increase muscle mass, power, maximal performance and overall metabolism, though these possibilities have been disproved.12 ,13 Other benefits attributed to Smilax supplements include increasing endurance or energy, promoting recovery, lowering body fat12 and enhancing immune function.13 Documented side effects include stomach upset and kidney problems (including increased urination) and possible interactions with other supplements or drugs.11 ,14 Typical doses for Smilax supplements are 5–10 ml of extract or 1–4 g dried belowground parts daily.14 Sports nutrition authorities have found no evidence of ergogenic benefits from Smilax supplementation; therefore its use is discouraged.

Concluding comments

Unfortunately, Part 34 does not contain any good news for athletes who are interested in supplemental products that can enhance athletic performance. In fact, the news can be unfortunate in the case of athletes who deliberately, or inadvertently, consume prohormone products. These products are banned under antidoping codes, and urine tests are often able to detect their intake, even in minute amounts. Since strict liability is applied to the inadvertent intake of these products,15 at best athletes who consume these products can hope to escape a positive doping test, while the worst case scenarios can include doping sanctions or health problems.


  • Competing interests None.

  • Provenance and peer review Commissioned; not externally peer reviewed.