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Br J Sports Med 2012;46:618–620. doi:10.1136/bjsports-2012-091198618

Nutritional supplement series

INTRODUCTORY REMARKS Quercetin was fi rst introduced to our A–Z series in the article on fl avonoids.1 In Part 33, the author of the fl avonoid review, Dr Nieman, updates this topic. We also cover another intriguing plant- based compound with proposed benefi ts as an antioxidant and stimulator of mitochondrial bio- genesis, resveratrol. Rhodiola rosea, a claimed adap- togen, concludes this issue.

QUERCETIN D C Nieman Epidemiological studies support multiple disease prevention benefi ts for individuals consuming foods rich in the fl avonol quercetin. In vitro and animal studies indicate that quercetin is a strong antioxi- dant and anti-infl ammatory agent, and exerts anti- pathogenic and immune regulatory infl uences.2 Quercetin supplementation studies in community- dwelling humans do not refl ect these positive bene- fi ts, but research is continuing in order to determine the proper outcome measures, dosing regimen and adjuvants that may amplify any perceived bioactive effects of quercetin in vivo.

Quercetin supplementation studies in athletes have focused on potential infl uences on post-exer- cise infl ammation, oxidative stress and immune dysfunction, illness rates following periods of physiological stress and exercise performance.

Results thus far have been negative for quer- cetin’s countermeasure effects on postexercise physiological stress indicators, such as immune perturbations.3–5 However, when quercetin sup- plementation is combined with other polyphenols and food components such as green tea extract, isoquercetin and fi sh oil, a substantial reduction in exercise-induced infl ammation and oxidative stress occurs in athletes, with augmentation of innate immune function.6

Quercetin exerts strong antiviral activities when cultured with a wide variety of pathogens. In mice, quercetin supplementation for 7 days before inoc- ulation with infl uenza virus and a 3-day period of heavy exertion partially reduced the exercise- induced increase in morbidity and mortality.7 A 12-week community trial showed a modest reduction in upper respiratory tract infections (URTI) among physically active subjects between the ages of 40 and 85 years consuming 1000 mg quercetin per day, but not among younger adults.8 Cyclists randomised to 1000 mg/day quercetin or

placebo for fi ve weeks experienced reduced URTI incidence during the two-week period following three days of exhaustive exercise.3

Quercetin supplementation over 7 days induces an increase in mitochondrial biogenesis and tread- mill endurance performance (37%) and running distance in wheels in mice.9 The quercetin-related effects on performance in untrained humans are modest and far below those reported in mice.10 About 10 different exercise studies have been con- ducted and, despite confl icting results regarding the effect of quercetin supplementation on endur- ance exercise capacity, a meta-analysis indicated an ergogenic effect which the authors described as being between trivial and small (~3%) but which was signifi cant.11 12

Future research should emphasise multiple types of performance measures, longer supplementa- tion periods in humans and combined ingestion with adjuvants that might augment any bioac- tive effects of quercetin in exercise. The potential synergism between initiation of exercise training and quercetin supplementation should be studied to determine if untrained subjects achieve ampli- fi ed performance outcomes. In general, querce- tin’s bioactive effects support athletic endeavour, but additional research is needed to defi ne better the optimal dosing regimen and adjuvants that might amplify benefi ts during heavy training and competition.

RESVERATROL M W Laupheimer Resveratrol is a natural polyphenolic fl avonoid antioxidant which may provide numerous health benefi ts such as the prevention of cancer, cardio- vascular disease and ischaemic injuries, as well as enhancing stress resistance.13 14 It is a freely avail- able food supplement and is found in the seeds and skins of grapes, red wine, mulberries, peanuts and rhubarb.13 14

Interest in resveratrol in sports medicine arose after animal studies assessed endurance perfor- mance of mice and found a dose-dependent increase in exercise tolerance, improved motor skills and increased number and activity of mitochondria in muscle cells. Resveratrol-treated mice had a sig- nifi cantly higher maximum VO2 rate, suggestive of an increased oxidative capacity. Resveratrol intake increases the ratio of oxidative to non-oxidative type muscle fi bres and increases muscle strength

1Human Performance Laboratory, Appalachian State University, Kannapolis, North Carolina, USA 2Department of Sport and Exercise Medicine, Queen Mary Hospital, University of London, London, UK 3Department of Sport, Faculty of Health & Wellbeing, Sheffi eld Hallam University, Sheffi eld, UK 4Australian Institute of Sport, Canberra, Australia 5Performance Infl uencers Limited, London, UK 6Green Templeton College, University of Oxford, UK

Correspondence to L M Castell, Green Templeton College, University of Oxford, Oxford OX2 6HG, UK; [email protected]

Received 20 March 2012 Accepted 20 March 2012

A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance—Part 33 D C Nieman,1 M W Laupheimer,2 M K Ranchordas,3 L M Burke,4 S J Stear,5 L M Castell6

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Nutritional supplement series

in resveratrol-treated mice.15 The resveratrol effects also seem to be dependent on the length of intake, as one of the actions proposed is a gene switch.16

There are no established doses for resveratrol but Kennedy (2010) showed in humans that resveratrol administration with doses of 250 mg and 500 mg, resulted in a dose-dependent increase in cerebral blood fl ow during task performance and enhanced oxygen extraction.17 Doses of 1600 mg per day in a 70 kg participant are regarded as safe,13-15 even long term.18

Resveratrol as a food supplement in sports medicine has not received much attention despite some basic scientifi c evidence that this substance could have multiple indications related to high-performance sports. Therefore, further studies are required to confi rm whether there are similar effects in humans.

RHODIOLA ROSEA M K Ranchordas R rosea is a herb part of the Crassulacae family and is also known as Arctic root, rose root and golden root. It grows in the moun- tainous and Arctic regions of North America, Europe and Asia.19 It is purported that R rosea possesses several ergogenic prop- erties such as increasing physical and mental performance,20 enhancing cognitive and neural function21 and free radical mitigation.22 It has been described as an adaptogen because of its cardioprotective effects.23

Although the majority of research investigating the effects of R rosea has been conducted in the animal model, there have been several studies done in humans. The dosages investigated in humans have ranged from 100 to 600 mg/day. Studies inves- tigating its effects on exercise performance have been mixed. R rosea supplementation in doses of 100 mg/day for 20 days and one acute dose of 200 mg/day were found to improve endurance exercise capacity by 6.5% and 5.0%, respectively.21 24 However, other studies have found no positive effects on VO2peak, peak power, lactate threshold25 and ventilatory threshold.26 Studies investigating R rosea supplementation on neural and cognitive performance have also produced mixed results. Doses of 100–555 mg/day have found positive effects on cog- nition21 27 28 but other studies have found no effect using doses 200 mg/day either acutely or for 5 weeks.24 R rosea contains phenylopopropanoids, phenolic compounds and fl avonoids; some studies have found that supplementation can increase antioxidant levels29 decrease muscle-damage markers20 and mitigate free radicals.22

Based on the available literature, it remains unclear whether R rosea supplementation in doses of 100–600 mg/day can enhance either mental and/or exercise performance. However, there is some evidence that R rosea does possess antioxidant properties. Further tightly controlled studies in well-trained athletes need to be conducted in order to determine any per- formance-enhancing effects.

CONCLUDING COMMENTS In summary, all three products show potential, both in vitro and in animal models, of properties ranging from antioxidant activity to regulation of cell signalling. However, particularly in the cases of quercetin and resveratrol, there is evidence of species differences and reduced translation of benefi ts seen in rodents to well-trained humans. Further work is needed to determine whether these compounds actually enhance athletic performance. Nevertheless, there is a strong interest

in investigating protocols in which a cocktail of these phy- tochemicals might work synergistically.

Competing interests David C Nieman is on the Scientifi c Advisory Board for Quercegen Pharma; this research has also been funded by Coca Cola.

Provenance and peer review Commissioned; not externally peer reviewed.

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