Fergal M. Grace

Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis

Objectives National dietary guidelines were introduced in 1977 and 1983, by the US and UK governments, respectively, with the ambition of reducing coronary heart disease (CHD) by reducing fat intake. To date, no analysis of the evidence base for these recommendations has been undertaken. The present study examines the evidence from randomised controlled trials (RCTs) available to the US and UK regulatory committees at their respective points of implementation. Methods A systematic review and meta-analysis were undertaken of RCTs, published prior to 1983, which examined the relationship between dietary fat, serum cholesterol and the development of CHD. Results 2467 males participated in six dietary trials: five secondary prevention studies and one including healthy participants. There were 370 deaths from all-cause mortality in the intervention and control groups. The risk ratio (RR) from meta-analysis was 0.996 (95% CI 0.865 to 1.147). There were 207 and 216 deaths from CHD in the intervention and control groups, respectively. The RR was 0.989 (95% CI 0.784 to 1.247). There were no differences in all-cause mortality and non-significant differences in CHD mortality, resulting from the dietary interventions. The reductions in mean serum cholesterol levels were significantly higher in the intervention groups; this did not result in significant differences in CHD or all-cause mortality. Government dietary fat recommendations were untested in any trial prior to being introduced. Conclusions Dietary recommendations were introduced for 220 million US and 56 million UK citizens by 1983, in the absence of supporting evidence from RCTs.

Anabolic steroid use: Patterns of use and detection of doping

Anabolic-androgenic steroids (AAS) were the first identified doping agents that have ergogenic effects and are being used to increase muscle mass and strength in adult males. Consequently, athletes are still using them to increase physical performance and bodybuilders are using them to improve size and cosmetic appearance. The prevalence of AAS use has risen dramatically over the last two decades and filtered into all aspects of society. Support for AAS users has increased, but not by the medical profession, who will not accept that AAS use dependency is a psychiatric condition. The adverse effects and potential dangers of AAS use have been well documented. AAS are used in sport by individuals who have acquired knowledge of the half-lives of specific drugs and the dosages and cycles required to avoid detection. Conversely, they are used by bodybuilders in extreme dosages with the intention of gaining muscle mass and size, with little or no regard for the consequences. Polypharmacy by self-prescription is prevalent in this sector. Most recently, AAS use has filtered through to ‘recreational street drug’ users and is the largest growth of drugs in this subdivision. They are taken to counteract the anorexic and cachectic effects of the illegal psychotropic street drugs. Screening procedures for AAS in World Anti-Doping Agency accredited laboratories are comprehensive and sensitive and are based mainly on gas chromatography-mass spectrometry, although liquid chromatography-mass spectrometry is becoming increasingly more valuable. The use of carbon isotope mass spectrometry is also of increasing importance in the detection of natural androgen administration, particularly to detect testosterone administration. There is a degree of contentiousness in the scenario of AAS drug use, both within and outside sport. AAS and associated doping agents are not illegal per se. Possession is not an offence, despite contravening sporting regulations and moral codes. Until AAS are classified in the same capacity as street drugs in the UK, where possession becomes a criminal offence, they will continue to attract those who want to win at any cost. The knowledge acquired by such work can only assist in the education of individuals who use such doping agents, with a view to minimizing health risks and hopefully once again create a level playing field in sport.

Impaired vasoreactivity in bodybuilders using androgenic anabolic steroids

Background  Anabolic androgenic steroids are used by some bodybuilders to enhance performance. While the cardiovascular implications of supraphysiological androgen levels requires further clarification, use is associated with sudden death, left ventricular hypertrophy, thrombo‐embolism and cerebro‐vascular events.

Blood pressure and rate pressure product response in males using high-dose anabolic androgenic steroids (AAS).

The literature regarding the blood pressure response to AAS use is equivocal. In addition, there is currently little data available on the Rate Pressure Product (RPP) response to anabolic androgenic steroids (AAS) use. The experimental aim of this study was to investigate the effects of AAS administration in combination with resistance training on blood pressure and rate pressure product in male amateur bodybuilders and compare the results with a morphologically matched, resistance trained control group. Subjects were divided into two groups (n=16 AAS users; n=16 controls). Systolic and Diastolic Blood Pressure, RPP. Resting Heart Rate and Body Composition measurements were obtained before (Pre), during (During) and 6-8 weeks following (Post) the AAS cycle in the AAS users with similar time intervals for the control group. No significant cardiovascular or morphological changes in the control group were found throughout the study. Significant increases in both diastolic (P<0.01) and mean arterial blood pressures (P<0.05) were found from Pre to Post cycle in the AAS group. RPP also increased significantly (P<0.01) from pre to post AAS cycle. All cardiovascular parameters returned to normal baseline measurements between 6 and 8 weeks post cycle. No blood pressure measurements throughout the study were consistent with clinically defined hypertension. The findings indicate that the AAS group exhibited significant increases in standard cardiovascular measurements compared with the control bodybuilders, and provides a contraindication to AAS use especially in borderline hypertensives.

Homocysteine induced cardiovascular events: a consequence of long term anabolic-androgenic steroid (AAS) abuse

Objectives: The long term effects (>20 years) of anabolic-androgenic steroid (AAS) use on plasma concentrations of homocysteine (HCY), folate, testosterone, sex hormone binding globulin (SHBG), free androgen index, urea, creatinine, haematocrit (HCT), vitamin B12, and urinary testosterone/epitestosterone (T/E) ratio, were examined in a cohort of self-prescribing bodybuilders. Methods: Subjects (n = 40) were divided into four distinct groups: (1) AAS users still using AAS (SU; n = 10); (2) AAS users abstinent from AAS administration for 3 months (SA; n = 10); (3) non-drug using bodybuilding controls (BC; n = 10); and (4) sedentary male controls (SC; n = 10). Results: HCY levels were significantly higher in SU compared with BC and SC (p<0.01), and with SA (p<0.05). Fat free mass was significantly higher in both groups of AAS users (p<0.01). Daily energy intake (kJ) and daily protein intake (g/day) were significantly higher in SU and SA (p<0.05) compared with BC and SC, but were unlikely to be responsible for the observed HCY increases. HCT concentrations were significantly higher in the SU group (p<0.01). A significant linear inverse relationship was observed in the SU group between SHBG and HCY (r = −0.828, p<0.01), indicating a possible influence of the sex hormones in determining HCY levels. Conclusions: With mounting evidence linking AAS to adverse effects on some clotting factors, the significantly higher levels of HCY and HCT observed in the SU group suggest long term AAS users have increased risk of future thromboembolic events.

Direct Hits to the Head during Amateur Boxing is Associated with a Rise in Serum Biomarkers for Brain Injury

Boxing exposes participants to the physiological response to high intensity exercise and also to direct body and brain trauma. Amateur boxing is increasing and females have also been included in the Olympics. The aim of this study is to assess the stress response and possible brain injury incurred during a match by measuring serum biomarkers associated with stress and cellular brain injury before and after combat. Sixteen male amateur boxers were studied retrospectively. The study population was divided into two groups: (a) a group that received predominantly punches to the head (PTH) and (b) a group that received predominantly punches to the body (PTB). Blood samples were taken before and five minutes after each contest. They were analysed for S-100B, neuron-specific enolase (NSE), creatine kinase (CK) and cortisol. The PTH group received direct contacts to the head (not blocked, parried or avoided) and to the body (n=8, age: 17.6 ± 5.3, years; height: 1.68 ± 0.13, meters; mass: 65.4 ± 20.3, kg). The PTB group received punches to the body including blocked and parried punches, but received no direct punches to the head, (n=8, mean ± SD, age: 19.1 ± 3.2 years; height: 1.70 ± 0.75, meters; mass: 68.5 ± 15 kg). Significant increases (P<0.05) were observed between pre- and post-combat serum concentrations in serum concentrations in PTH of S-100B (0.35 ± 0.61 vs. 0.54 ± 0.73, μg.L−1) NSE (19.7 ± 14 vs.31.1 ± 26.6, ng.ml−1) and cortisol (373 ± 202 vs. 756± 93, nmol.L−1). Significant increases (P<0.05) of creatine kinase were recorded in both groups. This study demonstrates significant elevations in neurochemical biomarkers in boxers who received direct blows to the head. However, further work is required to quantify this volumetric brain damage and long term clinical sequelae.

Androgens affect myogenesis In Vitro and increase local IGF-1 expression

PURPOSE The mechanism whereby anabolic androgens are associated with hypertrophy of skeletal muscle is incompletely understood but may involve an interaction with locally generated insulin-like growth factor (IGF) 1. The present investigation utilized a cell culture model of human skeletal muscle-derived cell maturation to test the hypothesis that androgens increase differentiation of human muscle precursor cells in vitro and to assess effects of androgen with or without IGF-1 on IGF-1 messenger RNA (mRNA) expression in human muscle precursor cells. METHODS Differentiation of muscle-derived cells was induced under standard low-serum conditions. Cultures were then exposed to androgen (testosterone (T)) at 50, 100, and 500 nM or IGF-1 (10-50 ng·mL⁻¹). Immunocytochemistry and real-time polymerase chain reaction (RT-PCR) were used to assess effects of androgens and IGF-1 after 3- (early) or 7-d (late) muscle differentiation, respectively; RT-PCR was used to quantify the effects on androgen receptor expression. RESULTS Under low-serum conditions, 3-d exposure to androgens or IGF-1 or both resulted in no significant increase in cellular myogenic commitment. After 7-d exposure, however, T and IGF-1 were both found to increase fusion index with no observable synergistic effect. T also increased IGF-1 mRNA generation (P < 0.0001), whereas exogenous IGF-1 (P < 0.001) reduced IGF-1 mRNA transcription relative to control. The T effect was reversible after treatment with flutamide, an androgen receptor antagonist. CONCLUSIONS Both T and IGF-1 increase myogenic commitment after 7-d exposure to a differentiation medium. With T causing a concomitant increase in IGF-1 mRNA underpinning IGF-1 as a central mediator in the cellular pathways associated with muscle hypertrophy, including those affected by androgens. The novel system described has the potential for elucidating the pattern of growth factor effects associated with androgens in skeletal muscle.

Anabolic androgenic steroid use in recreational gym users: a regional sample of the Mid-Glamorgan area

The aim of this study was to examine the extent of anabolic androgenic steroid (AAS) use in a sample of recrational gym users in the Mid-Glamorgan area in South Wales, UK. Further aims were to investigate: ” the types of substances being used ” consequences of use. Introduction : Previous literature pertaining to AAS use tends to use samples of athletes and competitive sports people. A minority of studies have used recreational gym users. Method : A previously validated questionnaire (Korkia and Stimson 1993) was administered to recreational gym users in the Mid-Glamorgan area. The three gymnasia included in this survey were reported to be popular with bodybuilding and AAS-using clientele. Results : From the distribution of 170 questionnaires, the response rate was 63%. AAS users were from all areas of society and reported various physiological and psychological side effects from AAS use. The most worrying discovery was the extent of AAS users reporting syringe sharing (20%).

Acute whole body UVA irradiation combined with nitrate ingestion enhances time trial performance in trained cyclists

Dietary nitrate supplementation has been shown to increase nitric oxide (NO) metabolites, reduce blood pressure (BP) and enhance exercise performance. Acute exposure to ultraviolet (UV)-A light also increases NO bioavailability and reduces BP. We conducted a randomized, counterbalanced placebo-controlled trial to determine the effects of UV-A light alone and in combination with nitrate on the responses to sub-maximal steady-state exercise and time trial (TT) performance. Nine cyclists (VO2max 53.1 ± 4.4 ml/kg/min) completed five performance trials comprising 10 min submaximal steady-state cycling followed by a 16.1 km TT. Following a familiarization the final four trials were preceded, in random order, by either (1) Nitrate gels (NIT) + UV-A, (2) Placebo (PLA) + UV-A, (3) NIT + Sham light (SHAM) and (4) PLA + SHAM (control). The NIT gels (2 × 60 ml gels, ~8.1 mmol nitrate) or a low-nitrate PLA were ingested 2.5 h prior to the trial. The light exposure consisted of 20 J/cm(2) whole body irradiation with either UV-A or SHAM light. Plasma nitrite was measured pre- and post-irradiation and VO2 was measured continuously during steady-state exercise. Plasma nitrite was higher for NIT + SHAM (geometric mean (95% CI), 332 (292-377) nM; P = 0.029) and NIT + UV-A (456 (312-666) nM; P = 0.014) compared to PLA + SHAM (215 (167-277) nM). Differences between PLA + SHAM and PLA + UV-A (282 (248-356) nM) were small and non-significant. During steady-state exercise VO2 was reduced following NIT + UVA (P = 0.034) and tended to be lower in NIT + SHAM (P = 0.086) but not PLA + UV-A (P = 0.381) compared to PLA + SHAM. Performance in the TT was significantly faster following NIT + UV-A (mean ± SD 1447 ± 41 s P = 0.005; d = 0.47), but not PLA + UV-A (1450 ± 40 s; d = 0.41) or NIT + SHAM (1455 ± 47 s; d = 0.28) compared to PLA + SHAM (1469 ± 52 s). These findings demonstrate that exposure to UV-A light alone does not alter the physiological responses to exercise or improve performance in a laboratory setting. A combination of UV-A and NIT, however, does improve cycling TT performance in this environment, which may be due to a larger increase in NO availability.

Manipulation of systemic oxygen flux by acute exercise and normobaric hypoxia: implications for reactive oxygen species generation.

Maximal exercise in normoxia results in oxidative stress due to an increase in free radical production. However, the effect of a single bout of moderate aerobic exercise performed in either relative or absolute normobaric hypoxia on free radical production and lipid peroxidation remains unknown. To examine this, we randomly matched {according to their normobaric normoxic VO2peak [peak VO2 (oxygen uptake)]} and assigned 30 male subjects to a normoxia (n = 10), a hypoxia relative (n = 10) or a hypoxia absolute (n = 10) group. Each group was required to exercise on a cycle ergometer at 55% of VO2peak for 2 h double-blinded to either a normoxic or hypoxic condition [FiO2 (inspired fraction of O2) = 0.21 and 0.16 respectively]. ESR (electron spin resonance) spectroscopy in conjunction with ex vivo spin trapping was utilized for the direct detection of free radical species. The main findings show that moderate intensity exercise increased plasma-volume-corrected free radical and lipid hydroperoxide concentration (pooled rest compared with exercise data, P < 0.05); however, there were no selective differences between groups (statexgroup interaction, P > 0.05). The delta change in free radical concentration was moderately correlated with systemic VO2 (r2 = 0.48, P < 0.05). The hyperfine coupling constants recorded from the ESR spectra [aN = 13.8 Gauss, and a(H)beta = 1.9 Gauss; where 1 Gauss = 10(-4) T (telsa)] are suggestive of oxygen-centred free radical species formed via the decomposition of lipid hydroperoxides. Peripheral leucocyte and neutrophil cells and total CK (creatine kinase) activity all increased following sustained exercise (pooled rest compared with exercise data, P < 0.05), but no selective differences were observed between groups (state x group interaction, P > 0.05). We conclude that a single bout of moderate aerobic exercise increases secondary free radical species. There is also evidence of exercise-induced muscle damage, possibly caused by the increase in free radical generation.