The adverse health consequences of the use of multiple performance-enhancing substances--a deadly cocktail.

CONTEXT: The harmful consequences of abuse of performance-enhancing substances (PESs), stimulants, and masking agents among athletes, recreational weight lifters, and physical trainers are common. However, the adverse health outcomes with severe unexpected and dramatic consequences are unrecognized or under-reported at the expense of short-term glory or body-image effects, especially in elite sports. OBJECTIVE: We report the case of a recreational weight lifter/physical trainer to help summarize the adverse health consequences and outcomes of polypharmacy among athletes and growing subsets in our population engaged in physical/fitness training. We show that in addition to the risk inherent to "stacking" of PESs, the users are predisposed to harmful consequences, including risk of exposure to toxic contaminants. DESIGN AND SETTING: A previously healthy man with chronic use of multiple PESs, stimulants, and masking agents presented to a tertiary-care hospital with jaundice and mild hepatitis with rapid progression into liver and multisystem organ failure. This is followed by a brief overview of the specific toxicity (arsenic) and PESs that contributed to the poor outcome in this case. CONCLUSION: Surreptitiously or self-administered cocktails of potential PESs including anabolic agents, emerging classes of GH-releasing peptides, androgen precursors, stimulants, and masking agents could lead to adverse consequences including early mortality, multisystem pathology, unmask/accelerate malignancy, and expose or predispose users to extreme danger from contaminants. This cautionary case reinforces the need to increase awareness and highlights the challenges that testing agencies, regulators, and clinicians face in the fast-developing licit/illicit trade of these products.

Refsum's Disease-Use of the Intestinal Lipase Inhibitor, Orlistat, as a Novel Therapeutic Approach to a Complex Disorder.

Refsum's Disease is an inherited metabolic disorder in which a metabolite of branched chain fatty acids accumulates due to lack of appropriate oxidative enzymes. Patients have elevated plasma phytanic acid levels and high concentrations of phytanic acid in a variety of tissues leading to progressive tissue damage. Besides retinal degeneration or retinal dystrophy associated with adult onset retinitis pigmentosa, additional symptoms include chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, anosmia, ichthyosis, as well as skeletal, cardiac, hepatic, and renal abnormalities. Current management includes avoidance of dietary sources of branched chain fatty acids and regular plasmapheresis to prevent accumulation of these compounds to ameliorate progressive neurological deficits. Two brothers with Refsum's disease who experienced progressive symptoms despite optimal diet and plasmapheresis were commenced on a novel therapy. We report the effect of the intestinal lipase inhibitor, Orlistat, which led to significant reduction (P-value <0.001 on 2-sample unpaired t-test) of mean preplasmapheresis phytanic acid levels with retardation of the progression of most of their dermatological and neurological symptoms.

Adjustment of direct high-density lipoprotein cholesterol measurements according to intercurrent triglyceride corrects for interference by triglyceride-rich lipoproteins.

BACKGROUND: Low plasma levels of high-density-lipoprotein cholesterol (HDL-C) and high triglyceride (TG) are strongly associated with cardiovascular disease (CVD). Clinical recognition of this high-risk population demands accurate measurement of HDL-C, whereas cost and clinical demand dictate that optimal HDL-C measurement requires fully automated methods that avoid manual precipitation. Commercial techniques use specific reagents to selectively expose and "directly" measure cholesterol in HDL. However, these "direct" methods may experience interference from the cholesterol content of triglyceride-rich-lipoproteins (TRL), leading to analytical overestimation of HDL-C, with subsequent underestimation of low-density-lipoprotein cholesterol (LDL-C) and of CVD risk. OBJECTIVE: The aim of this study was to develop a method to overcome this interference. METHODS: Serum/Li+-heparin plasma samples from consecutive patients were analyzed for HDL-C by the comparison of three generations of the Roche Diagnostics, HDL-C assay on a Hitachi-917 or Modular-PPE analyzer. HDL-C measurement was performed before and after removal of TRL by ultracentrifugation ("direct" HDL-C and HDL-UC, respectively). We examined the effect of TG on the relationship between HDL-UC and "direct" HDL-C. Analysis of variance multiregression analysis was performed for each generation of the commercial assay. RESULTS: We observed progressive TG interference that increased "direct" HDL-C by 10% to 15% or more in moderately hypertriglyceridemic samples (<600 mg/dL). Predictive equations were derived for each generation of the assay to estimate HDL-C in the absence of TRL. CONCLUSIONS: This study casts doubt on the specificity of "direct" HDL-C assays in the presence of hypertriglyceridemia. The use of assay-specific correction formulae to adjust for interference from TRL reduces the overestimation of HDL-C that influences CVD risk calculation, treatment, and follow-up of patients.