AimThe aim of this systematic review was to assess the quality and outcomes of clinical trials investigating the effect of St John's wort extracts on the metabolism of drugs by CYP3A. MethodsProspective clinical trials assessing the effect of St John's wor t (SJW) extracts on metabolism by CYP3A were identified through computer-based searches (from their inception to May 2005) of Medline, Cinahl, PsycINFO, AMED, Current Contents and Embase, hand-searches of bibliographies of relevant papers and consultation with manufacturers and researchers in the field. Two reviewers selected trials for inclusion, independently extracted data and recorded details on study design. ResultsThirty-one studies met the eligibility criteria. More than two-thirds of the studies employed a before-and-after design, less than one-third of the studies used a crossover design, and only three studies were double-blind and placebo controlled. In 12 studies the SJW extract had been assayed, and 14 studies stated the specific SJW extract used. Results from 26 studies, including all of the 19 studies that used high-dose hyperforin extracts ( > 10 mg day − 1 ), had outcomes consistent with CYP3A induction. The three studies using low-dose hyperforin extracts ( < 4 mg day − 1 ) demonstrated no significant effect on CYP3A. ConclusionThere is reasonable evidence to suggest that high-dose hyper forin SJW extracts induce CYP3A. More studies are required to determine whether decreased CYP3A induction occurs after low-dose hyperforin extracts. Future studies should adopt study designs with a control phase or control group, identify the specific SJW extract employed and provide quantitative analyses of key constituents.

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine-disrupting chemical exposure, and the influence of lifestyle factors such as poor-quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.

Background: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that limits glucose and results in the production of ketones by the liver and their uptake as an alternative energy source by the brain. KD is an evidence-based treatment for intractable epilepsy. KD is also self-administered, with limited evidence of efficacy, for conditions including weight loss, cognitive and memory enhancement, type II diabetes, cancer, neurological and psychiatric disorders. A commonly discussed side effect of KD in media and online forums is "keto flu," a cluster of transient symptoms generally reported as occurring within the first few weeks of KD. This study aimed to characterize the pattern of symptoms, severity and time course of keto flu as related by users of online forums.Method: Online forums referring to "keto flu," "keto-induction," or "keto-adaptation" in the URL were identified in Google. Passages describing personal experiences of keto flu were categorized manually with reference to pattern of symptoms, severity, time course, and remedies proposed.Results: The search criteria identified 75 online forums, 43 met inclusion criteria and contained 448 posts from 300 unique users. Seventy-three made more than one post (mean 3.12, range 2-11). Descriptors of personal experience of keto flu, reported by 101 of 300 users, included 256 symptom descriptions involving 54 discrete symptoms. Commonest symptoms were "flu," headache, fatigue, nausea, dizziness, "brain fog," gastrointestinal discomfort, decreased energy, feeling faint and heartbeat alterations. Symptom reports peaked in the first and dwindled after 4 weeks. Resolution of keto flu symptoms was reported by eight users between days 3 and 30 (median 4.5, IQR 3-15). Severity of symptoms, reported by 60 users in 40 forums, was categorized as mild (N = 15), moderate (N = 23), or severe (N = 22). Eighteen remedies were proposed by 121 individual users in 225 posts.Conclusions: Typically, individual posts provided fragmentary descriptions related to the flow of forum conversations. A composite picture emerged across 101 posts describing personally experienced symptoms. User conversations were generally supportive, sharing remedies for keto flu reflecting assumptions of physiological effects of KD.