Summary The prevalence of pre‐diabetes and of type 2 diabetes mellitus is increasing. Preventing disease progression is important to improve outcomes. Natural products are becoming popular alternatives to pharmaceutical products for preventative health and treatment of disease; however, the evidence to support the use of natural alternatives for pre‐diabetes and type 2 diabetes is lacking. Two such natural medicines include alpha‐cyclodextrin (marketed as FBCx), a fibre derived from corn starch that has been found to bind triglycerides in the intestines to prevent its absorption, aiding weight maintenance and lipid control, and hydrolysed ginseng extract (marketed as GINST15), a formula containing high amounts of Compound K, a metabolite of ginsenosides thought to be an active ingredient contributing to the anti‐hyperglycaemic effects of ginseng. This paper describes the rationale and design of a 12‐month randomized controlled trial to investigate the metabolic effects of these two products in people with pre‐diabetes and overweight or obesity. A total of 400 participants will be randomized to one of four groups (FBCx + GINST15, FBCx + placebo, placebo + GINST15, placebo + placebo) for 6 months, followed by 6 months of follow‐up. Participants will also receive lifestyle advice for healthy eating and weight loss. Data collected during the trial will include weight, waist circumference, body composition and blood pressure. Blood samples will also be collected to measure lipid profile and glycaemia. If the products are found to improve lipid and glucose levels, it will provide evidence for their use in people with pre‐diabetes to help reduce the risk of progression to type 2 diabetes.

IMPORTANCE Effective strategies for preventing type 2 diabetes are needed. Many people turn to complementary medicines, but there is little well-conducted scientific evidence to support their use. OBJECTIVETo assess the efficacy of α-cyclodextrin for cholesterol control and that of hydrolyzed ginseng for glycemic control in people with prediabetes and overweight or obesity. DESIGN, SETTING, AND PARTICIPANTSThis 6-month double-blind, placebo-controlled, randomized clinical trial, with a 2 × 2 factorial design, was conducted between July 2015 and October 2018 at 2 locations in Sydney, Australia. Eligible participants were aged 18 years or older, had a body mass index (weight in kilograms divided by height in meters squared) of 25 or higher, and had prediabetes within 6 months of study entry according to the American Diabetes Association guidelines. Data analysis was performed from May to August 2019. INTERVENTIONSParticipants were randomized to 1 of 4 groups to take active or placebo versions of each supplement (α-cyclodextrin plus hydrolyzed ginseng, α-cyclodextrin plus placebo, placebo plus hydrolyzed ginseng, or placebo plus placebo) for 6 months. All participants received dietetic advice for weight loss. MAIN OUTCOMES AND MEASURESThe primary outcomes were the differences in total cholesterol and fasting plasma glucose between groups after 6 months. The primary analysis used the intention-to-treat principle. Multiple predetermined subsample analyses were conducted. RESULTSA total of 401 participants were eligible for the study (248 women [62%]; mean [SD] age, 53.5 [10.2] years; mean [SD] body mass index, 34.6 [6.2]). One hundred one patients were randomized to receive α-cyclodextrin plus hydrolyzed ginseng, 99 were randomized to receive α-cyclodextrin plus placebo, 101 were randomized to receive placebo plus hydrolyzed ginseng, and 100 were randomized to receive placebo plus placebo. For 200 participants taking α-cyclodextrin compared with 201 participants taking placebo, there was no difference in total cholesterol after 6 months (−1.5 mg/dL; 95% CI, −6.6 to 3.5 mg/dL; P = .51). For 202 participants taking hydrolyzed ginseng compared with 199 participants taking placebo, there was no difference in fasting plasma glucose after 6 months (0.0 mg/dL; 95% CI, −1.6 to 1.8 mg/dL; P = .95). Use of α-cyclodextrin was associated with constipation (16 participants vs 4 participants; P = .006) and cough (8 participants vs 1 participant; P = .02). Use of hydrolyzed ginseng was associated with rash and pruritus (13 participants vs 2 participants; P = .006). Only 37 of 401 participants (9.2%) experienced these adverse events. (continued) Key Points Question Can α-cyclodextrin and hydrolyzed ginseng aid in cholesterol and glycemic control, respectively, in people with prediabetes and overweight or obesity? Findings In this double-blind, placebocontrolled, randomized clinical trial of 401 participants, there was no significant difference in total cholesterol in those taking α-cyclodextrin or in fasting plasma glucose in those t...

Aim: To update the available evidence on the efficacy and safety of complementary medicines to assist in weight loss by conducting a systematic review and metaanalysis of herbal medicines for weight loss.Methods: Four electronic databases (Medline, Embase, CINAHL and Web of Science) were searched from inception until August 2018. A total of 54 randomized placebocontrolled trials of healthy overweight or obese adults were identified. Meta-analyses were conducted for herbal medicines with ≥4 studies available. Weight differences of ≥2.5 kg were considered clinically significant.Results: As a single agent, only Phaseolus vulgaris resulted in a statistically significant weight loss compared to placebo, although this was not considered clinically significant. No effect was seen for Camellia sinensis or Garcinia cambogia. Statistically, but not clinically, significant differences were observed for combination preparations containing C. sinensis, P. vulgaris or Ephedra sinica. Of the herbal medicines trialled in ≤3 randomized controlled trials, statistically and clinically significant weight loss compared to placebo was reported for Irvingia gabonensis, Cissus quadrangularis, and Sphaeranthus indicus combined with Garcinia mangostana, among others, but these findings should be interpreted cautiously because of the small number of studies, generally poor methodological quality, and poor reporting of the herbal medicine interventions. Most herbal medicines appeared safe for consumption over the short duration of the studies (commonly ≤12 weeks). Some warrant further investigation to determine effect size, dosage and long-term safety.Conclusion: There is currently insufficient evidence to recommend any of the herbal medicines for weight loss included in the present review. K E Y W O R D Sherbal medicines, meta-analysis, systematic review, weight loss

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BackgroundCardiovascular complications are the leading cause of mortality in patients with end-stage kidney disease. Research indicates that the Mediterranean diet is protective of cardiovascular disease in the general population. Components of this diet have been trialled in haemodialysis patients with the aim of reducing the risk of cardiovascular disease and improving associated risk factors. Components include fish, fruit and vegetables in the form of fish oil supplements and vitamin and antioxidant supplements. This narrative review provides an overview of observational studies, and interventional and randomised controlled trials examining the association of these supplements with cardiovascular outcomes in haemodialysis patients.MethodsWe reviewed the relevant literature by searching English-language publications in Web of Science and references from relevant articles published since 1992. Eight-seven abstracts were reviewed and 38 relevant articles were included.ResultsThe extant literature suggests that risk of mortality is reduced in patients with a higher fish intake and those with higher serum omega-3 fatty acid levels. However, the pathways by which risk of mortality is reduced have not been fully extrapolated. While only a few studies have examined the effect of vitamin B supplementation in haemodialysis patients, these studies suggest that supplementation alone does not reduce the risk of mortality. Finally, studies examining vitamin E supplementation have drawn inconsistent conclusions regarding its pro-oxidant or antioxidant effects. Differences between studies are likely due to methodological variations in regards to dose, route of administration and treatment duration.ConclusionsNutritional and dietary supplementation in haemodialysis patients is an area which requires larger, more methodologically robust randomised controlled trials to determine if risk of cardiovascular outcomes can be improved.