Klupp 2014.

Study characteristics
Methods	Randomised controlled trial of G lucidum, or G lucidum plus Cordyceps sinensis capsules, versus placebo
Participants	Inclusion criteria At least 18 years of age Able to provide informed consent in English Have high fasting serum glucose ≥ 6.1 mmol/L Meet the diagnostic criteria for National Cholesterol Education Program Adult Treatment Panel III (NCEP‐ATPIII) for metabolic syndrome. Therefore, in addition to the high fasting glucose participants must have at least two of the following: waist circumference > 102 cm (men)/88 cm (women) fasting serum triglycerides ≥ 1.7 mmol/L HDL cholesterol  < 1 mmol/L (men)/1.3 mmol/L (women) BP ≥ 130/85 mmHg Exclusion criteria A known allergy to mushrooms Had taken G lucidum or C sinensis in the past 12 months Pregnant or breastfeeding Any medical or social condition or circumstance that might prevent completion or compliance with the requirements of this trial Any significant active medical or psychiatric condition that the medical practitioner deemed made the person unsuitable for involvement in this trial e.g. malignancy, heart disease Significant renal impairment (serum creatinine >160 mmol/L) Active hepatobiliary conditions including hepatitis (A,B or C); significant hepatic impairment (bilirubin > 30 mmol/L, serum ALT (alanine aminotransferase) or AST (aspartate aminotransferase) > 1.5 x the upper limit of normal) Had major surgery in the past month or expecting surgery during the trial Had an organ transplant History of abnormal haemorrhaging or had taken an anti‐coagulant in the last three months Currently using insulin treatment, or had done so in the past three months Any other active medical condition that might significantly interfere with glucose levels, such as systemic infection (e.g. tuberculosis, hepatitis, chronic sinusitis or any chronic sepsis) Recent history (3 months) of hypoglycaemic events Participants, baseline data presented as mean (SD) for intervention (I) and control (C) groups Average age, years: I 60.2 (0); C 57.1 (8.3) Duration of disease, years: I 7.1 (5.7); C 6.4 (5.2) FPG, mmol/L: I 8.7 (2.9); C 8.4 (2.7) HbA1c, %: I 7.7 (1.6); C 7.4 (1.4) Triglycerides, mmol/L: I 2.52 (2.79); C 2.25 (0.94) Systolic BP, mmHg: I 139 (17); C 135 (16) Diastolic BP, mmHg: I 82 (10); C 82 (11) BMI, kg/m2: I 3401 (6.8); C 34.3 (7.4)
Interventions	Intervention:G lucidum capsule (containing 372 mg G lucidum mushroom extract), and G lucidum with C sinensis capsules (containing 375 mg G lucidum mushroom extract and 125 mg C sinensis extract). Mushroom extract refers to a concentrated form of nutrients derived from raw mushrooms, and spores, which have different but condensed amounts of nutrients, act as the 'seeds' of the fungus for dispersal purposes. Dose: participants took capsules equalling approximately 4 g/day of either G lucidum, or G lucidum with C sinensis or placebo Participants were required to take 4 capsules twice daily, with food, for 16 weeks duration Control: placebo (provided by GMP Pharmaceuticals)
Outcomes	Primary outcome Fasting blood glucose HbA1c Secondary outcome For improving the other four diagnostic criteria of metabolic syndrome: systolic and diastolic BP triglycerides waist circumference hip circumference (secondary non‐NCEP measure) BMI (secondary non‐NCEP measure) HDL For quality of life: Short Form‐36: Standard Version 2 Australian language For other cardiovascular risk factors: high sensitivity C‐reactive protein total cholesterol LDL apolipoprotein A apolipoprotein B adverse effects
Notes	Data were collected at baseline and weeks 8 and 16 during intervention period. Follow‐up data was also collected at week 24 after 8 weeks washout from intervention
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote "These treatment sequences will be generated by Microsoft Excel computer randomisation strategies."
Allocation concealment (selection bias)	Low risk	Quote "Randomisation will be organised by a single research officer of the Centre for Complementary Medicine Research, but this process will be conducted completely external and unknown to the research team members listed in this protocol."
Incomplete outcome data (attrition bias) All outcomes	Low risk	86 participants were allocated to 3 groups and 9 withdrew from the study. However intention‐to‐treat analysis was used so that all participants were analysed according to the group to which they were randomised
Selective reporting (reporting bias)	Low risk	Compared to the trial protocol, all pre‐defined outcome measurements were provided in the unpublished report
Other bias	Low risk	The research was partly financially supported by a pharmaceutical company No other potential bias was noted
Blinding of participants and personnel (performance bias)	Low risk	Quote "The treatment sequence code will be stored in two separate locked and protected locations and these codes will be used to label pre‐prepared participant numbered medication containers. . ..There is no need for comparisons between intervention capsules either by the researchers or the participants. However, the interventions of Ganoderma lucidum, Ganoderma lucidum with Cordyceps sinensis and placebo will be indistinguishable in colour, smell, taste, size and weight." Participants were surveyed at each stage of data collection about which medication they thought they were taking. The ratio of total correct answers to total incorrect answers was 1:3
Blinding of outcome assessment (detection bias)	Low risk	Quote "Due to the use of pre‐randomised packaging and the nature of the intervention, the participants, the assessors, the therapists and the data analysts will all remain blinded for the duration of the trial."