Investigating the potential health benefits of ergothioneine supplementation for people with metabolic syndrome

INTERVENTION: Consenting participants will be randomised in a double‐blind fashion to one of three groups to receive either placebo (0 mg ergothioneine), 5 mg ergothioneine, or 30 mg ergothioneine for consumption as daily capsules (one per day) for 12 weeks. Participants will give blood samples and undergo anthropometric measurements at three timepoints, baseline, 6 weeks and 12 weeks. Randomisation and group allocation will be done based on predefined random allocation lists using simple stratification for sex (one each for males and females), with a block size of 6 and allocation list of 2:2:2; aiming to recruit 108 participants for n=36 in each group. The randomisation schedule will be carried out by a collaborator who will not be involved in any other part of this trial and who will also be blinded to the dose allocation (‘A’, ‘B’ or ‘C’) designated by the manufacturer and provided in a sealed envelope. The collaborator will maintain the lists matching screening IDs to randomisation IDs, along with the manufacturer’s sealed envelope for the duration of the trial. This envelope will only be opened before study completion in the case of a serious adverse event. CONDITION: Metabolic syndrome ; Not Applicable PRIMARY OUTCOME: ; 1.Recruitment and completion will be measured in the numbers of participants enrolling and completing all study visits; 2.Supplementation compliance will be measured both by capsule counting (participants returning packaging and untaken supplements) and the measurement of ergothioneine in plasma by HPLC at baseline, 6 weeks and 12 weeks; SECONDARY OUTCOME: ; 1.A primary serum marker of oxidative stress (specifically, lipid peroxidation), malondialdehyde (MDA), will be measured by high‐performance liquid chromatography (HPLC) at baseline, 6 weeks, and 12 weeks; 2.Serum markers of inflammation, tumour necrosis factor‐alpha (TNF‐a) and nuclear factor erythroid 2‐related factor 2 (Nrf2) will be measured by enzyme‐linked immunosorbent assay (ELISA) at baseline, 6 weeks, and 12 weeks. C‐reactive protein (CRP) will be measured in whole blood using a rapid point‐of‐care multi‐assay blood analyser at baseline, 6 weeks and 12 weeks. NADPH oxidase 4 (NOX4) will be measured by real‐time polymerase chain reaction (qPCR) at baseline, 6 weeks, and 12 weeks; 3.Serum markers of liver function, Alanine transaminase (ALT), will be measured by commercial assay kit at baseline, 6 weeks, and 12 weeks.; 4.Metabolic syndrome risk factors will be measured at baseline, 6 weeks and 12 weeks. Height will be measured by stadiometer at baseline. Body weight, blood pressure, waist circumference will be measured by beam scale, blood pressure monitor and tape respectively. Triglycerides (TAG), cholesterol‐high density lipoprotein (HDL) and fasting glucose will be measured in whole blood using a rapid point‐of‐care multi‐assay blood analyser at baseline, 6 weeks and 12 weeks; 5.Serum metabolites will be measured by liquid chromatography‐mass spectrometry (LC‐MS) at baseline, 6 weeks, and 12 weeks; INCLUSION CRITERIA: Participants must be 18‐70 years old, overweight or obese, and have risks of metabolic syndrome, defined by presenting with at least two of the six following criteria: 1. BMI >25 kg/m² 2. Abdominal obesity: high waist circumference (Asian/Asian British ‐ men =90 cm; women =80 cm; White and all other ethnic groups ‐ men =94 cm, women =80 cm) 3. Fasting glucose =100 mg/dl (5.6 mmol/l) or treatment for elevated blood glucose 4. Blood pressure =130/85 mmHg or treatment for elevated blood pressure 5. Triglycerides =150 mg/dl (1.7 mmol/l) or treatment for elevated triglycerides 6. Cholesterol‐high density lipoprotein (HDL‐C) < 40 mg/dl (1.0 mmol/l) for male or < 50 mg/dl (1.3 mmol/l) for female or treatment for low HDL‐C