Abstract
BACKGROUND: Despite the popularity of dietary supplements, their effectiveness and safety in patients with diabetes remain controversial. Furthermore, evidence from clinical trials may not be generalizable to real-world settings. This study examined the association between dietary supplement use and mortality outcomes among patients with diabetes based on a nationally representative sample of US adults. METHODS: This study analyzed data from National Health and Nutrition Examination Survey (NHANES) 1999-2018. Supplement users referred to adults with diabetes who reported the use of any dietary supplements in the last 30 days, and with a cumulative duration of ≥ 90 days. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between supplement use and all-cause mortality, and mortality from cardiovascular diseases (CVD), diabetes, and cancer. Subgroup analysis of different supplement classes (vitamins, minerals, botanicals, amino acids, fatty acids, probiotics and glucosamine) were also conducted. RESULTS: We included 8,122 adults with diabetes (mean age: 59.4 years; 48.7% female), of whom 3,997 (54.0%) reported using supplements regularly. Vitamins (87.3%), minerals (75.3%) and botanicals (51.8%) were the most popular supplements. At a median follow-up of 6.9 years, 2447 all-cause deaths had occurred. Overall supplement use was not associated with risk of all-cause mortality among patients with diabetes (HR = 0.97, 95% CI: 0.87 to 1.08, P = 0.56). Subgroup analyses suggested that amino acid use was associated with a lower all-cause mortality (HR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028), while the use of fatty acids (HR = 0.62, 95% CI: 0.42 to 0.92, P = 0.018) and glucosamine (HR = 0.69, 95% CI: 0.51 to 0.95, P = 0.022) supplements were significantly associated with lower CVD mortality. CONCLUSIONS: Our results derived from real-world data suggested that overall supplement use was not associated with any mortality benefit in patients with diabetes. However, there is preliminary evidence that suggests a protective effect of amino acid use on all-cause mortality, and a benefit of fatty acids and glucosamine supplement use on CVD mortality. Future large-scale longitudinal studies are needed to investigate the association between dietary supplement use and other intermediate diabetes-related outcomes, such as glucose control and reducing diabetes-related complications.