A Comprehensive Systematic Review Comparing Nutraceutical Supplementation (Magnesium, Chromium, Coenzyme Q10, Astaxanthin and Related Agents) on the Lipid Profile, HbA1c and HOMA-IR in Patients with Type 2 Diabetes Mellitus and Dyslipidaemia

Abstract

Introduction: Type 2 diabetes mellitus (T2DM) and atherogenic dyslipidaemia coexist in the majority of patients with cardiometabolic disease, and residual dyslipidaemic and insulin-resistant risk persists in a substantial proportion of patients despite optimal statin and glucose-lowering therapy. Nutraceutical supplementation—most prominently magnesium, chromium, coenzyme Q10 (CoQ10) and astaxanthin—has been proposed as an adjunctive strategy acting on mitochondrial bioenergetics, insulin-receptor signalling, lipid peroxidation and adipokine biology. The evidence base, however, is fragmented into single-agent trials that have never been compared within one analytical framework, and the dose-response architecture of these agents is poorly characterised in clinical practice. Methods: A comprehensive systematic review was conducted in accordance with PRISMA 2020. Eligible designs were RCTs, cohort, case-control, cross-sectional, and other observational studies; systematic reviews and meta-analyses were excluded from characteristics tables but retained for corroboration. Risk of bias was appraised with RoB 2 and Newcastle-Ottawa Scale; certainty rated with GRADE. Structured narrative synthesis with vote-counting and explicit dose-response analysis was performed. Results: Thirty-two primary studies (≥1,700 participants) met inclusion criteria, together with 16 systematic reviews/meta-analyses for corroboration. Fifteen outcome domains were analysed. Statistically significant improvements were demonstrated for all three co-primary endpoints. Magnesium 250-400 mg/day of elemental Mg significantly reduced HOMA-IR (3.8±1.1 versus 5.0±1.3, P=0.005) and HbA1c (P=0.04) in hypomagnesaemic T2DM patients. Chromium produced pooled reductions in fasting plasma glucose of 19.00 mg/dL (95% CI -36.15 to -1.85), HbA1c of 0.71% (-1.19 to -0.23) and HOMA-IR of 1.53 (-2.35 to -0.72). CoQ10 significantly reduced HbA1c by 0.37±0.17% (P=0.032) and, at 120 mg/day for 24 weeks, lowered triglycerides (P=0.020), LDL-cholesterol (P=0.016) and HOMA-IR (P=0.009). Astaxanthin 12 mg/day lowered LDL-cholesterol by 0.33±0.11 mmol/L and total cholesterol by 0.30±0.14 mmol/L (both P<0.05) and reduced malondialdehyde-modified LDL and HbA1c (both P<0.05). Dose-response synthesis identified a U-shaped optimum of 100-200 mg/day for CoQ10 on glycaemic endpoints and an inverse J-shaped optimum of 400-500 mg/day for total cholesterol; a non-monotonic chromium curve favouring doses below 200 µg/day for lipid endpoints; and a magnesium threshold effect conditional on baseline magnesium status. Discussion: The three agents act through non-overlapping mechanisms—magnesium as an insulin-receptor tyrosine-kinase cofactor, chromium through chromodulin-mediated amplification of insulin signalling, CoQ10 as a mitochondrial electron carrier and lipophilic antioxidant, and astaxanthin as a transmembrane carotenoid antioxidant—which explains the observed dissociation between glycaemic and lipid responses and supports rational combination rather than substitution. Efficacy is conditional rather than universal: magnesium works in hypomagnesaemia, chromium in the insulin-resistant phenotype, vitamin D in deficiency, and astaxanthin predominantly on the lipid and oxidative axis. Null trials in this review were characterised by replete baseline micronutrient status, short duration or supraphysiological dosing, which is consistent with a threshold-repletion model. Conclusion: Nutraceutical supplementation produces small but statistically significant and clinically coherent improvements in the lipid profile, HbA1c and HOMA-IR in adults with type 2 diabetes and dyslipidaemia, with agent-specific and non-monotonic dose-response relationships. These agents should be positioned as phenotype-targeted adjuncts to guideline-directed therapy rather than as substitutes for it, and future trials should be designed as baseline-status-stratified, dose-ranging studies with lipid and insulin-resistance co-primary endpoints.