Metabolic & Glucose
Insulin resistance is now recognized as one of the primary accelerators of biological aging — elevating inflammatory cytokines, damaging mitochondria, and accelerating cognitive decline. Addressing glucose regulation is among the most high-leverage longevity interventions, especially as metabolic dysfunction precedes disease by 10–15 years.
Berberine 500mg
Often called "nature's metformin." 116-patient RCT: HbA1c reduction comparable to metformin in T2D. Meta-analysis of 27 RCTs: total cholesterol −0.61 mmol/L, LDL −0.65 mmol/L, triglycerides −0.50 mmol/L. AMPK activator — the same pathway as metformin and rapamycin. Also activates autophagy and inhibits mTOR. Life Extension's version adds Ceylon cinnamon for synergistic glucose support.
Creatine Monohydrate 3–5g/day
500+ total studies make creatine one of the most researched supplements in existence. Beyond muscle performance: multiple RCTs show cognitive benefits in older adults and vegetarians (brain energy via phosphocreatine). Improves insulin sensitivity and glucose uptake in muscle tissue. Completely safe at standard doses — no "cycling" needed. Underused in longevity medicine relative to its evidence base.
Alpha-Lipoic Acid — Metabolic R-ALA
R-ALA improves insulin receptor sensitivity via GLUT4 translocation and reduces AGE (advanced glycation end-products) formation — a key mechanism in metabolic aging. Ziegler et al.: 600mg/day reduced diabetic neuropathy symptoms. Sustained-release form (Thorne ALA-SR) maintains stable blood levels. Also regenerates glutathione, vitamin C, and vitamin E — unique cross-category benefit.
Benfotiamine (Fat-Soluble B1)
Fat-soluble thiamine analog with 5× greater bioavailability than standard B1. Stracke et al. 2008: 900mg/day improved diabetic polyneuropathy. Mechanism: inhibits AGE (advanced glycation end-products) via transketolase activation. Particularly relevant for blood sugar management and neuroprotection in metabolic contexts.
Myo-Inositol
18 human RCTs for PCOS demonstrate improved insulin sensitivity and metabolic markers. Meta-analysis confirms meaningful HbA1c and fasting glucose improvements. Mechanism: insulin second messenger signaling. Also shows anti-anxiety effects. Particularly useful for women with hormonal metabolic dysfunction.
TMG (Trimethylglycine / Betaine)
Olthof et al. 2005: 6g/day significantly reduced plasma homocysteine. TMG is a methyl donor (SAMe cycle) with downstream effects on insulin signaling and liver fat metabolism. Essential cofactor for NMN supplementation. Also reduces homocysteine — an independent risk factor for cardiovascular disease and cognitive decline.