A physiology-based expert review synthesizing the evidence for micronutrient and omega-3 PUFA supplementation to slow or reverse modifiable determinants of unhealthy ageing, including inflammaging, immunosenescence, mitochondrial dysfunction, and progressive cognitive decline. The paper covers vitamins and essential trace elements (iron, selenium, zinc, copper) and identifies which RCTs provided positive versus mixed or negative outcomes.
Key numbers
- Zinc in zinc-deficient elderly populations: supplementation significantly reduces number of episodes and duration of acute upper airway infections (p. 11, citing RCT by Girodon et al. 1999, n = 725, adults over 65 years, two years, placebo-controlled).
- VITACOG trial: B6 (20 mg/day) plus B12 (0.5 mg/day) plus folate (0.8 mg/day) for 24 months in adults 70 years or older with mild cognitive impairment (n = 271) slowed cognitive decline (global cognition standardized units 0.03 to 0.11, p less than 0.0009) and reduced brain atrophy rate (0.76% vs 1.08% per year, p = 0.001) (Table 2, p. 13).
- Swedish selenium-CoQ10 RCT (Alehagen 2023, n = 441, adults with low selenium, 48 months): selenium 200 µg/day plus coenzyme Q10 200 mg/day reduced cardiovascular event rates and improved biomarkers insulin-like growth factor 1, adiponectin, and osteoprotegerin (p less than or equal to 0.02) (Table 2, p. 14).
- COSMOS multivitamin trial (Gaziano et al. 2012, n = 14,641, male physicians over 50 years, 11.2 years): reduced total cancer (HR 0.92, 95% CI 0.86-0.998, p = 0.04) and risk of first stroke (HR 1.01, 95% CI 0.91-1.10, p = 0.91 for stroke — non-significant) (Table 2, p. 14).
- DO-HEALTH trial (Bischoff-Ferrari 2025, n = 777, adults 70 or older, post hoc analysis): EPA plus DHA slowed biological ageing across 3 of 4 epigenetic clocks over 3 years (p. 15).
- AREDS (n = 3,640, ages 55-80): combination of antioxidants and zinc versus antioxidants alone reduced AMD progression (OR 0.75, 95% CI 0.52-0.98, p = 0.007) (Table 2, p. 13).
- Drugs impairing iron status: antacids, bile acid sequestrants, NSAIDs, opioids, PPIs (Table 1, p. 12).
- Drugs impairing selenium status: diuretics (increase urinary excretion), statins (interfere with selenoprotein synthesis) (Table 1, p. 12).
- Drugs impairing zinc status: diuretics, oestrogens, lipid-lowering drugs, RAAS inhibitors (Table 1, p. 12).
- Critical micronutrients for deficiency screening at age 50 or older: vitamins A, B-complex, C, D, E; iron; selenium; zinc; and EPA plus DHA (p. 17, Table 3 proposed blood panel).
Methods (brief)
Expert review commissioned by ESPEN (European Society for Clinical Nutrition and Metabolism). Literature was categorized as positive, mixed-neutral, or negative based on RCT effect on the primary outcome. Not a systematic review; selection may introduce bias. Analytical methods, LOD/LOQ, and CRM data are not applicable (review paper with no primary measurements).
Evidence fitness
Supports: characterization of RCT-level evidence for micronutrient supplementation outcomes in aging populations; identification of drugs that compromise essential metal status; scope of essential metal deficiency in older adults. Does not provide food concentration data or food-matrix contamination evidence. The expert opinion on screening strategies (Table 3 proposed blood panel, p. 17) is consensus opinion, not guideline-level recommendation.
Limitations
Not a systematic review; inclusion was based on expert selection, potentially introducing selection bias. Some included trials used self-reported intake data or observed null results despite known mechanistic effects. The paper explicitly notes that RCTs of micronutrients face challenges not applicable to pharmaceutical trials (participants already consuming the nutrient, U-shaped dose-response, variable baseline status). These limitations are acknowledged by the authors.
Related evidence
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