Vitamin B12

Study: A double-blind, placebo-controlled RCT conducted by the London School of Hygiene & Tropical Medicine, involving 200 adults aged ≥75 years with biochemical evidence of vitamin B12 insufficiency (serum B12 107–210 pmol/L) but without anemia or neuropathy. Participants received 1 mg/day oral vitamin B12 or placebo for 12 months to assess effects on electrophysiological indices of neurological function.

Findings: The trial found no significant improvement in neurological function (e.g., nerve conduction velocity, amplitude) in the B12 group compared to placebo. Secondary analyses showed no effect on cognitive function or general well-being, suggesting limited benefit in asymptomatic older adults with mild B12 insufficiency.

Study: A 27-month RCT in Hong Kong involving 271 diabetic outpatients aged ≥70 years with mild B12 deficiency (serum B12 150–300 pmol/L). Participants received 1,000 µg/day methylcobalamin or placebo, with an 18-month open-label extension. The primary outcome was cognitive decline (Clinical Dementia Rating, CDR, and Neuropsychological Test Battery, NTB).

Findings: B12 supplementation significantly reduced serum methylmalonic acid (MMA) and homocysteine levels (p < 0.0001), but there was no significant difference in cognitive decline (CDR or NTB scores) between groups, even after excluding smokers or analyzing high-MMSE subgroups. The study concluded that B12 supplementation does not prevent cognitive decline in this population.

Study: A population-based, double-blind RCT in Nepal involving 600 infants at risk of B12 deficiency. Participants received 2 µg/day vitamin B12 or placebo for 1 year to assess neurodevelopment, growth, and hemoglobin concentration.

Findings: B12 supplementation improved metabolic markers (e.g., reduced MMA and homocysteine) but had no significant effect on neurodevelopment, growth, or hemoglobin levels. The study does not support widespread B12 supplementation in marginalized infants from low-income countries.

Study: A randomized, double-blind RCT across three centers in Pakistan (April–July 2024) involving healthy adults with B12 deficiency. Participants received 1,000 µg/day Sucrosomial® B12 or conventional B12 formulations (Mecogen SL, B-SUB, Evermin, or Neuromax) for 7 days. Serum B12 levels were measured at days 0, 1, 3, 5, and 7.

Findings: Sucrosomial® B12 achieved significantly higher serum B12 levels (peak 454–496 pg/mL by day 5) compared to conventional formulations (peak 274–304 pg/mL). It crossed the deficiency threshold (200–300 pg/mL) within 24 hours, suggesting superior bioavailability for addressing deficiency, including in conditions like pernicious anemia.

Study: The B-PROOF study, a double-blind RCT in the Netherlands involving 2,919 adults aged ≥65 years with elevated homocysteine (12–50 µmol/L). Participants received 500 µg/day vitamin B12, 400 µg folic acid, and 600 IU vitamin D3 or placebo with vitamin D3 for 2 years. Outcomes included physical performance, handgrip strength, and fall incidence.

Findings: B12 and folic acid supplementation slightly reduced homocysteine levels, but the effect on physical performance was small and not clinically relevant. No significant differences were found in handgrip strength or fall incidence compared to placebo.

Study: A placebo-controlled trial involving 39 elderly subjects identified through community screening with low serum B12 (<200 pg/mL) but without macrocytic anemia or neuropathy. Participants received B12 therapy (dose not specified) or placebo to assess psychiatric state and general well-being.

Findings: No evidence was found that B12 supplementation improved psychiatric state or general well-being compared to placebo. Improvements observed in both groups were attributed to the therapeutic effect of trial participation.

Study: A longitudinal cohort study in Brazil involving patients with persistent visuoconstructive deficit (VCD) 10–16 months after mild COVID-19. Whole blood cultures from VCD patients and controls were used to assess leukocyte expression of 11 biomarkers and the effect of B12 supplementation.

Findings: Patients with VCD showed persistent upregulation of CCL11 and LIF biomarkers. B12 supplementation reduced CCL11 expression via methyl-dependent epigenetic mechanisms, suggesting therapeutic potential for VCD in long COVID. The study was limited by a small, female-only sample and pre-Omicron infections.

Study: A clinical trial in Turkey involving elderly subjects with low serum B12. Participants received folic acid and B12 supplementation (doses not specified) to assess effects on coronary flow reserve.

Findings: Supplementation improved coronary flow reserve, suggesting cardiovascular benefits in B12-deficient elderly individuals. Specific details on dosing and duration were not provided in the source.

Study: A 2016 RCT involving children with autism spectrum disorder (ASD), testing methylcobalamin (B12) injections (75 µg/kg every 3 days for 8 weeks) versus placebo. The study assessed behavioral and biomarker outcomes.

Findings: B12 supplementation showed no significant improvement in ASD symptoms compared to placebo. Some biomarker changes (e.g., reduced homocysteine) were observed, but clinical relevance was limited.

Study: A 2010 pilot RCT involving 30 children with autism, testing methylcobalamin injections (64.5 µg/kg every 3 days for 6 weeks) versus placebo. Outcomes included behavioral measures and glutathione metabolism biomarkers.

Findings: B12 treatment improved some behavioral measures and increased glutathione levels (indicating reduced oxidative stress), but effects were modest and not consistent across all participants.