Overview

A targeted trio of B vitamins that support neurotransmitter synthesis (B6), one-carbon/methylation pathways (B9 folate, B12 cobalamin), and myelin integrity (B12). Goldmind:Focus uses bioactive forms (pyridoxal-5′-phosphate, L-5-methyltetrahydrofolate, and methylcobalamin) at research-aligned doses to help sustain attention, processing speed, and mental energy. Low B-vitamin status becomes more common with age and is linked to worse cognitive outcomes, especially when homocysteine is elevated. Nutritionally they’re found: B6 (pyridoxine) in poultry, fish, potatoes; folate (B9) in leafy greens/legumes; B12 in animal foods and fortified products.

B6 (pyridoxine), B9 (folate), and B12 (cobalamin) all have some positive evidence for improving cognition, especially in cases of deficiency or elevated homocysteine. The effect sizes of each component on cognition are small (~0.1). Although they are water-soluble, megadoses can cause issues so aim for B6 < 20mg, folate < 1mg, B12 < 500mcg/day. These vitamins convert neurotoxic homocysteine to methionine/cystine–critical since elevated homocysteine is linked to brain atrophy and reduced cerebral blood flow.

More in-depth mechanisms of action:
• B6 (pyridoxal-5′-phosphate, PLP): Required co-factor for aromatic L-amino acid decarboxylase and glutamate decarboxylase -- enzymes that produce dopamine/serotonin and GABA, respectively. Even mild insufficiency biases towards lower GABA/serotonin tone, which can impair attention and stress control. 
• Folate (B9) + B12: Drive one-carbon metabolism, generating S-adenosyl-methionine (SAM) for methylation reactions that modulate gene expression and monoamine pathways; they also lower homocysteine, a risk factor for cognitive decline. B12 additionally supports myelin synthesis and neuronal integrity. 
• Structural brain protection in at-risk elders: In mild cognitive impairment (MCI) with higher baseline homocysteine, high-dose B6+B9+B12 slowed whole-brain and AD-related gray-matter atrophy; imaging changes tracked with slower cognitive decline.

Clinical studies supporting use (focus-relevant)

Older adults with memory complaints / cognitive impairment
• Durga J, et al. (FACIT Trial). RCT, n=818 adults 50–70 y with elevated homocysteine; 800 µg/day folic acid for 3 years vs placebo. Results: Better 3-year change in memory (ΔZ = 0.132) and information-processing speed (ΔZ = 0.087) vs placebo -- domains that typically decline with age. Estimated effect size: small (~0.13–0.20). 

• Smith AD, et al. (VITACOG). RCT in MCI, n=271 (MRI subset n=168); folic acid 0.8 mg + B12 0.5 mg + B6 20 mg/day for 24 months. Results: Whole-brain atrophy reduced (0.76%/y vs 1.08%/y; p=0.001), with ~53% reduction among participants with homocysteine > 13 µmol/L; slower cognitive decline tracked with less atrophy. Estimated clinical effect: small-to-moderate in high-homocysteine subgroup. 

• Douaud G, et al. (VITACOG MRI analysis). Same dosing; voxel-based morphometry showed marked protection of medial temporal and other AD-vulnerable regions, especially when homocysteine was above median, aligning structural benefit with slower cognitive decline. 

ADHD -- youth and adults
• Coleman M, et al. Double-blind crossover in hyperkinetic children (ADHD-like); pyridoxine compared with methylphenidate. Results: Behavioral improvement on pyridoxine in a responsive subgroup, indicating potential benefit in select children. Estimated effect: small-to-moderate in responders. 

• Ghanizadeh A, et al. RCT in children with ADHD on methylphenidate; 1 mg/day folic acid adjunct vs placebo for 8 weeks. Results: Improved aggression and quality-of-life vs control; ADHD symptom change modest. Positive as an adjunct for behavioral/emotional domains. 

• Lam NSK, et al. Systematic review across psychiatric conditions: L-methylfolate shows adjunctive benefits with good tolerability; ADHD evidence base is smaller but includes positive signals. 

Dose-relationships:
• Forms B6 as P-5-P, B9 as L-5-MTHF, B12 as methylcobalamin (bioactive, highly bioavailable forms).
• Doses generally aligned with human trials showing cognitive/mood benefits (e.g., B6 20 mg + folic acid 0.8 mg + B12 0.5 mg/day in MCI) and with long-term safety guidelines. See label for exact amounts. B6 and B12 in Goldmind:Focus are dosed lower than many studies to reduce the small likelihood of adverse effects.

Safety
• B6: Generally well tolerated at typical supplemental intakes; chronic very high intakes can cause sensory neuropathy -- stay well below upper limits.
• Folate (B9): Upper supplemental limit (as folic acid) exists to avoid masking B12 deficiency; using L-5-MTHF avoids unmetabolized folic acid and directly supports methylation.
• B12: Very safe; deficiency is linked to anemia, neuropathy, and cognitive symptoms; ensure adequate status if plant-based or with malabsorption risks. 

References
• Porter K, Hoey L, Hughes CF, Ward M, McNulty H. Causes, Consequences and Public Health Implications of Low B-Vitamin Status in Ageing. Nutrients. 2016;8(11):725.
• Lam NSK, Long XX, Li X, et al. The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review. Biomed Pharmacother. 2022;146:112541. 
• Durga J, van Boxtel MPJ, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults (FACIT): RCT. Lancet. 2007;369:208–216. 
• Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows brain atrophy in MCI (VITACOG): RCT. PLoS One. 2010;5:e12244.
• de Jager CA, Oulhaj A, Jacoby R, et al. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in MCI: RCT. Int J Geriatr Psychiatry. 2012;27:592–600. 
• Douaud G, Refsum H, de Jager CA, et al. Preventing AD-related gray-matter atrophy by B-vitamin treatment. Proc Natl Acad Sci USA. 2013;110:9523–9528. 
• Coleman M, Steinberg G, Tippett JN, et al. Pyridoxine in hyperkinetic children: double-blind crossover vs methylphenidate. Biol Psychiatry. 1979;14:741–751
• Ghanizadeh A, Sayyari Z, Mohammadi MR. Methylphenidate + folic acid vs methylphenidate: RCT in pediatric ADHD—QoL and aggression outcomes. Iran J Psychiatry. 2013;8(3):108–112. 
• Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review. Nutrients. 2016;8(2):68. 
• Linus Pauling Institute (OSU). Vitamin B6; Vitamin B12—neurotransmitter and methylation roles (reference pages). 

Regulatory note: Research indicates these B vitamins support cognitive processes via neurotransmission, methylation, and structural brain health, especially when correcting insufficiency/high homocysteine. Individual responses vary; not intended to diagnose, treat, cure, or prevent disease.