B-Complex

• Corrects and prevents B‑vitamin deficiencies that can cause fatigue, neuropathy, dermatitis/glossitis, and specific anemias (B12/folate) — strong evidence from clinical practice and deficiency trials. - Supports energy metabolism via roles as enzyme cofactors in carbohydrate, fat, and protein metabolism; may reduce fatigue if deficient, but limited benefit in replete individuals — strong mechanistic evidence; clinical effects mainly in deficiency. - Red blood cell formation (folate/B12) and prevention/treatment of megaloblastic anemia due to deficiency — strong evidence. - Periconceptional folic acid (often included in B‑complex) reduces neural tube defects — strong evidence from large RCTs and population programs. - Lowers homocysteine (B6, folate, B12) — strong biochemical effect; clinical outcomes mixed (little to no effect on MI overall; some reduction in stroke risk in low-folate regions) — moderate evidence for stroke reduction, mixed for cardiovascular events. - Migraine prevention with high‑dose riboflavin (B2 200–400 mg/day) — moderate-to-strong evidence; note many B‑complex formulas contain much lower B2 than used in trials. - May improve mood/stress and some cognitive measures in people with low or marginal B‑status — mixed evidence from RCTs and meta-analyses; effects are small and population-dependent. - May improve neuropathic symptoms when deficiency is present (e.g., B1, B12); limited evidence for benefit in non‑deficient neuropathies — emerging to moderate evidence depending on context. - One large RCT found reduced risk of age‑related macular degeneration with combined folic acid, B6, and B12; requires replication — moderate evidence.

• Common: Flushing, warmth, itching, and headache with niacin-containing products (dose-dependent; more common with immediate-release ≥50 mg). Bright yellow urine with riboflavin (harmless). Mild GI upset (nausea, dyspepsia). - Uncommon: Dizziness/hypotension (niacin vasodilation), rash or acneiform/rosacea flares (B12), diarrhea or constipation, palpitations during flushing. - Metabolic: Worsened glycemic control and elevated uric acid/gout flares with higher-dose niacin — uncommon; risk increases with gram-level dosing. - Hepatic: Elevated transaminases to hepatotoxicity with high-dose or sustained-release niacin — rare but serious; risk increases with doses used for lipid modification. - Neurologic: Sensory neuropathy (numbness, paresthesias, ataxia) with chronic high-dose pyridoxine (usually >100–200 mg/day over months; rare cases at lower chronic intakes). - Hematologic/neurologic masking: High folic acid can correct megaloblastic anemia while allowing neurologic damage from unrecognized B12 deficiency to progress — rare but clinically significant. - Electrolytes: Rare hypokalemia during initial intensive B12 therapy in severe deficiency. - Hypersensitivity: Rare allergic reactions; injection B12 reactions occur infrequently. - Most effects are dose-related; typical multivitamin-level doses are generally well tolerated.

Commonly used ranges in studies and supplements (formulations vary; optimal dose depends on individual status and indication): - Thiamine (B1): 25–100 mg/day in B‑complex; deficiency treatment can use 100–300 mg/day in clinical settings. - Riboflavin (B2): 1.3–25 mg/day in B‑complex; migraine trials used 200–400 mg/day riboflavin. - Niacin (B3, nicotinic acid/niacinamide): 16–100 mg/day in B‑complex; lipid-lowering uses 1–2 g/day prescription niacin (medical supervision only; higher adverse-effect risk). - Pantothenic acid (B5): 5–100 mg/day in supplements. - Pyridoxine (B6): 2–50 mg/day in B‑complex; neuropathy risk increases with chronic intakes >100 mg/day (some reports at ≥50 mg/day long-term). - Biotin (B7): 30–300 mcg/day in B‑complex; hair/nail products often use 2–5 mg/day (evidence for benefit outside deficiency is limited). - Folate (B9, folic acid or methylfolate): 400–800 mcg/day commonly; periconceptional 400–800 mcg/day is standard; upper limit for synthetic folic acid from supplements/fortified foods is 1000 mcg/day for most adults. - Cobalamin (B12: cyanocobalamin, methyl- or hydroxycobalamin): 6–1000 mcg/day in supplements; 250–1000 mcg/day often used when absorption is impaired. Note: Many benefits (e.g., migraine prophylaxis) use doses far above typical B‑complex content; product labels vary widely.

• Absolute/relative (driven mainly by niacin or high-dose components): Active liver disease or unexplained persistent transaminase elevation (avoid high-dose niacin-containing products); active peptic ulcer disease; history of severe niacin-induced flushing or hepatotoxicity. - Caution: Gout or hyperuricemia (niacin can raise uric acid); diabetes or insulin resistance (high-dose niacin may worsen glycemic control); hypotension or unstable cardiovascular status (niacin vasodilation can cause symptomatic drops in BP); gallbladder disease (niacin may affect bile acids); history of B6-induced neuropathy or concurrent high-dose B6 use; prior colorectal adenomas when using high-dose folic acid (evidence mixed regarding risk). - Hematologic/neurologic: Do not use high-dose folic acid to treat anemia without ruling out/treating B12 deficiency (risk of masking with neurologic harm). - Genetic/optic: Leber hereditary optic neuropathy or tobacco–alcohol amblyopia — avoid cyanocobalamin; consider hydroxocobalamin/methylcobalamin under medical supervision. - Oncology/antifolate therapy: Patients on high-dose methotrexate or other antifolate chemotherapy — folic acid may antagonize therapy; only use if and as directed by oncology. (Note: low-dose methotrexate for rheumatologic disease is commonly paired with folate per guidelines.) - Pregnancy/lactation: Prenatal folic acid is beneficial; avoid high-dose niacin and high-dose B6; stay within prenatal ranges unless prescribed. - Surgery: Consider stopping high-dose niacin-containing B‑complex 1–2 weeks before elective surgery due to potential hypotension, glycemic effects, and bleeding risk when combined with antithrombotics; coordinate with the surgical team.