MTHFR/Elevated Homocysteine Nutritional Support

Methyl B12

Each tablet provides 5,000 mcg of methylcobalamin and 1,000 mcg of folate as Quatrefolic

Synergistic blend of methyl-donating B vitamins quickly boosts tissue and brain levels to support numerous systems in the body like increasing metabolic energy, red blood cell production, mood regulation, nerve cell transmission, and cognitive function

Homocysteine (Methyl CPG)

Provides high concentration folate along with trimethyl glycine and key methylation vitamins B2, B6, B12 to promote DNA repair, homocysteine balance, neurotransmitter production, hormone balance, and healthy detox

Folate (active form) donates its methyl donor to vitamin B12 (cobalamin), forming methyl cobalamin.  This helps convert the amino acid metabolite homocysteine into amino acid methionine, consistently helping recycle homocysteine

Folic acid and vitamin B12 (Methyl CPG + Methyl B12)

0.2-0.8 mg as folic acid or 5-methylfolate (5-MTHF) per day, minimum 12 weeks for greatest benefit and maintenance for up to ~5 years, with optional 0.4-1.0 mg vitamin B12 for improved efficacy in patients with elevated homocysteine (3)(5)(6)(7)(10)(12)(15)(16)(21)(23)(34)(37)(38)

Folic acid provided primary effect on homocysteine reductions ranging between ~13-30% (3)(4)(5)(6)(7)(10)(12)(15)(16)(21)(22)(23)(26)(32)(34)(40)

Proportions of reductions in homocysteine were highly dependent on greater baseline homocysteine and lower baseline folate levels (5)(15)(16)(29)(37)

Higher folic acid doses ranging between 5-60 mg per day were safely used, but did not reduce homocysteine further than ingestion of 0.8 mg (16)(22)(29)(32)(40)

Most human evidence did not support greater folate bioavailability or efficacy in reducing homocysteine by 5-MTHF over folic acid, but it may provide extended retention of benefit upon discontinuation in patients with poor methylation capacity (2)

Vitamin B12 produced additional ~7% reduction in homocysteine (4)(5)(15)(16)(21) 

Individual trials showed benefit of adding vitamin B6 for further reductions in homocysteine, however this was not supported in meta-analyses (3)(5)(15)(16)(23)(34)

Males may have required higher folic acid dose ranges than women (6)

NAC (Acetylcysteine) 

Precursor to Glutathione, the master antioxidant in the body.N-acetylcysteine (NAC) 600 mg, 2-3 times per day, for 2-8 weeks (14)(24)(36)(41)

Reduced total homocysteine by 12-45% in healthy patients or patients at increased risk for CVD (9)(14)(24)(36)(39)

Oral formulations reduced total homocysteine in patients with end-stage renal disease by 21-25%, while intravenous formulations further reduce homocysteine during hemodialysis by ~90% (24)(27)(31)

Reduced SBP (~7.1 mmHg) and DBP (~3.3 mmHg) in hyperlipidemic men and SBP (~3.2 mmHg) in normolipidemic men; each 10% reduction in homocysteine is associated with 1.45-2.55 reduction in pulse pressure mmHg in patients undergoing hemodialysis (14)(27)(31)

Increased urinary excretion of homocysteine in its sulfonated form (36)

Omega-3 fatty acids

200-6,000 mg (~98-2,000 mg EPA/490-1,000 mg DHA) per day, for 1-12 months in patients with hyperhomocysteinemia or elevated homocysteine within normal ranges (8)(11)(13)(17)(18)(19)(25)(30)(42)(43)

Reduced homocysteine by 1.18-1.58 μmol/L on average using wide dose ranges, as shown in meta-analyses (8)(18)

Reduced homocysteine by ~2.5-4.0 μmol/L in patients with type II diabetes, patients on hemodialysis, or healthy adults using mid-range doses of 2,000-3,600 mg per day for 1-3 months and up to one year (11)(17)(25)(30)(42)(43)

Reduced homocysteine by ~1.6 μmol/L over 12 months in patients younger than 65 years, previously suffering from myocardial infarction (13)

Adjunct therapy with folic acid, vitamin B6, and vitamin B12 improved efficacy (8)(17)

Adjunct aerobic exercise and cognitive stimulation may be required for benefit in some populations, including older adults with mild cognitive impairment (19)