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Conclusion Breast cancer is a notable example where anti-angiogenic agents had constantly failed to make a significant impact on the survival of patients in clinical settings

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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