Homocysteine and Vitamin B

Niha Zubair, Arivale Clinical Research Scientist, PhD
Niha Zubair
Arivale Clinical Research Scientist, PhD

The potential of harm from B vitamin supplements coupled with the lack of demonstrated efficacy of homocysteine-lowering on disease endpoints leads us to conclude it is no longer judicious to recommend B vitamin supplements to lower homocysteine.

Evaluating the Latest Research

Here at Arivale, we’re always evaluating the latest research and updating our recommendations based on discoveries. As a Scientific Wellness® company, we take great pride in assuring our coaching recommendations are consistent with the latest evidence.

A new study is calling into question the wisdom of B vitamin supplements, not only at high doses, but at doses found in many multivitamins. Up until now, we have recommended B-vitamin supplements for Arivale Members who are working on lowering levels of homocysteine, an independent cardiovascular risk factor.

Normally we would not base our recommendations on a single study. However, this new study made us reevaluate our recommendations for lowering homocysteine. In this blog, we share the rationale for this decision.

What You Should Know About Homocysteine

Homocysteine is an amino acid and a breakdown product of protein metabolism. Studies show high homocysteine levels are associated with cardiovascular disease, cognitive decline, and depression.1,2  Taking vitamin B supplements-particularly folate, but also vitamin B12 or vitamin B6-is a well-documented way to lower high homocysteine levels.³

Although this sounds like it should be beneficial, researchers have observed a “homocysteine paradox”: Even though high homocysteine levels are harmful and vitamin B supplements lower homocysteine, evidence from multiple studies has not shown that using B supplements to lower homocysteine reduces the actual risk of cardiovascular disease, cognitive decline, or depression. The reasons for this paradox are unknown, but may relate to poor study design in some of the trials designed to look at B-vitamins and disease, or it may be due to some other physiological factor.

Potential Risks of Vitamin B Supplements

At Arivale, we do believe reducing high homocysteine levels (for members where this is a health risk) is important for optimizing your wellness. However, we are revising our recommendation for B-vitamin supplements in light of new research demonstrating the use of supplemental B vitamins-even at relatively low doses-may increase the risk of cancer (particularly lung cancer) and mortality.4,5

  • In a 2017 study, men who took vitamin B6 had a 40 percent increased risk in lung cancer, compared to those who didn’t take the supplement.4 Men who took vitamin B12 had a 30 percent increased risk in lung cancer. Both of these statistics accounted for age, race, education, body mass index, alcohol consumption, and smoking behavior, among other factors. The researchers additionally found that men who are smokers are even more at risk. No increased cancer risk was found in women in this study.
  • In 2009, an analysis of two clinical trials in patients with ischemic heart disease found those given folic acid plus vitamin B12 had an increased risk of cancer by 21 percent, cancer death by 38 percent, and death from any cause by 18 percent (all of these results were driven primarily by lung cancer).6 These findings were observed for both men and women and regardless of smoking status.

Other Ways to Decrease Homocysteine Levels

In spite of the homocysteine paradox, we believe there is good scientific evidence showing negative physiological effects of high homocysteine so lowering it in individuals where it is high is important for optimizing overall wellness. However, in light of the new information, we recommend whole-food dietary sources of B vitamins, rather than supplements, to lower homocysteine levels. Specifically, increasing dietary folate can help lower homocysteine levels.7-11 Foods rich in natural folate include leafy green vegetables, crucifers (like broccoli), and legumes. While popping a supplement might be easier than making room in your diet for these nutrient-dense foods, there are many other health benefits to these foods beyond lowering homocysteine, including getting lots of fiber and many vitamins and minerals. We recommend aiming for 400 mcg per day of dietary folate—primarily from naturally folate-rich foods or if need be from fortified foods. For reference, some foods that naturally contain folate include broccoli, a half a cup of cooked broccoli has 52 mcg (13 percent DV), and some whole grains such as millet, a cup of cooked millet has 33 mcg of folate (8% of DV). See here for more dietary sources of natural folate.

Don’t Throw Out Your B Supplements Yet

Before we get away from ourselves, let’s remember that vitamin B supplements can be helpful in some situations. Based on our evidence review, our concern is specifically about supplementation for the purposes of lowering homocysteine. Given the “homocysteine paradox,” the potential risk (lung cancer) outweighs the potential benefit (homocysteine reduction) considering the lack of evidence that lowering homocysteine with supplements reduces the risk of cardiovascular disease.

However, there are many health reasons one may decide to take B vitamins for specific conditions. For example, getting adequate levels of folate prior to and during pregnancy is very important for preventing certain birth defects. Because of this reason, the U.S. fortifies grain products with folate and prenatal vitamins typically contain B vitamins. Individuals who have had bariatric surgery or have GI disorders that impair nutrient absorption may also need a supplement to avoid insufficiency, as would anyone who has a measured deficiency in blood levels any of the B vitamins. Finally, your physician may have other, more specific and personalized reasons for recommending B vitamin supplements.  So, if your physician asked you to take a B vitamin, make sure you continue that recommendation!



  1. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 288, 2015-2022 (2002).
  2. Moorthy, D. et al. Status of vitamins B-12 and B-6 but not of folate, homocysteine, and the methylenetetrahydrofolate reductase C677T polymorphism are associated with impaired cognition and depression in adults. J Nutr 142, 1554-1560 (2012).
  3. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr 82, 806-812 (2005).
  4. Brasky, T. M., White, E. & Chen, C.-L. Long-Term, Supplemental, One-Carbon Metabolism-Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort. J Clin Oncol 35, 3440-3448 (2017).
  5. Ebbing, M. et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 302, 2119-2126 (2009).
  6. Ebbing, M. et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 302, 2119-2126 (2009).
  7. Chait, A. et al. Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease. Am J Clin Nutr 70, 881-887 (1999).
  8. Lim, H.-J., Choi, Y.-M. & Choue, R. Dietary intervention with emphasis on folate intake reduces serum lipids but not plasma homocysteine levels in hyperlipidemic patients. Nutr Res 28, 767-774 (2008).
  9. Pinto, X. et al. A folate-rich diet is as effective as folic acid from supplements in decreasing plasma homocysteine concentrations. Int J Med Sci 2, 58-63 (2005).
  10. Zappacosta, B. et al. Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia. Nutrients 5, 1531-1543 (2013).
  11. Ashfield-Watt, P. A. L. et al. Methylenetetrahydrofolate reductase 677C–>T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial. Am J Clin Nutr 76, 180-186 (2002).