Homocysteine, Folate and B Vitamins: What the Heart and Stroke Trials Found
Folic acid, B6 and B12 lower blood homocysteine, but did that prevent heart attacks and strokes? What the large trials and Cochrane review found, and why a blood marker is not an outcome.
Content last updated . This page has not been medically reviewed.
If you have sudden face drooping, arm weakness, trouble speaking, or chest pain, call 911 (US) or your local emergency service now. If you think you may have a vitamin B12 or folate deficiency, see a clinician: the NHS advises seeing a GP, and says some problems caused by the condition can be irreversible. [1] This page is information only. Do not treat a high homocysteine result on your own.
What homocysteine is and why B vitamins matter
Homocysteine is an amino acid in the blood. MedlinePlus explains that a homocysteine test is most often used to measure vitamin B6, B12 and folic acid levels, because those vitamins help break homocysteine down. [2] High levels were once suspected of causing heart disease. MedlinePlus now says routine homocysteine testing to screen for heart disease risk isn't recommended for everyone, and that studies have shown in most cases lowering homocysteine doesn't reduce the risk of heart attack or stroke. [2] For the B12 and folate blood tests themselves, see vitamin B12 tests.What the trials found
| Trial or review | Who and what | What the source found | Label |
|---|---|---|---|
| HOPE-2 | 5,522 people aged 55 or older with vascular disease or diabetes took 2.5 mg folic acid, 50 mg vitamin B6 and 1 mg vitamin B12 daily, or placebo, for about five years. [3] | Homocysteine fell by 2.4 micromol per liter in the active group while it rose by 0.8 in the placebo group, yet the main outcome did not differ (relative risk 0.95). Fewer had a stroke (relative risk 0.75), and more were hospitalized for unstable angina (relative risk 1.24). [3] | Biomarker improved; heart outcome no good evidence of benefit |
| CSPPT, China | 20,702 adults with hypertension and no earlier stroke or heart attack took enalapril with 0.8 mg folic acid, or enalapril alone, for a median of 4.5 years. [4] | First stroke 2.7% vs 3.4% (hazard ratio 0.79). The authors called this consistent with benefit in adults with hypertension and low baseline folate. [4] | Promising but limited (one population) |
| Cochrane review, 2017 | 15 trials, 71,422 people, all using B6, B9 or B12 to lower homocysteine. [5] | No difference in heart attack, death or serious adverse events; a small reduction in stroke (risk ratio 0.90). [5] | Mixed |
| JACC review, 2021 | Update of a systematic review of vitamin and mineral supplements for cardiovascular outcomes. [6] | Preventive benefits from folic acid and B vitamins for stroke, graded moderate quality. [6] | Mixed |
What this means, and what it does not
- Stroke is the one signal. Even there the effect is small: for enalapril plus folic acid, the Cochrane authors estimated about 143 people would need treatment for 5.4 years to prevent one stroke, and that evidence came from one mega-trial. [5]
- Heart attack and death showed no difference in the pooled trials. [5]
- Findings depend on who was studied. CSPPT enrolled adults with hypertension in China and compared enalapril plus folic acid with enalapril alone. [4] The Cochrane review excluded people with end-stage renal disease. [5] Results do not transfer to everyone.
- Form matters. These trials used folic acid. Nothing here supports methylfolate or other forms for heart outcomes. See folate vs folic acid vs methylfolate.
- Lowering a marker is not the goal. Treating a proven B12 or folate deficiency is clinician-led and has its own pages, vitamin B12 deficiency and folate deficiency.
Frequently asked questions
Does lowering homocysteine prevent heart attacks?
In the pooled trials it did not change heart attack or death from any cause. [5] MedlinePlus says that in most cases lowering homocysteine does not reduce the risk of heart attack or stroke. [2]
Do folic acid and B vitamins prevent stroke?
There is a small signal. The Cochrane review found a risk ratio of 0.90 for stroke. [5] The CSPPT result came from adults with hypertension in China. [4]
Should I have my homocysteine tested?
MedlinePlus says routine testing for heart disease risk isn't recommended for everyone; a provider may order it if you have been diagnosed with heart or blood vessel disease, or if you are at high risk of low B12 or folic acid. [2]
Is folic acid the same as methylfolate in these studies?
No. The trials above tested folic acid. [3] [4] Results should not be assumed for other forms.
Are there downsides to the B-vitamin combination used in HOPE-2?
That trial found more hospitalizations for unstable angina in the active group (relative risk 1.24). [3] Ask a clinician or pharmacist before taking B vitamins with medicines or health conditions.
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
How to read the evidence labels
Labels used on this page: established nutritional role / deficiency treatment, evidence in adequately nourished people, mixed, insufficient evidence, no good evidence of benefit. A drop in homocysteine is a biomarker change. A heart attack or stroke is a clinical outcome. They are not the same thing.
Safety and who should ask a clinician
- Medicines: NCCIH notes vitamin B12 has the potential to interact with certain medications. [7] See medication interactions and vitamin B12 and medicines.
- Kidney disease: the Cochrane review excluded people with end-stage renal disease, so its results do not cover them. [5] See vitamins and kidney or liver disease.
- High-dose B6: NCCIH reports that 1 to 6 g of oral pyridoxine a day for 12 to 40 months can cause severe sensory neuropathy. [7] See vitamin B6 toxicity.
- Pregnancy and children: these trials enrolled adults aged 55 and older or adults with hypertension. [3] [4] For folate in pregnancy, see vitamins in pregnancy.
References
- NHS. Vitamin B12 or folate deficiency anaemia. Read 2026-10-23.
- MedlinePlus (US National Library of Medicine). Homocysteine Test. Read 2026-10-23.
- Homocysteine lowering with folic acid and B vitamins in vascular disease. The New England journal of medicine 2006. PubMed abstract. Read 2026-10-23.
- Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA 2015. PubMed abstract. Read 2026-10-23.
- Homocysteine-lowering interventions for preventing cardiovascular events. The Cochrane database of systematic reviews 2017. PubMed abstract. Read 2026-10-23.
- Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar. Journal of the American College of Cardiology 2021. PubMed abstract. Read 2026-10-23.
- National Center for Complementary and Integrative Health (NCCIH). Dietary Supplements and Cognitive Function, Dementia, and Alzheimer's Disease: What the Science Says. Read 2026-10-23.