What is the relationship between homocysteine levels and hypertension, and can trimethylglycine (TMG) and grape seed extract help reduce blood pressure?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 17, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Elevated homocysteine levels are associated with an increased risk of hypertension, and reducing homocysteine levels through supplementation with B vitamins, trimethylglycine (TMG), and grape seed extract may help lower blood pressure. The relationship between homocysteine levels and hypertension is complex, involving mechanisms such as endothelial dysfunction, reduced nitric oxide production, and increased arterial stiffness 1. When homocysteine accumulates in the bloodstream, it can damage the inner lining of blood vessels, promote inflammation, and impair vasodilation, all contributing to hypertension.

  • Trimethylglycine (TMG, also known as betaine) has shown promise in helping lower blood pressure by serving as a methyl donor that helps convert homocysteine back to methionine, effectively reducing homocysteine levels.
  • Typical supplemental doses of TMG range from 500-3000 mg daily, divided into 2-3 doses.
  • Grape seed extract may also help lower blood pressure through its high proanthocyanidin content, which supports nitric oxide production, reduces oxidative stress, and improves endothelial function.
  • Effective doses of grape seed extract typically range from 150-300 mg daily.
  • Both supplements appear to work synergistically to address different aspects of blood pressure regulation, though effects are modest compared to prescription medications.

It's essential to note that these supplements should complement, not replace, conventional treatments for hypertension, and you should consult with a healthcare provider before starting them, especially if you're taking blood pressure medications or blood thinners 1. The most recent and highest-quality study suggests that B vitamins, including folic acid, vitamin B6, and vitamin B12, can reduce the risk of stroke by lowering homocysteine levels 1. However, the evidence for the effect of legume consumption on blood pressure is low, and more high-quality trials are needed to clearly define the benefits and mechanisms of legume consumption in blood pressure management 1.

  • Key considerations for patients with hypertension include monitoring serum B12 and homocysteine levels, as metabolic B12 deficiency is frequently missed and can have important consequences, including neuropathy, dementia, and an increased risk of stroke due to hyperhomocysteinemia 1.
  • Definitions of hyperhomocysteinemia that would justify treatment of an elevated homocysteine level range from 14 to 15 µmol/L, with a target homocysteine level <10 µmol/L considered optimal 1.

From the Research

Relationship between Homocysteine Levels and Hypertension

  • Elevated homocysteine levels are associated with an increased risk of cardiovascular disease, including hypertension 2
  • Homocysteine may contribute to the development of hypertension by impairing vascular endothelial and smooth muscle cell function, leading to endothelial dysfunction and altered vasomotor regulation 2
  • Elevated plasma levels of homocysteine can lead to oxidant injury to the endothelium, further contributing to the development of hypertension 2

Effect of Trimethylglycine (TMG) on Homocysteine Levels and Hypertension

  • There is no direct evidence in the provided studies on the effect of TMG on homocysteine levels and hypertension
  • However, studies have shown that folic acid supplementation can lower homocysteine concentrations and reduce the risk of cardiovascular disease, including hypertension 3

Effect of Grape Seed Extract on Blood Pressure

  • Grape seed procyanidins extract (GSPE) has been shown to decrease blood pressure in pre- and mildly hypertensive subjects when associated with nondrug intervention (diet and lifestyle modifications) 4
  • GSPE has been found to have beneficial cardiovascular effects, including improving blood pressure, microcirculation, and plasma oxidative status 4

Combination Therapy for Hypertension

  • Combination therapy is often necessary for optimal antihypertensive management, with the first choice being an ACE inhibitor plus a calcium antagonist 5
  • Folic acid supplementation has been found to be effective in reducing blood pressure and total homocysteine levels, as well as reducing the risk of cardiovascular and cerebrovascular events in patients with hypertension and hyperhomocysteinemia 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Homocysteine and essential hypertension.

Journal of clinical pharmacology, 2003

Research

Grape seed procyanidins in pre- and mild hypertension: a registry study.

Evidence-based complementary and alternative medicine : eCAM, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.