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Published on June 26, 2024

A RCT demonstrates a synergistic effect of vitamin B12 and omega-3 fish oil supplementation on lowering homocysteine levels and CVD biomarkers

Key Points

  • Homocysteine is associated with an increased risk of over 100 diseases or adverse outcomes, including almost all brain and mental health disorders, from childhood to old age, including dementia and Alzheimer’s, as well as a higher risk of cardiovascular (CVD) and metabolic diseases
  • In addition to supplementing with B vitamins, getting higher amounts of omega-3 fatty acids and vitamin D are known to decrease blood homocysteine levels; several previous studies have found a relationship between lower levels of homocysteine and higher blood levels of omega-3s and vitamin D
  • A study found that after 8 weeks of supplementation, homocysteine levels decreased by 22% with B12 only, 19% with fish oil only, and 39% with both supplements combined, demonstrating a synergistic effect of vitamin B12 and omega-3 fish oils on lowering homocysteine levels

Buy Your at-home Homocysteine Test from Food for the Brain Here


Homocysteine is a biomarker that is associated with an increased risk of over 100 diseases or adverse outcomes, including almost all brain and mental health disorders, from childhood to old age, including dementia and Alzheimer’s.

Learn More Here

Elevated homocysteine has also been associated with a higher risk of cardiovascular (CVD) and metabolic diseases. Research shows that higher homocysteine levels create pro-oxidation and pro-thrombotic status related to endothelial dysfunction, and leading to a higher risk of atherosclerosis, stroke, CVD events, and the progression of coronary artery disease (CAD).

Supplementing with B vitamins (including folic acid, B6 and B12) can reduce homocysteine levels, although taking B vitamins alone has not seemed to demonstrate benefit for lowering homocysteine related diseases such as CVD risk, indicating the need for other factors.

In addition to supplementing with B vitamins, getting higher amounts of omega-3 fatty acids and vitamin D are known to decrease blood homocysteine levels. Several previous studies have found a relationship between lower levels of homocysteine and higher blood levels of omega-3s and vitamin D.

Omega-3s in Combination with B Vitamins Effectively Lowered Homocysteine and CVD Biomarker Levels

A randomized controlled trial by Huang et al. aimed to see if there was a combined effect from the supplementation of both vitamin B12 and omega-3 fish oils on lowering levels of homocysteine, as well as ferritin, CRP, and other markers for cardiovascular risk.

30 participants randomly assigned to 3 groups:

  • 1000 ug B12 with 2g. fish oil per day
  • 1000 ug B12 only per day
  • 2 g. fish oil only per day

After 8 weeks of supplementation, homocysteine levels decreased by 22% with B12 only, 19% with fish oil only, and 39% with both supplements combined, demonstrating a synergistic effect of vitamin B12 and omega-3 fish oils on lowering homocysteine levels.

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Levels of uric acid, CRP, and ferritin also decreased significantly with fish oil and B12 plus fish oil supplementation. B12 supplementation alone was not significantly associated with any of the biochemical blood markers except homocysteine (Hcy).

“Our main findings were that high supplementation of fish oil alone or in combination with vitamin B-12 decreased plasma Hcy, ferritin, and CRP concentrations. Vitamin B-12 in combination with fish oil had synergistic effects on plasma Hcy concentrations.”

The study also confirmed previous findings showing that fish oil supplementation with or without B12 significantly lowered CRP concentration

Stay tuned for another upcoming post on the relationship between vitamin D and homocysteine!

Home Blood Spot Testing for Homocysteine is Now Available

This test is currently offered through Food for the Brain (FFB), another charity and friend of GrassrootsHealth, for a price of $59.95 (or subscribe and save up to 6%; GrassrootsHealth discounts do not apply to this test). While GrassrootsHealth is considering adding the homocysteine test to our study, we wanted to offer you the opportunity to test through FFB first and give us your feedback.

Buy Your at-home Homocysteine Test from Food for the Brain Here
Measure Your Vitamin D & Omega-3s Here

PLEASE NOTE This test requires a fasted blood sample. It is suggested that you perform the test first thing in the morning after 12 hours of fasting, i.e. no food or drinks.  For more information read Food for the Brain’s homocysteine FAQs here.  Email [email protected] with any questions you have about the test.


Make Sure You Are Also Getting Enough Vitamin D, Omega-3s, and Other Nutrients!

Having and maintaining healthy vitamin D levels and other nutrient levels can help improve your health now and for your future. Choose which additional nutrients to measure, such as your omega-3s and essential minerals including magnesium and zinc, by creating your custom home test kit today. Take steps to improve the status of each of these measurements to benefit your overall health. With measurement you can then determine how much is needed and steps to achieve your goals.  You can also track your own intakes, symptoms and results to see what works best for YOU.

Enroll in D*action and Test Your Levels Today!

How Can You Use this Information for YOUR Health?

Having and maintaining healthy vitamin D and other nutrient levels can help improve your health now and for your future. Measuring is the only way to make sure you are getting enough!

STEP 1 Order your at-home blood spot test kit to measure vitamin D and other nutrients of concern to you, such as omega-3s, magnesium, essential and toxic elements (zinc, copper, selenium, lead, cadmium, mercury); include hsCRP as a marker of inflammation or HbA1c for blood sugar health

STEP 2 Answer the online questionnaire as part of the GrassrootsHealth study

STEP 3 Using our educational materials and tools (such as our dose calculators), assess your results to determine if you are in your desired target range or if actions should be taken to get there

STEP 4 After 3-6 months of implementing your changes, re-test to see if you have achieved your target level(s)

Enroll in D*action and Build Your Custom Test Kit!

BLACK FRIDAY SALE! 20% off all orders! Use code: BF24. Sale ends Monday 12/2/24 at 11:59 PM PST. Offer does not apply to the T1D Prevention Test Kit.

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