10 Must-Knows About Homocysteine, 5-MTHF and B12

10 Must-Knows About Homocysteine, 5-MTHF and B12

For years, homocysteine has been a reliable marker in blood tests for increased risk of heart health concerns.

New research has linked chronically high levels of homocysteine to mood-related concerns, cognitive issues and memory concerns.

In This Article

Below are the top 10 things you should know about homocysteine.

  1. Homocysteine is a non-protein amino acid that is produced by the breakdown of the methionine, which is present in many foods such as cereals, legumes, seafood, meat and dairy products. (1) A sedentary lifestyle and diet high in these foods can dangerously increase long-term homocysteine levels. This is one reason I publish a free monthly seasonal eating guide, to encourage seasonal dietary shifts. >>> Sign up for my 3-Season Diet Challenge here
  2. Methionine is converted into homocysteine through a process of methylation. Methylation requires B vitamins (such as B12 and folate) to process the homocysteine and keep it at safe levels. When levels of folate and B12 are deficient, homocysteine levels rise. (2)
  3. Your annual bloodwork should include checking levels of homocysteine, B12 and folate. B12 and folate should be in the upper half of the normal range, and homocysteine should be below 7.8 umol/L which is lower than the commonly accepted value of 15 umol/L. Studies show that high-normal homocysteine levels are linked to the risk of heart circulation issues. (3)
  4. More and more people are being diagnosed with the MTHFR gene variant and have trouble converting folic acid into its active form, folate (to be precise 5-methyltetrahydrofolate or 5-MTHF). This results in folate deficiencies and higher-than-desired homocysteine level, suggesting a possible need for folate and B12 supplementation. (4,5)
  5. Numerous studies have compared the common supplement, folic acid, to its active form, folate (5-MTHF). In one study with heart patients who had the MTHFR gene mutation, researchers compared groups who were supplemented with either folate (5-MTHF) or folic acid. The folate (5-MTHF) group had 7 TIMES the amount of active folate in the blood compared to the group who took the folic acid supplement. (6)
  6. In another study, healthy participants were given low dosages of either folic acid or folate (5-MTHF). In the folate (5-MTHF) group, lowered homocysteine levels by 14.6% were observed. The folic acid group saw lowered homocysteine levels by only 9.3%. (6,7,8)
  7. The absorption of B12 is dependent on its breakdown during digestion. Heartburn, stress, medications, age and a host of other factors have been linked to reduced digestive strength and resulting B12 malabsorption. The combination of persistently low B12 and folate along with chronically high homocysteine has been linked to numerous health concerns. (2)
  8. One study in The New England Journal of Medicine concluded that persistently high homocysteine levels are an independent risk factor for cognitive health concerns. (9)
  9. High homocysteine levels can increase the risk of heart health concerns, but in another study of 924 middle-aged men, the men with the highest levels of homocysteine had 2 TIMES the risk of extreme mood swings compared to the men who had the lowest levels of homocysteine. (10).
  10. The active form of folic acid, 5-MTHF, is required for the production of neurotransmitters in the brain, which explains why healthy levels of 5-MTHFR and B12 are required for optimal mood and brain function. In fact, studies have linked a decrease in brain size (volume) to chronic deficiency of bioavailable B12. This decrease in brain volume is associated with compromised brain health and function. (11)


  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425139/
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164291/
  3. https://www.ncbi.nlm.nih.gov/pubmed/10779093
  4. https://www.ncbi.nlm.nih.gov/pubmed/24494987
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218540/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574248/
  7. https://www.ncbi.nlm.nih.gov/pubmed/16680068
  8. https://www.ncbi.nlm.nih.gov/pubmed/12486865
  9. https://www.ncbi.nlm.nih.gov/pubmed/11844848
  10. https://www.ncbi.nlm.nih.gov/pubmed/15585771
  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179651/

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Dr. John

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