1670 ROUTE 34 N. 3R FLOOR SUITE 3C WALL • NJ 07727
1670 ROUTE 34 N. 3R FLOOR SUITE 3C WALL • NJ 07727

MTHFR and Homocysteine


  • An intermediate of various biochemical pathways
  • Involved with production of glutathione, transfer of methyl groups 
  • Elevated homocysteine also called hyperhomocysteinemia contributes to inflammation and damage to blood vessels and other organ systems
  • Optimal levels of homocysteine are <9
  • High homocysteine levels indicate a deficiency of folic acid, B-6, B-12 and methyl donors

Methyl Donors

  • Methionine and homocysteine are identical except that methionine has an extra methyl (CH3) group
  • Methyl donors are needed to reconvert homocysteine to methionine 
  • Methyl donors include 5-methyl folate and tri-methyl-glycine (also known as anhydrous betaine), choline, lethicin

MTHFR (Methylene Tetrahydrofolate Reductase)  

  • An important enzyme that helps biotransform 5,10 methylene tetrahydrofolate into methylated folate
  • Some people have a variant of the normal gene known as the MTHFR gene (a single nucleotide polymorphism) which impairs proper methylation 
  • An MTHFR SNP can contribute to high homocysteine and related diseases

MTHFR Variants (or single nucleotide polymorphisms =SNP)

  • There are two relatively common SNP’s:
  • A1298C – clinically irrelevant – will not effect homocysteine levels – does not require any specific supplementation
  • C677T – can effect homocysteine levels – patient may need more folate or 5-methyl-folate
  • Utilizing the methionine pathway by adding methyl donors like trimethyglycine and choline can bypass the problem of MTHFR variants

Manifestations of Elevated Homocysteine

Sources of Methyl Groups

  • B vitamins – folate, B-6, B-12
  • Trimethylglycine (betaine) 
  • Choline
  • Methionine
  • SAMe

Metabolically Directed Approach to Elevated Homocysteine

  • Look for root causes of homocysteine elevation – chronic inflammation, hypothyroidism, poor diet, MTHFR variants
  • When replacing needed B vitamins, take into account the patient’s individual metabolic needs
  • For example, a Dysaerobic patient will benefit from folate, but may suffer from increased Dysaerobic imbalance from B-6 and B-12.
  • On the other hand, the Anaerobic patient’s imbalance will be exacerbated by folate, yet may benefit more from B-12 and B-6
  • In summary, the treatment for elevated homocysteine is best personalized depending on the patient’s individualized metabolic requirements and balance

Other Considerations

  • Avoid sugar, smoking and caffeine – all can increase homocysteine 
  • Low B-12 levels are not necessarily caused by low intake or decreased absorption, but also by increased utilization by abnormal bowel flora 

Hypothyroidism raises homocysteine

To learn more about Michael Rothman MD contact us today by giving us a call at (732) 268-7663, emailing us at [email protected] or by requesting an appointment online.

Schedule an Appointment or Consultation
Complete this quick form for more information, or to schedule an appointment or no-obligation 15-min phone consultation.