Diabetes Type II is highly prevalent and one of the fastest growing medical conditions in the United States.

The best way to reduce becoming a type 2 diabetic is by choosing a healthy diet and lifestyle. Period.

For many, the transition to a healthy lifestyle and diet takes time and may be difficult.

Thus, many are on medications which help stabilize blood sugar levels via various mechanisms.

These medications, especially when combined with the C677T MTHFR defect, may increase homocysteine levels due to the decreased amounts of methylcobalamin and methylfolate.

A published case study[1] provides evidence of this significant interaction:

Vitamin B12 deficiency may be induced by long-term use of metformin, which may in turn lead to hyperhomocysteinemia. Thus, hyperhomocysteinemia may increase the risk of vascular thrombosis in diabetic patients, when metformin is used and a homozygous methylenetetrahydrofolate reductase (MTHFR) C677T mutation is present. We report a 65-year-old Taiwanese diabetic woman who was treated with metformin for 6 years and who had suffered from swelling of the left lower extremity for 3 months. Ascending venography confirmed the diagnosis of proximal deep vein thrombosis, while hyperhomocysteinemia, megaloblastic anemia caused by vitamin B12 deficiency, and a homozygous C677T mutation of the MTHFR gene were also found. She had no identifiable venous thrombotic risk factors other than hyperhomocysteinemia, which seemed to be caused by both MTHFR C677T homozygous mutation and vitamin B12 deficiency. With the substitution of insulin injection for metformin, short-term supplement of vitamin B12, and anticoagulant therapy for the deep vein thrombosis, her anemia and hyperhomocysteinemia recovered rapidly. The deep vein thrombosis also responded well. Our findings highly suggested the role of metformin in causing vitamin B12 deficiency, which may serve as an additional risk factor for venous thrombosis in diabetic patients. Our report also highlights the need to check vitamin B12 levels during metformin treatment.

While this individual responded well to vitamin B12 alone, it is recommended to also supplement with methylfolate due to the C677T MTHFR mutation.

Talk with your doctor about supplementing you with methylcobalamin and methylfolate if you are taking Metformin.

Be sure to have your doctor evaluate your vitamin B12 levels – and ideally your methylfolate levels. Consider taking Active B12 with L-5-MTHF. This provides both methylcobalamin (active form of vitamin B12) and methylfolate. Begin by taking 1/2 tablet daily and work up. Work with your doctor to identify what amount is best for you.

Effective ways to evaluate your B12 level is to have your doctor check your:

  • MCV
  • MCH
  • urinary methylmalonic acid
  • WBC

Take Home Points:

  1. Type 2 Diabetes is mainly caused by poor dietary and lifestyle choices. Improve these areas and eliminate your diabetes.
  2. Metformin increases vitamin B12 deficiency.
  3. B12 deficiency causes potential for increased homocysteine.
  4. MTHFR C677T variants typically have increased levels of homocysteine – if untreated.
  5. The combination of MTHFR C677T and Metformin reduces one’s ability to adequately methylate.
  6. Supplement with vitamin B12 and methylfolate if using Metformin and/or having the C677T MTHFR variant.

Question for You:

  • You taking Metformin and have MTHFR? Were you aware of this connection?

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[…] of cardiovascular disease, which is a leading cause of death in patients with diabetes. Drugs like Metformin may increase homocysteine levels in people with MTHFR C677T. So it is especially important that people with diabetes treat […]

9 years ago

My son has a1298c. He has type 1 diabetes. Lantus, a long acting insulin was actually raising his blood sugar numbers. We are currently trying levemir and not getting great results.

8 years ago

Gail – my nephew has type 1 also. We are looking into genetic testing and nutrigenomics. He started methyl B12 but got all weepy and emotional. We are also looking at GABA supplementation. Have you found a nutrigenomic dr who specializes in type 1 or who will advise a type 1 diabetic? Dr. Ben, do you do that or know of anyone who does?

Jane Lee
8 years ago

Hi Dr Ben

Just a quick query – I am normal weight and was prescribed Metformin after a series of miscarriages (I was taking govnt recommended levels of folic acid as well) – My obstetrician told me “they don’t know why it [metformin] works but it just does…”. After starting Metformin I carried my child successfully (he is now 3 years old). I stopped the Metformin after giving birth. I have since learned I have the double C677T and am currently under treatment with a Natropath to figure out how best to balance my levels. I want to have another child and am determined not to do it via Metformin again – I am hoping that if I get the methylation working properly I wont need it. Do you concur? If I do all this and still start miscarrying again, do you think there is still a place for Metfornin or is it just too harmful to consider using again?

I really appreciate all your information and research. I am doing my best to spread the word among my friends who are suffering health issues that look likely to be related to the MTHFR gene mutations. Every doctor I come into contact with I mention it to and I am yet to find one that has ever heard of it. Hopefully if enough of us start raising it with our doctors, they will start to think it worth investigating further. Thanks

4 years ago

Hi Dr. Lynch,
I hate to bother you but was wondering if you could answer a quick question. I believe I most likely have an MTHFR mutation due to my health and family’s health history. I cannot get tested though because I live in France and those tests are illegal punishable by a 1500 euro fine. My doctor has prescribed me Metformin for pre-diabetis. I am not optimal on B12 as revelaed by a urine MMA test. i was mid- to high in the range 3.7 mmol/L ( <5.0). My question is will I be able to raise my B12 levels to optimal through oral substitution (methylcobalamin) and injections (hydroxycobalamin) plus oral methylfolate while taking the Metformin? Or should I raise my levels to optimal before starting the metformin then substitute throughout the therapy?

Thanks so much for the advice. I have read everywhere but don't find anyone talking about raising B12 levels while on metformin.

Have a great day! Melannie

7 months ago

I’ve just read that supplementing with 5-mthf should only be done for a short time, and that it can be dangerous.
Would you say that this is potentially true?

If yes, would should be taken instead, when stopping 5-mthf, to keep folate levels normal?

6 months ago

Metmorfin and Berberine have lots of similarities. Does it mean that berberine depletes B12 too?

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