Part of understanding the holistic approach to repairing chronic health disorders is researching and learning about the traditional ways to treat these chronic health disorders as well. Many patients who have type 2 diabetes often suffer from headaches, fatigue, and overall discomfort. Many patients who have been diagnosed with type 2 diabetes are put on a medication known as metformin to help reduce blood glucose levels. In a study done, metformin showed to be linked to vitamin B12 deficiency. Part of creating a holistic healing plan for patients who have type 2 diabetes is to use natural supplements to avoid medications and other deficiencies such as this.

After a long-term trial was performed, it had been concluded that type 2 diabetics who had routinely ingested metformin showed a vitamin B12  deficiency. To offset this effect, a vitamin supplement may be taken along with monitoring from the prescribing physician. Another method patients taking metformin may benefit from is approaching their diabetes management from a functional approach. A functional approach will help their body naturally repair itself with the end goal of stopping metformin medication if approved by their healthcare provider.

The study performed by Coen Stehouwer, MD, of Maastricht University in the Netherlands and colleagues online in BMJ noted that with 4.3 years of treatment in a randomized, placebo-controlled trial, the hazard ratio for developing vitamin B12 deficiency while on metformin was 5.5 relative to placebo (95% CI 1.6 to 19.1). One of the main takeaways the researchers concluded was that the deficiency persists and grows over time.  Shorter studies showing slight relation to vitamin B12 deficiency and metformin had been previously recorded, but this is the first long-term study that truly reveals the association.

Throughout this study, they analyzed data on 390 type 2 diabetes patients randomized to metformin or placebo in a study named HOME. This study was designed to examine the effects of metformin on metabolic parameters and micro- and macrovascular diabetic complications.

To being, the patients in the study were initially treated with insulin and no other medications during a 12-week start-up phase. Metformin or placebo was then added to insulin treatment for 52 months.

The average patients chosen for this study had been on insulin treatment to manage their diabetes for around 7 years and had been diabetic for 13 years with a hemoglobin level at 7.9%. The typical age for participants of this study was middle age around 61.

Calculating the data from the 52-month study concluded that although the vitamin B12 levels declined throughout the entire study, the most significant drop occurred during the first few months.

From a mean of about 355 pmol/L at the end of the run-in phase, B12 levels dropped to about 305 pmol/L after four months, and from there to 280 pmol/L over the next four years.

The study also revealed that falling vitamin B12 levels were associated with increased serum homocysteine. When last measured, patients with a deficiency (defined as less than 150 pmol/L) had mean homocysteine levels of 23.7 μmol/L versus 18.1 μmol/L among those with vitamin B12 levels of 150 pmol/L, classified as low, and 14.9 μmol/L for those with normal vitamin B12.

These differences were proven statistically significant, with P=0.003 for deficient versus low, and P=0.005 for low versus normal.

It should be noted that the researchers indicated there was no significant relationship between homocysteine levels and treatment assignments in the trial, but that the “relatively low incidence of vitamin B12 deficiency” probably accounted for the finding.

“As treatment with metformin continues, however, we expect that vitamin B12 levels will continue to decrease, making increases in homocysteine concentrations inevitable in time,” the researchers added.

In conclusion, these associations remained significant after adjusting for age, gender, insulin dose, smoking status, duration of diabetes, and previous metformin treatment.

Citing earlier research, Stehouwer and colleagues wrote that metformin appears to reduce B12 levels by inhibiting dietary absorption in the intestine. Calcium supplements can reverse the malabsorption.

Stehouwer and colleagues argued that the study results “provide a strong case for routine assessment of vitamin B-12 levels during long-term treatment with metformin.”

The HOME study was funded by Altana, Lifescan, Merck Santé, Merck Sharp & Dohme, and Novo Nordisk.

Study authors and editorialists declared they had no potential conflicts of interest.

Prescription medications are known to have a long list of side effects associated with drug therapy. According to this study, a downside of metformin is the result of a vitamin B deficiency. If possible, I encourage using a functional approach to heal the body to avoid side effects such as these and allow the body to naturally repair. – Kenna Vaughn, Senior Health Coach  




De Jager J, et al “Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial” BMJ 2010; DOI: 10.1136/bmj.c2181.

Gever, John. “Keeping Tabs on Vitamin B Advised with Metformin.” MedPage Today, MedpageToday, 21 May 2010,

Vidal-Alaball J, et al “Reduced serum vitamin B-12 in patients taking metformin” BMJ 2010; DOI: 10.1136/bmj.c2198.

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