Individuals with type 2 diabetes are often prescribed a drug called metformin. It is considered a cornerstone in the treatment of type 2 diabetes. A new study (1), published in the British Medical Journal has found that patients who are treated over long periods of time with metformin are at risk of developing vitamin B12 deficiency, which is likely to get worse over time. One of the reasons that metformin is frequently prescribed is that it is one of the few type 2 diabetes drugs that is associated with improvements in heart disease which is a major cause of death in individuals with type 2 diabetes. However, the fact that the drug seems to cause vitamin B12 deficiency is a serious issue. In the research paper the scientists state (1) “Our data provide a strong case for routine assessment of vitamin B-12 levels during long term treatment with metformin” Checking vitamin B-12 levels regularly could help to prevent deficiency and the effects associated with that.
It is estimated that over 240 million people around the world have type 2 diabetes and these rates are expected to rise as the number of people who are overweight or obese also rises. Overweight is a major risk factor for type 2 diabetes.
Vitamin B12 is essential to keep all nerves healthy, therefore it is essential for brain function. Vitamin B12 also maintains healthy red blood cells. In the diet, vitamin B12 comes from meat, fish, dairy, eggs, other animal products, and fortified breakfast cereals. Strict vegetarians, who avoid meat, and vegans, who avoid all animal products, are also at risk of B12 deficiency. Studies seem to suggest that anything in the stomach that affects the normal acidity and digestive processes, ranging from infections to acid reflux medications to aging, may also interfere with the absorption of vitamin B12.
Symptoms of vitamin B12 deficiency may include fatigue, mental changes, anaemia and nerve damage known as neuropathy. Unfortunately all of these symptoms may be missed and misdiagnosed as a consequence of the type 2 diabetes or aging rather than vitamin B12 deficiency (1).
The research (1) involved 390 individuals with type 2 diabetes who were receiving insulin treatment. 196 were given metformin three times daily for over four years, 194 were given an inactive placebo. Blood was taken at the start of the study and again at 4, 17, 30, 43 and 52 months to test the vitamin B12 levels. Those who had taken the metformin had a significant reduction in their vitamin B12 levels compared to the group receiving placebo, who has almost no change in their vitamin B12 levels. In the group receiving metformin the reduced levels of vitamin B12 persisted and became even lower over time. The authors write (1) “Our study shows that it is reasonable to assume harm will eventually occur in some patients with metformin-induced low vitamin B12 levels”
Compared with placebo metformin treatment was also associated with a reduction in folate levels and an increase in homocysteine levels. The authors of the study conclude that (1) “Long term treatment with metformin increases the risk of vitamin B-12 deficiency, which results in raised homocysteine concentrations. Vitamin B-12 deficiency is preventable; therefore, our findings suggest that regular measurement of vitamin B-12 concentrations during long term metformin treatment should be strongly considered”.
I have written about homocysteine previously, it is important because there is mounting research which suggests that elevated homocysteine levels are a risk factor for heart disease, especially among individuals with type 2 diabetes. To recap: Homocysteine is produced when the amino acid (the building blocks of protein) methionine is broken down in the body. Normal levels of homocysteine are important to help build and maintain body tissues, however elevated concentrations in the blood can be harmful and have been associated with an increased risk of heart disease and other disorders. At normal levels homocystein can be converted in the body into a harmless substance called cystanthionine. The conversion of homocysteine into this harmless substance depends upon various B vitamins (B6, B12 and folic acid). Having good levels of these B vitamins appears to be a very good way of preventing high homocysteine levels and low levels of B vitamins have been associated with raised homocysteine levels
The authors also note “it is likely that, if anything, we underestimated the impact of metformin treatment on the risk of clinically important vitamin B-12 deficiency. A further reason that we may have somewhat underestimated the adverse effects of metformin is that all participants in our trial received frequent dietary counselling, which may have attenuated the impact of metformin treatment on vitamin status and may not be available in routine clinical practice”. Further studies are needed to confirm the results and to see if giving patients specific dietary advice on vitamin B12 would solve the problem. It might be that regular screening of vitamin B12 would be necessary and also possibly supplementation.
“The reduction in vitamin B-12 concentration associated with metformin increased with time. Current guidelines indicate that metformin is a cornerstone in the treatment of type 2 diabetes, but make no recommendations on the detection and prevention of vitamin B-12 deficiency during treatment. Our data provide a strong case for routine assessment of vitamin B-12 levels during long term treatment with metformin” (1).
If you are currently taking metformin you may wish to speak to your doctor about screening for vitamin B12 and homocysteine levels. If you have been diagnosed with type 2 diabetes do not take a vitamin B12 supplement prior to checking with your medical doctor first. The vitamins of the B group work very well as a team and interact synergistically in many processess, if you decide to take a supplement it would be worth considering a multi-B vitamin supplement rather than single B vitamin supplement, or a broad spectrum multi-nutrient supplement.
(1) de Jager J et al. 2010. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ 2010;340:c2181
Written by Ani Kowal
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