Written by: Kelsey Schaffstall Young MS, RDN, CDN

 

Metformin and Vitamin B12 Deficiency

Metformin is one of the most commonly prescribed first-line therapies for Type 2
diabetes with ~120 million prescriptions filled worldwide (1).  Research has also shown an average
of 6-30% of patients using this drug could develop vitamin B12 deficiency making this an
extremely prevalent drug interaction to be aware of (2).  The mechanism by which vitamin B12
deficiency occurs in these patients is by decreased absorption. This means that even people
who are consuming adequate dietary vitamin B12 can be susceptible to deficiency while taking
Metformin.

Functions of Vitamin B12 and Symptoms of Deficiency

Vitamin B12 is a water-soluble vitamin that is bound to protein in food. It has many
important functions including supporting the function and development of the central nervous
system, synthesizing DNA and red blood cells, and acting as an important cofactor for enzymes (3).
Because vitamin B12 is bound to protein in food, digestion and absorption relies on breaking these
bonds so that free vitamin B12 can be utilized by the body. Stomach acid is required to release
vitamin B12 from food and Intrinsic Factor, a transport protein produced by the stomach, is
necessary for vitamin B12 to be absorbed in the small intestine (3).  Groups at risk of deficiency
include older adults who may have decreased stomach acid or Intrinsic Factor production,
vegans and vegetarians, people with gastrointestinal diseases affecting absorption such as
Celiac disease or Crohn’s disease, those who have undergone bariatric surgery, breastfeeding
women and infants, people taking Metformin, and those on medications that lower stomach
acid such as Proton Pump Inhibitors and H2 blockers (3).  Symptoms of vitamin B12 deficiency
include numbness and tingling of the hands and feet, anemia, palpitations, fatigue, memory
loss, and confusion (3).

Preventing Vitamin B12 Deficiency

The first step in preventing vitamin B12 deficiency is to identify it. The American
Diabetes Association now recommends that people taking Metformin should check their
vitamin B12 levels at least once per year (4).  You should also be sure to include a variety of foods
rich in vitamin B12 in your diet to allow your body as much opportunity as possible for
absorption throughout the day (3).  The best food sources of vitamin B12 include meat, fish, eggs,
dairy, and fortified foods such as nutritional yeast and dairy alternatives (3).  If you do not
consume animal products, try to incorporate fortified foods like cereals, nutritional yeast, or
dairy alternatives into your diet. Finally, consider vitamin B12 supplementation if you are at risk
of deficiency. Because supplements provide vitamin B12 in the free form as opposed to the
bound form, the bioavailability of supplements is 50% higher than from food which can provide
a necessary boost for those at risk (4).  Severe deficiency and malabsorption can be treated by
prescription injections, and oral vitamin B12 supplements are widely available. If you are

interested in how to optimize your nutrient intake and address any possible nutrient
deficiencies, work with your doctor and a Registered Dietitian to develop a nutrition and
supplementation plan that meets your specific needs.

 

References

1. Hirst JA, Farmer AJ, Ali R, Roberts NW, Stevens RJ. Quantifying the effect of metformin
treatment and dose on glycemic control. Diabetes Care. 2012;35(2):446-454.
2. Kim J, Ahn CW, Fang S, Lee HS, Park JS. Association between metformin dose and
vitamin B12 deficiency in patients with type 2 diabetes. Medicine (Baltimore).
2019;98(46):e17918-e17918.
3. Supplements NIoHOoD. Vitamin B12 Fact Sheet for Health Professionals.
https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/. Published 2021.
Updated April 6, 2021. Accessed2021.
4. Association AD. 8. Pharmacologic Approaches to Glycemic Treatment. Diabetes Care.
2017;40(Supplement 1):S64-S74.

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