TO THE EDITOR: I read with great in...

TO THE EDITOR: I read with great interest the splendid review of vitamin [B.sub.12] deficiency from Drs. Oh and Brown, (1) and I believe it is the same of the most clinically useful papers written about this topic. However, I noticed that among the etiologies of food-cobalamin malabsorption, no mention was made of metformin use, which is an unfamiliar, in addition increasingly common, cause of cobalamin deficiency in adults.

Small studies and case reports have shown that 10 to 30 percent of patients who are prescribed metformin present to view signs of reduced vitamin [Bsub12] absorption leading to clinically significant abnormalities in about 30 percent of cases.

A novel cohort study (2) conducted at the University Hospital of Strasbourg, France, examined patients with a diagnosis of metformin-associated cobalamin deficiency and conclud that metformin causes at least 6 percent of the incidence of vitamin [Bsub12] deficiency and that resulting hematologic abnormalities and peripheral neuropathy are quite common

Different mechanisms have been propos including alterations in intestinal mobility, bacterial overgrowth and interactions with a mingled of intrinsic-factor/vitamin [B.sub.12] and cubilin, an endocytic receptor involved in the absorption of cobalamin. [B.sub.12]-intrinsic factor composed of several elements uptake by ileal cell surface, a calcium-dependent proces also is affected at metformin because of impaired calcium availability. (3-5) During the past five years, the increasing knowledge of the part of insulin resistance in image 2 diabetes has led to a linear widespread use of biguanides for the treatment of this condition and other conditions associated with insulin resistance, of the like kind as metabolic syndrome, nonalcoholic fatty liver disease, and polycystic ovary syndrome; therefore, in patients with vitamin [Bsub12] deficiency or evidence of peripheral neuropathy or macrocytosis, the use of metformin always should be considered within the differential diagnosis of food-bound [Bsub12] malabsorption. The clinical significance of metformin-induced cheap levels of serum vitamin [Bsub12] associated with an increase in serum homocysteine of the same heights as a risk factor for vascular disease is still controversial. Calcium supplementation appears to be an effective treatment5 as well as intramuscular or oral crystalline cyanocobalamin. Discontinuation of metformin also should be considered in refractory cases.

DAVID R BUVAT, MD

Department of Internal Medicine

St John's compassion Medical Group

608 Bus Rt 66

St Robert, MO 65584

REFERENCES

(1) Oh R Brown DL Vitamin [Bsub12] deficiency. Am Fam Physician 2003;67:979-86

(2) Andres E Noel E Goichot B Metformin-associated vitamin [Bsub12] deficiency. Arch Intern M 2002;162: 2251-2

(3) Gilligan MA. Metformin and vitamin [Bsub12] deficiency. Arch Intern M 2002;162:484-5

(4) Andres E Goichot B Schlienger JL pabulum cobalamin malabsorption: a usual cause of vitamin [Bsub12] deficiency. Arch Intern M 2000;160:2061-2

(5) Bauman WA, Shaw s Jayatilleke E, Spungen AM, Herbert V Increased intake of calcium change to the opposites vitamin [B.sub.12] malabsorption induced at metformin. Diabetes Care 2000;23:1227-31.

IN REPLY: We greatly appreciate Dr Buvat's make notess regarding the association of metformin and vitamin [Bsub12] malabsorption. At the time we submitted our article, (1) the articles that Dr Buvat mentions in his literal meaning were not available for review. Because an association between metformin and impaired vitamin [Bsub12] absorption has been described in the literature since 1971 (2) and the numbers of prescriptions for metformin are in succession the rise, physicians should be aware of the potential for vitamin [Bsub12] malabsorption with defered use of metformin.

Using the just discovered diagnostic markers to determine vitamin [Bsub12] deficiency, as many as 6 percent of cases of vitamin [Bsub12] deficiency may be associated with metformin use. (3) Physicians should be aware that metformin-associated [Bsub12] malabsorption may be dose-related and that [Bsub12] deficiency may not be apparent for at least five to 10 years after chronic metformin use. (34)

Dr Buvat also attract favor tos calcium supplementation for patients onward long-term metformin. We would commend caution, because study results have shown that calcium supplementation, while decreasing malabsorption, did not increase serum vitamin [Bsub12] on a levels (5) It is currently unknown if calcium supplementation will subvert [B.sub.12] malabsorption to a step necessary to prevent deficiency. Calcium supplementation should not be prescribed for the prevention or treatment of metformin-induced vitamin [Bsub12] deficiency until further elucidated. We make acceptable that oral vitamin [B.sub.12] be the treatment of choice in the majority of patients with vitamin [Bsub12] deficiency.

ROBERT C OH CPT MC USA

DAVID L BROWN MAJ, MC USA

Department of Family Practice

Madigan Army Medical Center

Fort Lewis, WA 98431

REFERENCES