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Metformin

B12-Related Megaloblastic Anemia

B12 depletion impairs DNA synthesis in rapidly dividing cells, leading to macrocytic (megaloblastic) anemia, fatigue, pallor and, in severe cases, pancytopenia. This medication is commonly used for Diabetes.

Research

Clinical reviews identify vitamin B12 deficiency as a common cause of megaloblastic anemia; hematologic abnormalities often improve with replacement, underscoring the hematopoietic consequences of depletion.

Sources

Langan RC, Zawistoski KJ. Update on vitamin B12 deficiency. Am Fam Physician. 2017;96(6):384-389.; Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129(19):2603-2611.

Nutrients Depleted by Metformin

Some side effects may be linked to nutrient depletion caused by this medication.

  • Vitamin B12Depletion

    Long term treatment with Biguanides, such as Metformin or Metformin combinations with other drugs, are found in research to reduce vitamin B12 absorption due to it hindering the activity of a calcium-dependent mechanism. Insufficient levels of vitamin B12 can lead to higher circulating homocysteine levels and the elevated risk of neurological problems and cardiovascular diseases.

  • CoQ10Depletion

    Biguanide (anti-diabetic) drugs have been found in scientific evidence to decrease serum levels of coenzyme Q10. Type 2 diabetes can increase oxidative stress in the body, weakening its defenses and potentially harming cells. CoQ10, a powerful antioxidant, plays a crucial role in protecting cells from this damage. CoQ10 supplementation may help restore these levels, potentially improving mitochondrial function and protecting the kidneys from damage.

  • Folic AcidDepletion

    Research has shown that anti-diabetic Biguanide drugs may reduce folic acid absorption.  Folic acid is a powerful antioxidant and low levels make the body more susceptible to oxidative stress, which can damage enzymes involved in homocysteine metabolism, and subsequently increase its accumulation. Elevated levels of homocysteine (hyperhomocysteinemia) are a risk factor for various health problems including cardiovascular diseases, neurological problems, osteoporosis, and vision problems.

  • Thiamine Vitamin B1Depletion

    Biguanides, such as Metformin or Metformin combinations with other drugs, may contribute to reduced levels of thiamine (vitamin B1) in end-stage renal failure patients. Research has found metformin encephalopathy present in patients on hemodialysis for end-stage diabetic renal failure (ESRD). Patients with ESRD should consider having thiamine (vitamin B1) status monitored and supplementing with thiamine when levels are insufficient or deficient. 

Other Health Impacts of Metformin

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