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Metformin

B12 Neuropathy & Cognitive Decline

Sustained B12 deficiency damages myelin in the peripheral and central nervous system, resulting in paresthesias, gait disturbance, impaired proprioception and cognitive or mood changes. This medication is commonly used for Diabetes.

Research

Systematic reviews and observational data show associations between low B12 levels and peripheral neuropathy, myelopathy and cognitive impairment; neurological manifestations may become irreversible if depletion is prolonged.

Sources

Badar A et al. Neuropsychiatric disorders associated with vitamin B12 deficiency: an updated review. Cureus. 2022;14(2):e22052.; Dekker MJHJ et al. Vitamin B12 deficiency-induced neuropathy and cognitive impairment. J Nutr Gerontol Geriatr. 2024;43(1):1-15.; NHS. Vitamin B12 or folate deficiency anaemia – complications. 2017.

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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