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Metformin Micronutrient Depletions

Writer's picture: Dr. Amy Knaperek, PharmDDr. Amy Knaperek, PharmD

Let’s talk about Metformin. It is a medication used for diabetes in a class all by itself called Biguanides. Metformin decreases sugars made by the liver, decreases the amount of sugar absorbed in the intestines, and increases insulin sensitivity of the cells. Insulin is like a key that triggers cells to allow sugar to enter the cells so it can be used for energy. In pre-diabetes, metabolic disorder, and Type 2 diabetes, the cells are so saturated that they start to ignore the signal from insulin (called insulin resistance). So, insulin is knocking, but the cells are ignoring it. Metformin comes along and knocks a little bit harder, so cells take up more sugar.

Unfortunately, Metformin has some side effects. The main side effects include diarrhea, nausea, and vomiting, which is possibly due to the sugar that does not get absorbed in the gut. Everyone has genetic differences for how their bodies react to certain medications and Metformin is no exception. It is thought that one of these genetic variations results in Metformin staying in the intestines and increasing the GI side effects. Other side effects include metallic taste, headache, rash, and lack of energy. A rare side effect, due to reduced kidney function, is lactic acidosis.

So, now let’s talk about the micronutrients that Metformin can deplete: Vitamin B12 (cobalamin), folic acid (folate), and co-enzyme Q10. Vitamin B12 is important for red blood cell production, the formation of DNA in our cells, nerve function, metabolism, and energy production. A Vitamin B12 deficiency may lead to memory problems, nerve damage, an increased risk of Alzheimer's disease or dementia and mood changes. People with long-term, severe B12 deficiency can develop a type of anemia which manifests as weakness and fatigue. It is also linked with an increased risk of cancer and heart disease.

Folic acid is key to healthy cell growth and function, the making of DNA and RNA, and is necessary for the formation of red blood cells. Folic acid is also part of the methylation pathway which assists the body with detoxification. Folic acid also reduces the risk for birth defects and preterm birth. A folic acid deficiency can also show up as anemia (with weakness and fatigue).

This anemia often goes hand-in-hand with Vitamin B12 deficiency. In fact, Folic Acid supplementation can often disguise a Vitamin B12 anemia. Folic acid deficiency also shows up as difficulty concentrating, irritability and headaches. A person with folic acid deficiency may also have mouth or tongue sores and changes in skin, hair, or fingernail pigmentation. As mentioned previously, folic acid is part of the methylation pathway which is part of the body’s detoxification process. Changes to the MTHFR gene can inhibit the conversion of folic acid to its active form. This elevates homocysteine levels and increases systemic inflammation. Therefore, a folic acid deficiency can increase the risk of Alzheimer’s disease & dementia, cardiovascular disease & stroke, depression. There is also a higher risk for neural tube birth defects in women of child-bearing age if they do not have enough folic acid.

Co-enzyme Q10 acts as an antioxidant and is critical for muscle health. CoQ10 is needed to create energy in ALL our body’s cells. It can lower blood pressure, reduces platelet stickiness (to discourage clots & strokes), provides immune and cognitive support. CoQ10 deficiency can lead to physical and mental fatigue, difficulty concentrating, memory lapses, mild to moderate depression, and irritability. Chronic pain is also common with CoQ10 deficiency with frequent headaches or migraines, muscle and joint pain and an increased risk for developing fibromyalgia. Deficiency leads to a weakened immune system which makes people more susceptible to cold and flu viruses and chronic dental infections. The increased inflammation that can come from a CoQ10 deficiency can leads to high blood pressure, high cholesterol and heart failure.

I want to point out is the overlap of nutrient deficiencies with Metformin and signs and symptoms of diabetes progression. Diabetes can be a progressive disease. Nerve damage, development of heart disease, increased systemic inflammation (leading to high blood pressure, peripheral artery disease, and high cholesterol), and an increased risk for heart attacks and strokes.

All these things can happen if diabetes progresses, but they can also happen with Vitamin B12, Folic Acid and Co-Q10 deficiency. Sometimes a provider can confuse the nutrient deficiencies caused by Metformin as just the progression of disease. So, it is important to know if you take Metformin and start to experience numbness in your feet or legs, that it could be due to the medication you take and not just the progression of diabetes. Contact me, today, if you have any questions!


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