Vitamin B12 Deficiency can be caused by Metformin

Those taking metformin for diabetic prevention were 31 percent less likely to develop the disease. Metformin imitate the effect of calorie restriction which proven to increase life-span in all animal study.

Vitamin B12 is a water-soluble vitamin that your body does not make, which means you must get it via your diet or supplements. Vitamin B12, along with other B vitamins, is used by your body to convert the carbohydrates you eat into glucose that your body uses for energy.

Vitamin B12 also plays a role in the production of DNA and RNA and works closely with folate to make red blood cells and produce S-adenosylmethionine (SAMe). SAMe (S-adenosyl-methionine) is an amino acid derivative normally synthesized in the body. SAMe is used by the body in three important pathways: Methylation, synthesis of polyamines, trans-sulfuration. Read more on SAMe.

Vitamin B12 is also important for the maintenance of your central nervous system, including the conduction of nerve impulses and producing the myelin sheath, which protects and “insulates” your nerves.

A deficiency in vitamin B12 can be difficult to detect and may lead to numerous and blood test commonly not sensitive to pick up vitamin B12 deficiency. Nerve damage is well known issue but many lesser known symptoms like poor sleep at night and osteoporosis. If you take the diabetes drug metformin, it’s important to be aware that you’re at an increased risk of this potentially serious vitamin deficiency.

Diabetes Drug Metformin Linked to Vitamin B12 Deficiency

Researchers from Albert Einstein College of Medicine in New York City used data from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study to look into the effects of metformin use on vitamin B12 levels.

Data from participants taking metformin twice daily or those taking a placebo were included, and the participants had their vitamin B12 levels measured after five and 13 years.

Significant differences in vitamin B12 levels were found. Among those taking metformin, average vitamin B12 levels were lower and 4 percent were deficient compared to 2 percent in the placebo group.

Further, nearly 20 percent of those taking metformin had borderline low vitamin B12 levels compared to 10 percent of those taking a placebo. More people in the metformin group were also anemic, which is associated with vitamin B12 deficiency.

Neither the U.S. Food and Drug Administration (FDA) nor the American Diabetes Association formally recommends monitoring vitamin B12 levels in people taking metformin, but the researchers suggested patients ask their doctors to do so.

Why Low Levels of Vitamin B12 Are Often Missed

Most physicians do not routinely test their patients’ vitamin B12 levels. Even if you have yours tested, the levels considered “normal” is actually not optimum. Furthermore, the so-call normal range is very wide, 200 pg/mL to 1100 pg/mL, even though people at the lower end of this spectrum (between 200 pg/mL and 350 pg/mL) often have symptoms of vitamin B12 deficiency.

In fact, if your levels are below 600 pg/mL, you might be suffering from B12 deficiency. Integrative medicine practitioner Chris Kresser explains.

“In Japan and Europe, the lower limit for B12 is between 500 to 550 pg/mL, the level associated with psychological and behavioral manifestations such as cognitive decline, dementia and memory loss.

The Signs and Four Stages of Vitamin B12 Deficiency

The symptoms also progress in stages. Some of the initial signs of B12 deficiency include unexplained anemia and neuropsychiatric disorders, and gastrointestinal disorders or infection with Helicobacter pylori.

If you are also elderly or a vegetarian and have some of these symptoms, a B12 deficiency may also be suspect for causing these problems.

Low levels can also lead to mental fogginess, memory troubles, muscle weakness, and — one of the hallmark signs — fatigue. Vitamin B12 also plays a role in:

Proper digestion, food absorption, iron use, carbohydrate and fat metabolism Healthy nervous system function Promotion of normal nerve growth and development
Help with regulation of the formation of red blood cells Cell formation and longevity Proper circulation
Adrenal hormone production Healthy immune system function Support of female reproductive health and pregnancy
Feelings of well-being and mood regulation Mental clarity, concentration, memory function Physical, emotional, and mental energy

Vitamin B12 for Bone Health

Accumulating research also suggests low levels of vitamin B12 may wreak havoc on your bone health.

Research published in the New England Journal of Medicine (NEJM), for instance, revealed that mice deficient in vitamin B12 have growth retardation and fewer osteoblasts (cells responsible for bone formation). The researchers suggested that lack of vitamin B12 may interfere with growth signaling in the liver and its “downstream effect” on the osteoblasts. Meanwhile, low vitamin B12 status may increase the risk for bone fractures in older men.

Older women with low levels of vitamin B12 (below 208 pg/ml) also experienced significantly more rapid bone loss in the hips — a sign of osteoporosis — than women with higher levels of B12 in a separate study. A meta-analysis even found that raising vitamin B12 levels in older individuals lead to a reduction in fracture risk.

Vitamin B12 Is Crucial for Mental and Cognitive Health

Vitamin B12’s role in brain health and mental health is particularly significant and can cause a range of neurological disturbances that mimic depression, dementia and confusion, as well as serious mental illness .

According to a small Finnish study published in the journal Neurology, people who consume foods rich in vitamin B12 may reduce their risk of Alzheimer’s disease in their later years. For each unit increase in the marker of vitamin B12 (holotranscobalamin), the risk of developing Alzheimer’s was reduced by 2 percent.

Meanwhile, B-group vitamins may slow brain shrinkage by as much as seven-fold in brain regions specifically known to be most impacted by Alzheimer’s disease. Among participants taking high doses of folic acid and vitamins B6 and B12, blood levels of homocysteine were lowered, as was the associated brain shrinkage — by up to 90 percent.

Who Is Most at Risk of Vitamin B12 Deficiency?

Children fed a vegan diet may continue to be deficient in the vitamin for years even after animal foods are added to their diet. It’s extremely important for kids to receive adequate levels of vitamin B12 during these formative years. One study found children fed a vegan diet up until the age of 6 who had marginal vitamin B12 status may have impaired cognitive performance as adolescents.

As mentioned, when you get older the lining of your stomach gradually loses its ability to produce hydrochloric acid (the stomach acid suppressed by proton pump inhibitors), which releases vitamin B12 from your food. If you’re over 50, it’s safe to assume you are not absorbing vitamin B12 at an optimal level. Other factors may also influence your body’s ability to absorb vitamin B12 properly, including:

Intestinal dysbiosis Leaky gut or gut inflammation Low stomach acid
Pernicious anemia Medications including acid-suppressing drugs (antacids) and metformin Alcohol
Exposure to nitrous oxide

In general, those most at risk of vitamin B12 deficiency include:

Vegetarians and vegans Elderly people
People who regularly use proton pump inhibitors (PPIs) People taking metformin
People with Crohn’s disease, ulcerative colitis, celiac disease or irritable bowel syndrome (IBS) Women with a history of infertility or miscarriage

Since deficiency of vitamin B12 related to low stomach acid either due to aging of stomach enzyme system or prolonged intake of anti-acid like proton pump inhibitor, they also commonly deficient in protein.

Oral Vitamin B12 Supplements Are Difficult to Absorb

Supplementation could benefit but poor absorbability of oral vitamin B12 supplements.

Oral B12 supplements are grossly ineffective. The best form is methyl-cobalamin. Due to poor absorption, via injection is the most efficient, especially for people with absorption issues. Sublingual (under your tongue) sprays are also effective, as they allow the large B12 molecule to be absorbed directly into your bloodstream.

References :

  • The Lancet Diabetes and Endocrinology September 13, 2015
  • Journal of Clinical Endocrinology and Metabolism February 22, 2016
  • Reuters March 10, 2016
  • University of Maryland Medical Center, Vitamin B12
  • May 6, 2011
  • Journal of Clinical Endocrinology and Metabolism February 22, 2016
  • Reuters March 10, 2016
  • US Department of Agriculture August 2, 2000
  • Geriatrics. 2003 Mar;58(3):30-4, 37-8.
  • New England Journal of Medicine September 4, 2014
  • Osteoporos Int. 2014 Jan;25(1):131-40.
  • J Clin Endocrinol Metab. 2004 Mar;89(3):1217-21.
  • J Nutr Metab. 2013;2013:486186.
  • Neurology. 2010 Oct 19;75(16):1408-14.
  • Proceedings of the National Academy of Sciences May 20, 2013
  • Am J Clin Nutr. 2000 Sep;72(3):762-9.