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Articles April 2017 Issue

Vitamin B12 Deficiency: Are You At Risk?

Genetics and excess folate may increase your odds of vitamin B12 deficiency.

[Updated May 7, 2018]

VITAMIN B12 DEFICIENCY: OVERVIEW

Detecting and treating B12 deficiency early is important since it can potentially lead to irreversible nerve damage. Consider these factors:

1. Are you in a high risk group? Older adults, people with digestive tract disorders, those who’ve had surgery affecting the stomach or intestinal tract, vegetarians and vegans are among those more likely to be B12 deficient.

2. Certain medicines may increase risk of B12 deficiency. Antacids, proton-pump inhibitors (for acid reflux and stomach ulcers) and the diabetes drug metformin may contribute to B12 deficiency. In its 2017 diabetes standards of medical care, the American Diabetes Association included a new recommendation that doctors consider periodically measuring B12 levels in people treated with metformin, especially in those with anemia or peripheral neuropathy.

3. Is more than B12 testing needed? If B12 levels are in the low-normal range, your doctor may test markers associated with B12 deficiency, such as homocysteine and methylmalonic acid.


You may be consuming plenty of vitamin B12. But, is it getting where it needs to go in your body? New research suggests that, even after absorption (which is sometimes poor), genetic variations held by some people may reduce the vitamin's transport from the intestines to the body's tissues where it does its work. Plus, excessive intake of folate (a different B vitamin) might make this problem worse in people with specific genetics.

"Many common genetic variations (polymorphisms) impact how well the body uses vitamin B12," says Ligi Paul, PhD, a scientist in Tufts' HNRCA Vitamin Metabolism Laboratory. "People who have these variants may be at increased risk for vitamin B12 deficiency." Possible long-term results of low B12 include anemia (which decreases oxygen transport), reduced mental function, depression and peripheral neuropathy.

peripheral neuropathy

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Peripheral neuropathy is nerve damage causing pain and numbness, usually in feet and hands.

Role of Genetics in Vitamin B12 Deficiency

Recently, Paul and colleagues looked at data from 171 home-bound adults age 60 and older who all had normal B12 blood levels, even though nearly half (75) had been diagnosed with peripheral neuropathy. Everyone was evaluated for a common variant in a gene called TCN2. This gene tells the body how to make a protein (transcobalamin) that transports B12 from the intestines to the body’s tissues. The TCN2 variant decreases how much of the transport protein is made and its ability to bind B12. So, less of the absorbed B12 gets where it needs to go in the body.

Compared to people without the TCN2 variant, those who had two copies of the variant (one from each parent) were three times more likely to have peripheral neuropathy, despite having B12 blood levels in the normal range. Additionally, in people with two copies of the variant, those who consumed more than 800 micrograms (mcg) of folate daily (twice the Recommended Dietary Allowance or RDA of 400 mcg) were at seven times higher risk of peripheral neuropathy compared to people without the TCN2 variant who had high folate intake.

Nearly 1 in 5 (17%) people in the study had two copies of the TCN2 gene variant, which is similar to the rate in the general population. Notably, having only one copy of the variant wasn’t associated with significantly increased risk of peripheral neuropathy, regardless of folate intake. Even so, people with either one or two copies of the variant had significantly lower B12 blood levels compared to people without the variant, including after adjusting for dietary B12 intake.

The study, published in the American Journal of Clinical Nutrition, was observational, so it couldn't be determined whether the high folate intake directly increased risk of peripheral neuropathy in people with the TCN2 genetic variant. "We have observed an association between negative health outcomes and the combination of lower vitamin B12 status and high folate intake in multiple populations, but the mechanism for this relationship is uncertain," Paul says.

Balancing Vitamin B12 and Folate

The RDA for B12 is 2.4 mcg. Animal products, such as meat, fish, dairy and eggs, naturally contain B12. Because B12 is bound to protein in these foods, adequate stomach acid is needed to release B12 so it can be absorbed. Between 10 to 30% of older adults don’t produce enough stomach acid. Vitamin B12-fortified foods (and some supplements) contain a man-made form of B12 called cyanocobalamin, which is more easily absorbed. However, foods fortified with B12 also may have high amounts of added folate in the form of folic acid, so check nutrition labels. ("Folate" is a general term often used for both folate that occurs naturally in food and man-made folic acid.)

"It's not uncommon for older adults to get too much folate. But, it's not from eating too many leafy green vegetables," Paul says. "Rather, very high folate intake is usually from taking multivitamin supplements and eating highly-fortified foods, such as some breakfast cereals." Many multivitamin supplements geared to older adults supply 400 to 800 mcg folic acid. In Paul’s study, 93% of those with high folate intake (over 800 mcg daily) were taking multivitamin supplements containing folic acid. Avoid combining highly-fortified foods and supplements.

The research is too early to recommend having your genetics checked, but the study findings are relevant to older adults. "You can’t change your genetics," Paul says. "However, you can make sure you get enough folate but not too much." Use multivitamin supplements with high folate levels only when advised by your doctor (such as for women of child-bearing age to meet the folate RDA to minimize risk of certain birth defects). Don't restrict intake of foods that naturally contain folate, such as spinach, asparagus and broccoli; no adverse effects have been associated with these nutritious foods.

To learn more: American Journal of Clinical Nutrition, December 2016

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