High Folate Consumption May Increase Risk of Peripheral Neuropathy for Some Seniors

     Older adults who consume too much folate and who have a TCN2 Gene variation (referred to as GG) are three times more likely to have peripheral neuropathy. Scientists from the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts (USDA HNRCA) unearthed this remarkable finding. The American Journal of Clinical Nutrition has published this research study.

TCN2 Gene

The researchers did an epidemiological study with 171 adults aged 60 years and older. They found that persons with the GG variant of TCN2 were three times more likely to have peripheral neuropathy.

Roughly one in six individuals in the US, though variable by race or ethnic background carries two copies of the gene variation in TCN2. This gene encodes a member of the vitamin B12-binding protein family. Various tissues and secretions express this family of proteins that are otherwise referred to as R-binders.

TCN2 and other mammalian cobalamin-binding proteins may have evolved by the duplication of the common ancestral gene. And those persons who possess this gene variation are three times more likely to suffer from conditions related to vitamin B12 deficiency when compared to individuals without this variant.

Salient Features of the Research Study

  • Among the participants of the study those subjects with the GG variant and who consumed more than twice the RDA of 800 micrograms per day of folate, had seven-fold odds of peripheral neuropathy compared to those without the variant gene.
  • The investigators found no remarkable difference in likelihood among persons who ate less than 800 micrograms of folate per day.
  • "Due to the prevalence of the TCN2 variant, and because the average daily folate intake for U.S. adults over 50 is already more than twice the RDA, we believe that our findings highlight a potential concern for a large proportion of older Americans," said senior study author Ligi Paul, Ph.D., scientist in the Vitamin Metabolism Laboratory at the USDA HNRCA.
  • The authors warn that the design of the study does not allow for a cost and effect relationship. The investigators say that they have linked high folate intake with the possible risk of peripheral neuropathy, but they do not recognize it as a direct cause.
  • The researchers did not find whether the TCN2 gene affected the observed association between TCN2 polymorphism and peripheral neuropathy in this study.
  • In the total study population, the likelihood ratios were calculated based on 31 individuals with a GG variant out of the 171 people. The authors feel that increasing the sample sizes could improve the accuracy of the findings.


The researchers say that according to their data, older people should source their nutrients from balanced diet and not depend on supplements. They advise keeping the folate intake close to the recommended amounts.

Earlier findings suggest that excess folate intake could worsen associated neurological deficits in older adults. This study reinforces the above findings. Too much folate in pregnant women may increase the risk of autism in their offspring according to the researchers of Johns Hopkins University Bloomberg School of Public Health.

Excess folic acid consumption is linked with shortening of telomeres on human chromosomes and can reduce immunity levels in aged mice according to an earlier study by Dr. Ligi Paul and her colleagues.

The take home message for your clients from this study may be, though Folate is a necessary vitamin, excess intake may likely be harmful, and it is always wise to stick to the recommended amounts of folate. Please do share this story and let us know your valuable comments.

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