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Could niacin supplementation help prevent congenital malformations?

Chloe_Turner's picture

With all the advances in modern medicine, we still have 1 in 50 children being born with major malformations and half the time we cannot identify a cause. So when the results of a study investigating a common pathogenic gene variant in families with congenital malformations shows there is a potential identifiable risk factor and a potential preventative treatment, there is an anticipated buzz surrounding the research.[1]

Niacin (vitamin B3) is an essential nutrient and precursor for coenzyme nicotinamide adenine dinucleotide (NAD). NAD is required for ATP production, energy metabolism and for the production of macromolecules involved in embryogenesis and DNA repair; all of which are required for healthy foetal development.[1]

Tryptophan is the primary essential amino acid required for de novo NAD synthesis and in pregnancy this conversion of tryptophan into niacin, and then NAD, appears to increase.[2]

Niacin supplementation can be used to reduce tryptophan conversion in healthy adults, theoretically sparing tryptophan for serotonin production.[3] Niacin has also been used therapeutically to treat hyperlipidaemia, support healthy methylation, and in this newest study it was hypothesised that niacin supplementation may be able to prevent congenital malformations associated with NAD deficiency.[1]

Published in the New England Journal of Medicine, the research conducted by Shi and colleagues involved recruiting 13 families, with at least one member diagnosed with multiple congenital malformations, to undergo genomic sequencing. The methods used included whole exome sequencing (WES) of peripheral blood lymphocytes to screen all members of the 13 families to uncover whether there were any commonalities. 

Results of the study found two genetic variants in four patients, both of which impact upon enzymes involved in de novo NAD synthesis. NAD levels in the patients were as low as one-seventh of their unaffected family members, indicating a NAD deficiency.

Shi et al went on to mimic NAD deficiency in a mouse model, to successfully represent that NAD deficiency could be directly linked to congenital malformations. In the next stage of the research, pregnant mice with NAD deficiency were given niacin, which proved to be an effective prophylactic. To achieve this same result in humans, supplementing with 140mg of niacin was recommended.

When supplementing with niacin, the amide form nicotinamide would be preferred over nicotinic acid due its greater therapeutic range. And while the upper limit of nicotinamide is 900mg for healthy adult women, no tolerable upper limit of nicotinamide or nicotinic acid supplementation in pregnant women has been established due to lack of data.[4] 

Australian multivitamins designed for pregnancy contain 18-50mg of niacin at present. Unfortunately standardised supplementing with higher doses is unlikely to be recommended at this stage due to the preliminary nature of the research and lack of human data. 

While it is promising to see both a genetic variant that may be able to be screened for in the future in high-risk populations, and a potential prophylactic as simple as niacin, it is still very early days. Further investigations are required before any changes can be made to standardised supplementing of this nutrient in pregnancy.

References 

  1. Shi H, Enriquez A, Rapadas M, et al. NAD deficiency, congenital malformations, and niacin supplementation. N Engl J Med 2017; 377:544-552. [Abstract]
     
  2. Badaway A. Tryptophan metabolism, disposition and utilization in pregnancy. Bioscience Reports 2015;35:e00261. [Full Text]
     
  3. Braun L, Cohen M. Herbs & Natural Supplements, 3rd edition. Elsevier: Sydney, 2010.
     
  4. Niacin. NHMRC 2014. [Link

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Chloe_Turner's picture
Chloe Turner

Chloé is an Adelaide based Naturopath with 7 years experience working in the health industry before joining one of Australia’s leading nutraceutical companies as a practitioner consultant. At the heart of Chloé’s interests in functional medicine is her desire to see, and contribute towards, the increased collaboration of forces between biomedical science and traditional healing. Chloé’s focus in clinical practice is in autoimmune disease, treatment and prevention.