When those two little red lines pop up on a pregnancy test, it does not take long for most mothers to shift into full ‘operation healthy pregnancy’ mode. The standard list of things to do to shift the odds in your favor of having a healthy baby have not changed much over the decades and it's rare that a new recommendation gets added. However, a new study may do just that - adding take vitamin B3 (also called niacin) to the list.
It is rare that an entire story gets neatly wrapped up in one paper, but that is the case with this new report in the New England Journal of Medicine.
The study uncovers the link between defects in the biochemical pathway that is responsible for making the essential biomolecule nicotinamide adenine dinucleotide (NAD) and the cause of certain birth defects in the heart, kidney and spine and also miscarriages. NAD cannot be produced in the body in the absence of niacin.
The Australian research group, from the Victor Chang Institute in Sydney, started by sequencing the genomes of family members from four families who had multiple members affected. The sequencing led them to two genes that carried mutations in the families.
The two genes identified through the sequencing both encode proteins that are important players in a pathway called the kynurenine pathway. The enzymes, 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU) had mutations that caused these enzymes to have much less activity than those with no mutations. With these mutations in the enzymes, the pathway that normally makes NAD from tryptophan is stopped short. In fact, when the amount of circulating NAD was checked in the patients with the mutations, a reduced level was found. Shown below is the biochemical pathway that is disrupted by these mutations.
NAD is important in many biological processes, as it participates in redox reactions which are at the heart of the cell's metabolism. In this role, NAD is also important to the proper development of organs.
On top of using the family’s genome sequences, the researchers took the work further with experiments in mice. Using CRISPR gene editing technology, they made mice with the same mutations that they found in the people and found that those mutated mice presented with similar phenotypes than the affected humans.
Interestingly, when the mutant mice were given vitamin B3, there was a reduction in birth defects and miscarriages. Whether the human birth defects and miscarriages could be helped with Vitamin B3 supplementation still remains to be seen.
For more on the role of Vitamin B3, see my colleague Josh Bloom’s article "The Many Names and Faces of Vitamin B3" where he takes a deep dive into the topic.
This study is really important for two reasons; 1) this is the first time that NAD has been linked to miscarriages and birth defects 2) the result translates into a simple (potential) solution for women who have low Vitamin B3 levels during pregnancy - taking Vitamin B3 supplements.
However, taking Vitamin B3 is not a panacea for miscarriages and birth defects. There are still many miscarriages due to chromosomal abnormalities or other causes. Nor is it something that everyone should just start doing, without further study or without speaking to an obstetrician.
Vitamin B3 is included in a standard prenatal vitamin. However, if you happen to have one of these mutations, or other unrelated problems that lead to decreased vitamin absorption, it may be necessary to take more. The next step will be to develop an easy to use test to screen pregnant mom's for low vitamin B3 levels and make changes accordingly.
This paper is very exciting because, unlike most topics in science and medicine, this one study seems to have produced robust data using both human genomics and mouse data and produced a clear result. In a rare occurrence, there is even an easy fix. Ah... if only all of our medical conditions could have such clear solutions.
NAD Deficiency, Congenital Malformations, and Niacin Supplementation Hongjun Shi, N Engl J Med 2017; 377:544-552 August 10, 2017 DOI: 10.1056/NEJMoa1616361