August 10, 2017

expert reaction to vitamin B3 supplements and birth defects in mice

A new study published in the New England Journal of Medicine (NEJM) investigated vitamin B3 supplements and genetic birth defects in mice.

Dr Sarah Stock, Senior Clinical Lecturer in Maternal and Fetal Health, MRC Centre for Reproductive Health, University of Edinburgh, said:

“This is exciting new research which increases understanding of birth defects. The researchers studied 4 families who had babies affected by complex birth defects with abnormalities in heart, spine and kidneys and other systems  (a syndrome called VACTERL). They found genetic abnormalities linked to the defects, which caused a low level of a protein called NAD. When the researchers studied mice with the same genetic defects and low levels of NAD they discovered that the mice had similar birth defects. Increasing vitamin B3 in the diet of mice with the genetic defect increased NAD and prevented the abnormalities.

“The results suggest that some complex birth defects in babies (e.g. some cases of VACTERL) might be caused or worsened by low level of vitamin B3 in the mother. This suggests that vitamin B3 supplements might help prevent certain types of birth defects. However, it must be emphasised that this work was done in mice and it is much too early to say if women should start taking extra vitamin B3. More research is needed to discover if dietary supplements of vitamin B3 work in humans, and what doses are safe to be used.

“The causes of most birth defects and miscarriage are not well understood. Dietary supplements can prevent some other types of birth defects, for example, women should take folic acid from before pregnancy and in the early stages of pregnancy, to help prevent spina bifida (neural tube defects). However high levels of some vitamins can also cause birth defects (e.g. vitamin A). More research is required to find out if other types of diet and vitamin supplements can prevent problems, but at the moment all pregnant women and couples trying to become pregnant should try to follow recommendations to eat a balanced healthy diet.”

Prof Jean Golding, Emeritus Professor of Paediatric and Perinatal Epidemiology, University of Bristol, said:

“This is a solid piece of work as far as it goes. However, the press release is most misleading. This was a study that involved just 4 children with malformations from 4 different families. The authors showed that affected offspring had a rare genetic variant that altered the way in which they metabolised the vitamin niacin. The study then used mice with similar genetic defects for further experiments. They showed a high rate of malformations in the mouse offspring. However if they supplemented the pregnant mice with niacin, there were no malformations.

“The following should be noted. There is no study that showed whether the human population that were deficient in niacin had more malformations or miscarriages than expected. There was no supplementation study in humans to show that niacin prevented adverse outcomes of pregnancy in humans. The preventive study in mice only involved mice with the genetic defects.”

Dr Katie Morris, Senior Clinical Lecturer and Consultant in Maternal Fetal Medicine, University of Birmingham, said:

“This animal research is very exciting and the role of B vitamins and supplementation in healthy pregnancy has been extensively researched with the recommendation for folic acid supplementation to prevent spina bifida being the advice most women will recognise as an example of this. This research looks at vitamin B3 to prevent miscarriage and major birth differences and has found that in genetically engineered mice (so that they completely lack a particular enzyme to produce the vitamin) supplementation with vitamin B3 could reduce the pregnancy loss and prevent the multiple structural differences.

“While exciting, this discovery cannot be translated into recommendations for pregnant women who at most may be deficient in vitamin B3. In particular the doses used in this research were ten times the recommended daily doses for supplementation in women and it is known that high doses of vitamin B3 can cause side effects for the mother and the long term effects on pregnancy and health of children are not known. Most pregnancy complications, including structural differences in babies, are due to a complex interaction of factors such as genes, the environment and other conditions in the mother such as diabetes and obesity, and thus at present this finding is not relevant to pregnant women as  whole.”

Prof Simon Fishel, Founder, President and Head of R&D at CARE Fertility, said:

“Whilst an intriguing and potentially important scientific study, which has been well conducted, it must be recognised that miscarriage has many causes.  The largest single cause of miscarriage are chromosome errors – and what we find in mouse modelling needs to be of proven medical concern in humans.

“As vitamin B3 is fairly ubiquitous in the foods we eat, NAD deficiency is more likely to be associated with a defective gene, or metabolic process; so discovering who is, or is likely to require Niacin supplementation is crucial to understanding its value”

* ‘NAD Deficiency, Congenital Malformations, and Niacin Supplementation’ by Shi et al. was published in New England Journal of Medicine

Declared interests

Dr Sarah Stock: No conflicts of interest.

Prof Jean Golding: No conflicts of interest.

Dr Katie Morris: No conflicts of interest

Prof Simon Fishel: “I am employed by and a shareholder in CARE Fertility.”