Vitamin B3, found in Marmite, unproven to prevent miscarriage

“Like it or loathe it, but Marmite could help prevent millions of miscarriages and birth defects around the world” is the overly optimistic headline in The Daily Telegraph.

The news is based on research into just four families who have children with birth defects, with three of the families also having had miscarriages.

Researchers sequenced the families’ DNA and found all the children had similar mutations that prevent the synthesis and circulation of an enzyme called nicotinamide adenine dinucleotide (NAD) in the body. NAD is used by the body for cell signalling. Vitamin B3, also known as niacin, is thought to stimulate the production of NAD.

Mice bred to have the same mutations and who also had miscarriages or offspring with defects were given vitamin B3 supplements, and subsequently all went on to have healthy babies.

In theory, vitamin B3 supplements might be effective for women who are pregnant or trying to get pregnant and are deficient in B3. But the researchers didn’t look at this – they only looked at rare genetic mutations in four children and replicated them in mice. No pregnancy outcomes in women were studied.

It’s certainly too soon to start recommending that all pregnant women start taking vitamin B3 supplements in the same way they’re advised to take vitamin D.

If you’re worried about vitamin B3, one way of safely upping your intake is by eating things like Marmite (or Vegemite), chicken and green peas.

Unfortunately, there are many reasons why miscarriages and birth defects occur, many of which are currently unavoidable.

Where did the story come from?

The study was carried out by researchers from a range of medical and academic institutions across Australia, including the University of New South Wales, the University of Sydney, Macquarie University, the University of Adelaide and University of Queensland School of Medicine.

The research was funded by the Australian National Health and Medical Research Council, the Australian Research Council, the Australian National Heart Foundation, the New South Wales Government Office for Health and Medical Research, a Queensland Premier’s Fellowship, the Kirby Foundation, the Chain Reaction Challenge Foundation, and the Key Foundation.

The study was published in the peer-reviewed The New England Journal of Medicine.

The UK media were arguably guilty of taking the associated press release at face value, and we suspect that some journalists didn’t actually read the study itself.

The much quoted statement from the lead author – “This has the potential to significantly reduce the number of miscarriages and birth defects around the world, and I do not use those words lightly” – is currently not supported by the evidence.

This research does not necessarily translate into reducing miscarriages in women. Miscarriages and birth defects happen for a range of reasons, not just because of one rare genetic mutation that reduces vitamin B3.

What kind of research was this?

This two-stage laboratory study first involved genetic sequencing in families with children born with multiple birth defects that developed when the child was growing inside the womb.

Researchers then looked at similar disease-causing mutations in mice and the effect that increasing vitamin B3 in the diet had on preventing malformations in the growing foetus.

This type of research is interesting as it combines observations and genetic sequencing on humans with laboratory research on mice manipulated to have similar genetic mutations.

Increases in vitamin B3 would still need to be tested in humans with these particular genetic mutations to make sure this isn’t just effective in mice.

What did the research involve?

Researchers took four families that each had a child with multiple birth defects and carried out genetic sequencing. This technique is used to analyse the individual bases (nucleotides) of a person’s DNA. This can help spot when a particular gene is altered (mutated) or missing altogether.

Four families – two from Lebanon, one from Iraq and one from the US – who had babies born with multiple birth defects took part in the research. The families from Lebanon and Iraq were related by blood.

The children had various different defects, some of which included short stature and heart, limb, kidney and ear-related deformities. Three of the mothers had also had one or more miscarriages.

Researchers found certain genetic mutations that affect the production of a molecule called nicotinamide adenine dinucleotide (NAD). This is produced naturally in the body, but can also be supplemented by increasing the amount of vitamin B3 in your diet, as it’s also found in vitamin B3.

The researchers replicated the families’ genetic mutations in mice, which were then given supplements of vitamin B3 to see if this affected their future offspring.

What were the basic results?

The four families’ genetic mutations caused problems encoding two proteins called 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU). These are both involved in a pathway that produces NAD. The children with birth defects therefore had reduced levels of circulating NAD in their bodies.

Mice bred to have mutations that reduced the production of HAAO and KYNU, and therefore reduced levels of circulating NAD, also had miscarriages or offspring born with defects.

After the mice were given more vitamin B3 as part of their diet, thereby increasing levels of circulating NAD, all subsequent offspring were born healthy.

How did the researchers interpret the results?

The researchers concluded: “Disruption of NAD synthesis caused a deficiency of NAD and congenital malformations in humans and mice. Niacin (B3) supplementation during gestation prevented the malformations in mice.”

Conclusion

This early-stage laboratory research has pinpointed two potential genes that might be responsible for some miscarriages and birth defects. As well as identifying a problem, the researchers also managed to find a solution: the effect of these genes can be combatted by increasing vitamin B3 intake.

However, treating a very specific and uncommon cause of birth defects in mice is certainly not a sure set solution to “significantly reduce the number of miscarriages and birth defects around the world”.

We need future research to see if the same effect would happen in humans.

Also, three of the four children included in the study were the offspring of parents who were related by blood. This might mean that the type of genetic mutations studied in this research are more specific to the children of parents who are related.

A vitamin B3 supplement might have less of an effect on other types of mutations, but we can’t say at this stage.

Overall, it seems like upping vitamin B3 intake in mothers who are deficient might have the potential to help prevent miscarriage and congenital malformations.

Testing vitamin B3 levels in pregnant women or women trying to get pregnant to see if they’re deficient would identify those who might benefit the most.

And eating more foods like Marmite, meat such as turkey and chicken, or vegetables like mushrooms or green peas could be one way to get more vitamin B3. Long-term high-dose vitamin B3 supplements should be avoided as this can lead to liver damage.

The National Institute for Health and Care Excellence (NICE) currently recommends pregnant women take folic acid (400mcg per day) and vitamin D (10mcg per day) supplements. The use of multi-vitamin supplements is not recommended as these often contain vitamin A which can cause birth defects.

You can also reduce your risk of having a miscarriage by avoiding smoking and drinking alcohol, eating a healthy diet, and being a healthy weight.