Choosing a Place of Birth during COVID-19 (free eBook)
Sign up to get the free eBook download, “Choosing a Place of Birth During COVID-19”
Internet news outlets have been running with a press release from the Victor Chang Cardiac Research Institute, which claims to have made “one of the greatest discoveries in pregnancy research,” a “breakthrough” for the prevention of miscarriages and birth defects. All women need do is take mega doses of niacin—although a follow-up statement cautions that pregnant women shouldn’t run to the store to stock up just yet. Is there substance behind the hype? Let’s see.
The press release celebrates the publication of a study in the New England Journal of Medicine. According to the study, Institute researchers did a genetic analysis of the parents and children in 13 families in which some of the children suffered from a constellation of severe birth defects of the heart, spine, digestive tract, and kidneys, as well as cognitive deficits, a syndrome that goes by the acronym VACTERL, and in some families, there had been miscarriages as well. In four of the families, the parents carried a defective gene responsible for making an enzyme used in the pathway for making NAD, a substance that plays a key role in energy storage and transmission within cells, synthesis of the building blocks of DNA and RNA molecules, and in repairing damaged DNA and other cellular proteins. Affected children inherited the defective gene from both sides, and healthy children either had two normal genes or one of each.
Given NAD’s functions, it is plausible that disruption in the ability to make sufficient amounts of it would have profound effects on embryonic development. HG: Already we have problems with the claim of a “miracle cure” for birth defects and miscarriages. The other nine families had affected children but didn’t have a defective gene, not to mention that NAD deficiency would be expected to have global effects on development, and most malformations are isolated or limited in scope.
Lab assays confirmed that the defective genes disrupted the pathway to making NAD. Affected children had much higher levels of pre-NAD metabolites and much lower levels of NAD.
An interesting thing about NAD is that it can be made two different ways: the enzymatic pathway and a separate pathway that produces it from niacin. This gave the Institute researchers a way of testing their theory that NAD deficit could cause the cluster of severe anomalies. They used gene modification techniques to create a strain of mice with a similarly malfunctioning enzyme and conducted a series of experiments.
They began by mating mice, each of which had one defective and one normal gene, to test whether offspring with two defective genes had similar failure of the enzymatic pathway. Some of the mice embryos would get two defective gene copies, but they would still be able to make NAD from niacin. As expected, all embryos were normal, and embryos with a double defective gene all had high levels of upstream NAD metabolites. HG: Whoa! Mouse embryos with a double-defective gene were normal? Human children with a double-defective gene had the syndrome. If human embryos could make NAD from niacin, why weren’t they OK?
Next, they repeated the cross, but this time, the researchers fed the pregnant females a niacin-free diet. Mice pups with the double defective gene should be affected, but the mice with at least one normal gene should not because they could make NAD via the enzymatic pathway. HG: To repeat, if the human mothers were getting niacin from diet, prenatal vitamins, or both, shouldn’t the children with the double-defective gene have been able to make enough NAD using the niacin pathway, especially during the early weeks when organs are forming but not much niacin is needed because the embryo is still tiny? This blows another hole in the “niacin deficiency is a common cause of birth defects” theory.
A funny thing happened, though. Despite their mothers being fed a niacin-free diet, all the mice pups, including the ones with the double-defective gene, were normally formed. The researchers explain this by saying that the pregnant females, all of whom had one defective and one normal gene, were producing enough NAD via the enzyme pathway “to sustain normal embryonic development” p. 549. HG: Say what?? Are they saying the females were passing NAD to the embryos? It seems they would have to be because the double-defective gene embryos couldn’t make NAD by either pathway if they had no niacin to use as a substrate. And if NAD is transmissible via the placenta, then what’s the case for niacin supplementation?
The researchers went back to the drawing board. To preclude the females from making NAD via either pathway, they mated female mice with double copies of the defective gene with males that had one normal and one abnormal gene and fed the pregnant females a niacin-free diet. This time, all the mice pups died regardless of whether they had two defective genes, one, or both normal genes. The researchers attributed this to the double-defective gene females not being able to make enough NAD to sustain the pregnancy.
The researchers tried the same mating cross again and experimented with providing varying amounts of niacin. This time they were able to recreate the effects seen in the human families: embryos with at least one normal gene were normally formed, and embryos with double-defective genes developed the constellation of anomalies. Further supporting their theory of NAD involvement with anomalies, the severity and number of the malformations and the amount of embryonic NAD were dose dependent on the amount of niacin.
The study’s discussion section suggests that: “Supplementation with high-dose niacin . . . before and during pregnancy might prevent recurrence of disease in these four families” [emphasis mine] and modestly concludes: “Many genetic and environmental factors have the potential to cause NAD deficiency during gestation. We propose that cases of congenital malformation that occur because of a deficit in NAD be collectively referred to as NAD deficiency disorders” (p. 551), which is the most that can reasonably be said based on their data. HG: Not a word is said about, as the press release overview trumpets, “One of the greatest discoveries in pregnancy research,” “Vitamin B3 can cure molecular deficiencies which cause miscarriages and birth defects,” “Discovery promises to significantly reduce miscarriages and birth defects,” or “Findings expected to change the way pregnant women are cared for.”
Enough said. The question of whether evidence justifies the Institute’s claims can confidently be answered with “no.”
The Take-Away: Over-hyped language is a clue that extravagant medical claims, even when coming from an apparently respectable source, are almost certainly malarkey.