Niacin during pregnancy

Vitamin B3 may prevent some miscarriages, birth defects, study says

Story highlights

Your body needs vitamin B3 to make NAD, an essential molecule

Adding B3 to diet of mice with genetic defect prevented miscarriages, birth defects

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Vitamin B3 – found in meat and green vegetables – has been shown to prevent one genetic cause of birth defects and miscarriages, according to a new study.

Overall, birth defects and miscarriage are global problems, affecting up to 6% of babies and up to 20% of known pregnancies. A possible prevention, then, could help millions worldwide.

“Not only have we identified a cause of miscarriage, and of birth defects where the babies affected have heart and vertebral and kidney defects among others, but we’ve also discovered a prevention in the form of niacin, also known as vitamin B3,” said Sally Dunwoodie, lead author of the study and a researcher at Sydney’s Victor Chang Cardiac Research Institute.

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Based on the findings, Dunwoodie suggests that pregnant women should take high doses of vitamin B3, also known as niacin, to prevent miscarriages and certain types of birth defects.

However, some experts urge caution: High-dose supplementation has not been proved effective – or safe – for pregnant women.

Dunwoodie and her colleagues based their research on a New Jersey Medical School study that found at least a third of pregnant women have low levels of vitamin B3 during the first trimester, when a baby’s organ development begins. The research also discovered that vitamin B3 levels were low in 60% of women by the third trimester.

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The body needs B3 to make a protein known as nicotinamide adenine dinucleotide, or NAD. It is found in all living cells and is essential for them to make energy, repair genes and communicate with other cells.

But environmental pollutants and genetic mutations can disrupt a cell’s ability to produce NAD, leading to lower levels than needed to function normally.

In the study, published Thursday in the New England Journal of Medicine, Dunwoodie and her colleagues investigated the effects of a lack of vitamin B3 by sequencing the genomes of 13 families. Each of the families had children with birth abnormalities, affecting in particular the vertebrae, heart, kidney, anus, esophagus and trachea, or limbs.

The team detected gene mutations in some of the mothers associated with a deficiency of B3 and an inability to synthesize enough NAD.

The team followed this with experiments on mice engineered to have the same genetic defect.

With a regular diet, the pregnant mice had either miscarriages or pups with a range of severe birth defects.

However, once vitamin B3 was introduced into the diet of the pregnant mice, the miscarriages and birth defects ended, and all the pups were born healthy.

“This is exciting and very encouraging research,” said Dr. Lisa Waddell, deputy medical officer at the March of Dimes, which funds research and programs to end premature birth, birth defects and infant mortality.

Waddell, who was not involved in the study, warned that additional research in humans is needed before advising pregnant women to take B3 above and beyond the current US recommendation of 18 milligrams a day.

Dr. Sarah Stock, senior clinical lecturer at the University of Edinburgh who also was not involved in the study, said it is “exciting” in that it increases our understanding of birth defects.

“However, it must be emphasized that this work was done in mice, and it is much too early to say if women should start taking extra vitamin B3,” she said. More research is needed in humans, she agreed, and on what dose would be safe for women.

David Amor, a clinical geneticist and professor at the University of Melbourne, said “there is no reason to believe that dietary niacin deficiency is a major cause of birth defects in the general population. ”

Amor, who was not involved in the research, noted that the genetic condition studied by Dunwoodie and her colleagues is “likely to be very rare.”

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“A broader question is whether dietary niacin deficiency might play a role in birth defects, even in the absence of the genetic deficiency of NAD, and whether dietary supplementation of niacin might be of benefit to pregnant women in the general population,” he said.

Michael Fenech of the Commonwealth Scientific and Industrial Research Organization, a government agency for scientific research in Australia, said the new research is “an important discovery.” Fenech observed that high-dose niacin (140 milligrams a day), as recommended by the study authors for women with the identified gene mutation, is significantly higher than the recommended daily intake in the United States.

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The study provides “no evidence” to support this recommendation, he said. “Furthermore, this dose may not be safe given that the tolerable upper intake level for niacin is only 35 milligrams a day for adults.”

Stock noted that diet plays a vital role in a healthy pregnancy. “At the moment, all pregnant women and couples trying to become pregnant should try to follow recommendations to eat a balanced healthy diet.”

Waddell added that doctors already recommend that pregnant women take a multivitamin containing B3.

Effect of maternal dietary niacin intake on congenital anomalies: a systematic review and meta-analysis

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Review

. 2022 Apr;61(3):1133-1142.

doi: 10.1007/s00394-021-02731-9. Epub 2021 Nov 8.

Shanika Palawaththa^#¹, Rakibul M Islam^#¹, Dragan Illic¹, Kate Rabel¹, Marie Lee¹, Lorena Romero², Xing Yu Leung¹, Md Nazmul Karim³

Affiliations

¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
² The Alfred Hospital, The Ian Potter Library, Melbourne, VIC, 3004, Australia.
³ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. [email protected].

^# Contributed equally.

PMID: 34748060
DOI: 10.1007/s00394-021-02731-9

Review

Shanika Palawaththa et al. Eur J Nutr. 2022 Apr.

. 2022 Apr;61(3):1133-1142.

doi: 10.1007/s00394-021-02731-9. Epub 2021 Nov 8.

Authors

Shanika Palawaththa^#¹, Rakibul M Islam^#¹, Dragan Illic¹, Kate Rabel¹, Marie Lee¹, Lorena Romero², Xing Yu Leung¹, Md Nazmul Karim³

Affiliations

¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
² The Alfred Hospital, The Ian Potter Library, Melbourne, VIC, 3004, Australia.
³ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. [email protected].

^# Contributed equally.

PMID: 34748060
DOI: 10.1007/s00394-021-02731-9

Abstract

Purpose: The significance of niacin in embryonic development has clinical implications in the counseling of pregnant women and may be used to inform nutrition recommendations. This study, therefore, aims to review the associations between maternal periconceptional niacin intake and congenital anomalies.

Methods: A systematic search of Ovid MEDLINE, ClinicalTrials.gov, AMED, CENTRAL, Emcare, EMBASE, Maternity & Infant Care and Google Scholar was conducted between inception and 30 September 2020. Medical subject heading terms included "nicotinic acids" and related metabolites, "congenital anomalies" and specific types of congenital anomalies. Included studies reported the association between maternal niacin intake and congenital anomalies in their offspring and reported the measure of association. Studies involved solely the women with co-morbidities, animal, in vitro and qualitative studies were excluded. The risk of bias of included studies was assessed using the Newcastle-Ottawa Scale (NOS). A random effects-restricted maximum likelihood model was used to obtain summary estimates, and multivariable meta-regression model was used to adjust study-level covariates.

Results: Of 21,908 retrieved citations, 14 case-control studies including 35,743 women met the inclusion criteria. Ten studies were conducted in the U.S, three in Netherlands and one in South Africa. The meta-analysis showed that expectant mothers with an insufficient niacin intake were significantly more likely to have babies with congenital abnormalities (odds ratio 1.13, 95% confidence interval 1.02-1.24) compared to mothers with adequate niacin intake. A similar association between niacin deficiency and congenital anomalies was observed (OR 1.15, 95% CI 1.03-1.26) when sensitivity analysis was conducted by quality of the included studies. Meta-regression showed neither statistically significant impact of study size (p = 0.859) nor time of niacin assessment (p = 0.127). The overall quality of evidence used is high-thirteen studies achieved a rating of six or seven stars out of a possible nine based on the NOS.

Conclusion: Inadequate maternal niacin intake is associated with an increased risk of congenital anomalies in the offspring. These findings may have implications in dietary counseling and use of niacin supplementation during pregnancy.

Keywords: Birth defect; Congenital anomaly; NAD; Niacin; Pregnancy outcome; Vitamin B3.

Cited by

Response to the letter to editor: Can niacin supplementation prevent congenital malformations associated with maternal use of proton pump inhibitors?
Palawaththa S, Islam RM, Ilic D, Rabel K, Lee M, Romeo L, Leung XY, Karim MN. Palawaththa S, et al. Eur J Nutr. 2022 Nov 30. doi: 10.1007/s00394-022-03061-0. Online ahead of print. Eur J Nutr. 2022. PMID: 36449092 No abstract available.
Can niacin supplementation prevent congenital malformations associated with maternal use of proton pump inhibitors?
Vermorken AJM, Zhu J, Ma L, Cui Y. Vermorken AJM, et al. Eur J Nutr. 2022 Nov 28. doi: 10.1007/s00394-022-03060-1. Online ahead of print. Eur J Nutr. 2022. PMID: 36441236 No abstract available.

References

1. World Health Organization (2010) Sixty-third World Health Assembly: Resolutions and Decisions. WHO Press
1. Carmichael SL (2014) Birth defects epidemiology. Eur J Med Genet 57:355–358. https://doi.org/10.1016/j.ejmg.2014.03.002 - DOI - PubMed
1. Christianson A, Howson CP, Modell B (2005) March of Dimes: global report on birth defects, the hidden toll of dying and disabled children. March of Dimes Birth Defects Foundation
1. Perry M, Mulcahy H, DeFranco E (2017) Influence of periconception smoking behavior on birth defect risk. Obstet Gynecol 129:1S-2S. https://doi.org/10.1016/j.ajog.2019.02.029 - DOI
1. Yang J, Qiu H, Qu P, Zhang R, Zeng L, Yan H (2015) Prenatal alcohol exposure and congenital heart defects: a meta-analysis. PLoS ONE 10:e0130681. https://doi.org/10.1371/journal.pone.0130681 - DOI - PubMed - PMC

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Scientists: Vitamin B3 may prevent miscarriages and birth defects

Cathy Silver
BBC Health Correspondent

events.

Image copyright Getty Images

Taking vitamin B3 may prevent miscarriages and birth defects. Scientists came to this conclusion after testing on mice. nine0018

Researchers at the Victor Chang Institute in Sydney called the discovery a "double break" because they found both a cause and a preventive solution.

Every year, 7.9 million children are born with congenital malformations around the world, and scientists hope that the results of the study will be used everywhere.

However, according to some experts, these findings should not form the basis of recommendations for pregnant women.

The researchers analyzed the DNA of four families in which the mother had multiple miscarriages or children were born with multiple congenital malformations such as heart, kidney, vertebral or cleft palate problems. nine0011
They found mutations in two genes that caused the baby to lack a vital molecule known as nicotinamide adenine dinucleotide (NAD), which allows cells to produce energy and organs to develop normally.

The team leader, Professor Sally Dunwoody, replicated these mutations in mice and found that they can be corrected if the pregnant mother takes niacin (vitamin B3).

"You can increase NAD levels and completely prevent miscarriages and birth defects, and this will bypass the genetic problem," says the researcher. ". nine0011
"This is very interesting, but this finding cannot form the basis of recommendations for pregnant women who may be deficient in vitamin B3," says Dr. Cathy Morris, an expert in maternal fetal medicine at the University of Birmingham. "Doses used in this study , 10 times the recommended daily dose."

High-dose side effects are unknown, notes Morris, and complications during pregnancy are often due to a complex set of factors. nine0011

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Professor Jean Golding of the University of Bristol called the study "serious work" but cautioned against extrapolating the results too much, as the scientists examined the genetics of only four families and mice.

Professor Dunwoody now recommends that pregnant women take a prenatal multivitamin that includes the recommended 18 mg of niacin. nine0011
"But different people have different ability to absorb nutrients," she added, adding that body mass index and diabetes can affect how a woman's body produces NAD.

She also noted that while scientists do not know enough about women with insufficient levels of niacin in the body, this should be the subject of another study.

Pregnancy vitamins

☼ Vitamins are organic compounds necessary for life, the synthesis of which is absent or limited in the body (except for vitamin D, which is synthesized in human skin) nine0011
☼ The most at risk of developing micronutrient deficiencies are children during critical periods of growth and development, pregnant and lactating women

☼ Vitamins are found in foods in very limited quantities

☼ In nature, there are no products that contain all the vitamins necessary for the human body

☼ Water-soluble vitamins (group B vitamins, vitamins C, H, P) do not accumulate in tissues, therefore they must be ingested daily. Active forms as coenzymes are involved in metabolic reactions. nine0065 Fat-soluble vitamins (vitamins A, D, E, K) are able to accumulate in tissues. Their deficiency is less common. They are structural components of cell membranes and exhibit an antioxidant effect.

• A significant part of the population is deficient in vitamins B1, B2, B5, B6, C, D, E.

• Negatively affects the development of children, increases child mortality, impairs endurance, physical and mental performance, reduces the activity of the immune system, accelerates the aging of the body, reduces life expectancy. nine0011
Signs of hypovitaminosis:

• Increased fatigue

• Irritability

• Insomnia

• Reduced attention and memory

• Cracks and sores in the corners of the mouth

• Peeling and pustular skin diseases

• Bleeding gums

Hypervitaminosis:

• Only two vitamins are known - A and D, long-term intake of which in quantities exceeding the physiological need of the body by thousands of times can cause hypervitaminosis.

• Absolutely safe levels of intake of vitamins A and D exceed the daily requirement by 10 times, vitamins C and B6 - by 100 times, vitamins E, B1, B2 and folic acid - by more than 100 times.

Taking a complex of vitamins and minerals during pregnancy reduces the risk nine0011
• All congenital developmental defects in general;

• Anomalies in the development of the urinary tract by 85%;

• Neural tube defects by at least 50%;

• anomalies of the face, cleft lip or cleft palate by 25-50%;

• Some limb anomalies by 35%;

• congenital heart defects by 35%;

• Low birth weight. nine0011
Vitamin A (retinol)

• Structural component of cell membranes

• Regulates the growth and differentiation of embryonic and young body cells

• Participates in the photochemical act of vision

• Stimulates cellular immune responses

• Anticarcinogen

• Antioxidant

• At doses above 10,000 IU, it is toxic and increases the likelihood of kidney, genitourinary, and brain defects. nine0011
• The most dangerous time for an overdose of vitamin A is the first 7 weeks of pregnancy. Therefore, you should not take drugs with a high content of vitamin A.

Sources: butter, liver, carrots, spinach, apricots.

Vitamin B1 (thiamine)

• normalizes the activity of the heart

• Contributes to the normal functioning of the nervous system

• affects the metabolism of carbohydrates and fats nine0011
• Normalizes the acidity of gastric juice, motor function of the stomach and intestines

• Hypervitaminosis has not been described.

Sources: bread, cereals, yeast, legumes, meat, liver.

Vitamin B2 (riboflavin)

• Promotes tissue regeneration processes, including skin cells

• Hypervitaminosis not described

Sources: milk, cottage cheese, eggs, liver, meat, yeast. nine0011
Vitamin B6 (pyridoxine)

• Required for over 60 enzymes to work

• Participates in the synthesis of nucleic acids, amino acids, proteins

• In the processes of cell division

• in the mechanisms of nerve impulse transmission.

• Some researchers have linked high doses of vitamin B6 during pregnancy to congenital limb anomalies. Pregnant women should avoid large doses (10-20 times the daily requirement). nine0011
Sources: yeast, egg yolk, milk, beef, kidney, beans.

Vitamin B12 (cobalamin)

• Participates in the formation of erythrocytes - red blood cells

• Contributes to the normal functioning of the nervous system

• Mothers with low vitamin B12 levels, regardless of folic acid levels, are 5 times more likely to have babies with neural tube defects nine0011
• Up to 20% of children with autism are vitamin B12 deficient

• hypervitaminosis - the introduction of the vitamin, even in a thousandfold, compared with the physiological dose, did not have a toxic effect.

Sources: beef liver, kidney, heart, meat, cheese.

Folic acid (folacin, vitamin B9, vitamin BC)

• Participates in the processes of cell division

• in the process of formation of erythrocytes - red blood cells

• in the metabolism of carbohydrates and proteins

• deficiency leads to neural tube defects (back bifida, hydrocephalus, anencephaly), as well as other congenital malformations: cleft lip, cleft palate, anomalies of the limbs, lungs, congenital heart defects)

• Taking folic acid reduces the chance of neural tube defects by 75% nine0011
• Reduces the risk of preeclampsia (late toxicosis of pregnant women)

• May reduce the chance of a child having a brain tumor in childhood by more than 60%

• Hypervitaminosis has not been described.

Sources: Green parts of plants, cauliflower and Brussels sprouts, spinach, green onions, cereals, wheat germ, nuts, grain bread, legumes, citrus fruits.

Nicotinamide (vitamin PP, vitamin B5, nicotinic acid, niacin)

• Participates in redox processes

• Provides hydrogen and phosphate transfer

• There are no data on hypervitaminosis.

Sources: liver, yeast, grains, potatoes, eggs, beef, veal.

Pantothenic acid (vitamin B3)

Participates in the processes of metabolism of proteins, fats, carbohydrates

Deficiency is almost non-existent nine0011
Hypervitaminosis has not been described.

Sources: liver, yeast, bran.

Biotin (vitamin H)

Participates in the synthesis of fatty acids, glucose, purine nucleotides

in protein metabolism

Helps improve the condition of skin, nails and hair

Hypervitaminosis has not been described.

Vitamin C (ascorbic acid)

Participates in the formation and maintenance of the structure and function of bones, teeth, gums

Strengthens capillary walls.

Sources: black currants, green onions, herbs, tomatoes, rose hips, cabbage, citrus fruits.

Vitamin D3 (calciferol)

Regulates calcium and phosphorus metabolism

promotes their accumulation in bone tissue.

Sources: cod and beef liver, eggs, butter. nine0011
Vitamin E (α-tocopherol)

Ensures the functioning of red blood cells

Antioxidant

Antihypoxant

Immunomodulator

Non-toxic at 10-20 multiples of daily requirement dosages.

Sources: vegetable oil, beans, lettuce, liver, milk, buckwheat, oatmeal, broccoli.

Calcium

Participates in the mineralization of bones and teeth

secretion of key hormones, enzymes and proteins

regulation of nerve conduction

contraction and relaxation of smooth and skeletal muscles

Component of the blood coagulation system

Sources: milk and dairy products, nuts, rye bread.

Magnesium

Participates in the formation of muscle and bone tissue, in protein synthesis nine0011
Deficiency causes miscarriage, premature birth

Reduces the risk of preeclampsia (late toxicosis of pregnant women)

Sources: bran bread, buckwheat, oatmeal, legumes, walnuts.

Iron

component of hemoglobin

is part of a number of enzymes

Sources: meat, animal liver, lettuce, spinach, prunes, lemons, walnuts, pomegranates, apples, buckwheat and oatmeal, egg yolk, bread. nine0011
Zinc

Is part of about 70 enzymes

Participates in the division and interaction of immunocompetent cells

Sources: meat, fish, seafood, cashews, cheese, milk, eggs, baked potatoes.

Copper

Necessary for the normal functioning of red blood cells and iron metabolism

Sources: nuts, grains, legumes, meat, animal liver, egg yolk. nine0011
Iodine

Necessary for the formation of the nervous, immune and reproductive systems in the fetus

To maintain hormonal balance

Sources: sea fish, seaweed, meat, eggs, milk, beets, carrots, lettuce, potatoes, cabbage, cucumbers, apples, grapes.
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