Vitamin B3 Nicotinamide: A Promising Candidate for Treating Preeclampsia and Improving Fetal Growth

Invited Review

Vitamin B₃ Nicotinamide: A Promising Candidate for Treating Preeclampsia and Improving Fetal Growth

NOBUYUKI TAKAHASHI,^1,2,3 FENG LI,³ TOMOFUMI FUSHIMA,¹ GEN OYANAGI,⁴ EMIKO SATO,^1,2 YUJI OE,⁵ AKIYO SEKIMOTO,^1,2 DAISUKE SAIGUSA,⁶ HIROSHI SATO^1,2 AND SADAYOSHI ITO²

¹Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Miyagi, Japan
²Department of Medicine, Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University, Sendai, Miyagi, Japan
³Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, USA
⁴Tohoku University Hospital Pharmaceutical Department, Sendai, Miyagi, Japan
⁵Division of Feto-Maternal Medical Science, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan
⁶Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan

Up to 8% of pregnant women suffer from preeclampsia (PE), a deadly disease characterized by high blood pressure (BP), blood vessel damage, called endotheliosis (vascular endothelial swelling with narrowing of capillary lumen), and high levels of protein in the urine. PE is often associated with premature delivery, which is a risk factor of cardiovascular and metabolic diseases among the offspring. Accordingly, establishing drug treatments of PE is in immediate needs. Currently, many of anti-hypertensive drugs cause malformation of the fetuses and are contraindicated for pregnant women. Anti-hypertensive drugs that are allowed to be used for treating pregnant women could lower BP of the mothers and reduce the risk of maternal death due to cardiovascular diseases such as cerebral hemorrhage. However, these anti-hypertensives do not improve endotheliosis and proteinuria. In fact, they reduce blood supply to the placentae and fetuses, which could lead to fetal growth restriction (FGR) and fetal and neonatal death. Until now, the only treatment for preeclamptic women has been delivery of the baby and placenta. Using three mechanistically different mouse models of PE, we have found that vitamin B₃ nicotinamide (Nam) is the first safe drug that alleviates PE, and that Nam also alleviates or prevents miscarriage, prolongs pregnancy period, and improves the growth of the fetuses in mice with PE. Importantly, Nam has been used for pregnant and nursing women who have difficulty in taking sufficient meal. Nam could help treat or prevent PE and FGR associated with PE, if the treatment works in humans.

keywords —— endotheliosis; fetal growth restriction; nicotinamide; preeclampsia; premature delivery

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Tohoku J. Exp. Med., 2018, 244, 243-248

Correspondence: Nobuyuki Takahashi, M.D., Ph.D., Tohoku University Graduate School of Pharmaceutical Sciences, 6-3 Aramaki Aoba, Aoba-ku, Sendai, Miyagi 980-8578, Japan.

e-mail: ntakaha@m.tohoku.ac.jp