March 8, 2018
University Health Network
A simple dietary supplement (L-arginine) was found to
improve birth outcomes, paving the way for future clinical trials to test this
inexpensive and safe intervention.
A simple dietary supplement (L-arginine) was found to improve birth
outcomes, paving the way for future clinical trials to test this inexpensive
and safe intervention.
In their paper entitled, “Malaria in pregnancy alters L-arginine
bioavailability and placental vascular development,” Science
Translational Medicine, 7 March 2018, Toronto General Research Institute
(TGRI) and University of Toronto researchers report that Malawian women with
malaria in pregnancy had altered levels of L-arginine which were associated
with poor birth outcomes. L-arginine is an amino acid that improves blood flow
and circulation and that humans get from their diet, including eggs, meat and
In an experimental model of malaria in pregnancy, supplementing the diet of
pregnant mice with L-arginine increased blood vessel development in the
placenta and reduced low birth weight/preterm birth and stillbirth.
Preterm birth and stillbirth are leading causes of childhood death
accounting for an estimated 2 million deaths per year; however there are few
safe and effective interventions. Globally many of these poor birth outcomes
are associated with maternal infections such as malaria.
Led by Dr. Chloe McDonald and Dr. Kevin Kain at the Toronto General
Hospital Research Institute, University Health Network (UHN), the scientists
show that supplementing the diet with L-arginine prevented malaria from
depleting the L-arginine-nitric oxide (NO) pathway.
In the body, L-arginine is converted into nitric oxide, which is critical
for normal placental blood vessel development and healthy birth outcomes. By
the time a woman delivers, there are 250 kilometres of blood vessels in the
placenta, which provide essential oxygen and nutrients to the rapidly growing
“Our work shows that L-arginine is a critical component in regulating
a key pathway that promotes blood vessel development in the placenta.
Infections such as malaria can impair that pathway, restricting placental
vascular development. Ultimately this can result in poor birth outcomes which
can have long-term effects on babies who survive, including impaired brain and
behavioural development,” says Dr. McDonald, adding that research on safe,
effective ways of promoting healthy birth outcomes are urgently needed.
Dr. Kain notes that the L-arginine-(NO) biosynthetic pathway identified in
this research may be a common pathway underlying other conditions linked to
poor birth outcomes, be they in low or high-income countries such as Canada.
“Our findings have broad implications not only for malaria in
pregnancy (125 million pregnancies at risk each year), but also for other
globally important causes of adverse birth outcomes such as preeclampsia,”
says Dr. Kain, who is also Science Director, Tropical Disease Unit at the
Toronto General Hospital, UHN.
Since L-arginine can be given to women as a simple, safe, and inexpensive
food supplement, (in peanuts, for example) in pregnancy, Dr. Kain and Dr.
McDonald are now planning human clinical trials to assess its impact on human
Materials provided by University
Health Network. Note: Content may be edited for style and
McDonald, Lindsay S. Cahill, Joel R. Gamble, Robyn Elphinstone, Lisa M.
Gazdzinski, Kathleen J. Y. Zhong, Adrienne C. Philson, Mwayiwawo Madanitsa,
Linda Kalilani-Phiri, Victor Mwapasa, Feiko O. ter Kuile, John G. Sled, Andrea
L. Conroy, Kevin C. Kain. Malaria in pregnancy alters l-arginine
bioavailability and placental vascular development. Science
Translational Medicine, 2018; 10 (431): eaan6007 DOI: 10.1126