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A new study came out this month evaluating supplementation of l-arginine as a means of reducing preeclampsia risk. There was a lot of media coverage – you probably had friends and relatives sending you articles like this – and there’s been some discussion of it on the Preeclampsia Foundation forums as well.
Why did researchers think this might work? Well, partly for the same reason that smoking reduces risk of preeclampsia. It does so partly by activating a chemical pathway which uses l-arginine to build a protein called “nitric oxide synthase” (NOS). NOS is a vasodilator – it expands blood vessels - which could help to lower maternal blood pressure and which might increase blood flow to the placenta, reducing production of the chemicals that the placenta, which is shallowly implanted in preeclampsia, produces when it runs short of oxygen. Supplementation of l-arginine wouldn't change the initial shallow implantation of the placenta - or at least there is no known mechanism by which it might do this - but it might reduce or eliminate the symptoms of preeclampsia and allow delivery to be delayed.
Since smoking also causes many other pregnancy issues and lifelong health problems, and isn’t a way to reduce overall pregnancy risk, it is never recommended - nor should it be - to pregnant women as a way to reduce risk of preeclampsia. So, the hope is that supplementing something to turn up production of NOS will reduce risk of preeclampsia while not causing the horrendous problems associated with smoking.
Notice the word "might" all over the place. Mostly, this is guessing based on the current understanding of how this particular biological mechanism works, given what we understand about it at the moment. It's a hypothesis that has to be confirmed by testing the world. So, how did the researchers test this idea?
L-arginine can be provided to pregnant women in a dietary supplement. The study was conducted by randomly sorting pregnant women at high risk for preeclampsia into three groups and providing all three groups with nutritional bars to be eaten daily, starting at around 20 weeks gestation. One group got bars with both l-arginine and antioxidant vitamins, one received antioxidants alone, and the third group was given a placebo. The rate of diagnosis of preeclampsia was significantly lower in the group receiving both l-arginine and antioxidants than in the other groups.
So why is this still considered preliminary? Why aren’t MFMs all recommending l-arginine supplementation to patients?
One reason is that this new study contradicts other recent studies. Another research team found that preeclamptics have a higher level of l-arginine in their bloodstreams even without supplementation, and also have a high level of a protein that keeps l-arginine from helping to form NOS. If preeclamptics are already walking around with high levels of l-arginine, it doesn't make a whole lot of sense to suggest that even more would help lower their risk. Another recent trial of l-arginine supplementation in chronic hypertensives found that, while they needed fewer blood pressure medications during pregnancy, their rate of superimposed preeclampsia was the same as the control group. That might suggest that the population of chronic hypertensives wouldn't benefit from l-arginine supplementation at all, and that a new study would need to be conducted that excluded chronics from the trial.
It doesn’t make sense to accept the study results we like, and ignore the ones we don’t like – which makes it hard to know when to trust the research - so there will have to be further tests to determine why these studies don’t agree with one another. It would really help to understand these inconsistent results before designing further research into supplementation; particularly, it would help to understand why l-arginine plus antioxidants seems to possibly do something l-arginine alone does not do.
Another reason is the way the technical diagnosis of preeclampsia could skew the results. Although it’s true to say that, in this new study, fewer women supplemented with l-arginine and antioxidants met the diagnostic criteria for preeclampsia, that doesn’t seem to have actually changed outcomes at all. Even if fewer women have blood pressure above 140/90, that is merely one measure of disease progression in preeclampsia, because blood pressure is just a symptom. The different groups still delivered at the similar gestational ages, had infants with similar needs for NICU time, had similar rates of Caesarean, and so forth. It’s possible that preeclampsia was still occurring at the same rate in all populations, but that some women simply weren’t diagnosed since currently diagnosis is based only on blood pressure readings and proteinuria. (Hopefully, a diagnostic test will soon be available that measures other factors including levels of soluble FLT and soluble endoglin in the maternal bloodstream, and that doesn’t rely so strongly on blood pressure.) As the Experts are fond of saying, “treat patients, not diseases.” Many women have developed seizures or abruptions or HELLP syndrome without developing a diagnostic level of hypertension.
As always, it’s delightful to see serious research into potential preventative therapies for this disease. Even if preeclampsia rates cannot be reduced with something like a dietary supplement, finding a therapy which would allow delay of delivery for 48 hours – long enough for steroid shots to take effect – remains a high priority. If future studies confirm that supplementing l-arginine does lower maternal pressures safely, it might be able to be used to delay delivery of preterm infants until steroids are administered.
A special thanks to Dr. James Roberts at Magee-Womens Research Institute and Foundation, for his expertise and technical input, and Beth Frazer, for her graceful editing.
Northside Hospital CME, Atlanta, GA
August 21, 2015
7th Annual Perinatal Safety Summit, Las Vegas, NV
October 1-2, 2015