Arginine is an amino acid, a type of molecule used in the synthesis of proteins. Most of us get our amino acids from our diet, breaking down the protein in our food into its constituent parts and then reusing those amino acids to build new different proteins. Some amino acids must be consumed in our diet because our bodies cannot build them from scratch. But arginine is one of those amino acids that can in fact be synthesized from other amino acids and so it is actually not necessary to get it from food. The one exception might be premature infants who cannot synthesize the amino acid and there is some evidence that supplementing the feeding solution of hospitalized preterm infants prevents a condition called necrotizing enterocolitis (NEC). NEC occurs in 4-22% of very low birth weight and is caused by a lack of blood flow to the intestine which leads to tissue damage and infection. Supplementing the feeding solution given to preterm infants with arginine seems to reduce the incidence of NEC by about 20%. But these results come from 3 trials that in total had less than 300 patients which make the benefit a bit uncertain.
However most people reading this article are likely not currently preterm infants and are probably more interested in the purported cardiovascular benefits of arginine. In the body arginine is converted to nitric oxide in the cells that line the inside of blood vessels. Nitric oxide then initiates a chemical chain reaction that causes the smooth muscle surrounding blood vessels to relax. This in turn leads to the dilatation of the blood vessels and improved blood flow. Nitroglycerin, a medication commonly given to cardiac patients, has a similar mechanism of action. It too is converted into nitric oxide, which then leads to dilated blood vessels, improved blood flow, and consequently lower blood pressure and less angina. Nitroglycerin, whether as a spray, a pill, or a patch has been well studied in cardiology whereas arginine has much less evidence behind.
To some extent arginine, like nitroglycerin, can help lower your blood pressure. However, the magnitude of this benefit appears to be quite small and arginine only seems to lower your blood pressure by a few points. Thus the clinical significance of this blood pressure lowering is debatable. Also, the existing trials should be interpreted with caution given their small size (in total 11 trials only comprised 387 patients) as small trials are more prone to random error skewing the results. Also the varying doses of arginine used make any comparisons and attempts to combine the data statistically tricky.
But the most important factor to consider is that lowering your blood pressure is not the endpoint you should be keeping in mind. Physicians try to lower blood pressure, not as an end in and of itself but for the purpose of preventing heart attacks and strokes. These are often referred to as “hard outcomes” because they are the types of clinically meaningful events that we should care about. A 2006 JAMA study did in fact look at arginine vs. placebo given to patients who had suffered a heart attack. It failed to improve any measures of vascular stiff or heart function, although in and of themselves these endpoints would not quality as “hard outcomes.” The most important observation was that there were more deaths in the arginine group, which prompted the investigators to cancel the trial. A recent Cochrane review could find no data looking at arginine’s role in stroke patients. When it comes to “hard outcomes”, the evidence for arginine’s benefit appears to be lacking. In fact, arginine often carries a health warning that you should not take it if you have recently had a heart attack.
Ultimately, the story of arginine reveals an important subtlety in how we interpret the clinical evidence. The question to ask is, not so much whether arginine can dilate arteries, improve blood flow or lower blood pressure. To some minimal extent, it likely does do all of these things. The real question is whether it prevents clinically meaningful events like heart attacks, strokes, and death. For now at least, the best we can say about arginine is that the evidence suggests that it does not.
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