Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are naturally occurring forms of modified amino acids. They are created inside our cells when certain proteins are broken down or altered after their initial production, a process known as post-translational modification. While amino acids usually help build proteins and support health, these two molecules act differently – they can contribute to health problems when they accumulate.
ADMA works mainly by blocking an enzyme called nitric oxide synthase (NOS). NOS is essential for making nitric oxide (NO), a gas that helps blood vessels relax and stay flexible. When ADMA levels rise, NO production falls, leading to endothelial dysfunction – a situation where blood vessels do not dilate properly. This dysfunction is one of the earliest steps in the development of atherosclerosis, or the hardening and narrowing of arteries. High ADMA levels have been linked to an increased risk of heart attacks, strokes, and death from cardiovascular disease.
SDMA, once thought to be inactive, also plays a major role in health. Instead of blocking nitric oxide production, SDMA affects the way cells handle a substance called L-arginine, which is necessary for making nitric oxide. SDMA is now recognized as a very sensitive marker of kidney function. Unlike ADMA, which the body can partly break down, SDMA is mostly removed by the kidneys. When the kidneys are not working well, in conditions like chronic kidney disease (CKD), SDMA builds up in the blood.
High levels of ADMA and SDMA are consistently linked with worse outcomes across different groups of people. Those with higher levels have a greater risk of heart disease, strokes, and dying from any cause, even after adjusting for other risk factors. These associations are seen not only in patients with pre-existing kidney or heart conditions but also in healthy individuals.
Other health problems are also tied to elevated ADMA. For example, people with high cholesterol often have raised ADMA levels, which worsens their blood vessel function. Obese individuals with obstructive sleep apnea (OSA), a condition where breathing repeatedly stops during sleep, also tend to have higher ADMA, suggesting it could be a useful early warning sign.
At present, no specific drugs exist to lower ADMA or SDMA levels. However, understanding how these molecules are produced and cleared from the body could open new doors for future treatments, especially for preventing cardiovascular and kidney-related complications.
