Cardiovascular

Study Shows Potent Antioxidant Reduces Artery Cholesterol Buildup

Long-term supplementation with the antioxidant N-acetylcysteine (NAC) prevents blood vessel cholesterol accumulation in aged mice with high cholesterol.

By Yedida Bogachkov, Ph.D.

Key Points:

  • Six months of NAC treatment reduces cholesterol plaque build-up in the arteries of aged mice with high cholesterol.
  • NAC treatment reduces oxidative stress — damage caused to cells by oxidizing molecules. 
  • Pro-inflammatory molecules decrease with NAC, while anti-inflammatory molecules increase.

N-acetylcysteine (NAC) has long been used in clinical settings for acetaminophen (Tylenol) overdose. However, research has shown that it may also protect against DNA damage and support a healthy immune system, both of which are important parts of maintaining our health as we age. A more recent study shows that it may also protect our blood vessels from cholesterol buildup, further supporting healthy aging.

The study out of the University of Missouri was published in Atherosclerosis, and focused on mice that have high cholesterol due to a genetic mutation in their cholesterol receptors, also known as LDLR-/- mice. These mice are prone to developing atherosclerosis – an inflammatory disease characterized by cholesterol buildup in arteries – especially when placed on a high-fat diet. The researchers found that 6 months of NAC treatment reduced the progression of cholesterol buildup in these mice, but not when fed a high-fat diet. It also reduced oxidative stress and inflammation.

“Early and adequate NAC treatment could effectively attenuate inflammation and atherosclerosis progression,” the scientists wrote.

N-acetylcysteine Prevents Atherosclerosis Progression and Reduces Inflammation

The scientists supplemented the LDLR-/- mice with NAC for six months, starting at nine months (about 46 in human years). They found that NAC significantly reduced cholesterol buildup, as measured by plaque size, in the aorta. They found no difference in the plaque size after 3 months of treatment, indicating that long-term supplementation is needed to yield an effect. 

Furthermore, there was no effect on plaque progression when NAC was started at 18 months old (about 64 in human years), suggesting that NAC does not work when plaque buildup has progressed for too long. Notably, Zhu and colleagues found that when the mice were fed a high-fat diet, NAC had no effect, suggesting that NAC only works in conjunction with a balanced diet.

NAC reduces blood vessel lesions
(Zhu et al., 2022 | Atherosclerosis) N-acetylcysteine (NAC) Reduces Blood Vessel Lesions. Fifteen-month-old mice lacking an LDL cholesterol receptor (15M: LDLR-/-, blue) display blood vessel damage (Aortic Lesion Area) that is reduced after six months of NAC treatment (15M: LDLR-/-+NAC (6 months)). Red staining on the aortas in images indicates lesions.

Atherosclerosis is often considered an inflammatory condition, so scientists sought to determine whether NAC affects inflammation and oxidative stress, which often contributes to inflammation. Zhu and colleagues found that NAC treatment prevented the increase in oxidative stress, normally seen in the aortas of aging LDLR-/- mice. Furthermore, levels of some pro-inflammatory molecules were decreased while anti-inflammatory molecules were increased, indicating a reduction in inflammation.

NAC reduces oxidative stress
(Zhu et al., 2022 | Atherosclerosis) N-acetylcysteine (NAC) Reduces Oxidative Stress. NAC treatment for 3 (12M) and 6 (15M) months reduces oxidative stress (Mean Fluorescence Intensity) in LDLR-/- mice (blue), compared to untreated LDLR-/- mice (red), to similar levels as normal (gray) mice.

N-acetylcysteine for Cardiovascular Health

Zhu and colleagues show how NAC may be beneficial for the elderly by helping halt the progression of atherosclerotic plaques and helping reduce oxidative stress and inflammation. A recent clinical trial indicated that NAC can also be of benefit in another risk factor for atherosclerotic plaques, metabolic syndrome – a constellation of conditions, including high cholesterol, that increase one’s risk of heart disease, stroke, and type 2 diabetes.  

Furthermore, other studies have looked at GlyNAC – a combination of the amino acid Glycine and NAC. GlyNAC increases the lifespan of mice and improves the cognition and insulin sensitivity of older adults. Zhu and colleagues show that NAC on its own may be a helpful compound for maintaining cardiovascular health as we age. Both GlyNAC and NAC are available from many online retailers, however, given NAC’s use as a medication in a clinical setting, more research is needed before its safety and efficacy in maintaining cardiovascular health can be determined.

Model & Dosage

Model: Male LDLR-/- mice

Dosage: 1 mg/mL in N-acetylcysteine drinking water

Source

Zhu, Q., Xiao, Y., Jiang, M., Liu, X., Cui, Y., Hao, H., Flaker, G.C., Liu, Q., Zhou, S., Liu, Z.,
N-acetylcysteine attenuates atherosclerosis progression in aging LDL receptor deficient mice with preserved M2 macrophages and increased CD146. Atherosclerosis, Volume 357, 2022,
Pages 41-50, https://doi.org/10.1016/j.atherosclerosis.2022.08.008.

References

Panahi, Y., Ostadmohammadi, V., Raygan, F., Sharif, M.R., Sahebkar, A. The effects of N-acetylcysteine administration on metabolic status and serum adiponectin levels in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled trial. Journal of Functional Foods, Volume 99, 2022, 105299, https://doi.org/10.1016/j.jff.2022.105299.

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