Written by Harold Oster, MD. A mixture of activators of autophagy may have beneficial effects on oxidative stress and arterial stiffness in hypertensive patients.

blood pressureHypertension is a common risk factor for cardiovascular disease, and lowering blood pressure in hypertensive patients significantly decreases cardiovascular morbidity and mortality1. Much of the end-organ damage from hypertension is due to an increase in arterial stiffness, in part due to oxidative stress2,3. Autophagy, the body’s removal of harmful cellular components, results in an improvement in arterial stiffness by its effects on reactive oxygen species4. The nutraceutical compounds, nicotinamide, spermidine, trehalose, and polyphenols, are natural inducers of autophagy5-8.

Giuliano Tocci et al. studied the possible benefits of the compounds listed above on blood pressure, markers of oxidative stress, and arterial stiffness in patients with hypertension. Forty patients in a hypertension clinic were randomly assigned to take no supplement or a 10.5 gram mixture of nicotinamide, spermidine, trehalose, and polyphenols twice daily for two months. All patients were asymptomatic and had a systolic blood pressure of at least 140 mmHg and/or a diastolic blood pressure of at least 90 mmHg. At baseline, the participants completed a physical examination and were assessed for smoking and past medical history. The augmentation index and the arterial stiffness index9, non-invasive tests for arterial stiffness, were performed. Blood was tested for routine chemistries and analyzed for sNOX2-dp, H2O2, and H2O2 breakdown activation (HBA). When there is an increase in oxidative stress, sNOX2-dp and H2O2 are elevated, while HBA is decreased10,11. Blood was also analyzed for endothelin-1, a marker for endothelial dysfunction12, nitric oxide production, which correlates with normal endothelial function13, and the markers of autophagy, ATG5 and P6214. At the end of the study, the above tests were repeated.

The authors noted the following:

  • Based on inclusion criteria, 37 participants completed the study.
  • Blood pressure did not change significantly from baseline to the end of the study in the treatment or the control group.
  • In the treatment group, sNOX2-dp and H2O2 decreased, and HBA increased, suggesting an overall decrease in oxidative stress.
  • Nitric oxide production increased, and endothelin-1 decreased in the treatment group, suggesting improved endothelial function.
  • ATG5 levels rose, and P62 levels decreased, indicative of increased autophagy.
  • Arterial stiffness, documented by the augmentation index, increased in the control group compared to the treatment group.

Results of the study suggest that a mixture of nutraceuticals known to activate autophagy may have beneficial effects on oxidative stress and arterial stiffness in hypertensive patients. Limitations of the study include a small sample size and lack of a placebo in the control group.

Source: Tocci, Giuliano, Giuseppe Biondi-Zoccai, Maurizio Forte, Giovanna Gallo, Giulia Nardoianni, Emiliano Fiori, Luca D’Ambrosio et al. “Effects of two-month treatment with a mixture of natural activators of autophagy on oxidative stress and arterial stiffness in patients with essential hypertension: A pilot study.” Nutrition, Metabolism and Cardiovascular Diseases (2023).

©  2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical
Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

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Posted October 16, 2023.

Harold Oster, MD graduated from medical school in Miami, Florida in 1992 and moved to Minnesota in 2004. After more than 25 years of practicing Internal Medicine, he recently retired. Dr. Oster is especially interested in nutrition, weight management, and disease prevention. Visit his website at haroldoster.com.

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