Revving Up the Heart with Resveratrol
If you’ve ever claimed that you drink red wine for its heart-healthy benefits, you’ve likely heard of resveratrol. Recent research has added to the evidence that resveratrol is good for the heart — albeit in the form of supplements rather than sips of Merlot. In this article, learn more about the benefits of resveratrol and the results from a November 2020 study that looked at the effects of this compound on heart failure patients.
What is Resveratrol?
Resveratrol is a compound found in several foods, including red grapes, cocoa, peanuts, raspberries, blueberries, and cranberries. This plant-based substance boasts strong antioxidant and anti-inflammatory properties, creating red wine’s claim to nutritional fame over the past couple of decades. However, the small amount of resveratrol present in red wine is not enough to be clinically relevant. As a standard dose of supplemental resveratrol is up to 1,000 milligrams per day, you’d have to drink close to 40 liters of wine to get half that amount!
A more efficient way to get an adequate dose of resveratrol is through supplements. However, not all resveratrol supplements are created equal. Many supplements contain a blend of the two forms of resveratrol: cis and trans. Cis-resveratrol, commonly found in lower-quality or lower-priced supplements, is poorly absorbed. On the other hand, trans-resveratrol is the more bioavailable form of the compound, meaning your body can absorb and utilize it more effectively, allowing you to reap the benefits.
Researchers have studied resveratrol for its ability to boost the effectiveness of NMN (nicotinamide mononucleotide), a precursor to the health- and longevity-promoting compound NAD+ (nicotinamide adenine dinucleotide). Resveratrol also increases the activity of SIRT1, one of seven sirtuins — also known as “longevity genes” — crucial to cellular health and aging.
How Does Resveratrol Benefit Heart Health?
Resveratrol benefits heart health by fighting inflammation, providing potent antioxidant activity, and strengthening blood vessels and arteries, as discussed in a review published in Nutrients. Resveratrol also positively affects the cardiovascular system by increasing nitric oxide production — which helps blood vessels relax and improves circulation — and protecting the function of the power generators (mitochondria) in heart cells. It also promotes autophagy, the body’s internal recycling program that clears damaged and dysfunctional compounds. This process is essential for protecting the quality and function of heart cells; low levels of autophagy are linked to cardiovascular aging and disease.
Although resveratrol improves cardiovascular function in animal models of heart failure, atherosclerosis, hypertension, and heart disease, there are few human studies. Until now, the effect of resveratrol on heart failure in humans has not been researched.
The Study: Supplementing Heart Failure Patients With Resveratrol
Published November 2020 in the journal Antioxidants, this clinical trial looked at the effects of resveratrol supplements on people with heart failure, specifically systolic heart failure patients (also known as heart failure with reduced ejection fraction, or HFrEF).
One out of every five American adults is estimated to develop heart failure — when the heart cannot pump sufficient blood throughout the body. Many factors play a role in developing heart failure, including a history of heart disease, heart attacks, high blood pressure, obesity, and diabetes.
A driving force behind these cardiovascular-related diseases is high levels of inflammation and oxidative stress — when inflammatory compounds called reactive oxygen species accumulate, leading to cellular and DNA damage.
This small study randomized 60 patients with class II or class III heart failure to take 100 mg of resveratrol or a placebo for three months. Class II describes a mild disease, with symptoms including shortness of breath and some limitations on day-to-day life. Class III is more serious, making even light daily activities challenging to perform. All of the patients continued taking their prescribed heart failure medications during the trial.
At the start and end of the 3-month trial, the researchers used a battery of tests to measure cardiovascular health and function. This included echocardiography ultrasound exams, a six-minute walking test, a spirometry test to evaluate lung function, blood tests, RNA profile analyses of leukocytes (a type of white blood cells), and a questionnaire assessing their quality of life (QOL).
The Results: Resveratrol Reigns for Heart Health
1.Resveratrol Reduced Inflammation
Resveratrol lowered the inflammatory cytokines interleukin 1 and 6 (IL-1 and IL-6). High levels of these cytokines are strongly linked to adverse outcomes and progression of heart failure.
Similarly, galectin-3 levels were reduced in the resveratrol group. Galectin-3 is a pro-inflammatory compound secreted by macrophages that acts as a second biomarker for heart failure. Elevated galectin-3 is implicated in almost all cardiovascular diseases, as it reflects levels of fibrosis and inflammation. High galectin-3 levels are linked to increased risk of mortality in patients with acute or chronic heart failure, as seen in a study published in Clinical Research in Cardiology in February 2013.
2. Resveratrol Improved Ventricular Function
Resveratrol improved relaxation and contraction of the left ventricle, indicating an improvement in the heart's ability to pump blood. Another biomarker of heart failure severity called N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was significantly lower in the resveratrol group. NT-proBNP is elevated when the heart can’t pump blood effectively. It also mitigated measures for cardiac scar tissue, which accumulate after a heart attack and cause the heart to pump inefficiently.
3. Resveratrol Improved Lung and Exercise Capacity
It has been well-established that heart failure is detrimental to lung function. The resveratrol-treated group experienced significant benefits to lung function, including increases in measures of the amount of air that can be forcibly exhaled and the air capacity that can be inhaled. Possibly related to improved lung function, the resveratrol group also had significant increases in the distance they covered on the six-minute walk test.
4. Resveratrol Improved Quality of Life
Quality of life (QOL) questionnaires indicated that resveratrol supplementation significantly improved QOL scores, including questions regarding subjective health state, mobility, usual activities, and mood. However, there were no differences between groups with questions related to pain, discomfort, or self-care. As poor QOL is linked to worse outcomes and higher hospitalization rates in patients with heart failure, these results indicate that resveratrol may be able to benefit some of these subjective measures.
5. Resveratrol Reduced Leukocyte Activity
Resveratrol treatment reduced the activity of seven genes related to the mitochondria of leukocytes that produce energy, or ATP. Although resveratrol inhibited some parts of ATP synthesis in leukocytes, it did not cause mitochondrial dysfunction. This may be due to the decreased production of IL-1 and IL-6, as these inflammatory cytokines moderate leukocyte activity.
Overall, resveratrol reduced leukocyte activity; the researchers suggest that this may be cardioprotective in heart failure patients. Leukocytes are white blood cells that are elevated with several diseases, including heart failure. While leukocytes are essential to the immune system, they can contribute to heart disease by triggering inflammatory pathways when elevated. As described by authors of a January 2013 paper published in Science, leukocytes can be both “friends and foes of the heart.”
Key Takeaway From This Research:
This study showed that supplementing heart failure patients with just 100 mg per day of resveratrol improved several markers of heart failure severity and progression, including left ventricular function, lung capacity, exercise tolerance, and overall quality of life.
Resveratrol also exhibited anti-inflammatory activity, as seen by reduced levels of pro-inflammatory cytokines and biomarkers that reflect the severity of heart failure.
Although this study’s results are promising, it should be taken with caution due to the small sample size and short study duration. Future research should include studies with more patients and extended follow-up periods to fully assess resveratrol’s impact on heart failure in humans.
References:
Bonnefont-Rousselot D. Resveratrol and Cardiovascular Diseases. Nutrients. 2016;8(5):250. Published 2016 May 2. doi:10.3390/nu8050250
Breuss JM, Atanasov AG, Uhrin P. Resveratrol and Its Effects on the Vascular System. Int J Mol Sci. 2019;20(7):1523. Published 2019 Mar 27. doi:10.3390/ijms20071523
Dyck GJB, Raj P, Zieroth S, Dyck JRB, Ezekowitz JA. The Effects of Resveratrol in Patients with Cardiovascular Disease and Heart Failure: A Narrative Review. Int J Mol Sci. 2019;20(4):904. Published 2019 Feb 19. doi:10.3390/ijms20040904
Gal R, Deres L, Horvath O, et al. Resveratrol Improves Heart Function by Moderating Inflammatory Processes in Patients with Systolic Heart Failure. Antioxidants (Basel). 2020;9(11):1108. Published 2020 Nov 11. doi:10.3390/antiox9111108
Lok DJ, Lok SI, Bruggink-André de la Porte PW, et al. Galectin-3 is an independent marker for ventricular remodeling and mortality in patients with chronic heart failure. Clin Res Cardiol. 2013;102(2):103-110. doi:10.1007/s00392-012-0500-y
Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013;339(6116):161-166. doi:10.1126/science.1230719
