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Flavonols, Especially Quercetin, Linked to Less Frailty

This analysis was based on the Framingham Heart Study.

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In a new prospective cohort study, a higher intake of flavonols, and quercetin in particular, was linked to a significant decrease in the risk of frailty [1].

Flavonoids: not just flavor

Flavonoids are a class of polyphenolic compounds that include flavanols, flavonols, flavones, anthocyanins, and some others. Flavonoids are abundant in plant-based foods, including fruits, vegetables, berries, grains, tea, and wine. They have been studied extensively for their potential health benefits, including antioxidant, anti-inflammatory, and anti-cancer effects. In a recent study, flavanols found in cocoa extract were found to reduce cardiovascular mortality.

One flavonol called quercetin has been an object of increased interest for geroscientists. Its combination with the cancer drug dasatinib, D+Q, is a popular senolytic approach that has shown some success in preclinical and clinical trials [2]. Quercetin reduces oxidative stress and even increases lifespan in several organism models [3]. Quercetin is the most abundant in onions but most bioavailable in berries.

Flavonoids and frailty

This new prospective cohort study attempted to elucidate the role of flavonoids, their subclasses, and quercetin in particular in the prevention of frailty, a clinical syndrome that is characterized by a decline in physiological reserves and function across multiple organ systems. This decline contributes to morbidity and mortality by leaving the person vulnerable to sudden changes in health status triggered by relatively minor stressor events. Frailty is also a major cause of falls and impaired mobility in the elderly.

A recent meta-analysis has found that a healthy diet rich in flavonoids (such as the Mediterranean diet) might decrease the risk of frailty by 50% to 70% [4]. There have been also some interventional studies that showed a positive effect of flavonoids on frailty-related symptoms. In one such study, supplementation with blueberries, a rich source of flavonoids, led to gait improvements in elderly people [5].

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Quercetin lives up to expectations

This new study was based on the Framingham Heart Study and encompassed 1701 participants with no frailty at baseline (1998-2001). Frailty was then re-evaluated in 2011–2014. Levels of flavonoid intake were estimated using a food intake questionnaire. The sample was roughly equally distributed by sex, and the mean age at baseline was 58.4. Over an average of 12 years of follow-up, 13.2% of the participants developed frailty.

In a model adjusted for sex, age, energy intake, smoking status, cancer, cardiovascular health, and diabetes, the association between frailty and overall flavonoid intake was insignificant. However, when researchers dug deeper into individual subclasses of flavonoids, the picture became clearer. Each 10 milligram per day increase in flavonol intake was associated with a 20% decrease in the risk of developing frailty. Even more impressively, each 10 milligram per day increase in quercetin intake was associated with 35% lower odds of frailty onset.

Another significant result was age-dependent: among the participants younger than 60 years old, each 10 milligram per day increase in the intake of anthocyanins, another subtype of flavonoids that gives many fruits and vegetables their blue, purple, or black color, was associated with 52% lower odds of frailty onset. However, for participants aged 60 years and older, no significant association was observed.

Like any populational study, this one was laden with limitations, such as using a questionnaire to assess nutrient intake at a single time point along with having aΒ  relatively small sample size. However, such studies allow researchers to assess the effects of long-term dietary habits, which is nearly impossible in interventional studies.

In this prospective cohort study, although flavonoid intake was not significantly associated with the odds of frailty onset in middle-aged and older adults, higher intake of the flavonoid subclass, flavonols, was associated with reduced odds of frailty onset, which appeared to be driven by the specific flavonol, quercetin. The protective association between anthocyanins and frailty onset was primarily seen in participants below the age of 60 y. Although hypothesis-generating, this study highlights the potential of dietary flavonols and quercetin as a strategy to prevent frailty onset. Future research should focus on dietary interventions of flavonols or quercetin for treating frailty.

Conclusion

This interesting study suggests that not all flavonoids are equally protective against the onset of frailty, but some might have a robust effect. It confirms the known role of quercetin as a protector against various age-related conditions, which is likely due to its antioxidant activity. The results also highlight yet again the overall relevance of diet for healthspan.

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Literature

[1] Oei, S., Millar, C. L., Nguyen, T. N., Mukamal, K. J., Kiel, D. P., Lipsitz, L. A., … & Sahni, S. (2023). Higher intake of dietary flavonols, specifically dietary quercetin, is associated with lower odds of frailty onset over 12-years of follow-up among adults in the Framingham Heart Study. The American Journal of Clinical Nutrition.

[2] Hickson, L. J., Prata, L. G. L., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., … & Kirkland, J. L. (2019). Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine, 47, 446-456.

[3] Proshkina, E., Lashmanova, E., Dobrovolskaya, E., Zemskaya, N., Kudryavtseva, A., Shaposhnikov, M., & Moskalev, A. (2016). Geroprotective and radioprotective activity of quercetin,(-)-epicatechin, and ibuprofen in Drosophila melanogaster. Frontiers in pharmacology, 7, 505.

[4] Wang, Y., Hao, Q., Su, L., Liu, Y., Liu, S., & Dong, B. (2018). Adherence to the Mediterranean diet and the risk of frailty in old people: a systematic review and meta-analysis. The journal of nutrition, health & aging, 22, 613-618.

[5] Schrager, M. A., Hilton, J., Gould, R., & Kelly, V. E. (2015). Effects of blueberry supplementation on measures of functional mobility in older adults. Applied Physiology, Nutrition, and Metabolism, 40(6), 543-549.

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About the author
Arkadi Mazin

Arkadi Mazin

Arkadi is a seasoned journalist and op-ed author with a passion for learning and exploration. His interests span from politics to science and philosophy. Having studied economics and international relations, he is particularly interested in the social aspects of longevity and life extension. He strongly believes that life extension is an achievable and noble goal that has yet to take its rightful place on the very top of our civilization’s agenda – a situation he is eager to change.
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