Flavonoid-rich diet reduces risk of peripheral artery disease hospitalizations

Consumption of a diet rich in flavonoids, found in almost all fruits and vegetables, can lower the risk of hospitalization for peripheral artery disease (PAD), revascularizations or endovascular surgery, and lower extremity amputations, according to a study.

Therefore, “[e]nsuring the adequate consumption of flavonoid-rich foods, particularly in subpopulations prone to the development of atherosclerosis, may be a key strategy to lower the risk of PAD,” the researchers said.

A total of 55,647 participants of the Danish Diet, Cancer, and Health Study without PAD, recruited from 1993 to 1997, had their baseline data cross-linked with Danish nationwide registries. Flavonoid intake was calculated from food frequency questionnaires using the Phenol-Explorer database. The researchers then examined associations using multivariable-adjusted restricted cubic splines based on Cox proportional hazards models.

Overall, 2,131 participants had been admitted to a hospital for any PAD after a median follow-up time of 21 years (interquartile range, 20–22 years). A nonlinear association was observed between total flavonoid intake and total PAD hospitalizations, reaching a plateau at ∼750–1,000 mg/d. [Am J Clin Nutr 2021;113:187-199]

A 1,000-mg/d flavonoid intake correlated with a 32-percent lower risk of any PAD hospitalization (hazard ratio [HR], 0.68, 95 percent confidence interval [CI], 0.60–0.77), a 26-percent lower risk of atherosclerosis (HR, 0.74, 95 percent CI, 0.62–0.88), a 28-percent lower risk of an aneurysm (HR, 0.72, 95 percent CI, 0.59–0.88), and a 47-percent lower risk of hospitalization for other peripheral vascular disease (HR, 0.53, 95 percent CI, 0.42–0.67) than the median intake of 174 mg/d in quintile 1.

A higher total flavonoid intake also led to a reduced incidence of revascularization or endovascular surgery and lower extremity amputation. Notably, the association between total flavonoid intake and PAD hospitalizations varied according to baseline smoking status, alcohol intake, body mass index, and diabetes status.

“The main risk factors for PAD—age, smoking, and diabetes mellitus—can cause an increase in inflammation, arterial stiffness, and oxidative stress, and a decrease in nitric oxide (NO) bioavailability with a concomitant decrease in vasodilation,” the researchers said. [Circ J 2017;81:281-289]

“Flavonoids may impede the initiation and progression of PAD by restoring endothelial homeostasis through the augmentation of NO bioavailability and by attenuating inflammation through upregulation of the anti-inflammatory nuclear factor erythroid 2-related factor 2 pathway and downregulation of the proinflammatory NF-κβ pathway,” they explained. [Compr Rev Food Sci Food Saf 2018;17:1054-1112]

Furthermore, the present study found a robust association between a higher flavonoid intake and a lower PAD risk in current and former smokers, suggesting that flavonoids may play a role in lessening inflammation and oxidative stress in these individuals. This was supported by a previous study reporting an inverse relationship between fruit and vegetable intake and PAD incidence in smokers. [Arterioscler Thromb Vasc Biol 2017;37:1234-1240]

“The role that nutrition plays in the primary prevention of PAD is not well understood. Previous observational studies suggested that a diet characterized by low intakes of vitamins, dietary fibre, and PUFAs, and a high intake of red meat, was associated with a higher incidence of PAD,” the researchers said. [Lipids Health Dis 2017;16:254; Am J Clin Nutr 2017;105:651-659; Am J Clin Nutr 1993;57:917-921]

“Owing to the underlying pathogenesis of PAD, a review summarizing current knowledge on nutritional patterns among patients with PAD strongly advocated for a diet rich in foods with anti-inflammatory and antioxidant properties,” they added. [J Vasc Surg 2015;61:265-274]