*4.4.4 Flavonoids*

Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea, and wine. Nowadays, flavonoids are considered essential components in various applications such as nutraceutical, pharmaceutical, medicinal, and cosmetic. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function [59]. According to National Health and Nutrition Examination Survey (NHANES), a large, cross-sectional survey National Centre for Health Statistic (*n* = 9551 adults) showed that flavonoid consumption was inversely associated with obesity in both men and women in multivariate models. It was also observed that adults in the highest quartile of flavonoid intake had significantly lower body mass index and waist circumference than those in the lowest quartile of flavonoid intake (*P* < 0.03 and *P* < 0.04, respectively). The study also revealed that flavonoid intake was inversely related to C-reactive protein levels in women (p-trend, 0.01) [60]. The Nurses' Health Cohort Study (*n* = 2115 women, aged 43–70 years) reported that among flavonoid-rich foods, higher intake of grapefruit was significantly associated with lower concentrations of CRP and sTNF-R2. In spite of this, it was also reported in the study that flavonoids typically found in citrus fruits were modestly associated with lower plasma IL-18 concentrations [61]. Interestingly, a double-blind, placebo-controlled crossover study (*n* = 14, 35–53 years of age) reported that the supplementation of sea buckthorn flavonol extract for 4 weeks did not reduce CRP levels (*p* < 0.05) [15, 62].
