Flavanones represent a significant subgroup of flavonoids and offer various advantages for the human body, such as aiding in metabolic regulation and providing antioxidant properties. The objective of this research was to investigate the relationship between dietary flavanones and the prevalence of kidney stones among adults in the USA. Flavanones, including eriodictyol, hesperetin and naringenin, were sourced from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007–2010 and 2017–2018, utilising two 24-h dietary recall interviews. The definition of kidney stones was established through a self-administered questionnaire. To evaluate the relationships between dietary flavanones and kidney stones, a variety of statistical methods were utilised, such as multivariable regression analysis, restricted cubic splines (RCS) and subgroup analysis. Data from 9790 participants were included in this analysis, with 9·67 % of them indicating that they had experienced kidney stones. After adjusting for potential confounding factors, it was found that kidney stones exhibited a negative correlation with total flavanones and naringenin, with OR of 0·96 (95 % CI 0·93, 1·00) and 0·89 (95 % CI 0·80, 0·99) for the highest intake group compared with the lowest intake group. The RCS plot revealed a notable negative linear association between the consumption levels of total dietary flavanones and the risk of kidney stones, including naringenin. The results of the subgroup analysis indicated that no significant interactions were observed in each subgroup. Our research indicated that a higher intake of flavanones correlates with a lowered prevalence of kidney stones in adults.

In the present study, the aim was to investigate the correlation between the acute and habitual dietary intake of flavanones, their main food sources and the concentrations of aglycones naringenin and hesperetin in 24 h urine in a European population. A 24-h dietary recall (24-HDR) and a 24-h urine sample were collected the same day from a subsample of 475 people from four different countries of the European Prospective Investigation into Cancer and Nutrition study. Acute and habitual dietary data were captured through a standardised 24-HDR and a country/centre-specific validated dietary questionnaire (DQ). The intake of dietary flavanones was estimated using the Phenol-Explorer database. Urinary flavanones (naringenin and hesperetin) were analysed using tandem MS with a previous enzymatic hydrolysis. Weak partial correlation coefficients were found between urinary flavanone concentrations and both acute and habitual dietary flavanone intakes (Rpartial = 0·14–0·17). Partial correlations were stronger between urinary excretions and acute intakes of citrus fruit and juices (Rpartial ∼ 0·6) than with habitual intakes of citrus fruit and juices (Rpartial ∼ 0·24). In conclusion, according to our results, urinary excretion of flavanones can be considered a good biomarker of acute citrus intake. However, low associations between habitual flavanone intake and urinary excretion suggest a possible inaccurate estimation of their intake or a too sporadic intake. For assessing habitual exposures, multiple urinary collections may be needed. These results show that none of the approaches tested is ideal, and the use of both DQ and biomarkers can be recommended.

Flavanones are found specifically and abundantly in citrus fruits. Their beneficial effect on vascular function is well documented. However, little is known about their cellular and molecular mechanisms of action in vascular cells. The goal of the present study was to identify the impact of flavanone metabolites on endothelial cells and decipher the underlying molecular mechanisms of action. We investigated the impact of naringenin and hesperetin metabolites at 0·5, 2 and 10 μm on monocyte adhesion to TNF-α-activated human umbilical vein endothelial cells (HUVEC) and on gene expression. Except hesperetin-7-glucuronide and naringenin-7-glucuronide (N7G), when present at 2 μm, flavanone metabolites (hesperetin-3′-sulphate, hesperetin-3′-glucuronide and naringenin-4′-glucuronide (N4′G)) significantly attenuated monocyte adhesion to TNF-α-activated HUVEC. Exposure of both monocytes and HUVEC to N4′G and N7G at 2 μm resulted in a higher inhibitory effect on monocyte adhesion. Gene expression analysis, using TaqMan Low-Density Array, revealed that flavanone metabolites modulated the expression of genes involved in atherogenesis, such as those involved in inflammation, cell adhesion and cytoskeletal organisation. In conclusion, physiologically relevant concentrations of flavanone metabolites reduce monocyte adhesion to TNF-α-stimulated endothelial cells by affecting the expression of related genes. This provides a potential explanation for the vasculoprotective effects of flavanones.

Flavonols, flavanones and flavones (FLAV) are sub-classes of flavonoids that exert cardioprotective and anti-carcinogenic properties in vitro and in vivo. We aimed to estimate the FLAV dietary intake, their food sources and associated lifestyle factors in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. FLAV intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven study centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on FLAV was compiled using data from US Department of Agriculture and Phenol-Explorer databases and was expanded using recipes, estimations and flavonoid retention factors in order to increase its correspondence with the 24 h dietary recall. Our results showed that the highest FLAV-consuming centre was the UK health-conscious group, with 130·9 and 97·0 mg/d for men and women, respectively. The lowest FLAV intakes were 36·8 mg/d in men from Umeå and 37·2 mg/d in women from Malmö (Sweden). The flavanone sub-class was the main contributor to the total FLAV intake ranging from 46·6 to 52·9 % depending on the region. Flavonols ranged from 38·5 to 47·3 % and flavones from 5·8 to 8·6 %. FLAV intake was higher in women, non-smokers, increased with level of education and physical activity. The major food sources were citrus fruits and citrus-based juices (especially for flavanones), tea, wine, other fruits and some vegetables. We concluded that the present study shows heterogeneity in intake of these three sub-classes of flavonoids across European regions and highlights differences by sex and other sociodemographic and lifestyle factors.

Hesperidin (Hp), a citrus flavonoid predominantly found in oranges, shows bone-sparing effects in ovariectomised (OVX) animals. In human subjects, the bioavailability of Hp can be improved by the removal of the rhamnose group to yield hesperetin-7-glucoside (H-7-glc). The aim of the present work was to test whether H-7-glc was more bioavailable and therefore more effective than Hp in the prevention of bone loss in the OVX rat. Adult 6-month-old female Wistar rats were sham operated or OVX, then pair fed for 90 d a casein-based diet supplemented or not with freeze-dried orange juice enriched with Hp or H-7-glc at two dose equivalents of the hesperetin aglycone (0·25 and 0·5 %). In the rats fed 0·5 %, a reduction in OVX-induced bone loss was observed regarding total bone mineral density (BMD):+7·0 % in OVX rats treated with Hp (HpOVX) and +6·6 % in OVX rats treated with H-7-glc (H-7-glcOVX) v. OVX controls (P < 0·05). In the rats fed 0·25 % hesperetin equivalents, the H-7-glcOVX group showed a 6·6 % improvement in total femoral BMD v. the OVX controls (P < 0·05), whereas the Hp diet had no effect at this dose. The BMD of rats fed 0·25 % H-7-glc was equal to that of those given 0·5 % Hp, but was not further increased at 0·5 % H-7-glc. Plasma hesperetin levels and relative urinary excretion were significantly enhanced in the H-7-glc v. Hp groups, and the metabolite profile showed the absence of eriodictyol metabolites and increased levels of hesperetin sulphates. Taken together, improved bioavailability of H-7-glc may explain the more efficient bone protection of this compound.

Oranges are rich sources of flavonoids that are bioactive and may protect against age-related diseases. The absorption of orange flavanones may be affected by factors such as processing and subject anthropometric variables, and the bioactivity of the absorbed phytochemicals depends on how they are metabolised during absorption. In a randomised cross-over study, twenty subjects consumed a single portion of orange fruit (150 g) or juice (300 g) that contained the flavanones narirutin and hesperidin, and an additional 109 subjects across a broad age range (18–80 years) consumed the juice. Flavanone metabolites were measured in regularly collected samples of plasma and urine. After consumption of fruit or juice, flavanone conjugates, but not the aglycones, were detected in plasma and urine. The flavanone conjugates were shown to include the 7- and 4′-O-monoglucuronides of naringenin, the 7- and 3′-O-monoglucuronides of hesperetin, two hesperetin diglucuronides and a hesperetin sulfo-glucuronide, but no aglycones or rutinosides. Analysis of the plasma pharmacokinetic and urinary excretion data on a dose-adjusted basis indicated no difference in absorption or excretion of either flavanone between the fruit and juice matrices. In the extended urinary excretion dataset the individual variation was very large (range 0–59 % urinary yield). There was a small but significant (P < 0·05) decrease in the excretion of hesperetin (but not naringenin) with increasing age (P < 0·05), but the effects of sex, BMI and contraceptive pill use were shown not to be associated with the variation in flavanone excretion.

Some blood orange juice (BOJ) flavanones may have antioxidant, anti-inflammatory, anti-allergic, hypolipidaemic, vasoprotective and anticarcinogenic properties. The aim of the present study was to evaluate the pharmacokinetics of hesperetin and naringenin in human subjects after BOJ intake. In a cross-over study, seven healthy female volunteers consumed 150 and 300 ml BOJ corresponding to about 51–102 mg hesperetin and to 6–12 mg naringenin, respectively. Plasma samples were collected before, each hour for 8 h and 24 h after BOJ administration and analysed for their content of hesperetin and naringenin by liquid chromatography–MS/MS. The plasma concentrations of these compounds were dose dependent and the peak concentration (Cmax) was reached in 5·1 (sd 0·6) h after BOJ intake. The Cmax of hesperetin was 43·4 (sd 32·4) and 79·8 (sd 60·1) ng/ml after 150 and 300 ml intake, respectively. For naringenin the plasma peak was 16·4 (sd 11·9) and 34·0 (sd 20·6) ng/ml. Moreover, the conjugated forms of these flavanones represent more than 95 % of the plasma concentration. The results indicate that both hesperetin and naringenin are bioavailable after BOJ intake; naringenin seemingly more so than hesperetin.