An additional RCT reported age-dependent effects of quercetin on blood pressure . Supplementation of 150 mg quercetin/d for 6 wk resulted in a decrease in SBP by 2.6 mm Hg in the entire study group, by 2.9 mm Hg in the subgroup of hypertensive subjects, and by 3.7 mm Hg in the subgroup of younger adults aged 25–50 y. These observations suggest that the blood pressure-lowering effects of quercetin may be greater in younger than in older people. The authors hypothesized that improved endothelial function may be affecting younger and middle-aged individuals, and because with increasing age the arteries become stiffer, the potential to improve vascular function by nutrients and bio-active compounds decreased. However, differences between young and elderly subjects were not reported in this work, in which only differences between the total number of subjects and a younger subgroup were given, so these findings need to be confirmed in a study specifically designed to investigate those age groups. In summary, there is currently very limited evidence to suggest that the cardiometabolic response to food bio-active compounds is age dependent. From the 3 studies that have been identified, only 2 were specifically designed to test age-dependent effects of food bio-active compounds, grow raspberries in a pot with only one being controlled and showing significant effects on CVD risk biomarkers both acutely and after short-term supplementation .
These authors concluded that some of the beneficial effects of flavanols are age dependent and others not, with FMD, PWV, and DBP showing similar effects in both young and elderly subjects, whereas SBP and AIX improved only in the elderly. Taken together, it could be suggested that age is one factor affecting the variability in the vascular response to plant-food bio-active compounds.We identified 3 studies looking at differences between men and women in their response to CF intake .Ostertag et al. reported differences in the responses to the flavanol-containing chocolate compared with white chocolate between men and women. Platelet aggregation was significantly decreased in men but not in women 2 h after consumption of dark or flavanol-enriched dark chocolate and 6 h after flavanol-enriched dark chocolate compared with white chocolate. Sex differences in the effects of the chocolate on markers of platelet activation were also observed: platelet P-selectin expression was decreased only in men 2 h after consumption of flavanol-rich dark and white chocolate compared with standard dark chocolate; fibrinogen-binding was increased only in women 2 h after consumption of flavanol-enriched dark chocolate compared with white chocolate. The sex differences highlighted in this study are interesting, but their interpretation is somewhat problematic because of the absence of an appropriate control group matched for flavanols.
For example, a significant effect of white chocolate compared with standard dark chocolate was observed on platelet activation and ex vivo bleeding time in men only. Because white chocolate does not contain flavanols, the observed effect must be due to other components in the white chocolate that are probably also found in dark chocolate, somewhat compromising its use as a suitable control for determining the effects of CFs. Cocoa itself is complex and contains many other potentially bio-active compounds in addition to flavanols, again compromising interpretation of the effects and differences between sex. West et al. reported the effects of dark chocolate and cocoa-beverage consumption on markers of endothelial function on 30 middle-aged overweight adults. The CF intervention caused significant increases in basal diameter and peak diameter of the brachial artery and basal blood flow volume in both men and women. However, significant reductions in peripheral arterial stiffness in response to the cocoa treatment were observed only in women, evidenced as substantial decreases in the AIX . The effects of cocoa treatment in men were small and nonsignificant. However, it should be noted that the women had substantially higher AIX values at baseline, and this probably related to the differences in response between men and women. Finally, Ibero-Baraibar et al. reported that men derived a greater benefit from consuming a cocoasupplemented diet than did women, although this effect was observed only for changes in oxidized LDL . Improvements in many of the variables assessed were demonstrated between baseline and the end of the study, such as blood pressure and anthropometric or body composition variables, which was to be expected in response to the 15% caloric restriction provided by both diets.
LDL in the cocoa group was significantly lower than in the control group. After adjusting the data for weight and total and LDL cholesterol, it was shown that cocoa consumption significantly affected the change in oxLDL in men but not in women. To explain this difference, the authors refer to a previously reported difference in the antioxidant status between men and women, with men exhibiting poorer antioxidant status , making them more susceptible than women to an antioxidant effect of the flavanols . However, the physiological relevance of a change in oxLDL is unknown because this variable is not an established surrogate marker of CVD risk . In summary, a sex effect in response to plant-food bio-active compounds has been reported in very few studies, and all of those focused on flavanols. From the 3 articles identified to date, differences in the response between men and women were observed in the AIX and antioxidant status.Eight studies have reported the impact of genetic polymorphisms on the cardiometabolic health effects of green tea , coffee or caffeine , and plant sterols . The beneficial effects of green tea catechins may be predisposed by polymorphisms in genes encoding phase II metabolism enzymes during and after the consumption. The missense mutation rs4680 in the COMT gene, coding for methylation enzyme, results in a 40% decrease in enzyme activity. In a pilot study performed by Miller et al. , 20 subjects were given green tea extract capsules in a fasted state and with a high-carbohydrate breakfast. The modification in digital volume pulse stiffness index from baseline was observed to be different between genotype groups at 120 and 240 min, with a lower stiffness index in the GG individuals. The alteration in blood pressure from baseline was also observed to be different between genotype groups, with a bigger increase in SBP and DBP at 120 min in the GG group. It was observed that the AA group had a greater increase in plasma insulin concentrations at 120 and 180 min compared with baseline, although the glucose profiles were similar. No differences were observed in vascular reactivity evaluated by using laser-Doppler iontophoresis, total nitrite, plasma lipids, total antioxidant capacity, or markers of inflammation. The same investigators assessed the effect of the COMT genotype on the heterogeneity in response to green tea catechins regarding vascular reactivity and blood pressure in a study with 50 volunteers instead of 20 as in previous study . These subjects completed a randomized, double-blind, crossover study. Peripheral arterial tonometry, DVP, and blood pressure were evaluated at baseline and 90 min after intake of 1.06 g green tea extract or placebo. A genotype-treatment interaction was shown for the DVP reflection index with green tea extract in the AA COMT group. A genotypic effect was described for urinary methylated epigallocatechin during the first 5.5 h, with the GG COMT group having higher concentrations . Taken together, these 2 studies suggest that differences in small-vessel tone according to COMT genotype are evident after the acute administration of green tea extract. The response in serum cholesterol to diet may be modulated by the APOE, 32/33/34 alleles, best grow pots which is also a predictor of variation in the risk of CAD and CAD death. Strandhagen et al. tested the hypothesis that the APOE polymorphism may affect the cholesterol-raising effect of coffee. Onehundred twenty-one healthy, nonsmoking men and women aged 29–65 y were provided with 0.6 L filter brewed coffee/d for 4 wk.
APOE 32-positive volunteers presented significantly lower total cholesterol concentrations at baseline, but the cholesterol-raising effect of coffee was not significantly influenced by APOE allele carrier status. These results suggest that the APOE 32 allele is associated with a lower serum cholesterol concentration, but it does not seem to affect the cholesterol-raising effect of coffee. In a study with a similar design and similar study population, the hypothesis that methylenetetrahydrofolate reductase gene polymorphism, known to influence plasma total homocysteine , is associated with the effect of coffee on plasma homocysteine-raising effect has been investigated . The authors examined the impact of consumption of 0.6 L coffee/d supplemented or not with 200 mg folic acid on tHcy with respect to the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms. tHcy, at baseline, was higher in the 677TT genotype group than in the 677CC genotype group, and this group had a higher increase in tHcy on coffee exposure than did the 677CC and 677CT genotype groups. Supplementation with 200 mg folic acid, when compared with the placebo, decreased the tHcyincreasing effect of coffee in the 677TT genotype group. The A1298C polymorphism did not modulate tHcy concentration. Therefore, it was suggested that the homocysteine increasing impact of coffee is especially obvious in individuals with the homozygous 677TT genotype . Renda et al. evaluated acute blood pressure responses to caffeine and evaluated whether they are affected by candidate gene variants affecting caffeine metabolism: CYP1A2, adenosine metabolism , or catecholamine receptors. In this study, 110 healthy male subjects with moderate coffee consumption underwent ambulatory blood pressure monitoring at 6-min intervals for 2 h. Each volunteer was given, in a double blind design, 0.04 L of either a decaffeinated coffee preparation plus 3 mg caffeine/kg or the corresponding vehicle . Compared with decaffeinated coffee, caffeine significantly increased both SBP and DBP. Plasma caffeine and adrenaline increased after caffeine but not after decaffeinated coffee. Of the 11 gene polymorphisms analyzed, an association was detected between the adenosine A2a receptor TT variant and the a-2B adrenergic receptor I variant and the change in SBP in responses to caffeine . This study suggests that the variability in the acute blood pressure response to coffee may be due to the genetic polymorphisms of the adenosine A2A receptors and the a2-adrenergic receptors. The ATP-binding cassette heterodimeric transporters G5 and G8 were assumed to mediate intestinal cholesterol efflux, whereas NiemannPick C1 Like 1 protein is believed to be important for intestinal cholesterol influx. Individual or combined genetic polymorphism of these genes could explain interindividual variations in plasma cholesterol response after the consumption of plant sterols. Zhao et al. investigated the association between ABCG5/ABCG8 and NPC1L1 single nuclear polymorphisms and sterol absorption and corresponding plasma concentrations. The trial was a 4-wk crossover study with 82 hypercholesterolemic men presenting high compared with low basal plasma plant sterol concentrations who consumed spreads with or without 2 g plant sterols/d. For the ABCG8 1289 C>A polymorphism, the carriers of the A allele with high basal plasma plant sterol concentrations presented a 390% higher reduction in serum LDL cholesterol than did their low basal plasma counterparts. For the NPC1L1 haplotype of 872 C>G and 3929 G>A , volunteers carrying mutant alleles presented a 240% decrease in LDL cholesterol concentrations compared with the volunteers with the wild-type allele . The results demonstrate that genetic and metabolic biomarkers may predict interindividual lipid concentration responsiveness to plant sterol intervention and might be important in developing individualized cholesterollowering approaches. Plant sterol esters decrease serum TC and LDL cholesterol but with important inter individual variability. In a randomized, double-blind, controlled study, hypercholesterolemic subjects consumed a reduced saturated-fat and cholesterol diet for 4 wk followed by a 5-wk intervention during which they consumed a control spread or a spread with plant sterol esters . During sterol consumption, TC, LDL cholesterol, and apoB concentrations and the ratios of TC to LDL cholesterol and LDL to HDL were observed to be lower only in subjects carrying e2 or e3 allele of apoE gene, and serum TG decreased only in subjects carrying e2 allele. Thus, responses to plant sterols diverge depending on apoE genotype and might be of small important in apoE4 carriers. Plant sterols may disrupt the micellar solubilization of cholesterol by the bile acid pool, thus influencing intestinal cholesterol absorption. Plasma lipid variation relates to the promoter variant 2204A>C of the cholesterol 7 a-hydroxylase gene encoding for a-hydroxylase, an enzyme for bile acid synthesis. De Castro-Orós et al. hypothesized that this polymorphism could be linked with the inter individual variation in responses to plant sterol consumption. They investigated 67 volunteers with lipid responses to plant sterols documented in 2 studies. Compared with AA subjects, C-allele carriers presented higher decreases in TC and increases in ratios of lathosterol to cholesterol.