Samir Samman

Flavonoids-Chemistry, metabolism, cardioprotective effects, and dietary sources

Flavonoids are a group of polyphenolic compounds, diverse in chemical structure and characteristics, found ubiquitously in plants. Therefore, flavonoids are part of the human diet. Over 4,000 different flavonoids have been identified within the major flavonoid classes which include flavonols, flavones, flavanones, catechins, anthocyanidins, isoflavones, dihydroflavonols, and chalcones. Flavonoids are absorbed from the gastrointestinal tracts of humans and animals and are excreted either unchanged or as flavonoid metabolites in the urine and feces. Flavonoids are potent antioxidants, free radical scavengers, and metal chelators and inhibit lipid peroxidation. The structural requirements for the antioxidant and free radical scavenging functions of flavonoids include a hydroxyl group in carbon position three, a double bond between carbon positions two and three, a carbonyl group in carbon position four, and polyhydroxylation of the A and B aromatic rings. Epidemiological studies show an inverse correlation between dietary flavonoid intake and mortality from coronary heart disease (CHD) which is explained in part by the inhibition of low density lipoprotein oxidation and reduced platelet aggregability. Dietary intake of flavonoids range between 23 mg/day estimated in The Netherlands and 170 mg/day estimated in the USA. Major dietary sources of flavonoids determined from studies and analyses conducted in The Netherlands include tea, onions, apples, and red wine. More research is needed for further elucidation of the mechanisms of flavonoid absorption, metabolism, biochemical action, and association with CHD.

Zinc and Regulation of Inflammatory Cytokines: Implications for Cardiometabolic Disease

In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination.

The effect of supplementation with isoflavones on plasma lipids and oxidisability of low density lipoprotein in premenopausal women

Results of recent clinical studies have lead to the hypothesis that isoflavones are cardioprotective. The aims of this trial were to determine the effect of supplementation with isoflavonoid phytoestrogens on plasma cholesterol concentrations and its distribution among lipoproteins and whether supplementation with isoflavones influences oxidisability of low density lipoprotein (LDL) ex vivo. Fourteen healthy premenopausal women participated in a randomised cross-over trial lasting four menstrual cycles (approximately 4 months). The subjects were asked to consume 86 mg of isoflavones daily for the duration of two menstrual cycles followed by placebo for an equivalent period, or vice versa. Venous blood samples were collected initially and at the end of the second and fourth menstrual cycles for the determination of plasma lipid concentrations and the resistance of LDL to copper-induced oxidation ex vivo. Accustomed dietary intake of isoflavones and lignans during the placebo period were 6.87+/-3.0 and 1.80+/-0.22 mg/day (mean+/-S.E.M.), respectively, and these did not change during the supplementation period. The intake of other dietary components remained constant during the trial. Supplementation resulted in a 5-fold increase in urinary isoflavone excretion (12.2+/-14.2 versus 70.1+/-10.3 micromol/24 h, placebo and isoflavone periods, respectively, P=0.0001). No changes in the oxidisability of LDL (lag time of 32.9+/-3.1 versus 30.4+/-2.9 min) or the plasma concentrations of total cholesterol (4.03+/-0.21 versus 4.11+/-0.18 mmol/l) or triacylglycerol (0.67+/-0.04 versus 0.73+/-0.06 mmol/l) were observed following supplementation. However a significant period effect (P=0.024) was observed and a trend towards a carryover effect (P=0.086) was noted for the concentration of HDL(3) cholesterol. Further studies are required to clarify the potential effect of isoflavones on HDL metabolism and the interaction with plasma steroid hormones during the menstrual cycle.

Zinc and Redox Signaling: Perturbations Associated with Cardiovascular Disease and Diabetes Mellitus

Cellular signal transduction pathways are influenced by the zinc and redox status of the cell. Numerous chronic diseases, including cardiovascular disease (CVD) and diabetes mellitus (DM), have been associated with impaired zinc utilization and increased oxidative stress. In humans, mutations in the MT-1A and ZnT8 genes, both of which are involved in the maintenance of zinc homeostasis, have been linked with DM development. Changes in levels of intracellular free zinc may exacerbate oxidative stress in CVD and DM by impacting glutathione homeostasis, nitric oxide signaling, and nuclear factor-kappa B-dependent cellular processes. Zinc ions have been shown to influence insulin and leptin signaling via the phosphoinositide 3′-kinase/Akt pathway, potentially linking an imbalance of zinc at the cellular level to insulin resistance and dyslipidemia. The oxidative modification of cysteine residues in zinc coordination sites in proteins has been implicated in cellular signaling and regulatory pathways. Despite the many interactions between zinc and cellular stress responses, studies investigating the potential therapeutic benefit of zinc supplementation in the prevention and treatment of oxidative stress-related chronic disease in humans are few and inconsistent. Further well-designed randomized controlled trials are needed to determine the effects of zinc supplementation in populations at various stages of CVD and DM progression.

Vitamin B12 in Health and Disease

Vitamin B12 is essential for DNA synthesis and for cellular energy production.This review aims to outline the metabolism of vitamin B12, and to evaluate the causes and consequences of sub-clinical vitamin B12 deficiency. Vitamin B12 deficiency is common, mainly due to limited dietary intake of animal foods or malabsorption of the vitamin. Vegetarians are at risk of vitamin B12 deficiency as are other groups with low intakes of animal foods or those with restrictive dietary patterns. Malabsorption of vitamin B12 is most commonly seen in the elderly, secondary to gastric achlorhydria. The symptoms of sub-clinical deficiency are subtle and often not recognized. The long-term consequences of sub-clinical deficiency are not fully known but may include adverse effects on pregnancy outcomes, vascular, cognitive, bone and eye health.

The Effect of Zinc Supplementation in Humans on Plasma Lipids, Antioxidant Status and Thrombogenesis

The potential exists for zinc to influence numerous metabolic functions and to impact a range of diseases. In the present review we examine the reported relationships between zinc and plasma lipids, haemostasis and other factors postulated to play a role in atherogenesis. Ecological studies that investigated zinc intake or status, and incidence of coronary heart disease (CHD) reveal no consistent pattern. The conflicting observations may be explained by differences in the extent of CHD, site of atherosclerosis, or confounding factors. In most studies the diurnal variation in serum zinc concentrations, and the lifestyle factors that affect cholesterol metabolism were not explicitly considered. Results of randomised controlled trials show that low-density lipoprotein (LDL) oxidation and the concentrations of LDL-cholesterol (c), total cholesterol and triglycerides in plasma are unaffected by supplementation with up to 150 mg Zn/d. In contrast, plasma high-density lipoprotein (HDL)-c concentrations decline when zinc supplements provide a dose >50 mg/d. Limited data suggest that sustained hyperzincaemia predisposes individuals to thrombogenesis, whereas acute zinc depletion impairs platelet aggregation and prolongs bleeding time. In addition, Zinc supplements have been shown in some studies to decrease Cu/Zn-superoxide dismutase activity, primarily due to the antagonistic relationship between high zinc intakes and copper absorption. Besides the demonstrated adverse effect of zinc supplementation on plasma HDL-c concentrations in apparently healthy men, there is insufficient evidence to determine the role of zinc supplementation in influencing other risk factors for CHD such as antioxidant status and thrombogenesis.

Zinc and glycemic control: a meta-analysis of randomised placebo controlled supplementation trials in humans.

BACKGROUND Impaired zinc metabolism is prominent in chronic disorders including cardiovascular disease and diabetes. Zinc has the potential to affect glucose homeostasis in animals and humans and hence impact the risk of type 2 diabetes mellitus. METHODS A systematic review and meta-analysis of randomised placebo controlled trials was conducted to determine the effect of zinc supplementation on fasting blood glucose, HbA1c, serum insulin and serum zinc concentrations. Relevant studies for inclusion were identified from a literature search of electronic databases up to July 2011. RESULTS Fourteen reports (n=3978 subjects) were included in the meta-analysis. In the overall analysis, a small but statistically significant reduction in fasting glucose concentrations was observed (-0.19±0.08mmol/L, P=0.013) after zinc supplementation. HbA1c tended to decrease in zinc-supplemented individuals (-0.64±0.36%, P=0.072). No significant effect was observed for serum insulin concentrations. Plasma zinc concentrations increased significantly following supplementation (+4.03±0.81μmol/L, P=0.001). In secondary analyses of participants with chronic metabolic disease (types 1 and 2 diabetes mellitus, metabolic syndrome and obesity), zinc supplementation produced a greater reduction in glucose concentrations (-0.49±0.11mmol/L, P=0.001) compared to the effect that was observed in healthy participants. CONCLUSION The significant albeit modest reduction in glucose concentrations and tendency for a decrease in HbA1c following zinc supplementation suggest that zinc may contribute to the management of hyperglycemia in individuals with chronic metabolic disease.

The effect of boron supplementation on its urinary excretion and selected cardiovascular risk factors in healthy male subjects.

Boron (B) is an essential trace element for plants and its interrelationship with mineral and bone metabolism and endocrine function in humans has been proposed. Relatively little is known about the occurrence of B in the food chain and hence a biomarker which reflects its intake is required. Two studies were carried out to quantify the urinary B concentration of subjects consuming their habitual diet and the effect of supplementation. In addition, the effect of supplementation on plasma lipoprotein cholesterol concentrations and susceptibility to oxidation and plasma steroid hormones were determined. Boron excretion, obtained on two different occasions from 18 healthy male subjects, was found to be in the range 0.35–3.53 mg/day, with no significant difference between the two occasions. Supplementation with 10 mg B/d for 4 wk resulted in 84% of the supplemented dose being recovered in the urine. Plasma estradiol concentrations increased significantly as a result of supplementation (51.9±21.4 to 73.9±22.2 pmol/L;p<0.004) and there was a trend for plasma testosterone levels to be increased. However, there was no difference in plasma lipids or the oxidizability of low-density lipoprotein Our studies suggest that the absorption efficiency of B is very high and estimation of the urinary B concentration may provide a useful reflection of B intake. In addition, the elevation of endogenous estrogen as a result of supplementation suggests a protective role for B in atherosclerosis.

The nutritional and metabolic effects of boron in humans and animals

We have undertaken studies in humans and animals that aimed to obtain further information about the intake and excretion of boron (B) as well as its effects on markers of coronary heart disease. In humans, we have shown that the intake of B is 2.2 mg/d; its urinary excretion is 1.9 mg/d, and there appears to be little intraindividual variation. Supplementation with 10 mg of B/d resulted in the recovery of 84% of the dose in the urine and a significant increase in plasma estradiol concentration, but no effect on plasma lipoproteins. In rats, increasing the intake of B through the drinking water is reflected in the tissue concentrations, results in an increase in plasma testosterone and vitamin D, and results in a decrease in HDL cholesterol. It is clear that B has the potential to impact significantly on a number of metabolic processes.

Evaluation of the Micronutrient Composition of Plant Foods Produced by Organic and Conventional Agricultural Methods

The aim of the present analysis was to evaluate the micronutrient content of plant foods produced by organic and conventional agricultural methods. Studies were identified from a search of electronic databases (1980–2007, inclusive) as well as manual searches. A total of 66 studies (describing 1440 micronutrient comparisons) were identified. Thirty-three studies (908 comparisons) satisfied the screening criteria which considered cultivar, harvesting, and soil conditions. In studies that satisfied the screening criteria, the absolute levels of micronutrients were higher in organic foods more often than in conventional foods (462 vs 364 comparisons, P = 0.002), and the total micronutrient content, expressed as a percent difference, was higher in organic (+ 5.7%, P < 0.001) as compared to conventionally grown produce. The micronutrient content of food groups was more frequently reported to be higher for organic vegetables and legumes compared to their conventional counterparts (vegetables, 267 vs 197, P < 0.001; legumes, 79 vs 46, P = 0.004). This trend was supported by a mean percent difference in micronutrient content favoring organic vegetables (+ 5.9%, P < 0.001) and legumes (+ 5.7%, P < 0.001). Further research is required to determine the effect of organic agricultural methods on a broader range of nutrients and their potential impact on health.