Nutritional and lifestyle management of the aging journey: A narrative review.

With age, the physiological responses to occasional or regular stressors from a broad range of functions tend to change and adjust at a different pace and restoring these functions in the normal healthy range becomes increasingly challenging. Even if this natural decline is somehow unavoidable, opportunities exist to slow down and attenuate the impact of advancing age on major physiological processes which, when weakened, constitute the hallmarks of aging. This narrative review revisits the current knowledge related to the aging process and its impact on key metabolic functions including immune, digestive, nervous, musculoskeletal, and cardiovascular functions; and revisits insights into the important biological targets that could inspire effective strategies to promote healthy aging.

Acute dose-response effect of coffee-derived chlorogenic acids on the human vasculature in healthy volunteers: a randomized controlled trial.

BACKGROUND: Epidemiological studies have reported lower risk of cardiovascular disease with moderate coffee consumption. In addition, emerging evidence indicates that consumption of coffee beverages enriched in chlorogenic acids (CGAs) may influence blood pressure and endothelial function, suggesting that the beneficial cardiovascular effect of coffee may relate to its CGA content. OBJECTIVES: We conducted a double-blind randomized crossover trial to test the effect of acute consumption of a decaffeinated green coffee extract (DGCE), rich in CGAs, on endothelial function in healthy subjects. METHODS: We compared 3 different doses of DGCE (302, 604, and 906 mg, respectively) with a placebo. Endothelial function was defined as the percentage change in the internal diameter of the brachial artery in response to flow-mediated dilation (%FMD). In addition, we followed the plasma concentration-time profiles of 25 systemic CGA metabolites over 24 h after DGCE consumption and we explored the relation between systemic concentrations of CGAs and the effect on %FMD. RESULTS: The DGCE formulations containing different amounts of CGAs resulted in dose-proportional increases in overall total polyphenol concentrations. The systemic appearance of total CGAs was biphasic, in agreement with previous results suggesting 2 sites of absorption in the gastrointestinal tract. Compared with the placebo group, a significant FMD increase (>1%) was observed 8.5, 10, and 24 h after consumption of 302 mg DGCE (∼156.4 mg CGAs). The differences with placebo observed in the other 2 groups were not statistically significant. Evaluation of the relation between phenolic exposure and %FMD showed a positive tendency toward a larger effect at higher concentrations and different behavior of CGA metabolites depending on the conjugated chemical position. CONCLUSIONS: We demonstrated an acute improvement in %FMD over time after ingestion of a DGCE, explained at least partly by the presence in the blood circulation of CGAs and their metabolites. This trial was registered at clinicaltrials.gov as NCT03520452.

The Influence of Different Foods and Food Ingredients on Acute Postprandial Triglyceride Response: A Systematic Literature Review and Meta-Analysis of Randomized Controlled Trials.

The use of postprandial triglyceride (ppTG) as a cardiovascular disease risk indicator has gained recent popularity. However, the influence of different foods or food ingredients on the ppTG response has not been comprehensively characterized. A systematic literature review and meta-analysis was conducted to assess the effects of foods or food ingredients on the ppTG response. PubMed, MEDLINE, Cochrane, and CINAHL databases were searched for relevant acute (<24-h) randomized controlled trials published up to September 2018. Based on our selection criteria, 179 relevant trials (366 comparisons) were identified and systematically compiled into distinct food or food ingredient categories. A ppTG-lowering effect was noted for soluble fiber (Hedges' giAUC = -0.72; 95% CI: -1.33, -0.11), sodium bicarbonate mineral water (Hedges' gAUC = -0.42; 95% CI: -0.79, -0.04), diacylglycerol oil (Hedges' giAUC = -0.38; 95% CI: -0.75, -0.00), and whey protein when it was contrasted with other proteins. The fats group showed significant but opposite effects depending on the outcome measure used (Hedges' giAUC = -0.32; 95% CI: -0.61, -0.03; and Hedges' gAUC = 0.16; 95% CI: 0.06, 0.26). Data for other important food groups (nuts, vegetables, and polyphenols) were also assessed but of limited availability. Assessing for oral fat tolerance test (OFTT) recommendation compliance, most trials were ≥4 h long but lacked a sufficiently high fat challenge. iAUC and AUC were more common measures of ppTG. Overall, our analyses indicate that the effects on ppTG by different food groups are diverse, largely influenced by the type of food or food ingredient within the same group. The type of ppTG measurement can also influence the response.

Dose-response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Several intervention studies have investigated the relationship between cocoa flavanols and endothelial function. However, the shape of the association and the type of compounds responsible for the effects are largely unknown. OBJECTIVE: To examine the dose-response association between the consumption of cocoa flavanols and endothelial function, measured by flow-mediated dilation (FMD). DESIGN: Two investigators searched Scopus® for the relevant human intervention studies, which were pooled and meta-analysed. Heterogeneity in the findings was explored with various subgroup analyses. RESULTS: Fifteen published articles with 18 intervention arms met the inclusion criteria. Participants in these intervention groups received 80 to 1248 mg (mean: 704 mg) more flavanols than control groups. A significant improvement of FMD by 1.17% (95% CI: 0.76% to 1.57%) was calculated, with strong evidence of a non-linear association (inverted U-shape) between cocoa flavanols and FMD. CONCLUSIONS: This meta-analysis provides evidence that cocoa flavanols could significantly improve endothelial function, with an optimal effect observed with 710 mg total flavanols, 95 mg (-)-epicatechin or 25 mg (+)-catechin. However, there was substantial variation in the results that could not be explained by the characteristics that we explored, and there were significant risk-of-bias concerns with a large majority of the studies.

Milk Powder Fortified with Potassium and Phytosterols to Decrease the Risk of Cardiovascular Events among the Adult Population in Malaysia: A Cost-Effectiveness Analysis.

This study evaluated the cost-effectiveness of the consumption of a milk powder product fortified with potassium (+1050.28 mg/day) and phytosterols (+1200 mg/day) to lower systolic blood pressure and low-density lipoprotein cholesterol, respectively, and, therefore, the risk of myocardial infarction (MI) and stroke among the 35-75-year-old population in Malaysia. A Markov model was created against a do-nothing option, from a governmental perspective, and with a time horizon of 40 years. Different data sources, encompassing clinical studies, practice guidelines, grey literature, and statistical yearbooks, were used. Sensitivity analyses were performed to evaluate the impact of uncertainty on the base case estimates. With an incremental cost-effectiveness ratio equal to international dollars (int$) 22,518.03 per quality-adjusted life-years gained, the intervention can be classified as very cost-effective. If adopted nationwide, it would help prevent at least 13,400 MIs, 30,500 strokes, and more than 10,600 and 17,100 MI- and stroke-related deaths. The discounted cost savings generated for the health care system by those who consume the fortified milk powder would amount to int$8.1 per person, corresponding to 0.7% of the total yearly health expenditure per capita. Sensitivity analyses confirmed the robustness of the results. Together with other preventive interventions, the consumption of milk powder fortified with potassium and phytosterols represents a cost-effective strategy to attenuate the rapid increase in cardiovascular burden in Malaysia.

Nutrition in the Bin: A Nutritional and Environmental Assessment of Food Wasted in the UK.

The UK currently has the most detailed, directly measured data for food wasted in the home. This includes information on the exact types of food wasted. These data allow calculation of the nutrients within that waste, as well as its environmental impact. The results progress the conversation beyond how much food is wasted or its energy content; it permits the implications for nutrition and sustainability to be assessed in detail. Data for UK household food waste were expressed as an average waste per capita for each type of food. Each food type was matched with an item (or group of items) from the UK Composition of Foods (7th Ed). The level of nutrients wasted was compared to UK Reference Nutrient Intakes (RNIs) for adult women (19-50 years, used as a proxy for general population requirements). The data were normalized into "nutrient days" wasted per capita per year, then into the number of complete diet days (for 21 nutrients plus energy). Results show that approximately 42 daily diets were discarded per capita per year. By individual nutrient, the highest losses were vitamin B12, vitamin C, and thiamin (160, 140, and 130 nutrient days/capita/year, respectively). For protein, dietary energy and carbohydrates, 88, 59, and 53 nutrient days/capita/year, respectively, were lost. Substantial losses were also found for under-consumed nutrients in the UK: calcium, which was mostly lost via bakery (27%) and dairy/eggs (27%). Food folate was mainly lost through fresh vegetables/salads (40%) and bakery (18%), as was dietary fiber (31 and 29%, respectively). Environmental impacts were distributed over the food groups, with wasted meat and fish the single largest contribution. For all environmental impacts studied, the largest contribution came from agricultural production. This paper shows that there are areas where interventions preventing food waste and promoting healthy eating could work together (e.g., encouraging consumption of vegetables or tackling overbuying, especially of unhealthy foods). Food manufacturers and retailers, alongside governments and NGOs, have a key role to minimize waste of environmentally impactful, nutrient-dense foods, for instance, by helping influence people's behaviors with appropriate formulation of products, packaging, portioning, use of promotions, or public education.

Cost-effectiveness of milk powder fortified with potassium to decrease blood pressure and prevent cardiovascular events among the adult population in China: a Markov model.

OBJECTIVE: To model the long-term cost-effectiveness of consuming milk powder fortified with potassium to decrease systolic blood pressure (SBP) and prevent cardiovascular events. DESIGN: A best case scenario analysis using a Markov model was conducted. PARTICIPANTS: 8.67% of 50-79 year olds who regularly consume milk in China, including individuals with and without a prior diagnosis of hypertension. INTERVENTION: The model simulated the potential impact of a daily intake of two servings of milk powder fortified with potassium (+700 mg/day) vs the consumption of a milk powder without potassium fortification, assuming a market price equal to 0.99 international dollars (intl$; the consumption of a milk powder without potassium fortification, assuming a market price equal to intl$0.99 for the latter and to intl$1.12 for the first (+13.13%). Both deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the results. MAIN OUTCOME MEASURES: Estimates of the incidence of cardiovascular events and subsequent mortality in China were derived from the literature as well as the effect of increasing potassium intake on blood pressure. The incremental cost-effectiveness ratio (ICER) was used to determine the cost-effectiveness of a milk powder fortified with potassium taking into consideration the direct medical costs associated with the cardiovascular events, loss of working days and health utilities impact. RESULTS: With an ICER equal to int$4711.56 per QALY (quality-adjusted life year) in the best case scenario and assuming 100% compliance, the daily consumption of a milk powder fortified with potassium shown to be a cost-effective approach to decrease SBP and reduce cardiovascular events in China. Healthcare savings due to prevention would amount to intl$8.41 billion. Sensitivity analyses showed the robustness of the results. CONCLUSION: Together with other preventive interventions, the consumption of a milk powder fortified with potassium could represent a cost-effective strategy to attenuate the rapid rise in cardiovascular burden among the 50-79 year olds who regularly consume milk in China.

Mediation of coffee-induced improvements in human vascular function by chlorogenic acids and its metabolites: Two randomized, controlled, crossover intervention trials.

BACKGROUND & AIMS: Polyphenol intake has been linked to improvements in human vascular function, although data on hydroxycinnamates, such as chlorogenic acid (CGA) have not yet been studied. We aimed to investigate the impact of coffee intake rich in chlorogenic acid on human vascular function and whether CGAs are involved in potential effects. METHODS: Two acute randomized, controlled, cross-over human intervention trials were conducted. The impact of coffee intake, matched for caffeine but differing in CGA content (89, and 310 mg) on flow-mediated dilatation (FMD) was assessed in 15 healthy male subjects. In a second intervention trial conducted with 24 healthy male subjects, the impact of pure 5-caffeoylquinic acid (5-CQA), the main CGA in coffee (5-CQA; 450 mg and 900 mg) on FMD was also investigated. RESULTS: We observed a bi-phasic FMD response after low and high polyphenol, (89 mg and 310 mg CGA) intake, with increases at 1 (1.10 ± 0.43% and 1.34 ± 0.62%, respectively) and 5 (0.79% ± 0.32 and 1.52% ± 0.40, respectively) hours post coffee consumption. FMD responses to coffee intake was closely paralleled by the appearance of CGA metabolites in plasma, notably 3-, 4- and 5-feruloylquinic acid and ferulic-4'-O-sulfate at 1 h and isoferulic-3'-O-glucuronide and ferulic-4'-O-sulfate at 5 h. Intervention with purified 5-CQA (450 mg) also led to an improvement in FMD response relative to control (0.75 ± 1.31% at 1 h post intervention, p = 0.06) and concomitant appearance of plasma metabolites. CONCLUSIONS: Coffee intake acutely improves human vascular function, an effect, in part, mediated by 5-CQA and its physiological metabolites. STUDY REGISTRATION: The National Institutes of Health (NIH) on ClinicalTrials.govNCT01813981 and NCT01772784.

Effects of plant stanol or sterol-enriched diets on lipid profiles in patients treated with statins: systematic review and meta-analysis.

Efficacy and safety data from trials with suitable endpoints have shown that non-statin medication in combination with a statin is a potential strategy to further reduce cardiovascular events. We aimed to evaluate the overall effect of stanol- or sterol-enriched diets on serum lipid profiles in patients treated with statins by conducting a meta-analysis of randomized controlled trials (RCTs). We used the PubMed, Cochrane library and ClinicalTrials.gov databases to search for literature published up to December 2015. Trials were included in the analysis if they were RCTs evaluating the effect of plant stanols or sterols in patients under statin therapy that reported corresponding data on serum lipid profiles. We included 15 RCTs involving a total of 500 participants. Stanol- or sterol-enriched diets in combination with statins, compared with statins alone, produced significant reductions in total cholesterol of 0.30 mmol/L (95% CI -0.36 to -0.25) and low-density lipoprotein (LDL) cholesterol of 0.30 mmol/L (95% CI -0.35 to -0.25), but not in high-density lipoprotein cholesterol or triglycerides. These results persisted in the subgroup analysis. Our meta-analysis provides further evidence that stanol- or sterol-enriched diets additionally lower total cholesterol and LDL-cholesterol levels in patients treated with statins beyond that achieved by statins alone.

Acute effects of chlorogenic acids on endothelial function and blood pressure in healthy men and women.

Coffee is a rich source of polyphenols, primarily chlorogenic acids (CGA). Certain polyphenols and polyphenol-rich foods and beverages have been shown to improve endothelial function and lower blood pressure (BP). The aim of the present study was to investigate the acute effect of two doses of CGA (5-CGA) on endothelial function and BP. In a cross-over study, 16 healthy men and women received: (i) 0 mg purified 5-CGA (control group); (ii) 450 mg purified 5-CGA; (iii) 900 mg purified 5-CGA; and (iv) 200 mg purified (-)-epicatechin (positive control) in random order one week apart. Peak and continuous mean (60 to 240 s post ischaemia) flow-mediated dilation (FMD) was measured at baseline, 1 h and 4 h. BP was measured at baseline and every 30 min to 4 h. Plasma CGA and epicatechin levels were significantly increased at both 1 h and 4 h post their respective treatments. Peak FMD was not significantly altered by either dose of 5-CGA or the epicatechin, relative to control (p > 0.05). Relative to control, effects on continuous mean FMD response following 450 mg 5-CGA and 900 mg of 5-CGA (0.47 ± 0.16%, p = 0.016 and 0.65 ± 0.16%, p < 0.001, respectively) at 1 h and (0.18 ± 0.17%, p = 0.99 and 0.44 ± 0.16%, p < 0.05, respectively) at 4 h. There was no significant effect of any of the treatments on BP. In conclusion, the present study has found no significant effect of 5-CGA, at 450 and 900 mg, on peak FMD response. However, there were significant improvements in mean post-ischaemic FMD response, particularly at the 1 h time point in this group of healthy individuals.

Daily potassium intake and sodium-to-potassium ratio in the reduction of blood pressure: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of daily potassium intake on decreasing blood pressure in non-medicated normotensive or hypertensive patients, and to determine the relationship between potassium intake, sodium-to-potassium ratio and reduction in blood pressure. DESIGN: Mixed-effect meta-analyses and meta-regression models. DATA SOURCES: Medline and the references of previous meta-analyses. STUDIES ELIGIBILITY CRITERIA: Randomized controlled trials with potassium supplementation, with blood pressure as the primary outcome, in non-medicated patients. RESULTS: Fifteen randomized controlled trials of potassium supplementation in patients without antihypertensive medication were selected for the meta-analyses (917 patients). Potassium supplementation resulted in reduction of SBP by 4.7 mmHg [95% confidence interval (CI) 2.4-7.0] and DBP by 3.5 mmHg (95% CI 1.3-5.7) in all patients. The effect was found to be greater in hypertensive patients, with a reduction of SBP by 6.8 mmHg (95% CI 4.3-9.3) and DBP by 4.6 mmHg (95% CI 1.8-7.5). Meta-regression analysis showed that both increased daily potassium excretion and decreased sodium-to-potassium ratio were associated with blood pressure reduction (P < 0.05). Increased total daily potassium urinary excretion from 60 to 100 mmol/day and decrease of sodium-to-potassium ratio were shown to be necessary to explain the estimated effect. CONCLUSION: Potassium supplementation is associated with reduction of blood pressure in patients who are not on antihypertensive medication, and the effect is significant in hypertensive patients. The reduction in blood pressure significantly correlates with decreased daily urinary sodium-to-potassium ratio and increased urinary potassium. Patients with elevated blood pressure may benefit from increased potassium intake along with controlled or decreased sodium intake.

sigma(2)-receptor ligand-mediated inhibition of inwardly rectifying K(+) channels in the heart.

The sigma(2)-receptor agonist, ifenprodil, was suggested as an inhibitor of G protein-coupled inwardly rectifying potassium channels. Nevertheless, an analysis of the role of sigma(2) receptors in cardiac electrophysiology has never been done. This work aims i) to identify the roles of cardiac sigma(2) receptors in the regulation of cardiac K(+) channel conductances and ii) to check whether sigma(2)-receptor agonists exhibit class III antiarrhythmic properties. The sigma(2)-receptor agonists ifenprodil, threo-ifenprodil, LNP250A [threo-8-[1-(4-hydroxyphenyl)-1-hydroxy-propan-2-yl]-1-phenyl-1,3,8-triazaspiro[4,5]decane-4-one] (a derivative of ifenprodil devoid of alpha(1)-adrenergic and N-methyl-d-aspartate glutamate receptor-blocking properties), and 1,3-di(2-tolyl)guanidine were used to discriminate the effects linked to sigma(2) receptors from those of the sigma(1) subtype, induced by (+/-)-N-allylnormetazocine (SKF-10,047). The sigma(2)-receptor antagonist 3-alpha-tropanyl-2(pCl-phenoxy)butyrate (SM-21) was employed to characterize sigma(2)-mediated effects in patch-clamp experiments. In rabbits, all sigma(2)-receptor agonists reduced phenylephrine-induced cardiac arrhythmias. They prolonged action potential duration in rabbit Purkinje fibers and reduced human ether-a-go-go-related gene (HERG) K(+) currents. (+)-SKF-10,047 was completely inactive in the last two tests. The effects of threo-ifenprodil were not antagonized by SM-21. In HERG-transfected COS-7 cells, SM-21 potentiated the ifenprodil-induced blockade of the HERG current. These data suggest that sigma(2)-receptor ligands block I(Kr) and that this effect could explain part of the antiarrhythmic properties of this ligands family. Nevertheless, an interaction with HERG channels not involving sigma(2) receptors seems to share this pharmacological property. This work shows for the first time that particular caution has to be taken toward ligands with affinity for sigma(2) receptors. The repolarization prolongation and the early-afterdepolarization can be responsible for "torsades de pointe" and sudden cardiac death.