04 May 2020 In Phenolic compounds

Deficits in the cerebral microcirculation contribute to age-related cognitive decline. In a pilot study of postmenopausal women, we found that supplementation with a low dose of resveratrol, a phytoestrogen, for 14 weeks improved cerebrovascular and cognitive functions.

We have since undertaken a larger, longer term study to confirm these benefits. Postmenopausal women aged 45-85 years (n = 129) were randomized to take placebo or 75 mg trans-resveratrol twice daily for 12 months. Effects on cognition, cerebral blood flow, cerebrovascular responsiveness (CVR) and cardiometabolic markers (blood pressure, diabetes markers and fasting lipids) were assessed. Compared to placebo, resveratrol improved overall cognitive performance (P < 0.001) and attenuated the decline in CVR to cognitive stimuli (P = 0.038). The latter effect was associated with reduction of fasting blood glucose (r = -0.339, P = 0.023).

This long-term study confirms that regular consumption of resveratrol can enhance cognitive and cerebrovascular functions in postmenopausal women, with the potential to slow cognitive decline due to ageing and menopause.

04 May 2020 In Phenolic compounds

SIRT1 protects against several complex metabolic and ageing-related diseases (MARDs), and is therefore considered a polypill target to improve healthy ageing. Although dietary sirtuin-activating compounds (dSTACs) including resveratrol are promising drug candidates, their clinical application has been frustrated by an imprecise understanding of how their signals are transduced into increased healthspan.

Recent work indicates that SIRT1 and orthologous sirtuins coactivate the oestrogen receptor/ER and the worm steroid receptor DAF-12. Here they are further shown to ligand-independently transduce dSTACs signals through these receptors. While some dSTACs elicit ER subtype-selectivity in the presence of hormone, most synergize with 17beta-oestradiol and dafachronic acid respectively to increase ER and DAF-12 coactivation by the sirtuins.

These data suggest that dSTACs functionally mimic gonadal steroid hormones, enabling sirtuins to transduce the cognate signals through a conserved endocrine pathway. Interestingly, resveratrol non-monotonically modulates sirtuin signalling, suggesting that it may induce hormesis, i.e. "less is more".

Together, the findings suggest that dSTACs may be informational molecules that use exploitative mimicry to modulate sirtuin signalling through steroid receptors. Hence dSTACs' intrinsic oestrogenicity may underlie their proven ability to impart the health benefits of oestradiol, and also provides a mechanistic insight into how they extend healthspan or protect against MARDs.

04 May 2020 In Liver Disease

Background/Aims: Multiple meta-analyses and observational studies have reported that alcohol is a risk factor for liver cancer. However, whether there is a safe level of alcohol consumption remains unclear. We performed a systematic review and meta-analysis of the correlation between low-level alcohol consumption and the risk of liver cancer.

Methods: Nested case-control studies and cohort studies involving the general population published prior to July 2019 were searched. In total, 28 publications (31 cohorts) with 4,899 incident cases and 10,859 liver cancer-related deaths were included. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

Results: Compared with those with low levels of alcohol consumption, moderate and heavy drinkers (>/=1 drink/day for females and >/=2 drinks/day for males) had pooled ORs of 1.418 (95% CI, 1.192 to 1.687; p<0.001) for liver cancer incidence and 1.167 (95% CI, 1.056 to 1.290; p=0.003) for liver cancer mortality. The pooled OR for liver disease-related mortality for those with more than low levels of alcohol consumption was 3.220 (95% CI, 2.116 to 4.898; p<0.001) and that for all-cause mortality was 1.166 (95% CI, 1.065 to 1.278; p=0.001). The sensitivity analysis showed that none of the studies had a strong effect on the pooled OR. The Egger test, Begg rank correlation test, and the funnel plot showed no overt indication of publication bias.

Conclusions: Continuous consumption of more than a low-level of alcohol (>/=1 drink/day for females and >/=2 drinks/day for males) is related to a higher risk of liver cancer.

04 May 2020 In General Health

Understanding how dietary nutrients modulate the gut microbiome is of great interest for the development of food products and eating patterns for combatting the global burden of non-communicable diseases.

In this narrative review we assess scientific studies published from 2005 to 2019 that evaluated the effect of micro- and macro-nutrients on the composition of the gut microbiome using in vitro and in vivo models, and human clinical trials. The clinical evidence for micronutrients is less clear and generally lacking.

However, preclinical evidence suggests that red wine- and tea-derived polyphenols and vitamin D can modulate potentially beneficial bacteria. Current research shows consistent clinical evidence that dietary fibers, including arabinoxylans, galacto-oligosaccharides, inulin, and oligofructose, promote a range of beneficial bacteria and suppress potentially detrimental species.

The preclinical evidence suggests that both the quantity and type of fat modulate both beneficial and potentially detrimental microbes, as well as the Firmicutes/Bacteroides ratio in the gut. Clinical and preclinical studies suggest that the type and amount of proteins in the diet has substantial and differential effects on the gut microbiota.

Further clinical investigation of the effect of micronutrients and macronutrients on the microbiome and metabolome is warranted, along with understanding how this influences host health.

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