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Red wine polyphenols and their potential to target brain pathology in Alzheimer’s and Parkinson’s disease

In the August edition of Frontiers in Nutrition, a review summarises the current knowledge about the major classes of red wine polyphenols and places into perspective their potential to be considered as nutraceuticals to target neuropathology in Alzheimers disease and Parkinson’s disease.

Led by Mario Caruana of the Centre for Molecular Medicine and Biobanking at the University of Malta, the study report was part of a series called ‘Healthpromoting effects of traditional Mediterranean Diets.’

The authors state that “Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common age-related neurodegenerative disorders. Although AD and PD have different clinical and pathological features the causal mechanisms at the molecular level appear to overlap considerably. Among the various lifestyle factors that may prevent or slow age-related neurodegenerative diseases, epidemiological studies on moderate consumption of red wine, especially as part of a holistic Mediterranean diet, have attracted increasing interest”.

Epidemiological studies have found that a high adherence to the mediterranean diet is associated with a reduced risk of developing mild cognitive impairment (MCU) and AD and a reduced risk of progressing from MCU to AD. Other research suggest that light to moderate drinking (1-3 drinks a day) is significantly associated with a lower risk of any dementia and vascular dementia in individuals over 55. A further study found that the lowest odds for dementia were among older adults whose weekly consumption of alcohol was between 1 and 6 drinks, irrespective of beverage type. Specifically examining the role of red wine, a cohort study, the Copenhagen City Heart Study found that monthly or weekly wine intake among over 65s was associated with a lower risk of dementia, that was not found for other alcoholic drinks. Despite the overall positive association between red wine and cognitive health, it is still debatable as to whether people should start drinking or increase wine consumption to avoid dementia. More prospective cohort studies are needed to strengthen the evidence, the authors argue.

For risk of PD, a 2012 study found that a habitual dietary intake of flavonoids was protective. Males in the highest percentile of total flavonoid intake had a 40% lower risk of PD and intakes of anthocyanins from flavonoid-rich foods, including red wine were especially associated with a lower PD risk. However, most epidemiological studies do not support an association between alcohol or wine consumption and risk of PD. Red wine is particularly rich in specific polyphenolic compounds that appear to affect the biological processes of AD and PD, including flavonoids such as quercetin, myricetin, catechins, tannins, anthocyanidins, resveratrol, and ferulic acid.

There is now a consistent body of in vitro and in vivo data on the neuroprotective effects of red wine polyphenols (RWP) showing that they do not merely possess antioxidant properties, but may additionally act upon, in a multi-target manner, the underlying key mechanisms featuring in both AD and PD. These molecular mechanisms include (i) anti-inflammatory activities and antioxidant capacity, including free radical scavenging and metal chelation (ii) modulation of cell signalling pathways and (iii) antiamyloid action through direct binding with specific amyloidogenic proteins. “This wide range of actions highlights a key aspects that have repeatedly emerged from studies on natural polyphenols, including wine polyphenols: a remarkable ability to simultaneously and synergistically modulate multiple molecular targets, suggesting a greater potential for therapeutic efficacy in the complex pathogenesis of AD and PD,” the authors write.

The review explores the issue of red wine polyphenol bioaccessibility and bioavailability and conclude: “We have to be cautious in extrapolating findings from in vitro studies to in vivo situation, since much of existing in vitro data have utilised non-physiological concentrations of red wine polyphenols and used the original molecule instead of the in vivo metabolites produced upon digestion and of metabolic processing. Indeed, much of the recent data have consistently shown that the biological activities of metabolites may differ from the parent compound.”

More convincing large-scale clinical trials utilising red wine polyphenols are needed together with suitable biomarkers to objectively assess a risk reduction of AD and PD. Clinical intervention trials must be prioritised to support evidence derived from in vitro and in vivo studies, the authors state.

Source: Putative Role of Red Wine Polyphenols against Brain Pathology in Alzheimer’s and Parkinson’s Disease. Mario Caruana, Ruben Cauchi and Neville Vassallo. Front. Nutr., 12 August 2016. open access.

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