Phil Goodman
Well-Known Member
Unless I’m missing something there, it isn’t saying alcohol is the factor, but rather the other components in wine.
In this section, we will recapitulate the main preclinical evidence found in the literature for the effects of red wine and its components on brain health. We will specifically explore the primary mechanisms through which polyphenols exert their effects, starting with oxidative stress.
As already highlighted, oxidative stress is a relevant mechanism in several neurodegenerative diseases associated with cognitive disorders. In this context, compounds derived from red wine have shown a beneficial effect in several preclinical studies.
Starting from in vitro studies, red wine constituents and, in particular, flavonoids showed neuroprotective properties against oxidative stress, improving cell viability by acting on DNA replication and repair, increasing intracellular glutathione, directly lowering levels of reactive oxygen species (ROS), modulating several oxidative-stress-sensitive pathways, such as Nrf2, and preventing cardiolipin oxidation, mitochondrial fragmentation and dysfunction, and the influx of Ca2 [83,84,85,86,87,88,89].
Some in vivo data also confirm the antioxidant properties of red-wine-derived polyphenols, particularly anthocyanins. These compounds enhance glutathione levels and modulate several pathways associated with oxidative stress, such as the already-mentioned Nrf2 pathway [90,91].
However, it is important to note that in the study conducted by Gian C. Tenore and colleagues [92], red wine polyphenols were found to be associated with decreased expression of transthyretin in the murine choroid plexus. Transthyretin is a well-known neuroprotective factor and a sensor of oxidative stress.
Additionally, numerous preclinical studies, both in vitro and in vivo, demonstrated the neuroprotective efficacy of resveratrol against oxidative stress. Resveratrol has been shown to reduce glutamate toxicity in acute hippocampal slices by modulating ROS production, preventing mitochondrial dysfunction, and regulating glutamine synthetase activity [93].
Related to in vitro studies, the beneficial effects of resveratrol on oxidative stress have been confirmed in several models, including an acute oxidative stress model with Caenorhabditis elegans, where it also influenced lifespan [94].
The antioxidant activity of resveratrol in vivo appears to be primarily associated with the activation of several antioxidant enzymes, such as sirtuine 1 (SIRT1), heme-oxygenase-1, and peroxiredoxin-2 [95,96,97]. It is also noteworthy that in the article by N. Khodaie and colleagues [97], the antioxidative action of resveratrol via peroxiredoxin-2 is synergistically enhanced when combined with moderate concentrations of ethanol.
Other compounds derived from red wine have also been shown to be effective in preclinical studies in preventing oxidative stress, such as quercetin, procyanidin B2, and ethyl ferulate, with mechanisms similar to those outlined above [98,99,100,101].
Another mechanism by which compounds derived from red wine act in the context of neurocognitive diseases in the preclinical setting is neuroinflammation. In this regard, the vast majority of studies are specific to resveratrol. Resveratrol has been shown to reduce lipopolysaccharide (LPS)-induced cortical neurotoxicity in in vitro studies, also acting on microglia activation by inhibiting their production of pro-inflammatory cytokines and matrix metalloprotease and by also inhibiting prostaglandin E2 and NO production [102,103,104,105].
The effects of resveratrol on neuroinflammation are also confirmed in mouse models by acting on formyl peptide receptors 1 and SIRT1 [106].
Clinical evidence—In 2009, Robert Krikorian and colleagues [125] conducted one of the first controlled human trials, demonstrating how the daily consumption of Concord grape juice (CGJ), an extract from grapes, could improve learning memory in older adults with early memory decline. These results were linked with greater fMRI activation in the anterior and posterior regions of the right hemisphere [33], a result linked to a greater hemodynamic response and increased neuronal activity due to CGJ supplementation [23,126,127]. Similarly, the administration of a polyphenol-rich grape and blueberry extract has been shown to improve the speed of information processing and visuospatial learning [128,129].
Meanwhile there are studies which have done imaging of brains to show the actual atrophy.
Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study
Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function. Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015)...
Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15).
Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy).
Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were “alcohol dependent” according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data.
Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning.
Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall.
Not saying the study above proves it, and there have been other studies which indicate moderate drinking doesn’t cause the atrophy. But at the same time that doesn’t mean there are positive cognitive effects or neuroprotective benefits of alcohol. It just means that at best some people won’t be negatively affected on that front if they are careful about their drinking habits. But that could still leave concerns with regard to kidneys and liver, cancer, inflammation, etc.
