Health and Happiness May Be Found in a Daily Glass of Wine
Current
statistics show UK alcohol consumption to be on the decline, potentially due to
its frequently reported association with adverse health consequences. However,
it has been suggested that drinking in moderation may also offer protective
effects against chronic disease. A recent study by Horst et al. found
low-to-moderate and more frequent alcohol consumption to reduce risk of
diabetes [1].
After discussing these findings within the literature, focusing on risk of type
2 diabetes, cardiovascular disease and cognitive decline, it could be
concluded that following UK alcohol guidelines of drinking no more than 14
units of alcohol per week, but spreading this out across 5-7 occasions
and opting for wine more often than beer or spirits, may be appropriate
advice for the general population for drinking responsibly and optimising
health.
Alcohol is a widely consumed and legal
recreational drug, being drunk by 57% of adults in the UK [2]. It is produced by bacterial or yeast
fermentation of grains, fruit or vegetables, which yields carbon dioxide and
ethanol, the alcohol in standard beverages [3]. The amphiphilic nature of ethanol
means it can be passively absorbed across the epithelial membrane in the
stomach and small intestine. 10% of this is excreted in breath, sweat and urine [4], but the remainder is transported to
the liver for detoxification, primarily via the alcohol dehydrogenase pathway (ADH) converting
ethanol to acetaldehyde, and subsequently acetate [5]. However, excessive alcohol intake also induces the
microsomal ethanol oxidising system (MEOS).
Alcohol is preferentially metabolised
over other fuels due to its ease of conversion to acetyl coA and the absence
of hormonal regulation [6], stimulating storage of fats and
carbohydrates. However, products of alcohol oxidation also contribute to tissue
damage. Acetaldehyde, an intermediary in the process, is highly reactive and
toxic, forming adducts by interaction with proteins, lipids and DNA [7], impairing liver function [4]. Moreover, both the ADH pathway and
MEOS increase NAD+/NADH ratio, inhibiting the conversion of lactate
to pyruvate and malate to oxaloacetate, resulting in lacticacidosis and a lack
of precursors for gluconeogenesis [5]. It also reduces fatty acid oxidation, increasing glycerol
3-phosphate availability and enhancing re-esterification to triacylglycerols in
the liver by fatty acylcoA transferase [8]. Finally, acetyl coA produced from activation
of acetate in skeletal muscle and other extra hepatic tissues is directed towards
ketogenesis and fatty acid synthesis due to TCA cycle suppression, further
contributing to the pathogenesis of fatty liver disease [9] and hepatic failure.
Despite alcohol consumption being attributed to 5.1% of the overall global burden of disease [10], it has a great social significance, forming part of religious and cultural rituals, and being frequently shared with friends or relatives during a gathering or as part of a meal [11]. Additionally, moderate consumption is one component characterising a Mediterranean diet, a pattern frequently reported to reduce risk of chronic disease. A recently published study by Horst et al. that investigated the association between moderate alcohol consumption and diabetes made the headlines, where it was suggested that ‘drinking a few times a week could reduce diabetes risk’. This review will examine their findings within wider research to determine whether this claim is correct. Moreover, dietary advice should not be given solely focusing on reducing risk of one condition, so the effect of alcohol consumption on risk of cardiovascular disease (CVD) and dementia will also be discussed. This will allow for analysis of whether the current UK recommendations that advocate keeping alcohol consumption to a minimum and drinking no more than 14 units of alcohol per week [12] are appropriate and promote consumption of a quantity of alcohol for potential health optimisation.
Method
Study
population
Data from the Danish Health Examination
Survey (DANHES) 2007 to 2008 was used in which subjects aged ≥18 years completed
self-reported lifestyle, health and morbidity and further information was
obtained using the Danish citizen personal identification number.
Alcohol
drinking patterns
Lifetime abstainers were those who
reported never drinking alcohol and current abstainers were individuals who had
not drunk alcohol in the past year. For respondents who had drunk alcohol in
the last year, frequency of alcohol consumption and binge drinking were reported.
Average daily consumption of wine, beer and spirits was reported in ‘drinks’,
where one drink equalled 12g ethanol. Beverage-specific and overall weekly
alcohol consumption was calculated. Changes in alcohol consumption over the
past 5 years was questioned.
Diabetes
incidence data
The Danish National Diabetes Register provided
diabetes incidence data but it did not distinguish between type 1 and type 2.
Statistical
analysis
Participants were followed from baseline
until diabetes diagnosis, emigration, death, or end of study. Median follow up
time was 4.9 years. Risk of developing diabetes was estimated using an adjusted
Cox proportional hazards regression model. Analyses were conducted separately per
sex. Median values of alcohol intake were used as continuous variables to test
for a curvilinear association. Lifetime abstainers were excluded from the trend
analysis, and from those investigating the frequency of binge drinking and
beverage type.
A cubic spline model was used to examine
average weekly alcohol amounts, a log likelihood test was performed to test for
any interaction between drinking frequency and alcohol amount, and a
multivariate analysis excluding BMI was conducted to assess its effect on the
results.
Sensitivity analyses were performed,
excluding participants who had changed their alcohol consumption within 5 years
of baseline, selecting only participants aged 40 years or above at baseline to
bias towards type 2 diabetes, and excluding participants diagnosed by criteria
3 and 4 in the Danish National Diabetes Register.
Discussion
Holst
et al. found that light to
moderate alcohol consumption was associated with lower risk of diabetes
compared to abstainers [1]. This study did not differentiate
between type 1 and type 2 diabetes (T2D), however the relationship is consistent
within the literature findings regarding T2D risk in response to alcohol intake. It has been suggested that moderate alcohol enhances insulin
sensitivity [13] and reduces basal insulin secretion [14]. It could be that acetate modulates fat
oxidation and suppresses lipolysis [14], reducing release of NEFAs to
peripheral tissues, which causes insulin resistance [15]. However, studies in mice showed the
increase in insulin sensitivity to be independent of body fat alteration [16], so there is potential for other
physiological mechanisms to also exist. An increase in adiponectin in response to
alcohol consumption has said to explain 25-30% of the inverse association with
T2D risk [17] as adiponectin increases glucose uptake
and fat oxidation in muscles [18], the latter of which reduces lipid
accumulation and insulin resistance. In addition, there is as much as 45%
inhibition of gluconeogenesis in individuals consuming alcohol [16] as a result of the increase in NADH
from ethanol metabolism and the effects of adiponectin [19]. Consequently, potential for
hyperglycaemia, a major characteristic of T2D, is reduced. Finally, the alcohol
associated decrease in fetuin-A level [20], a hepatic glycoprotein involved in the
regulation of insulin signalling pathways, may aid in maintaining glucose
metabolism to reduce risk of T2D [21].
Although
moderate alcohol consumption has been shown to reduce risk of T2D compared to
abstention, a U-shaped relationship exists, such that there is also an
increased risk of T2D with heavy drinking. Koppes et al. reported a 30% reduced risk for subjects consuming 6-48g
alcohol/day compared to both non-consumers and those drinking ≥48g/day [22]. This may be due to the toxic effects
of alcohol on pancreatic islet cells, inhibiting insulin secretion [13] and subsequently decreasing tissue glucose uptake. It
is important to consider that the non-drinking group may not be homogeneous if
it includes ‘never’ and ‘former’ drinkers as ‘former’ drinkers may be likely to
have poorer health due to abstention in response to diagnosis of chronic
disease [23]. This could result in overestimation in
the degree of risk reduction for moderate consumption and the increase in risk
for non-consumers and heavy drinkers in comparison. Additionally, weak
confounder adjustment may result in the reporting of a greater risk reduction
for moderate consumption as moderate drinkers often have several clinical,
social and biological characteristics that favour a superior health status [24]. Nonetheless, the physiological
plausibility previously discussed suggests that moderate consumption of alcohol
may still offer beneficial effects on T2D risk.
Studies
considering the association between T2D risk and alcohol consumption suggest a
great variation in optimum quantity to consume. Li et al. suggested alcohol
at <30g/day to be associated with lower risk of T2D [25], Wei et al. the lowest incidence at 8-17g/day [13] and Carlsson et al. 30% reduced risk at 5-30g/day [26]. A standard drink in the UK is
generally considered to contain 12g alcohol, hence this equates to approximately
1-2 drinks/day. However, uncertainties within individual studies and the impact
of publication bias on meta-analyses may not allow for absolute recommendations
to be made. In particular, there is potential for bias resulting from
misclassification of subjects for both exposure and disease due to
under-reporting of alcohol intake [26] and its variability over time [27], as well as the frequent use of
diabetes self-reporting meaning undiagnosed cases would not be detected [17].
As
with the findings by Holst et al. [1], there is vast evidence to suggest that
there may be benefits to sex specific guidelines due to differences observed
between men and women. In general, the protective effect of alcohol consumption
in women occurs at a lower level of intake [25][28], which is likely due to the differences in ethanol
metabolism and body composition [29], resulting in higher peak blood alcohol levels in women
than men [6]. Nonetheless, it has been suggested
that there is a stronger association within women, which may potentially be due
to drinking pattern and type of beverage consumed [29]. Most notably, women are frequently wine drinkers. Wine is
often reported to offer a greater reduction in risk of T2D [30][31], with Huang et al. finding a 15% reduced risk from
wine consumption but no significant association when considering beer or
spirits [32]. Wine contains high quantities of
polyphenols. Flavonoid compounds, which have anti-inflammatory and antioxidant
properties may enhance insulin sensitivity [33], and non-flavonoid compounds such as resveratrol
may improve insulin signalling [34]. Moreover, it has been suggested that
red wine may be more favourable than white wine due to its maceration with the
skin of the grape resulting in a 10-fold higher polyphenol content [35], and the tannic acid it contains reducing
post prandial glucose response [31]. The lack of significant evidence for a
similar protective effect for beer consumption could be questioned due to it
also being a source of polyphenols [35]. However, it may be that its high
carbohydrate content attenuates any risk reduction from such compounds [31].
The
alcohol consumption quantities discussed tend to be specified as g/day, as
opposed to the traditional guidelines of alcohol intake per week. Holst et al. concluded that more frequent
alcohol consumption was associated with lower risk of diabetes independent of
amount of alcohol consumed [1], suggesting that 1-2 drinks/day may
confer greater health benefits than drinking the same amount of alcohol on
fewer occasions. This suggests that the alcohol induced improvement in insulin
sensitivity may be transient, potentially only lasting up to 24 hours before
returning to baseline [36]. Additionally, chronic alcohol
consumption saturates hepatic detoxification enzymes and induces CYP2E1
activity, part of MEOS, resulting in formation of reactive oxygen species, which are implicated in cancer
development [37]. Consequently, excessive alcohol
consumption should be avoided. The effect observed may, however, be confounded
by more frequent alcohol consumers drinking their beverage as part of a meal,
which would reduce the rate of alcohol absorption due to the retardation of
gastric emptying [6].
Nonetheless, promotion of more frequent consumption may encourage a more healthy
relationship with alcohol, reducing the social and economic burden of binge
drinking, and potential chronic health effects.
The
study by Holst et al. only considered
the effect of moderate alcohol consumption on risk of diabetes [1] but recommendations regarding alcohol
consumption should not be made based on evidence relating to one chronic
disease. However, it is also common for associations between moderate alcohol
intake and risk of cardiovascular disease to be reported, partially due
to the increase in adiponectin [38], which has anti-inflammatory activity. Further
to this, an umbrella shaped association has been observed between alcohol and
HDL-cholesterol concentration [39], where moderate alcohol increases HDL
cholesterol and hence the removal of lipid deposits in blood vessels, reducing
formation of atherosclerotic plaques [35]. A longer lag time to LDL oxidation has
also been observed following wine consumption [40], suggesting the beneficial effects of
antioxidant polyphenols. These compounds may also contribute to peripheral
vasodilation and inhibition of platelet aggregation due to reduced arachidonic
acid metabolism and synthesis of thromboxane A2 [41]. Finally, heavy alcohol intake
decreases nitric oxide (NO) bioavailability, adversely affecting vascular
homeostasis, yet is thought to increase its release from the endothelium [40].
Conversely,
alcohol has been hypothesised to enhance progression to neurodegenerative
disease [42] as a consequence of damage to brain
structure, metabolite toxicity, electrolyte imbalance or thiamine deficiency [43]. Although there are some
inconsistencies within the literature [44], there are indications that low and
moderate consumption may in fact offer neuroprotective effects, with potential
risk reductions of greater than 30% for Alzheimer’s disease and overall
dementia [42]. This is thought to be due to its
antioxidant content, the interaction with protein kinase C, a cognitive kinase
linked to control of memory and learning, and down regulation of nitric
synthase, reducing NO and its neurotoxic effects [43]. However, the demographic of greatest
interest when considering cognitive decline would be older adults. As lower
quantities of alcohol have greater effects in the elderly due to a decrease in
body water and lean body mass with age [42] it could be suggested that
age specific, as well as sex specific, recommendations may be appropriate to
promote alcohol intake within the beneficial range and limit risk of neurotoxic
effects.
Impacts
The wider literature has reinforced the results
of the study by Holst et al., who observed moderate alcohol consumption to reduce risk of diabetes [1]. Recommendations regarding inclusion of
specific foods or nutrients in the diet should not be made if they are likely
to have adverse health impacts; focusing solely on reducing risk of one chronic
disease may bring another to the forefront. Therefore, the effect on risk of
CVD and dementia have also been discussed, finding that moderate alcohol intake
may offer similar protective effects. Despite this conclusion, issues arise
when defining a ‘moderate’ level due to the great interindividual variation in
body composition and metabolic rate.
Both the frequency of drinking and
beverage type have been highlighted as important when considering the magnitude
of protection observed. The potential transient nature of the physiological
effects means it may be of most benefit to spread alcohol consumption
throughout the week, consuming a small amount each day. Not only may this offer
the greatest health benefits, but it would also reduce the risk of experiencing
negative effects from excess consumption such as toxicity, induction of MEOS
and symptoms of a hangover. Additionally, wine has been shown to be more
protective than spirits and beers due to its antioxidant content, suggesting this
beverage should comprise the greatest proportion of alcohol intake.
To conclude, if attempting to generalise
the literature findings for the general population it could be said that the
current UK guidelines, which advocate drinking up to 14 units of alcohol per
week, may be appropriate. This is where 1 unit is equal to approximately 8g of
alcohol. It could be of greatest benefit to spread this out over 5-7 days
which, in practical terms, equates to no more than one 175ml glass of wine, 1
pint of beer or 50ml spirits per day [45]. However, this should not be taken as
absolute recommendations as the large amount of uncertainty and potential for
bias within the literature due to the nature of the studies means that
protective effects may be observed at lower levels of consumption. It could
therefore be said that overall advice should be to drink responsibly, limiting excessive
or heavy drinking. Moreover, it seems that drinking an alcoholic beverage with a meal or
during a social occasion should not be discouraged as, in addition to the enjoyment it provides, it may have long term health
benefits and reduce risk of chronic disease.
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