Alcohol, Health & Longevity: How Much is Too Much?

The trademark social effects of alcohol result when it binds and activates the main inhibitory receptor in our central nervous system – the GABA(A) receptor – and the effect is one that peoples around the world have embraced as part of their customs and cultures. However, the metabolism of ethanol – the active ingredient in alcoholic drinks – produces a number of toxic byproducts that have deleterious effects and require elimination from the body, primarily by the liver. Excess consumption amplifies these toxic effects and is an established risk factor in a number of life-limiting non-communicable diseases (NCDs) including liver cirrhosis, stroke, cardiovascular disease and many cancers.

Alcohol also acts as a depressant in the central nervous system and so can have knock on effects on mental health. Furthermore, its high caloric content can contribute to weight gain, obesity [Albani V, et al., 2018] and type 2 diabetes [Baliunas DO et al., 2009]. The World Health Organisation attribute 2.6 million deaths each year to excess alcohol use. That is approximately 50% more than the global death count from COVID-19 in 2020, and is a recurring annual total.

In this article, we examine the peer reviewed scientific evidence for unbiased studies on alcohol consumption and its health effects. To this end, we ask a number of key questions: How does our body process alcohol? What NCDs does it contribute to and how? Are there any beneficial health effects seen with alcohol? How does it affect longevity and ageing? Ultimately – how much is too much?

HOW DO OUR BODIES PROCESS ALCOHOL: WHAT ARE THE PHYSIOLOGICAL EFFECTS?

Alcohol is readily absorbed in the gastrointestinal tract and crosses membranes by diffusion to enter the blood stream. Approximately 20% is absorbed in the stomach and 80% in the small intestine, from where it is distributed by diffusion and blood flow to all our tissues and fluids based on their relative water content. Alcohol crosses the blood-brain barrier for example. Drinking on an empty stomach results in faster absorption into the blood stream, via the small intestine, such that blood alcohol levels peak at a faster rate.

The form of alcohol contained in beverages is ethanol and, once absorbed into the body, it is used as an energy source in place of glucose, with metabolism taking place predominantly in the liver (but also in the pancreas, stomach and brain). It is broken down by enzymes and mutations in the genes for these enzymes mean that some individuals process alcohol more quickly than others.

The main initial byproduct of alcohol metabolism is acetaldehyde, a highly reactive toxin that causes tissue damage and the formation of molecular reactive oxygen species (ROS). Acetaldehyde is then further broken down into a less toxic compound, acetate. Chronic alcohol consumption leaves excessive acetaldehyde residue in our bodies causing toxicity across multiple pathways.

Alcohol consumption decreases production of anti-diuretic hormone in the pituitary gland resulting in increased urination and dehydration the following day. Alterations in neurotransmitter levels can be observed in several brain regions following drinking, including in GABA and glutamate [Fliegel et al., 2013] resulting in a number of potential positive and negative impacts on mood. On average it takes our bodies one hour to breakdown and eliminate 8 g of alcohol.

AN EVIDENCE BASED LOOK AT THE RISKS OF CHRONIC DISEASE DEVELOPMENT

CANCER

The International Agency for Research on Cancer (IARC-WHO group) has listed alcohol as a carcinogen for many site-specific cancers for over two decades. The latest to be added in 2010 were colorectal and female breast cancer due to mounting research evidence (IARC Working Group, 2010).

Looking in more detail at the scientific literature, several peer-review publications, have linked all types of drinking (from light to heavy) as a risk factor for several cancers in a dose-dependent manner. In a meta-analysis of 572 studies examining 23 types of cancer the most significant increase was observed for oesophageal (squamous cell carcinoma variant) and oral/pharyngeal cancer at ~five-fold (4.95 and 5.13 respectively) for heavy drinkers. This group also saw a 1.6 times increased risk for breast cancer.

A prior large-scale analysis of 53 epidemiological studies for breast cancer incidence in women has shown that the relative risk of breast cancer increased by 7% for each additional 10 g per day intake of alcohol [Hamajima N, et al 2002]. Another recent study in Australia, covering 225K+ individuals stipulated that drinking in a concentrated way, over 3 days, versus spreading the same amount over 4-7 days could increase breast cancer risk [Sarich, P et al., 2021].

CARDIOVASCULAR DISEASE

There are numerous studies that have evaluated the low-risk limits for developing cardiovascular disease (CVD) and conversely, potential cardio-protective effects of moderate drinking, with some conflicting results. For example, in a 2018 combined analysis of close to 600K current drinkers, published in The Lancet, life-limiting effects were observed for CVDs in a dose-dependent manner with increasing alcohol intake. These included incidence of stroke (+14%), fatal hypertensive disease (+15%), fatal aortic aneurysm (+24%) with each 100 g of additional alcohol consumed a week above a low baseline of 25 g.

The question has also been posed as to whether there is any evidence for cardio-protective effects at low intake levels. There have been large scale studies suggestive of a protective effect [E.g. Bell, S et al., 2017]. However, there is very strong evidence to the contrary. For example, a large scale meta-analysis of close to 4 million individuals has concluded there is no benefit to mortality or protective effect to drinking at a moderate to low level (1.3-24.9 g ethanol per day) [Stockwell et al., 2016]. Furthermore, both this and other research has specifically challenged the outcomes of studies showing the protective effects of moderate alcohol intake [Knott CS et al., 2015; Burton R, Sheron N et al., 2018]. They cite inherent bias in research to date, including the inappropriate selection of reference groups and confounding factors.

DEPRESSION AND MOOD

Alcohol elevates mood during consumption through increased firing in the brain reward circuits (dopamine pathways), and opioid release [Turton, S et al., 2020]. However, in the long term, it has been shown to decrease activity in the same neurons and disrupt and impair serotonin signalling [Turton, S et al 2020; Le Marquand D et al., 1994].

There is evidence that heavy alcohol use is comorbid (co-occurs) with psychiatric disorders. A study by Palzes et al., in  2020 in 2.7 million patients showed those with depression and anxiety were more likely than other psychiatric groups to be exceeding the weekly US limit for alcohol (> 196 g/week for men or >98 g/week for women). Several studies note that alcohol consumption, anxiety and depression can have a bidirectional relationship.

Furthermore, whilst alcohol has sedative effects and can make you fall asleep quickly, it is a significant disruptor of sleep. It decreases slow wave (deep sleep), and causes the shortening of sleep cycles so that you awaken early [Thakkar MM et al., 2015]. Both of the latter effects can lower mood, increase fatigue and contribute to hangover symptoms.

IMMUNE FUNCTION

Elevated blood concentrations of ethanol have been shown to interfere directly with the functioning of the innate and adaptive immune response. The former is cell-mediated and is a first line of defence against pathogens, and the second is antibody-mediated. In acute alcohol exposure, the ability of white blood cells to recognise key markers of bacterial pathogens is disrupted, and can result in an increased susceptibility to disease [Szabo G, Saha B. 2015].

Binge drinking, consuming between 57-74 g (~7-9 UK units) of alcohol, was shown to immediately suppress innate immunity and overactive it hours later [Afshar et al., 2015]. Other research shows that chronic intake reduced T-cell numbers, accelerated viral infection and impaired wound healing [Molina, PE et al 2010].

Several research analyses show a disruption in the gut microbiome after alcohol consumption, this includes overgrowth and dysbiosis or increase in ‘bad’ Vs ‘good’ bacteria. This has been linked to liver disease progression [Hartmann P et al., 2015]. The gut may also become more ‘leaky’ to pathogens after chronic intake. [Barr, T. et al., 2017; Sureshchandra, S. et al., 2019].  The only positive correlation seen in the gut was an increase in beneficial Bifidobacteria after a limited intake of red wine (max 272 ml). A de-alcoholized version also had the same effects which were attributed to polyphenols, also found in brightly coloured fruits and vegetables [Queipo-Ortuño MI, et al., 2012].

In the brain, chronic drinking has been shown to activate the innate immune system persistently, so it enters a state of inflammation, which can have implications for cognitive function, the development of dementia , Alzheimer’s and neurodegeneration [Coleman LG Jr, Crews FT. 2018].

LIVER DISEASE

The liver is the primary organ responsible for the metabolism of alcohol and chronic exposure impacts the liver most directly potentially leading to alcoholic liver disease. The first stage is steatosis (fatty liver), which is reversible but which can also progress to hepatitis and cirrhosis (fibrosis), and finally fatal liver failure. Cirrhosis has been cited as the leading cause of death due to alcohol among adults in Europe. Women have been shown to be more susceptible than men. In addition, obesity or a diet high in fat are also shown to increase the risk levels  [European Association for the study of the liver.].

Research sources state that 30-50 g (2-3 standard US drinks or 3.75-6.35 UK units) of alcohol per day over 5 years is enough to cause liver disease [Patel R, Mueller M. 2020]. 

HOW DOES ALCOHOL AFFECT LONGEVITY AND AGEING?

A large scale study looked at the effects of adopting 5 low-risk lifestyle-related factors on longevity in US adults, over a period of 30+ years, of which alcohol consumption was one factor [Li Y et al., 2018] concluded that, when all 5 lifestyle factors were adopted including moderate alcohol consumption (5-14.9g per day for women, or 5-29.9 g per day for men), life expectancy could increase by 12-14 years. In another 2018 study, primarily examining CVD risks, Wood and colleagues concluded that the threshold for the lowest risk of all-cause mortality in 600K individuals was about 100g of alcohol a week.

In a recently published study in the Netherlands [van den Brandt et al., 2020], 7,807 individuals born in 1916-1917, were asked to complete lifestyle questionnaires when they reached between 68-70 years of age. Those who reached the age of 90 were revisited. The study concluded that the highest probability of reaching 90 years of age was found for those drinking 5-15 g alcohol/day (35-105 g/week). Although not as significant, the risk estimates showed a deleterious effect of binge drinking on longevity, that suggests it should be avoided.

WHAT ARE THE SUGGESTED ALCOHOL CONSUMPTION LIMITS TO LIMIT HEALTH RISKS?

Low-risk limits recommended for alcohol consumption vary substantially across individual national guidelines. They are usually set in grams, ‘standard drinks’ or ‘units’ of alcohol depending on the part of the world and, in addition to volume, alcoholic strength is the other main element to take into account when measuring consumption. As what constitutes a unit in the UK, or a standard drink – a type of measure used in EU, US and Australian guidelines can differ – we state recommendations in grams for clarity. [NB: Conversions between international units and differences in standard drinks are available at the end of this article]

In the UK, the limit is currently set at a maximum of 112 g a week (equivalent to 14 UK units), with designated drink-free days advised. Daily recommendations state that women should not consume more than 16-18 g a day (2-3 UK units) and men 18 – 24 g a day (3-4 UK units).

In continental Europe, recommended limits can be much higher. For example, Spain has one of the highest upper limits of 168 g for women and 280 g for men. In France, the suggested limits were 140 g for women and 208 g for men, but have recently been drastically reduced to two drinks a day, or a maximum of ten drinks per week equating to 100 g.

In the US, health bodies state that men should not exceed two ‘standard drinks’ a day and women a single drink, where one standard drink equates to a bottle of 5% strength beer or a medium glass of wine (5 oz or 150ml). This equates to a weekly limit of 98 g a week for women and 196 g for men. Australian guidelines recommend no more than 140 g a week for both men and women.

SO HOW MUCH IS TOO MUCH?

It is clear that there is no definitive amount for risk thresholds for alcohol consumption, with different conclusions being drawn based on the specific disease outcome being studied, as well as other study parameters. Moreover, individual responses to alcohol consumption vary based on personal factors. In fact, the WHO states there is no safe daily intake level of alcohol, citing the best option is not to drink at all. However, when reviewing the scientific literature, we can make reasonable inferences given the research to date.

The risk of all-cause mortality likely rises from >100g of alcohol a week [Wood AM, et al., 2018]. This corresponds with the 105g limit in a Netherlands-based study for longevity [van den Brandt et al., 2020]. It is interesting to note, however, that 100g per week of alcohol is below nearly all national guidelines for current alcohol consumption, apart from the US recommended limit for women. 

Numerous studies point to a daily tipping point of 30 g a day, after which numerous deleterious effects including cardiovascular outcomes, cancer development and liver disease, become evident. Cancer risk can be dose dependent with the worst outcomes in those with heavy drinking at >50g a day. In the case of depression and mood disorders, thresholds of >196 g a week for men and >98g a week for women have been associated with poor outcomes [Palzes et al., 2020] More generally, a large body of evidence indicates that binge drinking should be avoided and is harmful to health and longevity outcomes.

Combining these weekly and daily suggestions, there seems to be some scientific consensus that 100-105g per week is an important threshold and that a daily intake of no more than 15-25 g per day, allowing for dedicated non-consumption days, is a reasonable limit to adopt for health and longevity purposes. These suggestions are generic and do not consider personal tolerances. Moreover, the specific recommendation of 15-25 g per day, within a 100-105 g week, has not been independently corroborated in specific studies.

CONCLUSIONS

Numerous high quality studies show that above a certain threshold alcohol consumption increases the incidence of several chronic and life-limiting diseases. Whilst the threshold is likely to vary from person to person, a reasonable weekly target, if alcohol is consumed at all, is to adopt is 105 g, whilst avoiding concentrated drinking in excess of 25 g per day. In UK terms, these limits practically correspond to 13 units per week, limiting daily intake to 3 units, and in the US to 7 standard drinks a week — with no more than 2 per day. Many people exceed these limits and the national guidelines of many countries are higher, which might suggest that national limits are rather liberal. However, the structure limits we identify are the limits at which, per the scientific literature reviewed, health risks are elevated across a wide section of subjects.  

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Conversions explained

1 UK unit = 8g alcohol

1 EU standard drink = 10g alcohol

1 US fluid oz = 29.57 ml (~30 ml)

1 US standard drink = 14g of alcohol

1 Australian standard drink = 10g of alcohol

1 UK pint = 568 ml

105 g/week is equal to:

13 UK units

6 (5.6 to be exact) medium glasses (175 ml) of wine (13.5%)

4 (3.9 to be exact) large glasses (250 ml) of wine (13.5%)

6.5 pints of low-strength beer (3.6%)

4.5 pints of strong beer (5.2%)

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Note from the author: Alcohol use can cause a huge variety of other issues, including intoxication related injuries, drink drive accidents, violence, aggression, causing harm to the unborn foetus, which are beyond the scope of this article. Drinking responsibly is a critical personal obligation.

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