Risks of Alcohol

The understanding of the risks involved in drinking alcohol has changed over time. This blog is on the current understanding of those risks.  Most of us probably have the general view that one to two drinks a day won’t hurt us too badly and may even do us some good.  Until recently, this was the general view of the USDA with their dietary recommendations.  In the last edition of those guidelines, the recommendations were no more than two drinks a day for men and one for women. The latest version now only recommends one drink per day for everyone.  Why the change, and are we headed downhill in our recommendations?

I have been looking over the latest research findings and the resulting recommendations and I am going to try to make some sense of them.  In the process, I am going to explain some of the pitfalls of research in this area and try to paint a more complete and nuanced picture of the landscape here.  I hope this helps us determine when, what, and how is a safe way to indulge in this enjoyable social custom.  So, drink up.

First, let’s start with the obvious and most painful lesson here.  Alcohol is addictive.  It has ruined countless lives, families, and fortunes over the years.  Things got so bad in this country that at one point we actually banned the stuff.  Obviously, that did not work and we shortly “unbanned” it.

A quick lesson here—What is a “drink”?  Typically, we define a drink as one can of beer, about 5 oz of wine, or 1.5 oz of hard liquor.  Each of these contain about 14 g of alcohol.  Heavy drinking is defined as more than 4 drinks a day for men and 3 for women or more than 14 per week for men and 7 per week for women.  A blood alcohol level above the maximum allowed (0.08%) can result from drinking about 4 drinks in a 2-hour period for women or 5 drinks for men.  This leads us to the clearest mortal danger from alcohol and that is drinking and driving.  About 10,000 people a year are killed on the roads in the US from drunk drivers.  That’s about 30 people a day.  So, before we get to the long-term disease effects of alcohol, please remember that alcohol is powerfully addictive and dangerous.

Before getting started, here is some full disclosure.  My wife and I probably consume somewhere near the recommended limit of about 2 drinks a day.  Since retiring I have enjoyed making a mixed drink for us a couple times a week.  We enjoy red wine with dinner.  We occasionally will have a beer after a hot day working in the garden.  The major problem that I see from this is that it is increasingly hard to stick to a weight loss diet, given all the calories in those drinks.

My interest, and I hope the interest of my readers (if you are still reading), is in the long-term effects of that glass of wine or a mixed drink at dinner.  Some say the benefits outweigh the risks.  Let’s examine this in some detail with particular emphasis on what has changed lately.  We will look at this one disease at a time.  So, grab a beer and let’s talk.

Mortality

And why not start with the end game, death, the Big D.  A thoughtfully conducted recent meta-analysis (a study of studies) on alcohol and the Big D showed no overall effect.[1]  This may seem surprising given what we know about alcohol-related traffic accidents, alcoholism, and other acute (relatively quick) deaths from alcohol.  A lot of data was collected, and it was indeed found that excessive intakes are associated with increased risk of death of about 20% but moderate intakes saw no overall effect.  There are certain complexities here that we will get into in a minute.

Cancers

Cancer is really a family of diseases that all involve uncontrolled cell growth.  The evidence here is   strong, but the overall effect is rather modest.  Globally, alcohol intake accounts for about 4% of cancer deaths.[2]  Intake contributes most significantly to oral cancer (20% of cases), pharyngeal cancer (22%), esophageal cancer (32%), liver cancer (17%), laryngeal cancer (15%), and breast cancer (4%).[2]  For people in our country, the cancer to be most concerned about is breast cancer; despite its low percent, the overall rate is high and so the alcohol effect is high.  A dose effect is also evident, the more alcohol, the higher the risk.  Other countries with higher rates of those other cancers should also be paying attention.  As best as the data will show us, there is no lower and safe limit for alcohol and breast cancer.  Therefore, if you have a high risk for breast cancer (multiple family histories, etc.) then this would be something to be concerned about.

Dementia

A meta-analysis in 2021 showed puzzling results when combining the findings from 13 studies of alcohol and Alzheimer’s disease.  When comparing drinkers vs non-drinkers, they found that drinking appeared to reduce the risk of Alzheimer’s disease by 32%.  But when they summarized the data on drinking level and overall dementia, they found only limited protection and only in women at the usual recommended levels.[3]  Based on this and other complexities that I will explain below, I would suggest that we not expect much help from alcohol in preventing dementia.

Hypertension

I had always thought and heard that a little alcohol helped lower blood pressure a little.  Apparently, I was wrong.  When a really comprehensive look at this was done in 2020, the overall results were that for each increase in 10 grams of alcohol daily, the risk of hypertension increases about 7%.[4, 5]  This is made more complex since men seem to have about a 14% increased risk and women have no increased risk.  In addition, Blacks have a higher risk than Whites and Asians.  That leads that an interesting start of a bad joke— “A Black man and an Asian women went into a bar…”

Cardiovascular Diseases

This is where it starts to get complicated. [6]  Typical studies of alcohol intake and disease will start by asking a group of people how much and what they drink.  Then those folks are followed for many years to see what diseases they get and die from.  This may seem straightforward but has problems.  Usually the “control group” are the teetotalers who never drink.  However, these folks are different in many ways from even modest drinkers.  It is difficult to know and to try to control these non-alcohol differences.  Since the advent of the genomic age a new approach has been undertaken.  First, careful research is done to find a set of genes that are associated with being a drinker of alcohol.  It may surprise you to know that this sort of study can be done and has, in fact, found a number of alcohol-related genes.  Then in the alcohol-disease studies, this set of genes substitutes for the alcohol people report they consume.  These types of studies go by the rather awkward name of Mendelian randomization studies.  If there are maybe 40 genes that are associated with alcohol intake, then a person with 25 of the alcohol-related versions of these genes is assumed to be consuming more alcohol than someone with only 10 of these alcohol-related versions.  The advantage is that this gene score approach is quite free of the teetotaler issues that we worried about above.

In many early studies, such as summarized in 2011, moderate alcohol intake reduced the risk of heart disease by about a quarter and had no effect on stroke levels. [7]  This type of information is where the scientific community, the press, and the public in general have gotten the impression that a little alcohol is protective while a lot may be harmful.

However, this has been changing as the results of more Mendelian randomization studies have come out.  Two recent studies of this sort have modified our thinking on this topic. [8, 9]  Both found no positive effects of moderate alcohol intake on heart disease.  The risk of gene-related alcohol intake on heart disease starts right from the first glass.  Heavier intake is associated with exponentially higher risk.  One of these studies went further and tried to explain the older protective findings.  They found that lifelong nondrinkers, on average, weighed more, smoked more, exercised less, and consumed less vegetables.  This would go a long way to explain why this “control group” got more heart disease than even moderate drinkers and would have the effect of making alcohol drinking appear healthy.

To backtrack slightly, these groups also found that their genetic alcohol score was a risk factor for hypertension, just as shown above, thus reinforcing what we thought we already knew.

We also know more about the physical effects of alcohol on the body that can add or subtract to the risk of heart disease.  We know, for example, that moderate alcohol intake can increase HDL cholesterol, adiponectin, and nitrous oxide (NO), three protective elements, and can also lower oxidative stress and inflammation, also lowering risk. [6]  But alcohol also raises LDL cholesterol and blood pressure. [8]  So, which effect prevails?  It now appears to be the negative effects of alcohol on heart disease.

Diabetes

We are discussing type 2 diabetes here, not the autoimmune disease, type 1 diabetes.  Earlier studies found that moderate alcohol intake did not change the risk of diabetes in men but lowered the risk by about 1/3 in women. [10]  Again, this would have encouraged us to have that extra glass of wine at dinner or maybe that extra beer after a hard day of work. However, more recent studies based on Mendelian randomization have found a 15% increase in risk for each additional drink per week.  That is a huge effect.  In addition, they found an 8% increased risk of obesity with each additional drink. [11]  These are rather astounding risks from alcohol.  So, dear reader, if you are overweight and also a regular moderate drinker, this appears to be a one ways ticket to your doctor’s office.  Sorry ‘bout that.

Extra Nerdy Stuff

The field of Nutrition has come under some criticism lately for its methods and its findings. [12]  I should probably write a blog about this.  The criticism largely comes from how hard it is to connect diet and chronic diseases.  This is exactly what we are reporting on here, people’s alcohol intake and their chronic disease risks years down the road.  The problem is that we are largely left with observational studies such as have been reported here.  It is nearly impossible to do long-term dietary trials.  Several that have been tried have been expensive and have not worked out very well.  A hypothetical example of this would be to ask a group of non-drinkers to start drinking moderately for 10-20 years and watch for new diseases.  One can see how impractical this would be.

One of the problems with these types of observational studies is that people are complicated and tend to change their habits.  We humans are also rather terrible at accurately reporting our habits and intakes.  Let’s take an example.  If you took part in a study on alcohol intake maybe 20 years ago, how would you have answered the questions about your drinking habits?  I know that my wife and I were considerably poorer and were limiting ourselves to a glass or two a week of wine from a cheap gallon jug that we treated ourselves to every so often.  Nowadays, as I said above, we are enjoying a much more liberal budget and tastes.  So, which is the accurate answer to the question of alcohol intake for the Root family?  Also, people who like mixed drinks are different in many ways from folks who drink beer or drink white wine or drink red wine.  So, who is that average alcohol drinker in these studies?  By the way, it has long been determined that it is not the drink itself but the alcohol that has the effect.  So, regarding which type of drink is safer, they are all the same.

These new Mendelian randomization studies have their own problems.  How do we know, for example, that alcohol-related gene variants do not influence heart disease apart from their effect on alcohol intake?  Or, to use the example above, we see that the alcohol-related gene score not only predicted diabetes but also obesity.  Can a “pure” diabetes score also predict obesity, which is a risk factor for diabetes?  Confusing.

We can look at the biological effects of both alcohol and of the alcohol-related genes.  This might help us understand the mechanism of how alcohol works.  A good idea but with its problems.  We now know that alcohol has both promotional and preventive effects in the body.  Which predominates?  Complicated.

Conclusion

How can we summarize these complex findings.  We have always known and still know that excessive alcohol is not good for us in many many ways in both the short term and the long term.  The scientific view on moderate drinking and the chronic diseases of old age has been changing.  We used to think that there was a sweet spot of 1-2 drinks a day that was both enjoyable and probably even beneficial.  We are now increasingly convinced that this is not true.  Alcohol has always been a toxin.  We probably should have realized that.  A famous guy from the Middle Ages name Paracelsus stated that “the poison is in the dose.”  He is often considered the father of both toxicology and pharmacology.  Alcohol is a prime example of this maxim.  A little alcohol is less toxic than a lot of alcohol, but it is still a toxin.  If you enjoy the immediate pleasures of a glass of wine or a gin and tonic, then you will want to be weighing this against future risks (as with so many of our personal habits like smoking or the use of seat belts).  If you know that you are at higher than usual risk for diabetes or breast cancer, you might want to reconsider those extra few drinks a week.  I will cautiously and occasionally raise a glass to that.  Remember, it’s complicated.

References

1. Zhao, J., et al., Association Between Daily Alcohol Intake and Risk of All-Cause Mortality: A Systematic Review and Meta-analyses. JAMA Netw Open, 2023. 6(3): p. e236185.

2. Rumgay, H., et al., Global burden of cancer in 2020 attributable to alcohol consumption: a population-based study. Lancet Oncol, 2021. 22(8): p. 1071-1080.

3. Xie, C. and Y. Feng, Alcohol consumption and risk of Alzheimer’s disease: A dose-response meta-analysis. Geriatr Gerontol Int, 2022. 22(4): p. 278-285.

4. Liu, F., et al., Race- and sex-specific association between alcohol consumption and hypertension in 22 cohort studies: A systematic review and meta-analysis. Nutrition, Metabolism and Cardiovascular Diseases, 2020. 30(8): p. 1249-1259.

5. Vacca, A., et al., Alcohol Intake and Arterial Hypertension: Retelling of a Multifaceted Story. Nutrients, 2023. 15(4): p. 958.

6. Li, H. and N. Xia, Alcohol and the vasculature: a love-hate relationship? Pflügers Archiv – European Journal of Physiology, 2023. 475(7): p. 867-875.

7. Ronksley, P.E., et al., Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ, 2011. 342: p. d671.

8. Biddinger, K.J., et al., Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease. JAMA Network Open, 2022. 5(3): p. e223849-e223849.

9. Millwood, I.Y., et al., Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China. The Lancet, 2019. 393(10183): p. 1831-1842.

10. Knott, C., S. Bell, and A. Britton, Alcohol Consumption and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of More Than 1.9 Million Individuals From 38 Observational Studies. Diabetes Care, 2015. 38(9): p. 1804-12.

11. Lu, T., et al., Dose-dependent Association of Alcohol Consumption With Obesity and Type 2 Diabetes: Mendelian Randomization Analyses. J Clin Endocrinol Metab, 2023.

12. Studies linking diet with health must get a whole lot better. Nature, 2022. 610(7931): p. 231.

The very day that I posted this, an important meta-analysis appeared in the literature on wine consumption and heart disease. [1] They found that when they combined the results of 14 studies that wine drinkers has a 22% lower risk of heart disease. Being a red wine drinker myself, I would certainly like these results to be true. However, I have my doubts, some of which were explained above. In addition, remember that most wine is drunk with meals, compared to other alcoholic beverages. Also consider the control group, the non-wine drinkers. This is quite a diverse group including exclusive beer and mixed-drink drinkers and also teetotalers. How different are these groups apart from the wine drinking? There are things we know and can measure, like smoking, and things we don’t know and can’t measure. We call these latter things unmeasured covariates.

There is also some rather unsubstantiated information out there (I am not quite calling it a myth) that the phytochemicals in red wine have health promoting properties. Held in very high regard is resveratrol, a polyphenol common in a number of plants including grapes. Here are some quick comparisons. There is about 0.3 mg of resveratrol in a glass of red wine. [2] Typical doses in clinical trials and in available supplements run between about 100 to 1000 mg per day. [3-6] So, to drink enough red wine to get an apparently therapeutic dose, you would have to drink about 65 gallons of red wine a day. Now, personally, I am up for the challenge, but others point to some drawbacks with resveratrol. [7, 8]

So, drink your red wine and enjoy it, but don’t expect any health miracles. Take it for what it is, a wonderful brew of a slightly toxic material that tastes great.

References

1. Lucerón-Lucas-Torres, M., et al., Association between Wine Consumption with Cardiovascular Disease and Cardiovascular Mortality: A Systematic Review and Meta-Analysis. Nutrients, 2023. 15(12): p. 2785.
2. Weiskirchen, S. and R. Weiskirchen, Resveratrol: How Much Wine Do You Have to Drink to Stay Healthy? Adv Nutr, 2016. 7(4): p. 706-18.
3. Boswijk, E., et al., Resveratrol treatment does not reduce arterial inflammation in males at risk of type 2 diabetes: a randomized crossover trial. Nuklearmedizin, 2022. 61(1): p. 33-41.
4. Mahjabeen, W., D.A. Khan, and S.A. Mirza, Role of resveratrol supplementation in regulation of glucose hemostasis, inflammation and oxidative stress in patients with diabetes mellitus type 2: A randomized, placebo-controlled trial. Complement Ther Med, 2022. 66: p. 102819.
5. Fatima, S., et al., Role of δ-tocotrienol and resveratrol supplementation in the regulation of micro RNAs in patients with metabolic syndrome: A randomized controlled trial. Complement Ther Med, 2023. 74: p. 102950.
6. Nikniaz, S., F. Vaziri, and R. Mansouri, Impact of resveratrol supplementation on clinical parameters and inflammatory markers in patients with chronic periodontitis: a randomized clinical trail. BMC Oral Health, 2023. 23(1): p. 177.
7. Mankowski, R.T., et al., Higher dose of resveratrol elevated cardiovascular disease risk biomarker levels in overweight older adults – A pilot study. Exp Gerontol, 2020. 131: p. 110821.
8. Salehi, B., et al., Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines, 2018. 6(3).