There is no single optimum for the amount of alcohol to be consumed by people

I received a (free) book in the mail the other day, which reminded me of my scientific past. I have mentioned in recent posts that I used to teach university students (studying biological science) about experimental design; and in the blog posts I have recently applied this knowledge to experiments concerning alcohol and health (eg. Why alcohol experiments are problematic).

Well, for my scientific research, one of the things I worked on was biological networks. You have all heard about Charles Darwin and the “Tree of Life”, the idea that all organisms are descended from ancestors, with modification. That is, a family tree (of people) becomes a bigger, and older, tree of all organisms, if we go back far enough in time. Well, this is only partly true, because there are all sorts of genetic inter-connections among those branches, so that it is actually a “Network of Life”.

I was one of the early people championing this idea, back 20 years ago. The book that I received is called: The Network of Life: a New View of Evolution, by David P. Mindell (June 2024. Princeton University Press). So, let’s look at this book here, and some ideas it covers related to the effects of alcohol on people. I need to present some background first, and then move on to the alcohol effects.

The network idea is that species share genetic material, via a process called horizontal evolution, so that evolution is actually a web of shared genealogy, instead of just from ancestor to descendant. Species are thus more interconnected than previously thought. Life is not a tree but a network (see the next figure). The complex example of our own history (Homo sapiens) is shown in the network diagram below (taken from Mindell’s book).

To establish my bona fides, at the end of this post I have listed a few of my professional publications related to this topic of evolutionary networks, including the introductory book that I wrote (Introduction to Phylogenetic Networks). My previous blog (2012—2020) was also on this topic: The Genealogical World of Phylogenetic Networks. *

My connection to this new book (and why I got a free copy) is indicated in the Preface: “I am enormously grateful to colleagues who read sections of the full draft of the book. Their insights, patience, and thoughtful commentary improved the book a great deal. This includes Ford Doolittle, Axel Meyer, David Morrison, Greg Gibson, James McInerney, Maureen Kearney, Mary Ellen Hannibal, Peter Alpert, Matt Kane, Jack Sites, Ed Braun, and Dan Graur.” That’s quite a list, but I made it to third! [I read the draft way back in 2022.]

For our main purpose here, in looking at alcohol and people, the author notes that:

“The Network of Life describes the drivers of horizontal evolution — inter–breeding and genetic recombination, the merger of species, horizontal gene transfer, and co–evolution. The network view of evolution that emerges supports a new symbiotic theory of health, which holds that the future health of humans, other species, and our shared environments depends on evolution and adaptations across life’s network.”

As the author points out, the old “Germ Theory of Disease” focuses on human disease itself, whereas the new “Symbiotic Theory of Disease” focuses on human and environmental health. That is, human diseases stem from infection with certain organisms, whereas human health actually stems from the capacity to recover from disease and injury, and to adapt to change over time. So, in the latter the focus is on both short-term and longer-term relationships of other organisms in human and environmental health.

Now, the author mainly restricts himself to the complex network that exists between any given species and the disease–causing organisms that surround and inhabit it. However, I wish to look here at the medical status of humans and their interaction with their environment. Obviously, in this blog, the aspect of the environment under discussion will be the alcohol that the people transfer from their environment into their own bodies.

The basic idea is that there is no static optimum for the nature of the interaction (alcohol in this case) under discussion, because the relationships are evolving in both time and space. The World Health Organization’s declaration (January 2023) that there is “no safe level” of alcohol consumption (that does not affect health) makes little biological sense.

The book’s author notes:

“What do we mean by health? Human health is often taken to be the the mere absence of illness. That view may work on a short time scale. But over longer time frames, health and sickness are not mutually exclusive conditions. Reacting to a flu virus with a fever, aching joints, nausea, and swollen lymph glands, the classic signs of sickness, is a sign of good health, as manifest by a healthy immune system. Sickness and health co–exist, and a long life includes many periods of injury and sickness, followed by recoveries ... Because health and sickness vary over time, there is no narrow or statistically defined normal or abnormal state of these conditions. Environmental health is similarly dynamic. At all levels, health is more about resilience, adaptability to trauma, and persistence over time than it is about absence of sickness.”

So, the idea that there could be a pre-specified amount of alcohol that humans can safely consume, medically, is naive. The amount that we could safely consume at one time in our life will not be the same as at another time. We adapt through time, based on what has already happened to us during our life — we meet our own medical needs over time by being resilient, and adjusting to change. There is no such thing as “normal” — it changes through time for each of us.

Furthermore, our body is a system of interactions among many components (organs, chemicals, micro–organisms). There is much evidence that the microorganisms in our body impact our behaviour. Their chemical compounds can and do stimulate our nervous system and brain, influencing our mood and actions. So, the host behaviour is not controlled by the host’s genes alone. There is no such thing as “normal” — it changes in space, as well.

Just as importantly, the amount of alcohol that we could safely consume thousands of years ago was not the same as now, nor will the amount we consume now be the same as a thousand years in the future. The human species has a long past (there is evidence of Neolithic wine, 8,000 years ago, at the site shown above**), and we will presumably have a long future (although we may change a lot during that time). There is the intriguing idea that our species has evolved while consuming alcohol, and interfering with that consumption might actually have negative effects on us.

For example, we know that reducing some of our previous environmental exposures has correlated with the increasing prevalence of allergies (Why our allergies are getting worse), and reducing exposure to some of our previous microbes may be correlated with the increasing prevalence of auto–immune diseases (The increasing prevalence of autoimmunity and autoimmune diseases). Thus, reducing our exposure to alcohol may actually have negative effects! [So might increasing it, of course.]

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Publications

Morrison, D.A. (2011) Introduction to Phylogenetic Networks. RJR Productions, Sweden. vi+216 pp. ISBN 978-91-980099-0-3. [Formally reviewed here.]

Morrison, D.A. (2005) Networks in phylogenetic analysis: new tools for population biology. International Journal for Parasitology 35: 567-582.

Morrison, D.A. (2010) Using data-display networks for exploratory data analysis in phylogenetic studies. Molecular Biology and Evolution 27: 1044-1057.

Morrison, D.A. (2013) Phylogenetic networks are fundamentally different from other kinds of biological networks. In W.J. Zhang (ed.) Network Biology: Theories, Methods and Applications (Nova Science Publishers, New York) pp. 23-68.

Bapteste, E., van Iersel, L., Janke, A., Kelchner, S., Kelk, S., McInerney, J.O., Morrison, D.A., Nakhleh, L., Steel, M., Stougie, L. and Whitfield J. (2013) Networks: expanding evolutionary thinking. Trends in Genetics 29: 439-441.

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* My networks blog went for 3,187 days (or 8 years 8 months 22 days). So far, this wine blog has gone for 3,036 days (8 years 3 months 22 days). So, I’m getting there. [Tom Wark suggests that the technology for wine blog publishing became “very accessible” around 2009 — his Fermentation blog actually started in November 2004, and moved on to a new platform in January 2022.]

** The Agricultural Revolution started 12,000 years ago, and the Wheel was developed 5,500 years ago.

Why alcohol experiments are problematic

I recently published a post (Has the WHO lost its way regarding alcohol?) pointing out that what is recognized to be the best form of scientific experiment is what is called a “double-blind treatment–control” experiment (or sometimes a “randomized controlled trial”, or RCT). This procedure cannot usually be done ethically on people, and therefore no-one has ever admitted doing it in medical science. So, we will never have the best possible scientific evidence about the effects of alcohol on human health.

This does not mean that we do not have experiments about wine and health. What the scientists do is the best that they ethically can; and some of the pros and cons of this process is what I will discuss in this post. I cover several different but important topics.

What the researchers do is to follow groups of drinkers and non-drinkers through time, and see how these people get on — this is called a “descriptive” study rather than a “manipulative” one (as described above), of which there are several types as listed in the above picture. Here, we are concerned with the first one in the list, “observational”. In this type of study, health and behavior experts measure all of the consistent differences they can find between the studied people, to see what matches their patterns of their drinking and non-drinking. The results of the famous 1926 study by Raymond Pearl are shown in the next graph, as but one early example.

Also, we should ideally do all of this in such a manner that the people involved do not know which of the experimental groups they are in, and nor do the people evaluating their behavior (this is what “double blind” means). Is this actually feasible? Of course not. We can’t force people into the experimental groups, we can only ask them to volunteer to participate. That is, we rely on self–reporting of their alcohol consumption (often via detailed questionnaires filled in by the participants). Let’s look at the consequences of this now.

Here, is one useful recent discussion of how we might justifiably proceed (Causal inference about the effects of interventions from observational studies in medical journals):

Building on the extensive literature on causal inference across diverse disciplines, we suggest a framework for observational studies that aim to provide evidence about the causal effects of interventions based on 6 core questions: what is the causal question; what quantity would, if known, answer the causal question; what is the study design; what causal assumptions are being made; how can the observed data be used to answer the causal question in principle and in practice; and is a causal interpretation of the analyses tenable?

This is all well and good, but the biggest recognized issue is how to choose the studied people. Basically, the choice should be literally random, but this is impossible. As a discussion of the problems with one example of this, we have:

• The Mendelian randomization by Millwood et al.: observations and expressions of concern

In particular, people volunteer to take part in experiments, and this can never be described as “random”. Notably, people’s admissions regarding their own drinking may not be accurate (see also: Wine ratings involve both the accuracy and bias of the raters). This is discussed here:

• Risky drinkers underestimate their own alcohol consumption
• Sources, under-reporting of alcohol consumption

As one specific example discussion (Reweighting UK Biobank corrects for pervasive selection bias due to volunteering):

Volunteers tend to be healthier and of higher socio-economic status than the population from which they were sampled ... Volunteer bias in all associations, as naively estimated in UKB, was substantial — in some cases so severe that unweighted estimates had the opposite sign of the association in the target population. For example, older individuals in UKB reported being in better health, in contrast to evidence from the UK Census.

So, we often end up with this rather jaundiced (but realistic) view:

• All moderate alcohol consumption studies are “all over the charts”

Moving on, another potential approach, to getting around the sampling problems discussed here, is to use animals as a substitute for humans (eg. mice or dogs). This generates a lot of emotional response from parts of the public, which I will not delve into here. Instead, I will focus on the actual experiments.

One useful discussion is (The flaws and human harms of animal experimentation):

Nonhuman animal (“animal”) experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology ... The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.

One important point is whether animal experiments actually lead to any benefit for human medical treatments. Sadly, it seems mostly not (Analysis of animal-to-human translation shows that only 5% of animal-tested therapeutic interventions obtain regulatory approval for human applications):

There is an ongoing debate about the value of animal experiments to inform medical practice, yet there are limited data on how well therapies developed in animal studies translate to humans. We aimed to assess 2 measures of translation across various biomedical fields: (1) The proportion of therapies which transition from animal studies to human application, including involved timeframes; and (2) the consistency between animal and human study results ... The overall proportion of therapies progressing from animal studies was 50% to human studies, 40% to RCTs, and 5% to regulatory approval.

I think that you can all see the bottom line here: things are not likely to get any better any time soon, regarding experiments of alcohol intake by humans. The medical scientists are doing the best that they ethically and practically can, in the real world. This, however, does not match what they would be doing in the theoretical world of scientific experiments, which is what would be the best for devising effective medical ideas.

Nevertheless, I am not the only one who has noted that there is: ‘No good evidence’ of risk from low-level alcohol consumption. Basically, the risks of one or two drinks per day are so low that they are very difficult to estimate; and drinking with meals also seems to be unproblematic (Drinking wine with meals linked to better health outcomes). Alternatively, there definitely are risks associated with heavy alcohol consumption, and people with known health problems related to alcohol may not have any safe level of consumption, as well as pregnant women. People with a family history of alcohol abuse also need to be careful.

The no- and low-alcohol conundrum

As I noted last week (Has the WHO lost its way regarding alcohol?), the World Health Organization has mistakenly taken a very negative formal stance with regard to alcohol consumption. I contended in that post that there is little basis for this stance. Nevertheless, many members of the public are taking this very seriously, and “mainstream media is creating a negative narrative about wine with click-bait headlines that can impact government policy as well as popular opinion and consumption for years to come” (Come Over October: creating a positive narrative about wine).

One wine-industry response to this has been the increased development of low-alcohol and no-alcohol wines (sometimes called No-Lo wines). This is thus a topic worth looking at here, because there is little historically acquired expertise for this process (see my earlier post: Low- and no-alcohol wines really do need to be the way of the future).

It is particularly worth noting (Nolo: wine's final frontier) that:

“The rise of no or low-alcohol [Nolo] wines goes hand in hand with the increase of those seeking a healthier life. The benefits of a traditionally alcoholic beverage without alcohol are huge. For those with addiction issues or who are simply taking a break from alcohol, it can psychologically offer the placebo-like adult sophistication of an alcoholic beverage without the associated health risks.”

So, this is an issue that goes way beyond wine, or even alcohol in general, especially for younger generations (eg. Millennials drive no-alcohol gains in the US). Nevertheless, in this blog post I will restrict my comments to the making of the No-Lo wines themselves.

It has been argued (The war on wine) that: “Nonalcoholic wine is ... a gross contradiction in terms — and just kind of gross.” That is, wine contains alcohol by definition, so removing it creates a false terminology. More importantly, removing (or even reducing) the alcohol has a very big effect on the texture and taste of the resulting drink. Jeff Siegel (The war on wine) covers this topic in detail, as does an anonymous commenter (The idea of dealcoholised wine is appalling).

There three current methods (What is dealcoholized wine?): vacuum distillation, reverse osmosis, and spinning cone. The first two require heating the grape juice to almost body temperature, to evaporate the unwanted components (ie. alcohol) — this does, indeed, sound like it would have a pretty serious effect on the wine. The third method is thus the most common, in which the liquid is sent down a vertical series of spinning cones — the spinning motion of the cones separates out the different components, including the alcohol.

What is most interesting, however, for we consumers is what wine-makers are going to do to address this issue, of the changed nature of the resulting NoLo wine. It seems very unlikely that they will do nothing for their product (see: 8 reasons to get excited about the no-alcohol category). However, it has been noted (The challenges of making low/no alcohol wine) that:

“It was striking how different the wines were. Removing even the smallest amount of alcohol affects the flavour; removing a chunk of it fundamentally alters the wine, demonstrating just how much impact alcohol has on wine flavour.”

This, then, is the conundrum. A wine is usually treated as having five components: sweetness, acidity, tannin, alcohol and body. Removing the alcohol actually affects all five of these, not just the fourth one. Something needs to be done to replicate the body, mouth-feel and perceived warmth associated with the equivalent alcoholic wine (The 5 characteristics of non-alcoholic wine).

Given all of this, it should come as no great surprise what the response has been: Why a fine de-alcoholised wine starts with an ‘undrinkable’ base. That is, we already know that, for example, if we intend to age a wine, then we need to start with a wine that is nothing like the intended drinking product: “a young Bordeaux or Barolo, for example, is intended to age and evolve for 20 years or more, and it is simply not going to be delicious after three years, unless you enjoy an astringently tannic mouthful” (How to define a good wine? It’s complicated). [On the weekend, my wife and I had a 2011 Rioja, which was perfect.]

So, it is no wonder that reduced alcohol wines need a pretty different starting point from usual, if they are to be any good at the end. That is: “vacuum distillation does result in the loss of 60% of the wine’s aromas, and 20% of the base product’s volume, and hence the need to exaggerate the aromatic profile before the process begins.” You can read the above article for a specific example (Why a fine de-alcoholised wine starts with an ‘undrinkable’ base).

Given this idea, we can now consider whether anyone has yet created what the wine media might consider acceptable, or even good. As one example, Dave McIntyre at the Washington Post, has  some suggestions: Even with the alcohol removed, these new wines are actually good.

More generally, it has been noted that Germany has been making non-alcoholic wines for more than a century (For the best nonalcoholic wines, look to Germany), and may thus have some pretty good examples of how to proceed.

Even here in Sweden there is progress. For example:

“Oddbird was started in 2013 by family therapist Moa Gürbüzer. After working with families struggling with alcohol-related problems, she saddled up and started Oddbird to create good wines without alcohol.”

I have tried a few of the wines, and they are perfectly acceptable (and are inexpensive).