What Are the Impacts of Alcohol on Health?

 With mounting evidence about the dangers of alcohol to our health, just what is the impact of alcohol on cancer risk? On cardiovascular risk? On overall mortality? Those questions are answered on this episode of Health Science Radio, which features two University of Colorado Anschutz Medical Campus professors discussing the latest studies on alcohol and health. The two doctors also talk about the changing patterns of alcohol consumption, current definitions of what constitutes a drink, their own internal conversations about alcohol and the need for more research. 

Transcript

Chris Casey:

Welcome to Health Science Radio where we talk with researchers at the University of Colorado Anschutz Medical Campus about the many ways they're innovating and advancing healthcare. Today, we'll be talking about a subject that's getting a lot of attention in the news – the connection of alcohol to cancer. There's a lot to dig into on this topic as well as the issues of alcohol consumption patterns and alcohol's effects to our general health in broad terms. My name is Chris Casey and I'm the director of digital storytelling at our Office of Communications. Joined here – and it's a pleasure as always – by Dr. Tom Flaig, our vice chancellor for research.

Tom Flaig:

Well, the pleasure is all mine as I like to say, and it's nice to be inside on kind of a cold January day.

Chris Casey:

It's inside, but we apparently neglected to think about heating this particular room. But anyway-

Tom Flaig:

I wasn't going to say anything, but you're correct.

Chris Casey:

We'll soldier through. Our guests today are Dr. Ned Calonge and Dr. Tyra Fainstad, both professors at the CU Anschutz Medical Campus. Dr. Calonge is the associate dean for public health practice at the Colorado School of Public Health and the chief medical officer for the Colorado Department of Public Health and Environment.

He is a professor of family medicine at the University of Colorado School of Medicine. Ned chaired the National Academies of Sciences, Engineering and Medicine Committee that was commissioned to review studies that looked into the relationship between moderate alcohol consumption and eight health outcomes. And we'll talk a little bit about that work he did later in the show.

Dr. Fainstad is an associate professor of medicine at the University of Colorado School of Medicine and practices clinically as a primary care doctor. She is the resident director for internal medicine learners at Lowry Internal Medicine in Denver. Also, Tyra co-created and co-directs Better Together, a national physician coaching program to mitigate burnout. So with that, Tom, I'll pass it over to you to jump into our interview.

Tom Flaig:

Well, looking forward to this topic today, and I must say this is a very timely topic as I watch in a variety of different medical news feeds. This particular topic of alcohol and health has been very, very prominent. And I'll say this, too, I'm a practicing medical oncologist, so I haven't studied this field as a researcher or done work in that, but I followed this sort of medical dialogue about the topic of alcohol and health for a long time and I have patients ask about this.

And I would say that for a long time, I think the way that a lot of people, again, that weren't deeply involved necessarily have thought about it in the provider side was that maybe a glass of red wine a day is sort of healthy and patients had that sense in physicians. And I think that thinking is being challenged or kind of rethought in recent years for a variety of reasons. So I think it's a very timely topic.

Before we jump into it, it might be good to just get some basic understandings of what the setting is. So one question I would have, and maybe this would go to you (Ned), how have alcohol consumption patterns changed over time from the pandemic, from before the pandemic and the types of consumption, the intensity of consumption? Is that something you could comment on?

Ned Calonge:

Sure. Before the pandemic, alcohol use was fairly stable. It would go up a little bit every year. There was a large jump during the pandemic. And just looking at retail sales, because it's a heavily regulated industry, sales went up 3%, which is the highest-ever measured increase in a single year. That was in 2020. So the impact of COVID was that a lot more alcohol was consumed. And I think there were some estimates from smaller studies that suggested up to a quarter of people kind of moved into the heavy drinking area. So, we haven't had enough experience with those sales since COVID but at least early data said we've kind of stayed at that higher level.

Tom Flaig:

Well, that's really interesting because I think, anecdotally, we sort of hear that. I've heard that again from patients and from non-patients. So to quantify that is really meaningful. So it sounds like levels have been pretty stable over time, but a 3% increase in the early part of the pandemic. You mentioned this concept too of a moderate or heavy drinking use. Could you just define what does that mean as you use that?

Ned Calonge:

The definitions that we used in the study were actually set by the Dietary Guidelines for Americans. So we used that definition. The study that I participated in was commissioned by the USDA, which is a key owner of the dietary guidelines for Americans. And they ask us to look specifically at moderate alcohol consumption. So, we use their definition.

So moderate would be up to one drink a day for women and up to two drinks a day for men. By exclusion then, anything over that constitutes heavy drinking. And between heavy drinking and alcohol use disorder, there's a lot of space. But I think that's kind of the continuum. We didn't work or look at light drinking, which would be less than occasional drinking. Those definitions are harder to pin down and there's much less research on the area.

Tom Flaig:

And then a drink is defined by the type of alcohol we're talking about.

Ned Calonge:

Yes. So the definition of a drink is based on 7 grams of alcohol, and so then you translate that to the different kinds of alcohol. So that would be like a single drink, a one-ounce drink of hard liquor, six ounces of wine, 12 ounces of beer in general. But recognize that alcohol content in wine and beer and spirits all varies a little bit, but those are the definitions we use.

Tom Flaig:

Yeah, really helpful to have that background information, what's going on. So, Tyra, maybe I just turn to you for a second. What do you hear from patients about this topic and maybe changes during the pandemic?

Tyra Fainstad:

I can absolutely support the increase in drinking, at least anecdotally from my perspective during the pandemic. I think the social isolation alone is probably a huge factor in that. A lot of people were not only unable or unwilling to go out and participate in their normal activities, but they were also dealing with a ton of grief and stress, and overwhelm. And alcohol is a really obvious coping mechanism that many human beings have. And so, I think all of that together created this huge upsurge in alcohol use that we've seen.

What I hear from patients right now is a lot of confusion, especially with these new recommendations that are coming out. In the last decade or so, there's been this one-liner thrown around about how maybe there is no safe level of alcohol (consumption), and many patients are familiar with those definitions that you just mentioned of one drink a day for women or two for men, but they don't know, I'm finding, what one drink constitutes.

And so many people are beer drinkers and they'll have an IPA that might have very high alcohol content or wine drinkers for instance have these enormous glasses of wine and nobody's actually measuring the ounces. And so I think while that's useful to have a rule of thumb, in practice, it doesn't pan out so well for patients.

Tom Flaig:

Yeah. And I think you've touched on this, but do you get a sense of what the average patient's beliefs are about the impacts of alcohol on health? Safe at a certain level, not safe at any level, maybe that's what you're saying is in flux.

Tyra Fainstad:

I think it's actually pretty generational. In my older generation of patients, there's generally a belief that moderate drinking is healthy and even beneficial, especially for cardiovascular health. People from the older generation were part of the era where we heard, gosh, a glass or two of wine a day will keep your coronaries clear and is part of a healthy Mediterranean diet. And there were lots of studies over a decade ago that people have heard of in the news. And of course, those are popular studies and so we hear a lot more about those than the ones that contradict it.

Interestingly, in my younger patients, and I classify them as younger than me, would be younger patients.

Tom Flaig:

Me too.

Tyra Fainstad:

I'm seeing a lot less drinking and in fact, they're a lot more concerned about the deleterious effects of alcohol. And interestingly, I'd say in the Gen Z generation, alcohol is not seen even as a cool, fun thing to do, generally. Of course, there's still high alcohol use disorder happening out there, but in general, it seems that the older generation seems to think that it's healthier than the younger generation.

Tom Flaig:

And maybe you (Ned) could flip things back over from an epidemiologic point of view, do you see those generational differences in alcohol use?

Ned Calonge:

We do see patterns change over time, although there are younger populations that may not go to the doctor that often where alcohol still serves as a rite of passage, it has this unique ability to add social ease to a situation. And so I think we do still see a fair amount of alcohol in younger people and I would wonder if it's kind of that, what do I want to say, 30 to 40 or 30 to 50-year-old folks who are investing in their future health who are making different decisions.

But there was a number I think quoted in our study that based on behavior risk factor survey, that at least 60% of Americans over age 15 have had at least one drink in that previous year. And so that's how ubiquitous it is. I get interesting responses to that both – that means 40% of people don't have a drink in a year and they're surprised or 60% sounds like a lot.

Tom Flaig:

Maybe I could just ask one more question here, Chris, before we move on, but as you think about the way to study this question and the measures, you can think of, what's the impact of alcohol on cancer risk? What's the impact of alcohol on cardiovascular risk or what's the impact of alcohol on overall mortality? Ned, do you think that's a correct way to tee it up or do you want to comment on any of those different spheres of thinking about this?

Ned Calonge:

Well, that's exactly the way that what they call the scope of task was presented to the National Academies by the USDA. So there were a number of specific health conditions for which there is interest on the impact of moderate alcohol consumption and those outcomes. And they were varied. There were eight different topics. I will tell you that three of them were on lactation. The three lactation questions were what happens to postpartum weight gain in lactating women who consume alcohol? And then what's the impact of alcohol on milk quantity and quality? And then what's the impact on neuromuscular development of a breastfed infant from a woman who was consuming alcohol? So even though I say eight questions, they're really only five.

Chris Casey:

Yeah. And Ned, so on that study, you were commissioned to review studies as I understand it that looked into the relationship between moderate alcohol consumption and eight health outcomes. Could you just talk a little bit about how you conducted those studies and what were any of the key findings, or are you allowed to elaborate at this point?

Ned Calonge:

I can talk about all of that and it's included in the final report, which is available online. If you put in NAS, which is short for National Academies of Science, Engineering and Medicine and then alcohol, it'll take you right to it. You can download the entire report for free. And there's a summary for people who don't want all of the details.

But we were specifically asked to review the literature since the previous dietary guidelines for Americans. So the DGA, I'll use that acronym, is produced every five years by the USDA. I say the USDA, that's who is the primary owner, but both the secretary of the USDA and the Secretary of Health have input into the final recommendations.

Alcohol was last looked at in depth in 2010. And so our study starts at 2010 and moves forward. The only exception is the DGA repeated a systematic review and report on all-cause mortality in 2020, or 2019 was when they finished that. And so we just went back to 2019 for all-cause mortality. The topics, the outcomes we were asked to look at, were all-cause mortality, cancer outcomes, and it basically left up to the committee which outcomes we wanted to look at in cancer. Then it did neurocognitive issues such as cognition decline with aging, Alzheimer's and related dementias. So those were those issues. Then the impact on moderate drinking on weight like obesity, weight gain and other measures of weight.

Then there's cardiovascular disease which the committee partitioned into non-fatal heart attacks, stroke and cardiovascular disease death. So those three outcomes. And then lactation, they were the three questions we talked about.

The way we did the study is a very structured approach to evidence review and synthesis called a systematic review. The approach to systematic reviews is so characterized that there is a database, an international database called Prospero, where you actually register your systematic review to add that quality control that whoever's doing it is following this very structured approach. The committee itself didn't do the systematic review. We did participate in scanning the literature, doing title and abstract reviews for what to send over to the contract systematic reviewers, and then ask them to provide us a meta-analysis of the results, which is like a weighted average of what the results were that we then used to make our findings and conclusions.

Chris Casey:

And were there any particular conclusions that you can highlight, especially with respect to maybe certain cancers?

Ned Calonge:

So I can easily talk about the major findings of the report. We used the U.S. Preventive Services approach to classify each one of our conclusions by certainty level. So a low certainty would be inadequate evidence to support a conclusion. Moderate certainty would be there's sufficient evidence to support a conclusion, and future research could actually find something different. And then high certainty is it's unlikely future research will change that outcome.

We had three moderate certainty findings, and those three certainty findings were: one, moderate alcohol consumption is associated with a lower risk of all-cause mortality; it's associated with a lower risk of cardiovascular disease death; and it's associated with a higher risk of breast cancer. So those were our three conclusions.

Just to add some additional context, when we decided to select and look at specific cancer outcomes, we included the National Cancer Institute's list of cancers known to be associated with alcohol. And so those would include oral cancer, pharyngeal cancer, esophageal cancer, laryngeal cancer, colorectal cancer. So those are the ones we focused on. We left liver cancer out because the association is with heavy drinking, not with moderate drinking. And so we just review that set of cancers.

Dr. Flaig, because you're a cancer expert, there are, I would say a set of emerging cancers of interest that are at least mentioned in the report, but we didn't do systematic reviews on, are things like prostate cancer, endometrial cancer, kidney cancer, which is interesting because it appears to be a protective effect. So we just mentioned those. And I think it's an area to keep an eye on in the future.

Tom Flaig:

You can certainly call me Tom, and I would just say that one of the things that happens to us is there's something in oncology mentioned in the news, right? There's an article that comes out or a patient will come in with an article sometimes, and I think what you're talking about is a level of evidence, right? In this systemic review or systematic review, there's a way there's threshold set.

I think that's one thing that I try to convey to patients oftentimes – well that's one article or that's a laboratory-based important information, but it's not a randomized prospective trial or it's not even a prospective trial or it doesn't have a control group. So I think one of the difficulties in this discussion and broader medical discussions is conveying, I think you've done very nicely here, how do we look at evidence and weigh evidence and making determinations?

Ned Calonge:

Yeah, I appreciate that. There's a couple other points I hope I could make about the specificity of the study that we performed. One of the criticisms of alcohol researchers, especially around this potential benefit associated with moderate drinking, that then goes away with heavy drinking. In fact, cardiovascular risk goes up, all-cause mortality goes up as soon as you hit kind of that heavy drinking area.

The criticism was that previous studies that you were talking about at the top of the podcast had a comparison group that was called non-drinkers. And the problem with that comparison group is it can include former drinkers. And former drinkers may have stopped drinking for a health-related reason including alcohol use disorder. So the concern was that there's this abstainer bias. By including sicker people in the comparison group, you're creating this appearance of a benefit associated with moderate drinking. Does that make sense?

Tom Flaig:

Mm-hmm.

Ned Calonge:

And so we excluded every study unless it had a never-drinking comparison group. So that limited the number of studies even since 2010, but gave us the ability to say there's not abstainer bias in our results. The other area we lost studies was on the upper end. So there are a lot of studies that compare ever drinking to never drinking, if that makes sense. And we only wanted to look at moderate drinking. So if you start to include the higher levels of drinking, you start to lose the ability to uniquely look at that moderate drinking exposure.

Tom Flaig:

And I think that's a very important discussion to have really, you have to set those standards and those expectations as you go into a structured review like this. And I think that as I talk to patients, that's one question they have, why do we get different signals? It depends on how you sort through the data and what criteria it is just strictly looking at these two groups of people... what are the criteria, the end points you can look at, whether it's cancer, cardiovascular, overall mortality.

Chris Casey:

And when you talk about the study, Ned, how do you align the actual amount of alcohol to be defined as a moderate amount? Is that aligning with the dietary guidelines figure?

Ned Calonge:

Yes. The exposure that we looked at was up to moderate drinking as defined by the DGA.

Chris Casey:

OK.

Ned Calonge:

So those are the comparisons we were both asked to make and we were able to make. So I think to your point, Tom, depending on how you construct the study, you can very well get different answers. What I feel strongly about and when I have been pushed by other interviewers, is that we're confident that looking at this data, these studies with the exclusion criteria we used, we're confident of the results of the associations that we found.

Chris Casey:

It just feels like there's a fair amount out there. And again, it goes to what you were saying, Tom, about people grab bits of information and they interpret it differently. But it just feels like there's a lot on alcohol and the dangers that are at odds with each other right now. For instance, the recent outgoing, I guess he is now outgoing, Surgeon General Vivek Murthy, advising that labels be put on alcoholic beverages in America stating clearly that this is a cancer-causing product, perhaps. And so that's what's been in the news just recently, adding just more at odds confusion, I think. Do you two feel this confusion ramping up?

Ned Calonge:

Since the reports came out, I've been immersed in the confusion and why our results are different. That's why talking about the study details itself is so very important. There are a number of authoritative sources that classify alcohol as a carcinogen. Once you do that, it's not difficult to understand why a surgeon general might want to say if it's a carcinogen, there's not a safe amount. So you can actually understand how you could get there.

Chris Casey:

Do you pick up on that as well, Tyra?

Tyra Fainstad:

Absolutely. And I think it's the WHO that's classified it as a class one carcinogen, which there are not very many things that we consume legally that are classified that way. It's like a handful and alcohol is in there saying basically what that means is we have evidence that alcohol alone causes cancer. And so it is a class one carcinogen.

Now the data, it's so murky, isn't it? The data is so murky because here we are with really good trials showing, gosh, it's not that clear and perhaps there is a safe amount. And then we have this bench research that shows what's going on at a cellular level. But is that really what's happening in vivo in everyday life? It's so unclear. I think what we're really lacking, certainly as a primary care doctor, I feel I'm really lacking that huge prospective randomized control trial that is correctly powered and looking at this in the right way. I know that those are in the works, but we don't have a really good one yet to guide us, especially in the area of moderate drinking.

The other area that feels unclear for me is even if and when we find out specifics about moderate drinking, there's still this really slippery slope between light and moderate drinking to heavy drinking, and it's hard to predict which patients are going to be able to stay there and which are not. And the risk of being a moderate drinker might be limited in cardiovascular outcomes or whatnot, but the risk to becoming a heavy drinker is huge, and perhaps that's the big safety problem we should be talking about.

Ned Calonge:

I really appreciate that point, and it's one that I often make about the things we didn't look at because the way the National Academies works is you're given a statement of task and you're supposed to stay within the statement of task. In the entire review process, which involves multiple other experts in the area, and if you deviate from the statement of task, you'll have a hard time getting out of review. And there are just a number of risks or outcomes we didn't look at.

So the risk of a moderate drinker proceeding to heavy drinking – alcohol is an addictive substance. You get this tachyphylaxis, so you have to drink a little bit more to get the same impact. So the normal progression is to move from light to moderate to heavy. And there's a certain number of people who will do that. And you're right, it's difficult to predict who, but that risk of becoming a heavy drinker and all of the other health outcomes was not what we looked at. That was one.

We also didn't look at things like motor vehicle crashes. And one of the things that's challenging is this concept of responsible drinking, which is a catchphrase that's used all the time in advertising around the alcohol products. Well, there's no definition of what responsible drinking is. And the issue is there's just this fine line, right, between I've imbibed enough where I'm safe to drive home and I over-imbibed. And I don't know too many people who are very skilled at knowing where they've moved from one point to the other.

Tom Flaig:

One of those other questions that I hear from patients occasionally is the type of alcohol – that I'm a wine drinker, just for example, I don't use a higher-octane alcohol. And so that's a difference thing. And again, I don't know if that's something you hear or something the studies have spoken to.

Tyra Fainstad:

Absolutely. I think patients know in general that liquor is an especially dangerous substance. And there was, I remember reading at some point, correct me if I'm wrong, a RCT, a randomized control trial, looking at wine versus I think it was gin, or maybe it was vodka or something. And they looked at, I believe it was some cardiovascular topic, and how are they affecting the cardiovascular lining of our coronaries, and wine is better, was the outcome.

And so that, of course, got publicized and spun, and I think everybody has their different takes on which one is best for the heart. And then there were some studies that came out that maybe conflicted with that, that were quieter. But there is this level of like, well, I never have a hard drink, but I stick to wine so that feels safe. Or, oh, I just have one beer a day, but perhaps that beer is something that's like 14% and they're feeling falsely safe there.

Ned Calonge:

Yes. When we created the systematic review, we included trying to look for evidence that would allow us to tease out differential impacts on the basis of the type of alcohol plus the pattern. Do you only drink with food? Do you drink without food? So there are a number of different dietary patterns that are of interest and that have been thought about or studied about having differential impact.

As we looked at the data since 2010, there just wasn't enough, there weren't studies to allow us to look at that level of specificity. One of the theories about wine being better isn't the alcohol – because the alcohol is the alcohol – but it's about the other things in wine – antioxidants and other things. And I think that's a theory that could be studied. And at least in this 14 years of evidence we reviewed, we didn't find enough data to make a conclusion.

Chris Casey:

Tyra, I'm curious with your work with Better Together, the program where you're looking into mitigating physician burnout, which is a huge issue as well. I'm curious, within physician burnout, I read into that stress, I read into that people struggling in their world and they'll reach for things, perhaps alcohol to allay that stress. So do you see an overlap between your work with the Better Together and the alcohol consumption problem? Certainly, physicians are drinking and probably at their conferences, they're having alcohol, et cetera. Could you just talk about what you've seen there?

Tyra Fainstad:

Absolutely. I mean, what an interesting time that we're in, I think. We have this mounting evidence that alcohol is bad for you, and yet it's deeply ingrained in our culture and society. And most physicians that I know drink at least socially. And so it's kind of everywhere. And alcohol provides this, I call it an easy button, to mitigate a feeling you don't want to feel or amplify a feeling that you do want to feel. So it's a pretty good coping strategy in the moment to grab a glass of wine after a hard day at work. And a lot of docs out there are having a lot of hard days at work, especially recently. We know that to be true.

So I'd say I definitely see and hear and coach and discuss alcohol use among physicians a lot in the Better Together physician coaching program. Most docs feel an immense amount of guilt or shame when alcohol is their method of coping, which then of course you enter this spiral where you're feeling so much shame and that feeling feels bad, which prompts you to reach for another glass of wine.

This happens with other substances too. I mean, sugar, social media, whatever your guilty pleasure is can be inserted there, but alcohol especially has that addictive quality. And so once you start down that road, I think our brains are hardwired to think, oh, great, the alcohol took the edge off. What an easy button at the end of my day. And then the cycle continues. We are not as hardwired to be able to look into the future and realize, gosh, I slept horribly tonight or I didn't function as well the next day. That link is less hard or less easy for our lower brains to make in the moment.

And so docs are stuck in this, too. It's such an interesting place to be simultaneously counseling my patients on healthy drinking and then going home and having that internal conversation with myself as I, too, reach for a glass of wine after a hard day at work. So, yeah, I think it's there. It's a difficult, complex problem.

Ned Calonge:

It's so interesting because we also see that it's built into social interaction. So you talked about social isolation and drinking, and I would also talk about social activity and social connectivity and drinking. So it's so common to get together with friends, we should go out for a drink. What a common phrase you hear all the time. And so we have built it into our culture and social connectivity. And the easy button is interesting because we also know that at least anxiety increases self-confidence in these kinds of uncomfortable social situations.

And so this complex relationship with alcohol, social interactions, how we use it as, I like that, an easy button, gets us to this point where it's so ingrained in our society that figuring out how to tease it out and to talk about the risks of even moderate alcohol and cancer and how that should affect people's decision making – it's just a difficult issue.

Chris Casey:

Yeah. As Tyra, we were talking a little bit before the show here. I think you made the observation back in the ’50s, physicians commonly were having a smoke during the course of their day. Well, that's been mostly eradicated now that we're what, 60 years, 50 years, hence that, 60 years, hence that. Do you forecast down the road like, say late 21st century, doctors will not be touching alcohol the way they eschew cigarettes now?

Tyra Fainstad:

I see it. I can see it. And I think even if the research around moderate alcohol doesn't point us in that direction personally, the risk of sliding from moderate to heavy use is great enough for me to avoid it and for me to counsel my patients in that way. The societal harms out there – drunk driving and aggressive behavior – there's this one scatterplot that I have in my mind from some study, I think it came out of the UK, where it looked at all of the different substances, both legal and illegal, and showed the amount of self-harm and the amount of societal harm together. And alcohol is up in the highest quadrant, up with cocaine and heroin.

I think partially because it's so accessible, but also because we're making really bad decisions and it causes that. And so in my mind, all of that together seems obvious that a cultural shift away from alcohol is needed in the way that we have done with tobacco. And so yes, I can imagine, I joke about it all the time with my patients that we'll be getting together in 50 years and patients will say, oh gosh, back in my 20s, even my doctor was telling me that she had a glass of wine with dinner. Can you believe it? Ha ha ha. And we're just in that. We're in the transition of it right now, which is such an interesting time to be in.

Tom Flaig:

Interesting. You think about societal norms and changes over time. So in this building where we are right now, President Eisenhower, over five and a half weeks, was coming back from a heart attack in 1950s. If you tour that space, which has been sort of recreated, there's a waist-high ashtray there. And Eisenhower did have a strong smoking history during the war. He did not smoke at that time. It was for his physicians. And there's an information board there talking about Eisenhower saying maybe you don't smoke in front of me as I'm sitting here in bed rest. So things have changed over time in that regard.

Tyra Fainstad:

Dramatically.

Chris Casey:

Wow, that's a nice anecdote. Thank you for sharing that. Well, I feel like we could go on about this all day. And part of the alcohol conversation that fascinates me is the potential neurodegenerative aspects of alcohol, too, like accruing over time and how that's contributing to the massive waves of Alzheimer's dementia we're facing down the road. And that could be a whole other episode, I think.

Ned Calonge:

We did review that in the study, and one of the things that was discouraging for me was that there wasn't more research. Again, I would get to the evidence that heavy drinking is associated with increases in risk of dementia and neurocognitive decline. Moderate drinking, it's not quite so clear. So there's a forest plot in the report. And a forest plot, it just kind of lines up the different studies and says what their kind of summary result was. We call it a point estimate and then kind of the variability, the confidence levels of those, and they're all lined up on a line.

And for Alzheimer's, it's on both sides of the line. And so we came away saying it's inconsistent, and we can make no conclusion. So I think this moderate drinking and neurocognitive decline where we also couldn't make a conclusion is an area where ongoing research could be very helpful. It becomes a little problematic because you have to use a prospective study. You have to start with people who don't have problems now and then follow them forward in time.

And those are harder, more expensive studies and not a randomized control trial, which would be nice. But the length of time to run an RCT on that specific topic is going to be really difficult to fund and continue. So I really appreciate that question. People would say, what was your biggest surprise? And it was like, there's not enough evidence.

Tyra Fainstad:

I think that's so important as a takeaway for patients as well, because a lot of patients read studies like this thinking, oh, they found some risks that... What I can imagine a patient saying is we found a risk in breast cancer and not a risk in heart disease or any of the other ones. And unfortunately, they conflate inconclusive evidence with it's safe. And so that's really what I try and push towards my patients is we still don't know. There are not enough studies.

Ned Calonge:

And the way I would say it is, no evidence of harm is not the same as evidence of no harm.

Tyra Fainstad:

Yes.

Ned Calonge:

And so really keeping those two concepts different is important.

Tyra Fainstad:

Very.

Chris Casey:

Well, a lot of subtleties and nuance within this huge issue. And I very much appreciate the way both of you articulated what your observations are on the topic and, Ned, with the study on the national scale. It's fascinating. And I think we could just continue. We should do a part two down the road somewhere because yeah, this has been a great discussion.

Tom Flaig:

One of the places we're leaving this discussion is high-quality research will lead us home. And I think in so many ways, going back to that research theme, it's research that these conclusions will drive future conclusions as well.

Ned Calonge:

There's a whole chapter in the report that no one reads, I'm convinced. And it's about the challenges of doing alcohol research. First of all, the exposures are all self-reported and we know that people under-report what they actually drink. But there are so many other issues about controlling for additional confounders, really doing high-quality research, and then specific recommendations for the future on every topic. So you're right, we need to use our best science to answer these questions.

Chris Casey:

I think that's a great place to end it. So thank you, Ned, and thank you, Tyra. Appreciate your insights today. Great discussion.

Tyra Fainstad:

Thank you.