Dr. Douglas Feinstein shares his team’s research into the link between alcohol consumption and brain health.
Is drinking alcohol ever a good idea for the brain? Research is conflicted. The MIND diet recommends a glass of red wine per day as part of its Alzheimer’s-prevention strategy, while other studies have found that drinking moderate amounts of alcohol may reduce dementia risk. Although researchers are confident that binge drinking is harmful, they are still not certain how much alcohol affects the brain. Some studies found that even drinking moderate amounts of alcohol harms the hippocampus, the brain’s memory center. A new study supports evidence that drinking excessive amounts of alcohol may lead to dementia.
- Dr. Douglas Feinstein doused rats’ microglial cells in alcohol. Microglial cells are known as the ‘janitors of the brain’ because they remove waste, including beta-amyloid, the toxic protein that’s found in the brains of Alzheimer’s patients.
- After pouring alcohol on the cells—the equivalent of drinking eight beers or an entire bottle of wine in one hour—Feinstein found that the cells’ ability to clear beta-amyloid dropped by 15 percent in one hour.
- He believes that if he had observed the cells for several more hours, their ability to remove this toxic protein from the brain would have continued to decrease.
It’s true that Feinstein saturated the cells with more alcohol than most humans would consume, but he said he used so much alcohol because he wanted to determine if alcohol affected the cells at all. Now, Feinstein and his team hope to test various levels of alcohol on the cells and eventually, on the rats. Feinstein’s results suggest that avoiding alcohol could keep the body’s microglial cells intact so they continue to remove waste from our brains. Feinstein hopes that someday researchers can determine what medication may prevent alcohol from having this effect on microglial cells so that people can continue to enjoy an occasional glass of wine.
Being Patient spoke to Feinstein about his study, whether it is safe to have a few glasses of wine per day, why alcohol is addictive and how far away researchers are from determining the effect of alcohol on the brain.
Being Patient: You focus on neuroinflammation, but your most recent animal study looked at alcohol and the brain. Can you tell us about that study?
Dr. Douglas Feinstein: I’ll give some background information about the kind of research that we’ve been doing for the past 15 or 20 years. Neuroinflammation is the main topic that we’re studying in the lab. That’s when you activate types of cells in your brain called glial cells; there are microglial cells and other types called astrocytes. These guys are normally sitting around there sort of patrolling your brain and doing useful things, like getting rid of junk and producing trophic factors [peptides or proteins that help neurons grow and survive]—making your neurons happy. In a variety of diseases, like Alzheimer’s, M.S., Parkinson’s and even with aging, the cells get activated in ways that can become toxic or detrimental.
Then about two years ago, I got involved in an alcohol project, which was looking at the effects of alcohol on these cells in the brains of animal models and also in cell cultures. Also, a lot of the work we’ve done over the years in my lab has focused on Alzheimer’s disease and what leads to plaque accumulation, but never previously looked at alcohol, so I just put these two things together for the first time, and luckily, we had some interesting results.
Being Patient: You’re looking at how alcohol affects rats’ brains. What did you find in your study?
Dr. Douglas Feinstein: We actually haven’t even done the studies yet in the animals. We’re isolating cells from the brains of animals, and then treating them in culture with alcohol. The gist of what we found, which was really surprising, is that when we treat the cells—and we’re using microglial cells, a specific cell type—with alcohol in a very high dose and look at the cells the next day for their ability to remove beta-amyloid from the cell dish, it was significantly impaired—roughly 15 percent. We only measured that over the course of an hour, so who’s to say what would’ve happened later on, but that’s the major effect: If you give a pretty high dose of alcohol to a bunch of happy cells, they don’t like to remove beta-amyloid as well as the control cells.
Being Patient: The microglia are often referred to as the ‘janitors of our brain’ because they clean out all of the gunk, making it difficult for plaques to build up in our brains. Is that an accurate description?
Dr. Douglas Feinstein: That’s a great explanation. You mentioned that there’s a lot of controversy surrounding studies on alcohol and the brain, so controversy is the fact that when we’re talking about neuroinflammation or neurodegeneration, these cells get activated and produce toxic molecules, but you have to remember that cells are not normally there to produce toxic molecules. These guys are there to remove debris and produce trophic factors, and what we found is that the alcohol doesn’t necessarily cause them to make more toxic factors, but it reduces their ability to carry out their beneficial function, so that’s also like a yin and yang of this process. One of their beneficial features is to remove amyloid as well as other junk by a whole variety of processes and we happened to focus on one of them, but there’s several others we hope to get to in the future as well.
Being Patient: Why did you douse the cells with so much alcohol? If you think about the effect that much alcohol would have on humans, do you think the amount you used is realistic?
Dr. Douglas Feinstein: There are many answers to that. One of the reviewers asked that question in a comment on our paper when we got it back for revisions. Oftentimes, when carrying out initial studies, we want to treat the cells with high doses of stuff to see if anything’s going to happen. If you hit them with a very high dose and nothing happens, then maybe you don’t want to go back and use lower doses. We make sure that the high dose doesn’t kill the cells, which it didn’t, so that was one of the reasons. Secondly, in terms of actual human consumption, the equivalent of what we used is pretty high: It’s about 0.3 percent, and I’m sure everyone knows that the legal drinking limits in a lot of states is 0.08 percent, so we’re about three to four times higher. This is the equivalent of drinking six or eight beers or shots, or something like that, within an hour, which is the equivalent of a bottle of wine per hour, so it’s a lot. Hopefully that’s a lot for most people, but it’s not for many people. For many people, that’s normal, or they consume even higher levels. If your alcohol blood levels are that high, you’re not in good shape. Unless you’re used to it, you may be in a stupor, you may be unconscious; if you’re much higher than 0.3 percent, like 0.4 percent, it could be lethal, depending on your health, age, gender, diet and all those types of things.
“I’m pretty confident that taking low amounts
—a glass of wine per day—as suggested by the
MIND diet and other diets, is probably
going to be good for you, if you’ve been doing it.”
Addressing the same question, we added the alcohol to the cells and it had a very high concentration upfront. Then, they’re in a chamber because they need 37 degrees and carbon dioxide and oxygen to survive, and during that time, the alcohol is evaporating, so to be honest, we did not measure the levels during the protocol, which was 24 hours. I suspect that by the end of the protocol, it’s probably pretty low. The average is probably midway between those two. This is actually very physiologically relevant because in humans, you drink a bit, even if you’re drinking normal amounts, and it’s being removed from your gut—it’s being evaporated—so to some extent, it’s a little bit more physiologically relevant, but it’s still a lot.
Being Patient: Even though you haven’t tested alcohol on the animals yet, do you know if animals react to alcohol the same way that humans do? How relevant is this test to humans?
Dr. Douglas Feinstein: This is the crux of basic research, which can be asked of any scientific study. I think it’s a good model, and from other studies that are being carried out that I’m aware of in alcohol research. The work I’m doing is part of a larger program project at U.I.C., and there’s five or six other investigators who are looking at alcohol’s effects in animal models. From their results, which involve consumption and overconsumption, and also withdrawal, many of the behavioral effects that they see replicate fairly well what happens in humans: the withdrawal effects and the addictive effects. In that aspect, I think it is pretty similar, but there may be one or two papers that have been published looking at the effects of alcohol consumption in Alzheimer’s mouse or rat models, so we really don’t know yet.
Being Patient: There is a lot that is unknown about alcohol’s effects on the brain. Diets like the MIND diet suggest that a glass of red wine per night is beneficial to your brain. But when you dig deeper into those findings, you discover that’s because red wine has resveratrol, which allows for better blood flow to the brain. Do we know whether or not a glass of red wine is good for you?
Dr. Douglas Feinstein: White wines are also made from the same red grapes; they’re just taken off the fermentation process a bit earlier, so they don’t pull out the pigments, but they still pull out a lot of the same chemicals. I’m not sure how much resveratrol is in white wine, but there’s a lot more in red wine. So they’re different in a lot of other factors. Reading the literature and some of the meta-reviews, where somebody has reviewed a lot of the reports, I’m pretty confident that taking low amounts—a glass of wine per day—as suggested by the MIND diet and other diets, is probably going to be good for you, if you’ve been doing it. That being said, if you’re not drinking anything, starting to drink any alcohol at all to reduce the risk of aging or development of disease, I think is not a good idea. Your body is not used to it. But if you’ve been doing that all your life or for many years, it’s probably fine. I think the recommended amount is one to two glasses per day. But it’s very conflicting; there are reports that even moderate drinking can have deleterious effects and this is a controversial area.
“If you’re not drinking anything,
starting to drink any alcohol at all to reduce the
risk of aging or development of
disease, I think is not a good idea.”
Being Patient: Can you tell us about the broader results from U.I.C.’s studies on alcohol? What have you learned from those studies?
Dr. Douglas Feinstein: The principal investigator of the larger project is Dr. Subhash Pandey in the Department of Psychiatry at U.I.C. The overall goal of that project is looking at an area of genetics—I’m a molecular biologist by training—called epigenetics. What this focuses on is the fact that your environment, diet, social interaction and everything affects your DNA—not causing mutations, but causing epigenetic changes outside of the genes. It’s modifying the structure of the chromatin and the bases, but not changing them. These changes are inheritable; when your cells divide, the new cells can have the same changes and when you have children, your children could inherit those. It’s looking at the epigenetic effects of alcohol in different parts of the brain. One big aspect is during withdrawal. It seems that withdrawal causes a lot of epigenetic changes, which contribute to the adverse effects: depression, anxiety, addition. The benefit is that there are drugs that are F.D.A. approved that can prevent that from happening. So the overall goal is to determine how alcohol causes epigenetic changes. And if we treat the animals, cells, or eventually people, with inhibitors, can we prevent that?
So in the context of Alzheimer’s disease, what we haven’t published but are also working on is that we saw these changes in these genes, which affect the clearance of beta-amyloid, so how does that happen? The idea is that we’re causing these epigenetic changes and that’s one of the next stages. We know alcohol is doing it, but how is it doing it? So that’s kind of the broad context of this whole program project.
Being Patient: Is it possible that the way our genes react to things is different for everyone and we each have a unique genetic code? For example, looking at cancer, some people can smoke their entire lives and never get cancer and other people get it in a matter of years. In your study, when looking at people’s microglia, do you think the whole system will act differently, depending on your genetic code?
Dr. Douglas Feinstein: I think that’s absolutely true. Again, when you ask, “Why are we using a high dose?” one of the reasons is to overwhelm the system and get everything going in the right direction. If we use moderate or lower doses, there’s so many differences between people. We do a lot of genetics here. Right now, we’re comparing identical twins and they have a few differences, but on average, siblings have 50 percent differences, so we’re all different by hundreds of thousands and millions of genes. Any process you look at in your body, including removing beta amyloid, involves dozens or hundreds of genes, so everyone’s got different genes and the effects person by person are going to be very different, which is why it takes so many people to do clinical trials. Between that and your diet and all the other factors, it makes it really difficult to get reproducible results.
Being Patient: Do we know why alcohol is addictive?
Dr. Douglas Feinstein: Many people probably know that the neurotransmitter, dopamine, plays a large role in addictive behavior and there’s data which shows that alcohol increases the release of dopamine to certain parts of your brain; that’s one of the reasons why it’s addictive. And withdrawal to some extent is an effort from your brain to compensate for the lack of dopamine in other ways. Then, when you follow it up with another drink, you’re taking that on top of a compensatory reaction, so it’s a circular process which is ongoing. It’s a self-replicating circle; it’s not a good thing. It’s a dopamine-related addiction, which is very interesting because there’s an connection between the role of dopamine, addiction and alcohol abuse in Alzheimer’s disease. There are a lot of neurotransmitters which are dysregulated in your brain if you have Alzheimer’s, M.S. or Parkinson’s. We study one of them called noradrenalin, which is highly related to dopamine. Noradrenalin also plays a role in alcohol addiction and anxiety, so there may be some interesting similarities or common pathways that alcohol affects, and the process of Alzheimer’s disease affects. It’s possible that the two together are synergistic.
Being Patient: How far away do you believe researchers are in finding answers about alcohol and the brain? Looking at Alzheimer’s disease, how far away are we in understanding whether or not a glass or two of wine can help someone with Alzheimer’s?
Dr. Douglas Feinstein: A while. In a practical sense, what I’m hoping to do is get funding to carry out comparable studies in some animal models, and if we get funding to do that, it will be two years. I’m hoping that other researchers will pick up on what we’ve just published and start looking at it themselves. If that happens, then things may accelerate a bit and maybe these two areas will advance a bit quicker. We’ve been looking for drugs for Alzheimer’s for a long time and there’s nothing out there yet. This is a subtle part of the disease process, so maybe it will be sooner. Maybe give it ten years until we can say, “You are OK to have a glass of red wine every night, but based on your DNA or background, you really shouldn’t.”
Being Patient: Are you hoping to find an answer to this question: If you don’t drink, will it help you prevent Alzheimer’s by keeping the system in place as it was designed—the microglia, the janitors of our brain working in the way that they’re designed to work?
Dr. Douglas Feinstein: Yes. Not drinking will keep them in line to continue what they’re doing. I think there’s a practicality that a lot of people for whatever reason do want to have a glass of wine. If it’s the case that this does cause some dysregulation, then maybe we could think about ways to allow that to continue, but to provide a medication, even something as simple as Ibuprofen—not that Ibuprofen is the answer, or aspirin, which might prevent alcohol from having those effects on the microglial cells. I don’t think we can prevent people from their habits, so it’s something that we have to live with and maybe adjust to. I don’t know if it’s pessimistic or optimistic, but it’s a practical solution.
This interview has been edited for length and clarity.