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00:04
Hey everyone, Mikki here. You're listening to Mini Mikkipedia. And today I wanna chat about a study that I discovered on Twitter last week around ketogenic diets and alcohol use disorder. And I've spoken previously about the therapeutic potential of a ketogenic diet in neurological conditions such as Alzheimer's, Parkinson's, multiple sclerosis, depression, anxiety, a whole host of different.

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diseases of the brain and also states. And I think it's just super interesting how the ketogenic diet can work to change how we feel and what we crave. And this particular study is on the back of other preclinical trials that shows the potential use of a ketogenic diet for people with alcohol use disorder. And some of the rationale for looking at this as part of a treatment plan for people with alcohol use disorder,

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is first of all, of course, it is a chronic relapsing condition and it accounts for 5% of deaths globally, which is a significant amount and is characterised by high levels of craving and drinking despite those negative consequences. Fewer than 4% of patients with AUD, alcohol use disorder, do receive an FDA approved medication to treat the disorder.

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efficacious for all patients and they can have clinical limitations due to side effects, which may reduce the adherence to the drug and subsequently be responsible for a relapse. So the authors suggest that there is a critical need to identify treatments that can reduce alcohol craving and consumption and then help in the success of people who are struggling to adhere to abstinence in this space.

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Now how does a ketogenic diet potentially work? Well, improving brain energetics by means of a ketogenic diet, which is a high-fat, low-carbohydrate diet, may be, as the author suggests, like a novel avenue for treatment for AUD. So acute alcohol intake shifts brain energetics, or the energy used by the brain, from glucose to acetate, which is an alcohol metabolite. In heavy alcohol drinkers and

02:30
In individuals with AUD, low brain glucose and high acetate metabolism persist beyond that acute intoxication. And the authors hypothesize that this contributes to alcohol withdrawal signs and symptoms, alcohol cravings and relapse due to that low acetate availability. Now, ketone bodies such as beta acetoacetate and acetone structurally resemble

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to the brain and may provide an alternative to glucose as an energy source in brain metabolism. And these authors have recently found that a ketogenic diet intervention reduced alcohol withdrawal, severity, and alcohol cravings in individuals with an AUD undergoing inpatient detoxification. And the diet does this by elevating blood and brain ketone bodies. And as I said at the start, there are preclinical models, which are studies utilizing rodents,

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have also demonstrated that a ketogenic diet reduces both alcohol self-administration and signs of alcohol withdrawal. So certainly in light of it being a safe, efficacious, therapeutic nutritional intervention, it is absolutely worth exploring in the context of alcohol use disorder. So in this study, participants had to have at least five years history of heavy drinking, which equates to at least five drinks a day,

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or four plus drinks a day on at least five days per month for men or women respectively. Alcohol also had to be specified as the drug of choice and participants also had to fill out questionnaires that asked them about their lifetime drinking history, their alcohol dependence on the alcohol dependence scale, and also a timeline follow back to assess daily alcohol consumption in the previous 90 days or three months.

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The individuals with the AUD were admitted to the National Institute on Alcohol Abuse and Alcoholism in-patient unit and while receiving treatment as usual, within two days were randomized either to a ketogenic diet or a standard American control diet for three weeks. And there were no significant differences in either demographic or clinical characteristics between the groups.

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history, they all had a mean intake of around 15 to 17 alcoholic drinks per day in the last 90 days. That's 15 units of alcohol, not necessarily actual drinks. And very similar in terms of years of education, smoking status, calories they were consuming, and number of females and males in the study. And age was also not significantly different.

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They enter the facility, the inpatient facility, and within two days, these groups are randomized to either a ketogenic diet or a standard American diet. And both of these diets were equal in the number of calories they provided. The ketogenic diet provided a classic four-to-one ratio of grams of fat to grams of carbohydrate and protein. And that is what is often used in a therapeutic ketogenic diet approach. It is different from what you would consider

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a modified Atkins approach where it's a little bit lower in fat and possibly higher in protein. So the 4 to 1 ratio ends up being that the diet is 80% of the calories coming from fat, 15% coming from protein, and 5% coming from carbohydrate. The standard American control diet is around 50% of calories coming from carbohydrates, 15% coming from protein, and 35% coming from fat. So for each meal at breakfast, lunch, and dinner, the diets consisted of a shake, a

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either a ketogenic diet or a controlled diet, that provided 70% of that meal calories. And then a ketogenic solid snack that provided 25% of those meal calories, which ensured double blinding. So the difference in breakfast really was in that shake, where people couldn't tell whether they were on the ketogenic diet or on the standard American diet, because the snack was the same between the two groups, and it was either scrambled eggs, yogurt with nuts.

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salad, chicken salad or a broth. And this was at breakfast, lunch and dinner. And the participants were allowed to drink water, as much water as they wanted, and were able to drink either tea or coffee with or without stevia, and or diet ginger ale with their meals. And so all of the meals were provided from the nutrition department metabolic kitchen, and all foods and beverages were weighed on a gram scale.

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And so what they found, there was no difference in diet expectation between the groups, which indicated that the blinding of the diet was successful. Now all participants had their beta hydroxybutyrate ketone levels on the day that they were enrolled of informed consent and before breakfast on the morning of each of the MRI scans used to determine changes in alcohol cravings. And this was in week one.

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two and three because it was a three-week study. And they measured the ketone levels via a finger stick and used precision extra blood ketone monitoring system strips. So all participants underwent three MRI scans in the first, second and third week of the diet initiation. And during those scans, participants were showed a total of 40 alcohol, 40 appetitve food and 40 neutral images.

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and they were randomly presented in an event related design using some sort of like software. So there were three runs showing 40 cues that included all three categories of those cues. So either food, either alcohol or just neutral images. And after the completion of the MRI sessions, participants were asked to rate the cues for their subjective valence. So how negative or positive did you find this picture? Either being very negative to very positive.

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And how much did you want to consume this right now from zero to six? So what were the results of the study? Well, first of all, what we know is that those that were in the ketogenic diet group, they had significantly increased beta hydroxybutyrate levels compared to the control group. So we knew that that group was successfully in ketosis because of the diet. So that BHB ranged from 1.6 in week one.

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In week two, it went up to 4.6. In week three, it was around the same at around 4.4. So this is definitely indicative of nutritional ketosis, which people qualify as being anything above 0.5 millimoles would be considered nutritional ketosis. And they were well and deep into ketosis. The slight decrease in week three compared to week two reflected two of the participants who weren't compliant with the ketogenic diet in week three.

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But overall, most participants were compliant and they were well within ketosis. And of course, they also measured the beta hydroxybutyrate levels of the control group and all of these levels were less than 0.2, indicating that they were complied to their control group and they were not in a ketogenic state. So the findings related to alcohol were super interesting. So self-reported alcohol cravings were largely reduced.

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in the ketogenic diet group, but not in the control group. And this was a trend downwards, though it was not a significant finding, potentially due to the numbers of the participants with two of the participants in the ketogenic diet group not adhering to the diet. But overall, the trend for alcohol cravings, self-reported, went down. Mean ratings of wanting alcohol cues relative to the neutral cues used in the MRI scans decreased over time in the ketogenic diet.

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but not in the control diet group. And there was a significant group times time interaction effect, which meant over time, this difference became significant. And just for what it's worth, there weren't any significantly different results when they were comparing the difference in the MRIs between food and neutral cues in either of the groups. So this was just in.

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how their brain responded to the pictures of the alcohol group. And there was also a main effect of the group on the alcohol over food neurological craving score with a lower overall neurological craving score in the ketogenic diet group compared to the control group. And at week three, those neurobiological craving scores correlated with the average three-week

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showing that the higher the ketone levels, there was a lower neurobiological craving for alcohol in those AUD participants. So that is super interesting, isn't it? What we have is a ketogenic diet group that demonstrated lower neurobiological craving score responses compared to the control group throughout the three-week intervention. And that

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correlated with the average beta hydroxybutyrate level on the days of the MRI scans. Moreover, the ketogenic diet compared to the control group demonstrated lower cravings of alcohol cues presented in the alcohol cue reactivity task, even though that didn't correlate with the neurobiological craving score. But these findings do provide novel insight into the effects of ketogenic diet on neural

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and add to these previously reported effects of the ketogenic diet, which increases that activation for both alcohol and food cues in those preclinical trials. So overall, these findings do provide evidence for the potential of a therapeutic benefit of a ketogenic diet in reducing alcohol wanting and neurobiological craving for alcohol. Now while the authors say that, you know, most of the research studying

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sort of conditioned effects of alcohol associated to its reinforcing effects, which are mediated by enhancing our sort of GABAergic, opioid and dopaminergic systems, so our neurotransmitter systems, they suggest it's possible that the ketogenic diet, sort of bioenergetics switch from glucose to ketones is also relevant in its reinforcing effects. And we know that that...

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certainly happens in a ketogenic diet state. You get that metabolic switch from being able to use ketone as an energy source. And this was potentially backed up by the fact that the neurobiological craving scores were negatively correlated with serum BHB levels of participants. So the craving scores went down as the ketone levels went up.

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So potentially a ketogenic diet could satisfy the altered energy requirements associated with chronic alcohol consumption through its metabolism of beta hydroxybutyrate. Also ketogenic supplementation could decrease ghrelin levels and appetite levels, which in turn may have reduced alcohol craving and brain reactivity to alcohol cues. And there are some sort of associations that we see with a ketogenic diet.

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and sugar cravings here too. So it may actually work on some of those same pathways. So their findings, they suggest, confirm the hypothesis that providing ketone bodies via a ketogenic diet during detoxification, which was when this was implemented, would attenuate the emergence of that alcohol craving. And they feel that the abrupt transition from the brain's consumption of ketone bodies, which occurs in alcohol use disorder, as an adaption to repeated alcohol intake,

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to the use of glucose as an energy source, which will reemerge with detoxification, might contribute to the alcohol withdrawal syndrome. So if you can continue to provide ketone bodies in the absence of alcohol, then that is going to diminish those alcohol cravings and potentially allow someone an easier process as they come off the alcohol withdrawal. So inducing ketosis with a ketogenic diet during that detoxification,

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could bolster or halt such an abrupt transition, thereby reduce alcohol withdrawal signs and symptoms, reduce alcohol craving, and reduce that conditioned brain reactivity to alcohol cues. So super interesting study, and just further demonstrates how, you know, powerful nutritional therapies could be, particularly in with regards to the brain, you know? And so I think that, like, this is certainly, this was not,

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put in as the main treatment for alcohol use disorder. It was part of the normal treatment regime that an inpatient would get when they were in an alcohol use disorder facility. And certainly it could be helpful for anyone, whether or not they are sort of inpatient or outpatient, dealing with alcohol cravings. It isn't outside of the realms of possibility to trial something like a ketogenic diet.

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if it's going to help you transition from heavy alcohol dependence into something that is abstaining from alcohol. And please don't think I'm suggesting to do this instead of treatment if you think you have alcohol use disorder or you recognize that you do. But certainly it would be worth discussing with anyone that you work with if this is the path that you are requiring to go down in terms of how it might be helpful. So,

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Yeah, hopefully that's of some use. I'll pop the link to this study in the show notes for you to sort of further explore. And of course, if you are currently seeking help and you think this could be a useful or an adjunct tool, then absolutely reach out because, you know, it's really great to have a team of people that you work with if this is something that you're sort of grappling with. And I certainly do that in my role and have helped clients with this. And so it's just really nice to see it in the published literature as well. And...

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I don't doubt that more and more of these studies will emerge over the years that hopefully fill some gaps in this space and just further contribute to our understanding of ketogenic diets and particularly with respect to alcohol use disorder. All right, team, hit me up if you've got any questions or comments on this. Interested to hear your feedback? You can find me on Facebook @mikkiwilliden

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on Instagram, threads or Twitter @mikkiwilliden or go to my website, mikkiwilliden.com and book a one-on-one call with me. All right team, have a great rest of your week. See you later.