Can the ketogenic diet be used as an effective treatment for alcoholism?

A 3-week RCT done by the National Institute of Alcohol Abuse and Alcoholism found that a ketogenic diet could reduce the need for detox medications, reduce alcohol withdrawal symptoms, and reduce alcohol cravings. The researchers also found that brain scans of participants using the ketogenic diet decreased inflammation and had positive changes in brain metabolism.

Introduction

In this blog post, I am not going to outline the symptoms or prevalence rates of chronic alcoholism. This post is not designed to be diagnostic or educational in that way. What I will do is tell you about a very well-done, high-level study using the ketogenic diet as a treatment for chronic alcoholism. And we will then discuss what the underlying mechanisms of treatment using a ketogenic diet could be based on what already exists in the research literature.

Ketogenic diet treats alcohol withdrawal symptoms in humans

The National Institute of Alcohol Abuse and Alcoholism did a 3-week inpatient study of chronic alcoholics. Participants were admitted to a hospital unit and detoxed. They were then randomly assigned to either a standard American diet or a ketogenic diet to see if it could make a difference.

They found that those who got the keto diet needed less detox medication (e.g., benzodiazepines), fewer alcohol withdrawal symptoms, fewer cravings for alcohol, and their brain scans showed decreased inflammation and changes in brain metabolism. (You can read the study here.)

As if those results were not stellar enough, there was an animal arm of the study that showed that rats given a ketogenic diet reduced alcohol consumption.

People are confused about how a ketogenic diet could help people who are chronic (hardcore) alcoholics, who cannot stop drinking, ruining their lives, relationships, and bodies. How could a dietary intervention like the ketogenic diet help to this degree?

What could some of the underlying mechanisms of treatment be?

Let’s apply some of what we already know about how the ketogenic diet can help treat mental illness from prior blog posts.

What are the neurobiological factors we see in chronic alcoholism?

In a previous post, we discussed the mechanisms by which a ketogenic diet could modify symptoms of anxiety. In another post, we discussed how it can treat depression. In this post we will see whether these same four areas of pathology are seen in alcoholism:

  • Glucose Hypometabolism
  • Neurotransmitter Imbalances
  • Inflammation
  • Oxidative stress

Alcoholism and Glucose Hypometabolism

Glucose hypometabolism is well-established as a pathological mechanism in alcoholism. We see hypometabolism in the fronto-cerebellar circuit and Papez’s circuit and in the dorsolateral, premotor, and parietal cortices. When brains cannot use fuel properly we will often see shrinkages in brain structures. A shrinkage in brain structures is a consequence of long-term brain hypometabolism. In the alcoholic brain we see severe shrinkage in the following brain structures:

  • cerebellum (balance, posture, motor learning, movement fluidity)
  • cingulate cortex (executive control, working memory, and learning; a connecting hub of emotions, sensation, and action)
  • thalamus (several functions, including Circadian rhythms)
  • hippocampus (memory)

When someone is a chronic alcoholic, their brain’s fuel source switches from using primarily glucose as fuel to something called acetate.

It has been known that a major source of acetate in the body comes from the breakdown of alcohol in the liver, which leads to rapidly increased blood acetate.

https://www.news-medical.net/news/20191024/Acetate-derived-from-alcohol-metabolism-directly-influences-epigenetic-regulation-in-the-brain.aspx

How would a ketogenic diet treat glucose hypometabolism in chronic alcoholism?

Acetate does not have to be made just from alcohol being broken down in the liver. It is also one of three ketone bodies that are made in ketosis. And so for the alcoholic brain, which has serious glucose hypometabolism and that relies on acetate for fuel, it makes sense that a ketogenic diet may provide energy rescue for the hypometabolism we see in this population.

We reasoned that the abrupt transition form the brain’s consumption of ketone bodies, which occurs in Alcohol Use Disorder (AUD) as an adaptation to repeated alcohol intake, to the use of glucose as energy source, which reemerges with detoxification, may contribute to the alcohol withdrawal syndrome.

https://www.science.org/doi/abs/10.1126/sciadv.abf6780

In other words, if your brain is used to one fuel (acetate) and then you completely withdraw the source of its preferred fuel, it makes sense that your cravings for that fuel would increase. That an energy crisis would occur in the brain. But if you replace that fuel in another way, that doesn’t destroy your body and your brain, through a ketogenic diet, your brain gets to have fuel while your body and brain are doing the hard work of healing. And eventually, as the metabolic health of your brain and body improve, your brain may be able to use glucose better as a substrate. But until that happens, you need a rescue fuel that is similar. And the ketogenic diet provides that.

Alcoholism and Neurotransmitter Imbalances

Some of the neurotransmitter imbalances seen in alcoholism include dopamine, serotonin, glutamate, and GABA.

Dopamine fuels our motivation and has important functions in our reward centers. It is seen as having a role in both acute intoxication and increases simply at the anticipation of ingesting alcohol. When people go through alcohol withdrawal there is a decrease in dopamine functioning, which may contribute to withdrawal symptoms and alcohol relapse.

The brains of alcoholics are seen to be depleted in serotonin, and it is thought that this contributes to behaviors around impulsivity and drinking alcohol.

Alcohol consumption increases GABA activity. GABA is an inhibitory neurotransmitter that we usually want a little more of because it makes us feel relaxed. But in the alcoholic brain, as they go through withdrawal, GABA is downregulated, meaning you cannot make enough of it.

The GABA systems in the brain are altered in situations of chronic alcohol exposure. As an example, in some regions of the brain, the expression of genes that encode components of the GABAA receptor is affected due to alcohol.

Banerjee, N. (2014). Neurotransmitters in alcoholism: A review of neurobiological and genetic studies. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4065474/

The receptors are dysfunctional from chronic alcohol consumption. This is why we so often give benzodiazepines to help with withdrawals in people attempting to abstain. It is an attempt to temporarily correct the neurotransmitter imbalance that comes from withdrawal.

On the other hand, glutamate is downregulated during alcohol consumption. In other posts on other disorders, particularly anxiety disorders, we see glutamate dominate neurotransmitter state. This could be why so many people self-medicate anxiety disorders using alcohol (e.g., social anxiety). In the alcoholic brain, glutamate is thought to contribute to the rewiring of the brain that creates hyperexcitability and craving during alcohol withdrawal.

How would a ketogenic diet help treat neurotransmitter imbalances seen in chronic alcoholism?

Ketogenic diets upregulate the production of several neurotransmitters for the alcoholic brain going through withdrawals. Ketogenic diets are shown to increase serotonin production, increase GABA, balance glutamate levels and dopamine levels.

One of the ways this is accomplished is through decreased inflammation, which we will discuss in the next section. When brains are suffering from neuroinflammation (spoiler: the alcoholic brain definitely has inflammation) it disrupts the balances and functions of neurotransmitters. Another way chronic alcoholism can disrupt neurotransmitter balance is through malnutrition. B vitamins, magnesium, and several other important micronutrient cofactors are depleted and not easily restored. Alcoholics may not prioritize a healthy diet, and even if they do there are changes that occur to the gut microbiome that can reduce the absorption of important vitamins and minerals. A lack of amino acid intake resulting from choosing alcohol over nutritious food can and will disrupt the brains’ ability to create neurotransmitters and produce enzymes that regulate neurotransmitter function.

Alcoholism and Neuroinflammation

Neuroinflammation occurs when there is some assault on the neurons. This can be from head trauma, substances getting through a leaky gut-brain barrier, or chronic alcohol use. This inflammation, when it gets out of hand, will cause the death of cells, usually next to one another. These cells swell up and their internal cell machinery breaks down. Eventually, these cells that are irreparably damaged from inflammation, will rupture and spill debris where they do not belong. This is not a normal or healthy cell death process. So the debris will then lead to a local inflammatory process as the body attempts to clean up the mess.

There are very specific effects that alcohol (aka ethanol) has in the brain that trigger neuroinflammation.

The neuroimmune system response to ethanol intake, in specific brain regions such as amygdala, hippocampus and frontal cortex [in mice], is involved in addiction and in behavioural deficits observed in alcoholism.

Haorah, J., Knipe, B., Leibhart, J., Ghorpade, A., & Persidsky, Y. (2005). Alcohol‐induced oxidative stress in brain endothelial cells causes blood‐brain barrier dysfunction. http://dx.doi.org/10.14748/bmr.v28.4451.

Neurodegeneration seen in chronic alcohol abuse comes from chronic neuroinflammation. This neuroinflammatory response is due to signaling by glial cells (TLR4) who initiate this form of cell death.

How does a ketogenic diet reduced neuroinflammation in those with chronic alcoholism?

A ketogenic diet has been shown to specifically decrease TLR4 cytokines, as well as regulate the inflammatory process. It does this by being a signaling molecule that is able to turn genes on and off to balance inflammation. This keeps inflammation down. And a brain that has been exposed to chronic alcoholism is one that is on fire.

Ketogenic diets can help quickly reduce this inflammation, improving the brains’ ability to repair, restore and heal. As we learned in the neurotransmitter balance section, inflammation must be down in order for neurotransmitters to be made in the right amount and balanced.

Neuronal membranes, which are an important part of brain cells, cannot function well if they are swollen and are dealing with impending cell death. Getting inflammation down with a powerful anti-inflammatory intervention, like the ketogenic diet, could only be beneficial. Study participants experienced much less inflammation than the control group and this reduction in inflammation may have been what helped these study participants to have such favorable results as they went through alcohol withdrawal.

Alcoholism and Oxidative Stress

Severe levels of oxidative stress occur in alcoholism. Oxidative stress refers to the burden that occurs when the body’s ability to deal with reactive oxygen species (ROS) is out of balance. People who do not consume alcohol create a certain amount of reactive oxygen species just breathing and creating energy and being alive. But in healthy individuals, this normal load of ROS is well-managed and does not seem to contribute to acute disease states (although we still age, unfortunately). As you can imagine, chronic alcoholism tips this balance in such a way that ROS is increased.

Less oxidative stress would be good for anybody, but it is particularly good for alcoholics. Why? Because alcohol is particularly good at damaging the blood-brain barrier.

Thus, oxidative stress resulting from alcohol metabolism in brain microvascular endothelial cells can lead to blood-brain barrier breakdown in alcohol abuse, serving as an aggravating factor in neuroinflammatory disorders.

Abbott, N. J., Patabendige, A. A., Dolman, D. E., Yusof, S. R., & Begley, D. J. (2010). Structure and function of the blood–brain barrier.  https://doi.org/10.1189/jlb.0605340

And that the blood-brain barrier is crucial to healthy brain functioning. It is the protection from assaults that the brain depends upon, and when those tight junctions get loose and let substances through that would not be, it causes a dangerous neuroinflammatory response. Chronic non-stop neuroinflammatory responses deplete nutrients trying to fight them, blow cells up, and cause inflammatory cytokines to increase inflammation. As reactive oxygen species goes up the body’s ability to handle it goes down, causing an increase in oxidative stress.

Alcoholics have a lot of oxidative stress going on in the brain, but they also have it in their bodies. Alcoholic fatty liver disease, a devastating disease process that happens in chronic alcoholism, is seen to create large amounts of oxidative stress.

Acute and chronic ethanol treatment increases the production of ROS, lowers cellular antioxidant levels, and enhances oxidative stress in many tissues, especially the liver.

Wu, D., & Cederbaum, A. I. (2009, May). Oxidative stress and alcoholic liver disease. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0029-1214370

How could a ketogenic diet reduce oxidative stress in those with alcoholism?

Ketogenic diets reduce oxidative stress in several ways, some of which we already discussed in previous sections. Less inflammatory cytokines lead to reduced inflammation and create less reactive oxygen species to be neutralized. One of the ways it does so is to upregulate (make more of) an endogenous (made in our body) anti-oxidant called glutathione. This is a very powerful anti-oxidant that you get more of on a ketogenic diet.

Cerebral metabolism of ketones has been shown to improve cellular energetics, increase glutathione peroxidase activity, reduce cell death and possesses anti-inflammatory and antioxidant capabilities in both in vitro and in vivo models.

Greco, T., Glenn, T. C., Hovda, D. A., & Prins, M. L. (2016). Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5012517/

Ketones do this by increasing something that cells really need and that can be decreased in chronic disease states like alcoholism. This important something is called nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and you can think about it as a co-factor, meaning cells need it in order to do something. More of this co-factor helps your body to use enzymes to activate powerful antioxidants in your body, such as glutathione.

Other ways a ketogenic diet improves oxidative stress are the improved cell membrane function we already reviewed. This improved cell membrane function leads to better synaptic regulation, creating better neurotransmitter balancing. The increase in mitochondria, the powerhouses of neuronal cells, gives the cell more energy for improved cell signaling and enough energy to clean and maintain the cell and all its parts.

Conclusion

The ketogenic diet is not just a theoretical treatment for alcohol use disorder anymore. It is my hope that people will use this powerful dietary and nutritional intervention to help them in their recovery journey. Particularly in those who have struggled or failed in the past using the current standard of treatment.

With the help of a medically supervised detoxification, the ketogenic diet treats alcoholism and likely, according to the animal study arm of this research, helps improve the likelihood of relapse prevention.

I want to encourage you to learn more about your treatment options from any of the following blog posts. I write about different mechanisms in varying degrees of detail that you may find helpful to learn on your wellness journey. You may enjoy the Ketogenic Case Studies page to learn how others have used the ketogenic diet to treat mental illness in my practice. And you may benefit from understanding how working with a mental health counselor while transitioning to a ketogenic diet can be helpful here.

Share this blog post or others with friends and family suffering from mental illness. Let people know there is hope.

You can learn more about me here. If you would like to contact me you may do so here. It is my honor to tell you about all the different ways that you can feel better.

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