Nutritional Ketosis: An Epigenetic Intervention On Bipolar Disorder and Obesity

Alex Harty 

The Epi-Action is the introduction of a ketogenic diet to my daily lifestyle, starting from the first day of class, August 2nd, 2023. I made the frictionless decision immediately after learning of a study Impact of a Ketogenic Diet on Metabolic and Psychiatric Health in Patients With Bipolar and Schizophrenia Illness thanks to Dr. Lucia Aronica.

Experimenting with methods to control and improve my health has been the central challenge in my adult life. I self-diagnosed Bipolar Disorder II as a senior at Notre Dame.

I experienced what I could only describe as hypomania, after tireless Googling. This coincided with the sudden loss of my best friend from grade school to an IED in Iraq where he served as a Marine.

Since that moment, I’ve had varying levels of stability, in my career, relationships and overuse hyper-palatable foods, alcohol and drugs. This has led me to use my focus on researching and self-experimenting nature as my best weapon against the grey matter shriveling (particularly in the left superior frontal gyrus (SFG))2.

Compounding the fact that the frequency and intensity of manic and depressive episodes drives the extent of neurodegeneration is the predictable decade early all cause mortality as well as ranking among the highest risk of suicide among people managing their mental illness.

So motivation is not lacking.


The ketogenic dieter’s primary source of fuel becomes the ketone bodies, which acts as an alternative to a glucose-fueled metabolism. The three ketone bodies are β-hydroxybutyrate (BHB), acetoacetate (AcAc) and acetone (Ac), with BHB constituting 70% of circulating ketone bodies.

There is a growing body of evidence demonstrating that ketone bodies work as epigenetic modulators, particularly β-hydroxybutyrate, in the regulation of chromatin histone post-translational modifications (PTMs), and thus in the transcriptional machinery.3

BHB, besides serving as an alternative energy source to glucose, also acts as a signaling molecule involved in many cellular functions, including epigenetic regulation of gene transcription. 

Recent findings suggest that ketone bodies coordinate cellular functions via a novel epigenetic modification—β-hydroxybutyrylation4,5—that integrates the classic DNA methylation and histone covalent posttranslational modifications (PTMs), including histone lysine acetylation, methylation and histone phosphorylation and ubiquitination (Figure 2).3

I’ve kept net carbohydrate intake below 50 grams (usually less than 25g) since August 2nd, 2023. Purchasing a keto-mojo ketone blood test kit and logging my weight are the primary datapoints in this project.


Implementing the ketogenic diet will decrease my percentage of body fat and level of obesity, as measured by BMI. This will improve my epigenetic markers, and if I were to conceive a child with a partner, those epigenetic markers would contribute to the offspring.

I predict the decrease in weight and body fat because of the satiating effect with decreased food cravings due to the high-fat content of the diet. A decrease in appetite-stimulating hormones, such as insulin and ghrelin, when eating restricted amounts of carbohydrate. A direct hunger-reducing role of ketone bodies—the body’s main fuel source on the diet.


Using’s Evidence Based KETO (which I invested in during the pandemic of 2020) I followed the simplest rule to implement the ketogenic diet.

  1. under 50 grams of carbs per day” is only a rule of thumb.
  2. Depending on the individual, the “carb threshold” below which ketone levels rise could be as low as 30 grams or as high as 80 grams.


The graphs below are my daily body weight weigh-ins logged via to my bluetooth scale every morning, after using the restroom, attempting to remain consistent in measurement.

If you noticed that this graph doesn’t include weight-ins for 8/2 and 8/3, they were both 225.8 lbs. I had not paired the scale to the Renpho mobile app.

As you can see there are missing weigh-ins from 8/8-8/19. I made a trip to my hometown of Columbus, Ohio to reconnect with my family for the first time in three years, the longest I’ve been away from them in my life.

This was both incredibly moving, but unpredictably stressful. The mood-fortifying ketogenic diet proved to be effective at flattening the slope of the peaks and valleys of my moods and weight management.

Despite not having my bluetooth graphing scale, I manually entered the daily weigh-ins, sharing the entries from 8/9-8/19 below.

  • 8/8 – red 👁 flight into Columbus International, ate breakfast with parents, no weigh-in data.
  • 8/9 – 223.2
  • 8/10 – 224.6
  • 8/11 – 223.8
  • 8/12 – 222.0
  • 8/13 – 222.6
  • 8/14 – 221.2
  • 8/15 – 222.2
  • 8/16 – 221.2
  • 8/17 – 223.8
  • 8/18 – 223.0
  • 8/19 – 223.8

The following graph shows the success of the weight loss hypothesis following the ketogenic diet. Across the duration of the class, I lost 5.5% of my bodyweight. I think this result seemed so effortless because I consistently felt full, I didn’t consciously feel hungry or restricted in any meaningful way.

While I did experiment with manually counting net carbs using pen-and-paper logging as well as the Cron-O-Meter app, though I wasn’t as consistent as I would have like to have been.

I wanted to be a little more flexible with my food choices while celebrating my niece Isla’s birthday. Therefore, I purchased the highest reviewed Ketone Blood Meter, Keto Mojo GK+ from Amazon for $50.

This allowed me to be more accurate in measuring my intermittent blood ketone levels and spend less time weighing every food I ate, with more time enjoying time with my family.



I was able to consistently eat foods with no or very low carbs throughout this epi-action experiment. Prior to starting this epi-action, I was in a multi-week plateau in weight loss. Losing weight from a mid May high of 257.5 lbs, I wasn’t able to break below 228 lbs. I’d frequently binge eat my favorite hyper-palatable foods, sometimes even whatever is in the kitchen and is relatively calorie dense.

This yo-yo cycle was becoming very frustrating, but I was determined to understand my behavioral patterns and how I can pivot. This open minded approach led to starting this epi-action experiment from day one of the class. I was convinced I got a 100% return on investment before the first class was over.

The most satisfying result of this epi-action is that I have not once felt the craving, urge or ravenous hunger to binge or eat sugar (and usually fat) dense foods. It’s shocking that I’m typing this, I don’t believe it. This is what I wished for myself, and I have more empathy for my past self, blaming myself for being undisciplined, weak and out-of-control. This isn’t just something I’m planning on continuing, I don’t want to change anything. It works for me.

My girlfriend thanks you, Dr. Aronica. I’m not secretly snacking on her food, only to say I’ll buy her replacements after. I’ve cooked more meals in the month of August for myself then I have in the past two years alone. My mood is more stable and I’m more energetic, thinking clearly in my estimation.


The major improvement I’ll be eating in my ketogenic diet is consistent, everyday servings of greens. Leafy: spinach and kale, and cruciferous vegetables: Broccoli, chopped beforehand of course. I was able to work these in during the month long trial, but not as consistent as I would like.

I didn’t detail the inputs, such as a food log, as well as I could have. This left less to analyze, but I did log full days worth on meals in cron-o-meter and almost a week in a notebook, with net carbs, fiber, calories, protein and fat grams logged in minute detail. I’m interested in collecting data, but in way that I find the most useful data to collect, without extraneous effort.


I will sustain the ketogenic diet by planning out an ideal day meal plan, constructed full of the methyl-donating nutrients and epigenetic modifiers that I learned about in class. The existing epi-nutrients that I already had been eating will be complemented by ones I haven’t been eating, but find palatable enough to eat, such as chicken/beef/pork liver, Brazil nuts and green tea.

The plan is to leverage my software development skills to create a personalized nutrition system in the form of a web or mobile application, simple and easy to use. Integrating lessons learned in this class, including the insightful work of Mahyar Rahmatian. When I complete a minimum viable product (MVP), I’ll be sure to share for all who are interested.


I took this class because I developed a fascination with epigenetics, especially diet-related interventions, in the pandemic of 2020. This class gave me structure, motivation, support and the social learning, all in the same context that I experienced in the pandemic. The depth of learning strengthened my initial curiousity, and I was able to apply the knowledge to my everyday life, already experiencing the benefits. I understand more about the most primal relationship I’ll ever have with the stuff that support me. I appreciate food on a level I didn’t know that I could, and I’m grateful to have the choice in what I eat. The optimizing of my dietary habits is a lifelong game and now I’m more energized than ever to play to win.



Epigenome Modulation Induced by Ketogenic Diets

Paola Ungaro,1,2 Immacolata Cristina Nettore,3 Fabiana Franchini,3 Giuseppe Palatucci,3 Giovanna Muscogiuri,2,3 Annamaria Colao,2,3  Paolo Emidio Macchia2,3,*


The largest area showing lower grey-matter volume in patients with bipolar disorder relative to controls was in the left superior frontal gyrus (SFG)

Xiuli Wang, MD,*Qiang Luo, MM,*Fangfang Tian, MM, Bochao Cheng, MD, PhD, Lihua Qiu, MD, PhD, Song Wang, PhD, Manxi He, MD, Hongming Wang, MM, Mingjun Duan, MD, and Zhiyun Jia, MD, PhD


Modulation of Cellular Biochemistry, Epigenetics and Metabolomics by Ketone Bodies. Implications of the Ketogenic Diet in the Physiology of the Organism and Pathological States

Arkadiusz Dąbek,1 Martyna Wojtala,1 Luciano Pirola,2 Aneta Balcerczyk1,*


New insights into the mechanisms of the ketogenic diet

Detlev Boison


Ketone bodies as epigenetic modifiers

Paola Ungaro,1,2 Immacolata Cristina Nettore,3 Fabiana Franchini,3 Giuseppe Palatucci,3 Giovanna Muscogiuri,2,3 Annamaria Colao,2,3  Paolo Emidio Macchia2,3,*