Transcribed with AI transcription services, errors may occur. contact Mikki for clarification

00:07
Hey everyone, it's Miki,k here. You're listening to Mini Mikkipedia on a Monday. And I've just recently attended the Metabolic Health Symposium that was put on by Low Carb USA. And I thought that I would share just a couple of things actually, it's gonna be a brief one, from the first day of the conference, looking at a ketogenic or low carb diet in a therapeutic sense for...

00:32
mental health. And this has definitely been an emerging area over the last couple of years. And you know, super interesting to listen to people who are sharing their personal experience using the ketogenic diet for conditions such as bipolar disorder, manic depression, schizophrenia, conditions like that, and also other potentially more common problems such as depression, anxiety and similar.

01:00
mental health issues. And so I wanted to just share a paper that was presented by one of the main authors, who is Laurie Calabrese. And she did a fantastic presentation talking about the complete remission of depression and anxiety using a ketogenic diet. And she's a medical doctor, she's a psychiatrist, and she shared three case studies with us that I thought was super interesting and could potentially be helpful for anyone in

01:29
a similar position where they do have a mental health disorder like depression and general anxiety disorder and a potential road that they could go down with regards to using ketogenic therapy to help support their mental health. And essentially, she presented on three adults with major depression and generalized anxiety disorder with complex comorbidity.

01:59
metabolic syndrome or metabolic issues in addition to the generalized anxiety and major depression. And I think a really interesting point that's come up from a number of the speakers in this conference is that these often go hand in hand, that many people who present with anxiety or depression also have metabolic problems along with it, such as elevated insulin, elevated

02:27
markers of inflammation such as high sensitive C-reactive protein, which is a general marker of inflammation in the body, and may also present with high blood pressure, increased waist circumference, things like that. So they often go hand in hand. And whilst many of us in, I guess, the lay public understand a ketogenic diet potential for conditions such as type 2 diabetes, fat loss that's often used.

02:56
and people with severe insulin resistance, it hasn't often been seen in literature that it could be helpful for anxiety and depression. This is where these case study publications are super interesting and super important, I think, because the more that doctors are able to publish their case study data, the more that it will present in the literature and be more accessible and available to people moving forward.

03:25
Dr. Calabrese mentioned some super interesting points from her case studies that she presented, which may be helpful for some people with regards to the type of ketogenic diet, what level of beta hydroxybutyrate that they were looking for when measuring it in the bloodstream, how they actually counseled the patient on their diet, and how quickly they saw the results from undertaking it. Because I think it...

03:51
allows people to set up their expectations if they're ever wanting to embark on a ketogenic diet with what they should expect if they're going to do it. What Laurie first sort of talked about in her presentation was essentially that there are some fundamental metabolic disturbances within neurons and throughout the body which involves insulin resistance, inflammation, oxidative stress.

04:14
and alterations of the gut microbiome, and these are all present in major depression and underlying anxiety disorders, and highlighting that these can be modulated through the use of echidogenic metabolic therapy. And she also noted that whilst psychiatric disorders have risen over the past several decades, there has been an absolute increase in prevalence of metabolic syndrome as well, with only 12.2% of US adults meeting the criteria for optimal metabolic health.

04:44
which does leave close to 88% of people metabolically compromised. She noted that metabolic syndrome affects almost a third of individuals with major depression, and it's a significant contributor to their morbidity and mortality, and it's rooted in impaired glucose metabolism and utilization. And insulin resistance is well described in many tissues, including the brain, where it's being investigated as a link between metabolic health and mental health conditions.

05:12
And preclinical models demonstrate that glucose intolerance is directly associated with anxiety and that insulin resistance triggers depressive behaviors. In brain tissue, insulin resistance results in something called glucose hypometabolism, which just means the brain can't use glucose, and it's a vicious cycle of unmet energy needs. In human studies, cerebral glucose hypometabolism is a feature of major depression and generalized anxiety disorder.

05:41
A ketogenic metabolic therapy is also known as a therapeutic ketogenic diet. It's a low carbohydrate, moderate protein, high fat diet that supports a fundamental metabolic shift from glucose to ketone bodies as a primary fuel source. Classic ketogenic metabolic therapies are formulated with strict macronutrient ratios, which are most commonly either four to one and three to one.

06:11
energy coming from fat as there is protein and carbohydrates. And this has been demonstrated to be really effective with intractable epilepsy and genetic disorders. And intractable means epilepsy that is unable to be treated just with medication. More recently though, there are modified ketogenic diets which have lower macronutrient ratios of 2.5 to 1, 2 to 1.

06:37
and 1.5 to 1, which have been utilized in research in clinical practice. And these do allow a more variety in the diet to meet micronutrient needs, which are much easier to sustain for an extended period of time. And so she's just spoke through just some of the implications of utilizing some of these modified ketogenic diets. To give you an example of a 2.5 to 1 ratio of fat to protein, you would have a...

07:06
Contribution of fat of 250 grams, protein would be 80 grams and carbohydrate would be 20 grams. And that was sort of the ratios that Dr. Calabrese was talking about in her presentation. And she presented on three case studies and talked about the time to response and remission, clinical challenges during the KNT, ketogenic metabolic therapy, and also the metabolic outcomes. And...

07:36
They used questionnaires to establish mood and general anxiety disorder. And they also correlated that with the beta-hydroxybutyrate that was drawn from capillary blood and also calculated a glucose-ketone index using the KetoMojo device. Improvement in quality of life was assessed by qualitative reports during clinical visits and also used a scale called the self-compassion scale and flourishing scale.

08:03
She really sort of stressed that the therapeutic intervention was used as a medical prescription with a properly formulated individualized ketogenic diet. And they also really focused on clinical support, lifestyle therapies like sleep, circadian rhythms, movement, community building, friends and family supports as well. So it wasn't just the diet. There was a lot of...

08:28
interaction with a registered dietician, a psychiatrist, there were follow-ups in metabolic monitoring and that clinician contact was frequent in person and virtually through online tools. So the first case that she presented was that of a 32 year old man and he had a lifelong history of previously unrecognized and untreated recurrent major depression as well as general anxiety disorder, obsessive compulsive disorder,

08:57
and binge eating disorder. And he experienced prominent inattention and distractibility since childhood. And he was on medication that was somewhat effective for a few years in his life. And he was unaware of the degree to which his complex symptoms had pervasively affected his functioning quality of life. So this resulted in his inability to sustain employment, financial insecurity, and also adverse interpersonal relationships.

09:27
He also had hypothyroidism with negative antibodies that he was being treated for. He didn't want any treatment for his hypertension and frequent snoring. And metabolically, he was obese with a BMI of 34.7 and a percent body fat of 36.1%, with a history of muscle cramping during exercise. So the diet that was initiated with him was a ketogenic metabolic therapy at 1.5.

09:53
to one ratio, so that's 1.5 grams of fat compared to carbohydrate and protein. And he chose to incorporate a time restricted eating window and consumed two meals a day within a four to eight hour eating window. He achieved a therapeutic nutritional ketosis with a mean serum beta hydroxybutyrate of above 0.8 millimoles per liter and a glucose ketone index of less than six within a couple of days.

10:22
and he had a high average beta hydroxybutyrate level of 4.6 millimoles within one week without any adverse effects. So he very easily fell into nutritional ketosis and he maintained adherence without the muscle cramping he'd experienced with exercise before the KMT due to close attention to electrolyte needs in supplementation during the KMT. Within one week, his generalized anxiety response had decreased from 16 to eight. So that halved within one week.

10:52
and was completely in remission six weeks later, which was amazing. His depressive symptoms completely remitted within five weeks of consistent therapeutic nutritional ketosis. His binge eating ceased within days of the KMT initiation, and he reported that he no longer gets over hungry and he no longer eats without realizing he's eating. The self-compassion scale increased from three to 4.6 over four weeks.

11:19
and the flourishing scale increased significantly from 44 to 53 at 14 weeks. This is just over three months. He reported increased mental focus, increased energy, renewed confidence and motivation to return to work. And within four weeks of initiating KMT, he secured a demanding full-time position, exceeding his previous experience. And after eight weeks, he was given additional responsibilities, handling them well, and began three online college courses.

11:49
which is so interesting. One thing she noted here, which I think is a really good clinical pearl, was that across the course of the intervention, they were photojournaling, taking pictures of each meal, submitting them, and then the registered dietician would look and go, that's amazing, get rid of the grapes, or yep, you're doing well, that's exactly what your plate should look like. Interestingly, at week 10, he reported fatigue during his exercise, because he exercised frequently, actually.

12:19
and photojournaling revealed only one meal a day frequently, rather than the two that he was prescribed, which was inadequate to meet his protein needs and his macronutrient micronutrient goals. So they actually realized after a couple of weeks, around that week eight or nine, that they weren't getting his photojournals in. And then when he reported fatigue, they subsequently got him to start submitting them again and realized he was under eating. This is a super-

12:48
thing that occurs with keto, which is what makes keto quite a successful fat loss diet actually, is that some people can feel super satisfied and not eat. And in this man's case, he needed to eat, yet he wasn't experiencing that hunger that might normally drive someone to eat and instead it was coming up as fatigue. In addition to that, because it was after eight or ten weeks, his body composition had significantly changed and he was a

13:17
whole lot leaner than what he had previously been. And he was really enjoying his new lean physique. So he's a little bit frightened or scared to eat more in case he would lose that. So of course this just required some consultation with the dietitian to assure him that he needed his micronutrients and macronutrients to be where they were prescribed in order to continue to see results and that the fatigue would be resolved

13:45
if he started eating more. So after that consultation, he quickly increased his intake to a minimum of those two meals a day with the increased fats that he was missing. And by 12 weeks, everything was reestablished again. So metabolically, over 12 weeks, he lost 16.8 kilos, his BMI decreased from 34.7 to 29.6, his body fat decreased from 36 to 28.7%,

14:15
without loss of lean body mass because he exercised throughout strength training. And his blood pressure, which wasn't being medicated for, normalized from 136 over 101 to 116 over 81. So this was a real clinical success. And I think of note is that it is easy to under eat during a ketogenic diet and it can go against what you're trying to achieve. And so once that was revealed with

14:43
case one, they were able to resolve any of the challenges he had and continue on. Now, I do want to talk about just one other case or another case that was mentioned, and that was of a 36-year-old married man who had a lifelong history of mood dysregulation, irritability, and trauma from adverse childhood experiences and recent work experiences. So he had a history of childhood onset generalized anxiety, panic disorder, and PTSD.

15:12
as well as recurrent major depression, which was moderately severe and persistent. His anxiety was unrecognized and untreated. And although he did not have a history of mania, hypomania, or mixed states, he had been treated throughout childhood and enlescent with citrulline, which was ineffective, with something called duloxetine for agitation, eschatalapram, and many other medications for things like fatigue, tremor, weight gain, hunger.

15:41
and tachycardia. He had actually discontinued all psychiatric treatment at age 19 but remained symptomatic for 15 years. Metabolically he was overweight with a BMI of 28.7 and a body fat percentage of 26.1. He had an elevated visceral fat level. He had a C-reactive protein of 2.5. His total cholesterol was higher than ideal. So when he adopted the ketogenic metabolic therapy...

16:08
within less than a week and increased his vitamin D3 to 5,000 international units a day with a K2. He added magnesium glycinate and replaced the sugar containing electrolyte drink to one free of added sugars. Interestingly, for this man, he struggled to meet his daily goals for FIC intake. And his serum ketones were variable and fluctuated between 0.2 and 1.8 throughout the first eight weeks of the day.

16:35
ketogenic metabolic therapy. Now this was interesting. So he reported new onset fatigue during exercise and he did actually exercise heavily. So he was exercising, he was doing a ketogenic metabolic diet and he wasn't achieving that consistent state of ketosis. And what they ended up doing was doing a test for his serum carnitine. So carnitine is a transporter of fatty acid in the bloodstream.

17:04
And sometimes there are people who might go on a low carb, high fat diet and still struggle with fatigue and energy. And what can be shown is that they really struggle to use that fatty acids for energy and therefore they're not getting the results that they would expect, either results through an increase in energy or even through fat loss or just the type of benefits you would otherwise see.

17:33
This man was doing a lot of exercise and he was low carb, so there wasn't a really adequate source of energy that he was able to use for that. So that is why he was fatigued. And they found this out by doing an evaluation and measuring his blood level of carnitine and saw that it was low. So he didn't get a baseline serum carnitine until eight weeks into the diet instead of getting it at week one where they were hoping he would get it. The results revealed...

18:01
that he was low in his carnitine levels. So in response to this, the registered dietician advised him to eat red meat because that's where we get carnitine, but they also supplemented him with acetyl-L-carnitine at three grams a day, and that was split into two doses with each of his meals. I don't know if you will remember this, but when I spoke to Dom Dagostino a couple of years ago now, taking L-carnitine was something he recommended, and he mentioned that

18:31
Many of the supplements for carnitine are actually a lot lower than what is considered useful if you are requiring it to be helpful with that transport of fatty acids, particularly with a ketogenic diet. And Dom, as I recall, he supplemented three to four grams a day just as what he did. And when they did the same with this man here, case study number two, the exercise fatigue resolved within days and he quickly achieved consistent therapeutic ketosis.

19:01
with a capillary beta hydroxybutyrate above 0.8 millimoles per liter. So this is really telling. And I would say what I found clinically important with this was the knowledge that, you know, if I have someone that is on a ketogenic diet and they are being really true to the diet principles and unable to achieve nutritional ketosis or feeling that fatigue, then you would absolutely want to try an acetyl-alcarnitine supplement at the dose

19:30
that is described here, you know, 1.5 grams twice a day to help improve the shuttling of fatty acid to be used for energy. Despite the fact that he had inconsistent sort of beta hydroxybutyrate levels, he did get an improvement in that generalized anxiety disorder within two weeks of initiating the ketogenic therapy. And that was completely resolved after four weeks and had remained there till the end of the trial.

20:00
And major depression was moderately severe at the initiation of the ketogenic diet, but it had responded at five and a half weeks and fully remitted at nine weeks, which coincided with the first week in which he achieved consistent beta hydroxybutyrate over eight millimoles. Self-compassion score increased from 2.7 to four over 12 weeks, and he reported having an increased mental focus.

20:25
more patience with coworkers and family, and stated he no longer felt a general pull of anger all of the time. In addition to that, he lost 21 pounds over the 12 weeks, 9.5 kilos. His BMI decreased from 27.8 to 24.9. Percentage body fat had decreased from 26.1 to 17.8, and he dropped his visceral fat level and his CRP normalized, decreasing from 2.5 to 1.

20:52
And one other thing I'll mention here is that he got a lot of those mental health benefits without even having the beta hydroxybutyrate level measured in his blood consistently above 0.8 millimoles. What this tells me is just the change in his diet from the foods he was eating before, the ketogenic therapy, which were highly refined and processed and carbohydrate-laden and nutrient poor to one which was a whole food animal-based ketogenic diet.

21:21
really improved his overall wellbeing despite the fact that he wasn't achieving that nutritional ketosis, which really I think speaks to how important diet quality is going to be when you follow a ketogenic diet or even just when you remove those foods. And there is research to show that just that improvement in diet quality can really help people with regards to feeling better and having a much improved mental wellbeing.

21:49
I do just want to mention the last case study she talked us through as well, which was a 34-year-old single woman who had a history of childhood adversity and trauma, PTSD, child onset general anxiety disorder, and recurrent severe major depressive disorder. She had developed anorexia in adolescence and later binge eating disorder with weight fluctuations up to 100 pounds. She had reported a long history of dietary attempts at weight loss, including the use of low-carb diets.

22:19
She also had been diagnosed with ADHD, the inattentive subtype. She had a long history of comorbidities, such as irritable bowel syndrome, hypothyroidism, obstructive sleep apnea, and chronic fatigue syndrome. She was medically obese with a BMI of 43.7. She had 52.2% body fat and a waist circumference above 35 inches. She had low HDL, and she had elevated insulin resistance score of 67.

22:49
So there was a lot going on with this woman. And she began KMT as adjunctive therapy to medication, which remained unchanged throughout the 12 weeks. Her initial mild transient fatigue resolved rapidly with no other adverse effects. And initially she wasn't that compliant to the ketogenic metabolic therapy because it was affected by travel, holiday events, and family pressure to eat processed carbohydrates and desserts.

23:15
And she realized quite quickly that her lack of preparation for the events, like the family events, contributed to difficulties adhering to her ketogenic metabolic therapy. And so she just adopted simple strategies to prepare ahead. And initially, the generalized anxiety disorder decreased from 12 to six within two weeks, even before being consistently adherent to the ketogenic diet. And by week three, when she had achieved consistent therapeutic ketosis,

23:43
Her mean beta hydroxybutyrate was 1.4 millimoles. Her generalized anxiety disorder score dropped to four for the first time. And one week later, her mean beta hydroxybutyrate was 2.1 and she reported binge eating had stopped. She could now ignore sugar cravings completely and she no longer related to struggles with hunger and cravings.

24:06
And interestingly, despite trying low carb diets before, the ketogenic metabolic therapy did not precipitate a return of anorexic thoughts, body preoccupation, or behaviors which she had lived with all of these years of her eating disorders. And she had learned to navigate social situations in restaurants more easily while maintaining that ketogenic metabolic therapy. She had a complete remission of depression after five weeks. And after a total of eight weeks, she said,

24:34
I do not have depression anymore. I've just noticed I'm happy all of the time." And her general anxiety disorder remitted after five weeks of consistent therapeutic ketosis also. Across the course of 12 weeks, this lady lost 28 pounds or 13 kilos and her BMI decreased from 43 to 37. Her body fat decreased from 52.

25:00
to 48 and her insulin resistance score decreased from 67 to 36. So she also saw some really great results even though initially she struggled because of the social events and just not being prepared. And the fact that her preoccupation with food and her body and her eating disorder had been with her her whole life, that resolved being on that ketogenic diet. And what Dr. Calabresi sort of related that to was that...

25:30
change in her beta hydroxybutyrate levels and the fact that they were above the 0.8 that they were trying to achieve. This is something else that she noted as well is that often we hear that you're in nutritional ketosis when your beta hydroxybutyrate is above 0.5, but what they realized was that you almost needed a bit of a buffer to ensure that you were properly in nutritional ketosis. It had to be just a little bit higher than that.

25:58
I just wanted to share that stuff with you because I find it super interesting the power of the ketogenic diet. And I note with some irritation when I see practitioners talk about the keto diet, like I don't agree with the ketogenic diet. Like it's something you agree or don't agree with. Like it's more of an opinion than an actual therapy. When someone says that, that just tells me they don't actually understand the use case for a ketogenic diet. What I definitely found interesting with all of these cases was that...

26:27
It really just improved the depressive scores and the general anxiety disorder. And because these are so prevalent in society, I just think that if you struggle with your mental health or you know people that struggle with their mental health, even if they're taking medication, this can really be something to explore. And it would be something I'd suggest you explore with a health practitioner just to make sure that you get it right. Because the last thing you want is to try it, get it wrong, and then think it doesn't work for you.

26:56
This is just three case studies, but I know that Dr. Calabresi uses this often in her practice and with great results. As a lot of the practitioners who I've heard talk today and researchers have also utilized the ketogenic diet for other neurological challenges. So hopefully you found it useful. I will pop this study up in the show notes as well so you can have a look at what she was referring to. And then, you know, reach out if you have any other questions.

27:26
So you can do that over on threads, Twitter, Instagram @mikkiwilliden, Facebook @mikkiwillidenNutrition, head to my website, mikkiwilliden.com. All right, team, have the best week. See you later.