Strategic Ketosis: Metabolic Memory, Neuroprotection, and Exogenous Supplement Risks

Key Quotes

"Immediately, I will notice, once I get to a certain concentration in my blood, and that's generally around, let's just call it, 0.7 millimolars measured with a finger prick, and then more as you get going, I need less sleep. So instead of 8 to 9 hours, 6 hours, 6 and a half hours, I wake up and I am wide awake. So that's another difference. I wake up and I am wide awake, alert, ready to go. I don't need an hour of booting up and tons of caffeine to get online. I am mentally sharper. My verbal acuity, my ability to think, just has a faster turnover."

Tim Ferriss highlights a personal benefit of ketosis: a significant reduction in sleep needs coupled with increased mental acuity and alertness. This suggests that ketosis can optimize physiological processes, leading to more efficient energy utilization for cognitive functions and rest.

"There are many benefits to being in ketosis, and a ketogenic diet, if we're going to go there, kind of has the benefits of fasting, and there are, for millennia, we know the benefits of fasting without the baggage, without the metabolic baggage, you know, the muscle loss, the fatigue. Obviously, you can't live in a, you know, that level of caloric deficit. But in regards to, you know, the practical applications of it, we know that being in a state of ketosis really quiets the mind, and I think that has major implications."

Dr. Dominic D'Agostino explains that a ketogenic diet offers benefits similar to fasting but without the associated drawbacks like muscle loss and fatigue. He emphasizes that ketosis has a calming effect on the mind, suggesting broad implications for cognitive and neurological health.

"The reason that the ketogenic diet became doubly interesting to me is that when I had Lyme disease the second time, which came with all sorts of co-infections like babesiosis and so on... I ended up weeks later slurring my speech, took me minutes to get out of bed because my joints hurt so much, forgetting friends' names... And basically at my wit's end, I said, 'Well, what can I control because a lot has not done the job?' And I went into strict ketosis. What does that mean? That means that I'm consuming moderate protein, probably getting at least 50% of my calories from fat and keeping my carbohydrates to less than 20 grams a day, probably at that point. And within three or four days, I'd probably say around day three or four, because I wasn't very fat-adapted at the time. My body wasn't well-trained to use fat because I wasn't doing intermittent fasting, which we'll come back to. And within three or four days, effectively all of my cognitive symptoms disappeared."

Tim Ferriss shares a personal account of using a strict ketogenic diet to overcome severe cognitive and physical symptoms associated with Lyme disease. He details the dietary parameters and the rapid improvement observed, suggesting ketosis can be a powerful therapeutic tool for certain health conditions.

"So the spirochete, Borrelia, that spirochete is essentially 100% glycolytic. And when you limit glucose availability and glycolysis, you are targeting the energy systems of that microbe. So that's one thing to think about. And it's well-established now, it wasn't three years ago, but a ketogenic diet, in particular beta-hydroxybutyrate elevated in the blood, stimulates the adaptive immune response. And that's essentially your body's ability to target foreign invaders and neutralize them."

Dr. Dominic D'Agostino provides a mechanistic explanation for why ketosis may be beneficial for Lyme disease. He posits that by limiting glucose, a primary fuel source for the Borrelia spirochete, and by enhancing the immune response through elevated beta-hydroxybutyrate, ketosis can target the pathogen and bolster the body's defenses.

"I think the science is still working to clarify that and make it less ambiguous the benefits that we are deriving from that. But that is kind of like, you know, one of the pitches for the fasting mimicking diet by Dr. Valter Longo, who was one of our keynote speakers at Metabolic Health Summit. And he's presented some really compelling research on that that opened my eyes to that. Five days of fasting can have, I think he presented the time, even three months of effects on sort of cardiometabolic biomarkers. In his case, this would be the fast mimicking diet. So a few hundred calories a day."

Dr. Dominic D'Agostino discusses the concept of "metabolic memory," drawing parallels to muscle memory. He suggests that periods of fasting or ketogenic dieting can create lasting positive changes in metabolic biomarkers, similar to how exercise builds muscle memory, potentially offering sustained health benefits even after the dietary intervention ceases.

"The biggest metabolic lever would be you have enhanced insulin sensitivity. And I think that has been the focus, for example, Ben Bikman wrote a book on this and, you know, doing hundreds of podcasts on insulin resistance, reversing insulin resistance and low carb ketogenic, you know, being effective for that. So that first and foremost, your insulin sensitivity is very high. Your fat oxidation is really high. And your glucose disposal is high. And if you're in a caloric deficit, your ketone uptake is very high."

Dr. Dominic D'Agostino explains that a primary benefit of a ketogenic diet, particularly for those with insulin resistance, is the significant improvement in insulin sensitivity. He highlights that this leads to enhanced fat oxidation, efficient glucose disposal, and high ketone utilization, especially when combined with a caloric deficit.

"The field is trending towards non-1,3-butanediol based exogenous ketones. And that could be free acids. It could be a triester with glycerol. And also the ketone electrolyte salts. But you could also avert part of this just by formulation. The issue is that companies have one molecule and then they test that one molecule. But I think formulation is the way to go. And companies don't kind of want to hear that because they have all their IP in like one molecule. But we've always been a formulation kind of based lab and always saw that these things always have drawbacks when used as a monotherapy. But when you start combining them together, that's when you get better therapeutic effects."

Dr. Dominic D'Agostino discusses the evolving landscape of exogenous ketones, noting a shift away from 1,3-butanediol-based formulations due to potential toxicity concerns. He advocates for a formulation-based approach, combining different ketone types and ingredients to optimize therapeutic effects and mitigate drawbacks, rather than relying on single-molecule products.

"I think in your context, it's hard to say like, you know, to give absolutes. But I would say you can get 80% of the benefits with a low-carb diet. Low-carb meaning, you know, 100 grams a day, just fibrous