Tim FerrissAll Things Ketones, How to Boost Cognition, Sardine Fasting, Diet Rules, & More — Dr. Dom D’Agostino
At a glance
WHAT IT’S REALLY ABOUT
Dom D’Agostino on ketosis, fasting strategies, biomarkers, brain, and immunity
- The discussion centers on how ketogenic diets, fasting variants, and exogenous ketones might be applied to brain health, including Alzheimer’s/dementia, with Dom D’Agostino emphasizing brain energy metabolism and neuroinflammation as key themes.
- Dom D’Agostino describes practical measurement and targeting of ketosis using glucose ketone index (GKI), notes common biases in home glucose meters, and underscores tracking broader cardiometabolic biomarkers such as HSCRP, insulin, and ApoB.
- He outlines “sardine fasting” as a fasting-mimicking approach he uses situationally and discusses why he prefers it over water-only fasting in certain contexts, including concerns about cancer cachexia.
- The conversation expands to metabolic psychiatry, cancer-related “ketone metabolic therapy,” and immune modulation, including the idea that ketogenic states may differentially affect innate versus adaptive immune activity.
- They cover concrete implementation details—meal timing, food choices, managing sleep disruption while fasting, and selective use of supplements—along with Dom’s cautious stance on rapamycin and nuanced views on wine consumption.
IDEAS WORTH REMEMBERING
5 ideasRaising ketones may produce noticeable, time-limited symptomatic changes in some dementia cases.
He described observing temporary, repeatable improvements in Steve Newport’s tremors and animation after coconut oil/MCT oil doses that raised ketones (roughly into the 1–2 mmol range), with effects waning after a few hours and returning with another dose.
He sees brain energy metabolism and immune/inflammation drivers as central to Alzheimer’s.
He framed Alzheimer’s/dementia as involving glucose hypometabolism plus multiple contributing factors (transporters, PDH activity, vascular issues, and inflammation), and said accumulating evidence suggests infections may contribute in some cases, linking this to immune-system involvement.
He emphasizes measuring ketosis with practical tools (GKI) while accounting for device bias.
He said he prefers Keto-Mojo for recommending to individuals because it calculates glucose ketone index (GKI) and, in his group’s comparisons, readouts aligned better with their lab assays than other approaches; he also noted consumer glucose meters can trend high versus lab draws.
He favors fasting-mimicking strategies that maintain nutrition, especially for cancer-related contexts.
He described “sardine fasting” (e.g., about a can/day) as a fasting-mimicking approach he uses situationally and encouraged in certain contexts; he tied its rationale to creating a caloric deficit while maintaining nutrition (especially omega-3s) and supporting favorable signaling (lower insulin/mTOR, higher AMPK) and GKI targets over several days.
He prioritizes inflammation and broader metabolic biomarkers over LDL alone when assessing risk.
He said HSCRP is a better indicator of cardiovascular disease risk than LDL cholesterol and highlighted tracking a broader cardiometabolic panel (insulin, A1C, triglycerides, ApoB, Lp(a), etc.), especially when interpreting ketogenic approaches.
WORDS WORTH SAVING
5 quotesI think the fifth horseman is really the immune system.
— Dr. Dominic D’Agostino
I like to do what I call, I mean, I kinda coined it, it's like sardine fasting.
— Dr. Dominic D’Agostino
I'd like to draw attention to that real quick because HSCRP is a better indicator of cardiovascular disease than LDL cholesterol.
— Dr. Dominic D’Agostino
I think the beauty of ketogenic therapies is that it's pleiotropic, right? So which means it's many mechanisms working in synergy.
— Dr. Dominic D’Agostino
I take melatonin not to sleep, but as a neuroprotective agent that has a whole host of beneficial effects for the brain, also Alzheimer's disease, also cancer, especially breast cancer.
— Dr. Dominic D’Agostino
High quality AI-generated summary created from speaker-labeled transcript.
