Summary
Dom D'Agostino fields listener questions on ketogenic diets and ketosis in this two-part AMA with Peter Attia's team, covering both general principles and specific protocols. Part one focuses on how ketosis affects different types of exercise performance, the nuances of achieving and maintaining nutritional ketosis, and Dom's research background in neuropharmacology and metabolic biochemistry.
Key Points
- Achieving nutritional ketosis typically requires limiting carbohydrates to 20-50g/day, with individual thresholds varying by activity level and insulin sensitivity.
- Endurance exercise performance can be maintained or improved on a ketogenic diet once fat-adapted (4-12 weeks), but high-intensity glycolytic efforts may suffer.
- Exogenous ketone esters raise blood BHB more effectively than ketone salts, but taste and GI tolerance remain barriers for most users.
- Protein intake on keto should not be excessively restricted -- 1.5-2.2g/kg supports muscle preservation without meaningfully impairing ketosis.
- Dom D'Agostino's research background spans neuropharmacology and metabolic biochemistry, grounding his keto recommendations in mechanism-level understanding.
- Blood ketone levels of 1-3 mmol/L represent the therapeutic range for most metabolic and cognitive benefits of nutritional ketosis.
Key Moments
Intermittent ketosis promotes metabolic flexibility even if you tolerate carbs
Dom D'Agostino explains that even healthy individuals who tolerate carbs can benefit from periodic ketosis, as it activates a genetic program for efficient fat burning and ketone production that persists like metabolic memory.
"I believe when you go into a state of ketosis, whether you do it with ketogenic diet or fasting, it changes, it actually activates a genetic program that actually can allow you to burn fat and make ketones more efficiently."
Five to seven days of restricted keto per month can replace a three-day fast
D'Agostino suggests that a 50% calorie-restricted ketogenic diet for five to seven days per month can achieve similar benefits to a three-day fast, targeting a glucose-ketone index of one to two for insulin suppression and autophagy.
"you could restrict calories like 50% on a ketogenic diet and do that for six days a month. And I believe you would achieve at least for me a glucose ketone index between one to two."
Breath ketone monitoring and the future of multi-analyte sensors
D'Agostino evaluates breath acetone meters alongside blood meters for ketone tracking, noting that breath devices correlate well in fasted states but can give false positives after meals or alcohol.
"The breath acetone does correlate well with beta hydroxybuty from my measurements. If you're in a fasted state, so it's exceptionally good in a fasted state."
