On a recent podcast, Dr. Dominic (“Dom”) D’Agostino — the neuroscience professor who has spent the last 15+ years researching ketosis and autophagy in his lab — shared the exact short “modified fasting” approach he now personally uses every 1–3 months instead of prolonged water fasting.
Here is what he said, verbatim or faithfully paraphrased:
The Protocol He Described
- Duration: 3–5 days (minimum 3, he stops at 5)
- Calories: ≈500 kcal per day
- Goal: create a large energy deficit while staying in therapeutic ketosis (low blood glucose + elevated ketones)
- Macronutrients he uses:
- Very low carbohydrate
- Moderate protein — about 50 g protein total (split into two ≈25 g meals)
- The rest from fat (he mentioned sardines, mackerel, egg yolks, liver, some low-carb vegetables)
- Exercise: light to moderate (brisk walking 1–2 hours/day or easy body-weight work) — he says it “magnifies the response”
- Frequency: once per month, or every 2 months, or every 3 months — whatever fits the individual
Why He Likes It Better Than Water Fasting
- “Way easier and almost effortless” compared to zero-calorie fasting
- Avoids electrolyte problems (electrolyte imbalance, blood-pressure drops, orthostatic hypotension)
- Still allows one or two small meals with the family → socially sustainable
- He personally feels higher energy and vitality on days 4–5 than at baseline
Effects He Reports (in himself and people he has guided)
- Rapid improvement in fasting insulin, triglycerides, hs-CRP, and fasting glucose — sometimes “remarkably different” in only 3–5 days
- These improved cardiometabolic markers stay in optimal range for weeks to months even after returning to a normal diet
- No measurable negative hormonal effects (LH, FSH, testosterone) when kept to 3 days; only minor effects at 5 days
- Better preservation of lean mass than his previous long water fasts
How It Triggers Autophagy (his exact mechanistic explanation)
- Ketogenic state alone increases autophagic flux (via insulin suppression)
- Adding a severe energy deficit amplifies it further
- Holding therapeutic ketosis + deficit for ≥72 hours is when autophagic flux is “maximized” (based on rodent data and human biomarker surrogates)
- Light exercise and moderate protein restriction provide additional stimulation
Who He Thinks Benefits Most
Almost everyone, but especially anyone with any degree of insulin resistance, elevated triglycerides, high hs-CRP, or less-than-optimal fasting insulin/glucose.
Cautions He Mentioned
- Beyond 5 days he has observed counter-regulatory hormonal effects (lower LH/FSH, lower testosterone)
- People who are already very lean (he gave BMI 19–20 as an example) probably should not do it
- Prolonged water fasts (7+ days) cut his testosterone in half in the past; this 3–5 day version does not
Frequency He Personally Uses
He used to do long water fasts and continuous ketogenic dieting for a decade, but now he has shifted to this 3–5 day modified version every 1–3 months while eating a normal (non-ketogenic) diet the rest of the time.
That is the entire protocol — nothing added, nothing exaggerated.
If you want to hear it in his own voice, the original interview is public on YouTube and podcast platforms
