The 3–5 Day Modified Fasting Protocol Dr. Dominic D’Agostino Actually Uses

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