Fasting-mimicking diet

A fasting-mimicking diet is a five-day, low-calorie, low-protein, plant-based eating plan built to trigger the biology of a fast while still letting you eat. It carries the only human fasting data that touches biological age — a median of about 2.5 years lower after three monthly cycles — but that figure comes from one exploratory analysis, on a score built from routine blood and blood-pressure readings rather than an epigenetic (DNA-methylation) clock, and the diet was supplied by a company in which two of the authors hold equity.

If the longevity framing appeals to you, one five-day cycle a year is a reasonable, low-stakes option — break it gradually. Don't buy it as a proven anti-aging treatment, and skip it if you are among the people who shouldn't fast at all.

What it is

The fasting-mimicking diet is one of four common ways of fasting, alongside daily time-restricted eating, alternate-day fasting and occasional multi-day fasts (see Fasting). For five days you eat a small amount of mostly plant-based food, low in calories and protein, designed to push the body into the same low-fuel state as a water fast. Several human trials have tested it, typically as three monthly cycles in a row. The version used in the trials below is sold commercially as ProLon, by the company that supplied the diet for the research.

The appeal is the same as for any fast: going long enough without much food turns down the body's growth signalling and switches on the cell's recycling system, autophagy. The fasting-mimicking diet's pitch is that you get that without days of eating nothing.

The biological-age result, and why to hold it loosely

The headline finding came from an exploratory look at stored blood samples from two trials. In one, 100 adults were randomly assigned to their normal diet or to five consecutive days of the diet once a month for three months. Three monthly cycles were associated with a biological age a median of about 2.5 years lower (an average of about 1.5), independent of weight loss. The same work reported lower insulin resistance, less liver fat measured by imaging, and a shift in the immune-cell profile toward a younger pattern.^[1]

Four things should temper how you read it:

It is not an epigenetic clock. The "biological age" is a composite score built from seven routine readings — albumin, alkaline phosphatase, creatinine, C-reactive protein (an inflammation marker), HbA1c (the three-month blood-sugar average), systolic blood pressure and total cholesterol.
It partly restates the inputs. The improvement tracked changes in four of those seven readings, including inflammation, blood pressure and blood sugar. So the 2.5 years is largely a re-expression of the short-term drops in those markers reported alongside it, not an independent sign that aging slowed.
Not everyone improved. Between a fifth and almost a third of participants on the diet came out biologically older, depending on the trial — though in the trial that reported it, almost two-thirds of the controls did too. The participants also started out healthier than average, scoring younger than their actual age before the diet began.
Commercial ties. The trial diet was supplied by the company that sells it, two of the authors hold equity in it, and the university involved has licensed the diet to the company and can receive royalties.

This was one analysis, not a trial designed to test biological age, and it measured an estimate rather than survival. Encouraging, not established. The same result is discussed in its mechanistic context under deregulated nutrient sensing.

Autophagy: one small first trial

The diet's central selling point — that it switches on cellular recycling — has only just been measured in people, in blood cells. A pilot randomised trial gave 30 healthy adults, average age about 49, one of two formulations of the diet or a control diet, and tracked autophagy in their blood cells. It describes itself as the first clinical trial to measure this. The authors report a trend toward higher autophagic flux with the commercial formulation, which persisted two days into normal eating; the other formulation showed only a later trend. The flux difference was not statistically significant (the significant change was in a static marker), the control group was leaner at the start, whether blood cells reflect what happens in other tissues is untested, the trial was sponsored by the diet's maker, and the authors call for larger studies.^[2]

A second pilot trial, of 46 healthy adults randomised to one of two 7-day fasting-mimicking diets or a normal-calorie diet, measured the fuel-sensing signals rather than biological age: in both fasting-mimicking groups fasting glucose fell by about 10% and IGF-1 (insulin-like growth factor 1, a growth signal) by about 35% compared with the control group. Like the autophagy trial, it ran a single cycle and had company involvement.^[3]

You don't need a fast to engage the system: two hours of hard cycling in trained athletes activated autophagy in muscle too, though the same duration at low intensity did not.^[4]

What hasn't been tested

Whether it makes anyone live longer. No trial of any fasting protocol has measured human lifespan, and none is likely soon.
Whether better blood numbers mean longer life. In the largest dietary-restriction experiment in mice, 960 genetically diverse female mice, restriction and fasting extended life — but the metabolic improvements they produced were not associated with living longer.^[5] That is exactly the assumption the diet's biomarker results rely on.
Anything beyond the short term. The human data cover three to four monthly cycles and a few days of autophagy measurements.

Safety and who should be careful

It is a form of fasting, so the usual fasting cautions apply: not for anyone with a history of disordered eating, during pregnancy or breastfeeding, for children and adolescents, for underweight or frail older adults, or for anyone prone to osteoporosis — bone-formation markers fall within days of a fast. Anyone with type 1 diabetes, or taking insulin, sulfonylureas or any other glucose-lowering medication, needs medical supervision because of the risk of dangerously low blood sugar. Menstrual changes are a stop signal: reproductive-hormone suppression belongs to deep energy deficits such as multi-day fasting. The full list is under Who should not fast.

How you end it matters. Reintroduce food gradually rather than breaking a multi-day fast with a large meal. The return to eating carries its own risk signal: in mice, a cancer-driving mutation arising during the burst of tissue renewal after a long fast led to more tumours than the same mutation during fasting or normal eating.^[6] Human relevance is unknown, but it argues against habitual very long fasts for anyone with a cancer history.

What to do

Get the daily basics first. A consistent 12–14 hour overnight fast captures most of what fasting realistically offers, at almost no cost.
If the longevity case appeals, one five-day cycle a year is reasonable. The evidence is real but small.
Don't pay for "reverses aging". The 2.5-year figure is a blood-test score from one analysis with commercial ties, not proof that you will age more slowly.
Break it gradually, and skip it entirely if you are on the list of people who shouldn't fast.