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BDNF and the brain

Also called: Brain derived neurotrophic factor

Written by Reviewed Sep 2026

The brain's switch to a new fuel during a fast is measured directly and solid in people. The claim that fasting raises BDNF was tested directly in people, and it did not happen.

What it is

BDNF is a protein that brain cells release. It helps brain cells survive, grow their branches, and form new connections. It also supports the strengthening of connections that sits behind learning and memory. The more brain cells fire, the more BDNF they make and release. It is one of the most studied molecules in brain research on exercise, rich surroundings, and how antidepressants work.

The suggested link to fasting is chemical. The ketone BHB blocks a group of enzymes that keep genes switched off. In theory, that would help switch on the BDNF gene, so a change in body fuel would turn into a more adaptable brain. It is a neat idea, and there is a large body of rodent research behind it.

This page splits two questions that usually get merged. Does the human brain change fuel during a fast? Yes, and that was measured three different ways. Does fasting raise BDNF in a person? That was tested directly, and it did not.

How it works

The fuel part first, because it is the part that holds up. The brain is about 2% of body weight, but it uses around 20% of the energy the body burns at rest. It stores almost no glycogen. It cannot burn long fats at any useful rate, because they do not get into the brain easily and brain cells have little ability to burn them. Ketones solve that. They are small, they dissolve in water, they are carried into the brain by doorway proteins, and brain cells burn them. After 3.5 days without food, sugar use in the brain's grey matter falls 26%, and blood flow to the brain does not change. The brain's uptake of BHB rises 13-fold, and ketones supply about a quarter of the brain's energy. By 5 to 6 weeks, they are its main fuel.

The BDNF part is where the story stops being shown in people. The rodent work measured BDNF in brain tissue on restricted diets. The work in people measures BDNF in blood from the arm, which is not the same thing. Most human BDNF in blood is stored in platelets, the small cells that help blood clot, and it is let out when blood clots. That is why BDNF in serum (clotted blood) is much higher than in plasma (unclotted blood), and why platelet count can skew the result. And how well blood BDNF reflects brain BDNF in people is not well known. Those are real limits of measurement. They are why the "no effect" result below is about BDNF in the blood, not about the brain.

What switches it on

In the rodent research, a restricted diet. In people, the thing that reliably moves blood BDNF is exercise, and hard exercise most of all.

On the timing
There is one direct test of the timing question in people, and it found nothing. A 20 hour fast lowered blood sugar and raised ketones, so the fast clearly did its job. It had no effect on BDNF in the blood. No study in people has measured BDNF in brain tissue during a fast, because there is no way to do that in a living person.

What has been measured

In people

How ketones feed the human brain is one of the best-measured things in all of fasting research. The BDNF claim has been tested twice in people. Once was by fasting. Once was by giving ketones as a drink, at a dose that clearly changed blood flow to the brain. Both found no effect on BDNF. The evidence on thinking and memory is thin and mixed. All of that belongs on the page together.

  • The biggest study, testing for harm (which is a different question from benefit). 122 people either started skipping breakfast for a 16 hour fast over 10 days, or were put on a waiting list. They did repeated online thinking tasks and rated their mood and focus twice a day. The fasting group did not think worse or feel worse than the others. They did feel less focused while fasting before noon, compared with after they broke the fast in the afternoon (Journal of Health Psychology, 2026).
  • An 8 week study with real brain measures. 40 older adults with insulin resistance and no memory problems were put on either 5:2 fasting or a healthy living diet. The fasting group lost more weight. The two diets had similar effects on insulin signals from brain cells (measured in tiny particles from the blood), on MRI estimates of brain age, on brain sugar, and on blood sugar and fat markers. Alzheimer's markers in spinal fluid barely changed. Both diets improved planning skills and memory, and the fasting diet did better on certain specific tests. The comparison group was on another healthy diet, not doing nothing (Cell Metabolism, 2024).
  • The second "no effect" result. It rules out the obvious objection that the fast was too short to raise ketones enough. 14 adults with obesity, average age 56, took 30 mL of a BHB ketone drink or a dummy drink three times a day for 14 days. Each person tried both. Blood flow in the main neck artery rose 12%, and flow in the arteries at the back of the neck rose 11%. Other measures of blood flow to the brain rose 10 to 12%. Scores on a symbol-matching thinking test improved by 2.7 correct answers, and that went along with the blood flow changes. But against the study's own prediction, the ketone drink did not change BDNF in the blood (Journal of Physiology, 2021).
  • The direct test, in 12 volunteers. It looked at a 20 hour fast, 90 minutes of light exercise, and hard exercise, alone and together, and measured BDNF in blood from the arm. The 20 hour fast lowered blood sugar and raised ketones, but had no effect on BDNF. Light cycling raised serum BDNF by 6%, whether people had eaten or fasted. That rise came from a 7% rise in platelets. Six 40 second bursts at 100% of peak effort raised BDNF 4 to 5 fold more than light exercise did. BDNF went along with lactate in the blood during the bursts. Changes in blood flow force in the brain did not match the BDNF changes (Journal of Physiology, 2023).
  • How the brain's fuel changed at 3.5 days, in 9 healthy volunteers. Sugar use fell 26% in grey matter and 27% in white matter. Blood flow to the brain did not change. The brain's uptake of BHB rose 13-fold, and ketones supplied about a quarter of the brain's energy needs (Journal of Cerebral Blood Flow and Metabolism, 1994).
  • Ketone levels measured directly inside the brain with a strong MRI scanner aimed at the back of the brain. They were 0.05 mmol/L before fasting, 0.60 after two days, and 0.98 after three. Brain lactate rose too (Journal of Cerebral Blood Flow and Metabolism, 2000).
  • The first measurement. Doctors placed tubes in the brain blood vessels of three patients with obesity through 5 to 6 weeks of starvation. It showed ketones had replaced sugar as the brain's main fuel (Journal of Clinical Investigation, 1967).

In animals and in cells in a dish

Nearly every public claim that fasting raises BDNF traces back to two rat studies from 2000 and 2001. They measured BDNF in rat brain tissue on restricted diets. They are real findings about the rat brain. The matching test in people was tried, and it did not find the same thing in the blood.

  • In rats: a restricted diet raised BDNF in the brain, and that protected brain cells from injury caused by overstimulation (Journal of Molecular Neuroscience, 2001).
  • In rats: a restricted diet raised the number of new brain cells and switched on BDNF in a memory area of the brain called the dentate gyrus (Journal of Molecular Neuroscience, 2000).
  • There are two possible reasons for the mismatch, and neither has been settled. It may be a true difference between species. Or blood BDNF may not reflect brain BDNF, which is the measurement limit described above. It may be both.
  • In mice, brain autophagy during fasting is worth noting here, because the two most relevant mouse studies disagree. One used glowing markers across the whole animal and found almost no recycling boost in the brain after 24 to 48 hours without food. A later study used a different way of detecting it and found strong recycling in brain cells at the same times. Any claim about fasting, the brain and cell clean-up should carry that disagreement.
  • The well-known write-ups that link the rodent findings to benefits in people are reviews. Much of what they pull together is rodent work (Nature Reviews Neuroscience, 2018).

Why it matters

This is the page where splitting people from other species does the most work. The popular version blends them into one confident paragraph, but the facts underneath point two ways.

What is solid, in people, and measured directly: the brain switches fuel during a fast. Three methods agree: tubes in the blood vessels, PET scans and MRI scans. Ketones supply about a quarter of the brain's energy by 3.5 days, and become the main fuel over weeks.

What is not: that fasting raises BDNF in a person. That was tested directly at 20 hours. The fast was checked, with blood sugar falling and ketones rising, and nothing happened to BDNF. A ketone drink, at a dose that clearly changed blood flow to the brain and one thinking test, also did nothing to BDNF.

And here is the comparison that matters if BDNF is what you care about. In the same people, in the same study, hard exercise moved BDNF 4 to 5 fold more than light exercise. How hard you exercise is doing that work, not the fast.

A claim you will see repeated

"Fasting increases BDNF" is one of the most repeated lines in this whole area. It comes from rat brain tissue on restricted diets, in work from 2000 and 2001. That work is real, and it is about rats. The result in people is "no effect", and it is a strong one, not a failed experiment. Blood sugar fell and ketones rose, so the fast worked, and BDNF did not move. A second study in people gave ketones directly, at a dose strong enough to change blood flow, and BDNF still did not move. Saying this is not a claim that fasting does nothing to the human brain. Brain BDNF has never been measured in a living, fasting person, and right now it cannot be. What can be said is that the blood test people point to as proof has been done, and it came back negative.

Sources

  1. Study in people2023
    Fasting for 20 h does not affect exercise-induced increases in circulating BDNF in humans

    Journal of Physiology

    12 volunteers tried a 20 hour fast, 90 minutes of light exercise, and hard exercise, alone and together. Fasting lowered blood sugar and raised ketones, but did not change BDNF, a brain growth protein, in the blood. Light cycling raised BDNF 6%, because platelets rose 7%. Six hard 40 second sprints raised BDNF 4 to 5 fold more than light exercise. Blood flow changes in the brain did not match BDNF changes.

    12 volunteers, examining the isolated and interactive effects of a 20 hour fast, 90 minutes of light exercise, and high intensity exercise on peripheral venous BDNF. Fasting decreased glucose and increased ketones (P less than or equal to 0.0157) but had no effect on BDNF (P greater than or equal to 0.4637). Light cycling raised serum BDNF 6 plus or minus 8%, mediated by a 7 plus or minus 6% rise in platelets. Six 40 second intervals at 100% of peak oxygen uptake raised plasma and serum BDNF and the BDNF-per-platelet ratio 4 to 5 fold more than light exercise. Cerebral shear stress changes did not correspond with BDNF changes.

  2. Study in people2021
    Short-term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross-over trial

    Journal of Physiology

    14 adults with obesity, average age 56, drank 30 mL of a ketone drink or a dummy drink three times a day for 14 days, then switched. Blood flow in two neck arteries rose 12% and 11%. A thinking speed test improved by 2.7 correct answers, in step with better blood flow. The researchers expected BDNF to rise, but it did not change.

    Placebo controlled double blind crossover, 14 adults with obesity, mean age 56, 30 mL of a beta-hydroxybutyrate ketone monoester or placebo three times daily for 14 days. Common carotid flow +12%, vertebral artery flow +11%, vertebral cerebrovascular conductance +12%, vertebral shear rate +10%. Digit symbol substitution improved by 2.7 correct responses, correlating with the cerebrovascular improvements. Contrary to the study's own hypothesis, beta-hydroxybutyrate did not change fasting serum or plasma BDNF.

  3. Study in people1994
    Brain metabolism during short-term starvation in humans

    Journal of Cerebral Blood Flow and Metabolism

    9 healthy volunteers were scanned before and after 3.5 days without food. The brain's use of sugar fell 26% in grey matter and 27% in white matter, evenly across the brain. Blood flow to the brain did not change. The brain's uptake of the ketone BHB rose 13-fold. By 3 days, ketones covered about one quarter of the brain's energy needs.

    9 healthy volunteers before and after 3.5 days of starvation. Cortical grey matter glucose metabolism fell 26%, white matter 27%, uniformly across regions, confirmed at 24% by an independent Fick determination. Cerebral blood flow unchanged. Net brain uptake of beta-hydroxybutyrate rose 13-fold. Ketones account for approximately one quarter of cerebral energy requirements at 3 days.

  4. Study in people2000
    Human brain beta-hydroxybutyrate and lactate increase in fasting-induced ketosis

    Journal of Cerebral Blood Flow and Metabolism

    Healthy adults had the ketone BHB measured inside the brain with a strong MRI scanner. It went from 0.05 mmol/L when fed to 0.60 after two days of fasting and 0.98 after three. Brain lactate rose from 0.69 to 1.47 mmol/L. Brain levels tracked blood levels closely.

    Occipital lobe beta-hydroxybutyrate by 4-tesla magnetic resonance spectroscopy in healthy adults: 0.05 plus or minus 0.05 mmol/L non-fasted, 0.60 plus or minus 0.26 after two days, 0.98 plus or minus 0.16 after three. Brain lactate rose from 0.69 plus or minus 0.17 to 1.47 plus or minus 0.22 mmol/L. Plasma and brain BHB correlated at r = 0.86.

  5. Study in people1967
    Brain metabolism during fasting

    Journal of Clinical Investigation

    Doctors sampled blood going into and out of the brain in three obese patients who went 5 to 6 weeks without food. Ketones had replaced sugar as the brain's main fuel.

    Cerebral vessel catheterisation in three obese patients through 5 to 6 weeks of starvation, demonstrating that beta-hydroxybutyrate and acetoacetate had replaced glucose as the predominant fuel for brain metabolism.

  6. Study in people2024
    Brain responses to intermittent fasting and the healthy living diet in older adults

    Cell Metabolism

    40 older adults with insulin resistance and no memory problems did the 5:2 fasting plan or a healthy eating plan for 8 weeks. The fasting group lost more weight. Otherwise the two plans did about the same for brain insulin signals, brain age on MRI, brain sugar, and blood sugar and fats. Alzheimer's markers in spinal fluid barely changed. Both plans improved planning and memory, and fasting did better on some measures.

    40 cognitively intact older adults with insulin resistance randomised to 5:2 intermittent fasting or a healthy living diet for 8 weeks. Intermittent fasting produced greater weight loss. The two diets had comparable effects on neuronal insulin signalling biomarkers in neuron-derived extracellular vesicles, the MRI brain-age-gap estimate, brain glucose by spectroscopy, and blood carbohydrate and lipid markers. Cerebrospinal fluid Alzheimer's biomarkers changed minimally. Both diets improved executive function and memory, with intermittent fasting benefiting more on certain measures.

  7. Study in people2026
    Stable cognitive performance while adapting to intermittent fasting: A randomised controlled trial

    Journal of Health Psychology

    122 people either started skipping breakfast for a 16 hour daily fast or waited their turn, over 10 days. They did online thinking tests and rated their mood and focus twice a day. The fasting group thought and felt just as well as the waiting group. They did feel less focused in the morning before eating than in the afternoon after.

    Randomised, waitlist controlled, N = 122, adapting to 16 hour breakfast-skipping intermittent fasting over 10 days with repeated online cognitive tasks and twice daily mood and concentration measures, analysed by Bayesian multilevel modelling. Fasting participants did not have lower cognitive performance or mood than controls, though they felt less concentrated while fasting before noon than after breaking the fast in the afternoon.

  8. Animal study2001
    Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury

    Journal of Molecular Neuroscience

    In rats. Eating less raised BDNF, a brain growth protein, in the brain. That protected nerve cells from damage caused by overstimulation. This paper and the next one are where almost every public claim that fasting raises BDNF comes from.

    Rat brain. Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury. This paper and the one below are the origin of essentially every public claim that fasting increases BDNF.

  9. Animal study2000
    Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats

    Journal of Molecular Neuroscience

    In rats. Eating less raised the number of new brain cells and switched on BDNF in a part of the brain called the dentate gyrus.

    Rat dentate gyrus. Dietary restriction increases the number of newly generated neural cells and induces BDNF expression in that region.

  10. Review of studies2018
    Intermittent metabolic switching, neuroplasticity and brain health

    Nature Reviews Neuroscience

    A widely cited review linking fasting, the body's switch from sugar to fat and ketones, and the brain's ability to adapt. It is a review, and much of the science it draws on was done in rats and mice.

    The influential synthesis connecting fasting, the metabolic switch and neuroplasticity. It is a review, and much of the mechanistic content it synthesises is rodent work.