Fasting and the brain: what does fasting do to autophagy and memory?

What happens in the brain when you fast?

The brain uses about a fifth of the body's energy, and normally almost all of it comes from glucose. When you fast, the liver's sugar store gradually empties over the first day. The liver then starts turning fat into ketones, especially beta-hydroxybutyrate (BHB), which the brain can use instead of glucose. PMID 29321682 PMID 6061736 PMID 16848698

Classic studies of prolonged fasting showed that after several weeks, ketones can cover more than half of the brain's energy needs. This shift from sugar to fat and ketones is what researchers call metabolic switching. The timeline below is approximate – it depends on what you ate before, how active you are and your body weight. PMID 29321682 PMID 6061736 PMID 16848698

Brain autophagy: what we know – and what we don't

Autophagy is the cells' clean-up system, in which worn-out proteins and cell parts are broken down and recycled. Nerve cells don't divide, so they depend on this clean-up working. Failing autophagy is seen in Alzheimer's and Parkinson's disease. The mechanism itself is covered in more detail in our article on autophagy. PMID 20534972 PMID 40345145

The often-cited evidence that fasting increases brain autophagy is a 2010 mouse study. After 24–48 hours of fasting, researchers saw a clear increase in autophagy in nerve cells. But mice have a much faster metabolism and lose weight quickly, so 48 hours of fasting for a mouse is nothing like 48 hours for a human. In humans, autophagy can only be measured in blood cells. An Australian trial found slightly higher autophagy in blood cells after 6 months of intermittent time-restricted eating compared with controls, but no increase from baseline. Claims that you must fast exactly 16, 24 or 72 hours to clean your brain therefore have no human evidence. PMID 20534972 PMID 40345145

Ketones, BDNF and brain energy

Ketones are not just fuel. In animal studies, BHB also acts as a signalling molecule that can raise the growth factor BDNF, dampen inflammation and make nerve cells more resilient to stress. The researchers behind the metabolic switching theory believe the alternation between fasting and eating is what matters – not hunger itself. PMID 29321682 PMID 6061736

In older people and in early Alzheimer's, the brain becomes worse at using glucose while it can still use ketones. That is why ketones are being studied as possible support for the ageing brain. However, this is still a research field with small studies, and fasting has not been shown to prevent dementia. PMID 29321682 PMID 6061736

What do human trials show?

There are only a few good randomised trials of fasting and the brain in humans, and they are small and short. A 2021 review concluded that animal studies are promising but human results are mixed. The table shows the key findings. PMID 38901423 PMID 40345145 PMID 34579042 PMID 32986097

The most interesting trial comes from the US National Institute on Aging. Forty older adults with insulin resistance were assigned to either 5:2 fasting or a healthy diet based on US dietary guidelines. Fasting produced more weight loss, but both groups showed better insulin signalling in the brain and a slightly younger brain age on MRI. Alzheimer's markers in spinal fluid barely changed. The message is that healthy food and weight loss do much of the work – fasting is one way to get there. PMID 38901423 PMID 40345145 PMID 34579042 PMID 32986097

More is not better: risks of long fasts

An overnight fast of 12–14 hours is unproblematic for most healthy people. If you fast for more than 24 hours, the risk of dizziness, headache, low blood pressure, salt imbalances and gout flares rises. With fasts of several days, the body also breaks down protein from muscle. PMID 31881139 PMID 32986097

After 60, muscle mass is one of the most important factors for staying independent. In the TREAT trial, participants on 16:8 eating lost part of their weight as muscle. Fasting without enough protein and strength training can therefore do more harm than good. The broader link with weight and blood sugar is covered in our article on time-restricted eating. PMID 31881139 PMID 32986097

Who should not fast – and when to seek help

For some groups, fasting can be outright dangerous. Always talk to your doctor before fasting longer than overnight if any of the following applies to you. PMID 31881139

• You have type 1 diabetes or take insulin or a sulfonylurea – risk of dangerously low blood sugar.
• You take SGLT2 inhibitors (e.g. empagliflozin or dapagliflozin) – risk of ketoacidosis, even with normal blood sugar.
• You have or have had an eating disorder.
• You are pregnant, breastfeeding or underweight.
• You are over 70, have lost weight unintentionally or struggle to maintain muscle mass.
• You take blood pressure medication, diuretics or lithium.
• Call your out-of-hours doctor (1813 in the Capital Region of Denmark) for severe dizziness, confusion, vomiting or palpitations while fasting. Call 112 for reduced consciousness or seizures.

A cautious 8-week plan for the brain

If you want to try fasting, start gently and track things you can feel: sleep, energy, hunger and weight. The plan below sticks to fasting patterns tested in humans and combines fasting with the habits that have the best evidence for the brain: exercise, sleep and blood pressure control. PMID 31881139 PMID 38901423

• Weeks 1–2: Finish dinner by 7 pm and have breakfast no earlier than 7 am. That gives a 12-hour overnight fast.
• Weeks 3–4: Extend to 14 hours if you feel well. Drink water, tea or black coffee during the fast.
• Weeks 5–6: Optionally try 16 hours on 2–3 days a week, or 5:2 with about 500–600 kcal on two non-consecutive days.
• Throughout: Eat 25–30 g of protein per meal and do strength training at least twice a week.
• Weeks 7–8: Assess sleep, energy and weight. Keep only what you can sustain – regularity matters more than fast length.