total recall

Intermittent fasting could significantly shape long-term memory

If our brains are anything like those of mice in a maze, fasting may hone recall skills.

A man walking on top of a labyrinth wall

We all know to eat “brain-boosting” foods like blueberries, fish oil, and turmeric. But what may be just as important as what you eat is when you eat it.

A growing number of animal studies on intermittent fasting get at just this concept — that by abstaining from food for part of, or all of a day over time, we can boost our brain’s function. But here’s the catch: Studies in mice or rats don’t mean that the same will be true in people — but there is a chance intermittent fasting works in similar ways in our brains. And that deserves further detailed study in humans.

For now, here’s what we know: studies that have put mice and other animals on intermittent fasting regimens have had surprising effects — including on long-term memory.

What’s new — Mice may not remember childhood memories. We cannot ask them, of course. But when mice are put on an intermittent fasting diet, they seem to retain information for much longer than their non-fasting peers.

The latest evidence of this is detailed in a new study published Tuesday in Molecular Psychiatry, in which researchers found that lab mice that ate every other day appeared to have better memory compared to mice that followed a restricted diet and mice that ate whenever they wanted.

The mice that fasted every other day performed better on a maze test than mice that ate 10 percent fewer calories per day (this reduction was decided on because the mice that fasted intermittently ended up eating 10 percent fewer calories overall). The only difference in their diet was timing.

The researchers put the mice in a Morris Water Maze, which forces mice to swim through a maze to reach the safety of an escape platform. After multiple times in the pool, they learn to take increasingly direct routes to the escape platform — that is, they start to remember the most efficient pathways.

Mice in a mouse swim-test remembered their way around best on an intermittent fasting regimen — unlike Alice.

Getty / Andrew_Howe

The mice that ate every other day performed better on this test after 10 days than each of the other groups of mice. Later, the researchers examined these mice’s brain tissue, noting that the intermittent fasting mice showed more neurons in the hippocampus — a brain area that plays a major part in memory and learning. These mice also showed an increase in activity in a gene called Klotho. This gene encodes for a protein that is thought to increase cognition in both mice and humans.

Taken together, these observations were likely related to one another — and to intermittent fasting, the researchers conclude.

Here’s the background — Intermittent fasting is often pitted against calorie restriction — i.e., a diet in which you eat fewer calories every day — because its proponents claim both regimens may hold a similar health benefit, but timed fasting isn’t as much effort as reducing food intake.

The reason why people stick to an intermittent fasting regimen more successfully than a diet is because during the “feeding” period they can eat whatever they want and not count calories. Theoretically, this approach may be useful as a treatment for conditions like diabetes, metabolic syndrome, and even diseases that affect the brain.

But the science into intermittent fasting isn’t clear cut — and one of the mysteries is whether it has a demonstrable effect that’s as good as or better than calorie-restricted diets. In one study, alternate-day fasting improved cognitive function in mice compared to a high-fat diet or a “regular” diet (eating whenever they wanted). In another study, also in mice, intermittent fasting appeared to lead to the creation of more brain cells and stronger connections between them. Intermittent fasting has also shown promise in decreasing signs of Alzheimer’s disease — but again, the study is in mice.

Why it matters — In the new study, researchers show that compared to undergoing a small degree of calorie restriction (10 percent), intermittent fasting may have a bigger brain health pay-off: Specifically, better memory retention, and more brain cells.

Importantly, intermittent fasting in this study is not being compared to more extreme calorie restriction, the researchers write. Such extreme diets are the norm in many other mouse-based experiments used to demonstrate the benefits of calorie restriction on health and the brain.

It’s possible in a lab to restrict a mouse’s diet by almost half — but it would be extreme for a human to follow that kind of regime. A 10 percent caloric restriction, however, is perhaps more realistic for humans to manage, and theoretically, potentially easier to achieve if you eat during allotted windows of time.

Intermittent fasting might have similar health benefits to simply eating less, and wouldn’t be as hard.

Ana Maria Serrano/Moment/Getty Images

What we don’t know — It’s still unclear whether or not the memory effect observed in mice holds true humans. Studies that have looked at the potential cognitive effects of intermittent fasting on human cognition are few and small. Studies on ketogenic diets, which are in some ways similar to fasting, have found limited success.

We also don’t know whether or not the brain benefits for the fasting mice were down to timing, or because they got more exercise. The authors note that the fasting mice were more physically active, so there may be a crucial element to this relationship that we need more research to tease apart.

The authors do, however, write that the next step in answering the question would be to conduct clinical trials that compare the effect of intermittent fasting to calorie restriction in people with certain conditions that affect the brain, like depression, anxiety, and Alzheimer’s disease for several months. Intriguingly, the gene they highlight in the new study, Klotho, may play a future role in developing medicines that mimic the brain-boosting effects of fasting. Intermittent fasting itself could also be used as the cognitive enhancer many (many) already believe it to be.

Abstract: Daily calorie restriction (CR) and intermittent fasting (IF) enhance longevity and cognition but the effects and mechanisms that differentiate these two paradigms are unknown. We examined whether IF in the form of every-other-day feeding enhances cognition and adult hippocampal neurogenesis (AHN) when compared to a matched 10% daily CR intake and ad libitum conditions. After 3 months under IF, female C57BL6 mice exhibited improved long-term memory retention. IF increased the number of BrdU-labeled cells and neuroblasts in the hippocampus, and microarray analysis revealed that the longevity gene Klotho (Kl) was upregulated in the hippocampus by IF only. Furthermore, we found that downregulating Kl in human hippocampal progenitor cells led to decreased neurogenesis, whereas Kl overexpression increased neurogenesis. Finally, histological analysis of Kl knockout mice brains revealed that Kl is required for AHN, particularly in the dorsal hippocampus. These data suggest that IF is superior to 10% CR in enhancing memory and identifies Kl as a novel candidate molecule that regulates the effects of IF on cognition likely via AHN enhancement.
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