Surely, we have all experienced the effect of hunger on our psyche at some point. English, with its great flexibility, has coined the term hanger, a combination of anger and hunger, to refer to the beast that makes us roar beyond our stomachs when we show bad mood due to hunger.
Spanish is not far behind and has a good repertoire of sayings about how appetite transforms us, and from there we know that "with an empty stomach, no one shows joy," but also that "hunger sharpens wit."
Science has already suggested that ghrelin, the hunger hormone generated in the absence of food - occasional, not malnutrition - is associated with a potential positive impact on attention and memory.
Now, a new study explores another factor related to nutrition and dietary patterns that may be involved in improving cognitive function: the profile of the microbiota generated by intermittent fasting.
A study conducted by scientists from the Biomedical Research Institute of Malaga and the Nanomedicine Platform (IBIMA BIONAND Platform) demonstrates that intermittent fasting significantly enhances memory and attention in adults with obesity, by reshaping the intestinal microbiota and reducing systemic inflammation.
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The study, whose conclusions are published in Gut, is led by Francisco J. Tinahones, Head of the Endocrinology and Nutrition Service at the Virgen de la Victoria Hospital in Malaga, and Isabel Moreno-Indias, from the Cellular and Molecular Endocrinology Group at IBIMA, along with Virginia Mela, from the Obesity, Diabetes, and Comorbidities Group also at IBIMA.
Fasting vs. Ketogenic and Mediterranean Diets
The research compared intermittent fasting (done on alternate days) with two other hypocaloric diets. Specifically, 96 obese adults (body mass index between 30 and 40 kg/m²) participated in a three-month randomized clinical trial. The volunteers were randomly assigned to the three different diet groups.
One group followed a balanced Mediterranean diet; a second group maintained a ketogenic diet (high in fats and low in carbohydrates, inducing a state of ketosis), and the third group adhered to alternate-day intermittent fasting, which consisted of alternating a day of regular intake, without intentional caloric restriction, with another day of very reduced intake: less than 25% of the usual calories.
As explained by Francisco J. Tinahones to this medium, "we chose to compare intermittent fasting with the Mediterranean and ketogenic diets, as these are more widespread. The low-carb diet has been known for quite some time, and the classic hypocaloric diet based on Mediterranean foods is what we have been using in the last decade." However, intermittent fasting "is a weight loss therapeutic strategy used more recently in clinical practice. It was interesting to compare these three strategies, especially considering the objective of this study, which aimed to see if they had any influence on cognition."
Regarding fasting, Professor Tinahones emphasizes the importance of healthcare professionals guiding patients who want to use this strategy to lose weight. "There are several options, such as 16-hour fasting, skipping breakfast or dinner. The alternate-day fasting strategy is also published in the literature; we found that the rates, losses, or patients abandoning this strategy over three months were very low," he comments.
There are several modalities within the alternate-day intermittent fasting: from exclusively consuming infusions or calorie-free products on fasting days to consuming around 300-400 calories, mainly based on proteins. "It must be guided by a healthcare professional and adapt the type of fasting to the individual's characteristics. Like any other hypocaloric diet, protein intake must be ensured for it to be a normoproteic intake," Tinahones emphasizes.
In the research, before and after the intervention period, all participants underwent standard neuropsychological tests to measure working memory, processing speed, sustained attention, and inhibitory control. In addition, inflammatory markers in blood (main proinflammatory cytokines) were analyzed, and the intestinal microbiota was sequenced. To delve into the mechanisms of action, in vitro studies were conducted with microglia (the main brain defense cell) derived from the patients undergoing intermittent fasting before and after the diet, as well as transplants of their microbiota in laboratory mice.
The study's result is that while the diets produced comparable weight loss (an average reduction of 7% of initial body weight), the intermittent fasting group showed better cognitive performance in the different tests compared to the other diets. Additionally, levels of systemic inflammation markers (such as ferritin and MCP-1) decreased significantly, suggesting a potent anti-inflammatory effect in addition to mere fat loss.
Regarding the microbiota, intermittent fasting reconfigured the bacterial community: genera related to chronic inflammatory responses and neurotoxicity decreased, while genera producing short-chain fatty acids (such as butyrate), known to strengthen the intestinal barrier and modulate brain microglial activity, increased.
Animal experiments confirmed that transferring this microbiota improved the "cleaning" of neuronal waste and reduced the proinflammatory activation of microglia due to obesity, an effect that could not be replicated with the mere administration of ketone bodies.
This finding was the most striking for the researchers. As Professor Tinahones points out, the hypothesis that intermittent fasting could have a positive neurocognitive impact, activating attention and reflexes, was "quite plausible" given the physiology of human beings, "who have gone through significant famine periods; when the hominid or man went several days without eating, it is logical that neurocognitively activated to be able to hunt or obtain food, otherwise, we would have disappeared as a species."
"What we did not have as a very certain hypothesis was that it would be the microbiota or the changes in the microbiota induced by intermittent fasting that mediated to activate that neurocognition." So the results derived from transferring the microbiota to animal models were surprising. "We did not expect that improvement in short- and long-term neurocognitive aspects of memory in the animal model when transferring the microbiota, nor that substances produced by the microbiota were responsible for reducing that brain inflammation and activating microglia."
The finding suggests that this dietary pattern could somehow influence the reduction of cognitive decline in certain neurological diseases. The study's author, a professor of medicine at the University of Malaga, cautions that this conclusion was not the objective of the study and points out that this is preliminary research, conducted in the short term and in an animal model, so "specifically designed studies will be needed to assess this eating strategy" in this hypothetical context.
However, he emphasizes that the study's conclusions "break with the traditional view that only calories matter. The same weight loss can have different impacts on health depending on the strategy used to achieve it."