Ketogenic diet and immune system

A striking relationship between the immune system and the very low-calorie ketogenic diet has been explored in a recent study.

Proven weight loss interventions improve biomarkers of oxidative and inflammatory stress in overweight and obese people, with a greater effect in patients treated with a very low-calorie ketogenic diet than in those subjected to a conventional hypocaloric diet or a low-calorie diet. bariatric surgery.

This follows from a recently published study, coordinated by researchers from the Center for Biomedical Research in the Physiopathology of Obesity and Nutrition Network (CIBEROBN) in Spain, carried out at the Hospital Clínico Universitario de Santiago de Compostela, in Spain, and led by Felipe Casanueva and Ana Belen Crujeiras. After evaluating nearly thirty inflammatory markers (cytokines) and oxidative stress markers in overweight and obese patients who have followed a ketogenic diet very low in calories and fat, it has been shown that nutritional ketosis (the deficit in the supply of carbohydrates , inducing fat catabolism and generating ketone bodies), along with diet-induced weight loss, further improves the immune response in obese patients compared to bariatric surgery or a standard low-calorie diet.

In the opinion of Ana Belén Crujeiras, principal investigator of the study, “these results highlight the possible usefulness of this nutritional strategy to combat obesity and its associated diseases, such as cancer and viral infections (such as COVID-19), as well as to promote healthy ageing.

Members of the research team. In front: Ana B. Crujeiras, Felipe F. Casanueva, Marcos C. Carreira. Behind: Maribel Rendo, Jesús Iglesias, Paula M. Lorenzo and Andrea G. Izquierdo. (Photo: CIBEROBN)

This study, carried out in Spain, is the first to exhaustively analyze the effect of the very low-calorie ketogenic diet on an extensive panel of inflammatory and oxidative stress biomarkers. Specifically, it has been evaluated whether nutritional ketosis induced by a weight loss intervention such as this type of diet in overweight or obese patients modulates the inflammatory state and oxidative stress compared to hypocaloric diet and bariatric surgery. To do this, in addition to including volunteers with normal weight, overweight and obese patients were recruited, who were randomly assigned to three intervention groups: very low-calorie ketogenic diet, hypocaloric diet or bariatric surgery.

The research confirms not only that excess weight increases circulating levels of proinflammatory cytokines and decreases anti-inflammatory ones, but also that patients undergoing different weight loss interventions experienced differential changes in circulating cytokine levels and biomarkers of oxidative stress. This effect was always greater and more noticeable in those patients who followed the very low calorie ketogenic diet, compared to those who followed a conventional hypocaloric diet or underwent bariatric surgery.

These effects were seen primarily during the phase where nutritional ketosis occurs. The changes produced after the diet mainly occurred in cytokines such as IL-11, IL-12, IL-2, INF-gamma, INF-beta, Pentraxin-3 or MMP1, which, after weight loss with this intervention, reach levels similar to those observed in people with normal weight.

Based on the evidence obtained, the authors of the study suggest that, after a weight loss intervention using a very low-calorie ketogenic diet, there is an improvement in inflammatory responses and in innate immunity.

Higher antioxidant capacity

According to the main researcher of the study, “the circulating levels of oxidative stress biomarkers are modulated, with a greater effect induced by diet, which can be attributed to nutritional ketosis given the correlation between the concentration of ketone bodies and oxidative stress biomarkers ”.

But, in addition, it can be seen how the effect of treatment with a very low-calorie ketogenic diet on oxidative stress markers is more notable in the acute phase of nutritional intervention, since it correlates positively with the highest concentration of circulating ketone bodies. In the words of the CIBEROBN researcher, “this intervention could increase mitohormesis”, that is, the adaptive response that occurs after an increase in mitochondrial activity together with an increase in the production of reactive oxygen species, “raising the capacity antioxidant, metabolic health and life expectancy”.

Positive effect on inflammation

This study arises from the evident correlation established between obesity and inflammation. Obesity is known to be characterized by chronic low-grade inflammation and excess visceral fat is a source of cytokines. In this way, people with obesity not only suffer from more inflammation, but are also subjected to greater oxidative stress, which promotes some comorbidities associated with obesity itself.

Given this pathophysiological situation, there was clinical interest in clarifying whether different interventions of proven efficacy to reduce body weight acted differently on inflammatory and oxidative markers, “something that until now had not been done as extensively and exhaustively as carried out in this study”, emphasizes Crujeiras.

As summarized by the research coordinator, Felipe Casanueva, “ketogenic diets very low in fat and normal protein allow not only rapid weight loss while maintaining muscle mass, but also have a positive effect on inflammation and the resolution of comorbidities linked to obesity. “An interesting field of research is opening up that will surely provide interesting insights in the future,” says Casanueva.

The study is titled “Immunomodulatory effect of a very-low-calorie ketogenic diet compared with bariatric surgery and a low-calorie diet in patients with excessive body weight.” And it has been published in the academic journal Clinical Nutrition. (Source: CIBEROBN)