Nutrition is always a hot topic, with people holding very strong opinions about the best diet plan to ensure long-term health. However, science is far from settled on how different diets can impact the immune system. To find out more, researchers from the US National Institutes of Health (NIH) took two of today’s most popular diets – vegan and ketogenic (or keto) – to look at how following them affects the body’s ability to fight disease.

In some respects, vegan and keto diets are kind of opposites of each other. Vegan diets, which contain no animal-derived products, tend to be lower in fat and higher in carbohydrates. By contrast, the point of the keto diet is to get the body into a state of ketosis, where stored fat is used as a fuel source, rather than sugars. To achieve this, it’s necessary to eat a very low-carb, high-fat diet.

Questions over which of these two diets is “best” have sparked a lot of debate, but this study was focused solely on the potential effects on the immune system.

The researchers recruited 20 people, with as diverse a mix of ethnicities, genders, body mass indexes (BMIs), and ages as possible. All participants tried both diets over the course of the study, following one for two weeks before swapping over. 

To ensure that everything could be carefully controlled, the group lived on-site at the Metabolic Clinical Research Unit for the duration of the experiment. They were allowed to eat as much as they liked as long as they stuck to the rules for vegan or keto, and were provided with snacks and meals that conformed to the correct diet.

Blood, urine, and stool samples were collected periodically for analysis. The scientists used a multi-omics analytical approach, combining lots of different types of data including biochemical, metabolic, and changes to the microbiome.

In general, the participants consumed fewer calories while on the vegan diet than when they were following the keto diet. As expected, the compositions of both diets varied massively – the vegan diet was roughly 10 percent fat and 75 percent carbs, whereas the keto diet was around 76 percent fat and 10 percent carbs. 

In a press release discussing the findings, the NIH explained that both diets caused “notable changes in all participants.”

Switching to a vegan diet caused rapid changes in pathways linked to the innate immune system, which includes the body’s defenses against viruses. It also boosted pathways linked to red blood cells, which could be due to its higher iron content. Swapping over to the keto diet quickly led to increases in processes associated with the adaptive immune system, such as cellular pathways linked to T and B cells. 

The keto diet also seemed to have more wide-ranging effects, with a greater number of blood proteins and body tissues being impacted. The authors also observed changes in amino acid metabolism, which could be explained by the keto diet’s higher protein content.

Both diets also caused shifts in the microbiomes of the participants, even after following the plans for such a short time. The order in which people followed the diets did not affect the results. 

The study authors noted that the effects were strikingly uniform considering the diversity of the participants involved, but say more research with larger samples is now needed to zero in on specific components of the immune system.

“Uncovering the principles by which nutrition regulates immunity in humans could greatly improve our ability to design personalized nutritional interventions that prevent and treat disease,” they write in their paper. 

“We believe that our present findings further highlight the great potential of highly controlled dietary interventions to better understand integrative physiology, improve human health and mitigate disease.”

The study is published in Nature Medicine.