Dietary breakthrough: Large-scale research evidences benefits of metabolic diets

09 Feb 2023 --- Following years of research by Dutch scientists from Wageningen University & Research (WUR), Maastricht University Medical Center (MUMC) and Radboud University Medical Centre (RUMC), a breakthrough discovery has been made about the health benefits of a personalized diet based on a person’s metabolic profile.

Additionally, nutrition was reaffirmed as an important strategy to improve cardiometabolic health, a significant underlying condition linked to obesity.

“It’s in a very preliminary phase and it’s very new research, that’s why it’s published at such a high level – nobody has done it,” Dr. Lydia Afman, associate professor of Human Nutrition and Health, WUR, who led the study tells NutritionInsight. 

“Many people say, ‘I’m better off with that diet’ or ‘I’m feeling better if I consume that’ and ‘it’s just a feeling.’ But nobody tested whether you’re better off if you are a certain phenotype.”

The findings provide a proof-of-concept that modulating dietary macronutrient composition based on tissue-specific IR phenotype with healthy, isocaloric diets can induce more pronounced, clinically relevant improvements in cardiometabolic health, independent of changes in body weight.

The research was conducted in a large-scale public-private partnership within the Top Institute Food and Nutrition (TiFN). Funding for the study was obtained from industrial partners DSM Nutritional Products, FrieslandCampina and Danone Nutricia Research and AMRA Medical. 

Personalizing nutrition to the metabolic level
The study published in Cell Metabolism tracked a three-month nutrition program of 242 participants. The program was adapted to their metabolic profile and the recommended diet complied with the “Guidelines for a good diet” of the Health Council of the Netherlands.

The research investigated the efficacy modulation of dietary macronutrient composition according to muscle insulin resistance (MIR) and liver insulin resistance (LIR) phenotypes and their effects on glucose homeostasis parameters, cardiometabolic health, health-related quality of life, and perceived well-being.Glucose, fat metabolism and sensitivity to the insulin hormone were measured before and after the experiment.  

“Normally, we just put people on a healthy diet, maybe high in carbohydrates or high in fat, that’s it. But now we looked at somebody’s metabolic phenotype – the way your metabolism reacts – if your insulin is working less in the liver or less in the muscle,” Afman explains. 

The participants’ glucose, fat metabolism and sensitivity to the insulin hormone were measured before and after the experiment. Insulin plays an essential role in the regulation of sugar metabolism. These are important indicators of the risk of diabetes and cardiovascular disease. The study did not focus on weight loss.

“This is the first study done, so of course, it has to be repeated because no one has done it before. All the participants were on a healthy diet – according to the dietary guidelines in the Netherlands – and they all improved their health. 

“When they were given one of the variations within those healthy guidelines – that fit their metabolic health phenotype – they fared even better and we saw an additional effect,” Afman outlines. 

“That’s the power of this study. This means if we do this again, in a more free-living population, because now they (the participants) had very strong dietary advice, weekly counseling and all the products were provided, especially the key products. If we did this in a more free-living situation, would we see the same results?”

The participants were divided into two groups based on their metabolic profiles. In the case of reduced insulin, cells cannot control sugar levels in the blood. This can lead to Type 2 diabetes and cardiovascular disease.    

The subjects were overweight (BMI above 25 kg/m2) but had no diabetes or cardiovascular disease at the time of the experiment.

The phenotyping conducted was not complicated – in that the participants received a glucose drink and had their insulin and glucose levels measured at various time points after consuming the drink. 

“It is very interesting that while the participants were on a healthy diet, there were still additional effects (better performance) when the diet was tailored to their metabolic profile,” Afman says.

Health benefits based on phenotype
Participants who were less sensitive to the effect of insulin in their muscles appeared to benefit more from a diet that is relatively high in protein. For example, low-fat diets with lots of dairy products and nuts, as well as dietary fiber from wholemeal products and vegetables. 

The participants with a reduced effect of insulin in the liver benefited more from a diet high in monounsaturated fatty acids, which can be found in olive oil and nuts, for instance.

“I see possibilities in the future. If you see that certain people will benefit from certain diets, then you can focus on that. Testing the phenotype is very important, of course. So, for instance, building a phenotype test that’s very easy to use at home could be helpful as well,” Afman explains.

There are indications from the research that parameters related to glucose metabolism and insulin action or resistance – such as plasma glucose and insulin concentrations and indices based on these concentrations – may predict the response to dietary modification.The study shows that adjusting the macronutrient composition of a diet based on the IR phenotype can improve cardiometabolic health.

The findings demonstrate that individuals with the MIR phenotype showed a more pronounced cardiometabolic health improvement upon a low-fat, high-protein, and high-fiber (LFHP) diet. In contrast, individuals with the LIR phenotype had the most significant cardiometabolic health benefit from a high-MUFA (HMUFA) diet.

Dietary approach
These findings provide evidence for the greater effectiveness of a precision nutrition strategy based on tissue-specific IR phenotypes over a “one-size-fits-all” dietary approach within the general dietary guidelines in improving cardiometabolic health.

A significant strength of the study is that it is the first to investigate the effects of modulating dietary macronutrient composition according to tissue-specific IR with a prospective, double-blind, randomized design in many individuals. 

The study is a proof-of-concept focused on specific IR phenotypes prevalent in about 30% of the overweight population. Future research has to demonstrate whether more metabolic and IR phenotypes that respond differentially to dietary macronutrient modulation can be defined.

In other relevant research developments, a separate study published in Cell Metabolism funded by the Medical Research Council found that eating a large breakfast was beneficial for appetite control, which plays a central role in weight management but did not affect metabolism.

By Inga de Jong

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