Whether or not a diet will work may be "written" in our genes. That's the main takeaway of an elaborate study recently published in the journal Genetics.
David Threadgill, Ph.D., of the Texas A&M College of Medicine and College of Veterinary Medicine & Biomedical Sciences, is the senior investigator, and William T. Barrington is the first author of the new paper.
Threadgill and his team started out from the observation that, despite national dietary guidelines, the number of Americans living with metabolic syndrome — an umbrella term for a group of cardiometabolic risk factors — has soared.
In Threadgill's opinion, this occurs because dietary guidelines are built on the false premise that one size fits all. "Dietary advice, whether it comes from the United States government or some other organization, tends to be based on the theory that there is going to be one diet that will help everyone," he says.
"In the face of the obesity epidemic," he continues, "it seems like guidelines haven't been effective." Threadgill and his team hypothesized that genetic differences might influence how someone responds to a diet.
The researchers tested this hypothesis in mice, which, as the authors explain in their paper, are similar to humans in genetic makeup, as well as in their predisposition to develop cardiometabolic illnesses, such as heart disease and diabetes.
Different diets for genetically distinct mice
To test their hypothesis, the researchers designed four genetically different strains of mice, to which they fed four different diets.
The diets were designed so that they were the equivalent of four historically popular human diets: the American/Western diet, the Mediterranean diet, the Japanese diet, and the Maasai/ketogenic diet.
The American diet was high in fats and refined carbs, the Mediterranean one was higher in fiber and included red wine extract, the Japanese diet consisted of rice and green tea extract, and the ketogenic diet was high in fat and protein but consisted of very few carbs.
"We matched fiber content and matched bioactive compounds thought to be important in disease," Barrington explains, in order to get the rodents' diets to be as similar as possible to the human ones.
The mice were also fed a control diet consisting of standard chow. The researchers monitored the mice's cardiometabolic health, measuring their blood pressure, blood sugar, cholesterol levels, and looking out for signs of a fatty liver.
Levels of physical activity were also monitored, as well as the rodents' appetite and food intake.
One size really doesn't fit all
Overall, the three "alternative," healthier diets did seem to work for most mice, but the fourth genetic strain responded very badly to the Japanese diet.
Although these mice "performed just fine on all of the other diets, [they] did terrible on this diet, with increased fat in the liver and markings of liver damage," says Barrington.
As for the ketogenic diet, two genetic strains responded very well to it, and two very poorly.
"One became very obese, with fatty livers and high cholesterol," Barrington says, while the other had more fat and became less physically active, despite maintaining a lean appearance.
"This equates to what we call 'skinny-fat' in humans, in which someone looks to be a healthy weight but actually has a high percentage of body fat," explains the first author.
As expected, the American-style diet increased obesity and metabolic syndrome in most mice. The Mediterranean diet, on the other hand, had mixed results, with some mice staying healthy, and others gaining weight.
'Precision dietetics' may yield better results
"[W]hat we're finding," Barrington continues, "is that it depends very much on the genetics of the individual and there isn't one diet that is best for everyone."
In their paper, the authors conclude:
"If similar genetic-dependent diet responses exist in humans, then a personalized, or 'precision dietetics,' approach to dietary recommendations may yield better health outcomes than the traditional one-size-fits-all approach."
The study's first author also shares some hopes for future research, saying, "One day, we'd love to develop a genetic test that could tell each person the best diet for their own genetic makeup."
"There might be a geographical difference based on what your ancestors ate, but we just don't know enough to say for sure yet," adds Barrington.