The promise of personalized nutrition

Studies find that a high-fat, low-carb diet improves
cholesterol levels in people with a particular gene variant

An international team of researchers led by Lu Qi at the Harvard School of Public Health recently reported in the Journal of Lipid Research that a high-fat, low-carbohydrate diet appears to improve cholesterol levels in obese people with a particular gene variant.

The researchers studied the effects of this diet in a two-year randomized trial called Preventing Overweight Using Novel Dietary Strategies, or POUNDS LOST, involving more than 700 obese individuals. They observed that individuals with a certain variant of the CETP gene ended up with increased levels of high-density lipoprotein (known as HDL or good cholesterol) and decreased levels of triglyceride six months into the trial.

The researchers then did a second independent, two-year randomized trial called the Dietary Intervention Randomized Controlled Trial, or DIRECT, with 171 obese individuals. Again, only those with the specific CETP variant on the high-fat, low-carb diet showed significant improvement in HDL and triglyceride levels.

The results from these trials “indicate that individuals with the CETP rs3764261 CC genotype might be more responsive to low-carbohydrate, high-fat weight-loss diets in raising HDL cholesterol and lowering triglyceride levels compared with those without this genotype,” the researchers wrote. “Our findings provide novel information to the development of effective strategies for dietary interventions and supportive evidence for the notion of a personalized dietary intervention based on genetic background.”

To understand these results, you have to know a bit about the cholesteryl ester transfer protein — the CETP in the genotype name.

CETP is a glycoprotein that regulates blood lipids by facilitating the transfer of cholesteryl ester and triglycerides between HDL and other lipoproteins. Mutations in the CETP gene affect CETP expression or activity, which affects HDL cholesterol levels. The variant CETP rs3764261 CC is a HDL cholesterol-decreasing mutation.

Previous genomewide-association studies had established that the CETP genetic variant rs3764261 has a stronger association with HDL cholesterol levels than  other loci across the human genome. However, investigations exploring the relationship between the CETP genetic variants and dietary fat intake thus far have been mostly short-term studies that detected either no association or associations that could not be replicated. The findings reported in the JLR paper confirm the association and provide the replication that had been lacking.

Qi and co-authors emphasize that they administered the diets under conveniently managed conditions, which facilitated adherence to the regimen by more than 80 percent of the participants throughout the duration of both trials. Also, they noted that study participants either highly restricted their saturated-fat intake or were counseled to avoid foods high in saturated fats.

Weight loss in individuals with the CETP rs3764261 CC genotype was insignificant during the first few months, with most of them regaining weight six months into the trials. The researchers say this indicates that weight loss is only partially dependent on restoration of HDL and triglyceride levels.

Also, they affirmed that even after adjusting for changes in body weight, the restoration of lipid levels remained significant, with the elevated HDL levels persisting throughout the two-year duration of the trials – an indication of the continuous beneficial effect of the high-fat, low-carb dietary intervention even after weight regain.

The team now will explore whether other genetic variants or mechanisms interact with dietary intervention and affect not just lipid levels but also other physiological traits, such as glucose, body fat and blood pressure.

Vivian Tang Vivian Tang is a graduate student at the School of Pathology and Laboratory Medicine at the University of Western Australia.