Can This Gene Boost Weight Loss on a Low-Carb Diet? (CETP)

The CETP gene codes for a protein called CETP (short for cholesteryl ester transfer protein) [R]. 

CETP helps balance cholesterol and triglyceride levels in the blood. Its main job is to transfer cholesterol and triglycerides between HDL and LDL cholesterol, helping to remove excess fats from the bloodstream. This gene is best known for specifically affecting levels of the “good” HDL cholesterol [R, R].

For this reason, the bulk of CETP research has focused on heart health. Whether CETP activity increases or decreases the risk of atherosclerosis and heart disease is still uncertain [R].

Yet, recent studies have uncovered a link between certain CETP variations and weight loss on ketogenic and other low-carb diets [R]. 

Controversial Effects on Heart Health Possibly Linked with Weight Loss

Before we jump ahead, it’s worthwhile going over CETP’s effect on the heart, since the same mechanism may underlie its role in weight management. 

On the one hand, CETP may help prevent atherosclerosis (artery hardening and clogging) by removing excess cholesterol. On the other hand, reducing CETP activity may help increase HDL and lower LDL to help prevent atherosclerosis [R, R, R, R, R].

We have yet to see exactly how CETP activity and different genetic variations may affect heart health, longevity, and well-being. 

Scientists believe that, by filtering out certain fats from the blood, some CETP variations may also have weight-busting potential–as long as carbs are out of the picture. 

This association is still inconclusive, though, since only a couple of studies on CETP and low-carb diets have been published so far. 

Remember that many other genetic and non-genetic factors also influence a person’s response to diet and their ability to lose weight. Dietary interventions should always be part of a holistic weight management program that takes these factors and your overall health into account. 

With this in mind, let’s review the nutritional strategies that different CETP genotypes might benefit from–and what this means for low-carb and ketogenic diet modifications. 

CETP is a gene that influences cholesterol and triglyceride levels. Certain variations may enhance weight loss in people on low-carb diets. 

Initial Study Suggests CETP Variations and Carb Restriction Act in Synergy 

Scientists have proposed that recently discovered CETP variations may act in synergy with low-carb diets. 

Mainly, both carbohydrate restriction and CETP can reduce triglycerides. Like carbohydrate restriction, some CETP variations may also remodel LDL and HDL cholesterol into less dangerous (bigger) particles and enhance fat burning. This ultimately leads to healthier weight loss [R].  

In fact, this new CETP association reveals an overlooked aspect of weight loss: fat metabolism in blood vessels. 

It’s well known that obese people are much more likely to have raised blood fats and other metabolic problems. Yet, lowering blood fat levels was never seen as a mechanistic prerequisite for weight loss until a study published in 2006 first pointed out this link [R]. 

The authors of the study suggested that the body needs to be efficient at processing and removing excess blood fats for people to lose weight when they follow carb-restricted diets–and CETP variations seemed to play in. 

The study included only 86 healthy adults who were told to restrict carbs to about 10% of total energy intake, a level that induces slight ketosis. 

This type of diet is also called a very-low-carb diet. Put simply, it’s the same as a liberal keto diet that provides about 50 g/day of carbs in a 2000 kcal/day regime. By comparison, the stricter keto version allows for only 20 g/day of carbs or less. 

On average, people on the very-low-carb diet lost around 14 pounds (6.4 kg) over 4-12 weeks, with large variability within the group. Once the researchers ruled out differences in caloric intake, gender, age, and activity, they concluded that genetics was a significant contributor [R]. 

The main CETP SNP researchers found a weight-loss association with was rs5883. Unlike some other better-known CETP SNPs, we still don’t know much else about rs5883 and how it might affect CETP activity [R]. 

The rare T allele (TT and TC genotypes) of rs5883 was much more frequent in people who lost more weight on a very-low-carb diet. 

For example, about 50% of people who lost the largest amount of weight–around 45 lbs (20 kg)–were carriers of the rare T allele. To put things into perspective, only about 6% of the general population carry this allele. 

Overall, it appears that most people (CC genotype) have a typical weight loss response to the very-low-carb, keto-style diet based on this CETP variation. They may still benefit from a low-carb diet, but their response seems to be less pronounced. 

A very-low-carb diet can still be a healthy choice for people with the CC genotype. But based on this study, they are likely better off focusing on other proven diets for healthy weight loss. 

Genetics aside, the authors emphasize that diet compliance is key. Sticking to the diet was important for weight loss independent of genetic variations. In the study, people lost about 1 lb for each additional week of staying on the very-low-carb diet [R]. 

People with TT and TC CETP rs5883 genotypes looking to lose weight seem to be well suited for keto-type diets.  Contrarily, those who carry the more common genotype (CC) lost less weight on average on the same diet.

Another CETP Variant Linked With Weight Loss from Low-Fat & Keto Diets

One of the best-studied CETP SNPs is rs3764261. Variations in this SNP have already been linked to everything from metabolic syndrome to high blood fats (HDL, LDL, and triglyceride levels) to macular degeneration to HIV infection. 

Two studies of about 900 overweight adults in total recently looked at rs3764261 in a new light. 

People with the CC genotype on a high-fat diet had larger increases in HDL cholesterol and decreases in triglycerides, compared to a low-fat diet at 6 months. They didn’t find any differences in response to these two diets among people with the AA and CA genotypes [R]. 

People with the CETP rs3764261 AA or CA genotype have a typical response to both keto- and low-fat diets. The health effects of low-fat diets are mixed. People who fall within this group might be better off choosing any weight-loss diet, as long as they’re getting enough heart-healthy fats and nutrients. 

People with the CETP rs3764261 CC genotype might experience greater benefits from the keto diet. They don’t do well on low-fat diets. 

SNP Summary and Table

You can see your genotypes for CETP in the table below. However, keep in mind that these associations are based on studies from certain ethnic populations — so you should interpret your results with caution if you are not descended from one of these specific groups!

Primary SNP: CETP rs5883

• ‘TT’ and ‘TC’ = Enhanced weight loss from a very-low-carb/keto diet
• ‘CC’ = Typical, less pronounced weight loss from a very-low-carb/keto diet

Secondary SNP: CETP  rs3764261

• ‘CC’ = Better response to the keto diet (↑ HDL, ↓ triglycerides); avoid low-fat diets
• ‘AA’ and ‘AC’ =  Typical blood fat levels in response to both keto- and low-fat diets;

Population Frequency

About 10% of the worldwide population carry the CT genotype for CETP rs5883; The TT genotype is extremely rare, while 90% of the population carry the CC genotype. Here are some interesting ethnic differences:

• 22% of people of African ancestry are CT and over 1% are TT 
• 10% of European descendants are CT
• Only 6% of Central and South Americans are CT, while TT is almost nonexistent (under 0.3%)
• The T allele is highly uncommon among East Asians, 99.8% of which are CC
• Similarly, almost 97% of South Asians are CC

When it comes to the other SNP, about 51% of people worldwide carry the CC genotype for CETP rs3764261; 9% are AA and 40% are AC. The CC genotype is somewhat less common among people of African ancestry (44%) and more common among people of East Asian ancestry (68%).