Saturated Fat and Your Genes (ACE gene)

There has been a decades-long debate about which type of fat is best: saturated fat vs polyunsaturated fat.

Those in the paleo and ketogenic world are quick to tout the benefits of saturated fat, while others, such as the American Heart Association, promote polyunsaturated fats[ref]. And most people remain just a bit confused about the arguments on either side…
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How does your body respond to saturated fat?

Genetic variants impact your response to dietary saturated fats, and studies show that a high saturated fat can increase the risk of cardiovascular disease when combined with certain gene combinations. Keep in mind that most of these studies are looking at higher saturated fat consumption along with a standard diet (some carbs, some protein, higher fat). Thus, the study results may not hold true for people on a ketogenic diet.

Let’s take a look at the science so that you can figure out what is right for your genes.

ACE (angiotensin-converting enzyme) gene:

The angiotensin-converting enzyme (ACE) plays a role in maintaining blood pressure at a normal level. It works within the body’s blood pressure regulation system, converting angiotensin I into angiotensin II.  Like most of our body’s systems, the right amount of angiotensin II is key: too much will cause blood vessels to constrict and a subsequent increase in blood pressure.

There is a fairly common genetic variant in the ACE gene that impacts levels of angiotensin-converting enzyme. About 20% of people have the ACE deletion/deletion genotype.

Researchers looked at the interaction between ACE deletion and saturated fat intake. People with the ACE deletion/deletion genotype had an increase in blood pressure on a diet higher in saturated fat. There was also an increase in heart disease. In people without the ACE deletion/deletion variant, saturated fat consumption had no effect on the risk of heart disease.[ref]

Another study found that a high-fat diet caused impaired glucose tolerance in people with ACE deletion. The study looked at the effects of a longer-term (6 weeks in the study) high-fat diet. For people with the ACE deletion/deletion genotype, 6-weeks on the high-fat diet doubled their risk for diabetes.[ref]

APOA2 gene:

The protein produced by APOA2 is a type of high-density lipoprotein (HDL).

Genetic variants can result in either APOA2 deficiency or hypercholesterolemia (high cholesterol).

The most commonly studied variant, rs5082, decreases the level of APOA2. It has been linked to increased BMI, visceral fat, HDL levels, and a lower risk of heart disease. The studies that looked at the interaction of this variant with different diets found an increased risk for obesity only in those who had a higher saturated fat intake ( >22g of saturated fat). The variant is also linked to ghrelin (hunger hormone) levels, so it is thought that impaired satiety signaling from the saturated fat may play a role in the higher intake of food for those with the variant.[ref][ref]

A study in the journal Nutrition took the link between saturated fat, APOA2 variant, and obesity one step further and looked into the role of saturated fat from dairy.  The conclusion was that higher-fat dairy increases the risk of obesity with the rs5082 G/G genotype.[ref]

TCF7L2 Gene:

TCF7L2 is a transcription factor gene that has been linked in numerous studies to an increased risk of type 2 diabetes.

• The variant causes a significant increase in triglycerides and total cholesterol when consuming a high saturated fat meal.[ref]
• Another study linked the variant to an increased risk of metabolic syndrome in women, with an even greater risk for those eating a diet higher in saturated fat.[ref]
• Both metabolic syndrome and high triglycerides are linked to an increased risk of heart disease in many studies.

APOE gene:

The APOE E4 allele increases the risk of Alzheimer’s disease. APOE is an apolipoprotein involved in cholesterol transport.

In addition to the well-known link to Alzheimer’s, the APOE E4 allele is also linked to an increased risk of heart disease. A meta-analysis of a bunch of studies shows a 42% increase in heart disease risk for E4 allele carriers.[ref] People with the APOE E4 allele tend to have higher LDL-c, total cholesterol, and HDL levels.[ref]

But the differences in cholesterol levels and other heart-related indices can vary a lot, based on saturated fat consumption.

A 2018 study found that replacing saturated fat with low-glycemic index carbohydrates was most effective at decreasing LDL cholesterol and triglyceride levels in people who carried the E4 allele.[ref]

If you want to know how to determine your APOE type, please see this full article on APOE. Note that this will also show your risk of Alzheimer’s disease (consider whether you want to know this).