Saturated Fat and Your Genes

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…

It may depend on your genes as to which answer is right for you.

Genetic Studies:

There have been several studies that investigated the effects of a high saturated fat diet on cardiovascular disease – stratified by genetic variants.

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.

A recent study looked at the interaction between a common variant of the ACE gene, known as the ACE deletion, and saturated fat.  It found that for those with the ACE deletion, a diet higher in saturated fat was significantly associated with increased blood pressure and heart disease. In those who were not homozygous for the deletion variant, saturated fat consumption had no effect on the risk of heart disease. About 20% of Caucasians are homozygous for the variant (a little more or a little less for other population groups).

Another study found that people on a longer-term (6 weeks in the study) high-fat diet had impaired glucose tolerance after eating when compared to their baseline diet, leading to a doubling in the risk for diabetes.[ref]

Check your 23andMe results for rs4343 (v4, v5):

  • A/A: typical response to saturated fat (ACE insertion/insertion)
  • A/G: typical response to saturated fat (heterozygous – ACE deletion/insertion)
  • G/G: ACE deletion/deletion  — high saturated fat diet may increase blood pressure and risk of heart disease.[ref] A long-term high fat diet may also impair glucose tolerance.

APOA2 gene:
The protein produced by APOA2 is a type of high-density lipoprotein (HDL). Genetic variants can result in either APOA2 deficiency or hypercholesteremia.

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]  Studies have also found that this variant is linked to a lower risk of heart disease.

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 did play a role in the risk of obesity with rs5082.

Check your 23andMe results for rs5082 (v4, v5):

  • A/A: typical
  • G/G: increased risk of obesity, especially with high saturated fat consumption; possibly lower risk of heart disease


TCF7L2 Gene:
TCF7L2 is a transcription factor gene that has been linked in many studies to type 2 diabetes risk.  A study looking at the effect of a high saturated fat meal on lipid levels found that for those with the minor allele there was a significant increase in triglycerides and total cholesterol.  Another study linked the variant to increased risk of metabolic syndrome in women with an even greater risk for those eating a diet higher in saturated fat.  Both metabolic syndrome and high triglycerides are linked to an increased risk of heart disease in many studies.

Check your 23andMe results for rs7903146 (v4, v5):

  • C/C: typical
  • T/T: increased risk of metabolic syndrome especially with high saturated fat consumption; increased risk of T2D


We are all different in our dietary needs. If you have the variants listed above, the American Heart Associations’ recommendation about cutting down on saturated fats may be worth considering. I don’t necessarily agree with their recommendation to replace saturated fat with industrially processed canola or vegetable oils, though, and I would also challenge you to read up on the inflammatory effects of high polyunsaturated fat (especially omega-6) consumption as well.

Natural ACE inhibitors include barberry (fruit). On the other hand, Echinacea has been shown to increase ACE activity.[ref]

Hibiscus sabdariffa, also known as Rosella or Sour Tea, is a traditional beverage that has been shown to inhibit ACE activity and reduce blood pressure.[ref] has a good article on the benefits and studies on hibiscus tea.


More to read:

High‐Saturated‐Fat Diet Increases Circulating Angiotensin‐Converting Enzyme, Which Is Enhanced by the rs4343 Polymorphism Defining Persons at Risk of Nutrient‐Dependent Increases of Blood Pressure

Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.