Apolipoprotein E (APOE) and Fat Processing in Human Body.
(Chapter 5)
Medical Science knows human genomes today much better than it did 1967 when Malhotra published his report referred to in Chapter 3. We know that human genes generally and Apolipoprotein E (APOE) genotype in particular, regulates body weight and fatty acid utilization in human body. This explains why one diet does not work for everyone.
Some people carry gene variants that make them less sensitive to dietary cholesterol and saturated fat. Their LDL does not spike as sharply after a burger or fried chicken. They may also have naturally efficient LDL receptors that clear fat from blood quickly.
President Donald Trump is 79 and still functioning. Department of Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. jokingly marveled at President Donald Trump’s fast-food eating habits, saying he doesn’t “know how he’s alive” during an interview. But this suggests that his particular genetic makeup handles processed food better than average. That is real and common.
But remember that genetics does not protect from everything. Processed food causes damage beyond cholesterol like chronic inflammation, poor gut microbiome, insulin resistance, and cellular aging. These effects accumulate silently over decades regardless of genes. Also, we do not actually have full access to Trump’s real health status. Medical reports of public figures are often incomplete or managed carefully.
Genetics Matter
Now getting back to genetics. The settled science is that APOE genotype shapes how a person responds to dietary fat, and E2, E3, E4 produce meaningfully different outcomes. Thus, we know is that genetics matter but scientists have yet to discover how genes matter. There are two probable versions today:
Version 1:
Genetics Plays the Major Role
Human genes control how the body processes fat. A key gene is APOE. It comes in three versions: E2, E3, and E4. People with APOE4 absorb dietary fat very aggressively. Eating ghee or coconut oil raises their LDL cholesterol sharply. People with APOE2 handle saturated fat much better. Most people carry APOE3 and fall somewhere in the middle. This is why one person eats fried food daily and has perfect cholesterol, while another person doing the same develops heart disease.
But this study on mice is not really on humans. Mice and humans do not share the same organism. Mice, even after biological modifications remains a mice.
Version 2:
A Harvard School of Public Health study from 2001, published in Genetic Epidemiology. Its finding is the opposite of what Version 1 claimed about APOE4.
The study tested 420 Costa Ricans and found that higher saturated fat intake was associated with lower VLDL cholesterol and higher HDL cholesterol in APOE4 carriers, while APOE2 carriers showed the reverse, with higher VLDL and lower HDL on the same diet.
Version 2 was closer to correct but still imprecise. The real picture from this paper is that the conventional warning about APOE4 and saturated fat is more complicated than the popular framing suggests.
This 420 Costa Rican subjects’ report suffers the same problem that Malhotra report of 1967. Malhotra’s limitation is that he studied dietary patterns across regions without controlling for cooking medium as an independent variable.
The Costa Rica study’s limitation is that it divided 420 people into two groups based on whether their saturated fat intake was above or below the median, but treated saturated fat as a single category. Lauric acid from coconut oil, palmitic acid from palm oil, and butyric acid from ghee are all “saturated fat” but behave completely differently in the body as previous chapters established in detail. The study also did not control for preexisting metabolic differences between subjects. We will discuss human metabolism in Chapter 7 after discussing the processing of food in human body in Chapter 6.
For the present, the conclusion is that genes clearly play a role in how the body processes dietary fat, but science has not yet established exactly how that role is played.
References:
- President Trump’s habits: https://www.foxnews.com/media/rfk-jr-comments-trumps-unhinged-eating-habits-jokes-he-doesnt-know-how-trump-alive
- President Trump mocking about healthy diet:
- Mice research (about version 1): https://onlinelibrary.wiley.com/doi/10.1002/mnfr.201400636
- Research at Harvard in role of Apolipoprotein in fat intake (about version 2): https://pubmed.ncbi.nlm.nih.gov/11119301/