This post is a work in progress.
Last update and review: November 14, 2019.
Rhonda Patrick, PhD, a popular online health educator, and a “specialist in ApoE4” and Alzheimer disease, wrote in a comment:
“saturated fat increases LDL particles and apoE4 also dramatically increases LDL particle number.”
Rhonda Patrick is wrong. As you can see in the slide below, among the Framingham cohort study with a large number of participants, LDL Cholesterol is the same in ApoE isoforms e4/- carriers and in the isoform e3/e3 carriers.
There are, however, frequent references in the published literature that associate ApoE isoform e4/- and higher risk of CVD, atherosclerosis and higher LDL-c. Thus, the 1994 study by Wilson et al.(3) enumerates a large number of studies that found high CVD risks for “ApoE4” carriers. However, if we examine the studies referenced by Wilson et al.(3), we see that the data are often weak, not statistically significant, and are often based on a small number of subjects.
The example of this is the study by Ehnholm et al., 1986(2). The researchers noted higher LDL-C in ApoE e4/- isoforms carriers based on a small group of subjects from Finland. There were only 3 subjects with e2/e4 isoforms. The results were not statistically significant.
Ehnholm et al.(2):
“The highest concentrations of LDL were seen in the
group of E 4/4 homozygotes. These differences were, however, not statistically significant.”
Wilson et al. (3) found higher odds ratios for CVD and other risks in ApoE isoform e4/- carriers. But Willson and colleagues do not provide data on the levels of LDL-Cholesterol, just the odds ratios for different subgroups.
Elosua et al. (1), who investigated the association of APOE genotype with carotid atherosclerosis in men and women in a large Framingham Heart Study, concluded that “APOE4 genotype was significantly associated with a higher ICA IMT (carotid intima-media thickness) ONLY in diabetic men”
A description of the Framingham cohort from the study by Elosua et al., 2004(1):
The Framingham original cohort began enrollment in 1948, with the recruitment of 5,209 men and women between the ages of 30 and 62 years. There were 3,532 participants in offspring study examination cycle 6 (1995–1998). A total of 3,378 (96%) of these participants underwent B-mode carotid ultrasonography;
APOE genotype data were available for 2,723 participants (81%).
1. There is no strong evidence that carriers of “ApoE”, ApoE isofrom e4/e4 and e3/e4, have higher LDL Cholesterol (LDL-c).
2. Higher LDL-c was not found to be a meaningful risk factor for cardiovascular disease.
3. Only male ApoE isoform 4 carriers with diabetes had higher level of atherosclerosis in a large study by Elosua et al.(1).
4. PhD scientists, health personalities, grassroots health conferences and internet community generate a lot of noise. Very few people do a diligent fact checking.
5. The noise about risks of low carb diets for “ApoE4” carriers is not confirmed. Low carb diets help to prevent metabolic syndrome and diabetes, the conditions that are even more deleterious for “ApoE4” carriers than for the rest of the population.
6. In my review of the literature, I have not discovered so far any hidden, enigmatic potential risks for “Apo4” carriers to be on a low carb diet. If, however, blood lipids or other blood markers are abnormal on a particular low carb diet, some modifications of the diet may be necessary (=Common Sense).
1. Elosua et al., J Lipid Res. 2004 Oct;45(10):1868-75. Epub 2004 Jul 16.
2. Ehnholm et al., J Lipid Res. 1986. 27: 227-235.
3. Wilson et al., JAMA. 1994;272:1666-1671.