Apo E4 and sterols: Lethal combination?

Phytosterols, or just "sterols" to its friends and neighbors, are a group of cholesterol-like compounds that are abundant in the plant world. Lately, however, sterols have proliferated in the processed food supply, thanks to the observation that sterols reduce LDL cholesterol when ingested by humans.

This must mean that sterols are good for you.

Uh oh. Wait a minute: There is a rare disease called sitosterolemia in which there is unimpeded intestinal absorption of all sterols ingested through diet. They must have really low LDL cholesterols! Nope. They develop coronary disease--heart attacks, angina, etc.--in their late teens and 20s. In other words, if sterols gain access to your bloodstream, they are bad. Very bad.

Conventional thinking is that only a modest quantity of dietary sterols gain access to the bloodstream. But there are two potentially fatal flaws in this overly simplistic line of thinking:

1) What happens when you load up your diet with "heart healthy" sterols, such as those in "heart healthy" margarines, mayonnaise, and yogurt, effectively increasing sterol intake 10-fold?

2) What happens in people with the genetic pattern, apo E4, that is carried by 25% of the general population that permits much greater intestinal absorption of sterols?

My prediction: Despite the fact that sterols reduce LDL, they may, in certain genetically-susceptible people, such as those with apo E4, increase risk for heart disease: heart unhealthy.

Here are two studies that suggest that greater sterol absorption in people without sitosterolemia are at higher risk for heart disease:

Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD

Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Münster (PROCAM) study

Comments (24) -

  • Kathy Hall

    2/11/2011 12:04:41 AM |

    Does this include the beta sitosterol that is in most prostate supplements?

  • Lucy

    2/11/2011 12:32:16 AM |

    How can I get tested for sitosterolemia?

  • Anonymous

    2/11/2011 1:08:44 AM |

    I know for a fact that Costco sells 5000+ bottles of CholestOff every WEEK! The stuff is a blend of sterols.

  • preserve

    2/11/2011 1:43:45 AM |

    Yeah costco also has "sterol" oatmeal bars.

    I try to stick to the freezer and wine section.

  • Anonymous

    2/11/2011 2:46:10 AM |

    I like how you state plainly it's "rare," and now your followers are going to start to believe themselves to have this ailment. I like your blog, but as of late, you're war on heart disease is imitating the ad baculum aspects of America's war on terror.

  • Davide

    2/11/2011 3:04:46 AM |

    Excellent article. I've had the same exact thoughts and that's why I don't take supplementary plant sterols.

    It's pretty comical. When people supplement with sterols, all they are doing is swapping some of their cholesterol in LDL particles with sterols. The sterols essentially take the place of the cholesterol in the blood. But both have the proclivity to cause atherosclerosis.

    So, the cholesterol lowering effect is just an illusion.

  • Anonymous

    2/11/2011 4:16:23 AM |

    I'm not so sure Apo E4 would even be considered 'rare' amongst those who have heart disease problems... or who are considered high risk.

    E4/E4 is quite rare, but E3/E4 isn't really. I think it's around 25% of the population, if I recall correctly. And I'd expect amongst those with heart issues, it'd be higher than that.

  • Anonymous

    2/11/2011 7:56:33 AM |

    So what do you eat if you are disp. to Apo E4. If I eat sat. fat my LDP
    rocket up. If I eat more veg. and fruit and lean mead it rocket dovn.
    Am I on the track??

  • Dr. William Davis

    2/11/2011 12:40:05 PM |

    Hi, Kathy--

    Yes, it does.


    In general, testing for sitosterolemia is not something I would recommend except in specific situations, in which case the various sterols in the blood can be measured.

    That was not the point of the discussion, but the far more common Apo E4 that affects 25% of the population, who thereby potentially hyperabsorb sterols.

  • Daniel A. Clinton, RN, BSN

    2/11/2011 3:46:49 PM |

    I can do you one better. This prospective cohort study (n=1137) found "Higher levels of HDL-C (>55 mg/dL) were associated with a decreased risk of both probable and possible AD and probable AD compared with lower HDL-C levels (hazard ratio, 0.4; 95% confidence interval, 0.2-0.9; P = .03 and hazard ratio, 0.4; 95% confidence interval, 0.2-0.9; P = .03). In addition, higher levels of total and non–HDL-C were associated with a decreased risk of AD in analyses adjusting for age, sex, education, ethnic group, and APOE e4 genotype." Here's the link to the abstract:  http://archneur.ama-assn.org/cgi/content/abstract/67/12/1491.
    Makes you wonder the REAL reason behind statin drugs.

  • Kevin

    2/11/2011 6:43:41 PM |

    I used beta-sitosterol for over a year.  I used it because I didn't want to take a 5-alpha reductase inhibitor such as Proscar.  But I developed the same side effects that Procar is known to cause:  Poor libido, gynecomastia and generalized muscle weakness.  I don't track cholesterol so I don't know what the beta-sit might have done to it.  Six months off the beta-sit and I'm just now starting to feel like a normal man again:  morning wood, etc.

  • Lucy

    2/11/2011 9:15:49 PM |

    That was my reason for asking... because I'm a 3/4

  • Anonymous

    2/12/2011 4:54:58 AM |

    Fructose Alters Brain Metabolism
    One of the competing theories to explain the obesity epidemic is a rise in fructose consumption causing alterations in hormone levels that increase appetite. UCSF med school prof Robert Lustig has a pretty good rant-lecture on the evils of fructose. Well, here's another study on part of the mechanism in the brain of how fructose might be causing increased obesity.

    PORTLAND, Ore. – The dietary concerns of too much fructose is well documented. High-fructose corn syrup has become the sweetener most commonly added to processed foods. Many dietary experts believe this increase directly correlates to the nation's growing obesity epidemic. Now, new research at Oregon Health & Science University demonstrates that the brain – which serves as a master control for body weight – reacts differently to fructose compared with another common sweetener, glucose. The research is published in the online edition of the journal Diabetes, Obesity and Metabolism and will appear in the March print edition.

    In humans the cortical brain control areas of the brain were inhibited by the influx of fructose.

    Functional MRI allows researchers to watch brain activity in real time. To conduct the research, nine normal-weight human study subjects were imaged as they received an infusion of fructose, glucose or a saline solution. When the resulting brain scans from these three groups were compared, the scientists observed distinct differences.

    Brain activity in the hypothalamus, one brain area involved in regulating food intake, was not affected by either fructose or glucose. However, activity in the cortical brain control areas showed the opposite response during infusions of the sugars. Activity in these areas was inhibited when fructose was given but activated during glucose infusion.

    This is an important finding because these control brain areas included sites that are thought to be important in determining how we respond to food taste, smells, and pictures, which the American public is bombarded with daily.

    The result increases the plausibility of fructose as a causal agent.

    "This study provides evidence in humans that fructose and glucose elicits opposite responses in the brain. It supports the animal research that shows similar findings and links fructose with obesity," added Purnell.

    If you want to reduce your weight also consider other theories for the cause of obesity including grains as a possible major cause.

    By Randall Parker 2011 February 09 05:42 PM  Brain Appetite

  • Dr. William Davis

    2/12/2011 4:57:38 PM |

    Hi, Peter--

    Thanks for catching that.

    Now fixed.

  • Might-o'chondri-AL

    2/12/2011 9:40:08 PM |

    Foods with naturaly occuring levels of Beta-sisterol: fruits like avocado, nuts like pecan & cashew, seeds like flax & pumpkin,
    legumes like soya & peanut, grains like wheat germ & rice bran, oils like corn & soy, plus herbs like Saw Palmetto & Pygeum. Once again it is good to recall that if something is good for you that doesn't automaticly mean more is better for you.

  • Gene K

    2/13/2011 7:29:32 PM |

    @Anon about naturally occurring sitosterol levels -

    As an APO E4 person, should I be concerned about my intake of avocado, flax seed, and tofu?

  • reikime

    2/13/2011 11:07:34 PM |

    couldn't leaky gut syndrome cause increased sterols in the bloodstream?

  • Anonymous

    2/14/2011 4:03:27 AM |

    So... how much sterols?
    For example almonds and other nuts are high in sterols. Lot of vegetables are high in sterols. In this blog nuts have been recommended often as well as a plant based diet. So does this change that?
    What should apoe4 people eat? They can't eat fat, now they can't eat vegetables? Is starving to death the only way to avoid heart disease?

  • Anonymous

    2/15/2011 7:12:55 AM |

    Also tofu and soy has been promoted which have esterols...

  • Kurt G. Harris MD

    2/16/2011 4:06:56 AM |

    Another benefit to total avoidance of plant oils!

    Miniscule n-6 means miniscule fat soluble sitosterols.

    Are you ready to advocate an animal-fat based diet for ApoE4 and the 45 total reported cases of sitosterolemia?

    If you worry about LDL, ApoE4 needs to be "low fat", but if you worry about early death and AD, I think high animal fat is the way to go for these folks.

  • Might-o'chondri-AL

    2/16/2011 5:42:19 PM |

    Isn't the problem for APOE4 the way the molecule degrades? Quite recently fish oil Omega 3 has been cited for allaying APOE4's side effects. The Omega 3 balances out the metabolite (an APOE4 protein fragment) that otherwise messes with the lipid structure of the mitochondria(s) membrane(s); it (fish oil) prevents dysfunction.

  • Janknitz

    8/24/2011 2:27:51 PM |


    I heard a report on this study on NPR yesterday.  It's important to note who sponsored the study in the first place.