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Despite the vast literature on phytosterols lowering blood cholesterol levels, there is to date no study investigating the ultimate proof of efficacy: lowering the incidence of coronary heart disease. This is probably the strongest argument against them. There are no studies with hard endpoints to confirm that the drop in LDL cholesterol from plant sterols translates to a drop in heart attacks. The reason is that even if people start out with a 10-year risk of a cardiovascular risk of 10%, you’d have to randomize about 30,000 people to phytosterols for a decade to detect such an effect. And at a more reasonable 10-year risk of 5%, you might have to enroll more than 300,000.
Now, one could argue that the cholesterol lowering is all we need to know, since basically lowering LDL cholesterol by any means appears to lower cardiovascular risk, whether by statins, other kinds of drugs, diet, or surgery. However, there was a big trial of extended-release niacin in a group of patients with LDLs starting down in the low 60s, and researchers saw a further 10-point drop after a few years that should have dropped risk by at least 5 or 6%, but failed to offer a statistically significant benefit in the end. So, there’s at least one example of that line of argument failing.
There is a drug called ezetimibe that does have a similar mechanism of action as phytosterols—that is, blocking cholesterol absorption. It partially blocks the cholesterol absorption receptor; so, cholesterol absorption is reduced by about 50%. When it was put to the test, it did indeed significantly improve cardiovascular outcomes. And the 13-point drop in LDL achieved by blocking cholesterol absorption with the drug is almost the exact same drop in LDL we’d expect from blocking cholesterol absorption with phytosterols, based on more than 100 randomized, controlled trials.
Does blocking cholesterol absorption work even if you don’t eat any cholesterol? Yes, because the bulk of the cholesterol flowing through our digestive tract is dumped there from our own liver’s production. It also works for those on statin drugs. In fact, adding two grams of phytosterols a day to your routine may be equivalent to like quadrupling your statin dose.
So, if you are going to try phytosterols to lower your LDL level, what’s the best dose, and what’s the best source? The recommended daily dosing is between two to three grams a day, based on dose-response curves like this, where the benefit appears to plateau at about those two or three daily grams. There’s a comparable benefit curve with plant stanols, which are similar molecules.
Plant sterols and stanols are absorbed better if taken with meals, because the maximum cholesterol load to the intestine occurs after gallbladder contraction and delivery of cholesterol-rich bile to the intestine. Indeed, the same dose of phytosterols may have more than double the LDL-lowering effect when taken with meals rather than between them.
The full LDL-cholesterol-lowering effect of plant stanol ester can be detected after just two weeks, and may last as long as you take them. But as soon as you stop, the cholesterol-lowering effect will be lost within a week or two.
Phytosterols in those kinds of doses are available in supplements and in fortified foods, which lower LDL equivalently. As I talked about before, the margarines are a total non-starter. Are there any healthy phytosterol-fortified foods? Not really that I can see. In Australia, there’s a plant sterol-fortified shredded wheat, but I don’t know if you can get it anywhere else.
That leaves us with supplements. It’s always good to have third-party certification of authenticity, though I think there’s only one USP-certified brand at the moment. But ConsumerLab also tested and approved three others. They’re all pretty expensive; so, I was excited to see you can get it in bulk, and you could presumably just sprinkle a bit on your food, but that presumption may be wrong. As the crystalline powder, it is much less efficient at inhibiting cholesterol. That’s why the initial studies a half century ago were using doses of around 10 to 20 grams a day. Then researchers figured out how to make them more soluble by making fatty phytosterol esters, which is what you see in the capsules. There are studies suggesting that free sterols block cholesterol absorption as much as esterified sterols, but they included equal parts of an emulsifier to improve absorption. A study showing free sterols could lower LDL similarly relied on some proprietary means for solubilizing it. Just for fun, I tried taking the bulk powder for a month and indeed saw zero effect, whereas I got a nice 17% drop in LDL taking the exact same dose in encapsulated ester form.
Normally, I’m not big on lab tests, but if you do start phytosterol supplements, I would get tested before and after a month or so on them. You should be able to get your cholesterol tested for free through your doctor, but these days you can get your cholesterol tested at low cost or free even without insurance or a doctor visit. While some individuals respond immediately and get a major shift in lipid profiles, others are much more resistant or even completely insensitive to plant sterols, or even worse. Just because the average response is around a 10% drop in LDL cholesterol, maybe you’ll get lucky and respond even better. These are all individual patients, and this first person saw a 38% drop! But it’s also possible you won’t respond as well— or, your cholesterol may actually go up. That unfortunate person on the end had a 33% increase in LDL; so, even though the average effect is good, you want to make sure it’s working for you.
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