Monday, March 9, 2009

Margarine and Phytosterolemia

Margarine is one of my favorite foods. To rip on. It's just so easy!

The body has a number of ways of keeping bad things out while taking good things in. One of the things it likes to keep out are plant sterols and stanols (phytosterols), cholesterol-like molecules found in plants. The human body even has two enzymes dedicated to pumping phytosterols back into the gut as they try to diffuse across the intestinal lining: the sterolins. These enzymes actively block phytosterols from passing into the body, but allow cholesterol to enter. Still, a little bit gets through, proportional to the amount in the diet.

As a matter of fact, the body tries to keep most things out except for the essential nutrients and a few other useful molecules. Phytosterols, plant "antioxidants" like polyphenols, and just about anything else that isn't body building material gets actively excluded from circulation or rapidly broken down by the liver. And almost none of it gets past the blood-brain barrier, which protects one of our most delicate organs. It's not surprising once you understand that many of these substances are bioactive: they have drug-like effects that interfere with enzyme activity and signaling pathways. For example, the soy isoflavone genistein abnormally activates estrogen receptors. Your body does not like to hand over the steering wheel to plant chemicals, so it actively defends itself.

A number of trials have shown that large amounts of phytosterols in the diet lower total cholesterol and LDL. This has led to the (still untested) hypothesis that phytosterols lower heart attack risk. The main problem with this hypothesis is that although statin drugs do lower LDL and heart attack risk, not all interventions that lower LDL lower risk.  LDL plays an important role in heart attack risk, but it's not the only factor.  Statins have a number of biological effects besides lowering LDL, and some of these probably play a role in its ability to protect against heart attacks.

Lowering total cholesterol and LDL through diet and drugs other than statins does not reliably reduce mortality in controlled trials. Decades of controlled diet trials showed overall that replacing saturated fat with polyunsaturated vegetable oil lowers cholesterol, lowers LDL, but doesn't reliably reduce the risk of cardiovascular disease. Soy contains a lot of phytosterols, which is one of the reasons it's heavily promoted as a health food.

All right, let's put on our entrepreneur hats. We know phytosterols lower cholesterol. We know soy is being promoted as a healthier alternative to meat. We know butter is considered a source of artery-clogging saturated fat. I have an idea. Let's make a margarine that contains a massive dose of phytosterols and market it as heart-healthy. We'll call it Benecol, and we'll have doctors recommend it to cardiac patients.

Here are the ingredients:

Liquid Canola Oil, Water, Partially Hydrogenated Soybean Oil, Plant Stanol Esters, Salt, Emulsifiers, (Vegetable Mono- and Diglycerides, Soy Lecithin), Hydrogentated Soybean Oil, Potassium Sorbate, Citric Acid and Calcium Disodium EDTA to Preserve Freshness, Artificial Flavor, DL-alpha-Tocopheryl Acetate, Vitamin A Palmitate, Colored with Beta Carotene.

And I haven't even gotten to the best part yet. There's a little disorder called phytosterolemia that may be relevant here. These patients have a mutation in one of their sterolin genes that allows phytosterols (including stanols) to pass into their circulation more easily. They end up with 10-25 times more phytosterols in their circulation than a normal individual. What kind of health benefits do these people see? Premature atherosclerosis, an early death from heart attacks, abnormal accumulation of sterols and stanols in the tendons, and liver damage.

Despite the snappy-looking tub, margarine is just another industrial food-like substance that I am highly suspicious of. In the U.S., manufacturers can put the statement "no trans fat" on a product's label, and "0 g trans fat" on the nutrition label, if it contains less than 0.5 grams of trans fat per serving. A serving of Benecol is 14 grams. That means it could be up to 3.5 percent trans fat and still labeled "no trans fat". This stuff is being recommended to cardiac patients.

When deciding whether or not a food is healthy, the precautionary principle is in order. Margarine is a food that has not withstood the test of time. Show me a single healthy culture on this planet that eats margarine regularly. Cow juice may not be as flashy as the latest designer food, but it has sustained healthy cultures for generations. The U.S. used to belong to those ranks, when coronary heart disease was rare.


Unknown said...

Great info. I'd love to see a post on canola oil too!

Unknown said...

Stephen said:
As a matter of fact, the body tries to keep most things out except for the essential nutrients and a few other useful molecules.

This suggests an interesting way of ranking food choices. I think lining them up both by "% of mass" and by "total mass" of stuff the body thinks is poisonous would make for interesting reading.

Stephen said:
Despite the snappy-looking tub, margarine is just another industrial food-like substance that will help you get underground in a hurry.

I'm pretty sure "food-like" doesn't belong in this sentence.

gunther gatherer said...

Stephen, great post.

How do you feel about nuts then? They have huge amounts of plant sterols, yet many native cultures eat them as a staple food.

Is it possible that the healthy hunter-gatherer cultures examined over the last 200 years or so are actually not eating an optimal diet?

I refer specifically to societies relying mainly on nuts and tubers. They could be now eating sub-optimal foods because they've hunted to extinction a lot of the animals in their ancient environment. Though HGs are healthier than us, they could be suffering from their geographic limitations too, no?

JC said...

You don't cite any research that plant sterols are unhealthy.I know they are used to treat an enlarged prostate,prostatitis and even prostate cancer.Dr A Katz(Columbia Univ)uses them in treatment of prostate issues.

BJ said...

Good post. Mailed it off to a buddy I just convinced to get off of the Country Crock and use real butter.

Are you saying that all those "healthy" plant and berry "antioxidants" don't get used by the body and therefore don't have a benefit. I've always been a little leery about that, just wondering what you think.


Robert Andrew Brown said...

Do sterols bind cholesterol into a less soluble compound that leads to greater excretion. Based on the above and this paper is that a possibility.

Discussion of the issues surrounding hydrogenated fats, excess Omega 6 lack of Omega 3, mineral and vitamin contents plus ancillaries is subject matter for an army of post.

David said...

The Lyon study showed that a canola-based margarine lowed cardiac mortality by 70% (patients were also encourage to adopt a "mediterranean diet," but it's unlikely any did so - but they did get the margarine for free, so they probably used it).

Anonymous said...

I like your use of the precautionary principle in reference to paleo foods. Ironically, I think its exactly that principle that mainstream health advocates believe they are invoking whenever they caution against consumption of red meat, animal fats or low carbs. There's clearly plenty of room for argument about what is the ideal diet. In the absence of certainty, it makes sense to err on the paleo side. Somehow the burden of proof has been turned around in exactly the wrong direction.

Robert M. said...

The link to the Colpo article is broken.

Colpo, "LDL Cholesterol:
"Bad" Cholesterol, or Bad Science?"

homertobias said...

This post reminds me of Michael Pollen. Margarine was the first "artificial food". It was originally labelled as artificial butter, was pasty white in color, and didn't become popular until yellow food dye was used to make it look like butter.

What is go great about artificial foods is that you can add and subtract the "purified" (and thus ruined) life saving cheap supplement du jour to form a new and improved product.

OK stephan, lets you and me get rich and stop wallowing around in academia. The perfect margarine.....Stanols not sterols. Stanols aren't absorbed. Sterols are. So Take Control and other Heart Healthy sterol containing products cause abnormal circulating sterol levels which the body has a very difficult time breaking down. Feeding abnormally high amounts of sterols to rats does cause arterial calcification. So stanols, maybe we can get the "Partially HYdrogenated" out of the label entirely. Just add another preservative that the public is less aware of. OK, lets throw out the artificial vitamins in benecol which really are passe'
Ok, we've eliminated the Vitamin A and Vitamin E. We'll keep the betacarotene coloring, its cheap. Whats HOT in vitamin world? Of course, omega 3 and Vitamin D. Great, they are both fat soluable. Vitamin D is dirt cheap. No problem. What about Omega 3's? Alpha Linolenic Acid is much cheaper than DHA or EPA. Who cares if humans can't absorb it. Nonabsorption is the whole point here. Their cholesterol will go down and they will be hooked. Once we have sufficient cash flow we could hire a bunch of lawyers and then covertly make more public the Norvit,Wenbit and Visp trials which linked increased Vitamin A intake (from retinol palmitate) with an increase in total mortality. We will also sharply up the public's awaremess of the difference between sterol and stanol esters.

I certainly enjoyed this fantasy. Time to go to work.

Swede said...

As a registered dietitian, I see these plant sterol margarines promoted without abandon! Every issue of the ADA Journal has ads for at least 2 margarines, and a multitude of other "fake foods" such as Ensure and Pediasure because "your child's diet may be lacking in certain important nutrients." What a joke. I can't believe that my profession, charged with giving dietary guidance, has been so severely brainwashed.

Anonymous said...

Great point regarding the misleading 'zero trans fat' labeling.

The deodorization process, which virtually all commercially available vegetable oils undergo, results in the creation of significant amounts of trans fats - 1-4% of the oil is converted to trans. This is not partial hydrogenation, and is not listed as such on labels.

But because the serving size is 14g, and the limit is .5g, you won't see any trans fat listed on the bottle of canola oil you buy in the store.

If you get 30% of your calories from fat, and all of that from commercial vegetable oil like soy, corn, canola, you'll easily ingest 3 grams of trans fats in a day, without seeing it on any label, or eating any partially hydrogenated foods.

Here's some of the detail on the deodorization process:,M1

Take a look at some of the changes in dietary fat over the last 100 years:

Robert M. said...

Amusing anecdote: in Quebec, it's against the law to dye margarine yellow, so it's stark white while the butter remains its natural yellow.

Robert Andrew Brown said...

Here is the other link I meant to post earlier.;jsessionid=4C3F43360E5F19FFB7C1D2BF0BEE145F?sequence=1

Stephan Guyenet said...


That's not a bad idea.


I don't worry about nuts in moderation. The body is probably equipped to handle normal amounts of phytosterols. The amount of stanols and sterols in these margarines is totally beyond what you can get from food. You'd have to drink something like a liter of soybean oil to get the phytosterols in a tbsp of margarine. I do stay away from the high-linoleic acid nuts except on occasion.

The question you raised about modern HG diets not being totally "optimal" is relevant. In the few thousand years preceding agriculture, HGs went through something called the "broad spectrum revolution", where their food base diversified to permit higher population density. They shifted from mostly large game to incorporating more plant foods like nuts, tubers and starchy seeds.

That's not to say they never ate those things before that, but the subsistence pattern seems to have shifted in a way that foreshadowed agriculture. So what may actually be more relevant to the "optimum" is what we did for the million years before that, which appears to be mostly eating large game.

That being said, modern hunter-gatherers are largely free of degenerative diseases, so it all depends on your definition of the word optimum. I think we're sufficiently adapted to a broad range of food sources, as demonstrated by modern HGs and healthy non-industrial populations.


Just look up "phytosterolemia" or "sitosterolemia" in PubMed to find research on the health effects of plant sterols. The main point is that massive doses of sterols/stanols have not been proven safe beyond reasonable doubt. What happens when someone takes these margarines for 20 years? What happens when a pregnant woman eats it? No one knows.


I don't have a solid answer for you, but I'm personally very skeptical of the benefits of plant antioxidants other than the essential ones (A, C, E) and a few others (CoQ10 etc.). Polyphenols (tea, veggies, berries) for example don't contribute significantly to serum antioxidant status. When you eat them, your serum antioxidant capacity does increase, but that seems to be because of your body secreting uric acid into the blood rather than the polyphenols themselves. The researchers who ascribe plasma antioxidant capacity to polyphenols are confusing correlation with causation.

And forget about those molecules contributing to antioxidant capacity inside cells. There just isn't enough that makes it that far. The cell is very selective about what antioxidants it lets do the job. Most cellular antioxidants are made and used on the spot.

theoddbod said...

luckily this stuff hasn't been approved for sale in Canada, hooray!

Stephan Guyenet said...


Yes, the way sterols/stanols seem to work is by preventing cholesterol absorption. That increases endogenous cholesterol synthesis and upregulates the LDL receptor, lowering LDL and total cholesterol.


True, but the margarine in the Lyon trial wasn't hydrogenated (aside from what's probably produced in normal canola oil refining). Participants reduced their overall intake of omega-6, and increased omega-3, including by increasing fish intake.

If the average person just replaced butter with margarine, they'd be increasing omega-6, keeping omega-3 the same (or possibly increasing it, if they bought a designer margarine), increasing trans fat intake, not changing fish intake and reducing their vitamin K2 and CLA intake. That doesn't have much to do with what Lyon participants did.

I acknowledge the Lyon result, I just think there are better ways of doing the same thing.


We're on the same wavelength.


Thanks, I fixed it.


I agree processed food is all about adding the latest miracle supplement on top of nutritionally bankrupt ingredients. Definitely a business opportunity! By the way, stanols are absorbed too, just to a lesser extent than sterols.


Yeah those "meal replacements" crack me up. They should call them "nutrition replacements".

Stephan Guyenet said...

US Food Trends,

Thanks, that's good information that most people aren't aware of.

Robert M,

That's hilarious! Score one for the dairy lobby.

JC said...$=relatedarticles&logdbfrom=pubmed


Anonymous said...

I have a question... my mom had CABGX4 and I am telling her to use Promise (formerly take control).

Her usual diet before the CABG was fast food several times a day, very low fiber, and rarely any fruits and veg. Lots of sugar, processed flour etc.

My point is this. If she is happy now eating baked fish with a little Promise and broccoli also with a little Promise, isn't this a much healthier diet than previously fast food and soda? I have a hard time believing that she is CLOSER to the grave with this eating change.

I think it is hard to be "perfect" even if margarine is "bad" and asking people for perfect is irresponsible.

I'd love to understand why a new diet of baked fish and vegetables is more deadly than a double cheeseburger fries and soda.

Thanks for your time!

Aaron said...

Rebecca, just tell your mom to eat veggies and fish with a little butter!

soda, fries, are always going to be toxic!

the double cheeseburger isn't that bad if it's grass fed beef (try to remove the cheese!). NO FIXINGS except for spices and or mustard.

Scott Miller said...

>>> I'm personally very skeptical of the benefits of plant antioxidants other than the essential ones (A, C, E) and a few others (CoQ10 etc.). Polyphenols (tea, veggies, berries) for example don't contribute significantly to serum antioxidant status. <<<

I've been saying this for years, yet I take a many different types of polyphenols from the plant kingdom, including polyphenols from blueberry, tea, grapes, pomegranate, tumeric, cocoa, pine bark, and several others.

I do NOT take them for any potential antioxidant benefit, though. Instead, they all have special benefits, such as triggering genes in heathy ways (just as vitamin D does), or creating nitric oxide within the arteries, allowing them to relax better.

I suspect there's a whole world of benefits you've yet to tap into because you're focused so much on a natural, paleo diet--but there are increased health benefits to be had outside this dietary circle.

Stephan Guyenet said...


I took a look at the study. I think it showed convincingly that feeding people massive doses of sterols for one year doesn't cause any gross abnormalities.

But their plasma sterol concentration was twice the normal value. What would that do over 10 years? People with phytosterolemia don't get heart attacks when they're one year old, it takes decades to develop. But they still end up getting them much earlier than the average person. Of course, they have sterol levels higher than the people in that study. I'm not saying it proves anything, but it's cause for skepticism, particularly in light of the fact that sterols haven't been shown to reduce heart attack incidence.


I can't say for sure which diet is worse, but I would definitely guess the fast food. I looked into Promise and it doesn't contain hydrogenated oils (although canola oil does contain a bit of tans fat created during the refining process). So that's at least one point in its favor.

But it is made with soybean oil, which is one of the worst oils for health. She'd be better off with butter.


I'm open to the possibility that certain polyphenols could have benefits outside of their antioxidant role. But they're basically acting like drugs at that point, influencing signaling cascades and enzyme activity.

Many healthy traditional cultures eat very little of the plant polyphenols that are so prized by modern nutrition research, which is the main reason I'm skeptical that they play a major role. Why would you need extra nitric oxide if you have good endothelial function to begin with?

Scott Miller said...

>>> Why would you need extra nitric oxide if you have good endothelial function to begin with? <<<

That's a loaded statement, right?

Most of us have not eaten well our entire life, and therefore these polyphenols can be used to improve health.

I ate crap for my first 38 years of life, and was developing numerous health problems. While food/diet is the primary source of health for any of us, I very much doubt I'd be as healthy as I am now without the aid of supplementing.

Additionally, it's extremely hard to get certain minerals like iodine in sufficient quantities from our food supply, and an estimated 95% of Americans are deficient.

Others, like lithium, have profound neurological protective benefits, and should be supplemented to help prevent age-relative cognitive decline.

My main message is that if absolute maximum healthy lifespan is your goal, you should incorporate tactics beyond diet and exercise, including episodic fasting or CR, supplements, and hormone supplements (beyond the age of 40).

No question that food/diet imparts the greatest benefit. But why leave incremental improved health on the table?

AngloAmerikan said...

if absolute maximum healthy lifespan is your goal, you should incorporate tactics beyond diet and exercise

That makes a lot of sense to me. Going Paleo is the safest route to a healthy and long life but to extend it significantly beyond the normal will require medical intervention. Drugs like aspirin, caffeine, nicotine and resveratrol etc could have their uses. Happy coincidences have occurred in nature where plants have developed chemical defenses against predation by insects that have proved very beneficial for the treatment of humans. With the knowledge we have now it is still a bit of a gamble though. Also surgical intervention. I read somewhere those that survive the longest are the ones who seek medical intervention for health issues like heart problems and simply refuse to give up no matter how old they are.

Sue said...

What about herbal liquid extracts? There would be quite a bit of sterols in those?

Stephan Guyenet said...


I'm skeptical that our understanding of nutrition is sufficient to be able to improve on a good diet with supplements. Short-term studies don't say anything about long-term effects. I'm willing to be proven wrong on this, but I haven't been yet.

It's easy to see mechanisms and think we can tinker with our health using supplements, but in the end we have only the dimmest understanding of the total long-term effects we're having on our body. It's like introducing new species to an ecosystem to take care of a pest species. Half the time, the new species ends up being a worse pest itself. There's no way to guess the effects these chemicals are going to have on our bodies in the long term because the system is too complex. A safer option is to stay within the body's natural operating parameters as much as possible.

I can believe that supplements could be used to treat specific illnesses in a drug-like manner. But improving general health and lifespan... that's a much taller order.

What evidence do you have that 95% of Americans are iodine deficient?


I don't know, it would depend on the extract. I don't think a normal amount of sterols is a problem. The amount in Benecol is totally beyond what you can get from foods and probably herbal extracts.

Dave said...

Hmmmm, the symptoms of phytosterolemia sound just like what happens to bunnies when you feed them lots of cholesterol. Another notch for the hypothesis that animals (including humans) effectively metabolize substances common in their foods, and not so much otherwise.

Unknown said...

Stephan, here's the most recent article I read on iodine deficiency:

I've read about this in many other places, too, but it would take some work tracking it down. I was personally deficient until I started taking supplements a few years back--and this was while eating a healthy diet--but I do not use salt which is the primary source for iodine for Americans because the soil is so depleted. And, as with vitamin D, the RDA-ish amount we're getting from foods/salt is sadly inadequate.

Rick said...

>I do stay away from the high-linoleic acid nuts except on occasion.

Which are the high-linoleic acid nuts?

Stephan Guyenet said...


Good point! Plant sterols also accumulate in the arteries and are associated with poor cardiovascular outcomes in some but not all studies.


Thanks for the article, I'll keep that in mind. Did you notice any changes in how you felt when you began taking iodine?


These aren't all nuts but I think you get my drift. This list is not comprehensive. Pecans, sunflower seeds, peanuts, pine nuts, brazil nuts. Some nuts lower in LA are macadamias, hazelnuts and almonds, in ascending order. Walnuts are a special case because they contain a lot of LA but also omega-3 ALA to balance it. Still probably not a good idea to gorge on them.

Aaron said...

Hey Stephan-- did you ever notice that green pastures adds an "antioxidant Sterol" to their fermented cod liver and skate liver products-- I'm contacting them to see how much they put in per dose!

Stephan Guyenet said...

You're kidding! That's bizarre. I wouldn't worry about it if the dose is small. Thanks for the heads up.

Aaron said...

Stephan-- contacted dave from green pastures and was told that a few drops of essential oil (some type) were put in every bottle- how that came to be known as "plant antioxidant sterol" i'll never know!

Scared me for a sec--- especially since I really value green pastures as a company.

fermented cod/skate products and butter oil are really gems- even if you believed nothing else on the WAP site-- those products are the real deal.

Stephan Guyenet said...


Hmm. I know they used to use rosemary oil as an antioxidant in their CLO, maybe that's what it is. It's discouraging that they wouldn't tell you what kind of essential oil they use.

Anonymous said...

Plant sterols deplete carotenoids. Canola oil is hepatotoxic. Some good articles about Promise shots and other at Natural Health News blog.

Rob said...

Plant sterols are a good component of an overall, natural cholesterol-managing lifestyle that also includes select soluble fibers, good fats as opposed to bad and a number of other nutrients. Without fortification, most of us get about 400mg per day. Vegetarians probably close to 2x that. Traditional diets probably closer to 1000mg/day. There is an extra-virgin olive oil fortified with additional plant sterols -- which is also high in monounsaturated fats. Product is produced by Kardea Nutrition. Kardea's wellness bars with sterols, fiber from oats and psyllium, and only 150 calories also are available in natural foods stores.

Unknown said...

Who wants to bet that Rob was paid to write that commente?

Stephan Guyenet said...


I see that your company sells sterol-enriched products. Promoting your product in the comments section of a post like this is... interesting. If plant sterols are so great, why do we have at least two enzymes dedicated to keeping them out of the bloodstream? Our digestive tract soaks up cholesterol like a sponge and rejects plant sterols. Then, if any get into the blood by accident, they are filtered out by the liver and promptly excreted in bile.

If plant sterols are so great, why did we evolve to treat them like a toxic substance?

Rick said...

I agree with the thrust of the article, especially the bit about the precautionary principle, but this bit is interesting:
"Decades of controlled diet trials showed that replacing saturated fat with polyunsaturated vegetable oil lowers cholesterol, lowers LDL, but doesn't touch total mortality or death from cardiovascular disease."

"Doesn't touch" presumably means that it doesn't improve things, but also that it doesn't worsen things. Doesn't that imply that butter & margarine are equally good/bad?

Sue said...

"Decades of controlled diet trials showed that replacing saturated fat with polyunsaturated vegetable oil lowers cholesterol, lowers LDL, but doesn't touch total mortality or death from cardiovascular disease."

"Doesn't touch" presumably means that it doesn't improve things, but also that it doesn't worsen things. Doesn't that imply that butter & margarine are equally good/bad?

No that doesn't imply that butter and margarine are equally good/bad.
It means that polys lower LDL but the effect of lowering LDL does not guarantee that one will not die from cardiovascular disease or something else. A person with lowered LDL is not protected from cardiovascular disease or death from something else.

Polys lower LDL but they also oxidise easily and are inflammatory. Remove the polys and you are better off.

Stephan Guyenet said...


You make a good point; it's one I've thought about as well. I still think excess n-6 is a problem for CHD, and here's why. If you look at the early interventions (pre-1970) where they replaced animal fats with industrial vegetable fats, some of them actually did find that CHD deaths increased dramatically. For example, the Anti-Coronary Club trial (1966) and the Rose et al. trial (1965).

Why did that effect disappear in the later trials? In my opinion, it's because the background diet already contained a lot of n-6 in the later trials. The difference in n-6 between pre- and post-diet was not as large as in the earlier studies.

Chironaut said...

Just because we have mechanisms for removing compounds from our system doesn't mean that they're bad. We certainly absorb a whole lot of compounds that are bad for us, such as ethylene glycol.