Are sterols the new trans fat?

By now, I'm sure you're well-acquainted with the hydrogenated, trans fat issue.

Hydrogenation of polyunsaturated oils was a popular practice (and still is) since the 1960s, as food manufacturers sought a substitute for saturated fat. Bubbling high-pressure hydrogen through oils like cottonseed, soybean, and corn generates trans fatty acids. These man-made fatty acids, while safe in initial safety testing, proved to be among the biggest nutritional mistakes of the 20th century.

Trans fatty acids have been associated with increased LDL cholesterol, reduction in HDL, oxidative reactions, abnormal rigidity when incorporated into cell membranes, and cancer. Trans fats still dominate many processed foods like chips, cookies, non-dairy creamers, food mixes, and thousands of others. They're also found prominently in fast foods.

Fast forward to today, and most Americans have become aware of the dangers of trans fats and many try to avoid them.

But I worry there is yet another substance that has worked its way into the American processed food cornucopia that has some potential for repeating the trans fat debacle: sterol esters.


Sterols are naturally-occurring oils found in vegetables, nuts, and numerous other foods in small quantities. Most of us take in 200-400 milligrams per day just by eating plant-sourced foods.

Curiously, the chemical structure of sterols are very similar to human cholesterol (differing at one carbon atom). Sterols, by not fully understood means, block the intestinal absorption of cholesterol. Thus, sterol esters, as well as the similar stanol esters, have been used to reduce blood levels of total and LDL cholesterol.

So far, so good.

The initial commercial products, released in the late 1990s, were Take Control (sterol) and Benecol (stanol), both of which were marketed to reduce cholesterol when 2-3 tbsp are used daily, providing 3400 – 5100 mg of sterol or stanol esters, about 10- to 20-fold more than we normally obtain from foods. Several clinical trials have conclusively confirmed that these products reduce cholesterol levels.

They do indeed perform as advertised. Add either product to your daily diet and LDL cholesterol is reduced by about 10-15%. In fact, in the original Track Your Plaque book, these products were advocated as a supplemental means of reducing LDL when other methods fell short.

In 2008, there are now hundreds of products that have additional quantities of sterol esters in them, such as orange juice, mayonnaise, yogurt, breakfast cereals, even nutritional supplements. Most of these products proudly bear claims like "heart healthy." Stanol esters have not enjoyed the same widespread application. (I believe there may be patent issues or other considerations. However, it's the sterols that are the principal topic here, not stanols.)

Now, here's where it gets a bit tricky. There is a rare (1 per million) disease called sitosterolemia, a genetic disorder that permits the afflicted to absorb more than the usual quantity of sterols from the intestine. While you and I obtain some amount of sterols from plant-based foods, absorption is poor, and we absorb <10% of sterols ingested. However, people with sitosterolemia absorb sterols far more efficiently, resulting in high blood levels of sterols that result in coronary disease and aortic valve disease, with heart attacks occurring as young as late teens or 20s. Treatment to block sterol absorption are used to treat these people.

There are also a larger number, though still uncommon (1/500) of people who have only one of the two genes that young people with sitosterolemia have. These people may have an intermediate capacity for sterol absorption.

Okay, so what does this have to do with you? Well, if you and I now take in 10-20 times greater amounts of sterol esters, do our blood levels of sterols increase?

Several studies now suggest that, yes, sterol blood levels increase with sterol ingestion. One study from Finland, the STRIP Study, showed that children who had double usual sterol intake increased blood levels by around 50%.

Similarly, a Johns Hopkins study in adults with only one of the genes ("heterozygotes") for sitosterolemia increased sterol blood levels by between 54-116% by ingesting 2200 mg of sterols added per day, despite reduction of LDL cholesterol levels.

Even people with neither gene for sitosterol hyperabsorption can increase their blood levels of sterols. But the crucial question: Do the blood levels of sterols that occur in unaffected people or in heterozygotes increase the risk of coronary heart disease? The answer is not known.

Despite the several clinical trials performed with sterol esters, all of them have examined LDL and total cholesterol reduction as endpoints, not cardiovascular events. It is conceivable that, while sterol esters reduce cholesterol, risk for heart disease is increased due to higher blood levels of sterols.

The question is not settled. For now, it is just a suspicion. But that's enough for me to steer clear of processed foods supplemented with these uncertain sterol esters. My previous recommendations for sterol ester products will be removed with the next edition of Track Your Plaque. Until we have solid evidence that there are no adverse cardiovascular effects of sterol esters, in my view they should not be part of anyone's heart-disease prevention program.

(The same argument does not seem to apply to stanol esters, such as that contained in butter-substitute Benecol, since stanol esters are not absorbed at all and remain confined to the intestine.)

Comments (16) -

  • lizzi

    9/13/2008 3:36:00 PM |

    My thoughts exactly.  I,too, used to use and recommend sterol ester containing margarine.  Stanols,as you pointed out, aren't absorbed, but who knows if they are worth the money. Obviously not everything that lowers our cholesterol is good for us. Still, lowering your cholesterol by 15% makes many of us feel like we just got an A+ on our report card, regardless of whether or not we have done something good for our health.
    I do believe that fish oil raises LDL cholesterol (probably large fluffy LDL) as it lowers triglycerides. But the evidence seems overwhelming that DHA and EPA are good for my health. But then I shudder about my report card.  Off smart balance, on Ghee, on 3,000 mg/day DHA/EPA.....

    Now they are esterifying fish oil. Lovasa, Big Pharma's new improved fish oil.  Now made more chemically stable. I wonder about it too. Is it the new trans fish oil?

  • Peter Silverman

    9/13/2008 8:28:00 PM |

    Since you wrote about how good almonds are for lowering LDL and how about half the calories don't get absorbed I have been eating close to half pound a day.  I wonder if that's a lot of sterol.

  • rabagley

    9/14/2008 1:54:00 AM |

    The next frankenfood.  Sigh.  When will we, as a culture, learn that it's extraordinarily difficult to synthesize something as nutritious and as wholesome as what nature provides?

    Give me butter, eggs, whole milk, chicken with skin on, and red meat with a healthy rind of fat any day of the week.  Twice on Sunday.

    On a diet dominated by those foods, my weight is steady as a rock and my lipid panel has never been better.

  • Anonymous

    9/14/2008 5:21:00 PM |

    The previous poster made an interesting comment abour esterified fish oil, which I am hoping Dr. Davis writes about one of these days.

    Fish oil's natural form is triglyceride, I believe, and there are only a couple of brands out there that sell this form. Everything else is ester.

    But is one form healthier than another? I know of 2 absorption studies that state omega-3 esters are the worst form regarding absorption. And are there any unknown health risks from taking altered Omega 3s long term?

    I'm personally sticking with the triglyceride form of fish oil for now, until this issue is studied properly.

  • lizzi

    9/16/2008 4:14:00 PM |

    A recent reference:  Vascular effects of plant sterols, Weingartner O, J Amer Clin Cardiol April 22, 2008.
       Mice with higher plant sterol levels had significantly more endothelial damage than those with low levels.

  • Anonymous

    9/17/2008 4:14:00 PM |

    Interesting discussion. I'm nurse practitioner (male). I've been fine tuning my diet and looking into fish oil's benefits for some time, as well as taking it.

    Would anyone know of non-esterified fish oil source(s) ?

    Also, with regards to the food content of esters, how do we know how to avoid them, since I can't seem to recall if labels display whether or not esters are part of the ingredients/manufacturing method.

    Thanks

  • Chipdouglas

    9/17/2008 4:20:00 PM |

    I'm a nurse practitioner (male) ever optimizing my diet, exercise and other modifiable risk factors for CVD.

    Regarding fish oil, would anyone know of company(ies0 manufacturing ester-free fish oil ? I recall one poster mentioning that most are esterified though.

    So far as foods, I don't think esters are shown on any food label--although I might be off. So, how would one avoid esters in foods, as it seems to be a growing issue.

    Many thanks.

  • Marilyn Mann

    9/18/2008 2:52:00 PM |

    Here's a post on this topic from another blog:

    http://www.gooznews.com/archives/001187.html

  • Anonymous

    9/18/2008 11:26:00 PM |

    "FACT: Researchers in Norway found that when 14 healthy male volunteers took equivalent amounts of omega-3 as ethyl esters or glycerol esters (triglyceride form), the absorption from both forms of omega-3 was just as good. As reported in the medical journal, “Thus, after administration twice daily for 14 days, the amounts of EPA and DHA in total serum lipids and in serum phospholipids were essentially identical for the two ester forms of the n-3 fatty acids.” [i]

    FACT: Another human study comparing the absorption of omega-3 fatty acids in the form of ethyl esters or triglycerides, showed that both were well absorbed and had produced results. According to the American Journal of Clinical Nutrition, “This study showed that n-3 fatty acids in fish oil given as ethyl esters or triglycerides were equally well absorbed.”[ii]"

    [i] The enteral bioavailability of eicosapentaenoic acid and docosahexaenoic acid is as good from ethyl esters as from glyceryl esters in spite of lower hydrolytic rates by pancreatic lipase in vitro. Biochim Biophys Acta 1993 May 20;1168(1):59-67

    [ii] Absorption of the n-3 eicosapentaenoic and docosahexaenoic acids as ethyl esters and triglycerides by humans. American Journal of Clinical Nutrition, 1991 Vol 53, 1185-1190


    "Res-Q 1250 offers an ethyl ester form of omega-3 which is appropriate for encapsulation (Res-Q 1250 Capsules), and a triglyceride form (Res-Q 1250 Liquid) which is appropriate for a liquid product."

    http://n3oceanic.blogspot.com/2008/09/triglycerides-versus-ethyl-esters-fact.html

  • susan

    10/6/2008 8:07:00 PM |

    I've noticed a huge increase in these and use them in both my cooking oil and margarine.  I wonder if I should switch?  It should just be common knowledge that there is a good and bad side to everything, I don't know why we are not more careful about this from the beginning.

  • Anonymous

    4/12/2009 7:24:00 AM |

    There is a review on plant sterol esters and hypercholesterolemia:

    http://eurheartj.oxfordjournals.org/cgi/content/extract/30/4/404

    It is open access !

  • Anonymous

    4/13/2009 7:50:00 AM |

    Interesting review on plant sterol esters! Seems to be a pretty hot discussion. Wounder why the stuff is still available !!!

  • patricia

    9/9/2009 4:31:11 PM |

    my 3 year old grandson has sitosterolemia and because of the way our food today is made with all the sterols to keep us healthy it is virtually impossible to buy him anything that it is ok for him to eat .   Plant sterols are in almost everything but not always advertised that they are there.   The long term outlook for our grandson is pretty bleak and i would be gratefull if anyone could give us some ideas on what it is actually possible for him to eat.

  • Anonymous

    9/10/2009 2:10:45 AM |

    To Patricia.  I am sorry that your grandson has sitosterolemia.  I am a 60-ish mother of three grown men and I raised them all on home cooking of whole foods: Fruits, vegetables, lean meats, lean dairy, cheese, yogurt, eggs, nuts, wild rice, small amounts of potatoes, olive oil and small amounts of butter. I was not a stay at home mom, either. It fascinates me that people have to ask the question, what to feed a child when you can't count on verity in packaging.  Please, feed them whole food, organic whenever possible.

  • buy viagra

    7/12/2010 1:37:38 PM |

    Sterol can be pretty dangerous as trans fat or sugar. So FDA must ban it too for the sake of our population. I wonder whatswhy FDA doesn't search healthy alternatives for us.

  • buy jeans

    11/3/2010 6:59:07 PM |

    They do indeed perform as advertised. Add either product to your daily diet and LDL cholesterol is reduced by about 10-15%. In fact, in the original Track Your Plaque book, these products were advocated as a supplemental means of reducing LDL when other methods fell short.

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Near-death experience with nattokinase

Near-death experience with nattokinase

This is a true story that I personally witnessed.

A 60-some year old man heard that nattokinase "thinned the blood." So he had been taking it for the past 6 months.

One week before he came to see me, he abruptly became quite breathless. He was unable to walk more than 20 feet or bend over to tie his shoes due to the breathlessness.

He came to see me in the office. I was alarmed by how breathless he was without signs of heart failure or other obvious explanation. I sent him for an immediate CT pulmonary angiogram. Within 30 minutes, we had the diagnosis: a large "saddle" pulmonary embolus, meaning a large blood clot that straddled the right and left main pulmonary arteries. One wrong move and . . . bang! He would have been dead within a couple of minutes, since a large clot can completely occlude the large arteries feeding the lung, essentially corking any blood circuiting through the lungs and back to the left side of the heart. (Causing, incidentally, electromechanical dissociation, in which the heart keeps beating for a few minutes but no blood is being pumped. CPR can keep you alive for a few minutes, then it's over.)

When I advised the patient of the diagnosis (after initiating the REAL anticoagulants), he said, "But I was taking nattokinase!"

Exactly. Blood clots are no laughing matter. They are potentially fatal events. Betting your life on some company's advertisement is nothing short of foolish.

Anyone who reads The Heart Scan Blog knows that I am an avid supporter of nutritional supplements. I even write articles and consult for the supplement industry. But I truly despise hearing unfounded marketing claims that some supplement companies will make in the pursuit of a fast buck.

There is no doubt that we need better, safer methods to deal with dangerous blood clots, whether in the lung, pelvis, or other areas. But, before anyone takes a leap based on the extravagant marketing claims made by a supplement manufacturer, you want to be damn sure there are real data--not marketing claims, REAL data--before you use something like nattokinase in place of a proven therapy.

Don't confuse the very interesting, though unpalatable, natto with nattokinase. Natto contains vitamin K2 and some other interesting compounds, including nattokinase.

Comments (22) -

  • Anonymous

    5/15/2010 10:41:58 PM |

    Interesting that your warning about nattokinese is FOLLOWED immediately by an advertisement for.... nattokinase extracts!

  • mongander

    5/16/2010 1:29:07 AM |

    Actually most nattokinase does not contain vitamin K2.  When nattokinase is extracted from natto, the K2 is separated and sold as another profitable byproduct.

  • Anonymous

    5/16/2010 1:29:07 AM |

    Wait a minute though! Was there any indication that he needed a real blood thinner before his clot? Maybe he was just taking it like a daily aspirin to "thin the blood" not for therapeutic blood anticoagulation. His clot was unfortunate but probably could have occurred with a cardiologist sactioned baby aspirin.

  • Dr. William Davis

    5/16/2010 1:07:24 PM |

    Anon--

    He was taking aspirin, as well.

    However, aspirin does NOT prevent deep vein thromboses that lead to pulmonary emboli, regardless of dose. Aspirin is a platelet-inhibitor, not a true "blood thinner" that works by way of clotting proteins.

  • sfr

    5/16/2010 2:18:50 PM |

    Was he using nattokinase as an excuse not to take his warfarin, or something like that? Otherwise it seems very unlikely that the nattokinase had anything to do with the clot. If anything, I'd worry about nattokinase causing bleeds, not clots.

  • Anonymous

    5/16/2010 5:58:24 PM |

    Curious if you ever recommend pycnogenol in cases where there is a risk of DVT? I believe there is at least one study showing a reduced risk of DVT in those who took pycnogenol.

    I'm not saying it's better than anti-coagulants, but it may be better than aspirin.

  • Myron

    5/16/2010 6:08:01 PM |

    Real anti-coagulants?  Like the red clover extract coumadin?  Patients on coumadin even with careful control often suffer excessive bleeding or more clots and strokes.    
    I guess the point is that clotting control is very difficult and that the number one drug is a natural medicine, herbal extract.

  • Anonymous

    5/16/2010 11:25:24 PM |

    One time, I was at a local vitamin shop when I saw that the supplement I was thinking about buying contained nattokinase.  Having read your blog and knowing what you think of nattokinase, I put the product back on the shelf.  The proprietor of the shop asked me why I did not want that supplement, because in his opinon it was a very good product.  I said that I did not want to take anything with nattokinase in it, and he said, "What do you have against nattokinase?"  I didn't bother to explain myself to him, figuring that I would just be wasting my breath.

  • Eric

    5/17/2010 1:37:14 AM |

    What is your opinion about doing higher dose mixed tocopherols, which do work on the clotting cascade. Or garlic and omegas which decrease platelet aggregation. What is your stand on normalizing your vitamin K content and then titrating your dosage of coumadin up to theraputic INR. As far as the nattokinase is concerned, do you like any of that style of enzyme? lumbokinase, serrapeptase. Although they don't have any effect on INR they should have an affect on FDPs

  • Paul

    5/17/2010 3:40:36 AM |

    That title is misleading.  People have been known to have near death cardiac events while taking fish oil, vitamin D3, and high dose niacin too.

    As well, on rare occasion, people have been known to have a recurrent DVT and/or PE while on warfarin therapy, even with an INR as high as 2.5.  Therefore, does that mean warfarin is an ineffective anticoagulant?  Of course not.

    This whole blog is about how we as individuals need to take control of our own health.  That just because we're taking a therapeutic medication or supplement, it does not therefore absolve ourselves from further investing in a life style that is proven to lower risk factors that may cause catastrophic health events.  

    I totally agree that some of the marketing claims made concerning nattokinase are inflated and frankly, unbelievable - particularly about its capabilities as a thrombolysis.  And I agree that if your doctor advices that you need heprin or warfarin therapy in order to prevent a catastrophic health event, you certainly need to heed that advice.

    But, count me down as someone who has extensively studied this subject and is still open to the possibility that nattokinase may contain some attributes in the prevention of venus thrombosis from a novel approach that needs further clinical investigation.

  • Dave

    5/17/2010 3:57:54 PM |

    Dr. Davis,

    I wouldn't be so quick to blast nattokinase because of this isolated incident or lack of research.

    Nattokinase is a "mild" blood thinner. Taking it once a day will not do more than relieve inflammation and slightly improve a person's circulation.

    A person would have to take it every 4 times a day (800 IU) on an empty stomach for if he desires a therapeutic effect. I would be curious if this patient of yours even took 200 IU per day (because a lot of products don't even contain that much).

    I have personally witnessed an improvement in circulation after taking nattokinase.

  • Dave

    5/17/2010 4:03:09 PM |

    I would like to add one more thing...

    I'm sure you have had experience with patients who took 400 IU of vitamin D in tablet form, and did not see any results after six months either. Was it because vitamin D is a worthless supplement, and should not be used?

  • Dave

    5/17/2010 4:42:33 PM |

    Sorry, I was misspoke about the dosage. Nattokinase is measured in fibrinolysis units (FU), not IU, and the effective dose ranges anywhere from 2,000-8000 FU per day.

    Also, here's actual scientific research (albeit small), not marketing hype, on nattokinase.

    http://www.ncbi.nlm.nih.gov/pubmed/19358933

    http://www.ncbi.nlm.nih.gov/pubmed/18971533

  • StephenB

    5/17/2010 6:40:37 PM |

    I've like the taste of natto from the moment I tried it. I am, however, a bit weird. ;)

  • Aaron

    5/17/2010 8:19:54 PM |

    Dr. Davis -- my question here is, could the nattokinase cause the blood clot (doesn't seem the be the case)?  Are you saying that it didn't matter that he was taking nattokinese because it doesn't reach the bloodstream to clear clots (so he would of had the clot anyway)

    Secondly, if he was taking nattokinese that had vitamin K2 <--- is it possible that increases in K2 might cause abnormal blood cloting?

  • Dr. William Davis

    5/17/2010 9:44:34 PM |

    Vitamin K2 does not cause blood clotting any more than topping up your gas tank makes your car go faster.

    Whether nattokinase has other effects is not my point. My concern is that people frequently ask if they should treat their DVT or pulmonary embolus with nattokinase. This is a death sentence. It should NOT be used for a such a purpose unless there were a large treatment trial proving equivalence or superiority to existing therapies.

  • Paul

    5/18/2010 12:50:58 AM |

    Eric,

    High dose mixed tocopherols use the same mechanisms as Wafarin/Coumadin.  They block the reabsorption of vitamin-K in the liver.  Vitamin-K is necessary for the liver to synthesize and release clotting proteins in the blood.  Warfarin/Coumadin is much, much more consistent than tocopherols in maintaining vitamin-K malabsorption and a safely prescribed INR range.  

    Titrating a Warfarin/Coumadin dosage never made sense to me. It is not toxic other than causing vitamin-K deficiency. What difference does it make if the dosage is 20 mg or 20 mcg to maintain a therapeutic INR?  Your liver will need to be equally deficient in vitamin-K no matter how you caused the deficiency.

    Garlic, ginger, ginkgo, curcumin, n-3, aspirin, N-acetylcysteine, Plavix, and yes tocopherols too all are anti-platelet agents.   They are effective at preventing arterial thrombosis, where anticoagulants have little effect. Conversely, anticoagulants are effective at preventing venous thrombosis, where anti-platelet agents (unfortunately) have little effect.

  • Michaela

    5/18/2010 7:36:40 AM |

    I'm giving my son nattokinase, one tablet daily and he also takes Vitamin K2. He has not been prescribed blood thinners, only aspirin which I stopped many months ago.
    Are you warning of not replacing prescribed blood thinners with natural therapies?
    If blood thinners have not been prescribed, is it of benefit to supplement with nattokinase?

  • rob_scheuneman

    5/18/2010 11:31:00 PM |

    Hi Dr. Davis

    I was wondering if you could help me with something.

    I've been monitoring my blood glucose recently with a basic monitor, and my readings would suggest that I am on the verge of impaired glucose tolerance, but not quite there yet.

    I was reading about continuous glucose monitoring systems. I would love to have on if these to more thoroughly monitor my blood glucose, but every model out there requires a prescription to obtain one. I don't understand this, because they are not dangerous in any way.

    Do you know of any way a non diabetic can purchase one of these?

    Any information you can give me would be greatly appreciated. Thank you.

    Rob

  • Anonymous

    9/25/2010 9:36:39 PM |

    Dr. Davis, i am a 45 year old female who recently started taking Lovasa for high triglycerides , i am also on garlic tabs and one baby asprin per day . Is is safe to replace the garlic and asprin with one tab of Natto- K per day and is it safe to take with Lovasa? I am about 20 lbs overweight do not drink or smoke and swim and or walk 3 days per week. i am genetically predisposed to high triglycerides but never had a problem until i gained the weight. Until i get the weight off i am trying a more natural approach. Help!

  • Kelly D

    8/10/2013 3:24:08 AM |

    Acta Haematol. 2010;124(4):218-24. doi: 10.1159/000321518. Epub 2010 Nov 13.

    In vivo evaluation method of the effect of nattokinase on carrageenan-induced tail thrombosis in a rat model.
    Kamiya S, Hagimori M, Ogasawara M, Arakawa M.
    Source
    Nagasaki International University, Sasebo, Japan. kamiya@niu.ac.jp

    Abstract
    Thrombosis is characterized by congenital and acquired procatarxis. Nattokinase inhibits thrombus formation in vitro. However, in vivo evaluation of the therapeutic efficacy of nattokinase against thrombosis remains to be conducted. Subcutaneous nattokinase injections of 1 or 2 mg/ml were administered to the tails of rats. Subsequently, κ-carrageenan was intravenously administered to the tails at 12 h after nattokinase injections. The mean length of the infarcted regions in the tails of rats was significantly shorter in rats administered 2 mg/ml of nattokinase than those in control rats. Nattokinase exhibited significant prophylactic antithrombotic effects. Previously, the in vitro efficacy of nattokinase against thrombosis had been reported; now our study has revealed the in vivo efficacy of nattokinase against thrombosis.

    PMID: 21071931

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