Another new wrinkle in the cholesterol story

One of the great marketing successes of the pharmaceutical industry has been the linkage between LDL cholesterol levels and heart disease. In essence, the message, “if your LDL cholesterol is high, you are going to die,” is powerful. Unfortunately, the data state otherwise.

It was known in the mid 1990s that oxidized LDL was the primary suspect in the development of atherosclerotic lesions; not natural, non-oxidized LDL. But it was also at this time that the first statin studies began to appear, and that gave the pharmaceutical industry a patented drug to “prevent” heart disease (2). It was such a good story to tell and an even better one to sell. Unfortunately, as I pointed out in an earlier blog, it has never held up well against unbiased scrutiny, especially in patients with high cholesterol levels but without any heart disease.

Part of the reason lies in the data. Shown below is the correlation of LDL cholesterol to heart disease

You can see from this data that there is a higher percentage of cardiovascular disease patients with high LDL cholesterol levels compared with very low levels, but not that much. This explains why about half the people who die from heart disease have normal LDL cholesterol levels (less than 130 mg/dl). It also means that high LDL cholesterol is not a very good predictor of heart disease.

On the other hand, a very different picture emerges if you look at the levels of oxidized LDL levels as shown below.

Even without a background in statistics you can see a very striking relationship in the prediction of heart disease with increasing levels of oxidized LDL levels.

So why don’t physicians use oxidized LDL levels as an indicator of heart disease risk? First, the test is much more difficult to do than a simple cholesterol test. Second, it ruins a great story that is easy to communicate to the patient. Third, the best way of reducing oxidized LDL levels is natural anti-oxidants, such as polyphenols, that have no patent protection (3,4). Reducing LDL cholesterol is simple. Just take a statin drug for the rest of your life. Reducing oxidized LDL cholesterol requires having plenty of antioxidants in your diet with polyphenols the most powerful.

Now there is another new entry into the LDL story. This is “super-sticky” LDL. In an online pre-publication, it was demonstrated that this new type of LDL particle may be even worse than oxidized cholesterol in promoting the development of heart disease (5). This “super-sticky” LDL comes from the formation of advanced glycosylation end products (AGEs). I described this formation of protein-carbohydrate linkages as an integral part of the aging process in my book, “The Anti-Aging Zone,” published more than a decade ago (6).

The best way to reduce the production of “super-sticky” LDL is to reduce blood sugar levels. This helps explain why individuals with diabetes are two to three times more likely to develop heart disease. The best way to reduce elevated blood sugar is the Zone diet. That’s why the latest dietary recommendations for the treatment of diabetes by the Joslin Diabetes Research Center at Harvard Medical School are essentially identical to the Zone diet.

Heart disease remains the number-one cause of death in America. Unfortunately, it is more complex than “taking a statin a day to keep death away”.


  1. Maor I and Aviram M. “Oxidized low-density lipoprotein leads to macrophage accumulation of unesterified cholesterol as a result of lysosomal trapping of the lipoprotein hydrolyzed cholesterol ester.” J Lipid Res 35: 803-819 (1994)
  2. Simvastatin Study Group. “Randomized trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).” Lancet 344: 1383-1389 (1994)
  3. Shafiee M, Carbonneau MA, Urban N, Descomps B, and Leger CL. “Grape and grape seed extract capacities at protecting LDL against oxidation generated by Cu2+, AAPH or SIN-1 and at decreasing superoxide THP-1 cell production.” Free Radic Res 37: 573-584 (2003) (ISSN: 1071-5762)
  4. Chen CY, Yi L, Jin X, Mi MT, Zhang T, Ling WH, and Yu B. “Delphinidin attenuates stress injury induced by oxidized low-density lipoprotein in human umbilical vein endothelial cells.” Chem Biol Interact 183: 105-112 (2010)
  5. Rabbani N, Godfrey L, Xue M, Shaheen F, Geoffrion M, Milne R, and Thornalley PJ. “Glycation of LDL by methylglyoxal increases arterial atherogenicity.” Diabetes 60 doi:10.2337/db09-1455 (2011)
  6. Sears B. “The Anti-Aging Zone.” Regan Press. New York, NY (1999)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

Share and Enjoy:
  • Print
  • Digg
  • StumbleUpon
  • Facebook
  • Yahoo! Buzz
  • Twitter
  • Google Bookmarks

Related Posts:

This entry was posted in Zone Health and tagged , , , by Dr. Barry Sears. Bookmark the permalink.

About Dr. Barry Sears

Dr. Barry Sears is a leading authority on the impact of the diet on hormonal response, genetic expression, and inflammation. A former research scientist at the Boston University School of Medicine and the Massachusetts Institute of Technology, Dr. Sears has dedicated his research efforts over the past 30 years to the study of lipids. He has published more than 30 scientific articles and holds 13 U.S. patents in the areas of intravenous drug delivery systems and hormonal regulation for the treatment of cardiovascular disease. He has also written 13 books, including the New York Times #1 best-seller "The Zone". These books have sold more than 5 million copies in the U.S. and have been translated into 22 different languages.

30 thoughts on “Another new wrinkle in the cholesterol story

  1. Dr. Sears,
    Question 1: When you suggest adding one EicoRx per day does that mean in addition to the 4 capsules per day for the average healthy person or substituting one of the 4 OmegaRx?
    Question 2: For the average person, how much oatmeal per week could replace that one EicoRx you recommend?

    • To make it easy, just add one additional EicoRx capsule for every four OmegaRx capsules. The extra omega-3 fatty acids will just make you smarter.

      Eating two bowls of slow cooked oatmeal per week can replace the one EicoRx capsule.

  2. Dr. Sears,
    Your recommendation to add one EicoRx capsule concerned me, and I asked in another of your blogs and you didn’t answer, because I’m taking 6 EicoRx capsules a day and have been all this year. I referred back to Chapter 12 of Enter The Zone where you discussed GLA where you have also said your recommendations for GLA. You imply a limited amount of supplementing with GLA but always fail to mention if a person should or should not take too much; to eat 2 bowls of oatmeal a week but why not eat atmeal every day? Why should a person limit oatmeal to 2 bowls a week or 3? Why do you limit oatmeal and GLA? You never explain this?

    Moreover, I’m not complaining about eating too much GLA or taking too many EicoRx capsules because, believe this, recently I noticed the 3 inch bald spot on the crown of my head that I’ve had for the last 20 years has grown back in and no sign of any bald spot. All the hair on my head is much thicker and grows faster as do my finger nails grow much faster which tells me I’m in the Zone. Are you aware that you’ve got a product much better than Rogaine?

    • Hi, Jockobono,
      You mentioned that you take sesame seed oil. Is that specifically for your condition or something everyone should do?

      • Dr. Sears,
        Thanks for your comment about EicoRX. I wondered if you’d comment on this regime?:
        4 OmegaRX
        1 EicoRX
        1 baby aspirin
        1 polyphenol
        Zone Diet
        I am a healthy 54 year old male, 5’7″, 136 lbs., work out daily, but strong history of cancer in my family, mother died at 44, brother at 37.

    • I have known the power of GLA since 1982. It’s controlling that power that remains a challenge. There is variability in an individual’s response to GLA. The blood is not a good test of that variability. That’s why I developed the Eicosanoid Status Report 20 years ago for my elite athletes to help me guide them for the appropriate use of GLA. Most people don’t have the time or patience to follow the guidelines for the use of that report which can be found on

      When GLA works, it works very well. When it spills over into excess AA, the results can be nasty. That’s why I recommend very low doses, if any at all, for most people unless I am working directly with them.

  3. Dr. Sears’ comment on EicoRx was awfully vague and he never seems to answer the tough questions.
    Not sesame seed oil, Joe. “Toasted” sesame seed oil is what you need to take. Dr. Sears recommends this but I can’t remember where I saw it. Do a search. It is expensive compared to the regular sesame seed oil and quite hard to find.
    I not only take a polyphenol capsule, I drink the sea health also = more polyphenols.

  4. Thanks, Jockobono,
    Have you checked out the site “IHerb”? If not, try it. Prices are very good and shipping is free over $40. You can find polyphenols at a decent price, but I don’t know how good they are. Interesting that he never seems to answer the tough questions, but it’s the tough questions that need answering, yes? And the tough questions arise out of very important concerns. Been checking out the Protein Power website. Been there?

  5. But you asked this on a weekend! Give the guy a break. I’d like to know more about this, too, is this steel cut oatmeal? I make it for my parents, my father loves it. They have blueberries a few times a day. They have had oatmeal for years and years. I made it yesterday with coconut milk instead of water, added sliced almonds and raisins and cinnamon and MCT oil and apple pieces. Am I helping them? Should I eat this more often myself? And can it be two times a week, or is it better several times a week? My father loves it and has it every day, with some wheat germ.

  6. Is there a way to measure levels of “super sticky” LDLs? (and a benchmark to compare it to?) Regarding oxidized LDL, it states it is a more difficult test…difficult as in most labs wouldn’t be able to do it and the cost would be prohibitive? Or is there a way to have that test ordered?


    • The best test for indication of the presence of super-sticky LDLs would be a HbA1C test that is commonly done for diabetics. Oxidized LDL tests are available and relatively inexpensive, but few labs do them because virtually no physician understands their predictive value and as a consequence they don’t order them.

  7. Did something get left out or deleted? Am I the only one to notice this? The text says “Part of the reason lies in the data. Shown below is the correlation of LDL cholesterol to heart disease” But there is no graphic for that. It then goes on to say “On the other hand, a very different picture emerges if you look at the levels of oxidized LDL levels as shown below.” for which there is a very convincing graphic. What happened to the first graphic? I tried two different browsers and got the same result.

  8. “the best way of reducing oxidized LDL levels is natural anti-oxidants, such as polyphenols”.

    Drum roll please; and the best source of said nutrients is …… low glycemic load green leafy vegetables, berries (and green tea). All staples in my zone diet.

  9. The chart & data for the total LDL levels can be found in the The Quebec Cardiovascular Study (the first large study demonstrating that heart attack can occur when a person’s LDL particle number is high and LDL level is low.)

    Recently in the AMORIS study, which enrolled a remarkable 175,000 participants and demonstrated the superiority of LDL particle number (measured as apoprotein B) in predicting heart attack risk.

    Lamarche B, Despres JP, Moorjani S, et al. Prevalence of dyslipidemic phenotypes in ischemic heart disease (prospective results from the Quebec Cardiovascular Study). Am J Cardiol. 1995 Jun 15;75(17):1189-95.

    Walldius G, Jungner I, Holme I, et al. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001 Dec 15;358(9298):2026-33.

  10. Joe,
    I have been buying regularily from iHerb for many years. I’m glad you are
    aware of this fabulous website company.

  11. I am a 60 year old woman who has been diagnosed with Rheumatoid arthritis. I am looking for alternative therapy other than methetrexate and Arava to deal with chronic Achilles tendonitis from RA. I have started taking EicoRx with each meal ( 3 per day). I am eating Quinoa flakes with blueberries, walnuts and almond milk every day. I am trying to eat foods with an alkaline pH. I have been following this diet for about 2 months and haven’t really seen any improvement yet. Are there any other suggestions you could give?

    • You will probably need much higher levels of EPA and DHA to reduce the cellular inflammation in the joints. I would also follow a more strict Zone diet where the carbohydrates come primarily from vegetables and a little fruit. I would also significantly reduce your intake of grains.

      • I would agree there. I started on a Paleo Diet (google Robb Wolf’s Paleo Solution) about 5 months ago. Have reduced fasting blood sugars to below 100. Have knocked my methotrexate down from 22.5mg/week to 17.5mg and am slowly reducing it by 2.5mg every 3 months. Take 5-6 grams (4 tsps) of Barleans Liquid Fish Oil daily along with 2 of Dr Sear’s Polyphenol Plus caps. Eliminated grains and dairy. Trying to shop organic and grass fed products – tough on my budget, but has reduced my RA symptoms and certainly improved my HBA1c. Try to eat organic raspberries,blueberries,blackberries and other fruits that have small impact on my blood sugars. Still work to do, but making progress. I’m also 60 years old.

        • People tend to forgot (or never got to Chapter 8 in The Zone) that the foundation of the Zone diet was based on the earliest published data on Paleolithic nutrition in an 1985 article in the New England Journal of Medicine. I am always constantly amazed by latest generation of dietary gurus that supposedly “discovered” something new. The unique aspect of the Zone diet was its explanation of how diet affects inflammation via eicosanoids.

  12. Pretty part of content. I just stumbled upon your blog and in accession capital to assert that I get actually loved account your weblog posts. Anyway I’ll be subscribing on your augment or even I success you get admission to consistently quickly.

Leave a Reply

Your email address will not be published. Required fields are marked *

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>