X Marks the Spot – T2D 30

Triglycerides and coronary disease

Gaizano et al. Circulation. 1997;96:2520-2525

Why should we care about high triglycerides? Doctors always obsess about LDL cholesterol and barely a word is heard about triglycerides, yet high blood triglycerides strongly and independently predict cardiovascular disease, almost as powerfully as LDL. Hypertriglyceridemia increases the risk of heart disease by as much as 61%. This is especially concerning since the average triglyceride level has been rising inexorably in the United States since 1976, along with type 2 diabetes, obesity and insulin resistance. An estimated 31% of adult Americans are estimated to have elevated triglyceride levels.

Hypertriglyceridemia by itself is unlikely to be causative in heart disease and represents an important marker of hyperinsulinemia. Patients with a rare disease called familial hyperchylomicronemia syndrome experience extremely high triglyceride levels their entire life, but rarely develop heart disease. Niacin is a medication effective at reducing triglycerides, but unfortunately, fails to reduce heart disease.

Triglycerides and High Density Lipoprotein

Despite the widespread perception that ‘cholesterol is bad’ fostered by medical authorities in the 1970s, this understanding is far too simplistic. Cholesterol does not float around freely, but travels around the bloodstream bundled with lipoproteins. Standard blood tests differentiate between low-density lipoprotein (LDL) and high-density lipoprotein (HDL). When most people discuss cholesterol, they refer to the ‘bad cholesterol’ or LDL.

But as far back as 1951, it was already known that high HDL (the ‘good cholesterol’) levels were protective against heart disease, later confirmed by the landmark Framingham studies. Low levels of HDL are a much more powerful predictor of heart disease than high levels of LDL. HDL is believed to be the key molecule in reverse cholesterol transport, the process whereby cholesterol from the tissues is removed and returned to the liver.

Low levels of HDL are found in close association with high levels of triglycerides. Over fifty percent of patients with low HDL also have high triglycerides. High levels of triglycerides activate the enzyme cholesterol ester transfer protein (CETP). This enzyme, important in cholesterol and lipoprotein exchange, reduces HDL levels.

Given this close association with triglycerides, it should be no surprise that low carbohydrate diets raise HDL, even independent of weight loss. By contrast, the standard low-fat diet minimally affects HDL. In one study, the low carbohydrate Atkins diet raised HDL fourteen times more than the ultra-low-fat Ornish diet.

Pharmaceutical companies invested billions of dollars developing drugs that raise HDL by inhibiting CETP. Torcetrapib, at that time, the most expensive drug ever developed raised HDL just as promised, but failed to reduce heart disease. Worse, it raised the risk of heart attack and death. It was killing people. The drug dalcetrapib raised HDL an impressive 40%, but also failed to deliver any heart benefits. As with triglycerides, low HDL does not cause heart disease, but is only an indicator.

What is clear, however, is that the lipid profile typical of the metabolic syndrome, high triglycerides and low HDL results from the excess of VLDL, which ultimately stems from hyperinsulinemia.

Hypertension

High blood pressure, called hypertension is commonly defined as a systolic blood pressure (the top number) greater than 140 or a diastolic blood pressure greater than 90 (the bottom number). This disease is often called ‘the silent killer’ because there are no symptoms associated with it, yet it contributes heavily to the development of heart attacks and strokes. Most cases are called ‘essential hypertension’ because no specific cause can be found for its development. However, hyperinsulinemia may play a key role.

Disproportionately high plasma insulin concentration in hypertensive patients was first reported in the scientific literature more than fifty years ago. Since then, multiple studies such as the European Group Study of Insulin Resistance have confirmed this relationship. High and rising insulin levels doubled the risk of developing hypertension in those who previously had normal blood pressures. A complete review of all available studies estimates that hyperinsulinemia increases the risk of hypertension by 63%.

Insulin increases blood pressure through multiple mechanisms. It influence all the key determinants of blood pressure – cardiac output, blood volume and vascular tone. Insulin increases the cardiac output, the contractile force of the heart directly.

Insulin increases the volume of blood in circulation by two mechanisms. First, insulin enhances sodium reabsorption in the kidney. Secondly, insulin stimulates secretion of anti-diuretic hormone, which helps reabsorb water. Together, this salt and water retention increases blood volume and thus causes higher blood pressure.

Vascular tone, how much the blood vessels are constricted in increased by insulin by increased intracellular calcium and activation of the sympathetic nervous system.

X Marks the Spot

The metabolic syndrome had been originally christened by Dr. Reaven as ‘Syndrome X’ because the symbol X is used in mathematics to denote the unknown quantity, which we are trying to find. In this case, Dr. Reaven had postulated that the various manifestations of Syndrome X all had an underlying root cause, which was then unknown. What is this mysterious X factor?

The current National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria for the diagnosis of metabolic syndrome are:

  1. Abdominal obesity
  2. High Triglycerides
  3. Low High Density Lipoprotein Cholesterol
  4. High blood pressure
  5. Elevated fasting glucose

Looking carefully at our diagram, we can now solve for the unknown ‘X’. The link between all these different diseases is hyperinsulinemia. Too much insulin causes each of abdominal obesity, high triglycerides, low HDL, high blood pressure and the high blood glucoses of type 2 diabetes.

X = hyperinsulinemia.

Syndrome X is hyperinsulinemia.

Not every disease manifests in every person. These symptoms cluster together, but there is individual variation in which appears first. One person may have high triglycerides, another person will have high blood sugars from insulin resistance, and yet another will only have high blood pressure. But having one increases the likelihood of having the others because they all share the same root cause.

The various facets of metabolic syndrome are all expressions of hyperinsulinemia. This is crucially important. Insulin resistance does not cause the metabolic syndrome. Hyperinsulinemia causes it. The power of framing the problem in this manner is that it makes the solution immediately obvious.

We need to lower insulin.

This presents the immediate and tantalizing hope that type 2 diabetes, and indeed the entire metabolic syndrome is actually a completely reversible disease.

27 Responses

  1. Thank you Dr. Fung!

  2. Thank you!! You make so much more understandable!!

  3. I am a Dr Fung disciple and have my TG/HDL ratio below 1.0. My goal is to lower my insulin. However you can not control a variable that can’t be measured. Insulin is not routinely measured.

    Has anyone found a large data base with lipid elements and insulin that has been used to develop a proxy for insulin in terms of routine lipid, glucose, or other primary care tests. It would be so useful for us insulin interested people.

    • Rimas V. Janusonis MD

      Jim – I’m a practicing physician using Dr. Fung’s principles. The TG/HDL ratio is a fairly good proxy for insulin levels (yours being <1 indicates low insulin levels). The higher the ratio, the higher the insulin. It's not perfect, but this would typically be covered by insurance (where it's more difficult to get insulin levels covered, at least in the US).

      • This isn’t borne out by my blood results. Here are my results (I replaced all the tabs with spaces, but we’ll have to see what happens in the software after I post this):

        Date HDL TGs TG/HDL Insulin
        mg/dL mg/dL uIU/mL
        10/31/16 54 147 2.72 33
        11/14/16 55 58 1.05 23.8

        I was so shocked by the 10/31 test, that I had the 11/14 test done. Note that there are only two weeks between the tests and note the dramatic differences between them for Trigs. Previous tests for insulin were 3.8 in 6/15 (TG/HDL = 2.45) and <3.0 in 9/15 (after fasting 4.5 days) (TG/HDL = 3.95). I have to pay for these tests myself.

        Note that I was in ketosis (as verified by blood ketones) the morning of the 10/31 test. And I had been in ketosis for a while. I still have no idea why my insulin was so high in 10/16 and 11/16.

        I do know that if you fast, your HDL goes down and your Trigs go up. For instance, on Monday, 2/29/16, I had a blood test taken after 12 hours fasting (and eating for days prior to that). On Friday, 3/4/16, after 4.5 days of fasting, I had another test taken. Here are the results (all in mg/dL):

        Date TC LDL HDL TGs TG/HDL
        2/29/16 168 103 52 65 1.25
        3/4/16 188 121 36 157 4.36

        As you can see, my HDL plummeted and my Trigs skyrocketed. I think that's a side effect of fasting, and is not deleterious in the long term. However, you can see that these values bounce around a lot and it's wise to not place too much emphasis on them.

        • thanks Bob for posting this. It clarifies some similar results I have been getting. I will make sure not to fast next time my doctor orders a blood test, so she can leave me alone re: cholesterol.

        • Terry teh

          Not uncommon, in my experience.To have yoyo bp n bs or even heart palpitations.

          I have a theory on this phenomena. As the body heal itself from fasting, autophagy, human growth hormones and other hormones n enzyme,es are secreted. Cholesterol is actually not a problem but indicates that the organs or cells are inflamed. This the body produces more cholesterol in an attempt to cover these inflammation.

          In short, the body is actually working harder to heal itself, hence these elevated. markers. So long as it is only temporary.

          I have continue with if n a low carb diet. And as the months goes by, more and more toxins manifest itself.recently, I have a very bad case of hives that will not go away for 4 months. The time I got it, I was a vegan for 3 weeks. Doctors could not figure out, how this could develop.at the same time my bp shot up from a stable 100/60 to 150/100. I just persist with it, n now hives are ok n my bp have come back to 110/70.

          A possible explanation from Chinese medicine is wet heat. That is so deep it is buried in our bones. Since the healing is happening continuously, it was time to expel this wet heat. In the long term if nothing is done this wet heat will manifest n cause way more damage than hives n elevated bp.

        • When fasting and changing life style to a low-carb (LCHF) temporarily your body makes various lab seem rotten. There is for instance temporary hyperlipidemia, high triglycerides, bad cholesterol profile…as you go on, after some time this should gradually adujst to more normal numbers. Your body is cleaning up, using your fat stores. Tuning hormones. It´s like you´re making general cleanup up of your house. First you take everything out of shelves, closets, attic, basement. For a while it seems like complete mess and unimaginable to tidy it up. As you go on cleaning step by step, you throw away things you don´t need, are broken or rotten. What is good and what you need you put back. Now, after some time, there is more space, fresh air and nice and tidy house.

          • Scott S

            Sona — What a nice metaphor! I started fasting daily (19/5) 3 months ago, lost 10 lbs of fat (6′ tall male 172/174 down to 162) and Trig UP, Chol UP LDL UP. Fasting Glucose 100! (vs. 80’s) and even BP UP but I was eating LOTS of Carbs.
            Now I’m adding the LCHF to fasting regimen and hopeful that will help my body “clean house,” as you put it so well!
            Thanks Dr Fung — these articles help me understand what’s going on with my Chronically high Trig and chol. and the key to lowering via Fast and Low Carb…
            I was getting hopeless re: Cardiac risk — but now feel I can do something to lower it and live longer.

      • Thank you Dr Janusonis for your insight and response. I’ll keep the ratio at or below one and call it good.

  4. Stephen T

    Wouldn’t it be nice if more doctors knew this?

  5. You put it all nicely together
    Dr. Hasanah

  6. awesome
    on point

  7. Dr. Fung given your excellent work on diet, fasting, calcium supplements, salt, bad fats, diabetes and insulin, thus I am surprised that you have fallen for bad pharma on the cause of cardiovascular disease.
    There is a large chorus of scientists who expose the cholesterol myth, yet it persists. The science supporting the association of cholesterol with cardiovascular disease is generated by Pharma. I would suggest as a starting with a Australian Broadcast Corporation documentary in 2 parts https://www.youtube.com/watch?v=sGIGXfIDaJo and https://www.youtube.com/watch?v=AY4eTGMe-EY

    For more go to my website at http://healthfully.org/rh/id7.html

    Prof. Uffe Ravnskov is the leading authority on the myth and causes of cardiovascular diseases. See the website he started at http://www.thincs.org/

  8. Am I understanding this statement incorrectly? Or, is there a typographical error here, where I have marked-(??) ?

    “Not every disease manifests in every person. These symptoms cluster together, but there is individual variation in which appears first. One person may have (low??) triglycerides, another person will have high blood sugars from insulin resistance, and yet another will only have high blood pressure. But having one increases the likelihood of having the others because they all share the same root cause.”

    Thanks for all your very valuable information.

  9. Luca Marenco

    “One person may have low triglycerides, another person will have…”
    You meant HIGH, not low?

  10. “Vascular tone, how much the blood vessels are constricted in increased by insulin…”
    Minor typo here just before the “X Marks the Spot” paragraph, with “in” instead of “is.” If you fix it, please delete this comment.

  11. What TG/HDL ratio do you recommend?
    Both you and Dr. Ted Naiman seem to be saying that high insulin is what damages our bodies and not so much the high glucose in the blood. So is it insulin that causes all of the damage in the bodies of diabetics and not sugar after all?

    Or is it glucose that actually does the damage b/c of insulin resistance caused by too much glucose in the diet which leads to more insulin getting pumped out to deal with the glucose which leads to insulin resistance which leads to more and more insulin in circulation and thus more insulin resistance and higher and higher blood glucose levels which leads to endothelial damage all over the body?

  12. Stephen T

    Pam, Dr Fung says that Syndrome X is hyperinsulinemia. Blood glucose is a symptom and treating it on its own isn’t getting to the root cause of the problem of, say, a diabetic.

    So, a diet containing too much sugar and carbohydrate eaten over too much of the day will chronically raise blood glucose and eventually lead to hyperinsulinemia. Eating LCHF reduces the level of the insulin spike, and fasting reduces the period when we are responding to food with insulin. In short, a lower level of insulin when we eat and no insulin over a much longer period.

    The last few posts should be very helpful to you.

  13. Genevieve

    My question is about low metabolism but I am asking here because it is the most recent post and has a better chance of being seen.
    My understanding is that fasting will not lower your metabolism like restricting calories does. Also, that eating more calories may increase your metabolism if you are at your set weight but after awhile of over eating you will gain weight.

    The question is what are the steps to lose wight by fasting but also increase a very low metabolism that is at around 1500 calories per day?
    Thanks!

    • Just fast and eat a low carb diet. Don’t count calories. Calories don’t matter. Long fasts will heal your metabolism faster than anything and change your set body weight (Thermostat) If you get Dr. Fung’s book The Complete Guide To Fasting all of your questions will be answered.

  14. Jason of Toronto you probably hear it a lot. But this hunge amunt of awesomness that you put into the world for free is phenominal. I have been following you for 2 years brought your books. listen to you podcast with the equally fab Jimmy. This balanced, well thought out and easy to consume information is such a valuble resource. I feel at last like there is hope that every health proffeson can turn this tidal wave of ill health and you are at the vangaurd of that movement. I commend you – you are changing lives, saving lives and educating people, in your precious ‘spare’time. I give you a high five and a ‘well done’ stamp on the hand.?

  15. Damage from high insulin is what drives vascular disease. Lipid levels are just markers of this, we could test insulin levels instead though but that would open up a very big can of worms, Pandora’s box even, and then you’d discover that the evil Pandora is guiding you down the garden path to more and more illness. Insulin in excess damages blood vessels directly, ironically we get plaques to try to repair the damage, let’s rip off the bandages and ignore the cause and proclaim ourselves treated!

  16. Diana Rodriguez

    Just got back my own cholesterol blood work. I can verify from my own experience that fasting seems to raise triglycerides. Everything looks mixed up from my previous blood work in December, and I’ve been LcHF and IF for almost a year. Did lab work April 17 and don’t like a 221triglyceride compared to previous 149 which was still too high as far as my thinking goes. I know other factors count, but my A1C dropped from 7.7 to 6.5. Not bad for someone who went off all insulin meds and metformin June last year. My blood pressure has been wonderful, averaging 104/66. Weight dropped 54 lbs, and lost 14 inches from waist. Have a ways to go. Still, what is Dr. Fung’s response to high triglycerides due to fasting.?

  17. TG = 40 / HDL 86 … 🙂

    There is something called the Atherogenic Index. A little bit more sophisticated than solely the Quotient.

    You can calculate it here:

    http://www.labor-limbach.de/Atherogener-Index.439.0.html?&no_cache=1

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