Watch as we discuss the important markers of heart disease and vascular disease risk. We will talk about how these markers can help you understand what your body is doing in the process of making or reversing atherosclerosis (plaque in the vessels). And, should you really be taking that STATIN (cholesterol lowering) drug? Get the scoop here as Dr. Nally very simply points out how the right diet can and will lower your cholesterol without the use of medications.
Research in the last 10 years points to the small-dense LDL particle as the atherogenic component of cholesterol (Hoogeveen RC et al., Arterioscler Thoromb Vasc Biol, 2014 May; Ivanova EA et al., Oxidative Med Cell Longevity, 2017 Apr). Studies in the last five years have identified that elevated small-dense LDL cholesterol correlates much more closely with risk for inflammation, heart disease and vascular disease (Williams PT, et al. Atherosclerosis. 2014 April; 233(2): 713-720.)
Recent research in the last three years demonstrates that small dense LDL cholesterol is a better marker for prediction of cardiovascular disease than total LDL-C (Hoogeveen RC et al., Arterioscler Thromb Vasc Biol. May 2014, 34(5): 1069-1077l; Ivanova EA et al., Oxidative Med Cell Longev. 2017).
Additionally, higher LDL-C is actually predictive of longer life and has been demonstrated to correlate with longevity (Ravnskov U et al., BMJ Open, 2016 Jun 12;6(6): e010401). And, a low LDL-C actually increases risk of early mortality (Schwartz I et al., Lancet 2001, 358: 351-55).
It is commonly understood that LDL-C will rise with increased saturated fat intake on a ketogenic diet. This has been know and reported in the scientific literature for over twenty years. This is to be expected, because LDL-C is really a measurement of three different LDL sub-particles (“big fluffy, medium, and small dense”). Increased saturated fat intake, while at the same time lowering carbohydrate intake, actually causes a shift in these low density particles to a bigger “fluffier” particle conformation (Griffin BA et al., Clin Sci (Lond), 1999 Sep).
The 2015 British Medical Journal, referenced above, analyzed the relevant 19 peer reviewed medical articles that included over 68,000 participants. This review showed that there is no association of high LDL-C with mortality (meaning that an elevated LDL-C does not lead to an increased risk of death from heart or vascular disease). I realize that, in stark opposition to the landmark review above, The American Heart Association’s Presidential Advisory published their position in the June 20, 2017 issue of Circulation. They stated that saturated fat is the cause of increased LDL-C and they further extrapolated that elevated LDL-C is associated with an increase in death by cardiovascular disease. This boldfaced claim is only based on one single small four year (2009-2013) literature review completed by the World Health Organization with a total of only 2353 participants, most of these studies only lasting 3-5 weeks (not nearly long enough to see fully effective cholesterol changes) and none of which had any focus on carbohydrate intake, insulin levels or LDL sub-particle measurement (Mensink RP, Geneva: WHO Library Cataloguing-in-Publication Data, 2016).
Based upon the most current scientific evidence above and my clinical experience, the large body of evidence above demonstrates the use of total cholesterol and LDL-C to determine vascular disease risk to be ineffective tools. A low carbohydrate/ketogenic diet lowers small dense LDL cholesterol, triglycerides and blood sugar and in many cases, the use of cholesterol drug (STATIN) therapy is not needed and ineffective in comparison with a ketogenic/carbohydrate restricted lifestyle.
“Won’t my cholesterol get worse and increase my risk of heart disease if I eat more fat?”
I get asked this question at least 3-4 times a day. The answer is, “NO. Not if you cut out the sugar and starch.”
“But, wait?! What about my heart? All that fat can’t be good for my heart?” they ask.
Cholesterol Defined
Let’s start with the contents of the standard cholesterol panel or “Lipid Panel.”
For the last 20-30 years the following labs have been looked at as the holy grail of heart disease risk:
Total Cholesterol
HDL (the measured number for “good” cholesterol)
LDL-C (the calculated number for “bad” cholesterol).
VLDL-C (the calculated number for very low density cholesterol)
Triglycerides
The first problem with this panel is that it makes you believe that there are four different forms of cholesterol. NOT TRUE!
Actually, cholesterol is a steroid precursor that either makes up a part of the lipoprotein molecule or is transported with the triglycerides as a passenger. The lipoproteins are just transporters made of lipid that are only slightly different from their passenger load (causing increased or decreased density). The proteins that are contained within the wall of the lipoprotein transporter is what makes them different. These lipoprotein particles can be thought of, simplistically as buses, carrying triglyceride passengers. Here size does matter, and size determines the function of the molecule at that moment in time.
Cholesterol is Really Just a Triglyceride Bus
These buses, big and small, carry the passengers up and down the vascular system of the body. Glucose can float freely through the blood stream, but the other form of fuel, triglyceride, must be transported via the “lipoprotein bus”. The triglyceride and cholesterol are actually the passengers inside the bus. But triglyceride presence in the system seems to change the density of the lipoproteins. So now picture big, medium and small buses . . . the high density lipoprotein (HDL), intermediate density lipoprotein (IDL) and the low density lipoprotein (LDL) buses.
Triglyceride Changes the Density of Cholesterol
The density of the bus gets lower as triglyceride levels rise and fewer cholesterol esters and proteins are bound. As HDL goes up, LDL-C goes down (Parker TS et al, Proc Natl Acad Sci USA, Feb 1986)
The second problem is the VLDL-C and LDL-C are actually calculated numbers and don’t actually reflect the true presence of the lipoprotein particles as the triglyceride number rises. For the accountants, mathematicians and engineers reading this that calculation is called the Friedwald Equation and is as follows:
This equation falls apart when the triglyceride level is greater than 400 mg/dL (4.52 mmol/L) or patients with hyperinsulinemia.
Total Cholesterol is the sum of the HDL, LDL, as well as intermediate density lipoprotein (IDL) & very low density lipoprotein (VLDL) which aren’t reported in the “Lipid Panel” above. So, total cholesterol is basically the sum of all the buses you have driving around.
The third key piece of information that the Lipid Panel above doesn’t tell you is the lipoprotein categories (HDL, LDL, IDL, and VLDL) are actually have three to four sub-types or sub-particles that are further differentiated by weight and size.
Image Credit: Berkley Heart Labs, Inc.
Improvement in cardiovascular risk, including improvement in cholesterol, inflammation and plaque formation have been the case with every patient I have used a high fat, low carbohydrate (ketogenic) dietary approach with over the last 12 years.
I’ve had so many people ask me how this works, and then, how to explain the changes to their primary doctors or cardiologist, I decided to write the following article. My intent is not to point the finger where others are wrong; but to identify how we, myself included, took a misstep along the path of scientific discovery. This misstep led to guidelines that, for over 45 years, have been accepted by medical students and clinicians as the “gospel truth.”
History of Cholesterol Measurement
The measurement of cholesterol, specifically total cholesterol, started in the 1950’s. There appeared to be a mild correlation of heart disease in countries who’s diets had higher fat intake. Ansel Key’s identified this apparent correlation in his Diet-Heart Hypothesis published in JAMA in 1957. He stated from his observational work that “the results of a fatty diet are hypercholesterolemia [elevated cholesterol].” A number of studies at the time showed that increasing fat intake in the standard diet increased total cholesterol; however, NO LINK to heart disease was ever proven (Ahrens EH, Jr, Lancet, May 1985).
Studies published by E. H. Ahrens, Jr. demonstrated that the cholesterol increased because of carbohydrate intake, not fat alone (Ahrens EH Jr, et al., Trans Assoc Am Physicians, 1961). The actual question, “Does increasing fat alone cause heart disease?” was never answered. The question, as well as known evidence based cholesterol reducing dietary approaches, were ignored in 1984 by the National Institutes of Health (NIH) Consensus Development Conference on Lowering Cholesterol to Prevent Heart Disease that was based heavily on epidemiological data rather than clinical reproducible science (Ahrens EH, Jr, Lancet May 1985).
Despite significant scientific evidence refuting the Diet-Heart Hypothesis, the 1984 NIH decision reflected politics and massive publicity campaigns.
Stop Demonizing My Eggs!
Since 1984, fat and cholesterol containing foods are treated like witches of Salem. As an example, eggs, specifically the egg yolk. (To this day, the chef at every breakfast bar I’ve ever visited asks if I want an egg white only omelet.) Interestingly, there is actually no scientific data association between whole egg consumption and heart disease. The science simply does not exist. Seriously, check for yourself.
You can’t extrapolate mortality risk based on a single small study that doesn’t actually identify correlation or causation. But the AHA did exactly that in 1961, and they are trying to do it again today. The MR-FIT study, largest study ever completed, is incessantly quoted as the study that demonstrates reduction in cholesterol leads to reduction in cardiovascular disease, but this trial was actually a failure and did not demonstrate improved risk by lowering cholesterol. In fact, the Director of the study, Dr. William Castelli actually stated, “. . . the more saturated fat one ate, the more cholesterol one ate, the more calories one ate, the lower people’s serum cholesterol…”
“We found that the people who ate the most cholesterol, ate the most saturated fat, ate the most calories weighed the least, and were the most physically active,” he said.
Diet-Heart Hypothesis Doesn’t Explain the French Paradox
To add to cholesterol confusion, the Diet-Heart Hypothesis does not explain the “European or French Paradox.” The French prefer cooking in butter instead of vegetable oil. In fact, the French eat 40% fat in their diet. And, more than 15% of that is saturated fat.
The French Paradox
Interestingly, the French and those that eat the most cheese, butter and whole eggs have the lowest rate of coronary vessel calcification and heart disease. Attempts to explain this away as epidemiological error or diet complexities have been published, but still never answers the underlying question, “Does increasing fat alone cause heart disease?” (Ferrieres J, Heart, Jan 2004).
According to the Diet-Heart Hypothesis, people with familial hypercholesterolemia should have much shorter lifespans and are at increased risk of early mortality or death. However, there is actually no scientific evidence of this. In fact, the Honolulu Heart Program study revealed that people with low cholesterol are the ones at significant risk of early mortality or death (Schwartz I, et al., Lancet 2001 Aug). Additionally, higher LDL-C is actually predictive of longer life and has been demonstrated to correlate with longevity (Ravnskov U et al., BMJ Open, 2016 Jun 12;6(6): e010401).
Saturated Fat Isn’t Bad
I hate to burst your bubble, but saturated fat is NOT linked to vascular disease, diabetes or increased mortality (de Souza RJ et al., BMJ 2015,351:h3978).
It is commonly understood that LDL-C will rise as you eat more saturated fat. This is normal on a ketogenic diet. It has been reported in the scientific literature for over twenty years. It is to be expected, because LDL-C is really a measurement of three different LDL sub-particles (“big fluffy, medium, and small dense”). Increased saturated fat intake, while at the same time lowering carbohydrate intake, actually causes a shift in these low density particles to a bigger “fluffier” particle conformation (Griffin BA et al., Clin Sci (Lond), 1999 Sep). We know that the small dense LDL particles are the atherogenic / inflammatory particles participating in the formation of vascular disease and directly correlate with triglyceride levels. We also know the big “fluffy” LDL particles actually reduce the risk of vascular disease (Griffin BA et al., Clin Sci (Lond), 1999 Sep).
Why Do Physicians Still Prescribe STATIN Medications?
So why have clinicians been pushing the use of STATIN medications to reduce risk of coronary heart disease? It started with the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). This was a study of over 3800 men treated with cholestyramine, a cholesterol lowering medication (JAMA, 1984 Jan. 20;251(3):351-64.). There was a very slight “absolute reduction” in coronary heart disease risk, 1.6% to be exact. LDL-C decreased, but there was no reduction in the risk of death. In fact, there was actually an increase in risk of all cause mortality in the cholestyramine group which was never emphasized.
Overall, cholestyramine reduced non-fatal heart attacks in 60 of the 3,806 men. In other words, one in 63 men improved with the use of this medication . . . not very impressive. However, statistics look more impressive expressed in terms of “relative risk.” Relative risk is the percent increase of those with no treatment from those with treatment. This is always a bigger number.
When the LRC-CPPT researchers calculated relative risk, the percent change between the treated and non-treated was 19%. This bigger number was reported as the “risk reduction.” For those that don’t know the difference between actual risk and relative risk, 19% sounds very impressive! (JAMA. 1984 Jan 20;251(3):351-64.)
False Evidence Emphasized By Relative Risk
This relative risk reduction drove the STATIN era we are well aware of today. Lipitor (atorvastatin) reduces heart disease risk by only 1%. However, when you use the term “relative risk reduction,” it has more psychological effect. Relative risk of 36% sells more drugs.
Crestor (rosuvastatin) was show to have an absolute risk reduction in heart disease by 1.2%. When run through the relative risk reduction statistic it has a claim of 44% relative risk reduction.
These big numbers emphasized false evidences in many clinician’s minds that reducing LDL-C must be really effectively reducing heart disease.
Knowing that the LDL-C doesn’t really give you a clear idea of heart disease risk. It becomes essential to know which type of LDL lipoprotein particle is the atherogenic or heart disease causing particle. Research now points to the small-dense LDL particle as the atherogenic molecule (Hoogeveen RC et al., Arterioscler Thoromb Vasc Biol, 2014 May; Ivanova EA et al., Oxidative Med Cell Longevity, 2017 Apr). Studies have identified that elevated small-dense LDL cholesterol correlates much more closely with risk for inflammation, heart disease and vascular disease (Williams PT, et al. Atherosclerosis. 2014 April; 233(2): 713-720.)
A Better Marker for Heart Disease Risk?
Recent research demonstrates that small dense LDL cholesterol is a better marker for prediction of cardiovascular disease than total LDL-C (Hoogeveen RC et al., Arterioscler Thromb Vasc Biol. May 2014, 34(5): 1069-1077l; Ivanova EA et al., Oxidative Med Cell Longev. 2017).
The 2015 British Medical Journal, referenced above, analyzed the relevant 19 peer reviewed medical articles that included over 68,000 participants. This review showed that there is no association of high LDL-C with mortality (meaning that an elevated LDL-C does not lead to an increased risk of death from heart or vascular disease).
In stark opposition to the landmark evidences above, the American Heart Association’s Presidential Advisory published their position in the June 20, 2017 issue of Circulation. I am well aware of their position. They claim that saturated fat is the cause of increased LDL-C. Further, they extrapolate that elevated LDL-C is associated with increase in cardiovascular disease death. This boldfaced claim is based on one single small four-year (2009-2013) literature review completed by the World Health Organization. It looked at very small studies lasting only 3-5 weeks and comprised in total only 2353 participants. That’s not nearly long enough to see fully effective cholesterol changes. And, none of the studies had any focus on carbohydrate intake, insulin levels or LDL sub-particle measurement (Mensink RP, Geneva: WHO Library Cataloguing-in-Publication Data, 2016).
Clinical Evidence Is Pointing to Ketogenic Lifestyles as a Key
In my office, I see up to 10% regression in carotid stenosis (blockage in the carotid arteries) each year when following a ketogenic dietary lifestyle. Evidence points out that higher fat intake and lowering of carbohydrate intake has a regression effect on plaque and thickness of the arterial wall. (Shai I et al., Circulation, Mar 2010.) And, increased small dense LDL cholesterol correlates with thickening of the carotid arterial wall (Gentile M et al., Clinica Chimica Acta,Naples, Italy Division of Cardiology, Nov 2013, DOI: 10.1016 / j.cca.2013.08.010)
Based on the large body of evidence that sits before us today, the use of total cholesterol and LDL-C to determine vascular disease risk are obsolete and ineffective tools. That’s why we focus on insulin, triglycerides and small dense LDL particles.
Are you worried about your cholesterol?
Is a ketogenic lifestyle right for you?
These are great questions that I hope I can answer. Check out this month’s Kickstart program if you’re just getting started. Or, click here to work with me individually on your ketogenic lifestyle and cholesterol.
On this evenings PeriScope video we talked about cholesterol. And, and you can see an updated, in depth discussion about cholesterol on my YouTube channel here. Please go check it out and if you find it helpful, please follow me here and on YouTube. The is the burning question on everyone’s mind who starts a Low-Carb, High Fat or Ketogenic Diet: “What will happen to my cholesterol if I lower my carbohydrates and eat more fat?”
The answer . . . it will improve!
How do I know this? I’m an obesity specialist. I specialize in FAT or lipids (to put it kinder scientific terms). To specialize in fat, one must know where it came from, what it’s made of and where it is going. And, this has been the case with every single patient I have used this dietary change with for the last ten years, myself included.
Lets start with the contents of the standard cholesterol or “Lipid Panel”:
Total Cholesterol
HDL-C (the calculated number for “good” cholesterol)
LDL-C (the calculated number for “bad” cholesterol).
Triglycerides
The first problem with this panel is that it makes you believe that there are four different forms of cholesterol. NOT TRUE! Actually cholesterol is cholesterol, but it comes in different sizes based on what it’s function is at that moment in time. Think of cholesterol as a bus. There are bigger busses and smaller busses. Second, triglyceride is actually the passenger inside the HDL and the LDL busses. And third, Total Cholesterol is the sum of the HDL, LDL, as well as ILDL & VLDL which aren’t reported in the “Lipid Panel” above.
The fourth thing that this panel doesn’t tell you is that HDL & LDL are actually made up of sub-types or sub-particles and are further differentiated by weight and size.
For our conversation, we need to know that the number of LDL particles (LDL-P) can actually be measured in four different ways and these measurements have identifed that there are three sub-types: “Big fluffy” large dense LDL, medium dense LDL, and small-dense LDL. Research has identified that increased numbers of small-dense LDL correlates closely with risk for inflammation, heart disease and vascular disease (1).
If you’ve been a follower of my blog for a while, you’ve seen this picture before. This picture illustrates why an LDL-C (the bad cholesterol measurement) can be misleading. Both sides of the scale reflect an LDL-C of 130 mg./dl. However, the LEFT side is made up of only a few large fluffy LDL particles (this is the person with reduced risk for heart disease) called Pattern A or a LDL healthy cholesterol level. Even though the LDL-C is elevate above the recommended level of 100 mg/dl, the patient on the left has much less risk for vascular disease (this is why you CAN’T trust LDL-C as a risk factor).
The RIGHT side of the scale shows that the same 130 mg/dl of LDL-C is made up of man more small dense LDL particles (called “sd LDL-P”) with a Pattern B type that is as increased risk for heart or vascular disease. This is where the standard Lipid Panel above, fails to identify heart disease and it’s progression.
Research tells us that the small dense LDL particle levels increase as the triglycerides increase. And we know that Triglyceride levels increase in the presence of higher levels of insulin leading to a cascade of inflammatory changes. Insulin is directly increased by the ingestion of simple and complex carbohydrates. Insulin also increases with the ingestion of too much protein. So, that chicken salad or the oatmeal you ate, thinking it was good for you, actually just raised your cholesterol. If you are insulin resistant, your cholesterol just increased by 2-10 times the normal level (see my article here on how insulin resistance causes this.)
“Ok, but Dr. Nally, there are four different companies out in the market measuring these fractional forms of cholesterol. Which one should I choose?”
There are actually five different ways you can check your risk.
Apolipoprotein levels. This can be done through most labs; however, this test doesn’t give you additional information on insulin resistance that the other tests can.
Berkley Heart Lab’s Gradient Gel Electrophoresis – This test gives a differentiation based on particle estimation between Pattern A and Pattern B
Vertical Auto Profile (VAP-II) test by Arthrotec – This test determines predominant LDL size but does not give a quantifiable lipoprotein particle number which I find very useful in monitoring progression of insulin resistance and inflammation.
NMR Spectroscopy from LipoScience – This test measures actual lipoprotein particle number as well as insulin resistance scores and will add the Lp(a) if requested. I find the NMR to be the most user friendly test and useful clinically in monitoring cholesterol, vascular risk, insulin resistance progression and control of the inflammation caused by diabetes. This test has the least variation based on collection methods if frozen storage is used.
Ion-Mobility from Quest – This test also measures lipoprotein particle number but does not include insulin resistance risk or scoring. Because the test is done through a gas-phase electric differential, the reference ranges for normal are slightly different from the NMR.
In regards to screening for cardiovascular risk, the use of all five approaches are more effective than the standard lipid panel. However, I have found that clinically the NMR Lipo-profile or the Cardio I-Q Ion-Mobility tests are the most useful in additionally monitoring insulin resistance, inflammation, and disease progression.
It is was the use of these tests that demonstrated to me the profound effect of carbohydrate restriction and ketogenic lifestyles on vascular and metabolic risk. We talk more about these tests on my YouTube video .
Hope this helps.
References:
Williams PT, et al. Comparison of four methods of analysis of lipoprotein particle subfractions for their association with angiographic progression of coronary artery disease. Atherosclerosis. 2014 April; 233(2): 713-720.
