Category: Risk Factors

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Dietary Fat, Carbohydrates and Metabolic Syndrome

Time makes us fat. It’s not a myth, it’s a biologic fact. When we get old we get fat. In December 1863, William Banting, an English undertaker who went to great lengths to treat his own obesity, wrote in his now famous Letter on Corpulence: … For I have been generally informed that corpulence is one of the natural results of increasing years...”

Of course getting fat wouldn’t be an issue if it didn’t affect our quality of life and our risk of disease. Banting also wrote: … “Yet the evil still increased, and, like the parasite of barnacles on a ship, if it did not destroy the structure, it obstructed its fair, comfortable progress in the path of life”.

However, obesity’s association with aging does not mean that getting fat with all its dire consequences is inevitable. In fact we know that some people never get fat, and some people get fatter than others. Nonetheless, although there are genetic influences and other factors we can’t control, we have to understand that to a great extent it’s about how we live our lives.

It’s well documented that obesity is associated with increased risk of high blood pressure, lipid disorders and type 2 diabetes, the three hallmarks of metabolic syndrome. However, keep in mind that although obesity travels with these conditions, it’s not necessarily their underlying cause.

Sometimes we tend to focus too much on obesity as a problem by itself. If we look at it a bit differently, it appears that some aspects of modern lifestyle, together with a number of known and unknown environmental and genetic factors, have created a metabolic disorder with multiple consequences, one of which is obesity. Other consequences of this disorder, apart from the hallmarks of metabolic syndrome, are cardiovascular disease, non-alcoholic fatty liver disease, polycystic ovary syndrome, cancer and dementia.

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Metabolic Syndrome and Insulin Resistance

If William Banting was alive today we would probably have diagnosed him with metabolic syndrome. He had no family history of obesity and did not consider himself lazy or inactive, and yet obesity crept upon him in his thirties.

The first description of metabolic syndrome can be traced back to Eskil Kylin (1889-1975), a Swedish physician and scientist who described a cluster of conditions, including high blood pressure, high blood sugar, obesity, and high levels of uric acid which can lead to gout. This was later to be named syndrome X or more commonly the metabolic syndrome.

The five conditions described below are used to define the metabolic syndrome. Three of these must be present in order to be diagnosed with the condition.

  • A large waistline.
  • A high triglyceride level in the blood.
  • A low HDL cholesterol level in the blood.
  • High blood pressure
  • Elevated blood sugar

Metabolic syndrome is not a rare disorder and its prevalence has been growing fast. It is believed that 70 million Americans suffer from this disorder.

In his Banting lecture, at the American Diabetic Association’s annual meeting in 1988, Gerald M. Reaven proposed insulin resistance as the underlying factor in metabolic syndrome. Since then it has been acknowledged that insulin resistance plays a key role and the term “insulin resistance syndrome” has been used by some specialists.

Insulin is a hormone secreted by the pancreas. It plays an important role for the metabolism of dietary carbohydrates. Insulin resistance is defined as a diminished response to a given concentration of insulin.  Most people with insulin resistance have elevated levels of insulin in their blood.

When the actions of insulin are impaired, carbohydrate metabolism becomes abnormal. This condition has been termed carbohydrate intolerance. It reflects the impaired ability of the body to metabolize carbohydrates when insulin resistance is present.

In his book, Why We Get Fat: And What to Do About It, Gary Taubes arguments that insulin plays a key role for the accumulation of fat in the body; … “First, when insulin levels are elevated, we accumulate fat in our fat tissue; when these levels fall, we liberate fat from the fat tissue and burn it for fuel”, … “Second, our insulin levels are effectively determined by the carbohydrates we eat”..

The Role of Carbs

The figure below is from a recently published paper by Richard D. Feinman and coworkers showing data from NHANES (National Health and Nutrition Examination Survey) indicating a large increase in carbohydrate as the major contributor to calorie excess in the United states from 1974-2000. The absolute amount of fat decreased for men during this period and showed only a slight increase for women.

Macronutrient consumption during the epidemic of obesity and type 2 diabetes. Data from the National Health and Nutrition Examination Survey (NHANES) by year, and from Centers for Disease Control and Prevention. Inset: Incidence of diabetes (millions of people with diabetes by indicated year). Data from Gross LS, et al.

During the same time period, obesity increased dramatically and so did the prevalence of diabetes.

Today, 70% of adults in the US are classified as overweight or obese, as compared with 40% just 40 years ago.  Whether the relationship between increased consumption of carbohydrates, and increased obesity and diabetes is causal or not is still a matter of debate. However the lack of any relationship between total and saturated fat consumption and the prevalence of obesity and diabetes is stunning.

However, to be fair, it must be emphasized that mortality due to coronary heart disease has dropped significantly in most countries during the last 40 years. Data on incidence are harder to find, particularly in the US, but evidence from many European countries suggests that incidence has fallen as well. So, fewer people are diagnosed with coronary heart disease and fewer people are dying from it. Nonetheless, the prevalence of heart disease is still very high. The population is aging and people often live with existing heart disease for decades.

Of course the dramatic fall in mortality due to coronary heart disease is due to multiple factors. Medical and surgical therapy has improved. Studies have also shown that less smoking, lower blood cholesterol and better control of blood pressure have all contributed markedly to lower mortality. Meanwhile however, increased prevalence of obesity and diabetes are working in the opposite direction.

What Do We Do About It?

The most effective way to solve a problem is to go for its roots. However, when it comes to the obesity epidemic and metabolic syndrome it gets complicated because we still don’t know, or at least we don’t agree, on the underlying causes. There are several potential contributors, among them are increased calorie intake, changes in the composition of our diets, less physical activity and changes in gut microbiome (the bacterial flora in our gut).

In a recent overview in The Journal of the American College of Cardiology, Carl J. Lavie MD and coworkers argue that progressive declines in physical activity over five decades have primarily caused the obesity epidemic. Their research has demonstrated very marked declines in occupation related physical activity and household management energy expenditure during the last fifty years.

Following the publication of Lavie’s paper, Larry Husten wrote an article on Forbes suggesting a possible conflict of interest. Husten writes:  …”The article downplays the role of calories and diet and does not include the words “sugar”, “soda”, or “beverage”. Three of the five authors of the paper report financial relationship with Coca Cola.” …

Gary Taubes argues that we don’t get fat because we overeat. He believes it comes down to hormonal imbalance; … “the stimulation of insulin secretion caused by eating easily digestible carbohydrate-rich foods: refined carbohydrates, including flour and cereal grains, starchy vegetables such as potatoes, and sugars, like sucrose (table sugar) and high fructose corn syrup. These carbohydrates literally make us fat, and by driving us to accumulate fat, they make us hungrier and they make us sedentary”.

Public health organizations and medical societies usually advocate a low-fat, high carbohydrate, energy deficient diet to manage weight.

The American Heart Association believes we should approach metabolic syndrome by reducing our weight; increasing our physical activity; eat a heart-healthy diet that’s rich in whole grains, fruits, vegetables, lean meats and fish, and low-fat or fat-free dairy products and avoid processed food, which often contains partially hydrogenated vegetable oils, and is high in salt and added sugar.

… carbohydrate restriction appears to be an effective method to deal with lifestyle induced metabolic disease, and its consequences. However, unless medical professionals and health authorities acknowledge the potential of this approach, we can’t expect much success.

In her recently published book, The Big Fat Surprise, Nina Teicholz writes about the changes in the American diet since the first dietary guidelines were published in the 1970s: … “Since the 1970s, we have successfully increased our fruits and vegetables by 17 percent, our grains by 29 percent, and reduced the amount of fat we eat from 43 percent to 33 percent of calories“…

Teicholz then reflects on the striking increase in obesity and diabetes in the US: … “In all it’s a tragic picture for a nation that has according to the government, faithfully been following all the official dietary guidelines for so many years. If we’ve been so good, we might fairly ask, why is our health report card so bad“…

Existing evidence indicates that carbohydrate restriction positively affects most of the essential features of metabolic syndrome. Weight loss is usually achieved, waistline is reduced, blood pressure is improved, triglycerides and HDL-cholesterol improve, there will be less insulin resistance, and glucose metabolism improves.

Despite the obesity epidemic occurring right in front of our noses, there is still disagreement on its fundamental underlying causes. Consequently, experts disagree on how to deal with it. Unfortunately, public health authorities have not been able to offer much guidance. Nonetheless, looking at all the available evidence, carbohydrate restriction appears to be an effective method to deal with lifestyle induced metabolic disease, and its consequences. However, unless medical professionals and health authorities acknowledge the potential of this approach, we can’t expect much success.

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The Triglyceride/HDL Cholesterol Ratio

Estimated reading time: 7 minutes

For years, measurements of blood cholesterol have been used to assess the risk of heart disease.

We have been intensively educated about the role of LDL-cholesterol (LDL-C), commonly nicknamed the bad cholesterol and HDL-cholesterol (HDL-C), often called the good cholesterol.

For many different reasons, lowering LDL-C has become a primary goal in cardiovascular prevention. There is substantial evidence available suggesting a relationship between LDL-C and the risk of coronary heart disease.

Medical professionals usually recommend lifestyle measures that lower LDL-C and statins (cholesterol-lowering drugs) are used by millions of people worldwide for the sole purpose of lowering LDL-C numbers.

However, to understand coronary heart disease and how plaques form in our arteries (atherosclerosis), we have to understand that focusing only on cholesterol is an oversimplification.

Because cholesterol is a fat substance, it can’t mix with water and can therefore not travel in blood on its own. The body’s solution to this problem is to bind fat molecules to lipoproteins that function as transport vehicles carrying different types of fats such as cholesterol, triglycerides (TG) and phospholipids.

It is important to understand that it is lipoproteins that interact with the arterial wall and initiate the development of atherosclerosis. Cholesterol is only one of many components of lipoproteins.

The Lipid Panel

A standard lipid panel includes total cholesterol, LDL-C, HDL-C, and TG. Although LDL-C usually gets the bulk of the attention, evidence suggests that other aspects of the lipid profile may not be less important. For example, non-HDL cholesterol is a strong marker of risk, maybe more important than LDL-C.

Relying on LDL-C alone can be misleading. For example, people with obesity, metabolic syndrome or diabetic lipid disorders often have raised TG, low HDL-C and normal or close to normal LDL-C. These individuals produce very low-density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) which may increase the risk of atherosclerosis.

Many studies have found that the triglyceride/HDL cholesterol ratio (TG/HDL-C ratio) correlates strongly with the incidence and extent of coronary artery disease. This relationship is true both for men and women.

One study found that a TG/HDL-C ratio above 4 was the most powerful independent predictor of developing coronary artery disease.

With the increasing prevalence of overweight, obesity, and the metabolic syndrome this ratio may become even more important because high TG and low HDL-C is often associated with these disorders.

Atherogenic dyslipidemia is a clinical disorder characterized by high TG/HDL-C ratio, elevated levels of apolipoprotein B, and high concentration of small LDL particles.

The Triglyceride/HDL Cholesterol Ratio. What Is Ideal?

The TG/HDL-C ratio can easily be calculated from the standard lipid profile. Just divide your TG by your HDL-C.

However, when looking at the ideal ratio, you have to check if your lipid values are provided in mg/dl like in the US or mmol/L like in Australia, Canada, and most European countries.

If lipid values are expressed as mg/dl (like in the US);

TG/HDL-C ratio less than 2 is ideal

TG/HDL-C ratio above 4 is too high

TG/HDL-C ratio above 6 is much too high

If you are using mmol/L (most countries except the U.S.) you have to multiply this ratio by 0.4366 to attain the correct reference values. You can also multiply your ratio by 2.3 and use the reference values above.

If lipid values are expressed as mmol/L (like in Australia, Canada, and Europe);

TG/HDL-C ratio less than 0.87 is ideal

TG/HDL-C ratio above 1.74 is too high

TG/HDL-C ratio above 2.62 is much too high

In this article, TG/HDL-C ratio is provided as in the US (mg/dl).

Triglyceride/HDL Cholesterol Ratio and LDL Particles?

Recently, analyzing the number of LDL particles (LDL-P) and LDL particle size has become more common. However, this method is not universally available, is expensive, and has not been widely applied in clinical practice.

High numbers of small, dense LDL particles are associated with increased risk for coronary heart disease in prospective epidemiologic studies. Subjects with small, dense particles (phenotype B) are at higher risk than those with larger, more buoyant LDL particles (phenotype A).

Interestingly, it has been found that the TG/HDL-C ratio can predict particle size. One study found that 79% of individuals with a ratio above 3.8 had a preponderance of small dense LDL particles, whereas 81% of those with a ratio below 3.8 had a preponderance of large buoyant particles.

Apparently, people with high TG/HDL-C ratio tend to have higher than average TG. Just like all other lipids, TGs have to be transported in the blood by lipoproteins; most are carried by chylomicrons and VLDL.

What happens under these circumstances is an interchange of lipids between lipoproteins. TGs are moved from VLDL into LDL and HDL in exchange for cholesteryl ester. The result is that LDL and HDL particles become cholesterol poor and rich in TG. Then, when TGs are removed from these particles, which usually is the case, the particles shrink and become smaller as they’re only transporting small amounts of cholesterol. This explains the relationship between high TG/HDL-C ratio and the number of small LDL particles.

However, the number of LDL particles present in the blood may be more important than particle size. Furthermore, particle number appears more important than how much cholesterol is carried within these particles. Blood levels of LDL-P and apolipoprotein B are strongly correlated with the risk of coronary heart disease. Both these measurements reflect the actual number of LDL-particles.

But, can the TG/HDL-C ratio reflect particle number? As a matter of fact, it can, to some extent. Take a look at the LDL-C, the amount of cholesterol carried in LDL-particles. A high TG/HDL-C ratio indicates that these particles are small. A small particle carries less cholesterol than a large particle. Therefore, a greater number of particles is needed to carry a certain amount of cholesterol if the particles are small than if they’re large. So, a high TG/HDL-C ratio likely reflects a large number of LDL-particles, unless LDL-C is very low.

Triglyceride/HDL Cholesterol Ratio and Insulin Resistance

Insulin resistance is a condition in which cells fail to respond to the normal actions of insulin. Most people with this condition have high levels of insulin in their blood. Insulin resistance appears to play a significant role in coronary heart disease and can predict mortality. The condition is common among individuals with abdominal obesity and the metabolic syndrome.

A study in which most of the participants were Caucasian and overweight identified TG/HDL-C ratio of 3 or greater as a reliable predictor of insulin resistance.

However, not all studies have found the TG/HDL-C ratio to be associated with insulin resistance. For example, in a relatively small study of 125 African American participants, neither fasting TG nor the TG/HDL-C ratio was shown to be a marker of insulin resistance.

Although confirmatory studies are needed, data suggests that an elevated TG/HDL-C ratio may be clinically useful for the prediction of insulin resistance.

How to Improve Your Triglyceride/HDL Cholesterol Ratio

Improving your TG/HDL ratio aims at lowering TG, raising HDL-C or preferably both.

If you are overweight, losing weight will probably lower your TG levels and so will reducing your intake of added sugar. Studies have found that high intake of fructose leads to high TG. High-fructose corn syrup is a major source of fructose.

Low-fat diets are usually not effective in lowering TG. In fact, low-fat, high-carbohydrate diets may raise TG. Adding omega-3 fatty acids, regular exercise and limiting alcohol may be helpful to reduce TG.

Similar methods may be useful for raising HDL-C. Losing weight, exercising and not smoking may help. In controlled trials, low-fat, high-carbohydrate diets decrease HDL-C, thereby raising theTG/HDL-C ratio.

In 1961, a group of investigators from the Rockefeller Institute, led by Pete Ahrens published a paper entitled “Carbohydrate-induced and fat-induced lipemia”.

The authors pointed out that fat-induced increase in TG following a meal is a postprandial phenomenon (we all have high TG for a few hours following a fatty meal) caused by chylomicrons is different from the carbohydrate-induced rise in TG (later found to be caused by an elevation of VLDL).

These findings have been confirmed in several more recent studies. Despite this, low fat, high carbohydrate diets are still being recommended as a primary option to reduce the risk of heart disease.

Although low-fat diets may help to lower LDL-C, low-carbohydrate diets are more effective in improving the TG/HDL-C ratio.

This suggests that solely selecting LDL-C as a target in cardiovascular prevention is an oversimplification, and may have led to wrong conclusions regarding the relationship between diet and heart disease.




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Can Further Lowering of Blood Cholesterol Save Lives?

For many years, lowering blood levels of low density lipoprotein cholesterol (LDL-C) has been a key target for individuals with cardiovascular disease (CVD) and healthy people at increased risk for developing such disease.

Statin drugs play a key role for risk reduction and are prescribed to millions of people worldwide. Apart from lowering blood cholesterol, these drugs have a number of effects that are potentially beneficial. For example, their anti-inflammatory effect may be of importance.

The death rate from CVD has declined rapidly during the last few decades in most developed countries. Research indicates that this may partly be due to statin therapy. However, despite the widespread use of statin drugs, CVD still contributes importantly to morbidity and mortality around the world.

A new class of drugs, so-called PCSK-9 inhibitors, appears to significantly lower LDL-cholesterol among individuals not taking statins as well as those already on statin therapy. Many experts believe these drugs may be helpful for individuals who don’t tolerate statins as well as those not achieving target levels of LDL-C on statin therapy. The new PCSK9 inhibitors are so-called monoclonal antibodies which are developed by biologic methods. They can not be administered orally and are usually given by a subcutaneous injection with a two to four weeks interval.

Cholesterol and Atherosclerosis

Atherosclerosis is a form of chronic inflammation resulting from complex interactions between lipoproteins, white blood cells, different components of the immune system and the normal elements of the arterial wall. This process can lead to formations of atherosclerotic lesions or plaques that often protrude into the lumen of the artery causing vessel narrowing which may ultimately affect blood flow. If this occurs in the coronary arteries, it may cause damage to the heart muscle and induce serious irregularities of heart rhythm. Rupture of an atherosclerotic plaque may lead to thrombosis causing an acute occlusion of the artery resulting in heart attack.

There are many factors that contribute to atherosclerosis, one of which is elevated blood cholesterol. Although cholesterol is important for many bodily functions, elevated plasma levels appear to play an important role in the initiation and progression of atherosclerosis. In animal models, atherosclerosis will not occur in the absence of greatly elevated levels of plasma cholesterol. High levels of plasma cholesterol also appear to be an important contributor to atherosclerosis in humans, although the threshold level that must be exceeded to produce clinically relevant disease appears much lower than that in animal models, possibly because lesion formation occurs over many decades. Atherosclerotic clinical events are uncommon among people with lifelong very low plasma cholesterol levels. It must be emphasised however, that it is lipoprotein that interact with the arterial wall and initiate the cascade of events that leads to atherosclerosis. Cholesterol is only one of many components of lipoproteins.

The Role of LDL and the LDL-Receptor

A causative role for cholesterol in itself has never been proven, although it appears that atherosclerosis will not occur without it being present in the arterial wall. Measurements of total cholesterol only indirectly reflect the lipoproteins that transport the bulk of cholesterol and are the most atherogenic. In fact, measuring the number of LDL-particles (LDL-P) appear more predictive of risk than the measurements of the cholesterol mass within these particles (LDL-C).

When inside the arterial wall, LDL can undergo a variety of modifications including oxidation, uptake by white blood cells called macrophages, formation of so-called foam cells and the initiation of inflammation. This cascade of events may ultimately result in an atherosclerotic plaque within the vessel wall. Obviously, cholesterol is not the cause of all this, but it is always involved. So, is it true that atherosclerosis is more likely to occur if plasma concentration of LDL-cholesterol is high than if it is low. The answer is yes, and it is supported by a number of scientific studies.

The liver is the gatekeeper for LDL and is responsible for its clearance. Liver cells express LDL-receptors on their surface, that bind LDL and remove it from the blood stream. After binding to the LDL-receptor, the LDL/LDL-receptor complex is moved to endosomes within the liver cells, where the LDL is released from the complex. The LDL receptor then moves back to the cell surface where it can bind to additional LDL-particles. This circle leads to removal of LDL-particles from the circulation which can be measured as a reduction in LDL-cholesterol levels. The free LDL left within the cells is transported to lysosomes and degraded into lipids, free fatty acids and amino acids.

PCSK9

PCSK9 (Proprotein convertase subtilisin-like/kexin type 9) is a protein that regulates the expression of LDL-receptors in the liver. PCSK9 is produced by liver cells and released into the blood stream. PCSK9 binds to the LDL-receptor on the surface of liver cells, together with LDL. It moves into the cell, together with the LDL-receptor/LDL complex. After LDL is released from this complex, the LDL – receptor/PCSK9 complex is taken up by lysosomes for degradation, preventing the recycling of the LDL-receptor to the cell surface. Thus, PCSK9 is responsible for the degradation of LDL-receptors and therefore plays a critical role in the regulation of LDL-cholesterol levels.

Interestingly, mutations on the human PCSK gene expression that lead to a loss of PCSK9 function are found in 1 – 3 percent of the population. These mutations have been associated with lower LDL-C and a significantly lower incidence of coronary heart events. Inhibition of the interaction between PCSK9 and the LDL receptor may potentially lower LDL-C. A monoclonal antibody directed against PCSK9 could potentially lower LDL cholesterol if it blocks the interaction of PCSK9 with the LDL – receptor on the surface of liver cells. This may allow LDL- receptors to recycle to the cell surface, after releasing LDL within the cell, instead of being taken up and degraded in lysosomes. Increased concentration of LDL receptors on the surface of liver cells may lead to increased clearance of LDL, which will be reflected as reduced levels of LDL-cholesterol.

PCSK-9 Inhibitors – Are They the New Wonder Drugs?

Whatever we think of cholesterol we have to keep an open mind about the new PCSK-9 inhibitors. There are large ongoing randomized clinical trials testing whether these drugs will prolong life and reduce the risk of future cardiovascular events among individuals with CVD. The results of these studies are eagerly awaited. The  may provide answers to a lot of unresolved questions regarding the lipid hypothesis.

Some of the popular “internet doctors” have slammed the PCSK9 inhibitors before they are scientifically tested. Many of them believe that lowering cholesterol is always harmful and that statins drugs are always bad. Of course, if you believe so, you won’t like the idea of PCSK-9 inhibition. But remember, don’t let cognitive dissonance steer your thought processes.

I’ve written a lot about statin drugs on my blog and I worry that they are prescribed to millions of individuals who don’t need them. I also fear that adverse effects of statins are underreported. However, statins are very important drugs for many patients and they are unfortunately often not prescribed when they should be. The world is not black and white and neither is the art and practice of medicine.

Apart from lowering LDL-cholesterol, the new PCSK-9 inhibitors also lower blood levels of non-HDL cholesterol, triglycerides, apolipoprotein B and lipoprotein(a). However, it is important to keep in mind that a change in these biomarkers induced by therapy does not always incur clinical benefit. Ezetimibe, a potent inhibitor of intestinal cholesterol absorption, has been shown to be safe, tolerable and effective at lowering LDL-C, non-HDL cholesterol andapolipoprotein B, each of which has been correlated with improved clinical outcomes, alone or in combination with a statin. However, randomized clinical rials have shown mixed results and with a few rare exceptions, the use of the ezetimibe is not recommended for cardiovascular risk prevention.

Whether treatment with PCSK9 inhibitors will positively influence the atherosclerotic process and reduce risk among individuals with CVD remains to be seen. It is also important to learn if there is any collateral damage. We will not know the answer to these questions unless they are tested by scientific methods. Until then, I won’t believe anyone who pretends to know the answer.

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Dietary Fat and Heart Disease – The Changing Landscape

Most of us know that the risk of heart disease can be modified by lifestyle. For more than fifty years, that’s what we’ve been taught by the people we trust, scientists, medical professionals and public health officials.

But the doubters have always been out there, and they ask questions. How do these people know what’s good and bad for us? Well, of course, we’re aware that their evidence is based on scientific data. But, is the data reliable and has it been interpreted correctly?

For decades we’ve been told that saturated fat, the type found in meat, butter, and cheese, raises the risk of heart disease. Health officials have urged the public to avoid saturated fat as much as possible, saying it should be replaced with unsaturated fats like that found in nuts, fish, seeds and vegetable oils. In fact, many consider this to be conventional wisdom, which basically means that it’s undebatable. However, recent research has challenged this view and the debate on the risk associated with consuming saturated fat has grown louder by the years.

One of the main reason saturated fat has historically had a bad reputation is that it increases LDL-cholesterol, the type of cholesterol that is supposed to raise the risk for heart attacks. But the effects of saturated fat on blood cholesterol are probably more complex than that. For example saturated fat also increases HDL-cholesterol, the so-called good cholesterol. However, the effect of polyunsaturated fat (PUFA) on blood cholesterol and traditional lipid profile is generally considered more favorable than the effect of saturated fat.

A few days ago, a scientific study published in the Annals of Internal Medicine caught the headlines of news media around the world. The main reason for the attention is the fact that the study did not find that people who ate more saturated fat had more heart disease than those who ate less. Furthermore, the study did not find less heart disease in those eating higher amounts of omega-6 PUFA or those eating more monounsaturated fat.

The study deserves our attention, not only because it challenges current wisdom and modern dietary guidelines, but because it summarizes a very large amount of data from three different types of studies. However, because it’s not an open access paper, and because it’s a landmark study, I thought it would be proper to summarize the main findings as I see them.

The Study Design

The study was performed by researchers from the UK, USA, and the Netherlands and was led by a team at the University of Cambridge in the UK. It was a systematic a review and meta-analysis of available scientific data addressing the association between dietary fatty acid intake, fatty acid biomarkers (measured in blood or adipose tissue), or fatty acid supplementation and the risk of coronary heart disease (CHD).

The investigators performed a systematic review of the scientific literature in order to find studies that fitted for their meta-analysis. The studies selected were both observational studies as well as randomized controlled clinical trials. To be eligible, the studies had to fulfill certain criteria. For example, observational studies were eligible if they were prospective in design with at least one-year follow-up and involved participants from a general population (not people with known heart disease). Intervention studies were eligible if they were randomized and recorded CHD outcomes. A total 72 studies of more than 600 thousand individuals were selected for the final meta-analysis.

In order to grasp the results of the paper, it is important to understand that the meta-analysis consisted of three parts. Firstly, the association between the intake of different dietary fats with CHD was studied. Secondly, the association of measurements of fatty acid biomarkers with CHD was addressed. Thirdly the association between fatty acid supplements and CHD was studied.

Saturated fat, Omega-6 and Monounsaturated Fat Don’t Affect Risk

There was no statistically significant association between dietary saturated fatty acid intake and the risk of CHD. Furthermore, intake of omega-6 PUFA was not associated with the risk of CHD. The authors of the paper, therefore, conclude: “Our findings do not clearly support cardiovascular guidelines that promote high consumption of omega-6 polyunsaturated fatty acids and suggest reduced consumption of total saturated fatty acids”.

When studying measurements of biomarkers, it is important to keep in mind that there are many types of saturated fatty acids and many types of PUFA’s. Palmitic and stearic acids are saturated fats that were not significantly associated with the risk of CHD. However, margaric acid was significantly associated with lower risk of CHD. Margaric acid is an odd-chain saturated fatty acid. It’s levels are moderately correlated with milk and dairy consumption. The findings support the possibility that odd-chain saturated fats reflecting milk and dairy consumption, may be less harmful in terms of risk for CHD. Arachidonic acid was the only omega-6 fatty acid that correlated with lower risk of CHD.

Studies of dietary intake and biomarker studies did not find any significant association between monounsaturated fat and the risk of CHD.

Dietary Long-Chain Omega-3 PUFA’s Are Protective

Dietary long-chain omega-3 PUFA was associated with lower risk of CHD. These findings were supported by the blood biomarker studies which showed some evidence that circulating levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid  (DHA) (the two main types of omega-3 PUFA) are associated with lower risk of CHD. Alfa-linolenic acid was neutral in terms of risk.

On the other hand, meta-analysis of omega-3 and omega-6 PUFA supplements suggests that supplementation with these nutrients does not significantly affect the risk of CHD. However, the authors point out that more data is needed because the available data is limited. There is a large ongoing trial on the effects of omega-3 PUFA in primary prevention (VITAL). This study will also address the efficacy of vitamin D.

Trans-Fats Increase the Risk of Heart Disease

Not surprisingly, dietary trans-fats were associated with increased risk of heart disease. However, only five published prospective cohort studies contributed to this analysis.

The Changing Landscape

For the last five years, a number of reports (1, 2, 3, 4, 5) have concluded that there is a weak association between the consumption of saturated fat or major foods that contain saturated fatty acids (meat and milk) and the risk of CHD. The above study certainly adds strength to these conclusions. It appears that the advice to encourage high consumption of polyunsaturated fatty acids and low consumption of saturated fats is not based on solid scientific evidence, and needs to be reconsidered. In fact, the study suggests that dietary fat composition me play a much smaller role for cardiovascular risk than previously thought.

Finally, a few questions need to be asked. Firstly, is this the final verdict? Well, I guess not. But certainly, these new results have to be taken seriously. Secondly, how did public health authorities manage to get it wrong for fifty years? Was it because the available scientific data was unreliable, or was it because the data was wrongly interpreted? Was it because the pieces of the puzzle had to fit into a preconceived notion? And thirdly, how will we get it right? How will the new landscape on dietary fats and heart disease be introduced to the public, and how will this landscape affect the food industry?

I know for sure that many experts will cover their ass by suggesting that the macro-nutrient approach is outdated, and they’re probably right. Dietary recommendations focusing on how much to eat of different types of fats and how much of our daily energy intake should be carbohydrates, protein or fat, are both misleading and impractical. So maybe we will soon see a paradigm shift in the way medical professionals and public health officials educate people about the effect of diet and nutrition on health and disease.

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Will the Popularity of LCHF Trigger a New Epidemic of Heart Disease?

Diets low in carbohydrate and high in fat (LCHF) have become increasingly popular lately. Many experts in the field of epidemiology and cardiovascular disease have expressed grave concern and warned that this change in dietary pattern may increase the risk of heart disease. Some have argued that LCHF poses a threat to public health in many countries around the globe.

A recent increase in butter consumption may reflect the magnitude of the problem and is by many considered alarming. Butter consumption hit a 44-year high in 2012, according to US government data, while margarine is at a 70-year low. In Germany today, butter outsells margarine by a three-to-one margin, and the gap is widening. A similar increase in butter consumption is reported in Scandinavia and many other European countries.

Although butter fits well with an LCHF lifestyle, choosing butter may also reflect the fact that people are changing their perception of food and searching for healthier alternatives. They’re moving away from highly processed foods and artificial ingredients.

The question whether LCHF is harmful or not touches the core of our understanding of the causes of heart disease and the reasons for the so-called coronary heart disease (CHD) epidemic. That’s why this debate is both important and challenging. Let me tell you why so many specialists believe LCHF may be harmful. Then, maybe you can have your say on the issue.

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The Coronary Heart Disease Epidemic

For the past 60 years, CHD has been a major health concern. Although initially most prominent in high income countries, today over 80% of the world’s deaths from cardiovascular disease occur in low and middle-income countries. An estimated 17.3 million people died from cardiovascular diseases in 2008, representing 30% of all global deaths. Of these deaths, an estimated 7.3 million were due to CHD and 6.2 million were due to stroke.

The clinical presentation of CHD varies greatly. Sometimes it is a silent chronic disease that progresses slowly. In other cases it is sudden, unexpected and unpredictable. Through the decades, CHD has brought to an end the lives of many people in their prime. It has robbed wives of their husbands and husbands of their wives. It has tragically, without warning, robbed young children and adolescents of their parents.

The most malignant form of CHD, acute heart attack (acute myocardial infarction) was relatively unknown in the beginning of the 20th century. Then came the epidemic. In the 1950s acute myocardial infarction was recognized as one of the most common causes of death in the industrialized world.

The symptoms were often dramatic and devastating. A previously healthy person was suddenly hit by severe chest pain, commonly associated with serious irregularities of heart rhythm, often resulting in sudden death. The survivors often had to deal with the consequences of damage to large parts of their heart muscle, sometimes resulting in heart failure, severely compromised quality of life and a shortened life span.

Although still an important cause of death around the world, the death rate from CHD has declined in the USA, Canada, Australia, New Zealand and all European countries. It is in the countries with the highest incidence that the greatest decline has occurred. Studies have reported up to 80 percent decline in mortality from CHD in the last 30 – 40 years in countries like the UK, Slovakia, Poland, Netherlands, Ireland, Finland, Iceland and Sweden. A recent Swedish study indicates that CHD deaths are still falling, both among the old and the young.

It is a bit unclear how much of the decline in death rate from CHD is due to a reduction of the incidence of the disease and how much is due to improved survival of those affected. Obviously prognosis has improved and some studies have reported declining incidence of CHD.

Another question is whether the decreasing trend in CHD mortality is due to changes in major cardiovascular risk factors, better medical and surgical treatment, neither of these or both.

Many investigators have used the so-called IMPACT model to analyze the role of preventive measures versus treatment measures on the death rate from CHD. All these studies report that more than half of the mortality decline is attributable to reductions in major risk factors.

The Role of Diet

Although there are some differences, the interpretation of the data from countries where the IMPACT model has been used follows a common path. Lowering of blood cholesterol appears to be an important contributor to the decline in mortality from CHD in many of these studies. Therefore, dietary measures aimed at lowering blood cholesterol are usually highlighted by investigators. The Icelandic experience is a good example.

Icelandic investigators reported an 80% decline in death rate from CHD between 1981 and 2006. Based on the IMPACT model approximately 73% of the mortality decrease was attributable to risk factor reductions. Among these, a reduction in blood cholesterol played the biggest role, and appeared more important than reduction in smoking, lower blood pressure and less physical inactivity. Importantly, adverse trends were seen for obesity and diabetes, increasing mortality by 4% and 5% respectively”

The investigators concluded that:

“The large fall in cholesterol between 1981 and 2006 reflects major changes in the Icelandic diet following the issue of Dietary Goals for Icelanders”.

These goals are very similar to the dietary goals for the U.S and most European countries. Let me quote the Icelandic paper again:

“The National policy is based in the dietary goals where the reduction of saturated fat, mainly from milk and dairy products, lamb and margarine, is greatly emphasized. The food policy and the dietary goals have greatly influenced nutrition education and awareness in the country”.

“Icelandic food supply data clearly demonstrate the subsequent changes. In the 1970s, the diet was characterized by high consumption of whole milk and dairy products, margarine, butter, lamb, mutton and fish. However, between 1981 and 2006 there was a 73% drop in whole milk and dairy consumption, and the supply of lamb and mutton decreased by 50%”. 

“From the 1990s, the consumption of total fat in percent energy has decreased from 40% to 36%. But more importantly, the composition of fat has also changed from more saturated and trans-fatty acids to cis-unsaturated”.

Sheep grazing on green grass in South Iceland

Interestingly, while these changes occurred, the consumption  of refined sugars increased (sugared beverages in particular) and fish consumption decreased. So, although less total and saturated fat may have contributed to lowering of blood cholesterol among the Icelanders, it is obvious that many of the alterations in dietary habits between 1981 and 2006 were of negative nature. This is also reflected by the fact that overweight and obesity more than doubled during the same time period.  

So, finally, here’s the point: If the decreased consumption of whole milk, dairy, lamb and mutton played such an important role in lowering cholesterol and reducing the death from CHD among the Icelandic people, LCHF must certainly pose a threat, but….

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Saturated Fat –  The Villain or a Red Herring 

So, once again it all comes down to saturated fat; dairy, butter and red meat. However, keep in mind that no food product contains only saturated fat and no other types of fat. Pure saturated fats or pure unsaturated fats are never consumed. For example, beef contains a high proportion of monounsaturated fat in addition to saturated fat. Dairy (milk, cream, cheese and butter) is the only food class where the proportion of saturated fat is much higher than the proportion of other types of fat.

Through the years we have been led to believe that saturated fatty acids (SFA) elevate blood cholesterol. We have also been told that high cholesterol will increase the risk of heart disease. Therefore, it’s easy to assume that consuming SFA will increase the risk of heart disease. However, the problem is that the effects of SFA on cholesterol and different lipoproteins have been oversimplified. Furthermore, the epidemiological evidence linking saturated fats with CHD was weak from the beginning.

Saturated Fat – The villain or a red herring

Although SFA may elevate total cholesterol and LDL-cholesterol, they appear to elevate HDL-cholesterol as well. Therefore, the availability of atherogenic lipoproteins doesn’t necessarily increase. Furthermore, SFA lower small dense LDL particles and raise large buoyant LDL particles. Large particles generally impose less risk than small particles. So, stating that saturated fats adversely affect blood lipids is misleading.

Although carbohydrates are less likely to elevate total and LDL-cholesterol, they often elevate triglycerides and lower HDL-cholesterol. These lipid changes may harbor negative cardiometabolic effects.

One of the first papers that advised decreased intake of SFA was published in 1961 by The American heart Association. Some of the support for this came from observational studies, including Ancel Keys Seven-Countries Study, which suggested a relationship between SFA intake and the risk of death from CHD.

Later, in the Nurses’ Health Study a greater ratio of polyunsaturated fatty acids (PUFA) to SFA was associated with lower risk of CHD. The Finnish Mental Hospital Study published 1979 found fewer deaths from CHD and lower rates of heart attacks in a hospital that administered dairy products in which SFA’s were replaced with PUFA’s, compared with regular SFA-containing dairy products. On the other hand, the intervention component of the Minnesota Coronary Survey did not show that increasing the amount of PUFA at the expense of SFA did result in less risk of CHD.

Intake of different types of fatty acid in relation to the risk of CHD was studied in the large Nurses’ Health Study. When carbohydrates were used for comparison, trans-fats were most strongly related to the risk of CHD. SFA intake was not significantly related to increased risk of CHD when compared with carbohydrates. So, replacing SFA with carbohydrates was a wash. In fact, a pooled analysis of large cohort studies indicated that there was a significantly greater relative risk for CHD with carbohydrates compared with SFA. However, MUFA’s and PUFA’s were associated with lower risk compared with carbohydrates.

A systematic review of of the evidence supporting a causal link between various dietary factors and coronary heart disease was published in 2009. The pooled analysis from 43 randomized clinical trials showed that increased consumption of marine omega-3 fatty acids  and a Mediterranean diet pattern were each associated with a significantly lower risk of CHD. Higher intake of polyunsaturated fatty acids or total fats were not significantly associated with CHD, and the link between saturated fats and CHD appeared weak.

For the last five years, a number of reports (1, 2, 3, 4, 5) have cast doubt on the association between the consumption of SFA or major foods that contain SFA (meat and milk) and the risk of CHD. These studied can’t be neglected when analyzing the current evidence for the association between SFA and heart disease.

Will the Popularity of LCH Trigger a New Epidemic of Heart Disease?

Trans-fats are the only type of fats that seem to impose more risk for CHD than carbohydrates. There’s no evidence that replacing other types of fats with carbohydrates will reduce risk. So, reducing carbohydrates and increasing fat consumption should not increase the risk of heart disease, unless carbohydrates are replaced by trans-fats. Therefore it is unlikely that the declining death rate from heart disease may be explained by decreased consumption of saturated fat. Furthermore, if trans fats are avoided there is no reason to believe that the popularity of LCHF will trigger a new epidemic of heart disease. 

It’s now 2014 and the death rate from CHD continues to decline, despite LCHF being around for quite many years now. If there comes a day when we will see a slowing of the decline or an increase in death rate, I guess many experts will blame changed dietary habits associated with the popularity of LCHF. In fact, a reversal of the decline in population cholesterol levels was recently reported in Sweden, where the popularity of LCHF is very high. However, as of today this has not been reflected in a reversal of the decline in mortality from CHD.

In most countries where the death rate from heart disease has fallen, overweight, obesity and type 2 diabetes have increased. Because obesity is strongly linked to cardiovascular risk, many experts are surprised that the incidence and death rate from CHD continue to decline. Most likely, there is a time lag between the increased incidence of obesity and death rate from CHD. Ultimately, if obesity trends are not reversed, it is unlikely that the decline in CHD mortality will continue.

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