chronic insulin resistance

I am a migraine specialist, but recently, I have had more opportunities to work with non-migraineurs to improve their general health. Patient by patient, I have learned that most of the steps I use in my migraine-prevention protocol result in significant improvements for many health conditions. With the use of proper nutrition alone, patients reverse their pre-diabetes, insulin resistance, prostate issues (PSA number), cholesterol issues (high triglycerides, high LDL, and low HDL), arthritis, migraines, and even fibromyalgia flareups. Here, I would like to summarize what I found is wrong with our current nutrition paradigm and how to correct it.

The Cholesterol Problem: A Convoluted History

In the mid-20^th Century, a charismatic and highly influential researcher (Ancel Keys), based on somewhat fraudulent data selection, “proved” that saturated fat causes cardiovascular disease (CVD). Keys came to this conclusion based on what has come to be known as the 7 countries study even though he originally studied the data from 22 countries. The data of 15 countries (including France) were not included because they didn’t line up with the original hypothesis that “saturated fat, particularly LDL cholesterol, causes CVD”.  This created later what was referred to as the French Paradox: how is it that the French have the fewest number of CVD and yet eat the most saturated fat?

Based on Keys’ “findings”, further research aimed at describing the connection of saturated fat and CVD. What they discovered was that for every person with a fatal heart attack, cholesterol (LDL in particular) filled the artery. Without further ado, they decided that cholesterol, particularly LDL (low density lipoprotein), must be the reason for CVD. Since cholesterol in the arteries seemed like it was made from fat, highly saturated fat is a solid lipid at room temperature, saturated fat was held responsible. This theory became the dogma and was subsequently taught to generations of medical professionals.

For many years, and to a great extent even today, it has been difficult to publish any result of studies in disagreement with the dogma. Information about unpublished data (by the NIH among others) has only recently surfaced. Read “The Big Fat Surprise: Why Butter, Meat and Cheese Belong in a Healthy Diet” by Nina Teicholz for a great explanation. The newly revealed data show that not only is saturated fat not responsible for CVD, but that it can, in fact, help reduce its occurrence.

Problems with Current Measures of Cholesterol

Although the original confusion about cholesterol and CVD stemmed from Ancel Keys, it was reinforced with laboratory testing methods that don’t quite measure what we think they measure (here). Briefly, although the original confusion about cholesterol and CVD stemmed from Ancel Keys, it was reinforced with problematic laboratory testing methods based upon incorrect assumptions.  Namely,

• LDL is not cholesterol but a lipoprotein ball that contains cholesterol as well as fat soluble vitamins and minerals.
• LDL is not measurable in the blood by conventional blood tests. It is calculated.
• Triglycerides are not measurable in the blood by conventional blood tests. They are estimated.
• VLDL is measured and an assumption is made that triglycerides/5 = VLDL, which is likely incorrect—see explanation later.
• The equation used (with the listed assumptions) to calculate LDL: 

LDL = Total cholesterol – HDL – (triglycerides/5)

The equation above has two unknowns, and thus, it is impossible to solve mathematically. The two items we can measure with conventional blood tests are total cholesterol and HDL. An assumption is then made that everything else they measure is VLDL. It is unclear how they can separate VLDL from the remaining “cholesterol” since the blood test doesn’t measure what are called chylomicron or remnant pieces of lipoproteins. It simply assumes that chylomicrons don’t exist if fasting preceded the blood test. Below is a picture of lipoprotein formations, within which there are cholesterol and fat-soluble vitamins and minerals.

Image used from Medscape

Fasting is required for a cholesterol blood test and is assumed that after 12 hours of fasting chylomicrons don’t exist, thus the above equation is valid; see Friedewald et al 1972. If chylomicrons do exist during blood test, it invalidates the equation. Healthy individuals’ liver releases glycogen when fasting. Glycogen is stored energy in the liver that is converted to glucose and released in the blood; the lack of existence of chylomicrons may not be true.

Therefore, the above equation doesn’t really give us reliable quantitative information about LDL and definitely no information about the amount of cholesterol in LDL. Even if we could measure LDL, it is still just a lipoprotein ball, as is HDL. In effect, with the current tests, we are counting cars on the freeway to determine how many people travel on that freeway; a very rough estimate at best, but more likely, just a misleading guess.

There is one test, however, that can assess cholesterol inside lipoprotein, but it is infrequently used. It is called the nuclear magnetic resonance (NMR) imaging and is based on atomic weight and motion.

Even if the Cholesterol Tests Were Accurate, Do They Tell Us Anything About CVD?

Let us assume that despite everything we have detailed so far, we can measure cholesterol from the conventional blood test or any other test accurately and that we know the precise amount of cholesterol that is carried in LDL; we still have to ask:

1. Does our cholesterol knowledge tell us anything about CVD?
2. Does saturated fat (or any fat) have anything to do with cholesterol?

To understand these two questions, we need to look at what cholesterol and fat are, how they are made, and from what raw materials.

What is Cholesterol?

Cholesterol is so important for the body that, unlike other nutrients, such as glucose with a very short presence in the body, cholesterol is kept for days and is reused. Twenty five percent of all cholesterol is in the brain, forming the white matter necessary for the insulation of axons to protect against voltage leaks. Voltage leaks occur in many diseases, such as seizures, migraines, multiple sclerosis, Alzheimer’s, Parkinson’s, and alike. In the brain, a cholesterol molecule stays functional much longer than days, often for weeks, months, sometimes for years. So what exactly is cholesterol?

Good and Bad Cholesterol

There is no such thing as good or bad cholesterol; we only have one type of cholesterol with the chemical formula: C₂₇H₄₆O. We have some differentiation within cholesterol in terms of size and the size variation is a representation of oxidative damage^1,2  but it is still the same exact cholesterol. It may have shrunk and folded on itself, became dense and sticky, caramelized. Indeed, the cholesterol inside LDL is found in 2 particle sizes: large fluffy (healthy) and small dense (damaged). The latter small, dense, damaged, caramelized ones are created by the pyruvate process by oxidation, and this cholesterol indeed participates in CVD. One should ask then why some cholesterol molecules become damaged and why some don’t. And also, is cholesterol and saturated fat connected? This is the heart of the matter, pun intended.

What is Fat?

Fat is made from fatty acids. All fatty acids are essential, meaning we must eat them. Our body cannot make them. There are two types of essential fatty acids: Omega 3 and Omega 6, within each of which there are three types: monounsaturated, polyunsaturated, and saturated fats.  Here is an example of a typical monounsaturated fat molecule: CH(CH₂)7COOH (oleic acid, making up about 83% of olive oil, a mostly monounsaturated fat). Here are two types of typical saturated fatty acids: CH3(CH2)₆COOH a short chain and CH₃(CH₂)24COOH a long chain fatty acid, and a typical polyunsaturated fatty acid is Linoleic acid C₁₈H₃₂O₂.

As you can see, all fatty acids have hydrogen tying down (bonding to) at least some of the oxygen. Whether the fatty acid is unsaturated or saturated depends on the number of hydrogen bonds. Monounsaturated has a single hydrogen bond, polyunsaturated more than one, and saturated has all oxygen tied down by hydrogen. The more saturated a fat is, the more stable are its bonds. Saturated fats last longer without going rancid, can be used at higher temperatures, and are solid at room temperature.

An important point about omega 3 and omega 6 is that humans are not able to convert the vegetable form of omega 3 (ALA), found in fruits, vegetables, nuts, grains, and seeds, into the animal form that the human body can use (DHA/EPA) efficiently. Therefore, the consumption of animal products and seafood is essential for all humans to meet the necessary omega 3 requirement of our brain, which is mostly made from DHA.

How Cholesterol is Created

The chemical formula for cholesterol is not the same as for any of the fat types; in the cholesterol molecule there is no opening for saturation with hydrogen anywhere. No fat of any type has the same configuration in carbon, oxygen, or hydrogen as cholesterol. Fats are fatty acids, whereas cholesterol is a waxy substance. Cholesterol has not much to do with fat. It is not created from fat. The body can acquire cholesterol two ways:

• Directly from cholesterol containing foods
• Making it from carbohydrates.

If we eat enough cholesterol, the liver doesn’t make more. In other words, the liver only makes as much cholesterol from carbohydrates as the body needs. Cholesterol is essential in cell functioning and, as a result, is closely regulated by the liver. Cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acid, and vitamin D. The cholesterol-making pathway is 37 steps long. The first step is Acetyl-CoA, a molecule generated by cellular respiration. It is produced in the second step of aerobic respiration after glycolysis and carries the carbon atoms of the acetyl group to the TCA cycle to be oxidized for energy production. Cholesterol is a byproduct of glycolysis. Glycolysis breaks down glucose and forms pyruvate with the production of two molecules of ATP. Cholesterol is not only integral to cellular respiration and the formation of ATP,  it is a product of that very function. Cholesterol is a result of glucose metabolism. This is crucially important knowledge. It goes against the dogma of “cholesterol is made from fat, therefore fat is bad”.

Cholesterol regulation is a key component of metabolic processes. When we don’t eat enough cholesterol from meats and eggs, more is made by the liver from carbohydrates. Glucose oversupply, starches, and fructose either convert to cholesterol—as noted earlier—or excess carbohydrates get packed away as future storage (visceral and ectopic fat) in and around our organs. This fat storage is initiated by insulin and is completed by our liver.

Triglycerides form visceral and ectopic fat, which are our energy reserves converted from the unused glucose and fructose. The liver’s capacity for this storage is limited and so it needs to expand in size to accept more. This is the cause of non-alcoholic fatty liver diseases, and then later, the need for more and more fat storage is what becomes insulin resistance,  that may lead to type 2 diabetes. So, by avoiding excess consumption of carbohydrates, the creation of dense, sticky, caramelized cholesterol particles can be prevented. From the cholesterol in LDL, these low-density, sticky, caramelized, damaged cholesterol particles are the only ones that contribute to CVD. However, when we reduce carbohydrates in our diet, we need to increase the consumption of fats.

There is no food that is pure saturated fat. All fats, no matter if it is in a leaf of lettuce or a pork belly, is a combination of saturated fat, monounsaturated fat, and polyunsaturated fat. They are not found separately in nature. What we can say is that some foods have less saturated fat than others. Some of the foods that have been excluded from recommended diets based on the fear of saturated fat are pork and beef:

Note in the above table that pork lard has more monounsaturated fat than saturated fat, so can we say that pork lard is saturated fat? It is important to see which fat type is closest to human fat because that is what we need to eat. If we look at the human body’s fat composition (this is very hard to find, so I put this together from several research papers), it is very similar to that of pigs, meaning that to maintain our health, we should consume the type of fats our body is made from, and thus, needs.

Carbohydrates and the Insulin Connection

At this point, your head is probably spinning from too much chemistry, but bear with me. If we don’t understand the chemistry, all sorts of errant assumptions about health and disease can be made and have been made. Most importantly, for generations we have failed to recognize that cholesterol comes from carbohydrates, not fats, and as result, millions of us have developed type two diabetes by following the accepted medical advice. Just how bad is it?

When Carbohydrates Dominate the Diet

Carbohydrates were elevated to primary consumption status at the same time fats were demoted. Of the three macronutrients: fat, protein, and carbohydrates, carbohydrates are the only non-essential macronutrients. There is not a single essential element in carbohydrates. Carbohydrates provide glucose (the body can make glucose from protein and fat), fructose (44% of fructose converts to glucose and the rest to triglycerides), vitamins (all vitamins in plants are also available in animals—including vitamin C if certain parts are eaten raw—and many vitamin in animal products are not found in plants).

Another note on vitamins: we consume most vitamins in order to help our immune system fight free radicals. Free radicals are only created in the pyruvate (glycolysis) step, which is participant only in the glucose metabolic process. If we stop eating exogenous glucose (carbohydrates), our need for antioxidants is greatly reduced. Fat-burning bypasses the pyruvate process and doesn’t generate free radicals³. Over 50% of protein converts to glucose⁴. However, the amount of free radicals generated from protein-converting is so small that only minimal free radicals are generated.

When the USDA removed “saturated fats” and everything that contained them from our diets, it replaced all that with vegetable oils (Omega 6 oils), transfats (artificially hydrogenated vegetable oils), and carbohydrates. Diabesity (diabetic obesity), increase in CVD, Alzheimer’s disease, cancer, arthritis, incontinence, PCOS, prostate problem, neurophathy, fibromyalgia, etc., followed.

The Problem with Grains

According to the celiac.org, 1% of the global population has celiac disease and 0.4% has been diagnosed to have wheat allergy—a large percent remain undiagnosed. The wheat allergy or sensitivity of those not yet diagnosed show up like arthritis, prostate concerns, PCOS, allergies, asthma, Crohn’s disease, IBS, etc. How can we tell? When they stop eating all grains (wheat, rice, corn, rye, oats, etc.,) for at least 2-6 months, their inflammatory markers improve and they reverse their health conditions. Grains are also responsible, in a large part, for CVD and potentially cancer, because grains are inflammatory, increase blood pressure, and narrow the arteries. It was a human genetic variant that allowed some of the damaging factors of grains to be mitigated: ACE and apolipoprotein B genes, because they relate to blood pressure and the cholesterol in LDL. Blood pressure and cholesterol are both factors that respond well to low-carbohydrate, and thus, low-grain diets, suggesting that the polymorphisms may be a protective adaptation against the cardiovascular effects of grains⁵.

In spite of all this knowledge, grains are considered to be the most vital nutrient on “My Plate” by the USDA. Furthermore, grains are indigestible and reduce nutrition absorption.  They also need to be fortified to get any nutrition while eating them. They are the most frequent carbohydrate items on our plate that have no nutrition, only glucose from starch.

Fruits, Vegetables, Nuts, and Seeds

Other carbohydrates are fruits, vegetables, seeds, and nuts. The ideal maximum blood glucose level is 99 mg/gL (equivalent to about 1 teaspoon, a little over 4 gr of glucose for an average person. By eating a medium size sour Granny Smith apple, we take in almost 23 gr carbohydrates, of which 10.225 gr is pure glucose. This is 2.5 times as much glucose as what the entire blood supply prefers to have, so eating a medium sized sour Granny Smith apple challenges the body to remove all that glucose from the blood very fast, a large amount of glucose staying in the blood is toxic. Mind you, this one apple, with all the trouble it caused, gives nearly no vitamins at all; no vitamin C noted in the USDA table, very few amino acids and no fatty acids, those would be the essential macronutrients. An apple offers nothing but glucose and fructose. Therefore, from what we now know about the connection of carbohydrates to cholesterol, part of that apple will become cholesterol, and since it is a carbohydrate and is converted to energy using the pyruvate process, it also creates more free radicals than if you, instead, ate a steak. And lastly, since this apple has much more glucose than what the body can use, and also a lot of fructose, whatever energy from this apple is not used, gets stored as body fat.

Diet and Insulin Resistance

Insulin resistance is not a disease. It is nature’s way of helping creatures pile up fat-reserves for times of scarce resources, like winter. The trick is the seasonality of insulin resistance; it is nature’s way of remaining alive in winter but returning to normal insulin levels during the lean times, normally hibernation or starvation, thereby, when spring appears with fresh food resources, the liver will have reversed all its fattiness and by then the visceral and ectopic fat would have shrunken by fueling the body all through the winter. This is an equivalent process to the ketogenic diet – see below.

Lack of seasonality in energy storage necessarily leads to chronic insulin resistance. Chronic insulin resistance is unhealthy, leads to type 2 diabetes, and/or obesity. While this would need a lot of explanation, in short: obesity and insulin resistance need not go hand in hand. Sumo Wrestlers are extremely obese but are completely healthy without any insulin resistance while very thin people may have insulin resistance (TOFI—thin outside fat inside). Thus, insulin resistance is strictly associated with extensive visceral and ectopic fat and not with “being fat.”

One can prevent chronic insulin resistance by either following in the footsteps of our evolutionary past with seasonality, or by permanently preventing fat accumulation when not observing any seasonality. This requires cutting back on carbohydrates. When we cut back carbohydrates, depending on the depth to which we reduce carbohydrates in our diet, the body may move to burn visceral/ectopic fat by entering the state of ketosis. Ketosis is not equivalent to keto acidosis. Ketosis merely means that the body switched from burning glucose to burning fat in the form of ketones—or to be more precise, burning β-Hydroxybutyrate (βHB)⁶. Just like any fire needs some kindle to be started, a proper fat-burning diet is started by eating fat—and plenty of saturated fat. The ketogenic diet doesn’t use glucose for fuel, but this doesn’t mean the body has no access to glucose. A large percent of protein converts to glucose, so those organs that need glucose, still receive it, but the body’s main fuel is fat.

As noted earlier, cholesterol is made from carbohydrates, and deformed cholesterol is a consequence of the pyruvate/glycolysis process (a carbohydrate metabolic process). Since fat doesn’t convert to cholesterol and doesn’t use the pyruvate process, the ketogenic diet reduces the chance for the creation of any damaged cholesterol within LDL.

The Ketogenic Diet

The ketogenic diet is really not a diet but a metabolic process, in which the main fuel of the body is fat. While glucose is also used, it is only used for those organs that must have glucose, such as red blood cells and the brain. The ketogenic diet burns ketone bodies—fat converted to body fuel. The ketogenic diet induces nutritional ketosis—not to be confused by diabetic keto acidosis, which is the outcome of type 2 diabetes. During nutritional ketosis, the body burns stored energy for fuel (visceral and ectopic fat). As a result, it is often used for weight loss. It is an ideal nutritional method to reverse insulin resistance, since it reverses non-alcoholic fatty liver disease by reducing fat storage.

The ketogenic diet is a strict version of the low carbs high fat diet with moderate protein consumption. A typical ketogenic diet is 80% calories from fat, 16% calories from protein, and 4% from carbs. The type of carbs that are permitted are mostly green leafy salads, spinach, broccoli and cauliflower, fruits like avocado, zucchini, etc., and some minimal raspberries and blackberries. The fats contain olive oil and animal fats. Some people in ketogenic diet also consume coconut oil. Coconut oil can only burn as ketones and so eating coconut oil prevents the burning of stored fat for fuel. Thus, coconut oil should not be consumed by those wishing to lose weight.

The strictest form of the ketogenic diet is used therapeutically for seizure cures. It appears that the ketogenic diet rebuilds the myelin (mechanism not yet understood), the layer made from fat and cholesterol (white matter in the brain) that coats neurons to insulate them from possible voltage leak. This more extreme form is also used to help other diseases where the white matter is damaged, such as Alzheimer’s disease, Parkinson’s disease, and Multiple Sclerosis, among others.

Since cancer cells feed on glucose—called the Warburg Effect, the ketogenic diet is also being tested for cancer treatment, so far with great success. For an example, see Andrew Scarborough and his recovery from Anaplastic Astrocytoma that was diagnosed in 2013.

LCHF Diet

There are nutritional concepts, other than the ketogenesis, that can help reverse some metabolic damage, such as the LCHF (low carbs high fat) diet. It is a comfortable alternative to the ketogenic diet for those who don’t wish to become fat burners, only want to reduce their chances for insulin resistance, obesity, and metabolic diseases that include non-alcoholic fatty liver disease as well as CVD.

The LCHF diet is still a carbohydrate burning diet, and as such, antioxidants are necessary, and fat is not burned. However, it removes most of those foods from the diet that appear to cause problems for many people, such as refined carbohydrates (all sweeteners, prepared, canned, and processed foods, juices, shakes, and smoothies. Some LCHF diets permit the use of some sugar substitutes), all grains (even gluten free grains are grains, so they are not part of the LCHF diet), all starchy vegetables (potatoes, yams, carrots), and the majority of fruits, with the exception of raspberries, strawberries, and blackberries.

LCHF diet encourages olive oil, coconut oil, and animal fats, lots of fish, all meat types, and dairy. The focus is on reduced carbohydrates, typically to around 100 net carb grams a day.

Individualized Nutrition

No single diet works for everyone. Genetic (heritable) and epigenetic (environmental) factors mostly determine what is healthy for a person and what is not. People whose ancestry is from Nordic environments will likely have trouble metabolizing foods that were not readily available in their location prior to commercialization, such as tropical fruits. Others, whose ancestry is more tropical, may end up with metabolic health issues from eating too much fat.

It is important to understand that the goal is not to just follow a nutritional regimen but to recognize the reaction of an individual to the food consumed.

What we see in the US, and increasingly around the world, is an epidemic created by the Standard American Diet (SAD) that assumes that all humans have identical metabolic processes. That this is not true should have been realized when Native Americans were changed to the SAD (sugar, soft drinks, grains) diet and they all became unhealthy. While the experts at that time perhaps didn’t understand what was happening, we understand it now. We need to maintain flexibility! Those suffering from metabolic disorders such as obesity, insulin resistance, type 2 diabetes, CVD, etc., should consider it a sign, a warning, and change their eating habits, change to a different nutritional base for health. Those who do well on SAD can carry on. The important point is to pay attention and be willing to change.

Sources

1. Gesquière L, Loreau N, Minnich A, Davignon J, Blache D. Oxidative stress leads to cholesterol accumulation in vascular smooth muscle cells. Free Radical Biology and Medicine 1999; 27(1): 134-45.
2. Al-Benna S, Hamilton CA, McClure JD, et al. Low-Density Lipoprotein Cholesterol Determines Oxidative Stress and Endothelial Dysfunction in Saphenous Veins From Patients With Coronary Artery Disease. Arteriosclerosis, Thrombosis, and Vascular Biology 2006; 26(1): 218-23.
3. Pigozzi F, Giombini A, Fagnani F, Parisi A. CHAPTER 3 – The Role of Diet and Nutritional Supplements A2 – Frontera, Walter R. In: Herring SA, Micheli LJ, Silver JK, Cd AEft, Young TP, eds. Clinical Sports Medicine. Edinburgh: W.B. Saunders; 2007: 23-36.
4. Coulston AM, Liu GC, Reaven GM. Plasma glucose, insulin and lipid responses to high-carbohydrate low-fat diets in normal humans. Metabolism 1983; 32(1): 52-6.
5. Salomón T, Sibbersen C, Hansen J, et al. Ketone Body Acetoacetate Buffers Methylglyoxal via a Non-enzymatic Conversion during Diabetic and Dietary Ketosis. Cell Chemical Biology; 24(8): 935-43.e7.
6. Reger MA, Henderson ST, Hale C, et al. Effects of Beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiology of Aging; 25(3): 311-4.

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