Apologies for the length of this post as I feel this topic requires a very full explanation.
There is no such thing as LDL cholesterol or HDL cholesterol, cholesterol is just cholesterol.
Cholesterol is a fat, and must be packaged within a complex particle called a lipoprotein, in order to enable it to be transported within blood, which is water based.
There are a range of lipoproteins, from large to small, known as Very Low-Density Lipoprotein (VLDL), Intermediate-Density Lipoprotein (IDL), Low-Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL). All of these lipoproteins can transport cholesterol as can red blood cells (RBC). When someone says LDL cholesterol (or LDL-C) they are actually referring to an LDL particle carrying cholesterol.
Cholesterol is critical for many functions in the body including operation of your immune system, your nerves and your brain plus the synthesis of hormones. Without it you will die.
Your liver makes the Very Low-Density Lipoproteins (VLDL) as a way of ferrying fatty-acids and cholesterol, via your blood, to different cells in the body. These fats must be transported in lipoproteins in blood, as blood is water based and wont mix with fats. The VLDL particles are loaded with Triglycerides, Cholesterol and other compounds for distribution.
The major source of the fatty-acids is excess dietary carbohydrates, proteins and alcohol that have been converted into fatty-acids by a process called De novo lipogenesis. The liver is actively trying to get rid of these fatty-acids. As the VLDL carrier deposits fatty-acids and cholesterol at each site around the body, it shrinks eventually becoming the size referred to as a Low-Density Lipoprotein (LDL). When it has delivered its load of fatty-acids and cholesterol, it returns to the liver and the process begins again.
Accordingly, when you eat excess carbohydrate your LDL level will rise and a low carbohydrate diet means your LDL level will usually fall. The (HDL) High Density Lipoprotein carries unused cholesterol from body tissues back to the liver. The impact of saturated fats on cholesterol levels is more fully explained further on in the book.
The surface of the LDL lipoprotein has a single copy of a receptor protein known as Apo B-100 which is like a key identifying the lipoprotein to each location as required, including to the liver on its return. If this receptor should become damaged in any way, then the particle is not recognized by any of the locations and it becomes an orphan particle.
There are a number of ways this receptor can be damaged with glycation being one and
oxidation another. Excess sugar in the blood can drive glycation and oxidative stress and oxidized oils in the diet, can drive oxidation of the LDL particle and receptor.
There are different theories about how atherosclerosis forms on artery walls, with the dominant theory called ‘The Diet-Heart Cholesterol Hypothesis’. In brief, this theory posits that saturated fat raises LDL cholesterol levels, which can become oxidized and can then penetrate artery walls causing damage. The body attempts to repair this damage resulting in arterial plaques.
These plaques can build up eventually closing off arteries and, if they detach from the artery walls, can cause blockages in critical parts of the body, such as the heart or brain. Depriving arteries of a blood supply can result in cell death followed by heart attack or stroke.
In a variation on this view, Professor Vladimir Subbotin has suggested that oxidized LDL cholesterol gets into your artery wall, not from inside the artery through the endothelial layer as usually proposed but, by being deposited there from the outside by the blood that supplies the artery walls. His argument is very compelling and, if true, indicates a sequence whereby an offending factor causes the initial thickening of arterial walls in the intima, which lies just behind the blood facing endothelial layer. This thickness calls for an additional blood supply which is provided by blood vessels feeding the artery walls (vasa vasorum) and growing into the intima layer. Oxidized LDL particles can accumulate at that point. Professor Subbotin posits that the commonly presented endothelial layer, as a single cell layer, is flawed, instead growing from birth into a 25-30 cell layer by about the age of 30.
A key driver for his view is that early stage oxidized LDL particle deposits occur at the endothelial / media junction multiple layers down from the glycocalyx rather than behind the surface endothelial layer. At these sites the blood vessels have already grown to supply the area with blood.
The glycocalyx is a fine hairlike layer on the inside surface of the blood vessels, only about 20 nanometers thick, that make them slippery, very much like the slippery layer on fish skin.
The Diet-Heart Cholesterol theory posits that the artery walls become 'sticky' by the action of contaminants in the blood, such as excess sugars, glycation or oxidized PUFA causing inflammation. This stickiness damages the glycocalyx and encourages oxidized LDL particles to adhere to the walls, starting the process of atherosclerosis. The damage in the artery walls then forms plaque. These plaques are the beginning of atherosclerosis eventually leading to arterial blockages and Cardio Vascular Disease (CVD).
Findings now suggest that higher levels of LDL can assist in regression of these plaques, whereas lower levels of LDL assist plaque progression. This matches the concept of cholesterol as part of both the immune system and the repair process.
Where does the oxidation come from? The most prevalent source of oxidization is believed to be oxidized Omega-6 seed oils (PUFA). It is nearly impossible for seed oils not to be oxidized and, greater oxidative stress in the body has been consistently measured following vegetable oil consumption in the diet. In contrast, saturated fats have a molecular structure that renders them very stable and unlikely to become oxidized, which means that they do not contribute to oxidative stress.
A suggested measure of oxidative stress is the ratio of HDL to triglycerides in your blood, using US units (mg/dL). Triglyceride level divided by HDL level will produce a result which ideally should be under 1.5 or better still close to 1.0.
Using my personal blood test result as an example,
Triglycerides = 62 mg/dL (0.7 mmol/L/)
HDL = 74 mg/dL (1.92 mol/L)
Ratio Trig / HDL = 62 / 74 = 0.84 (= good)
Apparently, research has identified that the Vegan diet will reduce HDL and raise Triglycerides which indicates an increase in oxidative stress from this diet. While researchers often cite the reduction in LDL that this diet causes as a good result, it is believed by other researchers that while the overall LDL has decreased, the level of oxidized LDL has significantly increased.
In an adjustment to the Diet-Heart Cholesterol Hypothesis, it is now considered that only cholesterol in oxidized LDL, sometimes referred to as small dense LDL, progresses the formation of plaques in arteries and this is primarily driven by inflammation, and oxidation, while non-oxidized LDL cholesterol (referred to as large fluffy LDL), is not a driver of atherosclerosis and may not deserve its label as bad cholesterol.
Inexplicably, low cholesterol levels are correlated with higher rates of overall mortality (not lower). In people over 60, higher cholesterol is in fact, more healthy, particularly in women. This is the opposite of conventional understanding. UK Dr. Zoe Harcombe PhD. has produced some great graphics by gender, showing deaths per 100,000 people vs cholesterol levels using WHO data from 192 countries, which clearly show this correlation.
Dr. Zoe Harcombe PhD. also states "Ancel Keys, the same man who did the brilliant Minnesota starvation experiment, spent the 1950's trying to show that cholesterol in food was associated with cholesterol in the blood. He concluded unequivocally that there was not even an association, let alone a causation. He never deviated from this view."
Cholesterol is a critical part of your immune system and this helps explain why LDL levels drop when people get infections. Cholesterol is an antioxidant, which could be the reason it rises as we age. Cholesterol at Cardio Vascular Disease (CVD) sites is now believed by many to help repair the artery damage and is not the cause of the problem.
There is an alternative view as to the cause of Atherosclerosis, and this view, called the Thrombogenic Process, seems to better fit the available evidence however, it has been actively suppressed, possibly because it doesn’t support the hugely profitable market for cholesterol lowering medications and low-fat foods. This view is well described with excellent references by Dr. Malcolm Kendrick in his book “The Clot Thickens”.
The Thrombogenic Process posits that various actions can damage the artery walls such as pollutants in the blood, high blood pressure, sickle cells, and other conditions that damage the glycocalyx (the slippery hairlike lining of the artery walls). These insults can arise from inflammation, high blood sugar, smoking, raised blood pressure, insulin resistance, steroid use, rheumatoid arthritis, toxins and many other causes. This damage produces blood clots (Thrombus) which can be as small as a rice grain, which then become plaques as the body sets about repairing the damage.
Blood clots draw in platelets and red blood cells that are rich in cholesterol and fibrin which build up the plaques. As part of the coagulation cascade, Endothelial Progenitor cells are attracted to the damage and build a new endothelium (artery wall layer) over the blood clot.
Finally, the presence or absence of Nitric oxide (NO) is important because it relaxes the artery, dilates blood vessels, prevents particles sticking to the glycocalyx and is a powerful anti-coagulant. It is also essential for erectile function suggesting that ED is a serious warning of impending atherosclerosis. NO is manufactured in the skin during exposure to sunlight. Low NO levels which are prevalent in people with insulin resistance will, therefore, exacerbate the risk of blood clots (thrombus). This also suggests that any condition that makes your blood less likely to clot is protective. High NO levels and daily aspirin fit this concept.
The problems resulting from blocked arteries or detached plaques can then cause heart attacks or strokes in line with other theories.
Cholesterol is not the villain in this theory, however, all the mechanisms that may cause artery wall (endothelium layer) damage do come into play.
It then follows that if you have a healthy glycocalyx, you have a major protective barrier against endothelial damage, formation of blood clots and cardiovascular disease.
How then does Type-2 diabetes lead to heart disease? By reducing nitric oxide synthesis, increasing endothelial damage, increasing blood coagulation, reducing the level of endothelial progenitor cells, damaging the glycocalyx and increasing glycation damage throughout the body.
I am convinced it is time to update our understanding of heart disease. The glycocalyx was only identified in 1963 and seen for the first time with an electron microscope in 1966. The ability of the endothelial cells to make NO was not understood until 1986, although it was recognized in 1980 that something was being produced that was relaxing blood vessel walls. Endothelial Progenitor cells in the blood were not identified until 1997. Up until then, it was assumed that existing endothelial cells spread from the edges of a plaque.
Based on these various scenarios and the many hours of reading and review I have studied, I now lean strongly towards the Thrombogenic Process. There are some strong clues as to its accuracy. Just as water comes in different forms of ice, steam and liquid, cholesterol also comes in different forms. Apparently the dominant form of cholesterol found in atherosclerotic plaques is not the form found in LDL particles, but it can be derived from the cholesterol found in red blood cells. The rapid action, by the Endothelial Progenitor cells, to build new endothelium over the plaque creates the appearance that the cholesterol has arrived from the vasa vasorum which aligns with the theory from Professor Vladimir Subbotin.
I believe that the strong efforts being taken to cancel Dr. Malcolm Kendrick, signal his message is no doubt true and a real threat to the massive drug profits from cholesterol lowering drugs. There are far too many inconsistencies with The Diet-Heart Cholesterol Hypothesis, such as the longer life span of women with higher cholesterol, the lack of any sort of progress reducing CVD following decades of cholesterol lowering medication, and large surveys (https://pubmed.ncbi.nlm.nih.gov/19081406/) finding that at least half the people admitted to hospital with CVD have average or low cholesterol levels. Strangely, instead of concluding that high cholesterol may not actually drive up CVD risk, they choose to double down on the diet-heart cholesterol theory suggesting the need for further reductions in cholesterol levels!
We have already discovered that cholesterol in our food has almost zero impact on the level in the body which explains why early recommendations to limit egg consumption have been dropped. We also understand that the saturated fat (SAT) we eat, has no link to LDL particles as it comes into the blood directly from the intestinal tract, packed in chylomicrons, not LDL. We know that plant sterols in omega-6 polyunsaturated seed oils (vegetable oils) can displace cholesterol in human membranes and that people with high levels of plant sterols can suffer from sitosterolemia which usually causes advanced severe atherosclerosis.
People replacing excess omega-6 polyunsaturated fats with saturated fats will reduce the plant sterols and, as a consequence, increase their cholesterol level. I believe that this is a good thing as it is returning the body to how it is supposed to be and just like temperature, oxygen saturation, hydration and salt levels, cholesterol is probably being managed by the body to an optimum level for you.
George Elder, Wellness Guide, Diet Research Reviewer, Author "Take Back Your Health", on Amazon
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