OBSERVATIONAL EVIDENCE
1. Michael Brown and Joseph Goldstein discovered that the number of functional LDL receptors on the surface of cells, especially liver cells determines the level of LDL in the blood. If the receptors are defective or too few in number, LDL builds up in the blood instead of being taken into the cells. Familial hypercholesterolemia (FH) is caused by the mutation of a single gene that does one thing; make LDL receptors. People with two copies of the mutation for FH have LDL levels 6 to 10 fold above normal and can have a heart attack as early as 18 months of age. People with one copy of the mutation have LDL levels 2 to 4 times above normal and develop clinical symptoms between the ages of 30 and 60. Dr. Ravnskov is in denial about the obvious dose response relationship. (1) In the era before the statins, FH patients aged 20 to 39 years old were 100 times more likely die of heart disease and 10 times more likely to die from all causes than someone in the general population. (2) In a later study, FH patients treated with statins lived just as long as people without FH. (3)
2. Atherosclerotic plaque contains a lot of cholesterol. In 1856 a German pathologist named Rudolf Virchow proposed that lipid accumulation in the artery wall caused atherosclerosis. In 1914 Nikolai Anitschkow also observed cholesterol crystals in advanced plaque in the aorta of cholesterol fed rabbits.
3. People with very low LDL tend to be protected from CHD, with the exception of alcoholics. (Alcohol lowers LDL and damages the endothelium at the same time.) The normal LDL cholesterol range is 50 to 70 mg/dl for modern hunter-gatherers, healthy human newborns, free-living primates, and other wild mammals (all of whom do not develop atherosclerosis). (4) And during the 80s, rural Chinese had an average serum cholesterol level of 127 mg/dl. And the men in rural China had a rate of CHD that was only 1/17th that of American men. This was in spite of the fact that close to 80% of them smoked. (5) According to the third report of the National Cholesterol Education Program (NCEP), "Only in populations that maintain very low levels of serum cholesterol, e.g., total cholesterol <150 mg/dL (or LDL cholesterol <100 mg/dL) throughout life do we find a near-absence of clinical CHD." (6)
4. People with an intermediate level of LDL have intermediate levels of heart disease. Virtually 100% of observational studies comparing people within the same country show an association between serum cholesterol and heart disease. (7,8,9)
5. The fact that HDL is protective and does the opposite of LDL is further proof of the harmfulness of elevated LDL. The INTERHEART study looked at 52 different countries and found that the ratio of apo-B (mostly LDL) to apo-A1 (HDL) could account for 50% of the risk of CHD mortality. (10)
EXPERIMENTAL EVIDENCE
6. Atherosclerosis can be induced in a great variety of animal species including vegetarian and carnivore species (e.g. insects, birds, cats, dogs, non-human primates etc.) by raising serum cholesterol high enough and maintaining it long enough. Atherosclerosis can also be reversed by lowering TC enough and maintaining it long enough. The lipid deposits and foam cells disappeared but some fibrous tissue remained. Some species, such as the dog and rat, do not get elevated TC from a diet high in saturated fat and cholesterol. But when a way was found to elevate their TC they also developed atherosclerosis. This is so consistent no matter which species is tested that it appears to be a scientific law that elevated LDL can cause atherosclerosis. (11 This can't be explained away by stress, inflammation or some infectious agent. In clinical trials, Dr. Esselstyn's group did better than Dr. Ornish's group even though Dr. Ornish used stress reduction and Dr. Esselstyn didn't. However Dr. Esselstyn's patients had lower LDL. And although adding inflammatory factors like infection can speed up atherosclerosis, oxidized LDL, foam cells and cholesterol crystals inside the artery wall provide their own inflammation. See point eight.
7. In a meta-analysis of 35 randomized trials using diet and/or medication for every 10 percentage points of cholesterol lowering, CHD mortality was reduced by 13% and total mortality by 10% (12). And a meta-analysis of 9 randomized trials shows that when statins are used for secondary prevention in elderly patients they can reduce all-cause mortality by 22% and heart disease mortality by 30%. (13)
8. Lowering LDL can halt and even reverse heart disease in humans. In the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, coronary atherosclerosis was virtually stopped in its tracks when LDL was maintained at 79 mg/dL. (14) And Dr. Esselstyn was able to reverse atherosclerosis by maintaining LDL at 81 mg/dL using a 10% fat, high fiber diet and a low dose statin. (15)
How does LDL cause atherosclerosis?
9. Last but not least elevated LDL is essential to the mechanism of atherosclerosis. Apo B lipoproteins (mostly LDL) diffuse into the artery wall that has been damaged by hypertension, smoking, or high blood pressure. They become oxidized and cause inflammation which attracts macrophages. Macrophages devour oxidized LDL and become foam cells which form plaque and produce more inflammatory chemicals. They grow and eventually rupture depositing cholesterol crystals in the plaque. The crystals penetrate the artery wall causing even more inflammation. Elevated LDL also impairs endothelial function, reduces nitric oxide production and promotes platelet aggregation which promotes clotting. There are other factors besides elevated LDL that contribute to heart disease like smoking, hypertension, diabetes, abdominal obesity, stress, inflammation, homocysteine, sedentary lifestyle and excess sucrose but according to the INTERHEART study the ratio of apo-B (mostly LDL) to apo-A1 (HDL) can account for 50% of the risk. (16,17,18,10)
10. People who know the most about the subject agree. Scientists studying atherosclerosis know more about the subject than anyone else and the vast majority think that cholesterol is connected to heart disease. This is according a scientist who supports the cholesterol hypothesis as well as a leading cholesterol skeptic. (19,20)
SUMMARY OF ANSWERS TO OBJECTIONS
11. Dr. Ravnskov wants you to trust him and ignore people who know more about the subject than he does. However, in the introduction he tells us that "high cholesterol is good; the higher the better." This statement is so ridiculous that you shouldn't take anything else he says seriously. Why? Every chemical in the body has a healthy range. Too high or too low causes disease. Your body needs glucose. It's a natural energy source, if you don't eat it your body will make it, but that doesn't mean that more is always better. If it's too high you have diabetes. If it's too low, you go into a coma and die. Your body needs LDL but that doesn't mean that more is always better. Too high or too low causes disease.
12. In Chapter 3, Dr. Ravnskov was not thinking clearly when he tells us that people with familial hypercholesterolemia (FH) live just as long as others. In the study he cites to make this claim it clearly says that the FH patients were taking statins. 3)
13. Uncontrolled observational studies are good for generating hypotheses but can't prove anything by themselves. However Dr. Ravnskov uses this kind of study to ridicule conclusions based on experimental studies when it's the experimental studies that can actually prove something.
14. CANCER - The book leads us to believe that low serum cholesterol causes cancer, but there is abundant observational as well as experimental evidence that contradicts this conclusion. Calorie restriction lowers serum cholesterol and reduces the risk of cancer and heart disease at the same time. Meta-analysis of statin trials show no increase in the overall risk of cancer even after 5 to 10 years of use. Countries with lower serum cholesterol like China have lower rates of prostate, breast and colon cancer than the U.S. Hunter gatherers with their low LDL levels are known for the near-absence of cancer. In clinical trials, the cholesterol lowering Ornish diet slows the growth of prostate cancer. And finally people with stable low cholesterol levels don't have higher cancer rates, just people whose cholesterol level has fallen recently. (21,22,23) The evidence not only proves that low LDL does not cause cancer, it strongly suggests that lifelong high LDL increases the risk of cancer. If it is discovered in the future that long term use of statins causes cancer in humans, it definitely won't be due to low LDL.
15. THE ELDERLY - Dr. Ravnskov claims that "old people with high cholesterol live the longest" based on associations in observational studies. He also claims "Cholesterol-lowering is only able to lower mortality in young and middle-aged men with heart disease." He is misinformed. A meta-analysis of 9 randomized trials shows that when statins are used for secondary prevention in elderly patients they can reduce all-cause mortality by 22% and heart disease mortality by 30%. (13) As he points out himself, associations in observational studies can be very misleading, it's the experimental evidence that carries the most weight and that clearly shows that people of all ages with heart disease live longer when they reduce LDL. Furthermore elderly people have higher cholesterol than young people and they also have more heart attacks than young people.
16. The reason that there's a stronger correlation between atherosclerosis and age than between atherosclerosis and serum cholesterol is because it takes a long time for elevated LDL to do its damage. To see the association all the autopsies would need to be performed on people of the same age.
17. In uncontrolled observational studies when comparing different countries, LDL and heart attacks are not always associated (France has higher LDL and fewer heart attacks than the United States). But HDL is also important and in France people have higher levels of HDL. And within France, people with higher LDL are still more likely to get heart disease. And according to the MONICA study of 21 countries including France, in men aged 55 to 64 years, 10-year population changes in serum cholesterol level alone explained 35% of the variance of change in fatal and nonfatal coronary events. (24)
18. When talking about statins, Dr. Ravnskov focuses on the absolute reduction which can be as little as 1% in short term studies of healthy people. He uses this to ridicule the effectiveness of medication. However in studies of elderly patients with heart disease you would expect the absolute risk reduction to approach the relative risk reduction of 30% if the study ran long enough.
19. Eating fish or taking fish oil with a high complex carbohydrate diet reduces triglycerides better than eating a high fat diet. (25)
20. STATIN SIDE EFFECTS - 10mg simvastatin is so safe it is sold over the counter in the UK. High dose statins on the other hand should probably only be prescribed to patients who have tried a low first and been screened for elevated liver enzymes etc. And statins deplete CoQ10 so anyone taking a statin should also take CoQ10. Should we believe every side effect is caused by low LDL? There are millions of people with LDL levels lower than the levels of people on high dose statins who are not known for muscle weakness or poor memory or liver problems. For example, the Masai don't seem to be suffering from muscle weakness or birth defects. And wild mammals with 50 to 70 mg/dL LDL are known for their excellent health. Almost all prescription drugs are dangerous if taken by the wrong person. But they can be life saving when taken by the right person. For people who don't want to take statins there are several alternative ways to lower LDL that are not likely to cause side effects.
SOME LIMITS OF UNCONTROLLED OBSERVATIONAL STUDIES (Observational studies are good for coming up with hypotheses, but experimental studies are good for proving cause and effect plus they carry more weight.)
1) ASSOCIATION DOES NOT PROVE CAUSATION: All knowledge of cause and effect starts with observing an association but not all associations indicate cause and effect. Low LDL and cancer are associated, but an observational study can't tell you which one is cause and which one is effect or if they're both caused by something else. Associations or lack of associations in an uncontrolled observational study can only suggest a hypothesis, not prove cause and effect or lack of it.
2) CONFOUNDING VARIABLES: Smoking, hypertension, diabetes, abdominal obesity, stress, excess sucrose consumption, alcoholism etc. are all risk factors for heart disease. Therefore, a study could show that elevated LDL was not associated with heart disease in people with low LDL who were also alcoholics and smoked and had hypertension because these variables add up to a greater risk than elevated LDL alone.
3) SOME VARIABLES EFFECT OTHER VARIABLES: For example, studies of saturated fat consumption are also measuring the effects of what people eat more of when they eat less saturated fat. For example, less saturated fat can be associated with a less heart disease if people replace it with something better like canola oil based margarine in the Lyon Diet-Heart Study. Less saturated fat can be associated with the same rate of heart disease if people replace it with something equally bad like sugar and white flour (like the MRFIT study). Less saturated fat can even be associated with or a higher rate of heart disease if people replace it with something worse like stick margarine that's high in trans fat.
4) LUMPING TOGETHER VARIABLES WITH DIFFERENT EFFECTS: Studies can fail to distinguish between saturated fat that makes the HDL:LDL ratio worse (like grain fed meat) and saturated fat that makes the HDL:LDL ratio better (like coconuts). A study could also assume that all meats contain a similar amount of saturated fat when grain fed meat can contain over 5 times more than grass fed meat.
5) PAST VERSUS PRESENT. Before statins or the link between saturated fat and heart disease was discovered, people with chest pain or survivors of heart attacks did not reduce saturated fat or take medication to lower cholesterol. When their LDL was measured it was likely to represent their lifetime average. Now LDL is routinely measured every time someone gets a complete physical, and dietary changes or prescription medication is recommended to high risk individuals long before they have a heart attack. Atherosclerosis is slowed and the heart attack is delayed for several years and occurs with lower saturated fat consumption and/or a lower LDL level. Today the LDL level of a heart patient admitted to the hospital is very unlikely to represent their lifetime average.
EXPERIMENTAL EVIDENCE THAT SATURATED FAT RAISES SERUM CHOLESTEROL
A meta-analysis of 395 metabolic ward experiments concluded that in typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol. (26)
The book tells us that metabolic ward studies of saturated fat don't count because the negative outcome might have been due to trans fat in hydrogenated vegetable oil instead of saturated fat. However, Dr. Stephen Phinney conducted a metabolic ward trial, during weight maintenance not weight loss like so many other studies, with nine healthy lean men. These men consumed nothing but meat, fish, eggs, cheese and cream (no hydrogenated vegetable oil) for 35 days. Their carbohydrate intake was less than 20 grams a day. Their blood cholesterol went up from 159 to 208 on average in 35 days. That is a 31% increase. The average adult in this country has a cholesterol level of 199. A 31% increase would give 261. The high risk category is anything over 240. (27)
These studies report the average for large groups, but there can be exceptions to the rule without making the conclusion about the average false. For example Jeanne Louise Calment smoked most of her life and lived to be 122 years old, but the average smoker's life is shortened by 10 years.
You might ask, what about hunter gatherers who eat a lot of meat and have low cholesterol levels? It turns out that wild elk, moose or whale meat are so low in palmitic acid that they could be part of an Ornish diet. For example whale meat contains about 1/75 as much as T-bone from feedlot meat. You can verify this for yourself by searching the USDA National Nutrient Database.
What about the Inuit? Some people claim their diet contains 75% saturated fat because of all the whale blubber they eat. It turns out that the animal food with the highest percentage of saturated fat is cream which contains 57%, so the claim of 75% is impossible for any group eating exclusively animal food. Compared to beef tallow, whale blubber contains much less saturated fat and much more MUFA and PUFA. In the fact the ratio of palmitic acid (which is the main saturated fatty acid in meat that raises LDL) to PUFA (which lowers LDL) is over 14 times greater in beef tallow. (36)
But hunter gatherers don't eat dairy. What about the Masai? Eighty two percent of their plant food additives contain potentially cholesterol lowering saponins and phenolics. (28) And they eat raw blood which exposes them to parasites which also lowers cholesterol. When Westerners eat a lot of animal fat and they're not losing weight their TC goes up drastically. So without statin-like chemicals and parasites in their food, the serum cholesterol of the Masai would be much higher. And their low serum cholesterol along with their low rate of CHD is further support for the lipid hypothesis.
What about Pacific Islanders? Don't they eat a lot of saturated fat and have a low rate of heart disease? Coconuts are different than feedlot meat. They contain mostly lauric acid instead of palmitic acid. And they don't raise LDL as much. And they improve the LDL/HDL ratio (29) while feedlot meat makes it worse.
According to a meta-analysis of 24 studies by Ip et al in 2009, LDL particle number was a better predictor of risk for cardiovascular disease than LDL subfractions. (30)
VERY HIGH ANIMAL FAT DIETS AND HEART DISEASE AND CANCER
These long term observational studies show that very high animal fat diets are associated with more heart disease, cancer and/or all-cause mortality than the control. This may not seem like very many, but there are only a few studies that focus on very high animal fat diets.
"Low-carbohydrate diets and all-cause and cause-specific mortality" by Fung et al published in 2010. A high-meat diet with about 20% saturated fat had 43% greater all-cause mortality and than an Eco-Atkins diet with 12% saturated fat. This was not an uncontrolled study; even though it's observational it's carefully controlled for the relevant variables. The high-meat group ate the same or less trans fat, omega-6 and refined carbs so there's no reason to think something other than the meat caused them to do poorly. This study is as good as any observational study gets, in spite of what Denise Minger says. She is nihilistic about any evidence against animal fat. To her, every study has a flaw and nothing is ever certain. But when it comes to uncontrolled observational studies of other cultures (evidence that's much weaker than the evidence she finds fault with), she accepts it without critical thinking. (34)
"Mediterranean and carbohydrate-restricted diets and mortality among elderly men" by Sjogren et al published in 2010. The low carb, high meat group had 48% greater all-cause mortality and 81% greater heart disease mortality than the group eating a Mediterranean Diet. (37)
Eating low carb with lots of fatty cuts of grain fed meat won't increase everyone's LDL or give everyone heart disease and cancer, but it may increase the risk for the average person.
EXPERIMENTAL EVIDENCE OF DIETS THAT SAVE LIVES IN PEOPLE WITH HEART DISEASE
In the 1950s, Dr. Morrison put 50 heart attack survivors on a 15% fat, high protein diet and another 50 survivors were told to eat as usual. Total cholesterol fell from 312 mg/dl to 220 mg/dl in the experimental group. That's a reduction of 29%. And over a period of 8 years, 38 patients eating as usual died while only 22 in the experimental group died. (31)
In the 1980s, Dr. Esselstyn used a 10% fat, high fiber diet plus low dose statins to reverse heart disease in 17 men and one woman. The average for total cholesterol and LDL was maintained at 145 mg/dl and 82 mg/dl respectively. We know it worked because of before and after coronary angiograms and cardiac PET scans. People given less than a year to live are alive and healthier over 23 years later. During that time no patient died of coronary artery disease, but one died of an arrhythmia. (15)
Dr. Ornish also reversed heart disease using a similar diet plus exercise and meditation but no statins. Since then Dr. Ornish has enrolled at least 3800 patients in demonstration projects (to demonstrate savings on surgery) which resulted in over 40 insurance companies including Medicare covering a program in diet and lifestyle for heart disease patients. According to Dr. Ornish, "In brief, we found that almost 80 percent of patients who were eligible for bypass surgery or angioplasty were able to safely avoid it for at least three years." (32)
In the Lyon Diet-Heart Study of heart attack survivors there was a 76% reduction in major cardiovascular events in the group eating a Mediterranean diet where they replaced saturated fat with canola based margarine. (33)
Low carb can be healthy if you do it right. If you have metabolic syndrome or can't eat grains, a low carb diet with regular meat, that includes 12% or less animal protein and 12% or less saturated fat has been shown to be healthier than the standard American Diet. Less animal fat gives even better lipid profiles. (34)
According to observational evidence, in the 50's and 60's Crete had the best longevity in the world. They ate 40% fat mostly from olive oil, but only 8% saturated fat. The total red meat, poultry and fish consumed in Crete was only about 2 ounces/person/day. Ancel Keys followed this version of the Mediterranean diet and lived to be 100 years old. (35)
Statins can lower LDL 50%. According to Dr. Ornish on average a 10% fat, high fiber diet can lower LDL by 40%. And according to [[ASIN:0307339114 Cholesterol Down: Ten Simple Steps to Lower Your Cholesterol in Four Weeks--Without Prescription Drugs]] there is a combination of specific foods and fibers, like apples and Metamucil that can lower LDL by 30%.
Dietary studies where people probably replaced animal fat with sugar and white flour like MRFIT and the Women's Health Initiative --- or replaced sugar and white flour with animal fat like a traditional Atkin's diet --- generally produce no reduction in heart disease mortality.
----
Just like a defense lawyer Dr. Ravnskov is advocating for his position and not even trying to be objective. People need to hear both sides. The book makes no mention of Dr. Morrison, Dr. Esselstyn, Dr. Ornish, the Mediterranean diet or the Eco-Atkins diet and it belittles or ignores other research that can save lives. Except for the warning about high dose statins, the book has little value. For heart patients young and old, trusting Dr. Ravnskov greatly increases the risk of heart attack and all cause mortality.
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