In Nature Medicine, November 2002, Volume 8 Number 11 pp 1211 - 1217, a section about atherosclerosis was introduced by Daniel Steinberg: Atherogenesis in perspective: Hypercholesterolemia and inflammation as partners in crime. Here is a letter, commenting Steinbergs article by Uffe Ravnskov. His covering letter follows as does the answer from the editor. Steinbergs paper is available on . (It is necessary to open a personal account, that is free) Uffe Ravnskov: High cholesterol does not cause atherosclerosis According to Daniel Steinberg there is no longer a cholesterol controversy (November 2002, p 1211). Actually the opposite is true: the cholesterol hypothesis can no longer stand against a large body of contradictory findings. For example, there is no correlation between blood cholesterol and degree of atherosclerosis at autopsy. Investigation by angiography reveals little or no association. Electron beam tomography, a new technique that allows the identification of intramural deposits, reveals an inverse correlation between LDL cholesterol and degree of coronary calcification. Most importantly, a large number of observational and experimental angiographic studies have failed to reveal exposure-response between the changes of total or LDL-cholesterol and changes of coronary atherosclerosis, and clinical trials have failed to find exposure-response between degree of cholesterol lowering and outcome.1,2 Steinberg also claims that high cholesterol is sufficient in itself to produce atherosclerosis, referring to reports of early cardiovascular disease in individuals with familial hypercholesterolaemia (FH). But these patients have been selected because of disease. A recent study of unselected individuals with FH traced backwards found that before year 1900 their mortality was lower than that of the general population.3 Also, if hypercholesterolaemia is a sine qua non for. clinically important atherosclerosis, it is difficult to explain why low, not high cholesterol is a risk factor for coronary heart disease for people above age 70, the period of life where the great majority of cardiovascular events occur.1,2 Steinberg joins many other apologists for the diet-heart theory in claiming that animal experiments prove that high cholesterol causes heart disease. The animals used most frequently in these experiments are vegetarian rabbits and mice, simply because omnivorous or carnivorous animals show small or no vascular effects when their cholesterol is raised by diet. But how do we know whether human beings react to high cholesterol as the herbivorous rabbit or as the omnivorous rat? Furthermore, no animal study has ever produced a heart attack solely by raising an animals cholesterol. What these studies have produced is fatty streaks, not atherosclerosis. According to Steinberg there is consensus regarding the sequence of events from hypercholesterolaemia to fatty streaks. The crucial question however is, whether fatty streaks develop into true atherosclerosis. Steinberg admits that there is no hypothesis to explain that development. This is no surprise because fatty streaks are seen equally often in populations where atherosclerosis is rare as in populations where it is prevalent,4 clearly indicating that fatty streaks are not the very forerunners of atherosclerosis. A link is missing. Ravnskov U. Is atherosclerosis caused by high cholesterol? Q. J. Med. 95: 397-403 (2002). Ravnskov U. A hypothesis out-of-date: The diet-heart idea. J. Clin. Epidemiol., in press. Eric J G Sijbrands E.J.G. et al. Mortality Over Two Centuries in Large Pedigree With Familial Hypercholesterolaemia: Family Tree Mortality Study BMJ 322, 1019-1023 (2001). Strong J.P., Eggen D.A., Oalmann MC, Richards M.L., & Tracy RE. Pathology and epidemiology of atherosclerosis. J. Am. Diet. Assoc. 62, 262-268 (1973). Uffe Ravnskov's covering letter: Editor With great surprise I read the introduction to your Special Focus on Atherosclerosis by Daniel Steinberg. In the attached letter-to-the-editor I have pointed to a few of the numerous erroneous and misleading statements from Dr. Steinberg. However, with a limit of 400 words it is impossible to expose the full width of Dr. Steinbergs disingenuous article. In addition to the objections in my letter I have therefore given a more detailed criticism as follows. The first misleading or ambiguous statement said that correcting hypercholesterolemia profoundly reduces morbidity and mortality from CHD, referring to the statin trials. Apart from the fact that Steinberg, like most other proponents of the cholesterol campaign, ignores the first, large statin trial, EXCEL, where total mortality increased by 150 % (0,5 % in the Lovastatin group, 0.2 % in the control group) already after one year,1 there is much evidence that the benefit exerted by the statins has nothing to do with their effect on cholesterol metabolism. This is most evident from the lack of exposure-response, as I have also mentioned in my letter. I would like to cite the authors of the CARE study2: In a multivariate analysis that included LDL concentration during follow-up, the change in LDL from baseline, expressed either as a percentage or absolute change in concentration, was not found to be significantly related to coronary events*. (* Indeed, because p was 0.97 for absolute change and 0.76 for percentage change; my comment) In addition, in a recent paper I analysed this problem in all angiographic studies, where exposure-response had been calculated, a total of five observational studies and 18 trials. Except for one trial no study found exposure-response; indeed, in two of the observational studies an inverse correlation was found between changes of cholesterol and changes of angiographic atherosclerosis.3 In the second section (Hypercholesterolemia as the initiator of atherosclerosis) Steinberg claimed that the benefit (of the statins) relates to the change in cholesterol in much the same way whether the cholesterol lowering is achieved with diet or with drugs. Apart from the fact, mentioned above, that the benefit was not associated with the change in cholesterol, the accumulated evidence from all controlled, randomised, unifactorial dietary trials did not find any effect on coronary or total mortality; in fact, the total number of deaths in the diet and the control arms were identical. This was shown by me in a previous review4 and confirmed last year by Hooper et al. in BMJ.5,6 Steinberg continues misquoting by claiming that drugs that lower cholesterol levels by different mechanisms have conferred benefit predicted by the extent to which cholesterol levels have been reduced. Not only has a meta-analysis of the non-statin trials shown that coronary mortality was unchanged after cholesterol lowering and total mortality increased, but also that the outcome was independent of the degree of cholesterol lowering, both within each trial but also between the trials.7 In the same section the reader is told that the risk for CHD is a smooth, continuous function of cholesterol level. Nothing could be further from the truth. In women, the risk is trivial. A review of eleven cohort studies, including more than 120,000 women, found an increased risk for coronary mortality in the fourth cholesterol quartile only (RR 1.56), whereas the risk for all cardiovascular and for total mortality was independent on the cholesterol level.8 In men, there are many populations where a high cholesterol level is not predictive of CHD. In Framingham, for example, a decreasing cholesterol level predicted an increased risk of coronary and total mortality. For each 1 mg/dl drop of cholesterol there was an 11 percent increase in coronary and total mortality.9 In Russia low cholesterol predicts higher coronary and total mortality.10 And as mentioned in my letter, high cholesterol does not predict CHD in the elderly either.11-13 Indeed, the higher the cholesterol level, the lower the risk.12,13 There is increasing evidence that inflammatory processes in the arterial walls, initiated by various factors, for instance microorganisms, homocysteine, toxic chemicals and/or free radicals), are the starting point for the production of raised lesions. Steinbergs article is a typical post hoc attempt to incorporate the cholesterol hypothesis with the new ideas, although all evidence has shown that high cholesterol is a biological marker, an innocent bystander without influence itself on the pathological processes. In my letter-to-the-editor I have referred to a paper in print . I have attached that manuscript (not corrected for linguistic errors). The editor asked Professor William S. Weintraub at Emory University, Atlanta, USA, a well-known supporter of the cholesterol campaign, to comment my review, and he also asked me to comment Professor Weintraubs comment. I have therefore also attached Professor Weintraubs dissent and my comment to his dissent. Yours sincerely Uffe Ravnskov, MD, PhD, independent researcher Magle Stora Kyrkogata 9, S-22350 Lund, Sweden Homepage: Mild atherosclerosis does not cause any symptoms. Generally, symptoms do not develop until the flow of blood through the arteries has been almost completely blocked. When symptoms do develop, they vary based on the location of the arteries affected. If atherosclerosis occurs in the coronary arteries, which supply blood to the heart, you may experience chest pain or numbness and tingling in your arms. If atherosclerosis affects the arteries that carry blood to your brain, you may experience difficulty speaking, numbness and tingling in your limbs and drooping facial muscles. These signs signal a transient ischemic attack, or mini-stroke. If the peripheral arteries, which carry blood to your legs, are blocked, you may experience leg pain or an increase in the temperature of your leg. Read more: Bill asked me if I could give you some basic information on niacin and atherosclerosis. I�d be happy to do that. Not knowing your husband�s medical history and lifestyle � or his blood type � I won�t be able to be too specific, but, I�ll at least give you some information to think about. If you have any questions, or I can be of any other help to you, please don�t hesitate to call. Concerning the niacin � I can only speculate that your doctor has your husband taking that to attempt to lower his cholesterol. To my knowledge, niacin is not a potent chelator (pulls minerals out of the body). It has been used as a vasodilator, but � there are other substances that may work better. They�ve done some studies that show a benefit with taking niacin, however, the side effects outweigh the benefits. It�s pretty bad on the liver, and it is recommended that people who consume any more than a moderate amount of alcohol NOT use high-dose niacin therapy � for that reason. You have to take very high doses of it to get therapeutic cardiovascular effects. And, it�s not a very comfortable supplement to take--- hot flushes, palpitations, shortness of breath, insomnia, vomiting, abdominal pain, sweating, blurred vision��. If chelation is something you�re interested in, I know many people who have gone through IV EDTA chelation therapy with fantastic results. One doctor that several people have gone to is Dr. Rebecca Roberts, D.O. These were people whose only other option was triple bypass surgery�and it was averted. There are a couple of substances that I know of that are used as oral chelators � penicillamine and oral EDTA. They would both need to be prescribed by an MD. Others can be found in a health food store. They are � garlic, vitaminc, zinc, and the amino acid cysteine. Oral chelation isn�t as quick as IV chelation, but, it has long-term benefits � such as lowering cholesterol, which in turn, has been found to decrease the likelihood of atherosclerosis. Plus, oral chelation offers a continual protection against a stressful and polluted environment. However, if there is already atherosclerotic damage to the vascular system, IV chelation may be the best route to take--- then follow up with the oral therapy. This would all be something you would need to discuss with an MD or OD. Health food stores carry several oral chelation combinations, I believe. Some other things to think about would be your husband�s homocysteine level, lipoprotein A level, C-Reactive protein level, his thyroid function, and his fasting insulin levels. High insulin levels are known to increase the risk and promote atherosclerosis. Alcohol greatly increases insulin. It would also be good to know his fasting blood sugar levels. Thyroid tests that I know are very good diagnostically are the TSH, Free T3, Free T4, Reverse T3, and anti-thyroid antibody test. All those, along with a lipid panel, can give you a very good picture of cardiovascular health and would allow you to work on the cause of the problem � not just treat the symptoms. There are nutritional supplements that are known to reduce homocysteine levels. They are B6, B12, folic acid, and TMG. It has been found that homocysteine is more important than cholesterol in promoting heart disease. It�s the homocysteine that goes through the vascular system and shreds it. Cholesterol is what is used in an attempt to patch up the damage homocysteine does. That�s why it�s automatically assumed that cholesterol is the culprit � but the homocysteine is the problem. It has been found, actually, that niacin may elevate homocysteine levels. NOT GOOD !! Vitamin E and C are also very good at lowering homocysteine. I know of many cardiovascular MDs who send their patients to health food stores to buy homocysteine modulators. Actually, it has been found that it�s unhealthy to have a cholesterol much lower than 200. Cholesterol keeps the vascular system intact. If it goes too low, you risk hemorrhagic stroke. All of the steroidal hormones also come from cholesterol. If it�s too low, then you risk an imbalance in testosterone and DHEA levels ( which normally decrease with age anyhow). Garlic is also a very potent chelator- as I mentioned -and highly beneficial to the heart. The therapeutic dosage is one fresh clove once or twice a day. It thins your blood, so you have to be careful and not already be on blood thinners. (Aspirin thins the blood,too, but also can cause gastric problems.) The best way to take garlic is mash up a clove (at a time when it�s socially acceptable � like before bed, maybe) and mix it with teaspoon or tablespoon of fish oil. I know that sounds awful, but, in the health food stores, you can get a brand that is either lemon or orange flavored. It�s really good. Just mix them and swallow without chewing. The fish oil is another thing that is VERY beneficial for the heart and cholesterol (hence, atherosclerosis ). There has been a lot of research lately on the essential fatty acids especially omega-3. Policosanol and red yeast rice are very good for cardiovascular health, too. It has also been found that supplementing with calcium and magnesium (in a ratio of 2:1 or 1:1) and potassium are beneficial for heart health. If you have inadequate calcium intake, then the body pulls it from the bones and teeth. This is then circulating in the blood stream, and is usually what gets deposited in the arteries and binds to cholesterol deposits. You must take it with magnesium, though. Magnesium in known to be a very potent vaso-dilator. L-carnitine and Co Q10 are also good nutritional supplements for the heart. Using the supplement DHEA has been found to protect against cholesterol oxidation � which is one of the precursors to atherosclerosis � but only if you don�t have an existing cancer. DHEA increases the production of estrogen and testosterone. The estrogen is a growth hormone and promotes tumor growth of any kind. Estrogen is not something that you want a lot of in your body. As mentioned above, the essential fatty acids (fish oil) are great for the cardiovascular system. It is known to reduce fibrinogen, lipoprotein A, C-reactive protein, total cholesterol and homocysteine. It also improves insulin sensitivity. I would try to stay away from any type of vegetable oils � they are omega 6 and can cause inflammatory conditions when out of balance with the omega 3 fish oils. Ginger is an herb that is very good, as is gugulipid, gingko, and hawthorne berry. Olive leaf extract has been found to include beneficial cardiac properties such as antioxidants, antiaggregates, antiarrhythmics, anti-inflammatories, COX inhibitors, diuretics, hypotensives, vasodilators, antihyperlipidimics, and plaque fighters. Vitamin K has been found to modulate calcium levels and reduce arterial calcification. It has been found to keep calcium in the bones and out of the arteries. Another good supplement to take with any medical condition is milkthistle � which is known to be the best or one of the best liver tonic herbs. The liver is responsible for detoxifying everything, so it constantly needs to be helped. Hypothyroidism can cause a very high cholesterol and LDL and increase the risk of cardiovascular disease and adult onset diabetes. No matter what you do to remedy atherosclerosis, if the underlying cause is hypothyroidism, then it�s like banging your head against a wall. It may work for a while, but, it will come back. There are many good supplements that can help improve a sluggish thyroid or help it do it�s job a little better. It�s always better to try to get the thyroid to do it�s job by supporting it nutritionally or with supplements. But, in many instances, if it doesn�t respond to natural therapies, the only option is to take a small amount of natural desiccated thyroid hormone. This would need to be prescribed by an MD and, in most cases, they prescribe a synthetic thyroid drug called Synthroid. This is something I don�t recommend as it only contains synthetic T4 which is not the active thyroid hormone. The natural desiccated thyroid contains both T3 � which is the active hormone � and T4 plus a little T2 and T1. A few of the natural thyroid hormones are Armour, Nature-throid, and West-throid. A lot of times if you can correct the thyroid, the cholesterol (and atherosclerosis) will leave. At least it won�t get worse. Chelation might be the only way to �clean out� the arteries. This is just what I�m thinking right now. If your husband is taking any type of cardiovascular drugs, you must be very careful with taking any supplements. The interaction between drugs and supplements, in this case, could be very drastic. Not knowing anything about your husband, I can�t say what would be best or what he should not do. Remember too, that nutrition plays a very big role in health. You can take all the supplements or drugs in the world, but if you are eating foods that are causing problems, relief may be short-lived. There is not one set diet that anyone should use for any certain disorder. Before I work with any client, I find out their blood type. My protocols are based around biochemical individuality � of which blood type is a great marker. I hope this gives you something to think about or helps in some way. If you have any other questions or I can help in any other way, please don�t hesitate to call. I see clients out of Lakewood Ranch Spine and Sport in the plaza with Publix. Good luck, Sue