Maybe Cholesterol Isn't The Cause Of All The Heart Disease
I would like to bring some very important information to your attention: research that needs to be given to us, the general public who has made such a fuss about cholesterol. This excerpt comes from a newsletter by Dr. Ray Strand
http://www.raystrand.com
The complete version of this newsletter is included
below this introduction.
Homocysteine is a by-product of protein metabolism. Our bodies need protein to live and one of the essential proteins (amino acids) is called methionine. This protein is found in large quantities in our meats, eggs, milk, cheese, white flour, canned foods, and highly processed foods. Our body needs this essential amino acid to survive; however, as you can see from the list of foods that contain large quantities of this nutrient, we are not deficient in it. When methionine is utilised in our bodies, it is broken down into homocysteine, which in turn is changed into either cysteine or back to methionine again. Cysteine and methionine are benign products and are not harmful in any way. However, the enzymes needed to break down homocysteine into cysteine or back to methionine need folic acid, vitamin B12, and vitamin B6 to function at their optimal levels. If we are deficient in these nutrients, the blood levels of homocysteine begin to rise. Many researchers now believe that elevated levels of homocysteine in our blood are directly related to deficiencies of folic acid, vitamin B6, and vitamin B12 in our bodies. In other words, increased homocysteine levels are primarily due to a nutritional deficiency. When these nutrients are given in supplementation, these homocysteine levels fall significantly within just a few weeks.
Well, there are really two sides to this problem. One is the amount of methionine in your diet that your body is required to metabolize and break down. This requires becoming careful with the amount of meat and dairy products you are consuming. Isn’t it interesting that these are the same foods that are high in saturated fat and cholesterol? Elevated homocysteine is now being incriminated in other diseases as well. The most recent studies have shown the significant elevation of homocysteine in patients with dementia, especially Alzheimer’s dementia. Studies are also showing an increased risk of inflammatory bowel disease, cancer, and many other diseases in patients with elevated homocysteine levels.
Here is a quick (and VERY simplistic) lesson on
cholesterol: HDL & LDL This may help you to remember
which is which. Picture a big, hollow, empty cement
culvert (your blood vessel). Along comes cars (blood
cells) carrying some HDL: high density cholesterol. The
BMW drives very fast…so fast that nothing can catch it
and it's gone before you know it's been there. Now along
comes a clunker, with a load of low density cholesterol.
It chugs along, and everything sticks to it. It's fat
and not nice, whereas the BMW with its HDL is clean and
quick. Which do you want?
Dr Ray Strand's Bionutrition Newsletter
January/February 2002
Homocysteine
Have you ever heard of homocysteine before? Or better yet, have any of you had your doctor recommend a blood test to check your personal homocysteine level? After reading this chapter, I am sure that you will wonder why your doctor has not performed this test on you. Homocysteine is as important as cholesterol when it comes to cardiovascular disease; however, very few patients have ever heard about it or even know what it is. It is estimated that elevated homocysteine levels in your blood, by itself, is responsible for approximately 15% of every heart attack and stroke in the US and world today. That would mean 225,000 heart attacks and 24,000 strokes each year in the US along with 9 million people who have cardiovascular disease are directly the result of elevated homocysteine in your blood. I believe that there is some value in learning more about this major killer, especially when you realize that it can be corrected by taking some B vitamin supplements for pennies a day.
Dr. Kilmer McCully was a promising pathologist, researcher who graduated from Harvard Medical School in the mid 60’s. He landed a prestigious position as an Associate Pathologist at Massachusetts General Hospital and Assistant Professor of Pathology at Harvard Medical School. He was known in his hometown in Colorado as the "boy scientist." He had always enjoyed research that involved the connection of biochemistry with disease. Early in his career he was fascinated with a couple of cases involving young children who had a rare genetic disease called homocystinuria. These children did not posses the enzymes necessary to break down an essential protein called methionine. This caused a severe elevation of a by-product called homocysteine. In both cases the cause of death was because of severe atherosclerosis (hardening of the arteries). In fact, most of these children with homocystinuria do not live to become teenagers because they die from either a heart attack or stroke. Dr. McCully reviewed the autopsy findings and slides and determined that the arteries in these children appeared very much like an elderly man’s arteries that had severe atherosclerosis. However, these same changes in their arteries were noted in infants and young children who had homocystinuria. This led Dr. McCully to wonder whether mild to moderate elevations of homocysteine over a lifetime could be the cause of heart attacks and strokes in the average patient.
Dr. McCully reported his theory in several medical journals in the late 60’s and early 70’s and was initially met with some enthusiasm. Dr. Benjamin Castle, the chief of his department, supported Dr. McCully and showcased his work before a prestigious panel of experts. However, by the mid 70’s, the homocysteine theory had lost momentum, which in a large part was due to a new department chief, Robert McCluske. His funding and support were cut, and he was moved to an inferior lab in the basement. Since much of the funding for his research came from outside the institutions, Dr. McCully was forced to seek more funding on his own or close his doors. The key issue for Dr. McCully was money, and he was out. Discouraged and disappointed with the lack of support from fellow researchers and the inability to obtain further grants, he gave up. Dr. McCluske had already told him that Harvard was not going to support his research anymore because he had not proven his theory.
Since his position at Harvard Medical School and Massachusetts General Hospital went hand in hand, both jobs formally ended January 19, 1979. Around the same time, a former classmate at Harvard who went on to become the director of the Arteriosclerosis Center at M. I. T. attacked his ideas as "errant nonsense" and a "hoax that is being perpetrated on the public." The director of public affairs at Massachusetts General also informed Dr. McCully that he did not want him associating his "theories" with Harvard or Mass. General. Kilmer McCully’s hypothesis clearly challenged the cholesterol-heart attack theory, which was gaining tremendous momentum at about the same time. All future research into the prevention of heart disease was aimed at the cholesterol theory of heart disease. McCully was out the door, and it had been closed loudly behind him.
Dr. McCully was certainly ahead of his time. But why the hostility toward a man who was simply trying to find the underlying cause of the number one killer in today’s world. To add insult to injury, Dr. McCully could not find another job. With his need to support his family and children who were now reaching college age, he frantically looked for a new job. A pattern soon became apparent to Dr. McCully. His new potential boss would initially meet him with enthusiasm, only to have the job offer turned down later. This went on for over two years. Finally, he heard rumors of "poison phone calls" from Harvard. Eventually he went to a friend of his who was a prominent lawyer in Boston. After his friend had made a few phone calls, it was over. Dr. McCully had landed a job as a pathologist at the Veterans Affairs Medical Center in Providence, RI. His primary responsibility was for the practice of anatomic and clinical pathology in the care of US veterans. His research had to take a back seat; however, he was now at least able to support his family.
Dr. McCully was certainly ahead of his time. However, as you will learn later, he was right on track. Dr. Thomas James, a cardiologist and president of the University of Texas Medical Branch who was also the president of the American Heart Association in 1979 and 1980 was quoted as saying, "It was worse because you couldn’t get ideas funded that went in other directions than cholesterol. You were intentionally discouraged from pursuing alternative questions. I’ve never dealt with a subject in my life that elicited such an immediate hostile response."
Renewed Interest in Homocysteine
In 1990, Meir Stampfer, a Professor of Epidemiology and Nutrition at the Harvard School of Public Health, revived the interest in homocysteine. He looked at the blood levels of homocysteine in 15,000 physicians who were involved in the Physician's Health Study. Stampfer reported even mildly elevated levels of homocysteine were directly related to an increased risk of developing heart disease. Those men who had the highest level of homocysteine had three times the risk of developing a heart attack when compared with those who had the lower levels. This was the first large study that showed the possibility that homocysteine might be an independent risk factor for heart disease. This was a major turning point, and the interest in McCully's original theory was revitalized.
Dr. Jacob Selhub reported in the New England Journal of Medicine in February of 1995 that high plasma levels of homocysteine were directly related to an increased risk of carotid artery stenosis (narrowing of the two main arteries supplying blood to the brain). He also noted that most of these patients with high homocysteine levels also had low levels of folic acid, vitamin B12, and vitamin B6 in their body. The higher the level of homocysteine in their blood, the greater the stenosis of the carotid arteries. Another large prospective study out of Tormso, Norway, showed the higher the homocysteine level, the greater the risk of developing a heart attack. What were once considered normal levels for homocysteine were now being shown to be dangerous. Homocysteine seemed to be as strong of a risk factor as cholesterol, hypertension, and smoking. Of even more concern was the fact that when elevated levels of homocysteine were found in patients who also had one or more of these other major risk factors (hypertension, elevated cholesterol, or smoking), the risk of vascular disease increased dramatically. It is evident that the lower our homocysteine level, the better. In the Journal of the American Medical Association, Boushey and associates reviewed 27 previously published studies relating homocysteine to various forms of vascular disease. These authors concluded increasing levels of homocysteine was an independent risk factor for coronary artery disease, stroke, and peripheral vascular disease. They also reported the overwhelming majority of these patients who had elevated levels of homocysteine also had nutritional deficiencies of folic acid, vitamin B6, and vitamin B12. These authors estimated 10 to 15 percent of every heart attack and stroke in this country was caused by elevated homocysteine levels alone.
There was not only renewed interest in Dr. McCully’s theory but now it was becoming a fact that homocysteine was indeed an independent risk factor for cardiovascular disease. Even the old-line supporters of the cholesterol camp like Claude Lenfant, director of the National Heart, Lung and Blood Institute was quoted as saying, "If the risk of elevated homocysteine is not entirely proven, it is an extremely important area of research." Over the past 5 years, the medical evidence is beyond dispute--homocysteine is an independent risk factor for coronary artery disease, stroke, and peripheral vascular disease.
What Is Homocysteine Anyway?
I am sure by now you are asking yourself, "What is homocysteine anyway?" Homocysteine is a by-product of protein metabolism. Our bodies need protein to live and one of the essential proteins (amino acids) is called methionine. This protein is found in large quantities in our meats, eggs, milk, cheese, white flour, canned foods, and highly processed foods. Our body needs this essential amino acid to survive; however, as you can see from the list of foods that contain large quantities of this nutrient, we are not deficient in it. When methionine is utilized in our bodies, it is broken down into homocysteine, which in turn is changed into either cysteine or back to methionine again. Cysteine and methionine are benign products and are not harmful in any way. However, the enzymes needed to break down homocysteine into cysteine or back to methionine need folic acid, vitamin B12, and vitamin B6 to function at their optimal levels. If we are deficient in these nutrients, the blood levels of homocysteine begin to rise. Many researchers now believe that elevated levels of homocysteine in our blood are directly related to deficiencies of folic acid, vitamin B6, and vitamin B12 in our bodies. In other words, increased homocysteine levels are primarily due to a nutritional deficiency. When these nutrients are given in supplementation, these homocysteine levels fall significantly within just a few weeks.
Homocysteine is very irritating to the fine lining of the artery called the endothelium as you learned last chapter. One of the primary problems is the fact that it increases endothelial dysfunction. Scientific research has shown us that the underlying mechanism for this injury is oxidative stress. It is a major cause of inflammation to the artery. It also has been shown to increase the oxidation of LDL cholesterol, decreases the production of nitrous oxide (this in turn causes artery spasm and endothelial dysfunction), proliferation (increase in the size and amount--narrowing the artery further) of the smooth muscles in the artery, and increases clot formation. None of these effects on the artery are good. This is why you see children with congenital homocystinuria never seeing their teenage years. Their vessels are so inflamed that the process of atherosclerosis is accelerated beyond belief. This is why even a mild elevation of homocysteine in your blood is so dangerous. The amazing reality is the fact that all of these devastating changes in our arteries are totally reversed when our homocysteine levels are lowered by consuming folic acid, vitamin B6, and vitamin B12. Unlike cholesterol, which the body needs for the production of certain cell parts and hormones, homocysteine provides no health benefit. The higher the level of homocysteine is, the greater the risk of cardiovascular disease. On the contrary, the lower the level of homocysteine, the better. There is no threshold below which homocysteine becomes okay. You want your homocysteine level as low as possible.
Most labs will report the normal range of homocysteine levels between 5 to 15 micromols/L. However, the medical literature finds that when this level rises much above 7 micromols/L there begins an increased risk of developing cardiovascular disease. Most patients are going to want to have homocysteine levels below 9 and if it gets above 12, you are in serious trouble. Whenever there is a new entity or risk factor that develops, the testing standards are far behind. This happened with cholesterol and will happen with homocysteine. So don’t be pacified by your physician, who might tell you that having a homocysteine level of 13 or 14 falls well within the normal range and you should not worry. I remember when the normal range of cholesterol was from 140 to 320 as late as 1975. You want to get your homocysteine level down to at least 9 if you have no sign of cardiovascular disease and below 7 if you already have evidence of cardiovascular disease.
How Do I Lower My Patient’s Homocysteine Level?
Well, there are really two sides to this problem. One is the amount of methionine in your diet that your body is required to metabolize and break down. This requires becoming careful with the amount of meat and dairy products you are consuming. Isn’t it interesting that these are the same foods that are high in saturated fat and cholesterol? Obviously, we need to replace these foods with more fruits and vegetables as well as vegetable protein. I realize that methionine is an essential amino acid; however, in the American and Western diet we will never be short changed and not get enough.
The other side of the coin is providing enough folic acid, vitamin B6, and vitamin B12 in order that the enzyme systems needed to break down homocysteine can work effectively. It is interesting to note that all of the studies that have shown the harmful aspects of elevated homocysteine have also shown the depleted levels of these B vitamins. I recommend that all of my patients take 1000 mcg of folic acid, 50 to 100 mcg of vitamin B12, and 25 to 50 mg of vitamin B6. This level of supplement is provided in the Usana Essentials. Remember, the lower the homocysteine level the better. I want to see everyone’s homocysteine level below 7 if at all possible. When my patients have an initial homocysteine level above 9, I will start them on supplemental B vitamins and recheck their blood level within 6 to 8 weeks. With this B vitamin regime, homocysteine levels will tend to fall somewhere between 15% and 75%. However, not all homocysteine levels will respond adequately to just the B vitamins. This is an indication to me that these patients simply have an overall problem with "methylation." Methylation deficiency is now felt to be one of the major underlying problems in some of our major chronic degenerative diseases, especially some cancers and Alzheimer’s dementia. When this happens we need to provide the body with what are becoming known as "methyl" donors. The least expensive "methyl" donor, which has an excellent effect on homocysteine levels, is called betaine or trimethylglycine (TMG). If the homocysteine have not come down to the desired level, I add between 1 to 5 grams of TMG daily (you would need to get this from the local health food store) to the supplemental B vitamins in order to bring the homocysteine down to respectable levels. Many studies have tried to increase the folic acid up to 5000 mcg in this situation in an attempt to bring down these resistant elevated homocysteine levels. However, I have not found it very effective to increase the folic acid above 1000 mcg. It is much easier to add a little TMG to the patient's supplement program and the results are usually much better. TMG is able to provide the "methyl group" needed to more efficiently lower homocysteine.
The Cholesterol Theory versus the Homocysteine Theory
You see a lot of concern in the medical literature about how these two theories of heart disease relate to one another. However, once you understand that the underlying cause of atherosclerosis or hardening of the arteries is inflammation caused by oxidative stress, it becomes clearer. Remember, atherosclerosis is an inflammatory disease. The greatest causes of inflammation are free radicals, "oxidized" cholesterol, and homocysteine. The oxidative stress created by these products damages the endothelium, promotes chronic inflammation in the artery, and leads to narrowing of the artery by muscle proliferation and plaque formation. Homocysteine damages the endothelium and creates increased "oxidized" LDL cholesterol. The "oxidized" LDL cholesterol collects in the monocyte white cell, which then becomes the foam cell. This inflammatory process produces more "oxidized" LDL cholesterol and attracts more white cells to the subendothelial space. In short, this is a vicious cycle. Our goal then is to attempt to break up this cycle. This is accomplished by:
Lowering LDL cholesterol first through diet and exercise. The lower the amount of native LDL cholesterol, the less LDL cholesterol available to become "oxidized." If diet and exercise are not enough to bring this down to acceptable level, cholesterol-lowering drugs may be needed.
Optimal nutritional supplementation, which should include all the various antioxidants and their supporting nutrients, which includes the level of B vitamins mentioned above. This allows you to build up your body’s natural antioxidant defense system as well as providing adequate B vitamins to completely metabolize and thus lower homocysteine levels.
Aggressively treat any disease process that increases oxidative stress--high blood pressure, diabetes, obesity, cigarette smoking, etc.
By attacking all sides of this disease, the underlying inflammatory process can be significantly reduced or even prevented. When patients in my office present more than one risk factor for heart disease, the rate at which this process develops accelerates significantly. That is why I cringe whenever I see a diabetic patient walk into my office that has hypertension, elevated cholesterol, elevated homocysteine levels, and is a smoker. The medical literature has shown us that when you start adding up risk factors for heart disease 1 plus 1 is not 2 but 6 or 8 or 10. Smoking is known to cause more oxidative stress than any other toxin. Diabetics will modify their "oxidized" LDL cholesterols even more by attaching a sugar molecule to it. This makes the "oxidized" LDL cholesterol even more atherogenic. This may be the main reason that 80% of our diabetics will die from a cardiovascular disease. All of these risk factors for coronary artery disease--hypertension, smoking, diabetes, elevated cholesterol, insulin resistance, elevated homocysteine, obesity--increase the number of free radicals our bodies produce, therefore increases oxidative stress, which in turn increasing inflammation in our arteries.
You can now appreciate why over half the people who suffer heart attacks have normal cholesterol levels. Heart disease is simply not a disease of cholesterol--it is an inflammatory disease. So why did it take 25 years after Dr. McCully presented his hypothesis on homocysteine for the medical community to pay attention to it? Dr. Charles Hennekens, a professor at Harvard Medical School and chief of preventive medicine at Brigham and Women’s Hospital, cites the example of aspirin. "For years now, we’ve known about these large benefits of aspirin in treating (patients) who have suffered an acute heart attack and survivors of heart attacks, and yet we have underutilization of it." he says. "At an F.D.A. advisory committee meeting recently, I joked that if aspirin were half as effective, 10 times as expensive and on prescription, maybe people would take it more seriously." Well, at least the pharmaceutical companies would take it more seriously and they would definitely share those health benefits with the doctors. Like aspirin, the B vitamins needed to control homocysteine levels are readily available and inexpensive. "It’s inescapable that there’s just not the commercial interest for supporting research in homocysteine," Dr. Meir Stampfer says, "because nobody’s going to make money on it."
Was this the underlying reason that Dr. Kilmer McCully lost his research funds and lost his job at Harvard? Just look at the amount of money that has been made by the medical community and the pharmaceutical industry by lowering your cholesterol. It has been simply billions and billions of dollars each and every year. Who has educated you about the risk of high cholesterol? Who is taking out that full-page ad in the USA Today to tell you the importance of lowering your cholesterol. Why hasn’t someone taken out a TV or newspaper ad to inform you about the importance of lowering your homocysteine? Who is going to make money off of vitamin B12, vitamin B6, and folic acid? Sad to say, you begin to see the "Economics of Medicine." Dr. McCully takes his own follow the money approach: who stands to gain? "The most dramatic improvements in longevity over the last couple of hundred years have been through public health, not through medicine," he says. "But public health is notoriously unprofitable. People don’t make a profit preventing disease. They make a profit through medicine--treating critical, advanced stages of disease."
A Public Health Issue
The U.S. Food and Drug Administration has realized that folic acid deficiency in our diet is a public health issue. In January 1998, the FDA mandated that all food products made with cereal or flour must be fortified with 140 micrograms of folic acid for every 100 grams of flour. This was primarily done as a way to prevent neural tube defects in our children. It has been well documented that mothers who are taking folic acid in supplementation prior to becoming pregnant actually decrease their risk of having a baby with a neural tube defect (hydrocephalus or spina bifida) by over 70%. A study reported by the NEJM in 1998 also looked at how fortified cereals reduced homocysteine levels in patients with coronary artery disease. This study showed that homocysteine levels were decreased on an average of 3.4%, which is basically insignificant.
There is still one unanswered question when it comes to the issue of homocysteine. Does lowering your homocysteine level truly decrease your risk of developing cardiovascular disease? Most physicians will claim that they have a wait and see attitude about homocysteine. This means they are waiting until clinical trials are completed that will hopefully answer this question. There are three major studies presently in progress, which are the Vitamin Intervention for Stroke Prevention trial, the Women’s Antioxidant Cardiovascular Disease Study, and the Heart Outcomes Prevention Evaluation. However, Dr. Andre Bostom reported a perspective in the Annuals of Internal Medicine voicing his concern that these clinical trials are already being undermined by the FDA’s decision to fortify cereals. The control group will end up getting more folic acid than these studies had originally planned. He feels that these studies will lower their expected treatment effects by about 20 to 25% because they are now being compared to a control group that is getting more folic acid. He concludes that these studies will be underpowered to substantially test the specific hypotheses that lowering homocysteine will decrease the risk of developing cardiovascular disease. After reading this chapter, would you rather be in the control group or the treated group? I am afraid that it will be years before this question is answered in any definitive way.
However, this did not stop a group of researchers from projecting the potential cost savings if vitamin B supplements were given to patients with known coronary heart disease. This study was reported in the August 22, 2001 issue of the JAMA (Journal of the American Medical Association). These researchers projected that if everyone with coronary heart disease took vitamin B supplements that there would be 310,000 fewer deaths over a ten-year period of time. There could be even greater cost savings if all male patients over 45 and all women over 55 took vitamin B supplements. Obviously, these researchers also took into account the fortification of our cereals. We are just beginning to realize the cost-effectiveness and cost savings we would realize if everyone was taking nutritional supplements.
Elevated homocysteine is now being incriminated in other diseases as well. The most recent studies have shown the significant elevation of homocysteine in patients with dementia, especially Alzheimer’s dementia. Studies are also showing an increased risk of inflammatory bowel disease, cancer, and many other diseases in patients with elevated homocysteine levels. Let me ask you a simple question. Would you rather have a high or low homocysteine level? Are we going to wait another 25 years to answer the question of whether there is a health benefit of lowering your homocysteine level? I don’t know about other physicians but I am checking homocysteine levels on all my patients routinely.
Dr. Kilmer McCully--The Conclusion
Michael Stacey wrote a story in the August 10, 1997 issue of the New York Times Magazine. He titled his story, "The Fall and Rise of Kilmer McCully." He ends this story with an interesting perspective:
McCully reveals, briefly, the shadow of disappointment that must have loomed larger two decades ago. "Last October," he says, "the pathology department at Mass. General had a reunion and invited me, and I saw one of the people involved in my leaving the department. "Well," he said to me, "it looks like you were right after all." It’s 20 years later. My career is almost over. There’s really not much that can be done about 20 lost years, is there?"
Worse, the political and economic forces that undid McCully back then may be more intense today. Last April, The New England Journal of Medicine published an article titled "The Messenger Under Attack--Intimidation of Researchers by Special-Interest Groups," which detailed three cases of harassment by advocacy groups, physicians’ associations or academic consultants who often failed to disclose their close ties to drug companies. With more and more pressure groups weighing in on what research gets financed and promoted, the article said, "Such attacks may become more frequent and acrimonious."
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The information shared on these web pages is for educational purposes only. Every effort has been made to make this web page as accurate as possible. It is the review of scientific evidence and my personal clinical experience in using nutritional supplements. This information is not intended for self-diagnosis, treatment, or the justification for accepting or declining any medical treatment for any health problems or diseases. Any application of the information presented in these web pages is at the reader's own discretion. Therefore, any individual who has a specific health problem should consult his or her health care provider licensed in his or her state of residence before starting any nutritional program.
Users of this web site shall not hold Dr. Strand, or any associated persons or entities, liable for any use or misuse relating to the information provided. This information is provided to the general public and it is the sole responsibility of persons using this information to consult with his or her health care provider licensed in his or her state of residence prior to using this information.
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Ray Strand, M.D.
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