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Preventing Degenerative Disease - Heart Disease/Stroke - Diseases of the Heart Muscle - Homocysteine

Homocysteine - Dr. Ray Strand
Coenzyme Q10

HAVE YOU EVER HEARD OF HOMOCYSTEINE? OR BETTER YET, HAS your doctor ever recommended a blood test to check your personal homocysteine level' Probably not. After reading this chapter I guarantee you will wonder why. Few people have ever heard of this substance, and fewer still realize that it poses just as great a threat as cholesterol when it comes to cardiovascular disease.

It is estimated that by itself, an elevated homocysteine level in the blood is responsible for approximately 15 percent of all the heart attacks and strokes in the world today-that means 225,000 heart attacks and 24,000 strokes each year in the U.S. In addition are the 9 million people who have cardiovascular disease as a direct result of elevated homocysteine levels.' Needless to say, I believe there is great value in learning more about this major killer, especially when you realize that you can correct it simply by taking B vitamin supplements.

What is Homocystein?

The history of homocysteine research is a fascinating one, beginning with the career of Dr. Kilmer McCully. A promising pathologist and researcher who graduated from Harvard Medical School in the mid-1960s, Dr. McCully enjoyed studies that involved the connection of biochemistry with disease. His reputation was strong, and he soon landed prestigious positions as an associate pathologist at Massachusetts General Hospital and as an assistant professor of pathology at Harvard Medical School.

Early in Dr. McCully's career, he became particularly interested in a disease called homocystinuria. This presented itself in children who had a genetic defect that kept them from breaking down an essential amino acid called methionine. These children showed a tremendous buildup of a by-product called homocysteine. McCully reviewed two separate cases involving young boys with this defect who died of heart attacks. This was quite amazing, since both of these boys were not even eight years old. When he examined the boys' pathology slides, he discovered that the damage to the arteries was eerily similar to that of an elderly man who had severe hardening of the arteries. This led Dr. McCully to wonder whether mild to moderate elevations of homocysteine that were present over a lifetime could be a cause of heart attacks and strokes in the average patient.2

As seen in the case of the two boys, homocysteine is an intermediate byproduct that we produce when our bodies metabolize (break down) an essential amino acid called methionine. Methionine is found in large quantities in our meats, eggs, milk, cheese, white flour, canned foods, and highly processed foods. Our bodies need methionine to survive; however, as you can see from the list of foods that contain large quantities of this nutrient, we in the U.S. have plenty of it. Our bodies normally convert homocysteine into either cysteine or back to methionine again.

Cysteine and methionine are benign products and are not harmful in any way. But here is the catch: the enzymes needed to break down homocysteine into cysteine or back to methionine need folic acid, vitamin B12, and vitamin B6 to do their job. If we are deficient in these nutrients, the levels of homocysteine in the blood begin to rise.

So why haven't we heard of this before? We must turn back to Dr. Kilmer McCully.

Right Stuff-Wrong Era

McCully reported his homocysteine theory in several medical journals in the late sixties and early seventies and was initially welcomed with great enthusiasm. Dr. Benjamin Castle, the chief of his department, fully supported Dr. McCully and showcased his work to a prestigious panel of experts. But by the mid-seventies, the homocysteine theory had lost most of its momentum.

Dr. Castle retired, and the new chief of the department asked Dr. McCully to seek his own research funding or to leave. His lab was moved into the basement. McCully fought long and hard, but eventually time and money ran out:

in 1979 the new department chief informed Dr. McCully that Harvard was terminating him because his theory about homocysteine and heart disease had not yet been proven.3

Since McCully's positions at Harvard Medical School and Massachusetts General Hospital went hand in hand, he lost both jobs inJanuary of 1979. A former classmate from Harvard who was then the director of the artenosclerosis center at MIT labeled McCully's ideas "errant nonsense" and a "hoax being perpetrated on the public."3 Soon the director of public affairs at Massachusetts General also asked Dr. McCully not to associate his homocysteine theories with the hospital or with Harvard.4 McCully was shut down for good.

Dr. Kilmer 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? What was the motive for such pessimism and verbal attacks? Could the heavily funded research on cholesterol at the time have been the reason?

At that time the cholesterol-heart attack theory was gaining tremendous momentum, and Kilmer McCully's hypothesis clearly challenged its future. Dr. Thomas James, cardiologist, president of the University of Texas Medical Branch, and the president of the American Heart Association in 1979 and 1980, said, "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."5

With all opposing theories silenced, the cholesterol theory went great guns. Drug companies began making their billions, and everyone was convinced that heart attacks and strokes were simply the result of too much cholesterol in the bloodstream. Wouldn't you say they did an excellent job in selling this to the medical community and to the general public?

Renewed Interest in Homocysteine

In 1990 Dr. Meir Stampfer revitalized interest in Dr. McCully's homocysteine theory. A professor of epidemiology and nutrition at the Harvard School of Public Health, Stampfer looked at the blood levels of homocysteine in fifteen thousand physicians who were involved in a health study. Dr. Stampfer reported that even mildly elevated levels were directly related to an increased risk of developing heart disease. Those men who had the highest levels of homocysteine experienced three times the risk of developing a heart attack when compared with those who had the lowest levels.6 This was the first large study that showed the possibility of homocysteine as an independent risk factor for heart disease.

In February 1995 Dr. Jacob Selhub also reported in the New England Journal of Medicine that high plasma levels of homocysteine were directly related to an increased risk of carotid artery stenosis (the narrowing of the two main arteries supplying blood to the brain). In addition Selhub noted that most patients with high homocysteine levels also had low levels of folic acid and vitamins B12 and B6 in their bodies.7

Another large case-control study, The European Concerted Action Project, indicated that the higher the homocysteine level, the greater the risk of developing a heart attack.8 What were once considered normal levels for homocysteine were suddenly becoming recognized as very dangerous levels.

Of even more concern to the researchers was the fact that when they found elevated levels of homocysteine in patients who also had one or more other major risk factors (hypertension, elevated cholesterol, or smoking), the risk of vascular disease increased dramatically. The results of these clinical trials provided evidence that the lower our homocysteine levels are, the better.

Suddenly researchers accepted as fact that homocysteine was indeed an independent risk factor for cardiovascular disease. Even the old-line supporters of the cholesterol camp, such as Claude L'enfant, director of the National Heart, Lung and Blood Institute, said, “even if the risk of elevated homocysteine is not entirely proven, it is an extremely important area of research."9 Today the medical evidence is beyond dispute: homocysteine can help cause coronary artery disease, stroke, and peripheral vascular disease

Show Me the Money! The Economic Powers of Medicine

You can now appreciate why more than half the people who suffer heart attacks have normal cholesterol levels. Why did it take twenty-five years after Dr. McCully presented his hypothesis on homocysteine for the medical community to pay attention? Dr. Charles Hennekens, a professor at Harvard Medical School and chief of preventive medicine at Brigham and Women's Hospital, cites a parallel example. "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 FDA advisory committee meeting recently, I joked that if aspirin were half as effective, ten 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. The situation here is similar. Like aspirin, at a cost of pennies a day vitamin B supplements can effectively lower the majority of elevated homocysteine levels. "It's inescapable that there's just not the commercial interest for supporting research in homocysteine," Dr. Stampfer says, "because nobody's going to make money on it.""

Take a look at the amount of money the medical community and the pharmaceutical industry have made by lowering cholesterol with synthetic drugs. Billions and billions of dollars roll in each and every year. Have you ever considered who educated you about the risk of high cholesterol? Who is taking out that full-page ad in USA Today to tell you the importance of lowering your cholesterol? Pharmaceutical companies. Why hasn't someone taken out a TV or newspaper ad to inform you about the importance of lowering your homocysteine? There is not nearly as much money to be made in the sale of vitamin B12, vitamin B6, and folic acid. Sad to say, we are caught in the ripple effects of the economics of medicine. Could this possibly have been the underlying reason that Dr. Kilmer McCully lost his research funds and his job at Harvard?

Dr. McCully takes his own follow-the-money approach, asking who stands the most to gain by not educating people about the dangers of homocysteine. "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."'7

Is There a Healthy Level of Homocysteine?

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, the greater the risk of cardiovascular disease. Conversely, the lower the level of homocysteine, the better. There is no threshold below which homocysteine becomes okay. You want your homocysteine level to be as low as possible.

Most labs will report the normal range of homocysteine levels between five and fifteen micromols/L (micromols per liter of blood). The medical literature finds that when this level rises much above seven micromols/L, however, an increased risk of developing cardiovascular disease becomes apparent. Most patients will want homocysteine levels below seven. If your level rises above twelve, you are in serious trouble.

Whenever the medical community discovers a new entity or risk factor, testing standards lag far behind. This happened with cholesterol and will happen with homocysteine. Therefore, do not be pacified by your physician, who might tell you that having a homocysteine level of ten or eleven falls well within the normal range and not to worry. You want to get your homocysteine level down to at least nine if you have no sign of cardiovascular disease; and below seven if you already have evidence of cardiovascular disease or have other risk factors of heart disease.

How Do I Lower My Homocystein Level?

There are really two sides to this problem of high homocysteine levels. One is the amount of methionine in your diet that the body has to metabolize and break down. This requires that you become 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 diet, we will always get more than enough.

The other side of the coin is providing enough folic acid, vitamin B6, and vitamin B 12 so that the enzyme systems needed to break down homocysteine can work effectively. It is interesting to note that all studies that have shown harmful aspects of elevated homocysteine have also shown depleted levels of B vitamins. I recommend that all of my patients take 1,000 mcg (micrograms) of folic acid, 50 to 150 mcg of vitamin B12, and 25 to 50 mg (milligrams) of vitamin B6.

Remember, the lower the homocysteine level, the better. I want to see everyone's level below seven if at all possible. When my patients have an initial homocysteine level above nine, I start them on supplemental B vitamins and recheck their blood level within six to eight weeks. With this B-vitamin regime, homocysteine levels tend to fall somewhere between 15 and 75 percent. But

not all patients will respond adequately to just the B vitamins. This is an indication to me that these patients simply have an overall problem with methylation, the biochemical process used by the body to reduce homocysteine to benign or non-harmful products in the body.

Methylation Deficiency

Methylation deficiency is responsible not only for elevated homocysteine levels but is also one of the key underlying problems in some of our major chronic degenerative diseases, especially some cancers and Alzheimer's dementia. In fact as I am wnting this chapter, a study has just reported that a new test has been discovered for determining who may be at higher risk of developing Alzheimer's dementia. I read the results of this study with great anticipation. Can you guess what the new test checks? Yes-the homocysteine blood level.'3 We have been doing this test in my office for the last several years because it points out the fact that elevated homocysteine levels are not only an indicator of vitamin B deficiency but also serve as an indicator for decreased levels of "methyl" donors in our body. Methyl donors are not only necessary to decrease homocysteine levels in the body, but they also produce important nutrients needed by the brain.

The least expensive methyl donor, which has an excellent effect on homocysteine levels, is called betaine or trimethylglycine (TMG). If the homocysteine level has not come down to the desired level, I add 1-5 g of TMG to the daily supplemental B vitamins.

Dr. Kilmer McCully: The Conclusion

A story was published on August 10, 1997 in the New York Times Magazine entitled "The Fall and Rise of Kilmer McCully." It detailed the end of his story and offered an interesting perspective to our concerns here:

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?”14

Worse, the political and economic forces that undid McCully back then may even 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.'''5

McCully knew the dangers of homocysteine. I'm sure he also knew that taking B vitamins in supplementation is not only inexpensive insurance against these dangers but safe as well. He was up against a political giant. But the truth is now clear. We are left to wonder why are doctors are still so reluctant to check their patients' homocysteine levels and why they are not recommending B vitamins to all of their patients. What your doctor doesn't know may be killing you. Especially when you consider the fact that homocysteine is an important, if not a greater, risk factor for heart disease than cholesterol.

Ultra-sensitive CPP

As the medical community begins to realize that coronary artery disease is decidedly an inflammatory and not a cholesterol disease. more clinical studies are appearing in the medical literature advising physicians of effective ways to evaluate patients. Several studies have looked at various products in the body that give us evidence of the amount of inflammation that is present in the arteries.

One such highly preferred blood test is the highly sensitive C Reactive Protein (hs CRP). This test measures the arterial inflammation currently present. This test is actually a better predictor of who is going to develop heart disease than a cholesterol level is. Why shouldn't it be? In fact doing highly sensitive CRPs allows the physician to identify those patients who have normal cholesterol levels and may still be at increased risk of developing cardiovascular disease.

Homocysteine Blood levels

Checking patients' fasting homocysteine blood levels is not only easy but also critical in determining whether they are problematic or not. Hopefully, as the test becomes more standardized between labs it will become more affordable. Presently, a serum homocysteine level test costs between S45 and S150.

Heart Calcification Scores

Most medical centers have now made modifications to their CT scanners so they can determine the amount of calcification.or plaque buildup, present in coronary arteries. This is a simple, noninvasive procedure, but its cost usually ranges between S250 and S600. I recommend this test for all patients with significant risk factors for or a strong family history of heart disease.

If the test does show calcifications. it gives a doctor some feel for how serious the problem is and how aggressively to treat the patient. Remember, more than 30 percent of the time the first sign of heart disease is sudden death. I have found this tool to be very helpful and motivating for my patients.


I challenge you to ask your personal physician to perform one or all of these tests on you. You may want to check with your insurance company first to make sure these tests are covered. Along with traditional chemistry profiles and cholesterol panels, these help determine which patients are at increased risk of developing cardiovascular disease. Obviously, it should be every doctor's focus to prevent or slow down this process in his patients so that they never have to end up in the surgeon's hands. Doesn't that appeal to you as well?

Cardiomyopathy: New Hope for a Cure

WAYNE IS A LIFETIME FRIEND. WE GREW UP TOGETHER IN A SMALL town along the Missouri River in South Dakota. His father was my baseball coach all the way through high school, and even though Wayne is younger than me, we always seemed to be competing neck and neck in sports. In fact when I was a senior, I set a local high school track record in the half-mile; Wayne broke it two years later. Wayne and I both went on to attend the University of South Dakota where we ran together on the USD track team. Following our years at the university, Wayne continued his athletic pursuits, was an aggressive cyclist, and still ran on occasion. I admired his continued drive to stay in peak physical condition.

Knowing his athleticism, then, I was quite concerned when my friend walked into my office one mid-summer day Wayne's color was poor, and he complained that his heart felt like it was going to jump right out of his chest. My former competitor looked tired and washed out as he informed me that he had come down with a severe flu about three months earlier and just never seemed to get over it. It seemed that anything he did completely wore him out. He was the manager of a restaurant and didn't know how he could continue working-it was that taxing to his body.

As I examined my friend, I noted right away that his heart was indeed beating rapidly and irregularly. Wayne's heart sounded like a washing machine. It was clear that he was in serious trouble, and I informed him that he needed to be admitted to the hospital.

Wayne went directly to the hospital, where one of our local cardiologists examined him. An x-ray revealed that Wayne's heart was significantly enlarged, so the doctor immediately ordered an echocardiogram (a sound-wave study of the heart). The results were shocking: Wayne's ejection fraction (a measure of how strong the heart is beating) was only 17 percent. A normal ejection fraction is between 50 to 70 percent. When an ejection fraction drops below 30 percent, the patient is a possible candidate for a heart transplant. Wayne's heart was huge, filled with blood clots, and in a trial fibrillation (beating irregularly). His situation was critical.

The cardiologist then performed a cardiac catheterization, in which he injected a special dye into Wayne's heart and coronary arteries. His arteries were fine, but his heart had definitely suffered trauma. The next test, a biopsy of the heart muscle, showed that as a result of suffering a viral infection of the heart, Wayne had developed cardiomyopathy (extreme weakness of the heart muscle). The infection had most likely occurred in the spring when Wayne contracted what he believed was the flu. He'd actually contracted a viral myocarditis, which caused severe damage to his heart.

The cardiologist prescribed the blood thinner Coumadin and placed Wayne on several other medications in an attempt to strengthen his heart. He was then able to leave the hospital, though he was very weak and could hardly move.

Follow-up studies of Wayne's heart a few weeks later showed that his ejection fraction had improved to 23 percent. The cardiologist wasn't very optimistic, though, and felt that this was probably the most Wayne's health would ever improve. His heart was still filled with blood clots, and he still was in a trial fibrillation.

The only other option the cardiologist had to offer was the possibility of sending Wayne to Abbott Northwestern in Minneapolis, where he could be put on a heart-transplant list.

You can imagine how difficult it was for me to discuss this with my patient, my friend. I also had to inform Wayne's parents, two people I had grown to love and admire, that their son's life was in serious jeopardy To make matter~ more painful still, they had recently lost a younger son to lung cancer. 1 seemed like I was a messenger of hopelessness.

Wayne wanted to hold off going to Minneapolis and instead work with the local cardiologist and visit me on a regular basis. We placed him on a potent antioxidant and mineral supplement while he continued with his other medications. His blood clots finally cleared, and the cardiologist was able to convert Wayne's heart rhythm back to normal with electrical shock therapy.

About this same time my wife, Liz, and I were flying to the great Northwest when she showed me an article she was reading about a study on a natural nutrient, Coenzyme Q10 Liz handed me the article written by Dr. Peter Langsjoen, a cardiologist and biochemist practicing in Tyler, Texas. Dr. Langsjoen had been able to significantly improve the health of his cardiomyopathy patients by simply adding supplements of the nutrient called CoQ10 to their daily medications.'

As soon as I returned home, I thoroughly researched the medical literature about the use of CoQ10 and decided that it was safe to try with my friend. What did Wayne have to lose? I asked him into my office the next day and started him on a dosage of CoQ10 similar to what Dr. Langsjoen had been recommending.

Because Wayne was being so closely monitored by his cardiologist, I did not see him for three or four months, and when he did return to my office, he came to discuss the possibility of applying for total disability income. My hopes sank. Total disability? Wayne explained that because he had not worked for the past eight months, his friends and business acquaintances had strongly urged him to consider going on disability. When I asked how he was doing, however, he told me that he was feeling fine and was actually able to ride his bike an average of five miles a day. He was even able to run a little.

Grinning, I told Wayne that I would have difficulty recommending him for disability when his activity level had so dramatically improved. I suggested that we get another echocardiogram to see how his heart was doing. He agreed. I was astonished when I got the results. Wayne's ejection fraction was back into a normal range at 51 percent! The only explanation for his miraculous improvement was lots of prayer and the nutrient CoQ10.

The next week I ran into Wayne's cardiologist in the doctors' lounge, and I happily shared what had happened with our patient. But the cardiologist didn't reflect my enthusiasm. He simply did not believe me. In fact this doctor insisted that Wayne's echocardiogram be repeated on "his" machine.

Wayne was called to his cardiologist's office, but I didn't hear anything on the results for several weeks. When a letter finally did come, I learned that Wayne's ejection fraction on the cardiologist's machine was 58 percent. Yes! That is even better, I thought.

A week after I received the letter, I was grabbing a snack in the doctors' lounge when the cardiologist approached me. Our interaction was a bit different this time. Amazed at Wayne's improvement, the doctor was anxious to see some of the research studies on CoQ10. I told him I would send copies of the studies right over.

"Ray," he said, "you remind me of a doctor I used to listen to on the radio during my commute into work. He would talk about all these medical studies on nutrition and supplements. I was sure he was off his rocker. Slamming his topics became one of our favorite pastimes at the hospital. Man, we shredded him good."

The cardiologist continued, "The most critical doctor was Jim. In the doctors' lounge he would trash this radio guy up one side and down the next. This continued over the next few months until one day Jim's partner confronted him. 'Jim, if you feel this strongly about the subject, why do you take nutritional supplements?'

"Well, Jim replied, 'just in case I am wrong."'

Wayne did not go on disability and is back to working full time. His first visit to my office occurred more than four years ago. My friend is now able to do all that he wants to physically and his follow-up echocardiograms continue to show that his ejection fraction is normal.

Let me assure you, though, that Wayne's heart has not been "cured." He still has cardiomyopathy. But with the addition of the nutrient CoQ10, Wayne's heart has its needed fuel source, which now allows his heart to compensate for its weakened state.
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