Antioxidant Vitamins Prevent Heart Disease: Verification from the American Heart Association
Richard A. Passwater, Ph. D.
The good news is that the American Heart Association (AHA) is learning that vitamins prevent heart disease! The bad news is that it has taken them nearly twenty years. "Most of us in medicine have poo-pooed megadoses of vitamins, but this research has a good ring to it," AHA president Dr. W. Virgil Brown of Emory University told reporters covering the AHA annual science writer's meeting in Galveston, Texas. 
When Prevention magazine held a press conference in 1975 to report my study of the effectiveness of vitamin E in preventing heart disease, one reporter asked me how long would it take for this research to be used by medical doctors.  I replied, "In the past, it would have taken twenty years, but with the improved communications of today, it should take only about ten years."
Although it has taken longer than I had expected, the research pace is quickening. Medical researchers can't help but see the many articles showing that the real heart disease culprit is oxidized lipoprotein, and now they will be seeing several articles on how antioxidant nutrients prevent these harmful reactions from occurring. Also, many researchers have read the recent article in the American Journal of Clinical Nutrition showing the single most reliable risk factor for heart disease is a deficiency of vitamin E! Soon this information will trickle down to "practicing" physicians.
In the meantime, I note that physicians at the forefront of research are starting to take vitamin supplements themselves. The number of physicians who teach at Harvard Medical School and who take vitamins regularly has essentially doubled in the last ten years.  In 1982, fourteen percent admitted to taking vitamin supplements, today twenty-three percent take vitamin supplements. I suppose that they were impressed by the Harvard study that showed that beta-carotene cut heart disease in half. 
Notice that we are not hearing so much about cholesterol at the first level of research these days. We virtually never hear about dietary cholesterol anymore in research. The point that I made in 1972 in American Laboratory and again in 1975 in "Supernutrition: Megavitamin Revolution," and further expanded upon in my 1977 book, "Supernutrition For Healthy Hearts," that dietary cholesterol wasn't an important factor in the majority of people has now been well taken. [5-7]
The importance of this is that the public can now pay better attention to the most important factor instead of being sidetracked by minor factors or factors that don't even apply to the majority of the population.
Also, we have now learned to use genetic markers to tell just who should be concerned about dietary cholesterol and blood cholesterol levels. The rest of us, which is actually the most of us, have to pay more attention to our antioxidants. If we don't know if we are genetically prone to abnormal cholesterol metabolism, then we can watch our cholesterol and antioxidants both. My point is that even in cholesterol-sensitive people, antioxidant protection is more important than cholesterol level. Don't concentrate on the minor problem and ignore the major factor. 
A reporter called to ask why I have said all along in my books that vitamin E prevented heart disease, and others are just now "discovering" that fact? I said there were three main reasons:
I don't have the space here to review the cholesterol theory, but other more promising explanations including the vitamin B-6 deficiency, insulin excess, chromium deficiency, estradiol excess and fibrinogen excess relationships seem certain to account for many cases of heart disease. These theories are discussed in my newest book, "The New Supernutrition."  Of course, the newest research on antioxidant nutrients and oxidized lipoproteins is also discussed more fully in the book.
The Big "News"
Yes, it has been startling to read twice this year in USA Today that vitamins prevent heart disease. [12,13] The news made the front page once, and the first page of the "Life" section the other time.
The latest news is that Dr. Ishwarlal Jialal of the University of Texas Southwestern Medical Center in Dallas showed that Vitamin E could block the adverse changes to low-density lipoprotein (LDL) that leads to plaque formation and blockages in arteries. Actually, as I will show in another article in this series, the oxidation of LDL and/or high-density lipoprotein (HDL) causes most of the cases of heart disease.
Dr. Jialal explained, "researchers are now of the opinion that fats in the bloodstream become lodged in artery walls and begin to clog arteries only when their transporters , the lipoproteins, have chemically combined with oxygen to turn rancid."
Smoking promotes the oxidation of lipoproteins, as do fats when they are not protected from oxidation by antioxidant nutrients such as vitamins C and E, and beta-carotene. Normally, smokers and diabetics have low levels of vitamin C in their blood, unless they take supplements.
Beta-carotene and vitamins C and E have previously been shown to block the oxidation of LDL "in the test tube." Dr. Jialal said that his is the first study to demonstrate that an antioxidant nutrient can actually prevent LDL oxidation in the body.  It may be only a matter of semantics as to who was the first to actually show "prevention of LDL oxidation in humans."
This special AHA symposium for science writers helps communicate research results to the public. The research reported there by Dr. Jialal was previously published in Arteriosclerosis and Thrombosis.  Twelve men were given 800 IU of vitamin E daily and their blood was monitored for LDL and oxidized-LDL content for three months. Dr. Jialal reported that there were no adverse effects from taking the 800 IU of vitamin E daily. That is not news in itself, but at least now cardiologists have heard it at an officially sanctioned AHA symposium.
In an interview, Dr. Jialal said that in the test tube, vitamin C seems to have the greatest potency (95%) at blocking oxidation of blood fats, followed by beta-carotene (90%) and vitamin E (45%).  However, it was easier to follow the progress of the experiment in people using vitamin E. Another study examining the efficiency of vitamin C will be forthcoming. He also suggested that giving combinations of these antioxidants would be even more effective.
Yes, they will find synergism -- the same synergism of these antioxidants that I have found in my longevity and cancer experiments -- but they haven't even thought of selenium yet. Selenium is a mineral required in two enzymes that reduce "background" free radicals which would otherwise be available to promote oxidation of LDL. The same is true for zinc, copper and manganese being required in the enzyme superoxide dismutase (SOD).
Just two months before, USA Today reported a related story from the regular annual meeting of the AHA in Anaheim.  There Dr. JoAnn Manson of Brigham and Women's Hospital in Boston described her study of the diets of 87,245 nurses over more than eight years. She found that women who take supplements of more than 100 IU of vitamin E daily have thirty-six percent fewer heart attacks than those who consume less than thirty IU daily.
Dr. Manson also found that women who consumed 25,000 IU of beta-carotene daily had 40 percent less stroke and 22 percent fewer heart attacks than those women who consumed less than 10,000 of beta-carotene daily.
Also in 1991, it was "news" that people with angina pectoris (chest pain due to heart disease) have low levels of vitamin E. [17,18] As we will see later, this is really very old news that has been ignored for decades.
Add to this, the fact that many medical researchers are still reeling from the disclosure that vitamin E deficiency is the single most important risk factor in predicting heart disease incidence. 
Perhaps Dr. Jialal's group is not the first to publish that supplements of vitamin E (tocopherol) inhibit the oxidation of LDL in humans. Dr. Hermann Esterbauer's group at the University of Graz (Austria) has reported that the "oxidation of polyunsaturated fatty acids in LDL is preceded by a sequential depletion of antioxidants in the following order: alpha-tocopherol, gamma-tocopherol, lycopene and beta-carotene. Oxidation of LDL can begin only when these antioxidants have been depleted...The effectiveness of vitamin E in protecting LDL from oxidation varied from person to person...The present study clearly shows that in humans, the oxidation resistance of LDL can be increased by vitamin E supplementation." [20,21]
These news stories are breaking faster than I can provide you with a background to help explain the biochemistry involved. In this series of articles on antioxidants and heart disease, I have been building a foundation for discussing this newest research. Last April, I discussed how oxidized-LDL accumulates in macrophages (special white blood cells) causing their death, and in turn, these "dead" macrophages accumulate and injure the arterial lining resulting in plaque formation 
Then in September, I discussed the structure and function of LDL, HDL and their receptors.  Hopefully, these articles have provided the background to better to understand the role of oxidized-LDL and oxidized-HDL in causing heart disease, and to see how the antioxidant nutrients, such as vitamins C and E, and beta-carotene are protective.
A good review article for the professional was recently published in "Circulation." 
The First Evidence of Prevention
The newest research is much more sophisticated than my 1974-5 epidemiological study. This is what is needed to convince the closed-minded skeptics, and this is what I have been working so hard to bring about. I have spent considerable time promoting the concept that antioxidant nutrients protect against heart disease and cancer, and cajoling other researchers to look into this line of research.
As science reporter Judith Randall wrote in the New York Daily News in 1975, "Passwater hopes his findings will spur the scientific community to mount a more sophisticated research effort to prove or disprove what he has found." "While some experts believe," he said, "that vitamin E has no role to play in medicine, it is really more important that the scientific community get in there and prove or disprove what I have found." 
Reporter Susan Fogg of the Globe-Democrat National Service, reported my findings and then checked with the National Institutes of Health.  A spokesman there said "So far the scientific data collected does not indicate that vitamin E prevents heart disease, but it is only useful in the amelioration of vitamin E deficiencies, and such deficiencies are almost unheard of."
"Passwater, who is one of the nations foremost experts in fluorometry, which is the use of fluorescent materials to trace the biochemical effects of drugs and other substances in body tissues, said the data from this study should prompt further research into what role vitamin E plays in heart disease." "Passwater said that he had spoken with researchers at the National Heart and Lung Institute, but they could not help him for fear of being put in jeopardy."
That restrictive environment continued to prevail. During the next year, after extensive lecturing and writing to researchers led to no follow-up studies on my research, it became apparent that the conventional approach was not going to work. This led to my coming to the Health Industry, and I am so glad that the Solgar Nutritional Research Center was established in 1977 to allow me to continue my research!
My 1974-5 Study Showing Vitamin E Prevents Heart Disease
My study of 17,894 persons between the ages of 50 and 98, showed that heart disease dropped dramatically among those taking vitamin E over a long period of time. I found that the length of time vitamin E was taken was more important than the amount. This trend was especially apparent above nine years of usage.
I found that taking 400 IU or more of vitamin E daily for ten years or more was strongly associated with reducing the incidence of heart disease prior to eighty years of age to less than ten percent of the normal rate.
Among persons taking vitamin E over ten years, I found only four suffered from heart disease out of a total of 2,508. Ordinarily, in a sample of that size, approximately 836 persons would be expected to suffer from heart disease. Appropriate statistical models reveal that high confidence can be given to the statement that taking 400 IU of vitamin E daily for more than ten years will lower the heart disease incidence to ten percent of the then current (1975) age-adjusted rate of 32 per 100 to 3 per 100.
I found that those who took 1200 IU of vitamin E daily for four years or more also had a dramatic decrease in heart disease incidence, though not as strong as the prior group.
Among persons who took 1200 IU of vitamin E daily for four years or more, their incidence of heart disease was reduced by about one-third. Instead of the expected 32 per 100 age-adjusted rate, the statistics showed that there is high confidence that the rate is only 10 per 100.
The observation that length of time taking vitamin E is strongly associated with reduced heart disease is strong statistically. The Spearman-Rho statistical association value was 0.96, where 1.00 is perfect association. The correlation is significantly different from zero or chance occurrence at the 0.01 level. Figure 1 shows the relationship between the years of taking vitamin E and heart disease incidence.
Now the reason seems obvious. For any given age, this means that the longer time taking vitamin E, the longer the arteries have been protected from oxidized-LDL. Protection was started earlier and the arteries are cleaner.
The details of my study are published in several books and articles available to the general public. [8, 27-31]
Heart Disease Has Two Components
The path to a heart attack is a two-step process. First "foam cells" (macrophages filled with oxidized-LDL) adhere to the artery lining. These cells promote the infiltration of various substances through the artery wall into its middle layer. Now the artery can be said to be "diseased" as a plaque is formed in the artery interior. As the plaque expands, the wall is pushed out and the opening where the blood flows through is narrowed. Thus, blood flow is decreased to the heart tissue. The narrowed artery also damages the blood platelets passing through, making the blood "sticky" and encouraging clot formation at the plaque site.
Figure 2 shows the relationship between the two steps. Until recently, most of the emphasis of vitamin E research has been on its ability to safely prevent clots from forming. Now many researchers are looking at how vitamin E prevents the first steps in this process from occurring as well. The process is further explained in my new book, "The New Supernutrition."
The Pioneers of Treating Heart Disease and Vitamin E
Drs. Evan and Wilfrid Shute used vitamin E in their treatment of heart disease. It was their great clinical success with tens of thousands of heart patients that led to my 1974-5 study of vitamin E and the prevention of heart disease. I was researching how the antioxidant nutrients slowed the aging process, and I kept getting asked about vitamin E and heart disease. My study was designed to learn more about how much and how well vitamin E helped people. It was a coincidence that these data were so striking that I could discover the relationship between vitamin E and the prevention of heart disease.
The Drs. Shute were physicians and they were trained to think primarily in terms of cure, rather than prevention. They recognized coronary thrombosis for what it is -- blood clots forming in the coronary arteries that prevent blood from nourishing the heart. This leads to death of tissue (an infarct) in the heart (myocardium) -- hence the term "myocardial infarction."
The Drs. Shute knew that vitamin E helped keep the blood free-flowing and their observations convinced them that vitamin E would also help dissolve clots. They also found that vitamin E sped healing of the heart and facilitated the growth of new blood vessels around the damaged area (collateral circulation).
Earlier I mentioned that angina pains occur most frequently in vitamin E deficient persons. The Drs. Shute knew this, and found that vitamin E supplementation relieved angina -- although not as well as nitroglycerine.
Eventually, the Drs. Shute expanded their thoughts to prevention. Hopefully, my study encouraged their thinking. They had good reason to believe that vitamin E could help keep clots from forming in the first place, and thus prevent heart attacks. Dr. Evan Shute pointed out in a Shute Institute booklet, "Prevention is everything. Fortunately, alpha-tocopherol offers hope in this respect, for vitamins characteristically prevent what they relieve." However, he had no formal studies to prove his point -- only clinical observations of thousands of patients.
In 1974, Dr. Evan Shute wrote to me explaining that "my brother keeps quoting Kay and Ochsner on antithrombin, but I believe that vitamin E is a fibrinolysin and acts in that way to protect against clotting, etc." 
Reducing heart attacks by reducing the tendency of blood to clot is a different concept than preventing damage to arteries which narrows them and induces clots to form. Preventing clots is attacking the problem at the second stage, whereas preventing plaque formation is to attack at the first stage. It is better to keep the arteries from being narrowed in the first place, as this ensures an adequate blood flow to all of the heart tissue. Isn't it fortunate that vitamin E will stop both processes?
The Drs. Shute had no studies or knowledge of using vitamin E to prevent the atherosclerotic process -- that is they saw no relationship as to how vitamin E could prevent cholesterol deposits. However, they knew that cholesterol deposits were not just simply a matter of eating cholesterol. In fact, in 1974, Dr Evan Shute wrote to me saying in several letters that he appreciated my views on cholesterol. "I was especially struck with the item on cholesterol, as I, like you, don't believe in it." 
Dr. Evan Shute reviewed and critiqued my manuscript for "Supernutrition: Megavitamin Revolution" and kindly offered suggestions. He told me that my stance on cholesterol was especially helpful and wished me "good luck." He commented, "The clouds don't look so dark as they did 25 years ago. A fellow needs lot of patience." 
In 1977, Dr. Evan Shute reviewed my book, "Supernutrition For Healthy Hearts." In the review, he said, " Richard Passwater, Ph. D. does an excellent job in his new book, "'Supernutrition For Healthy Hearts.' He explains, once and for all, that cholesterol does not cause heart disease...It is one of the best books I have on my shelves and I highly recommend it as part of your library."
Later, his son, Vere Shute, wrote to tell me not only did Dr. Shute highly recommend my book, but that the Shute Institute provided patients with copies of both "Supernutrition: Megavitamin Revolution" and "Supernutrition For Healthy Hearts." 
I remember many extensive talks with Dr. Evan Shute in which we chatted about how vitamin E helped so many conditions from healing the heart to wound healing. He wrote in 1974, "The fibroblasts are inhibited and the epithelial cells have a chance to cover the wounds over before the granulation tissue pushes up from beneath."  I was given - and still treasure - his lecture slides of 1949 showing how vitamin E "miraculously" healed patients suffering from burns, diabetic gangrene, and other otherwise disfiguring problems.
I toured with Dr. Wilfrid Shute throughout Australia in 1980. He told me that he found my study enlightening and that he also liked my observation that the heart disease death rate started declining in pace with the increasing use of vitamin E supplements.
Prodding the Establishment to Consider Vitamins
Yes, I have been on a mission! I am glad that the establishment is now taking vitamins seriously. I used to be part of the "establishment. I was a research biochemist for Allied Chemical Corporation, F & M Scientific Corporation, Baxter-Travenol Laboratories, and American Gerontological Research Laboratories.
However, my studies showing the antioxidant vitamins slowed the aging process, and prevented cancer were not well accepted at that time. I remember how my research was criticized in Chemical & Engineering News. Although I was able to successfully defend my research in Chemical & Engineering News and to publish in American Laboratory and International Laboratory, I was unable to publish anywhere else because of the suggestion that vitamin supplements were beneficial. [35-38] That's why I took my research directly to the public with "Supernutrition: Megavitamin Revolution" in 1975, and with the heart study in 1976.
In 1978, I challenged the AHA to debate me. On Good Morning America, I debated a leading cholesterol and heart disease researcher from the University of Miami, and he admitted that dietary cholesterol was not important to normal healthy persons. On the backcover of my book, "Supernutrition for Healthy Hearts," I challenged in large print -- "No one has ever shown that eating cholesterol causes heart disease. If anyone can step forward and prove that eating cholesterol causes heart disease, I will donate all of my proceeds from this book to the American Heart Association."
Indeed, I have been on a mission. I have challenged researchers and cajoled them into checking out this research. Maybe I didn't have the patience at first that Dr. Evan Shute mentioned, but I did have persistence.
There were clues in several papers in obscure journals that "know-it-alls" never bothered to look for, let alone study. And when I would show these to vitamin E critics, they would simply dismiss them as "not a controlled double-blind cross-over study," or "that's just an animal study" or "too few people in the study" or whatever they wished to use as an excuse for not wanting to pay attention. They had closed minds and didn't want to be confused by facts. The last thing they wanted was an "interesting lead" regarding vitamins.
I made this my goal -- to force them to pay attention and not just offer lame excuses. I went on the lecture circuit to pointedly goad the critics into trying to prove me wrong or to shut up. They ignored me at first, but I became more sophisticated in how I could bring pressure upon them to try the studies I proposed. Those who were open-minded enough to look into vitamin E, became interested, but they still had to bootleg the research because they couldn't get funding. Eventually, the little presentations and abstracts at meetings - given as "tack-ons" to other research, turned into scientific papers and now it seems even into full clinical studies.
Today I am pleased that so many heart researchers and a growing number of AHA officials are in agreement with the what I have been teaching for twenty years. Life can be rewarding!
True, the news about cancer and antioxidants that the establishment became excited about in 1991 is essentially the same as I reported in 1973. The news that is now interesting the AHA is what I suggested in 1972 and determined in 1974-5. But, until the establishment is convinced, the job is not done. More research and clinical trials are needed. They are underway regarding the cancer studies, but the heart studies are not even designed yet. However, last year, the National Heart, Lung and Blood Institute brought together about 30 scientists involved in this research to consider designing such clinical trials for antioxidants and heart disease.
I believe that many of you would be interested in the story about how difficult it was for vitamin E to be introduced to the health food market, so I will discuss the battle fought by Jud Ryon in the 1940s in an upcoming article.
All rights, including electronic and print media, to this article are copyrighted to Richard A. Passwater, Ph.D. and Whole Foods magazine (WFC Inc.).