Antioxidants Studies

As everyone knows, eating and drinking are necessary for life. Less well known, however, is the fact that the body generates what are called free radicals in the process of turning food into energy. Free radicals are chemicals that are capable of damaging cells and genetic material. But eating is not the only way free radicals spring into being. The food we eat and the sunlight we feel also generate free radicals.

To be sure, free radicals come in many shapes, sizes, and chemical configurations. The characteristic feature of this chemical is that it soaks up electrons from bodily substances that yield them, which can leave the “loser’s” structure or function radically altered. Free radical damage can change the instructions coded in a strand of DNA; it can also make a circulating low-density lipoprotein (LDL, sometimes called bad cholesterol) molecule more likely to get trapped in an artery wall. Free radicals also have the potential to alter a cell’s membrane, changing the flow of what enters the cell and what leaves it.

Fortunately, we aren’t defenseless against free radicals. The body puts up natural defenses against free radicals by making molecules that smothers the errant chemicals. We also extract free-radical fighters from food. Often called “antioxidants”, certain kinds of food give electrons to free-radicals without themselves turning into electron-scavenging substances. There are many different substances that can act as antioxidants. The most familiar ones are vitamin C, vitamin E, beta-carotene, and other related carotenoids, along with the minerals selenium and manganese. They’re joined by glutathione, coenzyme Q10, lipoic acid, flavonoids, phenols, polyphenols, phytoestrogens, and many more.

However, the term “antioxidant” can be misleading. These substances do not emit chemical properties that fight so much as they emit properties that facilitate. Indeed, some substances that act as antioxidants in one situation may be prooxidants—electron grabbers—in a different chemical milieu. Another big misconception is that antioxidants are interchangeable. This is not true. Each anti-oxidant has unique chemical behaviors and biological properties. It is believed, and has been strongly corroborated through scientific study, that anti-oxidants evolved as parts of elaborate networks, each substance having a different role to play. It follows that no single substance can fulfill the function of every other substance.

Health Benefits of Antioxidants: What’s the Buzz?

Antioxidants came to public attention in the 1990s. It was then that scientists began to understand that free radical damage was involved in the early stages of artery-clogging atherosclerosis, and that the chemicals may contribute to cancer, vision loss, and a host of other chronic conditions. A number of studies stated that people with low intakes of antioxidant-rich fruits and vegetables were at greater risk for developing these chronic conditions than were people who ate sufficient amounts fruits and vegetables. Clinical trials tested the impact of single substances, especially beta-carotene and vitamin E, on cancer, heart disease, and similar maladies. But even before the results of these trials were in, the media, and the dietary supplement and food industries began promoting the benefits of “antioxidants.” Foods such as frozen berries and green tea were hyped as being rich in antioxidants. The consequences of this publicity were predictable: certain foods were labeled as rich in antioxidants and were marketed as such in stores; the makers of dietary supplements began touting the disease-fighting properties of all sorts of antioxidants.

In the meantime, the results of the actual trials were mixed. Most have not found the hoped-for benefits. And research teams reported that vitamin E and other antioxidant supplements didn’t protect against heart disease or cancer. One study even showed that taking beta-carotene may actually increase the chances of developing lung cancer in smokers. However, some of the trials reported benefits. One such study found that taking beta-carotene is associated with a modest reduction in the rate of cognitive decline.

The rather most, if not downright disappointing, results of the antioxidant trials have not stopped the commercial interests from misrepresenting the benefits of antioxidants in order to make money. Antioxidant supplements are a $500 million dollar industry that continues to grow. Antioxidants are still added to breakfast cereals, sports bars, energy drinks, and other processed foods, and they are promoted as additives that can prevent heart disease, cancer, cataracts, memory loss, and a host of other conditions. The claims made by the food and dietary supplement industries often distort the data. It is true that the package of antioxidants, minerals, fiber, and other substances found naturally in fruits, vegetables, and whole grains help prevent a variety of chronic diseases; but there is no solid evidence that high doses of antioxidants can accomplish the same feat. The conclusion is clear: randomized, placebo-controlled trials—which, when performed well, provide the strongest evidence—offer little support that taking vitamin C, vitamin E, beta-carotene, or other single antioxidants provides substantial protection against heart disease, cancer, or other chronic conditions. The results of the largest such trials have been mostly negative.

Heart Disease and Antioxidants

Vitamin E, beta-carotene, and other so-called antioxidants are not a panacea for heart disease and should not be promoted as such. In the Women’s Health Study, 39,876 initially healthy women took 600 IU of natural source vitamin E or a placebo every other day for 10 years. The results of the study showed that the rates of major cardiovascular events and cancer were no lower among those taking vitamin E than they were among those taking the placebo; however, a 24 percent reduction in total cardiovascular mortality was observed, which can be considered a quite significant result.

Earlier large vitamin E trials, conducted among individuals with previously diagnosed coronary disease or at high risk for it, generally showed no benefit. In the Heart Outcomes Prevention Evaluation (HOPE) trial, the rates of major cardiovascular events were essentially the same in the vitamin E (21.5 percent) and placebo (20.6 percent) groups, although participants taking vitamin E had higher risks of heart failure and hospitalization for heart failure. (3) Another trial, the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI), showed mixed results; there were no preventive effects after more than three years of treatment with vitamin E among 11,000 heart attack survivors. Nevertheless, some studies suggest potential benefits among certain subgroups. A recent trial of vitamin E in Israel, for example, showed a marked reduction in coronary heart disease among people with type 2 diabetes who have a common genetic predisposition for greater oxidative stress. In any case, Beta-carotene, as was shown in the Physicians’s Health Study, does not provide any protection against heart disease or stroke.

There have been combinations, but the findings are complicated and unclear. In the Supplementation en Vitamins et Mineraux Antioxydants (SU.VI.MAX) study, 13,017 French men and women took a single daily capsule that contained 120 milligrams of vitamin C, 30 milligrams of vitamin E, 6 milligrams of beta-carotene, 100 micrograms of selenium, and 20 milligrams of zinc, or a placebo, for seven and a half years. The vitamins had no effect on overall rates of cardiovascular disease. In the Women’s Antioxidant Cardiovascular Study, vitamin E, vitamin C, and/or beta-carotene had much the same effect as a placebo on myocardial infarction, stroke, coronary revascularization, or cardiovascular death, although there was a modest and significant benefit for vitamin E among women with existing cardiovascular disease.

Cancer and Antioxidants

There is also no conclusive proof that antioxidants help prevent cancer. Scientists need more time to determine the impact of antioxidants on the risk of getting cancer. In the long-term Physicians’ Health Study, cancer rates were similar among men taking beta-carotene and among those taking a placebo. Other trials have also largely showed no effect, including HOPE. The SU.VI.MAX trial showed a reduction in cancer risk and all-cause mortality among men taking an antioxidant cocktail but no apparent effect in women; it is possible that this is a result of the men in the study having low blood levels of beta-carotene at its beginning. A randomized trial of selenium in people with skin cancer demonstrated significant reductions in cancer and cancer mortality at various sites, including colon, lung, and prostate. The effects were strongest among those with low selenium levels at baseline.

Age-Related Eye Disease and Antioxidants

The effects of antioxidants on age-related eye disease may be one of the most hopeful leads scientists have. A six-year trial, the Age-Related Eye Disease Study (AREDS), found that a combination of vitamin C, vitamin E, beta-carotene, and zinc provided some protection against the development of advanced age-related macular degeneration in people who were at high risk of the disease. Lutein, a naturally occurring carotenoid found in green, leafy vegetables such as spinach and kale, may also protect vision. It is too early to tell what the impact of lutein supplements may be. The trials of such substances have been relatively short, and their ability to slow or prevent age-related macular degeneration has not been ascertained. A new trial of the AREDS supplement regimen plus lutein, zeaxanthin, and fish oil is underway, and it could yield better information.

Potential Hazards of Antioxidants

There have been a few studies which showed that the consumption of antioxidants, as opposed to being beneficial in all instances or at least harmless in fact can interfere with the health of the consumer. The first trial which showed this possible negative effect was undertaken in Finland where heavy smokers were fed beta-carotene. Because of their smoking habits there was a already a lung cancer risk but it was noticed that a significant increase in the incidence of lung cancer amongst the trial group as opposed to the placebo. The trial was stopped so conclusive results are hard to deduce.

A different test which was conducted with heavy smokers exposed to asbestos being fed beta-carotene and vitamin A. This too shows an increase in the incidence of Lung cancer. It must be emphasized that not all trials of Beta-carotene have been negative. A physicians health study which only had a few smokers did not show any significant differences even when followed up after 18 years.

In a separate study showing possible negative effects of a variety of health supplements showed a higher incidence of skin cancer in women being fed supplements of Vitamins C & E, Beta-carotene, selenium and zinc.

Conclusions to be drawn from the above studies, amongst others, is that it is known that although free radicals have been shown to contribute to the incidence of heart disease, cancer, Alzheimer’s and even vision loss, there is no automatic conclusion that can be drawn that antioxidants will fix the problem. And certainly not when consumed away from their normal context.

Studies to date do not show conclusive evidence one way or another but there is certainly no strong evidence to suggest that antioxidants are effective against disease. A rider must be mentioned and that is that the trials conducted till now have been short in duration, conducted with people some of whom had an existing disease.

There has been a noticeable benefit to the consumption of beta-carotene on cognitive ability after 18 years. This is exceptional as it is the only study to have continued so long. (Physicians health follow up study) Nevertheless there is abundant evidence suggests that eating whole fruits, vegetables, and whole grains—all rich in networks of antioxidants and their helper molecules—provides protection against many of these scourges of aging.

Clarification with regard to supplemental studies

There are any number of studies conducted on any number of vitamins and other dietary supplements that are often contradictory. The picture presented to the consumer is confusing and will often seem frustrating in that instead of clarifying things these studies muddy the waters.

Examining exactly what the vitamins trial study did will often go some way to explaining the varying results. Here are a few items to check when looking at apparently conflicting vitamins studies.

  • What was the precise dosage taken by the participants and how long was the study’s duration. This is significant as few studies will have identical dosages and identical time spans. A study in Vitamin D showed that a dosage of 700 plus IU per day had a significant protection against fractures whereas a study of people taking only 400 IU per day showed no such effect. The same applies to the duration as the build up of the protective mechanisms is not a short process.
  • The age, health and life styles of the participants. Studies drawn from young, active gym going participants is likely to differ significantly from heavy drink and smoking office workers. Exercise and other lifestyle choices such as diet affect out health and how the body responds to vitamins.
  • At what stage is was the supplement fed to a study participant. If studying the effect of a supplement on someone already suffering from a disease it may be found that something taken at the onset has a differing effect from something taken when a disease is far advanced. An example being that Folate supplements are only effective against neural tube defects in the early stages of pregnancy.
  • How were the results tabulated and calculated. This is a significant problem as measurement as to benefit may and probably will vary widely. Heart disease is a wide subject and a measurement of coronary thrombosis may miss out on the incidence of strokes.

B Vitamins and Heart Disease

Can B vitamins keep your heart healthy?

Sadly, the death of two young children who had died of massive strokes were the catalyst for a 1968 investigation. The Boston pathologist who investigated the death of the children found that they had extraordinarily high levels of a protein breakdown product in their blood. Both children’s arteries were blocked by cholesterol as well, resembling more closely the arteries of a middle-aged unhealthy person than those of a young child. These discoveries led to the hypothesis that elevated levels of this breakdown product (know as homocysteine) had contributed to the process of hardening of the arteries. This condition is called atherosclerosis. So, what is the connection between B vitamins and heart health?

Folate, vitamin B6 and vitamin B12 are instrumental in the body’s ability to convert homocysteine into methionine. Methionine is one of the 20 substances that help the body to build new proteins. Insufficient levels of any or all of these B vitamins can hamper the conversion process, driving homocysteine levels up. Sufficient levels of these vitamisn, on the other hand, can help to keep homocysteine at a safe level.

Many studies over the last few decades have shown that high levels of homocysteine can be associated with an increase in the risk of heart disease and stroke. Some studies have also shown that there is a causal relationship between high intakes of folate and the lower incidence of cardiovascular disease, hypertension and strokes. There cannot be a direct link made, however, between higher homocysteine levels and lower folate levels to an increased risk of heart disease. In other words, it cannot be definitely stated that lower homocysteine levels by taking more folic acid and other B vitamins will lower one’s risk of having a heart attack, stroke or other heart-related condition.

There have been several randomized trials involving B vitamins and heart health, but they have not conclusively shown any relationship between the two. In the studies adutl participants who had a history of heart conditions or who were in the upper risk categories for heart disease were given either a placebo or a pill that contained high doses of vitamins B6, B12 and folic acid. The result of the study was that taking the high doses of the three B vitamins did lower the levels of homocysteine present in the body, but that that reduction did not lead to a reduction in the number of cardiac events in the participants. There is some suggestion that the participants in this study were already too far gone in terms of heart health for the B vitamins to have an effect.

Recently, analysis of several studies seems to suggest that taking folic acid supplements can reduce the likelihood of a stroke in a person who had never before suffered a stroke. The risk reduction does not occur, however, in people who have already had a stroke. Further, folic acid was most effective in promoting heart health when combined with vitamins B6 and B12 as opposed to when it is consumed in isolation.

In the United States and in Canada, since the governments in those countries have mandated that certain products such as bread and pasta be fortified with folic acid, the rate of death from stroke has fallen dramatically. In the UK, where folic acid fortification is not yet mandated, there has been no significant change in the rate of death from strokes.

The long and the short of it is this: Folic acid supplementation may reduce the risk of heart disease in people who have lower levels of folate in their systems. This will typically include those people living in countries where folic acid fortification of food is not yet the rule. In countries where people already get adequate levels of folic acid from their food, further supplementation, even levels that are much higher than can be found in a standard multivitamin, has not been sufficiently shown to be of any significant benefit and, actually, may cause harm.

Currently, what constitutes a sufficient daily intake of B vitamins isn’t clearly defined. The definition would likely change over time anyway, as more data are collected from randomized trials. Currently in the United States, folic acid fortification of food has led to an increase in the percentage of adults who have adequate levels of folate in their systems. Still, only a small percentage of American adults currently get the recommended daily intake of all B vitamins derived just from their diets alone.

Heart disease

Once you’ve been through menopause and the levels of estrogen in your blood have decreased, your risk for heart disease increases. Protecting your heart helps safeguard your old age.

Heart disease is the world’s biggest killer. Although a woman’s risk of heart disease, also known as coronary disease, does not reach the same level as a man’s until she is 75, it’s still a leading cause of death for women. In heart disease, the arteries that supply your heart with oxygen and nutrients become narrowed by atherosclerosis (commonly known as “hardening of the arteries”). This restricts the supply of blood and oxygen to your heart. Unfortunately, for many women the first indication that something’s wrong is a heart attack.

It’s important to appreciate that heart attacks rarely strike suddenly. In the great majority of cases, your heart and circulation will have been unhealthy for a long time, even if you didn’t know it. Heart disease is a degenerative condition: It builds up over a number of years. In addition, most experts agree overwhelmingly that heart disease can be caused (and prevented) by your diet and lifestyle. If your diet and lifestyle are healthy, your risk of developing heart disease decreases significantly, compared with a woman whose diet and lifestyle are unhealthy.

Causes

Most of us know the main risk factors for heart disease already: a lack of exercise coupled with a diet that is high in saturated fat and sugar, being overweight or overstressed; smoking; diabetes; high blood pressure, or a family history of heart disease; and stroke. Essentially, of those risk factors within your control, leading an unhealthy, sedentary life puts a strain on your heart and potentially shortens your life.

Increased risk for coronary disease is also associated with the process of aging, and there’s also a relationship between heart health and a woman’s midlife transition through menopause. Before menopause, a woman’s hormones (especially estrogen) offer some protection for her heart and blood vessels.

To understand how you can reduce your susceptibility to heart disease, it’s important to look in more detail at the risk factors within your control.

Understanding Cholesterol

Although the word cholesterol has negative associations for most of us, cholesterol has a positive function in your body as well as a negative one. Cholesterol is a type of fat that exists in all your cell membranes. Eighty percent of cholesterol is produced by your liver, and only 20 percent comes directly from your diet. It’s essential to the healthy functioning of your body, and you could not live without it. Cholesterol is the starting point for many of your hormones, including the sex and stress hormones; and it’s vital for nerve transmission, the formation of vitamin D (which you need for healthy bones), and the formation of bile. Problems occur only when you take in excess cholesterol from foods that are naturally high in cholesterol, or when your body starts to produce too much.

You may be surprised to learn that foods with fats do not have to contain cholesterol; it’s found only in animal products (meat, dairy products, butter, and eggs). Vegetable products are cholesterol-free: An avocado and olive contain fat, but neither contains cholesterol. Furthermore, foods such as shellfish contain very little fat but a high level of cholesterol, and nut butters (such as peanut butter), which we often perceive to be unhealthy, are high in fat but low in cholesterol.

In order for cholesterol to travel in the bloodstream, it has to combine with a protein, after which it’s known as a lipoprotein. There are two main types of lipoprotein that carry cholesterol around your body. Low-density lipoproteins (LDL, or “bad” cholesterol) are responsible for carrying cholesterol via the arteries to the cells of your body. High-density lipoprotein (HDL, or “good” cholesterol) collects cholesterol from the tissues and returns it t the liver for disposal. When you have high levels of LDL, cholesterol can deposit on damaged and inflamed arterial walls. These deposits, which also consist of saturated fats and calcium (that’s why cardiologists talk about calcification of arteries), are called arterial plaque or atheroma. These cause atherosclerosis (hardening), which can lead to blocked arteries and, as a result, high blood pressure.

Checking your cholesterol

To check your cholesterol, your doctor will give you what’s known as a “lipid” test. You need to know not only your total cholesterol level but also the separate levels of LDL and HDL (so that you know how much of your cholesterol is good and how much is bad). You also need to know your level of triglycerides (blood fats) because high levels of these have been linked to a higher risk of strokes and heart disease. Make sure you haven’t eaten or drunk anything (except water) from 10pm the night before your tests.

How your heart works


About the size of your fist, your heart lies just to the left of your breastbone and is a complicated pump responsible for circulating blood, oxygen, and nutrients through your body. It’s divided into four chambers: The right atrium and left atrium are the upper chambers of the heart, and the right ventricle and left ventricle are the lower chambers. The heart muscle contracts in two stages to squeeze blood out of the heart. This is known as systole. When the heart relaxes – known as diastole – blood fills up the heart again, and the whole process (which takes a fraction of a second) is repeated.

The heart has arteries that carry blood away from the heart. Capillaries (small blood vessels) connect arteries to veins. The veins then carry blood back to the heart. Heart disease can occur when arteries clog up with plaque.

Cholesterol and iron

Generally, your body needs iron for energy and to nourish your muscle cells. Without good levels, you’ll become anemic, which can cause you to feel tired all the time. However, having too much iron in your system and supplementing with iron can also be bad for you. Iron oxidizes LDL “bad” cholesterol; only once it’s oxidized does LDL seem to damage the arteries.

The fact that after menopause you’ll no longer have periods means that iron can build up in your system (you lose iron when you bleed). For this reason, it is recommended that you have regular blood tests to asses your iron levels, as well as the tests to establish your levels of cholesterol. Take iron supplements only if a blood test reveals that your blood levels are low. Many breakfast cereals are fortified with iron – avoid eating these after menopause, too. (however, don’t’ try to cut iron-rich foods out of your diet).

Your Diet

Quite simply, the best thing you can do for your heart is to eat a healthy, balanced diet. It’s especially important to increase your intake of oily fish, nuts, seeds, and oils – because these foods are good sources of essential fatty acids (EFAs), which are known to prevent heart disease. The omega-3 fish oils are particularly important because they not only help lower bad cholesterol (LDL) and increase the levels of good cholesterol (HDL). Phytoestrogens are another food group that has this effect on LDL and HDL. They have the added benefit of helping to lower your body’s levels of triglycerides (blood fat).

Try to boost your intake of antioxidants which are found in brightly colored fruits and vegetables. These important nutrients reduce your risk of heart disease by attacking the harmful free radicals that cause cell damage in your body. If you have a family history of heart problems, take a good antioxidant supplement.

Fats and your heart

There are two kinds of fat that are particularly bad for your heart health.

Saturated fat Regardless of your age and time of life, you should try to reduce your intake of foods that contain saturated fat, which as animal products and deep-fried foods, which clog up your arteries.

Trans fats For a healthy heart, you need to avoid trans fats altogether. These harmful fats, found in hydrogenated products such as margarine, as well as in ready-made meals, cookies, and other processed foods, can’t be properly broken down in the body, so they remain in the system, like a sort of plastic. Increasing your consumption of trans fats by only two percent can increase your risk of heart disease by a massive 30 percent overall.

Fat Facts: How Excess Fat Storage Can Grow A Deadly Organ

Adipose tissue, or body fat, can be stored either subcutaneously (under the skin) or viscerally (surrounding the internal organs). The location on the body where fat is stored varies depending on gender, race, and genetics. For instance, during times of weight gain, women tend to store fat around the hips and thighs, while men deposit around the middle. Thus, the broad generalization is that women resemble “pear” and men resemble “apples” Besides the external/cosmetic result, the internal/clinical ramifications of fat storage depend on the location as well.

Adipocytes, or fat cells, make up adipose tissue and play a critical role in energy regulation and homeostasis. During infancy, adipocytes are brown in color and function completely opposite to the white adipocytes found in adults. Brown adipose tissue utilizes energy to mitochondrial uncoupling proteins that convert the brown adipocytes into the white adipocytes, which function as energy storage facilities.

As energy intake exceeds energy consumption, these white adipocytes will store this extra energy as triglycerides. During starvation, the body depends on the adipocytes to release excess energy stores in the form of free fatty acids. However, if the body is in a constant state of excess energy, the adipocytes steadily enlarge. Once an adipocyte reaches its maximum capacity, the cell divides (also known as hyperplasia) leaving the body with additional repositories for energy reserves.

The body’s ability to create new adipocytes all but diminishes after puberty. Only in extreme cases does adipocyte hyperplasia occur in adulthood. This shows how being overweight as a child can lay the foundation for a lifetime of obesity. Weight gain as an adult is mainly achieved through adipocyte enlargement or hypertrophy. This simple action seems to be the key contributor to the varying and catastrophic effects of obesity.

During hypertrophy, the adipocyte secretes various molecules known as adipokines. These adipokines act as signaling messengers and are believed to be involved in some of the harmful side effects and co-morbidities associated with obesity. The key concept is that adipose tissue is a highly active metabolic and endocrine organ and can lead to serious consequences if increased significantly by weight and by size.

Increased weight gain makes it more difficult to feel full. Leptin is one of the hormones secreted, and it acts as a circulating signal to reduce appetite. Obese individuals are subject to high concentrations of leptin, which can develop into a resistance to the hormone in the muscle, liver, and hunger-related neurological pathways. Due to the leptin signal resistance, obese individuals have difficulty feeling satiated during or after a meal.

Data suggest that adipocyte secretions are involved in metabolism and the onset of type 2 diabetes. Though there are conflicting results, numerous studies suggest there is an increased resistin concentration in the body as a result of increased adiposity. Researchers suggest that the higher resistin concentration is correlated to insulin resistance. Additionally, as fat mass increases, TNF (tumor necrosis factor)-alpha increases. TNF-alpha negatively impacts blood sugar absorption by the liver and muscle and signifies another potential cause of insulin resistance.

Excess is always a concern, and more fat can lead to heart disease and even cancer. In obese individuals, adipocytes are more regularly releasing energy in the form of triglycerides. Elevated levels of triglycerides are linked to atherosclerosis and thus believed to increase the risk of heart disease and stroke. Adipose tissue also releases oestrogen, which when unchecked by the necessary countering hormones (progestin or estradiol) can increase the risk of cancer.

New Insight Into Cardiovascular Disease

A seldom-measured amino acid that is circulating in your blood may be an indication of cardiovascular disease. It is called homocysteine, and an increasing number of physicians and researchers are acknowledging that high levels of the chemical are associated with heart disease and stroke.

A summary of 15 studies revealed that elevated homocysteine levels produced a 70 percent increase in the risk of coronary artery disease and a greater risk for stroke. Previous studies have shown connections with schizophrenia, Alzheimer’s disease, hypothyroidism and anemia.

However, the evidence is not conclusive. “Five other studies found no link between homocysteine and cardiovascular disease,” says Oklahoma City internist Dr. E. Randy Eichner, a member of the Editorial Board of The Physician and Sportsmedicine, “but six studies did find a relationship. I think the balance of scientific evidence favors a homocysteine/CAD link.”

Atlanta cardiologist Dr. John Cantwell agrees with Eichner. “I recognize it as a possible risk factor, but the only time I measure it is when a person has a family history of heart disease without the more obvious risk factors.”

Dr. M. Rene Malinow, professor of medicine at the Oregon Health Sciences University and one of the nation’s leading homocysteine researchers, says we don’t yet know for sure that it is a cause of atherosclerosis. “We will have to wait for the results of clinical trials, and that could take several years.” Adds Malinow, “Although it is a relatively new risk factor by itself, it is possible that a high homocysteine level combined with traditional risks, such as hypertension or smoking, is even more significant.

Even those who think homocysteine is related to heart disease are not sure why it may have a harmful effect. One theory is that, in elevated amounts, it irritates the inner lining of the arteries and could cause blood clots to form. There is even a possibility that homocysteine levels increase after a stroke, not before.

Prevention

The good news is that a high homocysteine count can be prevented or treated by getting adequate amounts of folic acid (folate). Cantwell tells patients who have high levels to take 0.4 mg of folic acid per day, as well as a multivitamin supplement that includes B6 and B12. A high intake of folate by itself can mask other medical conditions, including a type of anemia.

The U.S. Food and Drug Administration has mandated that all enriched grain products be fortified with folate. Check the labels on cereal boxes. Most of them provide 25 percent of the daily folate requirement and many contain 25-35 percent of daily vitamin B6 and B12 needs. If you are eating a well-balanced diet, you probably don’t need the supplements.

Screening

Homocysteine screening is not very common. The American Heart Association is taking a very conservative position on the issue, saying that it’s too early to recommend general screening. Cantwell points out that the one-year cost of a folate and multivitamin supplement is approximately equal to the cost of a screening test.

Americans are well informed of the risk factors associated with heart disease. Sooner or later, a new one — elevated homocysteine levels — may be added to that list.

Folate is also good for unborn babies.

Who is at risk for Alzheimer’s?

We’re all at risk now by virtue of the fact that we are part of an aging population. It’s clear that the biggest risk for Alzheimer’s disease is aging. That’s why we know so much about it now. In this century the population is aging more successfully than ever before.

Alzheimer’s wasn’t as prevalent because we weren’t living as long?

Yes. At the turn of the century the average age life expectancy for males in some European cities was only 40 or 50-years-old. Now it’s 20 or 30 years more than that. So we didn’t see the population coming into the age that put them at risk for developing the disease.

Talk about the vascular connection

The connection has been known for a long time, ever since Alzheimer described the disease. There’s a small protein called amyloid that gets deposited in the brains of those that suffer from Alzheimer’s disease. There’s always been a question of how it causes the disease and if it has any normal functions. We started to look into that problem several years ago. One of the things we found was that when amyloid comes anywhere near blood vessels, it causes them to constrict and stay constricted. That was a novel finding, and there are several implications. This might be part and parcel of the Alzheimer process, that there may be a tendency of the vessels in the brain to close down and stay closed down. Of course that would have implications for delivering oxygen and nutrients to the nerve cells in the brain.

So this connection happens years before the amyloid?

Yes. One of the interesting aspects of this is that in full-blown Alzheimer’s disease you have aggregations of amyloid that precipitate out. They come out of solution and form plaques in the brain. Our findings occur with much lower concentrations. So the implication is some of the affects that we’re looking at occur many years early on before the disease really becomes full-blown and recognized in the way that we see it clinically.

Would you be able to see the vessels closed on an MRI or something?

I wish we could, but it’s very difficult to do that in humans. We have done animal studies that show that. The animals that produce too much amyloid do close their vessels, and they stay closed. That gives them significant problems.

Is this the same as somebody who has cardiovascular disease? If they have cardiovascular problems, would they be at a higher risk for Alzheimer’s?

If you have a little bit of Alzheimer’s and you have a little bit of cerebral vascular disease or even cardiovascular disease, those things can combine in a way that makes them both work. You can see individuals that have a slight amount of Alzheimer’s disease pathology and normally wouldn’t have any symptoms. If they have cerebral vascular problems on top of that, then they start to display symptoms.

People might see that and say, “If I had a heart attack, then I might be an Alzheimer’s patient later on.” Is that true?

If you have a heart attack then you usually have some form of atherosclerosis or some form of vascular disease. Quite often it extends to elsewhere in the body. Yes, that does put you at risk for increasing the expression of Alzheimer’s disease. In other words, it does put you at risk for having Alzheimer’s symptoms before you normally would if you just had Alzheimer’s alone.

Now that you understand this connection, where do you go from here?

What we’ve been working on for the last couple of years is finding out exactly why the vessels close down. To start with, we thought that it was mediated by free radicals. These substances increase with age and are generally thought to be bad news in a number of conditions. However, what we actually found out is the vessels close down because they began an inflammatory response. It’s the same as when you first scratch yourself the skin blotch is white because there’s an immediate inflammatory response. In fact, the blood vessels in the brain are doing something very similar when they come into contact with amyloid.

How would you treat this?

If we block the actual molecular mechanisms, the chemicals that are switched on inside cells, we can stop the effect. We’ve already demonstrated that in the experimental situation. Now what we have to do is demonstrate that in the clinic. That’s the next step.

Could drugs used for cardiovascular disease be used?

Yes. One of the first drugs we’ve investigated that blocks this effect in the experimental situation has been used for other conditions. It’s never been used for Alzheimer’s disease, but it has been used for cardiovascular disease. It’s that kind of drug that we want to test in a clinical situation.

What are those drugs?

We don’t have the full FDA approval to say.

Do antioxidants help?

As far as the vessel discovery is concerned, antioxidants mop up free radicals, and free radicals seem to make the situation much worse. That was one of the first things we found. So we’re not pursuing that in the clinic.

Using the cardiovascular connection as an identifier, it could be years before we see Alzheimer’s. How do you treat current Alzheimer’s patients if it’s already beyond that?

One of the other groups of patients that we look at are people that don’t have Alzheimer’s disease but are before that stage. They are memory-impaired but don’t have full-blown Alzheimer’s disease. If we follow a group like that, then we know that a certain percentage, quite a high percentage convert to Alzheimer’s disease every year. They would be an ideal population for us to give this medication to. That would be a much better intervention than waiting until folks have full-blown disease. That group is a target population for us.

So people who already have it might not benefit from this?

It’s generally recognized that once you’ve had the disease for five or six years then there’s very little that medical intervention can do now. The real target populations are those folks that are in the very early stages of Alzheimer’s disease or who would develop Alzheimer’s disease in the next several years. Right now those are the groups that we are actively recruiting into our study.

How do you identify those people?

We have sophisticated memory screens that give evaluations. These evaluations look at every aspect of memory and distinguish those effects that are truly pathological from those that are simple forgetfulness, which we all suffer from in one form or another.

Will you identify whether or not the amyloid is present?

We can’t detect amyloid in the brain. There’s no known way for us to do that at this stage. What we have to do is identify individuals who have memory impairment but don’t have full-blown Alzheimer’s disease and recruit those into our studies knowing that the largest majority of those will in fact develop the disease over a four- or five-year-period.

If I know somebody in my family who has it, what are my chances of developing Alzheimer’s?

One’s risk for the disease is definitely increased if you have a family history. However, the reality of that statement is it’s such a prevalent disorder, if most of us look far enough into our family histories we’ll find a case of Alzheimer’s disease. That’s just another way of saying that as we get to be 80 or 90 we’re all at risk for the disease. However, if you have a strong family history in addition to age, your risk is increased still further.

Are men or women more at risk?

Men and women are equally at risk for the disease. Men tend to die from other things before they get Alzheimer’s disease. So there’s an imbalance in the absolute numbers in the population. If you just take 100 women and 100 men, they’re equally at risk for the disease as they age.

News Source: Ivanhoe Newswire – 1999