Vitamin E and other antioxidants in the prevention of cardiovascular disease

Oxidative stress is believed to play a crucial role in the initiation and progression of atherosclerosis disease. Steinberg and colleagues were among the first to postulate that modified low-density lipoprotein (LDL) could account for the accumulation of lipid within macrophages, a critical early step in the formation of the atherosclerotic plaque. In the early phases, native LDL may amass in the subendothelial arterial space and may be minimally oxidized by resident vascular cells through the activity of such enzymes as 12/15-lipoxygenase. In turn, this minimally modified LDL leads to the production of chemotactic factors and granulocyte and macrophage colony-stimulating factors, which enhance recruitment of circulating monocytes and their differentiation to macrophages in the vessel wall.

Plaque stability is believed to be influenced by levels of inflammatory mediators locally, which may stimulate expression of a number of proteolytic enzymes that lead to plaque fragility and rupture. These inflammatory actions encourage further oxidization of LDL, leading to both structural and functional changes in the vessel. Macrophages avidly accumulate LDL particles modified by oxidation or acetylation through a number of scavenger receptors, including CD36 and scavenger receptors A-I/II, leading to the formation of foam cells and development of the atherosclerotic plaque. At the same time, oxidized LDL species are directly toxic to vascular cells, and lead to endothelial injury and dysfunction, disabling, among other things, the intrinsic antiplatelet effects of this protective barrier, as well as the generation of nitric oxide, with deleterious effects on vascular tone and reactivity.

The importance of oxidized LDL in atherogenesis has been further confirmed by the use of specific antibodies to oxidized LDL, which have been shown to be local to atherosclerotic lesions in the vessel wall. Oxidative stress may con­tribute to atherogenesis by mechanisms that are not necessarily linked to LDL oxidation. For example, free radical oxygen species such as superoxide anion can rapidly react with and inactivate nitric oxide, enhancing proatherogenic mechanisms (e.g. leucocyte adherence to endothelium, impaired vasorelaxation, platelet aggregation).

Although enzymatic and nonenzymatic oxidation of LDL seems to be involved, its relevance in the evolution of human atherosclerosis is still unclear. An important matter of discussion is the evident discrepancy between experi­mental and clinical trials with antioxidants, that, in fact, provided divergent results. Most trials with antioxidants in experimental models of atherosclerosis demonstrated that this treatment is able to retard the progression of athero­sclerosis while the results of clinical trials are conflicting, in that positive as well as negative effects has been reported. The investigation of antioxidants for prevention of atherosclerosis stems from observational trials that demonstrated the existence of an inverse relationship between the consumption of antioxidant vitamins and the risk of cardiovascular events. However, meta-analysis of the observational studies indicated that among antioxidant vitamins, vitamin E was the only one that exerted a beneficial effect against atherosclerotic complications.

On the basis of these data almost all the trials have been based on the assumption that supplementation with vitamin E would represent a useful approach for preventing cardiovascular disease. However, candidates for anti­oxidant treatment were not accurately defined: any patient at risk of cardiovascular events has been indiscriminately enrolled in those trials. We argue that antioxidant status represents an important marker of oxidative stress, its determination may be useful for better identifying candidates for antioxidant treatment. In order to substantiate this hypothesis, data inherent to oxidative stress and antioxidant status in patients at risk for cardiovascular disease and in patients included in observational and interventional trials have been reviewed. As antioxidant vitamin E has been the subject of the most important research in this field, our analysis is essentially concentrated on the clinical relevance of this vitamin in patients with cardiovascular disease.

What You Need to Know about Olive Oil and Other Fats

Fat. Does the word make you cringe? Fat is bad, bad, bad … isn’t it? Eating fat makes us overweight, gives us heart attacks, causes cancer, wrecks our health … doesn’t it? If it says “fat free,” it must be healthy … isn’t that true?

Yet, if fat is so bad, how is it that in certain Mediterranean regions such as the Greek island of Crete during the 1950s, where heart disease and other chronic disease rates were startlingly low, fat consumption was about equal to fat consumption in America? Cretans during this time in history were among the longest-lived people in the world. Yet their diet was full of fat.

According to researcher Ancel Keys, Cretans consumed 3 to 4 ounces (or about 1/2 cup) of olive oil per day, per person. That’s a lot of fat! Keys reported that the people of Crete drenched their salads in it, dunked their bread in it, poured it on their potatoes. Some Cretan farmers even drank a wine-glass full of the stuff for breakfast! Why weren’t the people on this tiny island suffering from the same health problems as Americans during the 1950s and 1960s, those health problems we’ve been told had (and still have) everything to do with too much fat in our diets?

Perhaps Crete is an anomaly? Yet studies from other countries reveal similarly striking results. Heart disease rates in the southern, or rather the Mediterranean, regions of Italy, Spain, and France were also remarkably low, even though percentage of fat calories varied greatly around the region.

Yet not every country could get away with fat consump­tion to the degree enjoyed in the Mediterranean. Keys’s studies of fat consumption and diet also included Finland, the country with the most coronary heart disease and the shortest life spans in Europe. Keys examined middle-aged men in Finland to determine why coronary heart disease was so common in this country, even among men who were thin­ner and more physically fit than many of the overweight, less fit American men in Keys’s studies. Blood cholesterol levels of the Finnish men proved to exceed average levels in American men.

Subsequent dietary surveys revealed that the typical diet in Finland was extremely high in saturated fat. According to Keys, meals included “great mounds of butter,” and it was not unusual to see “grown men down a couple of glasses of rich milk.” Keys also relates watching Finnish loggers take “slabs of cheese the size of slices of sandwich bread, smear them a quarter of an inch deep with butter and eat them with a beer as an after-sauna snack.”

Other studies conducted by Keys revealed that among pa­tients with very high blood cholesterol levels, diets very low in fat produced dramatic drops in cholesterol levels within one week, and studies examining the effects of different types of fatty acids—saturated, monounsaturated, and polyunsaturated—on blood cholesterol levels revealed that saturated fatty acids tended to raise blood cholesterol levels the most.

It would seem, then, that the type of dietary fat, not just fat in general, is specifically related to the risk of developing coronary heart disease and other chronic diseases. Does this mean some fat is “good” and some fat is “bad”? That we should eat all of one and none of the other?

Actually, the fat issue is a complex one, and not simply a matter of “bad” and “good,” as the media often imply. For instance, just because the Cretans drowned their food in olive oil doesn’t mean we can do the same and remain slim with unclogged arteries. The residents of rural Crete had far more active lifestyles than most Americans today. Also, sci­entists now know that fat per se isn’t bad. On the contrary, fat is beneficial and even necessary to a healthy, fully func­tioning body. However, certain types of fat in differing pro­portions do apparently tend to be more or less beneficial to health.

Americans eat a lot of saturated fat, mostly from animal sources. The residents of Crete during the days of Ancel Keys’s research were eating almost all their fat from plant sources, namely olive oil. What’s the difference? While oil of any type is 100 percent fat and has the same number of calories as any other oil, each oil or fat type has a different composition—its own ratio of saturated to monounsaturated to polyunsaturated fatty acids. And the fatty acid makeup of an oil appears to make all the difference. The fatty acid com­position in, say, a cheeseburger, is far different from the fatty acid composition of a calorie-equivalent portion of olive oil.

Let’s look back at Greece. According to Keys, at the time of his research, the general Greek population received ap­proximately 20 percent of their calories from olive oil alone, with total fat intake ranging around 35 percent. (People liv­ing on the island of Crete had total fat intakes exceeding 40 percent of daily calories, again, mostly in the form of olive oil, as reported in the American Journal of Clinical Nutri­tion.) Keys describes the rural Greeks, who were accus­tomed to traditional eating habits and who couldn’t afford richer foods, as “remarkably healthy.”

The wealthier popu­lation of Athens, on the other hand, tended to eat food more inspired by the French school of cooking (more prevalent in non-Mediterranean, northern France), which is relatively heavy on butter and cream compared to olive oil. Although no study has proven a direct correlation between these var­ied diets in Greece and heart disease, Keys could not “help but mention” that Athens had no shortage of wealthy coro­nary heart disease patients. Keys’s observations signifi­cantly complicate the simplified message Americans have been accustomed to hearing over the past fifteen years or so: that fat is bad and we should eat less of it. Fat is not “bad.” We need fat to function. The trick is how to consume it in a way that maximizes our health and gives us the best possible protection against chronic diseases like coronary heart dis­ease and cancer.

How Vitamins, Minerals and Other Supplements Can Boost Your Brain to the Max

Whether you are young, old, or in between, taking vit­amin-mineral supplements can improve brain func­tion, possibly boost performance on IQ tests, improve mood and memory, and slash the chances of brain deteri­oration as you get older. Indeed, the evidence is so com­pelling that it seems incredible everyone is not taking vitamins, minerals, and antioxidants to keep their brains functioning at peak levels for a lifetime.

As Dr. Denham Harman, professor emeritus at the Uni­versity of Nebraska, and others demonstrated in animals or humans as long ago as the 1950s, your brain, general health, and longevity are initially shaped long before you are born by the vitamins and antioxidants your mother ingests during pregnancy and even before conception.

A string of studies, many done a decade ago and seemingly lost to public consciousness, have found that giving multi-vitamins and specific vitamin supplements to schoolchild­ren can dramatically increase IQ scores. Research among adults of all ages also finds that certain vitamin and min­eral supplements improve mood, learning ability, memory, attention span, eye-hand coordination, and reaction times, even in people who show no overt signs of deficiency.

Further, mountains of stunning evidence have piled up in the last few years, documenting that middle-aged and older people can stave off intellectual deterioration and even retrieve mental faculties thought lost forever by tak­ing vitamins, particularly antioxidant vitamins and B vita­mins. In one remarkable finding, vitamin E equaled a potent pharmaceutical drug in treating the most dreaded brain disease of all—Alzheimer’s. Vitamins also protect the brains of normal healthy people. A recent random survey of 880 elderly men and women by European researchers showed that those with high vitamin and antioxidant blood levels had stronger intellectual powers, less depression, and less risk of losing their brains to dementia.

Then why isn’t everyone downing vitamin supplements to maximize mental functioning? Since vitamins and min­erals are generally safe in required doses and relatively inexpensive compared with remedies needed to rectify the potential damage to society in health and educational costs of not taking vitamins, why isn’t the practice more wide­spread and medically encouraged?

One reason is conventional nutrition still maintains that the brain is not impaired unless the body is in a state of classic malnutrition, induced only after serious and pro­longed deficiencies. Such malnutrition, characterized by overt physical signs of wasting away and rock bottom blood levels of nutrients, is considered rare in Western countries.

However, more daring researchers argue that the brain is the target of subtle deficiencies that leave it secretly impoverished long before any physical signs of conven­tional malnutrition are noticeable. It’s well known that a wide range of vitamins and minerals are linked to psycho­logical functioning and that many such nutrients are miss­ing in typical high-fat, highly processed diets. “What is adequate to prevent physical signs and symptoms of mal­nutrition may not be adequate to prevent impaired mental function,” says researcher Steven J. Schoenthaler at Cali­fornia State University.

Even the tiniest deficiencies could cause subtle and undetected disruption in psychological functioning, con­tends David Benton, a world-renowned research psycholo­gist at University College in Swansea, Wales. “Cognitive activity,” says Dr. Benton, “involves the summated activity of many billions of neurones, and countless biochemical pathways and their associated enzymes. It may well be that relatively small dietary deficiences that are dismissed as causing only minor changes to the activity of a single enzyme, will along with many other similar minor effects, have a measurable and potentially important cumulative influence on cerebral functioning.”

Much evidence, in fact, raises the specter that modern western society is rife with a pernicious form of “subclin­ical” (symptomless) or “marginal” malnutrition that leaves no obvious traces of brain malfunction. The brain may get enough vitamins and minerals to appear to function “nor­mally.” But is it really operating at optimal levels? Some researchers believe substantial segments of the population do not get nearly the levels of vitamins and minerals needed to optimize brain function. Deterioration in mental func­tion previously attributed to “normal aging,” may, in fact, be at least partly due to subtle undetected and correctable deficiencies of specific vitamins needed by the brain, says Katherine Tucker, associate professor of nutritional epidemiology at Tufts University. “It’s a new and powerful idea,” she says, “with accumulating evidence to support it.”

It seems obvious that the poor-quality, high-fat, low-vitamin diets of many Americans, sadly, including school­children, are inadequate to fuel peak brain performance, and that undernourished brains might perk up when sup­plied vitamin and mineral supplements. In short, our brains quietly survive and endure on poor diets in a permanent state of lethargy that we accept as “normal” because we can’t imagine otherwise. We are unaware that we have the potential to be smarter and feel better—that our brains, when properly nourished, can reach for and achieve more and function at higher levels.

BOTTOM LINE: Vitamins, impressive studies show, can help ensure maximum brain functioning from birth to old age.