by Mark F. McCarty, Ph.D.
Ironically, an essential nutrient which probably has greater promise than any other for human cancer prevention, first came to scientific attention as a toxin that was poisoning animals.
When Marco Polo made his legendary trip to China, his party passed through a region in which most of his horses became very ill; in the horses most severely affected, their hooves literally fell off! This was one of the first recorded instances of a disease which is now known as "blind staggers".
Investigations early in the twentieth century established that blind staggers is only encountered in areas where the soil is very rich in the mineral selenium, and in which special plants grow ("indicator plants" of the genus Astragalus) that accumulate selenium from the soil. Blind staggers develops in animals that graze on these selenium-rich indicator plants and is thus a manifestation of selenium toxicity. Selenium poisoning can lead to nausea, garlicky breath, flu-like symptoms, loss of hair, fingernails or hooves, neurological problems, liver damage, and in severe cases respiratory failure and death. In the recent past, selenium earned notoriety as a suspected cause of the poisoning of birds at California's Kesterton Reservoir.
Selenium as an Essential Antioxidant
Selenium's reputation as a toxin was well established in the mid 1950s when Dr. Klaus Schwarz, a German physician-scientist who had emigrated to the United States, made a breakthrough in understanding a perplexing form of liver failure in rats known as dietary hepatic necrosis. For reasons that were then unclear, rats developed fatal liver degeneration when fed a vitamin E-deficient diet in which the sole source of protein was torula yeast. Surprisingly, the vitamin E deficiency did not result in liver failure when brewer's yeast was the source of protein. Although some scientists suspected that torula yeast was harboring a toxin, Schwarz and his colleague, C.M. Foltz, hypothesized that torula yeast was lacking some hitherto unknown essential nutrient that was adequately supplied by brewer's yeast. Years of painstaking trial-and-error work were finally crowned with success when they discovered that the mineral selenium present in brewer's yeast and virtually absent in torula yeast could completely prevent liver failure when added in tiny amounts to the torula yeast-based diet
Schwarz recognized that either vitamin E or selenium could prevent liver damage, but that simultaneous deficiency of both resulted in fatal liver failure. Schwarz coined the term "ambogenous" to refer to two nutrients which can in effect "pinch hit" for each other in maintaining healthful physiological function.
Since vitamin E was known to protect cells from the damaging effects of highly reactive compounds known as "free radicals", produced not only by certain toxins and high energy radiation but also by normal metabolism, it was logical to expect that selenium likewise was somehow contributing to protection from free radicals. This supposition was verified when, in 1973, scientist John T. Rotruck and colleagues published their demonstration that selenium is an obligatory component of the crucial antioxidant enzyme "glutathione peroxidase"
Hydrogen peroxide and organic peroxides are normal by-products of metabolism. If allowed to react with free atoms of iron or copper, peroxides break down to yield the hydroxyl radical most viciously reactive and dangerous of the free radicals. For this reason, cells contain two types of enzymes glutathione peroxidase and catalase that can dispose of peroxides, converting them to water and other harmless products. The dependence of glutathione peroxidase on nutritional selenium clarifies the antioxidant role of this essential trace mineral.
The discovery of selenium's nutritional essentiality quickly had a major impact on the livestock industry in many regions of the world. Livestock experts soon discovered that a number of diseases of obscure origin afflicting livestock only in certain specific regions disorders such as white muscle disease in sheep and cattle, mulberry heart disease in pigs, and exudative diathesis in poultry were in fact selenium-deficiency diseases encountered only in areas where the soil was quite low in selenium. Addition of selenium to animal feeds rapidly eliminated these diseases and literally saved the livestock industry in New Zealand and other low-selenium regions.
Humans appeared to be less prone to selenium deficiency disease, perhaps because most humans are omnivorous. (Since selenium is essential for animals but not for plants animals raised on low-selenium feeds or forage tend to retain as much dietary selenium as possible, with the result that the meat of these animals tends to be a better source of selenium than the plants they eat.) Nevertheless, research by Chinese scientists established that two distinct pediatric syndromes encountered only in certain regions of China a severely deforming arthritis and an often fatal heart failure syndrome were in fact selenium deficiency disorders readily preventable by selenium supplementation.
China in fact is a fascinating "laboratory" for assessing the impact of selenium nutrition, since some parts of this country have selenium soil levels that are extremely low, whereas in other areas the selenium level is so high that many people suffer from a "selenosis" syndrome characterized by loss of hair and nails, garlic breath, and flu-like symptoms.6
The Cancer Connection
A possible connection between selenium status and cancer risk was first raised by early studies reporting that high (toxic) selenium intakes induced liver cancer in rats. Subsequent efforts by other scientists to confirm this finding failed to do so; apparently, the initial investigators had misinterpreted selenium-induced liver damage as cancer.7
Working at Roswell Park Memorial Institute in the early 1960s (not long after selenium's nutritional essentiality was established), Dr. Raymond Shamberger and colleagues envisioned an anticarcinogenic role for selenium. Knowing that free radical-generating drugs increase the yield of cancers in carcinogen-treated mouse skin, they hypothesized that topical application of certain antioxidants including selenium might lessen the incidence of skin cancers. Their study documented a profound reduction of skin cancer incidence in the carcinogen-treated mice given topical sodium selenide indeed, the selenium was far more effective than any other antioxidant they tested.8 Their report, published in 1966, encouraged a great number of subsequent animal studies which over the next two decades demonstrated that selenium was the most versatile and potent anticarcinogenic agent known, at least with respect to animal models of cancer induction.
In subtoxic dietary concentrations (0.5 - 0.2 parts-per-million of diet) higher than those needed to optimize the activity of glutathione peroxidase, selenium has been found to protect rodents from virtually every carcinogen tested, often reducing tumor yield by 50% or more.7-11 Selenium is effective when administered prior to the carcinogen, but also often is effective when selenium supplementation begins several days after the carcinogen is given.12 (Thus, oncologists would say that selenium is protective with respect to both the "initiation" and "promotion" phases of cancer development.) Dietary selenium is also protective in hairless rodents exposed to excessive ultraviolet light, preventing both inflammation and induction of skin cancers.13,14 Finally, selenium has been shown to protect mice from virally-induced breast cancer.15 The roster of cancer scientists responsible for these findings is impressive and includes Drs. Shamberger, Gerhard Schrauzer, Maryce Jacobs, A. Clark Griffin, John Milner, Diane Birt, Karen Burke, and Clement Ip.
The potency of selenium's anticarcinogenic activity is no less remarkable than its versatility. A rat consuming dietary selenium at 1 part-per-million is getting about 20 mcg of selenium daily only 1/50th of a milligram. Although many other nutrients, phytochemicals, and drugs show anticarcinogenic activity in various animal models, none do so in such a tiny dose.
How on earth does selenium provide protection from such a wide array of carcinogenic insults? Phytochemicals such as those found in cruciferous vegetables or green tea seem to work primarily by modifying the metabolism of carcinogens such that they are detoxified and excreted, preventing them from interacting with DNA to induce mutagenic damage. While there is limited evidence that selenium can favorably influence carcinogen metabolism in certain animal cancer induction models,16 its effect in this regard does not appear to be as regular or substantial as that achieved with many phyto-chemicals. It seems more likely that selenium promotes the efficiency of DNA repair after activated carcinogens have damaged DNA; unless this DNA is quickly repaired, a permanent mutation in the genetic code may result that can contribute to the generation of a cancer. At least two published scientific studies suggest that selenium may indeed expedite repair of carcinogen-damaged DNA.17,18
However, this mechanism obviously cannot account for protection afforded by selenium administered substantially after carcinogen treatment, nor for protection from mammary tumor viruses. An alternative suggestion offered recently is that selenium may promote a protective process called "apoptosis", whereby damaged cells literally "commit suicide".19,20 Such a mechanism would presumably reduce the production of genetic mutations, but might also help rid the body of pre-cancerous cells that have already sustained mutations. There is growing evidence that apoptosis plays an important role in determining whether mutated pre-cancerous cells can survive to give rise to malignant tumors.21,22
Yet another possibility is that selenium controls cancer incidence by boosting the immune defenses. In rats, in roughly the same sub-toxic concentrations that are anti-carcinogenic, selenium stimulates the type of immunity (cellular immunity) that attacks cancers and virus-infected cells.23,24 It is not yet clear whether immune stimulation contributes meaningfully to the anticarcinogenic actions of selenium, and indeed the role of immune surveillance in controlling cancer incidence is now in doubt.25 Perhaps the immunostimulant impact of selenium will have greater relevance to control of infectious disease. Drs. Julian Spallholz and Lydia Kiremidjian-Schumacher have made prominent contributions to our understanding of selenium's impact on the immune defenses of rodents.
Surprisingly, recent research suggests that selenium's antioxidant function may have little or nothing to do with its anticarcinogenic actions in carcinogen-treated animals. Drs. Howard Ganther and Clement Ip have presented evidence that a metabolite of selenium, methylselenide, may be primarily responsible for selenium's anti-carcinogenic effect;26 this metabolite is not one of the most effective sources of selenium for glutathione peroxidase. (And recall that the optimally anticarcinogenic selenium intakes are far higher than those required to maximally activate glutathione peroxidase.) Presumably, methylselenide mediates some of the protective effects discussed above, but how it does so is entirely unknown.
However, it must be noted that induction of cancer with massive doses of carcinogens in animal studies, may not be an accurate model for "spontaneous" cancer incidence in animals or humans. There is now evidence that much of the mutagenic damage that arises spontaneously in DNA results, not from attack by carcinogens or mutagens, but rather from damage to DNA by free radicals that are produced by normal metabolism.27 When free atoms of iron encounter hydrogen peroxide (or organic peroxides) in the immediate neighborhood of DNA, dangerous hydroxyl radicals are generated that can attack DNA and alter its structure, promoting mutation.28 Since good glutathione peroxidase activity is crucial for minimizing cellular levels of peroxides, it is logical to expect that poor selenium nutrition, by compromising glutathione peroxidase activity, will result in increased oxidative damage to DNA and thus increased cancer risk. However, this concept requires further verification in scientific studies.
Evidence for Human Cancer Protection
All of this data from animal studies is fascinating, but what is the relevance to human cancer risk? Dr. Shamberger and colleagues were the first to attempt to address this question. Since soil selenium levels vary a great deal from region to region in the United States and throughout the world, and since the food crops raised in these soils show a corresponding variability in selenium content, it is reasonable to expect that, if increased selenium intakes can indeed lower human cancer risk, the incidence of many cancers should in fact be lower in areas with selenium-rich soils. In the early 1970s, using recent agricultural data regarding the selenium content of soils throughout the U.S., Dr. Shamberger published evidence that age-adjusted cancer rates did in fact tend to be lower in states with above-average selenium soil levels.29,30 Although Dr. Shamberger's analysis was subject to certain criticisms for example, many of the high-selenium areas were in the less industrialized portions of the country Drs. Larry Clark and Gerald Combs (then both at Cornell) re-analyzed the data previously examined by Shamberger, using much more sophisticated statistical methods, and concluded that Shamberger in fact was right that the incidence of most major types of cancer did indeed tend to correlate inversely with soil selenium levels.30,31 Meanwhile, Dr. Gerhard Schrauzer had conducted similar analyses on an international scale, and did indeed find that, with the exception of stomach and liver cancer, cancer incidence tended to be lower in countries with greater estimated selenium availability.32
The most exciting epidemiological work of this type (so-called "ecologic" studies) was conducted in China. China is an ideal laboratory for such studies because there are extreme variations in soil selenium content from region to region and, until recently, people tended to live in a single area all their lives, eating primarily locally grown foods. (Contrast this with the U.S., where soil selenium variations are less dramatic, many people move frequently, and most of the food we eat is not locally grown.) Dr. Shu-Yu Yu and colleagues measured the selenium content of blood stored in blood banks in 30 different regions of China, and used this data to classify the regions as either high-selenium, medium-selenium, or low-selenium (10 regions per group).
They then looked at total death rates from cancer in the low-selenium, medium-selenium, and high-selenium groups of provinces. Incredibly, they were in the ratio of 3 to 2 to 1! That is, the cancer death rate in the high-selenium regions was only about one-third that of the low-selenium regions!33 This finding, published in 1985, was criticized for technical reasons by other epidemiologists (for example, Dr. Yu did not use age-adjusted death rates), and received very little serious attention from scientists or the media. Nevertheless, Dr. Yu's findings were so stark and dramatic that, even making ample allowances for technical flaws, they strongly suggested that increased selenium intakes, within a non-toxic range, could have a major impact on human cancer mortality.
The impact of selenium nutrition on human cancer risk has also been addressed in so-called case-control studies. Several studies which found lower blood selenium levels in cancer patients than in age-matched healthy control subjects, were not given much weight, as it was suggested that progressive growth of the cancers may have been responsible for the reduced blood selenium (that is, that the cancers caused the low selenium status, rather than vice versa.)
This objection has been addressed in prospective case-control studies. In studies of this type, thousands of healthy subjects donate blood, which is kept in frozen storage for many years. When some of the donors subsequently develop cancer some years later, one or more donors who have remained healthy are chosen as an age- and sex-matched control for each cancer patient; the frozen blood samples from the cancer patients and their matched controls are then retrieved and analyzed.
If good selenium status does indeed provide protection from cancer, one would expect that selenium blood levels from the subjects who subsequently developed cancer would, on average, be lower than the selenium levels found in the matched controls. In fact, studies from Europe and the United States found precisely that.34-40
However, not all of the prospective case-control studies had positive outcomes;41-45 for example, a very large study which used toenail clippings from thousands of American nurses to evaluate selenium status, failed to observe lower selenium levels in those who subsequently developed cancer.42 It is not terribly surprising that some studies of this kind did not suggest a protective effect of selenium in the U.S., where people move frequently and eat food from many different parts of the world, a single determination of selenium in blood or toenail clippings may offer a relatively inaccurate assessment of lifelong selenium exposure. This problem is compounded by the fact that normal variations in selenium intake in the U.S. are relatively modest (at least in those who don't take supplements), so the impact of these variations on cancer rates will be correspondingly modest. Thus, the fact that some of the case-control studies did not have positive outcomes does not deal a crippling blow to the hypothesis that selenium may prevent human cancer.
Selenium Passes the "Acid Test" Unfortunately, epidemiological studies of this sort can only establish correlations, not causations. Even if higher blood selenium levels were correlated with lower cancer incidence in every epidemiological study ever done, this would not in itself prove that increased selenium intakes cause the reduced cancer risk. For example, there might be some unknown third factor which prevents cancer while promoting higher blood selenium levels. The "acid test" for proving a causative relationship is a double-blind clinical trial. Thus, if people receive either a selenium supplement or a matching placebo for many years, and the subsequent incidence of cancer is significantly and substantially lower in those who (unknowingly) received the selenium, it can reasonably be concluded that the increased selenium intake did indeed prevent cancer.
Unfortunately, when dealing with a disease that has a gradual onset over many years such as cancer, it is extremely difficult and expensive to organize such a study. Usually, millions of dollars in funding are required, as well as the cooperation of hundreds of subjects and dozens of physicians for a number of years. Given the fact that selenium had received little publicity, was often thought of as a toxin, and had no wealthy pharmaceutical sponsors (as had the antioxidant vitamins), it is not surprising that data from controlled supplementation studies was not available until recently.
The first findings from controlled cancer prevention studies with supplemental selenium were published by Dr. Shu-Yu Yu and colleagues.46 Working in Qidong County, which has a very high incidence of liver cancer associated with endemic hepatitis B infection, Dr. Yu chose 226 subjects who were at high risk for liver cancer as indicated by the presence of hepatitis B antigen in their blood.
They were randomly divided into two groups of 113 subjects each; one group received daily tablets providing 200 micrograms of selenium as high-selenium yeast, while the other group received matching placebo tablets. Supplementation continued for four years. At the end of this time, five cases of liver cancer had developed in those receiving the placebo, whereas none occurred in those taking the daily selenium supplement; there was less than one chance in twenty that this disparity arose by chance.
Simultaneously, Dr. Yu recruited 2,474 family members of people who had developed liver cancer (and thus were judged to be at increased risk for this disease). This group also was randomized to receive either 200 micrograms of yeast-selenium daily or a matching placebo. During the two years of this study, 13 of the 1,030 controls developed liver cancer, as compared to 10 of the 1,444 subjects receiving selenium. The incidence of liver cancer was thus 45% lower in the selenium-treated group, and again there was less than one chance in twenty that this difference represented a statistical fluke.
In conjunction with these two studies, Dr. Yu's group measured parameters of DNA damage (unscheduled DNA synthesis, micronucleus frequency) in whole blood cells drawn from the various groups after prolonged supplementation with selenium or placebo. In both studies, both indices of DNA damage were found to be significantly lower in those who had received selenium.
In one township of Qidong county, a small amount of selenium was added to the salt used in that township in 1984. The residents of this township continued to use this specially-treated salt for five years; at the end of this time, age-adjusted incidence of liver cancer had fallen by 35%. In four neighboring townships which did not receive selenium, no reduction in cancer incidence occurred during this time.
Dr. Yu's groundbreaking and crucial findings received no discernible publicity in the U.S. They were not published in a "name" medical journal, primary liver cancer is not one of the most common cancers in the U.S., many American scientists are too arrogant to give serious attention to studies done in Third World nations (even if they had thriving civilizations when our forbears were living in caves!), and most of the media had only heard of selenium as a poison that was killing birds.
Meanwhile, a much larger Chinese chemoprevention study co-sponsored by the U.S. National Cancer Institute was in progress in Linxian province, which is notable for its high incidence of esophageal cancer. 29,584 volunteers were randomized to receive one of four nutritional supplements daily; one of these groups received 50 micrograms of yeast-selenium in conjunction with RDA-level doses of vitamin E and beta carotene. When the study was concluded after five years, cancer mortality and total mortality had been reduced significantly by 13% and 9%, respectively, in those receiving the regimen including selenium.47 The less dramatic effects observed in this study are most likely attributable to the much lower dose of selenium used; nevertheless, even a 13% decrease in cancer mortality represents a tremendous reduction in human suffering. Owing to the inclusion of trivial doses of vitamin E and beta carotene in the supplement regimen, this study failed to unambiguously document a protective effect of selenium per se, and many people assumed that the better known antioxidant vitamins were responsible for the benefit.
The Breakthrough Clark Study Were it not for the dogged efforts of Dr. Larry Clark, the epidemiologist whose previous work had confirmed a correlation between increased selenium availability and lower cancer risk in the U.S., it seems likely that most Americans would still be totally in the dark with respect to the protective benefits of selenium nutrition.
Back in the early 1980s, Dr. Clark properly recognized that only a randomized, double-blind clinical study conducted in the United States could demonstrate to the satisfaction of American medical scientists that supplemental selenium had real protective potential for Americans. Since research funding was not readily available, Clark decided to attempt a study that might document selenium's cancer preventive potential in a relatively short time using a relatively small number of volunteers. He reasoned that people who had a past history of (non-melanoma) skin cancer were at high risk for developing additional skin cancers within just a few years. Since selenium had the capacity to prevent ultraviolet or carcinogen-mediated skin cancer in rodents, it was reasonable to expect that it likewise would reduce skin cancer incidence in humans, as suggested by some of Dr. Clark's own epidemiological research.48,49 So Clark decided to conduct a double-blind study to evaluate selenium's potential for human skin cancer protection.
The major agencies for funding clinical research initially showed little interest in Clark's proposal presumably they viewed selenium as too toxic, and were skeptical of the relevance of animal studies with sub-toxic selenium doses. But fortunately Clark was able to get started with a small grant from Nutrition 21, the San Diego company that had introduced high-selenium yeast for human supplementation back in 1975. Nutrition 21 also offered to donate the yeast-selenium tablets and matching placebo tablets required for the study.
Clark then began to enlist the aid of dermatologists and dermatology clinics in the southern states along the Atlantic coast (the Carolinas, Georgia, Florida), where soil selenium levels are relatively low. Volunteers were sought who had had a past history of non-melanoma skin cancer. Since several Veteran's Administration clinics agreed to participate, the majority of subjects enrolled in the study were males. Also, almost all the participants were white, as skin cancer is relatively rare in black people, owing to their protective pigmentation. As matters developed, it was quite propitious that the average age of the volunteers was around 63 an age group in which risk of cancer is relatively high.
The subjects were randomly chosen to receive either a daily tablet providing 200 micrograms of yeast-selenium, or a matching placebo made with regular yeast. To eliminate bias on the part of either the subjects or the physicians evaluating them, none of the participants knew who were getting the selenium supplements that is, it was a double-blind study.
Dr. Clark was encouraged by the enthusiasm and dedication of the dermatologists working with him, and a timely grant from the American Institute of Cancer Research kept the study going. As years passed and more subjects were enrolled, Clark was eventually able to persuade the American Cancer Society and the National Institutes of Health to provide more substantial funding.
Subject enrollment continued gradually but steadily from 1983 to 1990, by which time a total of 1,312 people had entered the study. In 1990, Dr. Clark decided to take a preliminary "peek" at the data (the subjects and their dermatologists remained unaware of who was getting the selenium). In one sense, the interim findings were disappointing the supplemental selenium did not seem to be preventing skin cancer. But when Clark looked at the incidence and mortality from other types of cancer he was gratified to observe a strong trend toward reduced cancer incidence and mortality in the subjects who were receiving selenium. Owing to the fact that a relatively large number of mostly elderly subjects had been recruited and followed for a number of years, a sufficient number of cancer cases were occurring in this group to enable an assessment of selenium's potential for preventing many of the killer cancers common in the U.S. With the help of the National Cancer Institute, Clark incorporated a cancer screening protocol into the study, and redefined the aims of the study to examine selenium's impact on incidence and death rate from all cancers.
In 1994, Dr. Clark and his colleagues took a look at cancer incidence and mortality in the study group by the end of 1993; the average enrollee had been monitored for an average of seven years at that time. Perplexingly, the incidence of non-melanoma skin cancer did not differ significantly between the subjects getting selenium or placebo. But when all other cancers were considered, the findings were dramatic cancer incidence had been 42% lower in those receiving the yeast-selenium 70 cases vs. 117 in the placebo group. The statistical significance of this difference was extremely high chances were less than 3 in 10,000 that the selenium hadn't really worked and this difference had arisen by chance. And the total cancer death rate had been 52% lower in the selenium group 28 deaths vs. 58 deaths in the placebo group a finding which likewise had exceptionally high statistical significance.
Clark looked at the findings from each of the seven clinics participating in the study, and found that in each of these clinics, cancer incidence had been lower in subjects receiving selenium. Also, in all but one of these clinics, the cancer death rate had been lower in those getting selenium. Such uniform results could hardly have been expected if the selenium weren't really preventing cancer. Since Clark knew that some medical scientists would be skeptical of the decision to redefine the goals of the study in mid-course (to look at total cancer incidence rather than just skin cancer), he looked at the total cancer incidence and mortality in the three years following this "mid-course correction" and found that they were 42% and 52% lower (respectively) i
Clark looked at the findings from each of the seven clinics participating in the study, and found that in each of these clinics, cancer incidence had been lower in subjects receiving selenium. Also, in all but one of these clinics, the cancer death rate had been lower in those getting selenium. Such uniform results could hardly have been expected if the selenium weren't really preventing cancer. Since Clark knew that some medical scientists would be skeptical of the decision to redefine the goals of the study in mid-course (to look at total cancer incidence rather than just skin cancer), he looked at the total cancer incidence and mortality in the three years following this "mid-course correction" and found that they were 42% and 52% lower (respectively) in the selenium group during this time results identical to those of the overall study. Clark also looked at the individual types of cancer. Not every type of cancer had occurred with sufficient frequency to determine whether selenium had influenced its incidence female-specific cancers were underrepresented because only a quarter of the participants were women but it was possible to conclude that selenium had significantly reduced mortality from lung cancer and decreased the incidence of both colorectal and prostate cancer. The 64% reduction in colorectal cancer incidence and 69% reduction in prostate cancer incidence were particularly striking. No type of cancer was significantly more frequent in those receiving the selenium.
Although the study had been scheduled to run through 1998, these interim results were so striking, definitive, and important that the committee monitoring the study voted to discontinue the study early and quickly publish the results of the findings through 1993.50
Plans are now afoot to set up a far larger controlled study that will enroll subjects from across the U.S., include a majority of women, and perhaps look at the impact of various doses of selenium. Needless to say, no signs of selenium toxicity were seen in the Clark study, as the daily supplemental selenium dose was a modest 200 micrograms. This dose is enough to increase the total selenium intake of most Americans by 3-to-5-fold, yet it is clearly safe.
In a region of China where daily selenium intake is estimated to be about 700 micrograms, no toxicity is noted.6 However, in a region where intakes are often in excess of 3,000 micrograms daily, selenosis is encountered. In animal studies, the minimal toxic intake is nearly a hundred-fold higher than a nutritionally adequate intake. Clearly, within reasonable limits, selenium supplementation is quite safe.
Looking to the Future With the publication of the Clark study, selenium at last seems poised to come into its own as one of the leading nutritional antioxidants with much greater cancer preventive potential than any of the other essential antioxidants. In addition, there is reason to believe that good selenium status may also have a favorable impact on risk for heart disease. This is suggested by several case-control studies demonstrating lower blood selenium levels in people who either have or subsequently develop heart disease.51-53 Animal studies show that the antioxidant activity of selenium is important for optimal production of the protective vascular hormone prostacyclin, which helps ward off blood clots.54-56 Although selenium may not prove to be as big a "star" as vitamin E when it comes to preventing heart disease, it more than compensates with its remarkable, versatile anticarcinogenic activity. Another fertile area for future clinical investigation will be to assess the impact of relatively high supplemental selenium intakes on immune function. If selenium's clinical effects in this regard are comparable to those reported in animals, it may have potential for boosting the flagging immune defenses of the elderly or of other subjects with impaired immune capacities.
In this regard, recent evidence suggests that good selenium nutrition slows the production of HIV particles in people who are HIV-positive.57 It is conceivable that the Clark study used too low a dose of selenium to achieve the protection from ultraviolet light and skin cancer noted in rodents receiving relatively high selenium intakes.
The late Dr. Robert Donaldson, certainly one of the first physicians to administer high-dose selenium to cancer patients (he reported that doses of yeast-selenium as high as 2,000 micrograms daily were well tolerated by his patients), noted that he seemed to be less prone to sunburn on his long fishing trips while he was using 1,000 micrograms of supplemental selenium daily. If selenium can lessen ultra- violet damage to the skin, this may slow the "aging" of the skin while reducing skin cancer risk.
Clearly, clinical selenium research is just getting started. Now that its exciting potential for health promotion is clear, and a more rational perspective on its safety can be expected, we can anticipate that medical scientists will embark on an aggressive exploration of the physiological effects, clinical applications, and protective benefits of this fascinating nutrient.
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