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LE Magazine December 2004
Getting Serious about Selenium
By Dale Kiefer

Is More Selenium Better?
Dr. Clark has written that selenium intake greater than that required to correct a selenium deficit may be needed to achieve this effect. In other words, meeting the US adult recommended dietary allowance (RDA) of 55 mcg per day is probably insufficient to achieve full cancer-preventive benefits. Dr. Combs points out that selenium appears to be anti-tumorigenic at levels that are“substantially greater than those associated with maximal expression of the known SeCys-containing enzymes.”

The RDA is based on the amount of selenium required to adequately produce the glutathione peroxidases (which, you will recall, require selenium), but it does not account for the potential benefits of selenium in excess of the bare minimum required to manufacture the antioxidant glutathione peroxidase enzymes. “Even individuals with nutritionally adequate selenium intakes may benefit from selenium supplementation,” writes Dr. Combs.29

In a subsequent journal article, he reiterated this concern. “The findings of [Dr. LC Clark and colleagues (including Dr. Combs), published in the Journal of the American Medical Association (JAMA), in 1996]28 suggest that selenium intakes of approximately twice the levels of the new [RDA], or more, can have such beneficial health effects.”30

While Dr. Combs does not advocate changing the RDA at this time, he admits, “It’s a murky area. I think it’s one we’re going to be revisiting.” The RDA provides a guideline to the average daily dietary intake level that is sufficient to meet the nutritional needs of the majority of healthy individuals. However, in recognition of the fact that some nutrients may offer additional benefits at higher levels, tables of tolerable upper-intake levels (UL) were also created. The UL reflects the maximum daily intake of a given nutrient that is considered safe. For selenium, the UL for adult men and women is 400 mcg per day.31

In a majority of studies examining selenium’s effects on disease in humans, daily doses of 200 mcg of supplemental selenium were used. Although the National Health and Nutrition Examination Survey (NHANES III, from 1988 to 1994) determined that the diets of most Americans provide enough selenium to meet recommended amounts of the essential nutrient,32 supra-nutritional amounts may be necessary to achieve cancer prevention.3 As Dr. Combs points out, “It’s safe to take up to 200 mcg per day of selenium.”

Dr. Combs is now affiliated with the USDA’s Agricultural Research Service. Earlier this year, he published an article in the British Journal of Cancer that further elucidated the findings of the NPC trial. “Selenium treatment can promote [programmed suicide] in prostate cancer cells, and possibly, impair their proliferation through antiangiogenic effects,” wrote Dr. Combs. He noted that risk reductions were most dramatic among men entering the trial with the lowest levels of selenium.33

Another paper published last summer reviewed research conducted in seven countries, and concluded that gender may influence selenium’s cancer-preventive effects. “Available data support the hypothesis that cancer risk in men is more profoundly influenced by selenium status than cancer risk in women,” wrote the Indiana-based researchers. They noted the need for still more research into selenium’s benefits.34

A preponderance of evidence indicates that high-dose selenium supplementation reduces the incidence of cancer in animals. Of more than 100 published studies on more than 20 animal models of cancer (including spontaneous and virally and chemically induced cancers), more than two thirds found evidence of significant reductions in tumor incidence with selenium supplementation. Furthermore, it appears that methylated forms of selenium—which are produced in the highest amounts in the body when there is excess selenium intake—are the active compounds offering cancer chemoprevention.35

Gastrointestinal disorders such as Crohn’s disease may interfere with nutrient absorption, resulting in trace-mineral deficiencies, but it is estimated that otherwise healthy Americans consume, on average, about 130 mcg per day of selenium. Men tend to ingest slightly more selenium than women.36 Smoking is associated with a reduction in plasma selenium. People living in the South and Northeast have somewhat lower dietary intakes of selenium, due to differences in selenium concentrations in the soil (and thus food) in those regions.37 The RDA of selenium for women who are pregnant or breast feeding is greater than the 55 mcg per day recommended for other adults, due to the need to provide adequate selenium for the developing fetus and to nourish the newborn with immunity-boosting selenoproteins.31 In fact, studies have shown that adequate selenium content in breast milk is directly related to the healthy development of the breast-feeding infant’s immune system.38,39

Indispensable to Brain Health
Some of the most intriguing selenium research concerns selenium’s critical importance to brain health. At least three published studies have linked selenium deficiency to undesirable mood states, and several studies indicate selenium’s importance to normal brain function. When individuals are selenium deprived, even for long periods, the brain hoards available selenium,40 and the turnover rate of some neurotransmitters is affected.41 Studies have found a significant association between low selenium levels and rapid cognitive decline in the elderly.40,42 When the brains of Alzheimer’s patients were examined for selenium status, they contained only 60% as much of this essential nutrient as the brains of control patients.40

Since the brain is deficient in an enzyme responsible for removing damaging peroxidation products such as hydrogen peroxide, selenium-based antioxidant proteins must shoulder the job alone.43 Many studies show that when selenium status is marginal, supplementation improves mood. Three separate studies have correlated low selenium status with a greater incidence of depression, anxiety, hostility, or confusion.40,44-46

A report published recently in the Journal of Nutrition implicates selenoprotein P as a key player in brain biochemistry. Deletion of the selenoprotein P gene in genetically altered mice has been associated with neurological dysfunction and decreased brain levels of selenium.47 Selenoprotein P acts as an antioxidant in the brain, and possesses the ability to promote neuronal cell survival.48

It is interesting to note that alterations in selenium concentration have been reported in the blood and brains of Alzheimer’s patients.48 As another recent scientific paper notes, most of the 25 known selenoproteins can be found in the brain, but their individual contributions to brain health and function remain to be elucidated.49 In any event, it is clear that selenium is indispensable to normal brain function.47,50

Uncertain Effects on Heart Health
Although it is well established that selenium exhibits both antioxidant and anti-inflammatory properties in the body, it remains unclear whether it directly affects cardiovascular health. Given that glutathione peroxidase combats lipid oxidation and reduces platelet aggregation—which reduces clot formation and thus decreases the risk of stroke or heart attack—it seems likely that selenium will eventually prove to be cardioprotective.3,51 Much work remains to be done in this area of inquiry, however.52 As leading selenium researcher Margaret P. Rayman has written: “Any condition associated with increased oxidative stress or inflammation might be expected to be influenced by selenium status. There is some evidence that this is the case in rheumatoid arthritis, pancreatitis, asthma, and systemic inflammatory response syndrome.”3

A Final Caution
Excessive selenium intake results in the rare condition known as selenosis, characterized by garlic-scented breath, brittle hair and nails, and neurological disorders. It is unwise, therefore, to exceed the recommended daily supplemental dose of 200-400 mcg of selenium. It also bears mentioning that among food sources of selenium, only Brazil nuts represent a potentially concentrated source, which varies depending on selenium content in the soil where the nuts were grown. The National Institutes of Health’s Office of Dietary Supplements estimates that one ounce of Brazil nuts contains, on average, 544 mcg of selenium. By contrast, the next most concentrated common food source—oil-packed light canned tuna—provides just 63 mcg of selenium in a three-ounce serving. Therefore, if you supplement with selenium, it may be wise to consume Brazil nuts only occasionally.


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