Selenium is an essential micronutrient in humans, with a recommended daily allowance of 0.055 to 0.070 milligrams (mg) per day.
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While Keshan disease and Kashin-Beck disease have been linked with selenium deficiency, there are other factors such as protein intake, fluoride intake, and stress which interact with this nutrient to produce clinical symptoms.
Some research findings point to an association between selenium deficiency and the development of coronary heart disease; however, the presence of confounding factors warrants the need for further studies.
The biological mechanism underlying the cardioprotective effect of selenium could be its antioxidant action, which prevents harmful lipid oxidation. Lipid oxidation is considered to be the root event in atherosclerosis, as this process precipitates inflammation and platelet aggregation at the site of an atheromatous plaque. Despite this observation, observational studies have yielded conflicting results as to the association between cardiovascular disease, or its risk factors such as hypertension, and selenium levels in the body.
While there is some evidence that selenium supplements help to reduce total blood cholesterol levels while also increasing the ‘good’ high-density lipoprotein (HDL) levels, these findings do not support a role for selenium supplementation in the occurrence of fatal or nonfatal cardiovascular events. In short, there is a general lack of evidence supporting the notion that selenium supplementation either prevents or mitigates the development or progression of cardiovascular disease.
Several studies have repeatedly suggested that selenium levels are inversely linked to cancer incidence rates, while selenium supplementation in either its organic or inorganic form can reduce the incidence of several types of cancer. Biologically, this is plausible, as selenium has known effects on the immune system, endocrine regulation, antioxidant and anti-inflammatory effects, as well as on DNA repair processes and apoptosis which, taken together, provide potential mechanisms for its cancer-suppressive effects.
Patients with prostate, lung, and colorectal cancers, among others, appear to have lower blood selenium levels. Additionally, mortality rates in these patients appear to drop in direct correlation with higher selenium levels. Other studies have also suggested that selenium may protect against cancer in men, while a selenium-allitridum combination may be protective in women.
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Selenium supplementation has demonstrated a modest protective effect against lung cancer; however, this observation was only confirmed in selenium-deficient individuals. Skin cancer incidence rates were found to be unaffected with the incorporation of selenium supplements. In fact, some research suggests that the rate of squamous cell carcinomas actually increased with selenium supplementation.
A Cochrane review showed that the highest versus the lowest intake category of selenium had a cancer risk lowering of 31%, with a cancer mortality risk reduction of 45%. Bladder cancer risk was found to be reduced by 33%, whereas the incidence of prostate cancer decreased by 22%.
Another study indicated that the risk of gastrointestinal cancers might be lowered with selenium supplementation. Despite this observation, current research fails to confirm any benefit of selenium on the development of colon, rectal, esophageal, or stomach cancers.
A double-blind randomized control trial (RCT) titled the Nutritional Prevention of Cancer Trial found a 52-65% reduction in the risk of prostate cancer in individuals who consumed 200 micrograms (µg)/day of selenium for 6 years. It should be noted that the risk was found to be the lowest in men who had low baseline prostate-specific antigen (PSA) levels of 4 ng/mL or less.
The largest clinical trials to date, which included the viz, SELECT and SU.VI.MAX trials, provided 200 µg of selenium in the form of selenomethionine, with alpha-tocopherol, or a supplement containing alpha-tocopherol, ascorbic acid, beta-carotene, zinc in addition to selenium, respectively, with placebo controls. Each of these trials failed to find evidence of anti-cancer protection in their test subjects. In fact, the only patients who were found to experience some type of benefit were those who were low-risk, such as those with low PSA levels. Moreover, an insignificant increase in risk, or no change in risk, was found to arise in men with a high PSA level.
At present, therefore, the marketing of selenium supplements is accompanied by a qualified claim as to its cancer-protective effects.
Type 2 diabetes mellitus
Higher selenium levels have also associated with lower rates of type 2 diabetes. Some studies also showed that type 2 diabetics had higher selenium levels in toenail clippings, whereas larger studies found the converse to be true.
The minute difference between selenium levels in diabetics as compared to nondiabetics diminishes the significant role of selenium in type 2 diabetes. However, more data continues to accumulate in favor of the protective effect of higher selenium intake against type 2 diabetes.
Lower selenium concentrations are found in older people, as well as those who are chronically or seriously ill. This reduction in selenium levels has been hypothesized to cause deteriorating mental capacity as a result of the loss of antioxidant activity. However, this link has not been confirmed in an NHANES data analysis of 4,809 elderly people.
Thus, selenium supplementation cannot currently be advised as a prophylactic against memory impairment. The SU.VI.MAX study supplemented almost 4,500 people between the ages of 45 to 60 with multiple antioxidants in addition to selenium, thus making it difficult to assess the unique role of selenium in the positive effect that was observed on both episodic memory and semantic fluency 6 years after the conclusion of the study. Another systematic review determined that there was a general lack of support for selenium supplementation in delaying or preventing Alzheimer’s disease.
Since the highest concentration of selenium in the body is in the thyroid gland, selenium deficiency could potentially play a role in thyroid function. This was supported by the results of the SU.VI.MAX study, and another Danish study, both of which showed that selenium levels were inversely related to the risk of thyroid enlargement in women.
Selenium supplementation has demonstrated a beneficial effect on ophthalmic outcomes, quality of life, and disease progression when used by individuals with pre-existing thyroid disease. However, when used by healthy individuals, no beneficial or adverse effect on thyroid function has been discovered.
A small study on 151 pregnant women who were positive for thyroid peroxidase antibodies suggested that selenomethionine supplementation might have a protective effect against postpartum thyroiditis. However, selenium supplementation may worsen the hypothyroid status in the presence of iodine deficiency.
Protection against the toxicity of chemotherapeutic drugs
It is known that selenium levels in hair and blood are lowered by cisplatin. Some research indicates that cisplatin-induced neurotoxicity might be alleviated by selenium supplementation; however, the clinical evidence of benefit is not strong enough to mandate supplementation.
Other doubtful situations
There is no evidence to date that confirms the utility of selenium supplementation for those with asthma or atopic dermatitis. Patients with psoriasis also did not report any positive response to selenium supplementation.
Though serum selenium levels are often significantly lowered in very ill people, selenium supplementation has not demonstrated any observable effect on mortality or the risk of infection.
Patients with hepatitis C failed to show biochemical or viremic improvement with a mixed supplement containing selenium. Infertility due to poor sperm function did not show any positive change following selenium administration.
Other situations where the benefits of selenium supplementation are in doubt include:
- Alcoholic liver disease – Selenium has been studied for its potential to reduce the duration of hospitalization and mortality rates in alcoholic liver disease. Further studies are still needed.
- Burns – Selenium supplementation may cut down hospitalized time; however, healing rates remain unaffected.
- Arsenic poisoning – Selenium may reduce the risk of arsenic poisoning if the environment is high in arsenic. Further studies are still needed.
- HIV progression - Research findings conflict on the effectiveness of selenium supplementation in reducing the progression of HIV.
- Stroke – Some scientific evidence points to a benefit for the administration of selenium within 24 hours of a stroke in terms of recovery percentage; however, further investigation into this effect must still be conducted.
- Post-mastectomy lymphedema – Selenium supplementation may prevent bacterial infection of the arms and legs following surgery. Further studies are still needed.
- Pregnancy-induced hypertension – The development of high blood pressure might be prevented by selenium supplementation for 6-8 weeks; however, more work is still required to confirm this association.
- Post-surgical hemorrhage – Current research indicates that selenium should be stopped at least 2 weeks before an elective surgical procedure to prevent hemorrhage during and following surgery.
In short, the list of conditions for which selenium has yet to be proven as a useful remedy includes arthritis, ovarian cancer, pancreatitis-related mortality, muscular dystrophy, cancer mortality, rheumatoid arthritis, life-threatening sepsis, primary biliary cirrhosis, inflammatory bowel disease, macular degeneration, hay fever, chronic fatigue syndrome, mood disorders, cataracts, and avian flu.