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Selenium Controversial Health Effects

By Dr Liji Thomas, MD

Selenium is an essential micronutrient in humans, with a recommended daily allowance of 0.055 to 0.070 mg/day. 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 it to produce clinical symptoms.

Cardiovascular disease

Some research findings point to an association between selenium deficiency and the development of coronary heart disease, but the presence of confounding factors means that further study is required. The biological mechanism underlying the cardioprotective effect of selenium could be its antioxidant action which prevents harmful lipid oxidation, the root event in atherosclerosis, which precipitates inflammation and platelet aggregation at the site of an atheromatous plaque.

However, conclusive evidence as to this is still awaited, with observational studies yielding conflicting results as to the association of cardiovascular disease, or its risk factors such as hypertension, with selenium levels in the body.

While there is some evidence that selenium supplements help to reduce the total blood cholesterol, and to increase the ‘good’ HDL levels, the findings do not support a role for selenium supplementation in the occurrence of fatal or nonfatal cardiovascular events. In short, evidence is lacking that selenium supplementation either prevents or mitigates the development or progression of cardiovascular disease.

Cancer

Other studies have repeatedly suggested that selenium levels are inversely linked to cancer incidence rates, while selenium supplementation with either organic or inorganic forms of selenium reduces the incidence of several types of cancer. Biologically, this is plausible, with the known effects of selenium on the immune system, endocrine regulation, antioxidant and anti-inflammatory effects, as well as those on DNA repair and apoptosis providing a mechanism for its cancer-suppressive effects.

Patients with prostate, lung and colorectal cancers, among others, appear to have lower blood selenium levels, and mortality in these patients drops in direct correlation with higher selenium levels. Other studies suggest that selenium may protect against cancer in men, while a selenium-allitridum combination may be protective in women.

Selenium showed a modest protective effect against lung cancer, that too only in selenium-deficient individuals. Skin cancer incidence rates were unaffected, while some research suggests that the rate of squamous cell carcinomas actually went up with selenium supplementation.

A Cochrane review showed that the highest vs the lowest intake category had a cancer risk lowering of 31%, with cancer mortality risk lowering of 45%. Bladder cancer risk was less by 33%, and prostate cancer incidence less by 22%.

Another study indicated that the risk of gastrointestinal cancers might be lowered, but the conclusion required validation, and current research fails to confirm any benefit of selenium on the development of colon and rectal cancers, or on esophageal or stomach cancer.

A double-blind RCT (Nutritional Prevention of Cancer Trial) found a 52-65% lowering of prostate cancer risk with 200 mcg/day of selenium for 6 years, the risk being lowered the most in those men who had a low baseline PSA (4 ng/mL or less).

The largest clinical trials to date, viz, the SELECT and the SU.VI.MAX trials, provided 200 mcg 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. Both of these failed to find evidence of such protection, or only in low-risk patients, such as those with low PSA levels, while there was an insignificant increase in risk, or no change in risk, 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

Similarly, higher selenium levels were also associated with lower rates of type II diabetes. Some studies also showed that type II diabetics had higher selenium levels in toenail clippings, but larger group research found that the converse was true.

The minute difference between toenail selenium in diabetics and nondiabetics makes this relationship probably non-significant. However, more data continues to accumulate in favor of the protective effect of higher selenium intakes against type II diabetes.

Cognitive decline

Lower selenium concentrations are found in older people, as well as in chronically or seriously sick people. This might be associated with deteriorating mental capacity, because of the loss of antioxidant activity. However, this link has not been confirmed in a NHANES data analysis of 4,809 elderly people.

Thus, selenium supplementation cannot now be advised as a prophylactic against memory impairment. The SU.VI.MAX study supplemented almost 4,500 people from 45 to 60 years with multiple antioxidants in addition to selenium, making it difficult to assess the unique role of selenium in the positive effect on episodic memory and semantic fluency observed 6 years after the conclusion of the study. Another systematic review ended with the conclusion that the role of selenium supplementation in delaying or preventing Alzheimer’s disease is unproved as of date.

Thyroid disease

Since the highest concentration of selenium in the body is in the thyroid gland, selenium deficiency could well 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, but only in women.

However, the effect of selenium supplementation on pre-existing thyroid disease showed a beneficial effect on ophthalmic outcomes, quality of life and disease progression, but no effect on thyroid function in healthy people.

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, but the clinical evidence of benefit is not strong enough to mandate supplementation.

Other doubtful situations

There is no evidence to date that selenium helps to improve the course of the disease in asthma or in atopic dermatitis. Though serum selenium levels are often significantly lowered in very ill people, selenium supplementation did not have 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. Psoriasis did not show any response to selenium.

Other situations where the benefits of selenium supplementation are in doubt include:

  • Alcoholic liver disease – may reduce the duration of hospitalization and mortality.
  • Burns – may cut down hospitalized time, but healing rates remain unaffected.
  • Arsenic poisoning – may reduce the risk of arsenic poisoning if the environment is high in arsenic.
  • HIV progression - research findings conflict on the effectiveness of selenium supplementation.
  • Stroke – some evidence points to a benefit for the administration of selenium within 24 hours of a stroke in terms of recovery percentage.
  • Post-mastectomy lymphedema – selenium supplementation may prevent bacterial infection of the arms and legs following surgery.
  • Pregnancy-induced hypertension – the development of high blood pressure might be prevented by selenium supplementation for 6-8 weeks.
  • Selenium and 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 is yet to be proved useful 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.

References

Further Reading

Last Updated: Feb 25, 2016

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