Introduction

Selenium is a trace element widely and irregularly distributed in the environment. Its availability and content in food may vary significantly depending on the region.

The daily requirement for selenium is among 200 and 250 micrograms (or a minimum of 1 microgram per kilo body weight and per day). Selenium occurs in animal and vegetal foods.

The essentiality of selenium in human nutrition was derived from its anti oxidative action, as a part of the glutathione-peroxidase system (GPx).

A deficit in selenium will result in a decrease of the GPx activity, and therefore, in an increase of cell damage which cannot be counter-balanced by other anti oxidative systems. Selenium is the main defense against oxidants.

What is mostly ignored, is that a selenium deficiency may also result in a thyroid hormone utilization defect.

Selenium deficiency symptoms appear in whole population groups when the selenium content in the diet is inadequate.

Selenium toxicity states are rare.

Studies

Numerous studies have been published documenting the preventive effect of supplementation with selenium on the occurrence of cancer.

In the Linxian study selenium supplementation resulted in a 13 percent reduction in cancer mortality.

"Between 1986 and 1991, 29,584 persons took part in a randomized nutritional intervention trial in Linxian, China, an area whose residents had chronically low intakes of several nutrients and high rates of esophageal and gastric cancer as well as stroke. Using a one-half replicate of a 2(4) factorial design, we randomized individuals to one of eight groups which received combinations of four supplements: retinol and zinc (factor A), riboflavin and niacin (factor B), vitamin C and molybdenum (factor C), and beta-carotene, alpha-tocopherol (vitamin E), and selenium (factor D). Deaths that occurred during 5 years of supplementation were ascertained and classified according to cause. At the end of the supplementation period, we measured blood pressure readings and determined the prevalence of hypertension. Participants who received factor D had reductions in total mortality (9%) and total cancer mortality (13%)."

(International Epidemiology Institute, Rockville, MD. Vitamin/mineral supplementation and cancer risk: international chemoprevention trials. Proceedings of the Society for Experimental Biology an Medicine, 1997; Nov., 216(2):291-6)

In another study, selenium supplementation resulted in 35.1 percent less precancerous lesions.

"An intervention trial was undertaken among the general population of 130,471. Individuals in five townships were involved for observation of the preventive effect of Selenium. The 8-years follow-up data showed reduced liver precancerous lesion incidence by 35.1% in selenized table salt supplemented vs. the non supplemented population. On withdrawal of Se from the treated group, PLC incidence rate began to increase.."

(Yu SY; Zhu YJ; Li WG. Cancer Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biological Trace Element Research, 1997 Jan., 56(1):117-24.)

In a recent double-blind trial, selenium supplementation reduced prostate cancer incidence by 63 percent.

" A total of 974 men with a history of either a basal cell or squamous cell carcinoma were randomized to either a daily supplement of 200 microgram of selenium or a placebo. Patients were treated for a mean of 4.5 years and followed for a mean of 6.5 years. The selenium treatment was associated with a significant (63%) reduction in the secondary endpoint of prostate cancer incidence. ."

(Clark LC; Dalkin B; Krongrad A; Combs GF Jr; Turnbull BW; Slate EH; Witherington R; Herlong JH; Janosko E; Carpenter D; et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. British Journal of Urology, 1998 May, 81(5):730-4.)

There was no effect of selenium on the existing skin cancers in this trial. Detractors use this fact to pretend that Nutraceuticals in general and selenium in particular are useless for cancer prevention.

National Cancer Institute

The National Cancer Institute recognizes the power of selenium to prevent lung, colorectal, and prostate cancer.

Read the communication of the National Cancer Institute Information Resources.

Selenium Monitoring

The selenium status of a person can be assessed by monitoring the selenium plasma and urine level and the selenium content of a hair sample. Human plasma should not contain less than 100-150 and more than 2,800 nanograms of selenium per milliliter. Urine may contain from 50 to 100 nanogram per milliliter. Hair should contain 27 micrograms/g.

"Erythrocyte and plasma selenium and glutathione peroxidase specific activities, hair and fecal selenium, and urinary selenium excretion were increased by and were linearly related to L-selenomethionine dose. Hair selenium was most sensitive to L-selenomethionine dose, with an 84-fold increase in the 300 micrograms selenium/(kg-d) group relative to controls (r = 0.917). Daily urinary selenium excretion (80-fold, r = 0.958), plasma selenium (22-fold, r = 0.885), erythrocyte selenium (24-fold, r = 0.920), and fecal selenium (18-fold, r = 0.911) also responded strongly to L-selenomethionine. Erythrocyte and plasma glutathione peroxidase specific activities increased 154% and 69% over controls, respectively. Toxicity was associated with erythrocyte selenium > 2.3 micrograms/mL, plasma selenium > 2.8 micrograms/mL, and hair selenium > 27 micrograms/g. Plasma, erythrocyte, and hair selenium concentrations may be useful for monitoring and preventing the toxicity of L-selenomethionine administered to humans in cancer chemoprevention trials.."

(Hawkes WC; Willhite CC; Craig KA; Omaye ST; Cox DN; Choy WN; Hendrickx AG. Effects of excess selenomethionine on selenium status indicators in pregnant long-tailed macaques (Macaca fascicularis). Biological Trace Element Research, 1992 Dec, 35(3):281-97.)

Selenium and Health

Selenium blood levels are lower in patients with stomach, colon or rectum cancer.

"Selenium concentrations in the full blood and erythrocyte and plasma GSH-Px activity were determined in patients with cancer of the stomach, colon and rectum. The results were compared with those in the group of healthy subjects. Blood samples were collected into heparinized tubes prior to surgery. Selenium concentrations in the full blood and plasma were lower (75.5 ng/mL and 56.2 ng/ml, respectively) in patients with the cancer of the stomach than healthy subjects (99.5 ng/ml and 78.5 ng/mL, respectively; p < 0.0001). Concentration of this element in both full blood and plasma was also lower in patients with cancer of the colon and rectum (77.7 ng/mL and 61.0 ng/ml, respectively; p < 0.0001). Erythrocyte and plasma GSH-Px activity was also significantly lower (p < 0.001) in patients with cancer of the stomach than in healthy subjects, and amounted to 13.6 U/g Hb and 188 U/L, respectively. Activity of this enzyme in patients with cancer involving lower segment of GI tract amounted to 15.9 U/g Hb and 190 U/L of plasma, and was significantly lower (p < 0.001) than in normal subjects in whom it amounted to 21.0 U/g Hb and 256 U/L of plasma.."

(Pawlowicz Z; Zachara BA; Trafikowska U; Nowicki A. [Low levels of selenium and activity of glutathione peroxidase in blood of patients with gastrointestinal neoplasms]. Polski Tygodnik Lekarski, 1993 Jun 21-28, 48(25-26):554-6)

"To investigate the relationship between serum Se contents and the risk of cancer, 4857 serum samples were obtained from cancerous (2730) and non-cancerous patients (2127). In this cohort the incidence of cancer in the non-cancerous patients was followed for the subsequent 3 years. The serum Se level of non-cancerous patients who later developed cancer during the 3 years was determined and compared with that of the non-cancerous patients. A high incidence of cancer was observed in the lower serum Se patients of the non-cancerous group. ."

(Ujiie S; Itoh Y; Kikuchi H. [Serum selenium contents and the risk of cancer]. Gan To Kagaku Ryoho Japanese Journal of Cancer and Chemotherapy, 1998 Oct, 25(12):1891-7)

The implications of a selenium deficiency involve more than only a defect of the enzyme Glutathione Peroxidase.

A selenium deficiency also results in thyroid hormone utilization defect, with all the consequences it.

Selenium deficiency triggers hypothyroidism because four selenium atoms are essential parts of each of the deiodases enzymes. The deiodase enzymes activate thyroid hormone.

More specifically, the thyroid gland produces two thyroid hormones: tetraiodothyronine (T4), and triiodothyronine (T3). T4 is less active than T3. To become active T4 has to be changed into T3 by the deiodase enzymes that--the name says it all--remove one atom of iodine from T4, a four iodine atoms molecule, making a T3, a three iodine atoms molecule out of it.

This enzymatic reaction do not occurs in the thyroid gland, it occurs mainly in the liver and to a lesser extend in almost all organs, brain included.

" The three isozymes catalyzing deiodination of thyroid hormones and iodothyronines derived thereof exert a major role in tissue- and development-specific expression of thyroid hormone action in target tissues by activating the prohormone T4 to thyromimetically active T3 or by inactivating the prohormone T4 or active T3 in non-target tissues at inappropriate time points. These three isozymes, in cooperation with the enzymes responsible for non-deiodinative degradation of iodothyronines, thus act as "guardians of the gate" to nuclear thyroid hormone receptors and other cellular target sites for thyroid hormone action. Strict and distinct hormonal, nutritional and nerval regulation of expression of the deiodinase isozymes warrants a closely coordinated control of thyroid hormone action, which directs growth, differentiation, and basal metabolic functions in the developing and the adult organism both in the periphery and in the central nervous system. The integrative action of this essential homeostatic and dynamic ancient hormone system in higher vertebrates is under the influence of two essential trace elements, iodine and selenium, which both are inadequately available for man and life stock in great parts of the world.."

(Kohrle J. Thyroid hormone deiodination in target tissues--a regulatory role for the trace element selenium? Experimental and Clinical Endocrinology, 1994, 102(2):63-89.)

See the role of mineral deficiency in the actual Balkan tragedy .

Selenium in Food

Selenium deficiency in the soil, in the vegetables and in food is frequent. The deficiency may involve whole countries with consequences for large group of the population. The scarcity of selenium in Linxian is well documented. In many other countries or part thereof the soil is also deficient in selenium.

"Data on selenium (Se) deficiency in Serbia are presented following 10 years of research. We studied the Se content in ores, stream sediment, soil, cereal crops, and garlic grown in these soils, food, and human serum and hair from 55 communities. Most of the results indicated a serious Se deficiency. In some communities, the Se content of grain, garlic, and human serum and hair approached that of the low-Se belt in China.

We assume that an extremely low Se level in the human population could be a risk factor for the development of Balkan nephropathy (BN) and for the very high incidence of urinary tract tumors (UTT) in endemic areas, as well as for the high mortality rates of other cancers."

(Maksimovic Z; Djujic I. Selenium research in Serbia, Yugoslavia. Journal of Environmental Pathology, Toxicology and Oncology, 1998, 17(3-4):165-71.)

Table 1: Selenium content in microgram per one hundred gram of edible food. (Table of Trace Element Contents in Japanese Foodstuffs. From a publication by Yasuo Suzuki and Sumizo Tanusi, 1993)