Selenium
	Chemoprevention of colorectal tumors: role of lactulose and of other agents.
	Biochemical basis of selenomethionine-mediated inhibition during 2-acetylaminofluorene-induced hepatocarcinogenesis in the rat.
	Selenium: a quest for better understanding.
	Selenium as a risk factor for cardiovascular diseases.
	[Selenium, glutathione peroxidase, peroxides and platelet functions]
	Deliberations and evaluations of the approaches, endpoints and paradigms for selenium and iodine dietary recommendations.
	The role of metals in ischemia/reperfusion injury of the liver.
	Effect of selenium on 1,2-dimethylhydrazine-induced intestinal cancer in rats.
	[Overview--suppression effect of essential trace elements on arteriosclerotic development and it's mechanism]
	Selenium in health and disease: a review.
	Assessment of selenium and vitamin E deficiencies in dairy herds and clinical disease in calves.
	Aortic and iliac artery thrombosis in calves: nine cases (1974-1993).
	[Selenium concentration in blood and Duchenne-type progressive muscular dystrophy]
	Antioxidant status and neovascular age-related macular degeneration
	Effects of hepatic stimulator substance, herbal medicine, selenium/vitamin E, and ciprofloxacin on cirrhosis in the rat
	Induction of renal damage in rats by a diet deficient in antioxidants
	Sudden infant death syndrome (SIDS): oxygen utilization and energy production.
	Prospects for nutritional control of hypertension
	The decline in stroke mortality. An epidemiologic perspective
	Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione peroxidase GSH-Px)-levels in asymptomatic versus symptomatic human immunodeficiency virus-1 (HIV-1)-infection
	Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection
	Selenium and HIV in Pediatrics
	Antioxidant status and lipid peroxidation in patients infected with HIV
	Selenium mediated inhibition of transcription factor NF-kappaB and HIV-1 LTR promoter activity
	[Diabetes mellitus--a free radical-associated disease. Results of adjuvant antioxidant supplementation]
	Biochemical and morphological changes in the lenses of selenium and/or vitamin E deficient rats.
	Myopathy and HIV infection
	Protective role of orally administered selenium and vitamin E towards cardiotoxicity induced by anthracyclines in the rat
	Enhancement of the antineoplastic effect of anticarcinogens on benzo[a]pyrene-treated Wistar rats, in relation to their number and biological activity.
	Critical reappraisal of vitamins and trace minerals in nutritional support of cancer patients.
	The effect of dietary levels of selenium on radiation resistance and radiation-induced carcinogenesis
	Differential induction of growth arrest inducible genes by selenium compounds
	Selenium deficiency associated with cardiac dysfunction in three patients with chronic respiratory failure
	A possible beneficial effect of selenium administration in antiarrhythmic therapy.
	An expanded concept of "insurance" supplementation--broad-spectrum protection from cardiovascular disease.
	Antioxidant status of hypercholesterolemic patients treated with LDL apheresis
	The role of free radicals in disease
	Status of antioxidants in patients with diabetes mellitus with and without late complications
	Selenium supplementation in the diets of patients suffering from ulcerative colitis
	Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group.
	Possible immunologic involvement of antioxidants in cancer prevention.
	Potential of food modification in cancer prevention
	Selenium-enriched garlic inhibits the early stage but not the late stage of mammary carcinogenesis
	Effect of an aqueous extract of selenium-enriched garlic on in vitro markers and in vivo efficacy in cancer prevention
	Multiple sclerosis: A diathesis?

Chemoprevention of colorectal tumors: role of lactulose and of other agents.

Ponz de Leon M; Roncucci L
Dept. of Internal Medicine, University of Modena, Italy.
Scand J Gastroenterol Suppl (NORWAY) 1997, 222 p72-5

Chemoprevention can be defined as an attempt at cancer control in which the occurrence of the disease is prevented by the administration of one (or more) chemical compounds. Main problems in chemoprevention studies are the choice of a suitable drug, the choice of an appropriate intermediate or definitive end point, and the definition of the population which should be investigated. Main classes of chemopreventive agents include vitamins, non-steroid antinflammatory drugs, minerals such as calcium or selenium, and other antioxidants such as N-acetylcysteine. Chemoprevention is particularly appealing in colorectal cancer, either because these lesions develop through a multistep process, or owing to the concept of "field carcinogenesis'. Between 1985 and 1990 we carried out a controlled study in which antioxidant vitamins or lactulose were used in an attempt to prevent the recurrence of colorectal polyps after their endoscopic removal. Among the 209 patients who could be evaluated, polyps recurred in 5.7% of the individuals who were given vitamins (A, C and E), 14.7% of patients given lactulose and 35.9% of untreated controls (chi 2 = 17.1, P < 0.001). The study suggested that either antioxidant vitamins or lactulose could be effective in reducing the recurrence rate of adenomatous polyps. In a subsequent on-going study, lower doses of the same vitamins were tested versus N-acetylcysteine (60a 40% reduction of the recurrence of polyps (ver sus controls) in individuals given N-acetylcysteine, while the effect of lower doses of vitamins was less appreciable. Definitive results of the study should be available by the end of 1998.

Biochemical basis of selenomethionine-mediated inhibition during 2-acetylaminofluorene-induced hepatocarcinogenesis in the rat.

Mukherjee B; Sarkar A; Chatterjee M
Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.
Eur J Cancer Prev (ENGLAND) Dec 1996, 5 (6) p455-63

Supplementation of selenium in the form of selenomethionine (8 ppm) in drinking water daily has been found to be highly effective in reducing cancer incidence in male Sprague-Dawley rats fed 2-acetylaminofluorine (2-AAF) (0.05%) in the basal diet daily for 16 weeks. Selenomethionine treatment before initiation, during initiation or during the selection/promotion phases of hepatocarcinogenesis has been found to be effective in elevating hepatic microsomal cytochrome b5, cytochrome P-450 contents, triphosphopyridine nucleotide-cytochrome c-reductase and cytosolic aryl hydrocarbon hydroxylase activities to a statistically significant level measured either in the hyperplastic nodules or in the non-nodular surrounding liver parenchyma compared with 2-AAF control rats. Moreover, selenomethionine treatment throughout the study also decreased the cytosolic 1-chloro-2,4-dinitrobenzene conjugated glutathione-S-transfer ase and microsomal UDP-glucuronyl transferase activities to a significant level when compared with 2-AAF control rats. Furthermore, direct correlations between hyperplastic nodules and non-nodular liver areas were observed with the hepatic selenium content and also with the rates and patterns of hepatic drug metabolism. Selenomethionine was also found to protect and improve the histopathological indices without any toe haematoxylin and eosin staining. Our results establish the fact that selenium is particularly protective in limiting the action of 2-AAF during the initiation phase of hepatocarcinogenesis.

Selenium: a quest for better understanding.

Badmaev V; Majeed M; Passwater RA
Sabinsa Corporation, Piscataway, NJ, USA.
Altern Ther Health Med (UNITED STATES) Jul 1996, 2 (4) p59-62, 65-7

Selenium is an essential trace element in nutrition for the prevention of disease in humans. Epidemiological studies indicate an association between low nutritional selenium status and increased risks of cardiomyopathy, cardiovascular disease, and carcinogenesis in various sites of the body. The role of selenium supplementation in the prevention and treatment of AIDS-related pathology has been considered. Selenoproteins discovered in mammalian cells may account for the essentiality of selenium in the body's antioxidant defense; thyroid hormone function; immune system function, particularly the cellular immunity; formation of sperm; and functioning of the prostate gland. The seleno-organic compounds, primarily L-(+)-selenomethionine, generally are recognized as safe and effective forms of selenium supplementation. The nutritionally recommended dose of elemental selenium is estimated at 50 to 200 mg per day. There is, however, increased discussion of a pharmacological dose of selenium, significantly higher than the nutritional dose of the microelement, to treat active conditions. One way of increasing the tissue levels of selenium is to combine its ingestible form with a nutrientilability enhancing compound. (87 Refs.)

Selenium as a risk factor for cardiovascular diseases.

Neve J
Universite Libre de Bruxelles, Institut de Pharmacie, Belgium.6277
J Cardiovasc Risk (ENGLAND) Feb 1996, 3 (1) p42-7

Selenium is a powerful antioxidant regulating the activity of the glutathione peroxidase enzymes, which catalyse the detoxification of hydrogen peroxide and organic hydroperoxides. Selenium deficiency has been implicated in the aetiopathogeny of Keshan disease, an endemic cardiomyopathy observed in China, and in other cases of congestive cardiomyopathy in subjects on artificial nutrition. However, the evidence from case-control and prospective studies for an association between low selenium status and cardiovascular diseases remains controversial. Mechanisms whereby selenium protects against such diseases include increased resistance of low-density lipoproteins against oxidative modification, modulation of prostaglandin synthesis and platelet aggregation, and protection against toxic heavy metals. The therapeutic benefit of selenium administration in the prevention and treatment of cardiovascular diseases still remains insufficiently documented.

[Selenium, glutathione peroxidase, peroxides and platelet functions]

Vitoux D; Chappuis P; Arnaud J; Bost M; Accominotti M; Roussel AM
Laboratoire central de biochimie, hopital Lariboisiere, Paris, France.
Ann Biol Clin (Paris) (FRANCE) 1996, 54 (5) p181-7

In the last five years, there has been a renewal of interest in the protective role of selenium in vascular disorders, inspired by experimental evidence that this trace element could modulate leukotriene and prostaglandin synthesis in both endothelial cells and platelets. In people living in low-selenium areas, a relationship has been established between a decrease in plasma selenium and an increase in the risk of coronary disease, atherosclerosis, platelet hyperaggregability and synthesis of proaggregant and proinflammatory compounds like thromboxane A2 and leukotrienes. Selenium, as an essential part of glutathione peroxidase, takes part in the reduction of hydrogen peroxides and lipid peroxides. The concentration of these peroxides, in turn, regulates the activities of cyclooxygenase and lipooxygenase pathways, ultimately influencing the production of eicosanoids and modulating the balance between a proaggregatory and antiaggregatory state. Recent evidence shows that selenium, via its action on glutathione peroxidase activity, may be primarily responsible for the regulation of the endogenous hydroperoxide level. In human platelets, the activity of glutathione peroxidase is particularly high and is very sensitive to the requirement of selenium. This sensitivity could explain why platelets of selenium-deficient subjects show increased aggregation, thromboxane B2 production and synthesis of the lipoxygenase-derived compounds. In these deficient subjects, selenium administration increases platelet glutathione peroxidase activity and inhibits platelet hyperaggregation and leukotriene synthesis. These results support the hypothesis that selenium supplementation has a positive effect on platelet aggregation in selenium-deficient subjects. In France, more than 10% of the population is selenium-deficient and long-term supplementation with low doses of selenium could have a beneficial effect on the prevention of both thrombosis and coronary heart disease in these subjects. (35 Refs.)

Deliberations and evaluations of the approaches, endpoints and paradigms for selenium and iodine dietary recommendations.

Levander OA; Whanger PD
U.S. Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, MD 20705, USA.
J Nutr (UNITED STATES) Sep 1996, 126 (9 Suppl) p2427S-2434S

Information is presented regarding the approaches that have been used to establish dietary recommendations for selenium and iodine. In the case of selenium, activity of the selenoenzyme glutathione peroxidase has served as a convenient biochemical endpoint for judging nutritional status. However, there are differences of opinion among various nutritionists as to whether full expression of this enzymatic activity is required for adequate nutriture, thereby resulting in differences in dietary recommendations. Endpoints for assessing selenium overexposure are much less satisfactory, but toxicological standards for selenium have nevertheless been established. Thus far, no nutritionists have attempted to shift the paradigm for determining dietary selenium recommendations away from prevention of deficiency disease to prevention of chronic degenerative disease (e.g., cancer). In the case of iodine, urinary excretion of the element is the most widely used endpoint for judging nutritional status. Numerous epidemiological surveys have been conducted to determine the level of urinary iodine excretion that is consistent with prevention of goiter, the most common endpoint of iodine deficiency. Because dietary iodine is essentially quantitatively excreted in the urine, determination of the latter in goitrous areas will allow an almost direct estimation of those intakes at risk of developing deficiency disease. Iodine toxicity is complicated by the fact that some persons are quite tolerant to the element whereas others are highly sensitive to it. There are relatively complete data sets concerning exposure vs. human health effects for both selenium and iodine so that sounder bases probably exist for their dietary recommendations than for many other trace elements.

Selenium is an essential trace element in nutrition for the prevention of disease in humans. Epidemiological studies indicate an association between low nutritional selenium status and increased risks of cardiomyopathy, cardiovascular disease, and carcinogenesis in various sites of the body. The role of selenium supplementation in the prevention and treatment of AIDS-related pathology has been considered. Selenoproteins discovered in mammalian cells may account for the essentiality of selenium in the body's antioxidant defense; thyroid hormone function; immune system function, particularly the cellular immunity; formation of sperm; and functioning of the prostate gland. The seleno-organic compounds, primarily L-(+)-selenomethionine, generally are recognized as safe and effective forms of selenium supplementation. The nutritionally recommended dose of elemental selenium is estimated at 50 to 200 mg per day. There is, however, increased discussion of a pharmacological dose of selenium, significantly higher than the nutritional dose of the microelement, to treat active conditions. One way of increasing the tissue levels of selenium is to combine its ingestible form with a nutrient bioavailability enhancing compound. (87 Refs.)

The role of metals in ischemia/reperfusion injury of the liver.

Arora AS; Gores GJ
Center for Basic Research in Digestive Diseases, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Semin Liver Dis (UNITED STATES) Feb 1996, 16 (1) p31-8

No abstract.

Effect of selenium on 1,2-dimethylhydrazine-induced intestinal cancer in rats.

Jao SW; Shen KL; Lee W; Ho YS
Division of Colon and Rectal Surgery, National Defense Medical Center, Tri-Service General Hospital Taipei, Taiwan, Republic of China.
Dis Colon Rectum (UNITED STATES) Jun 1996, 39 (6) p628-31

PURPOSE: This study was designed to determine the cancer prevention and therapeutic effects of selenium on rats treated with 1,2-dimethylhydrazine (DMH). METHODS: One hundred sixty Spraque-Dawley male rats were divided into seven groups and received 20 mg/kg/week DMH, subcutaneously for 20 weeks. Two different dosages of selenium (8 and 4 ppm) were administered to the rats through drinking water during DMH treatment (B and C groups) or one month before and during DMH treatment (D and E groups). The rats of Groups A (control group), B, C, D, and E were killed immediately after the last DMH injection. The incidence of intestinal cancer in each group was compared. Eight ppm selenium was also administered to rats after DMH treatment (Group F), and survival times were observed and compared with Group G (treated with DMH only). RESULTS: Rats of Groups B and D received 8 ppm selenium and had a significantly decreased incidence of intestinal cancer (from 65.8 percent (Group A) to 33.3 percent (Group B) and 27.8 percent (Group D); P = 0.0225 and 0.0038). Rats receiving 4 ppm selenium had a relatively decreased incidence of intecent (Group A) to 44.4 percen t (Group C) and 47.1 percent (Group E) but P > 0.05). Survival time of Groups F and G showed no difference. CONCLUSIONS: Eight ppm selenium provided via drinking water has a significant intestinal cancer prevention effect in the presence of a high dose of DMH (20 mg/kg x 20 weeks), and the cancer therapeutic effect of selenium is doubtful in this animal model.

[Overview--suppression effect of essential trace elements on arteriosclerotic development and it's mechanism]

Saito N
Nippon Rinsho (JAPAN) Jan 1996, 54 (1) p59-66

It is known that the peroxidation of LDL is a trigger for developing arteriosclerosis. The oxidized LDL is produced by either oxidative stress or a few oxidant. Selenium decreased in serum and some organs of stroke-prone spontaneously hypertensive rats (SHRSP), which is a cofactor of glutamine peroxidase. Serum magnesium decreased in patients with diabetes mellitus, with ischemic heart disease, with essential hypertension and with cerebral vascular lesions. Calcium to magnesium ratio was higher in some organs of SHRSP as compared to Wistar Kyoto rats (WKY). These changes accelerated vascular lesions in SHRSP. (21 Refs.)

Selenium in health and disease: a review.

Crit Rev Food Sci Nutr (UNITED STATES) Apr 1997, 37 (3) p211-28

Selenium (Se) was discovered 180 years ago. The toxicological properties of Se in livestock were recognized first; its essential nutritional role for animals was discovered in the 1950s and for humans in 1973. Only one reductive metabolic pathway of Se is well characterized in biological systems, although several naturally occurring inorganic and organic forms of the element exist. The amount of Se available for assimilation by the tissues is dependent on the form and concentration of the element. Se is incorporated into a number of functionally active selenoproteins, including the enzyme glutathione peroxidase, which acts as a cellular protector against free radical oxidative damage and type 1 iodothyronine 5'-deiodinase which interacts with iodine to prevent abnormal hormone metabolism. Se deficiency has been linked with numerous diseases, including endemic cardiomyopathy in Se-deficient regions of China; cancer, muscular dystrophy, malaria, and cardiovascular disease have also been implicated, but evidence for the association is often tenuous. Information on Se levels in foods and dietary intake is limited, and an average requirement for Se in the U.K. has no been established. Available data suggest that intake in the U.K. is adequate for all, except for a few risk groups such as patients on total parenteral nutrition or restrictive diets. (122 Refs.)

Assessment of selenium and vitamin E deficiencies in dairy herds and clinical disease in calves.

Vet Rec (ENGLAND) Oct 19 1996, 139 (16) p391-4

Because of the very low concentrations of selenium in the dry matter of grass, grass silage, hay and maize silage Slovenian dairy herds need to be supplemented with selenium. Selenium in the form of mineral and feed mixtures maintained adequate mean (sd) blood serum selenium concentrations of 43.9 (27.6) to 65.3 (18.5) micrograms/litre in lactating cows, but in late lactation and in the dry period when only mineral mixtures were used, about 60 per cent of the cows had marginal serum selenium concentrations, mainly because of the low intake of the mineral supplement. In 18 herds which were either unsupplemented or irregularly supplemented with selenium, the mean (sd) concentrations in blood serum were 13.7 (5.5) micrograms/litre and 17.4 (9.2) micrograms/litre, respectively, for selenium and 2.98 (2.72) mg/litre and 1.62 (1.73) mg/litre for vitamin E, indicating that under extensive farming conditions in Slovenia the lack of both micronutrients may be responsible for nutritional muscular dystrophy in calves. Among 37 clinical cases, cardiorespiratory signs predominated in 25 of the calves and skeletal myopathy was dominant in 12. A very low mean serum selenium concentration [9.7 (7.2) micrograms/litre] and typically high activities of aspartate aminotransferase (AST) [1125 (373) U/litre] and creatine kinase (CK) [9169 (3681) U/litre) were observed for the myocardial form of the disease, and 2797 (550) U/litre and 22,650 (13,500) U/litre were observed for the skeletal form of the disease. A highly significant (P < 0.0001) difference in the selenium concentration of liver dry matter between the regularly supplemented [402 (207) micrograms/kg] and irregularly supplemented [173 (69) micrograms/kg] herds was observed. If a minimum value of 300 micrograms/kg of liver dry matter is accepted as the criterion for the determination of adequate selenium status, 93 per cent of the samples from the irregularly supplemented herds were selenium deficient. A similar proportion was estimated to be selenium deficient when the criterion was taken to be 30 micrograms selenium/litre of blood serum.

Aortic and iliac artery thrombosis in calves: nine cases (1974-1993).

J Am Vet Med Assoc (UNITED STATES) Jul 1 1996, 209 (1) p130-6

OBJECTIVE--To identify common clinical and diagnostic features of calves with aortic or iliac artery thrombosis that might aid in antemortem diagnosis of this condition. DESIGN--Retrospective case series. ANIMALS--9 calves < or = 6 months old in which aortic or iliac artery thrombosis was confirmed at necropsy. RESULTS--All calves had an acute onset of paresis or flaccid paralysis of 1 or both hind limbs. Affected limbs were hypothermic and had diminished spinal reflexes and diminished pulse pressures. Diagnosis was definitively established in 2 calves by use of angiography. All 9 calves died or were euthanatized. CLINICAL IMPLICATIONS--This condition is rare and could be mistaken for more common diseases of young cattle, such as traumatic injury of the axial or appendicular skeleton, vertebral osteomyelitis, nutritional muscular dystrophy associated with vitamin E or selenium deficiency, injury to the sciatic or femoral nerves, or clostridial myositis.

[Selenium concentration in blood and Duchenne-type progressive muscular dystrophy]

Nippon Rinsho (JAPAN) Jan 1996, 54 (1) p134-40

The concentration of selenium (Se) and the activity of glutathione peroxidase (GSH-Px) in plasma and erythrocytes were measured in healthy men and in patients with Duchenne-type progressive muscular dystrophy (DMD). In healthy men, the Se concentration in erythrocytes showed a steep rise with aging and ascended gradually in plasma. The GSH-Px activity in both plasma and erythrocytes clearly increased with aging. The relationship between the Se concentration and the GSH-Px activity in healthy men showed a parallel rise with aging, but the coefficients of correlation were not very high (r = 0.44 and 0.56 in plasma and erythrocytes, respectively. In DMD patients, on the other hand, the Se concentration in erythrocytes decreased steeply with aging, and it decreased gradually in plasma. The GSH-Px activity in both plasma and erythrocytes apparently increased as in healthy men with aging, but the level was about 80% of that of healthy men. When selenite (Se+4) is added to the whole blood in vitro at 25 degrees C, it is rapidly taken up by erythrocytes (within several minutes) and is then released into plasma (a period of 30 min), then subsequent reuptake by erythrocytes is proceeded slowly. Our attention was attracted to the pattern of selenite release from erythrocytes of DMD patients.

Antioxidant status and neovascular age-related macular degeneration

ARCH. OPHTHALMOL. (USA), 1993, 111/1 (104-109)

We evaluated the hypothesis that higher serum levels of micronutrients with antioxidant capabilities may be associated with a decreased risk of neovascular age-related macular degeneration by comparing serum levels of carotenoids, vitamins C and E, and selenium in 421 patients with neovascular age-related macular degeneration and 615 controls. Subjects were classified by blood level of the micronutrient (low, medium, and high). Persons with carotenoid levels in the medium and high groups, compared with those in the low group, had markedly reduced risks of neovascular age-related macular degeneration, with levels of risk reduced to one half and one third, respectively. Although no statistically significant protective effect was found for vitamin C or E or selenium individually, an antioxidant index that combined all four micronutrient measurements showed statistically significant reductions of risk with increasing levels of the index. Although these results suggest that higher blood levels of micronutrients with antioxidant potential, in particular, carotenoids, may be associated with a decreased risk of the most visually disabling form of age-related macular degeneration, it would be premature to translate these findings into nutritional recommendations.

Effects of hepatic stimulator substance, herbal medicine, selenium/vitamin E, and ciprofloxacin on cirrhosis in the rat

Gastroenterology (USA), 1996, 110/4 (1150-1155)

Background and Aims: Cirrhosis is a potentially lethal condition for which there is no proven effective therapy. The aim of this study was to compare the effects of hepatic stimulator substance, traditional Chinese herbal medicine, selenium plus vitamin E, and ciprofloxacin treatment on biochemical and histological features of fibrosis in rats with carbon tetrachloride (CCl4)/ethanol-induced cirrhosis. Methods: One hundred twenty adult Wistar rats were divided into six study groups (20 rats/group): healthy controls, CCl4/ethanol-injured rats left untreated, and CCl4/ethanol-injured rats treated for 4 weeks with either hepatic stimulator substance, traditional Chinese herbal medicine, a combination of selenium plus vitamin E, or ciprofloxacin. After the 4-week treatment, rats were killed and the following parameters of hepatic fibrosis were determined: hepatic hydroxyproline and proline levels, serum hyaluronic acid concentrations, and histological staining of hepatic tissue. Results: Hepatic fibrosis was significantly improved in all four treated groups compared with the untreated CCl4/ethanol-injured controls. Improvements were most striking in the groups treated with traditional Chinese herbal medicine and ciprofloxacin. Conclusions: The data indicate that hepatic stimulator substance, traditional Chinese herbal medicine, selenium plus vitamin E, and ciprofloxacin significantly decrease the amount of hepatic fibrosis caused by CCl4/ethanol injury in rats.

Induction of renal damage in rats by a diet deficient in antioxidants

Nutrition Research (USA), 1996, 16/9 (1607-1612)

Male albino rats, age 28 days, were fed a diet containing both vitamin E (10 g/kg) and selenium (5 mg/kg) or a diet lacking these antioxidants. Animals were examined for renal function after 4, 8, 12 and 16 wk on the respective diets. After 8 wk, animals on the deficient diet weighed less than controls (15%, p<0.01), and this became more pronounced by 16 weeks (25%, p<0.01). Expressed on a body weight basis, kidney wet weights did not differ between the two groups of animals. Urine volume increased in the animals fed the deficient diet at 8 weeks (66%, p<0.01) and this was maintained at 16 weeks (35%, p<0.01). Similar increases were observed for the rates of excretion of urinary total protein (77% elevation at 16 wk, p<0.01) and urinary acid phosphatase (51% elevation, p<0.01). At 16 wk, the specific activity of renal acid phosphatase in the animals given the deficient diet was reduced in cortex (57%, p<0.01) and medulla (20%, p<0.01), but not in papilla. These data indicate that dietary antioxidant deficiency causes progressive and pronounced renal damage.

Sudden infant death syndrome (SIDS): oxygen utilization and energy production.

Med Hypotheses (ENGLAND) Jun 1993, 40 (6) p364-6

Reid found selenium (Se) deficient soils were a common factor in two populations with the highest incidence of SIDS world-wide (Indian population of King County Washington State, USA and the population of Canterbury, New Zealand). Reid compared a map of the selenium responsive livestock areas in New Zealand with areas of low soil iodine (I). She found that the 1989 report of areas of the highest SIDS incidence coincided with Se responsive livestock areas combined with low soil iodine. Foster found the 1983-84 incidence of SIDS in USA has the strongest positive correlation with the incidence of goitre in World War I troops (1916). Sodium and strontium were positively related. Emery found a hypernatraemic SIDS victim in a very cold environment. Robertson and Parker associated increased sodium (Na) (used in Scunthorpe, England, as a water softener) with increased incidence of SIDS. Godwin's study of White Muscle Disease in lambs describes Se protection. Skeletal muscle mitochondria from dystrophic animals showed lowered respiratory rates with palmitoyl-dl-carnitine and acetyl-dl-carnitine as substrate. Dystrophic organelles failed to respond to ADP. Rognun found elevated hypoxanthine and an enhanced immune response in most SIDS victims. A syndrome associated with potassium deficiency has been described as a killer of healthy, young Asian men, most often during sleep. This paper describes the interactions of sodium (Na), potassium (K), selenium (Se), and iodine (I) to some factors affecting the utilization of oxygen and the production of energy. (19 Refs.)

Prospects for nutritional control of hypertension

Med Hypotheses (ENGLAND) Mar 1981, 7 (3) p271-83

Sodium restriction is not the only nutritional measure likely to prove valuable in the treatment and prevention of hypertension. The hypotensive effects of central adrenergic stimulation can be promoted by supplementary tyrosine, insulin potentiation (as with GTF), and (possibly) high-dose pyridoxine. Insulin potentiators (GTF) and prostaglandin precursors (essential fatty acids) should have direct relaxant effects on vascular muscle. A high potassium, low sodium diet, coenzyme Q, and prevention of cadmium toxicity (as with dietary selenium) may act to offset renally-mediated pressor influences. Functional combinations of these measures might prove to be substantially effective, in which case they would offer considerable advantages over potentially toxic drug therapies.

The decline in stroke mortality. An epidemiologic perspective

Ann Epidemiol (UNITED STATES) Sep 1993, 3 (5) p571-5

The evidence that treatment of hypertension prevents stroke is incontrovertible. Several observations, however, suggest that improvements in the prevalence of antihypertensive treatment cannot explain all of the recent decline in stroke mortality. Changes in nutritional patterns may explain some of the observed decline. Prospective studies have demonstrated conclusively an independent, increasing risk of hemorrhagic, but not thrombotic, stroke at higher levels of alcohol use. Stroke mortality is associated inversely with fat and protein intake. Dietary sodium has been linked to stroke in ecologic studies but not in prospective studies. Ecologic studies have suggested that foods high in vitamin C and potassium protect against stroke; an inverse association of potassium intake with fatal stroke has been demonstrated in cohort studies. Two studies in humans also suggest a protective effect of serum selenium against subsequent stroke. Determination of the influence of nutrients on stroke incidence offers tantalizing opportunities for future research and possibly, intervention.

Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione peroxidase GSH-Px)-levels in asymptomatic versus symptomatic human immunodeficiency virus-1 (HIV-1)-infection

European Journal of Clinical Nutrition (United Kingdom), 1997, 51/4 (266-272)

Objectives: Antioxidant defense status was investigated in HIV-infected patients by measuring serum selenium, erythrocyte glutathione peroxidase (GSH-Px) activity, plasma thiol (-SH) and glutathione (GSH) concentrations along with the assessment of the clinical stage and surrogate markers of HIV-disease. Design, setting and subjects: Serum selenium levels were determined cross-sectionally in 104 sequentially selected HIV-infected patients (83 outpatients and 21 patients with ongoing AIDS defining events). The patients were classified into three stages of the disease, I, II and III according to the 1993 Centers For Disease Control (CDC) classification system for HIV-infection. GSH-Px activities, plasma SH and plasma GSH concentrations were determined in a subset of 24 patients at stage I and 12 patients at stage III with an active AIDS-defining disease. Results: Mean serum selenium levels were lower in CDC stage II (68.7 plus or minus 20.9 microg/l; P < 0.01; n = 34) and stage III (51.4 plus or minus 14.7 microg/l; P ( 0.01; n = 37) HIV-infected patients than in healthy subjects (89.2 plus or minus 20.9 microg/l; n = 72) and stage I patients (82.3 plus or minus 20.5; microg/l; n = 33). Serum selenium levels were positively correlated with CD4-count (r = 0.42; P < 0.001; n = 104) and inversely with levels of soluble tumor necrosis factor receptors type II (r= -0.58; P < 0.01; n = 35), neopterin (r = -0.5; P < 0.001; n = 80) and beta2-microglobulin (r = -0.4; P < 0.001; n = 94). Hepatitis C virus (HCV) and HIV-coinfected patients at CDC stages I and II showed markedly lower selenium concentrations compared to HIV-infected patients without concomitant HCV-infection. Serum selenium and GSH-Px activity in hospitalized AIDS patients was significantly lower as compared to asymptomatic patients and healthy subjects, whereas plasma SH and GSH concentrations were lower in both, asymptomatic -and AIDS-patients, than in the controls. Conclusion: The results show that stages I-III of HIV-disease are characterized by significant impairments of antioxidative defenses provided by selenium, GSH-Px, SH-groups and GSH.

Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection

Biological Trace Element Research (USA), 1997, 56/1 (31-41)

Serum selenium levels were determined cross-sectionally in 57 HIV- infected patients who were classified according to the Centers for Disease Control (CDC) 1993 classification system. Mean serum selenium levels were lower in CDC stage II (58.7 plus or minus 12.2 microg/L; p < 0.01; n = 18) and stage III (47.6 plus or minus 11.3 microg/L; p < 0.01; n = 19) HIV-infected patients, than in healthy subjects (80.6 plus or minus 9.6 microg/L; n = 48) and stage I patients (73.6 plus or minus 16.5 microg/L; n = 20). Serum selenium levels were positively correlated with CD4 count, CD4/8 ratio, hematocrit, and serum albumin (r = 0.42; r = 0.39; r = 0.48; and r = 0.45; p < 0.01, respectively) and inversely with serum levels of thymidine kinase (r = - 0.49; p < 0.01; n = 49) and beta2-microglobulin (r = - 0.46; p < 0.001; n = 49). In addition, serum selenium levels in 20 randomly selected AIDS-free individuals (CDC I: n = 10; CDC II: n = 10) were inversely correlated with serum concentrations of interleukin-8 (IL-8) and soluble tumor necrosis factor receptors (sTNFR) types I and II. There was no correlation with serum immunoglobulin A and total serum protein levels. The results show that the progressive deprivation of serum selenium in HIV- infection is associated with loss of CD4+-cells and with increased levels of markers of disease progression and inflammatory response.

Selenium and HIV in Pediatrics

J. NUTR. IMMUNOL. (USA), 1994, 3/1 (41-49)

An important role for selenium in immune processes has been described, with selenium appearing to affect non-specific immune indices, humoral immunity, cell-mediated immunity and cytotoxicity. Whereas low plasma selenium levels have been correlated with decreased natural killer (NK) cell activity, as well as proliferative response of lymphocytes to mitogens in vitro, supplementation with selenium has been associated with enhanced lymphocyte response to phytohemagglutinin (PHA) and pokeweed (PWM) and with enhanced NK activity when administered in physiological ranges, but not at pharmacological doses. The investigation of selenium status in HIV-1 infection is of particular interest, in light of studies documenting low plasma selenium levels and decreased glutathionine peroxidase activity in adult patients with AIDS. Moreover, alterations in selenium levels have been associated with immune dysregulation in early HIV-1 infection. As examination of pediatric nutritional status in HIV-1 disease has been restricted in scope, this study was designed to characterize selenium status and examine its relationship to immune function, in HIV-1 infected children.

Antioxidant status and lipid peroxidation in patients infected with HIV

CHEM.-BIOL. INTERACT. (Ireland), 1994, 91/2-3 (165-180)

Deficiency in antioxidant micronutrients have been observed in patients with AIDS. These observations concerning only some isolated nutrients demonstrate a defect in zinc, selenium, and glutathione. An increase in free radical production and lipid peroxidation has been also found in these patients, and takes a great importance with recent papers presenting an immunodeficiency and more important an increase in HIV-1 replication secondary to free radicals overproduction. We have assessed different studies, trying to obtain a global view of the antioxidant status of these patients. In adults we observe a progressive decrease for zinc, selenium, and vitamin E with the severity of disease, except that selenium remains normal at stage II. However, the main dramatic decrease concerns carotenoids whose level at stage II is only half the normal value. To understand if these decreases in antioxidant and increases in oxidative stress occur secondary to the aggravation of the disease or, conversely, are responsible for it, we undertook a longitudinal survey of asymptotic patients. The preliminary results of this evaluation are presented. Paradoxically, lipid peroxidation is higher at stage II than at stage IV. This may be consecutive to a more intense overproduction of oxygen free radicals by more viable polymorphonuclear (PMN) at the asymptomatic stage. The free radicals production and lipid peroxidation seem secondary to a direct induction by the virus of PMN stimulation and cytokines secretion. N-Acetyl cystein or ascorbate have been demonstrated in cell culture to be capable of blocking the expression of HIV-1 after oxidative stress and N-acetyl cysteine inhibits in vitro TNF-induced apoptosis of infected cells. In regard to all these experimental data, few serious and large trials of antioxidants have been conducted in HIV-infected patients, although some preliminary studies using zinc or selenium have been performed. In our opinion it is now time to evaluate in humans the beneficial effect of antioxidants. The more promising candidates for presenting synergistic effects when associated with N-acetyl cysteine seem to be beta-carotene, selenium and zinc.

Selenium mediated inhibition of transcription factor NF-kappaB and HIV-1 LTR promoter activity

Archives of Toxicology (Germany), 1996, 70/5 (277-283)

The eukaryotic transcription factor NF-kappaB is involved in the inducible expression of various inflammatory genes as well as in HIV-1 replication. Activation of NF-kappaB is induced by prooxidants and several stimuli eliciting oxidative stress, such as cytokines, lipopolysaccharide, UV irradiation and other mediators. Various antioxidants inhibit NF-kappaB activation in response to these stimuli. In this study, we have investigated the effects of selenium, an integral component of glutathione peroxidase (GPX), on NF-kappaB activation. In selenium-deprived Jurkat and ESb-LT lymphocytes, supplementation of selenium led to a substantial increase of GPX activity. Analysis of DNA binding revealed that NF-kappaB activation in response to TNF was significantly inhibited under these conditions. Likewise, reporter gene assays using luciferase constructs driven by the HIV-1 long terminal repeat showed a dose-dependent inhibition of NF-kappaB controlled gene expression by selenium. The effects of selenium were specific for NF-kappaB, since the activity of the transcription factor AP-1 was not suppressed. These data suggest that selenium supplementation may be used to modulate the expression of NF-kappaB target genes and HIV-1.

[Diabetes mellitus--a free radical-associated disease. Results of adjuvant antioxidant supplementation]

Z Gesamte Inn Med (GERMANY) May 1993, 48 (5) p223-32

Our investigations carried out in patients with diabetes mellitus revealed oxidative stress loads. The study presented here was to clarify whether a therapy with antioxidants can contribute to an improvement of prognosis. 80 patients affected with a long term diabetic late syndrome were randomised and arranged to 4 groups of n = 20 each. In contrast to a control group these patients received 600 mg of alpha lipoic acid or 100 micrograms of selenium (sodium selenite) daily or 1200 IE of D-alpha-tocopherol respectively for a time of 3 months. In comparison with the control group all groups treated in an antioxidative way showed significantly diminished serum concentrations of thiobarbituric acid reactive substances and of urinary albumin excretion rates. The symptoms of distal symmetric neuropathy measured according to the thermo- and vibration sensitivity also improved in a highly significant manner. The results prove that oxidative stress plays a promoting role in developing of long term diabetic late complications and that a therapy with adjuvant antioxidants may lead to a regression of diabetic late complications.

Biochemical and morphological changes in the lenses of selenium and/or vitamin E deficient rats.

Biomed Environ Sci (UNITED STATES) Jun 1994, 7 (2) p109-15

The activities of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) and free radicals were measured, and the morphological changes were observed in the lens of control rats, selenium-deficient (SeD) and/or vitamin E deficient (VED) rats. The activities of GSH-Px in the lens of SeD rats decreased significantly. The GSH-Px activities of lens were positively related to erythrocytes selenium level. There was a free radical at g = 2.0015 in the rat lens of all groups, but the content of free radicals in the lens of SeD group was significantly higher than that of the control group. The free radical content of lens was negatively related to erythrocytes selenium level, as well as the GSH-Px activities in the lens. In vitro, ultraviolet radiation caused the generation of another kind of free radical (g = 2.0097) in the lens of all groups, but the amount of the free radical in the lens of the SeD group was also significantly higher than that of the control group. The activities of SOD and GSSG-R in VED rat lens were significantly decreased. The amount of MDA in the lens of SeD and/or VED rats were significantly increased. The results showed that the decrease of antioxidative capability in the lenses of SeD and/or VED rats accelerated the lipid peroxidation and generation of free radicals. Although only early morphological changes in SeD and/or VED rat lens were observed, it is considered that selenium and vitamin E deficiency may be involved in the occurrence of cataract.

Myopathy and HIV infection

Current Opinion in Rheumatology (USA), 1995, 7/6 (497-502)

Skeletal muscle involvement may occur at all stages of HIV infection. The most simple classification of muscular disorders in HIV-infected patients is 1) HIV-associated myopathies, 2) zidovudine myopathy, 3) HIV wasting syndrome, and 4) opportunistic infections and tumoral infiltrations of muscle. Immunohistology for major histocompatibility complex class 1 antigen and histochemical reaction for cytochrome c oxidase are helpful in correctly classifying a myopathy as HIV polymyositis or zidovudine myopathy. Studies of cytokine expression in HIV-infected patients and of supplementation with compounds such as carnitine or micronutrients such as selenium might yield new insights into the pathogenesis and treatment of the various AIDS- associated muscular disorders.

Protective role of orally administered selenium and vitamin E towards cardiotoxicity induced by anthracyclines in the rat

Nutrition Clinique et Metabolisme (France), 1996, 10/2 (69-76)

Adriamycin-induced cardiotoxicity could be due to free radical formation, which induces lipid peroxidation and membrane damage. We have studied the effect of oral supplementation with selenium (Se) and/or vitamin E (Vit. E) on myocardiopathy in rats treated by adriamycin (ADM). Animals were divided intby ADM (ADM) or NaCl 0.15 M solution (Control group = C); standard diet (SD); ADM I and C I; SD with Se; ADM II and C II; SD with Vit. E; ADM III and C III; SD with Se and Vit. E; ADM IV and C IV. All rats received ADM or saline solution by the intraperitoneal route. Ascitis and survival were observed throughout 18 weeks and hearts were studied histologically. Survival was 100% for controls while median survival was 12 (ADM I and II), 14 (ADM III) and 16 weeks (ADM IV) in treated rats. Ascitis was significantly less marked in ADM IV compared with ADM I (p = 0.02). Heart weight was decreased in ADM I, II and III compared with those of controls (p = 0.001) while it was similar to controls in ADM IV. Cardiac lesions studied by semi-quantitative histology were less severe in ADM IV. Se associated with Vit. E could prevent cardiac toxicity induced by ADM treatment and may be helpful to clinicians in chemotherapy using anthracycline.

Enhancement of the antineoplastic effect of anticarcinogens on benzo[a]pyrene-treated Wistar rats, in relation to their number and biological activity.

Cancer Lett. 1994 Jul 29. 82(2). P 153-65

Naturally occurring anticarcinogens, such as vitamins C and E, and the microelement selenium were found to inhibit the induction of benzo[a]pyrene-induced malignant tumors in Wistar rats to various extends. The antineoplastic effect of the tested anticarcinogens is gradually increased according to the number of inhibitors selected. To date the maximum action against malignancy is manifested by use of the above three inhibitors. In the group of rats receiving vitamins C, E and selenium, the prolongation of life induced by adding more than one anticarcinogen to the treatment regime reached, and in some cases surpassed, the normal life expectancy of the rats. It is expected that by adding even more anticarcinogens, the antineoplastic potency (Ap) of the inhibitors will be further improved. These results encouraged us to conduct a clinical trial in terminal human cancer cases, in conjunction with the usual treatments of surgery or chemotherapy and irradiation.

Critical reappraisal of vitamins and trace minerals in nutritional support of cancer patients.

Support Care Cancer. 1993 Nov. 1(6). P 295-7

The potential of a high intake of fresh fruits and vegetables in cancer prevention is well established. Epidemiological studies support carotene, vitamins A, C, E and selenium as the active compounds. Antioxidant properties and direct effects (e.g. inhibition of N-nitrosamine formation or cell-to-cell interactions) are invoked. The role of other trace elements is less clear. The modulation of immune function by vitamins and trace elements remains important and affects survival. In established cancers, the site-specific differences in the diet/cancer relation require appropriate dietary changes, e.g. low fat (20% by energy) in breast cancer, or high vegetable or fruit intake in lung cancer. Single high-dose supplements (e.g. vitamin C) have proved to have no curative or life-prolonging effect. Chemotherapy and radiation increase the requirements for antioxidant compounds. Supplementation can diminish the damage induced by peroxidation. Carefully planned and monitored trials that establish the optimal intake of micronutrients as adjuvants in cancer patients are required.

The effect of dietary levels of selenium on radiation resistance and radiation-induced carcinogenesis

Nutrition Research (USA), 1996, 16/3 (505-516)

Combined (internal plus external) radiation exposure of the population and emergency workers, as a result of the Chernobyl accident, increased the oncogenic risk, and to reduce it is a problem of the utmost importance. A long-term experiment in 400 rats exposed to radiation following the Chernobyl pattern showed that a selenium-enriched diet started after exposure caused a longer average lifespan and a 1.5 - 3.5 fold decrease of leukaemias and other malignancies, e.g. breast, thyroid and lung cancers, etc., at late times. Selenium was first demonstrated to provide protection against late effects which is equivalent to a whole-body dose reduction by 1.4 Sv (140 rem). The dietary levels of selenium used were above those accepted as physiological but considerably below toxic ones (10, 30 and 100 microg Se/day per capita).

Differential induction of growth arrest inducible genes by selenium compounds

Biochemical Pharmacology (USA), 1997, 53/7 (921-926)

The effects of two types of selenium compounds on the expression levels of growth arrest and DNA damage-inducible (gadd) genes and on selected cell death genes were examined in mouse mammary MOD cells to test the hypothesis that the diversity of selenium-induced cellular responses to these compounds could be distinguished by unique gene expression patterns. Whereas the expression patterns of known cell death-related genes (bcl-2 and bax) were not informative with respect to the cellular response patterns upon exposure to selenium compounds, time-dependent and selenium species-specific induction patterns were observed for gadd34, gadd45 and gadd153 genes. It was also observed that the MOD cells expressed a truncated p53 transcript but no detectable immunoreactive P53 protein, indicating a null p53 phenotype. The fact that selenium compounds induced growth arrest and death of these cells and that these compounds induced specific patterns of expression of gadd genes indicates that these genes may mediate some selenium-induced cellular responses. The findings further imply that selenium compounds may be effective chemopreventive agents for human breast carcinogenesis, in which p53 mutations are frequent.

Selenium deficiency associated with cardiac dysfunction in three patients with chronic respiratory failure

Japanese Journal of Thoracic Diseases (Japan), 1996, 34/12 (1406-1410)

We encountered three patients with chronic respiratory failure who had heart failure of cardiac arrhythmias and low levels of serum selenium. All three had tracheostomies and had received long-term parenteral nutrition that had not included selenium. All three also had refractory cardiac dysfunction, which was manifested in edema, heart failure, and various tachycardias. We suspected that selenium deficiency had caused their cardiac dysfunction. Serum selenium concentrations were found to be much lower than normal in all three, so 100 microg/day of selenium was administered in addition to their tube feedings. Cardiac function improved after replacement of selenium. These cases show the need for preventing selenium deficiency in patients with chronic respiratory failure during long-term administration of parenteral nutrition.

A possible beneficial effect of selenium administration in antiarrhythmic therapy.

J Am Coll Nutr (UNITED STATES) Oct 1994, 13 (5) p496-8

OBJECTIVE: The following review of the literature on the importance of Selenium (Se) in myocardial homeostasis and of the pharmacology of this trace metal, represents an attempt to search, without prejudice to other possible explanations, for a rationale of a beneficial effect of Se substitution as an adjuvant to antiarrhythmic therapy. BACKGROUND: For several years, in the early 1980s, I had to deal with the problem of a serious ventricular arrhythmia (non-sustained and sustained ventricular tachycardia) which was remarkably resistant to a battery of the most potent antiarrhythmic agents. Eventually, dramatic improvement, lasting for a period of 8 years, was achieved with Flecainide, which, however, left unsolved the episodic occurrence of disabling ventricular bigemini. Over the most recent period of 1 year and 8 months, there was a sudden and unexplained return to unbroken normal sinus rhythm. Among the multiplicity of possible reasons for this fortunate development, the concurrent introduction of Se substitution appeared as the most obvious, though very tentative explanation. Substitution of this trace metal preceded the extinction of ventricular bigemini by 1 week and actually represented the sole modification of otherwise reasonably standardized conditions of antiarrhythmic therapy, life style and diet. (25 Refs.)

An expanded concept of "insurance" supplementation--broad-spectrum protection from cardiovascular disease.

Med Hypotheses (ENGLAND) Oct 1981, 7 (10) p1287-1302

The preventive merits of "nutritional insurance" supplementation can be considerably broadened if meaningful doses of nutrients such as mitochondrial "metavitamins" (coenzyme Q, lipoic acid, carnitine), lipotropes, and key essential fatty acids, are included in insurance supplements. From the standpoint of cardiovascular protection, these nutrients, as well as magnesium, selenium, and GTF-chromium, appear to have particular value. Sophisticated insurance supplementation would likely have a favorable impact on many parameters which govern cardiovascular risk--serum lipid profiles, blood pressure, platelet stability, glucose tolerance, bioenergetics, action potential regulation--and as a life-long preventive health strategy might confer substantial benefit. (111 Refs.)

Antioxidant status of hypercholesterolemic patients treated with LDL apheresis

Cardiovascular Drugs and Therapy (USA), 1996, 10/5 (567-571)

Oxidation of low density lipoprotein is involved in the pathogenesis of atherosclerosis. Epidemiological studies suggest a negative correlation between the occurrence of cardiovascular diseases and blood concentrations of lipophilic antioxidants such as vitamins A and E and beta-carotene. Trace elements, such zymes glutathione peroxidase and superoxide dismutase. The aim of this study was to determine the antioxidant and trace element status of patients with severe hypercholesterolemia who had been treated with dextran-sulphate low-density lipoprotein apheresis in comparison with two control populations, normocholesterolemic subjects and untreated hypercholesterolemic patients. Our results showed that, patients treated with LDL apheresis, compared with normocholesteromic subjects, were not deficient in vitamin E, beta-carotene, and copper, but had low plasma levels of selenium, zinc, and vitamin A. The low selenium and vitamin A levels were due to the LDL apheresis treatment, and the hypercholesterolemia might have provoked the low plasma levels of zinc.This study pointed out the potential benefits of supplemental selenium, zinc, and vitamin A in patients being treated with LDL apheresis.

The role of free radicals in disease

Australian and New Zealand Journal of Ophthalmology (Australia), 1995, 23/1

Evidence is accumulating that most of the degenerative diseases that afflict humanity have their origin in deleterious free radical reactions. These diseases include atherosclerosis, cancer, inflammatory joint disease, asthma, diabetes, senile dementia and degenerative eye disease. The process of biological ageing might also have a free radical basis. Most free radical damage to cells involves oxygen free radicals or, more generally, activated oxygen species (AOS) which include non-radical species such as singlet oxygen and hydrogen peroxide as well as free radicals. The AOS can damage genetic material, cause lipid peroxidation in cell membranes, and inactivate membrane-bound enzymes. Humans are well endowed with antioxidant defences against AOS; these antioxidants, or free radical scavengers, include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), beta-carotene, coenzyme Q10, enzymes such as catalase and superoxide dismutase, and trace elements including selenium and zinc. The eye is an organ with intense AOS activity, and it requires high levels of antioxidants to protect its unsaturated fatty acids. The human species is not genetically adapted to survive past middle age, and it appears that antioxidant supplementation of our diet is needed to ensure a more healthy elderly population.

Status of antioxidants in patients with diabetes mellitus with and without late complications

AKTUEL. ERNAHR.MED. KLIN. PRAX. (Germany), 1994, 19/3 (155-159)

The role of antioxidative vitamins in the therapy of diabetes mellitus is of growing importance. The development of diabetic late complications (cataract, retinopathy, nephropathy and neuropathy and others) is associated with an increased presence of free radicals, and therefore, elevated oxidative stress of the human body. The aim of the present study was the evaluation of the vitamin and selenium status of diabetics. Thirty-eight patients of the age of 35-58 years had been diabetics for 8-27 years and their plasma concentration of haemoglobin was 6.7-7.5%. The diabetics of type I were treated with a functional insulin therapy with dietary restrictions, whereas the type II diabetics received oral antidiabetica (sulfonyl urea, biguanids) and had to comply with a fixed diet. Any supplementation of vitamins was omitted. The nutritional intake was monitored by a weighed record over 7 days. The plasma concentrations of vitamin A, beta-carotone, K and E were determined by reversed-phase-PLC. For the assessment of vitamin C concentrations, a photometric method was used, and selenium concentrations was determined by electrothermal atomic absorption spectrometry. Mean values of plasma concentrations were: vitamin A 36-50 microg/dl, beta-carotene 35-42 microg/dl, vitamin K: 0.5-0.6 ng/ml, vitamin E: 1.1-1.6 mg/dl, selenium: 72-75 microg/l. The values of vitamin C concentration of the diabetics type I without late complications and of type II diabetics were at 0.8 mg/dl and, therefore, at the borderline. Diabetics of type I with late complications showed marginal values of 0.6 plus or minus 0.3 mg/dl. The critical value for the prevention of scorbut has been fixed at 0.4 mg/dl. The results of this confirm the importance and efficiency of vitamins, especially of ascorbic acid. Positive effects of this antioxidative vitamin in respect of the prevention of diabetic side effects and subsequent disease should therefore be expected.

Selenium supplementation in the diets of patients suffering from ulcerative colitis

Stedman J.D.; Spyrou N.M.; Millar A.D.; Altaf W.J.; Akanle O.A.; Rampton D.S.
J.D. Stedman, Department of Physics, University of Surrey, Guildford, Surrey GU2-5XH United Kingdom
Journal of Radioanalytical and Nuclear Chemistry (Hungary) , 1997, 217/2 (189-191)

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) in which there is recurrent inflammation of the mucous membranes of the colon. Inflammation is accompanied by the production of reactive oxygen species (ROS) including, amongst others, hydrogen peroxide. Selenium in the form of the selenoprotein glutathione peroxidase (GSH-Px) acts as a catalyst in the reaction which reduces hydrogen peroxide to watch. It may therefore beneficial to supplement the diets of patients who suffer from UC with selenium. In this preliminary study nine patients suffering from moderate UC were supplemented with selenium-beta tablets (300 microg Se per tablet) twice daily. Blood samples were taken at the start of the trial and at 1, 2 and 4 week intervals. Freeze-dried serum samples were analysed for their selenium content using the technique of instrumental neutron activation analysis (INAA). Samples were also analysed by particle induced X-ray emission (PIXE) to monitor other trace elements levels. Selenium concentrations were found to increase during supplementation and iron concentrations to decrease. Stool frequency was also found to improve suggesting that ROS may be important in the pathogenesis of UC.

Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group.

Cancer Res. 1994 Apr 1. 54(7 Suppl). P 2029s-2031s

In Linxian China, the esophageal/gastric cardia cancer mortality rates are among the highest in the world. There is suspicion that the population's chronic deficiencies of multiple micronutrients are etiologically involved. We conducted two randomized, placebo-controlled nutrition intervention trials to test the effects of vitamin and mineral supplements in lowering the rates of esophageal/gastric cancer. In the first trial, the dysplasia trial, 3318 adults with a cytological diagnosis of esophageal dysplasia received daily supplementation with 26 vitamins and minerals in doses typically 2-3 times the United States Recommended Daily Allowances, or placebos, for 6 years. The second trial, the general population trial, involved 29,584 adults and used a one-half replicate of a 2(4) factorial experimental design which tested the effects of four combinations of nutrients: A, retinol and zinc; B, riboflavin and niacin; C, vitamin C and molybdenum; and D, beta-carotene, vitamin E, and selenium. Doses for these daily supplements ranged from 1 to 2 times the United States Recommended Daily Allowances, and the different vitamin/mineral combinations or placebos were taken for a period of 5.25 years. As part of the general population trial, and end-of-intervention endoscopy survey was carried out in a small (1.3%) sample of subjects to see if supplementation affected the prevalence of dysplasia and early cancer. Herein we review the methods of these trials and the results of the endoscopic survey. Fifteen esophageal and 16 gastric cancers were identified in endoscopic biopsies from the 391 subjects evaluated from two villages, and nearly all were asymptomatic. No significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen with any of the four supplement groups. However, the prevalence of gastric cancer among participants receiving retinol and zinc was 62% lower than those not receiving those supplements (P = 0.09), while participants receiving beta-carotene, vitamin E, and selenium had a 42% reduction in esophageal cancer prevalence (0.34). We have reported separately that cancer mortality over the entire 5.25-year period was significantly reduced among those receiving beta-carotene, vitamin E, and selenium. The findings from the overall trial and the endoscopic sample offer a hopeful sign and should encourage additional studies with these agents in larger numbers of subjects.

Possible immunologic involvement of antioxidants in cancer prevention.

Am J Clin Nutr. 1995 Dec. 62(6 Suppl). P 1477S-1482S

The people of Linxian County, China have one of the world's highest rates of esophageal cancer. Two intervention trials were conducted to determine whether supplementation with specific vitamins and minerals could lower mortality from or incidence of cancer in this population and whether supplementation with multiple vitamins and minerals would reduce esophageal and gastric cardia cancer in persons with esophageal dysplasia. About 30,000 general population (GP) subjects in the GP trial were randomly assigned to one of eight intervention groups according to a one-half replicate of a 2(4) factorial experimental design and were supplemented for 5.25 y with four combinations of micronutrients at doses from one to two times the US recommended dietary allowance (RDA). About 3000 subjects in whom dysplasia was diagnosed in the dysplasia trial were randomly assigned to groups receiving daily supplementation with 14 vitamins and 12 minerals at two to three times the US RDA or placebo for 6 y. Results of the dysplasia trial indicate that in individuals with esophageal dysplasia, micronutrient supplementation had little effect on T lymphocyte responses. In contrast, male participants in the GP trial who were supplemented with beta-carotene, vitamin E, and selenium showed significantly (P < 0.05) higher mitogenic responsiveness of T lymphocytes in vitro than those not receiving these micronutrients.

Potential of food modification in cancer prevention

CANCER RES. (USA) , 1994, 54/7 SUPPL. (1957s-1959s)

This presentation focuses on research that could theoretically be applied to implement the strategy of general population chemoprevention. The concept is based on the premise of enhancing foods with known anticarcinogens through either agricultural methods or food-processing technologies. Two areas of our work are described: (a) garlic cultivated with selenium fertilization and (b) foods high in conjugated linoleic acid. Both selenium and conjugated linoleic acid are powerful chemopreventive agents in the animal tumor model. The rationale of delivering these two specific compounds through the food system will be developed. Preliminary studies will be su carcinogen-induced mammary cancer in rats. Finally, the advantages of using foods to provide anticarcinogens to the general population as part of a chemopreventive strategy will also be discussed.

Selenium-enriched garlic inhibits the early stage but not the late stage of mammary carcinogenesis

Carcinogenesis (United Kingdom) , 1996, 17/9 (1979-1982)

Previous work has shown that the efficacy of cancer prevention by selenium-enriched garlic (Se-garlic) is primarily dependent on the action of selenium. Additionally, supplementation of Se-garlic inhibited the post-initiation phase of mammary carcinogenesis when it was given continuously to the animals. In this report, experiments were carried out in which treatment with the Se-garlic was started after carcinogen dosing (DMBA or MNU) but was restricted to either the early or late stage of neoplastic progression. The results from these two models showed that a short-term exposure to the Se-garlic for 1 month immediately following carcinogen administration was just as effective in cancer prevention as the continuous exposure regimen (5 months), suggesting that the Se-garlic may irreversibly alter the process of clonal expansion and/or selection of transformed cells during their early stage of development. Plasma and mammary tissue selenium levels essentially returned to basal levels at 1 month after withdrawal of supplementation. These observations imply that the outcome of cancer protection by short-term Se-garlic intervention was not due to a slow turnover, and therefore a lingering presence, of selenium in the target organ or in the circulation. The above finding was in contrast to that of a second study in which Se-garlic was supplemented starting at 13 weeks after carcinogen treatment. With this protocol, the number of new tumors and the number of new tumor-bearing rats found during the intervention period (weeks 13 to 22) were not statistically different between the control and supplemented groups, suggesting that Se-garlic had a minimal effect on the later stages of mammary carcinogenesis.

Effect of an aqueous extract of selenium-enriched garlic on in vitro markers and in vivo efficacy in cancer prevention

Carcinogenesis (United Kingdom) , 1996, 17/9 (1903-1907)

Previous work has shown that the efficacy of cancer prevention by selenium-enriched garlic (Se-garlic) is primarily dependent on the action of selenium. An aqueous extract containing 43 microg Se/ml was prepared from lyophilized Se-garlic powder by the Soxhlet method. The activity of this Se-garlic extract was evaluated in a transformed mammary epithelial cell culture model for its effect on cell morphology, cell growth, cell cycle progression and the induction of single and double stranded breaks in DNA. Comparisons were also made with a similarly prepared extract from regular garlic, Se-methylselenocysteine (a major water-soluble seleno-amino acid identified in Se-garlic) and selenite (used for fertilizing Se-garlic). In contrast to the regular garlic extract which produced little or no modulation of the above parameters, treatment with the Se-garlic extract resulted in growth inhibition, G1 phase cell cycle arrest and apoptotic DNA double strand breaks in the absence of DNA single strand breaks. This pattern of cellular responses was duplicated with exposure to Se-methylselenocysteine. Selenite, on the other hand, induced cell cycle blockage in the S/G2-M phase, and a marked increase in DNA single strand breaks (a measure of genotoxicity) in addition to growth suppression. The chemopreventive efficacy of the two garlic extracts was also investigated in the rat methylnitrosourea mammary tumor model. Both extracts were supplemented in the diet for 1 month immediately following carcinogen administration. Significant cancer protection was observed with treatment by the Se-garlic extract (at 3 p.p.m. Se in the diet), while little benefit was noted with treatment by the regular garlic extract. Based on the above in vitro and in who findings, it is hypothesized that the Se-garlic extract, in part via the action of Se-methylselenocysteine, is able to inhibit tumorigenesis by suppressing the proliferation and reducing the survival of the early transformed cells. Furthermore, the data also support the concept that the moduss of novel forms of selenium for cancer prevention.

Multiple sclerosis: A diathesis?

GAZZ.SANIT. (MILANO) (ITALY), 1973, 22/1 (37-39)

The incidence of multiple sclerosis among predisposed subjects is higher in cold climates, and is compounded where trace metals, such as copper, selenium and cobalt, are lacking in the diet. The importance of trace elements in various metabolic processes is discussed, including the etiology of multiple sclerosis. Screening children, removing those at risk to warmer climates and further research into trace metal physiology are recommended.