Selene-Activ

[Nutrition Adviser Product Information]

Overview

Selene-Activ has been formulated to provide the trace element selenium in a 200 mcg daily dose with a specific combination of antioxidant vitamins and minerals and the addition of alpha-lipoic acid and the plant extract sulforaphane.

This antioxidant food supplement has been designed to provide 200 mcg of selenium to make available a product that matches levels of this trace element used in the latest research studies.

In addition to selenium, the vitamins C and E are provided, which have long been shown to have a protective effect individually, as well as synergistically, with selenium on a cellular level.

Alpha-lipoic acid is one of the latest vitamin-like substances now commercially available, which not only has been shown to enhance the antioxidant function of vitamins C and E, but acts as an antioxidant in its own right, whilst also playing a part in the more efficient utilisation of blood glucose. The latter action is thought to not only lessen free radical formation on a cellular level, but also play a part in helping to optimise the energy production process.

The addition of sulforaphane not only offers protection against harmful endogenous and exogenous toxins, but it also supports the detoxification processes in the liver as well as disarming free radicals.

Selenium - General information

Facts in short

• Selenium is an essential trace element required only in microgram doses by the human body.
• Daily requirement and toxic doses are not widely separated (daily safe level 450 mcg for male adults/toxic dose 900 mcg).
• Until 1969 selenium was mostly associated with its induction of blind staggers and 'alkali disease' in sheep and cattle in areas with high selenium levels.
• The reason for its late recognition as an essential element is the overlap of its action with vitamin E, which made it more difficult to elucidate the function of selenium.(1)
• The British Government recommends a daily intake from the diet of 75mcg for men and 60mcg for women. However, the average intake has currently been estimated to be 43mcg per day.(2) The drop has been considerable between the seventies and mid nineties, most likely due to the use of European wheat, which has a lower selenium content, and a general reduction of bread and cereals consumption.

Function of selenium

Selenium is required as a co-factor for the enzymes glutathione peroxidase and thioredoxin reductase. These enzymes form part of the body's antioxidant enzyme systems that deal with the neutralisation of hydrogen peroxide and lipid peroxides.

Research indicates that the various antioxidant enzymes enhance the body's ability to deal with free radicals, which are destructive molecules or atoms created by pollutants such as cigarette smoke, smog or exposure to ultraviolet light. It appears that oxidative damage is a common denominator in the ageing process as well as certain major diseases such as heart disease, cancer, diabetes, cataract and macular degeneration. (3)

Epidemiological studies indicate low intakes of selenium are linked to a higher incidence of certain cancers. Out of eight trials that have been carried out on humans to assess the influence of selenium on the incidence of cancer, seven of them have shown selenium to have a positive effect. Selenium yeast is the most common form used in these trials and the results indicate that this is the most effective form so far for the reduction of most tumours. (4)

A clinical trial showed that individuals who had normal blood selenium levels, when given a daily dose of 200mcg of selenium, had a significant increase in the ability of lymphocytes to kill tumour cells (118%) as well as an 82% increase in the activity of white blood cells referred to as “natural killer cells”. (5)

In addition, research shows that the mineral selenium exerts antioxidant activity in its own right as well as being required for immune system function. Selenium has been shown to enhance T-cell responses, antibody synthesis and to protect immune cells. This trace element has the ability to alter platelet aggregation by decreasing the ratio of thromboxane to leukotriene production and to act as an antagonist to heavy metals such as lead, mercury, aluminium and cadmium. (6) Recently a link between selenium status and mood has been suggested, particularly in connection with its role in thyroid function. (7) Selenium also plays a role in spermatogenesis. (8)

Common deficiency signs and symptoms

Age spots, cancerous changes, cataracts, heart disease, infections, muscle inflammation, pale finger nail beds and pancreatic insufficiency.

Toxicity symptoms

These can be caused by the ingestion of 900 mcg of selenium per day over a prolonged period of time. Toxicity symptoms include nausea and vomiting, garlicky odour on the breath, hair loss, abnormal nail growth and loss of fingernails.

Food Sources and Availability of Selenium

Brazil nuts, grain, fish, meat (offal).

Selenium enters the food chain through plants. The amount absorbed depends on soil selenium content, chemistry, microbes and rainfall.

The trace element selenium in Wassen Selenium-ACE is provided in the form of high selenium yeast, which would appear to be a form that is similar to that found in cereal grains.

As the soil levels of selenium vary, it is difficult to guarantee that a sufficient amount may be obtained from the diet in spite of a good general diet. Grain is an important source for selenium, however, as this staple food is now sourced from Europe, rather than the United States or Canada, it would appear that it has become a less prominent one. Generally the intakes of selenium in Europe are low compared to those in the United States. (6)

Alpha-lipoic Acid

Alpha-lipoic acid was first isolated in 1951 and is known by a number of names which include 2-dithiolane-3 petanoic acid;1,2-dithiolane-3 valeric acid; and thioctic acid. (9) It is not designated as an essential nutrient, as the body is able to synthesise alpha-lipoic acid, however, it is readily absorbed from an oral dose.

Research indicates that taking a larger dose of alpha-lipoic acid, which can be obtained from food supplements, may strengthen the protective 'cellular shield' often associated with antioxidant nutrients. Alpha-lipoic acid is a powerful lipophilic scavenger of reactive oxygen species and may also operate in vivo (in partnership with its reduced form: dihydrolipoic acid) by recycling or sparing vitamins C, E and glutathione. (10,11,12)

Insulin stimulated glucose uptake is thought to be positively affected by alpha-lipoic acid. (13) Poor blood sugar transport at the cell membrane has been shown to cause the glycation of protein. This process results in sugar-damaged proteins, which are referred to as 'advanced glycosylation end products' (AGE's). AGE's are likely to be responsible for the kidney damage and tendency to atherosclerosis seen in diabetes. Alpha-lipoic acid inhibits glycation of proteins. (10) In Germany alpha-lipoic acid has long been given to diabetes sufferers in high doses with positive effects. (13) These benefits can probably be explained by the ability of alpha-lipoic acid to protect against the formation of AGE's as well as reactive oxygen species. The latter probably being responsible at least in part of many of the complications of diabetes inluding polyneuropathy and cataract formation. (10)

Alpha-lipoic acid is involved in other mechanisms which could influence the course of disease e.g. activation of transcription factors and their binding to DNA and inhibition of apoptosis. (10)

Sulforaphane

Organic isothiocyanates, also known as mustard oils, are widely distributed in plants, many of which are consumed by humans. They are responsible for the acrid flavour and odour of condiments such as mustard and horseradish, and the biting taste that develops when cruciferous vegetables are eaten. Sulforaphane has been isolated as a potent isothiocyanate inducer. Research indicates that isothiocyanates have a double effect in helping detoxify harmful substances from the body by firstly down- regulating Phase I enzymes and inducing Phase II enzymes that help with the detoxification of unwanted metabolites in the body.

The Phase I enzymes (cytochrome P-450 enzyme system) turn unwanted substances into a form that is easier to dispose from the body. However, this process can, in certain instances, increase toxicity of the intermediary metabolites formed, before they are worked on by Phase II Enzymes, which are involved with the final step of their removal. (15)

Initial research indicates that it is through the Phase II enzyme system, by which sulforaphane indirectly exerts its antioxidant and a cell protective effect. (16,17,18)

Sulforaphane and selenium have been showed to work synergistically (19) by upregulating thioredoxin reductase 1 expression, a selenium dependant enzyme present in subcellular locations , protecting the cells against oxidative damage. Thioredoxin reductase plays a key role in the regulatory mechanism of the cell including apoptosis and cell signalling. The results using selenium and sulforaphane separately, did not have the same protective effect.

Vitamin E

Vitamin E is a lipid phase antioxidant, playing an especially important role in all cell membranes where it protects unsaturated fatty acids and cholesterol. This vitamin has also been linked to healthy muscle function and fertility in both males and females. (20)

Vitamin C

This vitamin is classed as a water phase antioxidant, which also regenerates vitamin E. Research studies indicate that vitamin C has an immune boosting effect in those who have low intakes of this vitamin. In addition, it is important for the synthesis of procollagen of connective tissue cells, especially during periods of growth. Glycosaminoglycan (GAG) formation may require ascorbic acid as sulfate carrier. GAG's are part of the 'gel matrix' of the ground substance between all cells in all organs. Strong connective tissues play a part in making the body more resistant to unwanted micro organisms and increase the resilience of certain body tissues to wear and tear. An example is the pressure exerted on arteries by blood pressure. The adrenal medulla is one of the tissues with the highest vitamin C concentration, where this vitamin is involved in the production of hormones closely linked with stress control. (20)

Zinc

This mineral is involved in the activity of more than 300 enzyme systems in the body. (21,22)

Zinc plays a part in virtually every aspect of immunity, which includes T cells and thymic hormone levels as well as white blood cell count. (23,24) Research indicates that zinc, like vitamin C, possesses antiviral properties against several virus strains including the cause of common cold. According to a double blind trial, zinc-containing lozenges significantly reduced the average duration of the common cold. (25) Zinc is used to make one form of the antioxidant enzyme superoxide dismutase, which plays an important part in the protective mechanism of the body.

Conditions where selenium and antioxidants have been found helpful

Arthritis

According to J. R. O'Dell et al, 101 patients with seropositive rheumatoid arthritis were found to have significantly lower serum selenium concentrations, than 29 normal, healthy controls. It is speculated that selenium concentrations might modulate the effects of viral or other types of infections in subjects with the appropriate genetic background. Therefore selenium deficiency might enhance the development or progression of rheumatoid arthritis. (26)

A. Peretz et al. conducted a study to test the effect of selenium supplementation on Rheumatoid Arthritis (RA) sufferers. They concluded that the administration of selenium in addition to conventional treatment was beneficial in RA patients and that the clinical applications of selenium supplementation deserve to be explored on a larger scale, not only in rheumatic diseases but also in various inflammatory diseases and immune disturbances. (27)

Immunology

Luke Olmsted, Gerhard N. Schrauzer, Manuel Flores-Arce and Jim Dowd outline the possibility that with sufficient administration of the trace element selenium the body's system, which fights viruses, is enhanced. (28)

Howard T. Petrie et al. describe 'in vitro' experiments using selenium, which indicate that this trace element has a positive effect on immune regulation and that it enhances certain immune function, which may explain its protective effect against cancer. (29)

A three and a half year study was carried out by Marianna K. Baum et al. measuring specific immunologic and nutritional factors on survival in HIV-1 disease. The results indicate that selenium deficiency is an independent predictor of survival for those with HIV-1 infection. (30)

Oncology

Larry Clark at the Arizona Cancer Centre, USA, carried out a study to establish the effect of 200 mcg selenium (in the form of selenium yeast) on basal and squamous cell carcinomas of the skin. This multi-center, double-blind, randomised, placebo-controlled cancer prevention trial involved a total of 1312 patients with a history of basal cell or squamous cell carcinomas of the skin, and lasted from 1981 to 1993. Selenium treatment did not protect against the development of basal or squamous cell carcinomas of the skin. However, significant reductions were observed in total cancer mortality, total cancer incidence and incidences of lung, colorectal and prostate cancers. (31)

Opthalmology

Allen Taylor et al. describe how antioxidant vitamins E, C and betacarotene along with glutathione peroxidase protect the lens of the eye and thus help prevent or delay the onset of Age-Related Macular Degeneration. (32)

Geriatrics

A group of 22 elderly institutionalised subjects were assigned to a 6-month trial with either 100 mcg of selenium yeast or placebo on a daily basis. Plasma concentrations of the selenium supplemented group increased from 0.84 ± 0.26 to 1.55 ± 0.33 mmol/L after two months and the values plateaued thereafter. In accordance with previous studies in animals and in vitro, this investigation demonstrates for the first time immunostimulatory properties of selenium-enriched yeast in elderly humans. (33)

In the paper entitled "Antioxidants and immune response in aged persons: overview of present evidence" Simin Nikbin Meydani et al. outline that increased oxidative stress, possibly due to lower consumption of antioxidant nutrients, contributes to the decline of T cell-mediated function in aged persons. Increased intake of some antioxidant nutrients (vitamin E, beta-carotene and glutathione) enhances the immune response in aged persons. (34)

Pancreatitis

According to this study, in three cases of pancreatitis, amongst those who were supplemented with antioxidants, further attacks were held at bay during a 5-year follow-up period. (35)

This double-blind double-dummy crossover trial showed that those given antioxidant nutrients whilst suffering from a form of pancreatitis did not have an attack, whilst some of those on placebos did. In this study it was expressed that micronutrient antioxidant therapy offers a new approach to the treatment of recurrent (non-gallstone) pancreatitis and /or pancreatic pain. (36)

The case history of a 10-year old boy with calcific pancreatitis is reported. His theophylline clearance of 450ml/kg/h was several times higher than normal, indicating induction of cytochromes P450. Painful attacks disappeared concurrently with administration of antioxidants. The possible relevance of these findings is discussed in the context of chronic pancreatitis in childhood. (37)

Cardiology

Nigel G. Stephens et al. carried out a study to assess the effect of vitamin E (alpha-tocopherol) in the inhibition of oxidation of low density lipoprotein and thus its possible role in the prevention of atherosclerosis. It was concluded that in patients with angiographically proven symptomatic coronary atherosclerosis, alpha-tocopherol treatment substantially reduces the rate of non-fatal myocardial infarction, with beneficial effects apparent after 1 year of treatment. (38)

Jukka T. Salonen et al., carried out a longitudinal study in Finland involving a cohort of middle aged men who were followed up for 24 months. The researchers investigated the interaction between serum copper, selenium and low-density lipoprotein cholesterol concentrations with regard to the progression of carotid atherosclerosis. The data obtained during this study provided evidence of a synergistic effect of copper (a pro-oxidant), a low serum concentration of selenium and low-density lipoprotein cholesterol concentration in atherogenesis. (39)

References:

1. Schwarz K, Foltz CM, The Journal of Biological Chemistry, Volume 233, 1958: Factor 3 activity of selenium compounds. Nutr Rev. 1989 Apr;47(4):108-10.

2. Food Surveillance. Ministry of Agriculture, Fisheries and Food. Joint Food Safety and Standards Group. No. 126. October 1997

3. Cheraskin, E., Antioxidants in Health and Disease: The Big Picture, Journal of Orthomolecular Medicine, Vol. 10, No. 2, 1995

4. Whanger, PD, Selenium and its relationship to cancer: an update dagger. Br J Nutr 2004; 91(1):11:28

5. Kiremidjian-schumacher, L. et al, supplementation with selenium and human immune cell functions; II, Effect on cytotoxic lymphoytes and natural keller cells. Boil Trace Elem Res 41:155-127

6. McKenzie RC, Rafferty TS, G. J. Beckett, Selenium: an essential element for immune function, TRENDS Immunology Today, 1998; Vol. 19(8): 342-345,

7. Sher L, Role of thyroid hormones in the effects of selenium on mood, behavior, and cognitive function, Medical Hypotheses, 2001. 57(4) : 480-483

8. Wallace E., Calvin H. I, Ploetz K., Cooper G. W., Functional and developmental studies on the role of selenium in spermatogenesis, Selenium in biology and medicine, Combs G. F., Levander O.A. Spallholz J.E. Oldfield J. E. eds., Vol. A. New York: AVI, 1987; 181-96

9. Reed L. J., DeBusk B. G., Gunsalus I. C. et al., Crystalline a-lipoic acid: a catalytic agent associated with pyruvate dehydrogenase, Science, 1951; 114: 93-94

10. Packer L, Witt E. H., Tritschler H. J., Alpha-lipoic acid as biological antioxidant, Free Rad. Biol. Med., 1995; 19: 227-250

11. Podda M., Tritschler H. J., Ulrich H, Packer L., Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency, Biochem Biophys Res Commun, 1994; 204: 98-104

12. Xu DP, Wells W. W., a-lipoic acid dependent regeneration of ascorbic acid from dyhydroascorbic acid in rat liver mitochondria, J. Bioenerg Biomembr, 1996; 28: 77-85

13. Estrada DE, Ewart HS, Tsakiridis T et al., Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thiocotic acid:participation of elements of the insulin signaling pathway, Diabetes, 1996; 45: 1798-1804

14. Nichols TW, a-Lipoic Acid: Biological Effects and Clinical Implications, Alternative Medicine Review, 1997, Volume 2, Number 3, 1997

15. Yuesheng Zhang & Paul Talalay. Anticarcinogenic Activities of Organic Isothocyanates: Chemistry and Mechanisms. Cancer Research 1994; 54 Suppl: 1976s-81s.

16. Gao X, Dinkova-Kostova AT, Talalay P, Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, mouse leukaemia cells against oxidative damage: The indirect antioxidant effects of sulforaphane. Proc Natl Acad Sci 2001; 98(26): 15221-226

17. Brooks JD, Paton VG and Vidanes G, Potent Induction of Phase 2 Enzymes in Human Prostate Cells by Sulforaphane. Cancer Epidemiology Biomarkers & Prevention 2001; 10:949-54

18. Wu L, B. Juurlink HJ, The impaired glutathione system and its up-regulation by sulforaphane in vascular smooth muscle cells from spontaneously hypertensive rates. Journal of Hypertension 2001; 19:1819-25

19. Zhang J et al, Synergy between sulforaphane and selenium in the induction of thioredoxin reductase 1 requires both transcriptional and translational modulation. Carcinogenesis, 2003. 24(3):497-503

20. Maria C. Linder (Editor), Nutritional Biochemistry and Metabolism with Clinical Applications, Prentice-Hall International Inc., 1991

21. McCall KA et al, Function and mechanism of zinc metalloenzymes. J Nutr 2000; 130(5s Suppl): 1437S-46S

22. Prasad AS. Zinc: an overview. Nutrition, 1995; 11:93-99

23. Dardenne M et al, Contribution of zinc and other metals to the biological activity of the serum thymic factor, Proc. Natl Acad Sci, 1982; 79: 5370-5373

24. Bogden J. D. et al., Zinc and immunocompetence in the elderly: Baseline data on zinc nutriture and immunity in unsupplemented subjects, Am J Clin Nutr 1987; 46:101-109

25. Eby GA, Davis DR, Halcomb WW, Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimirob Agents Chemother 1984;25:20-24

26. James R. O'Dell, Susan Lemley-Gillespie, William R. Palmer, Arthur L. Weaver, Gerald F. Moore, Lynell W. Klassen, Serum selenium concentrations in rheumatoid arthritis, Annals of the Rheumatic Diseases, 1991, Vol. 50, pp376-378

27. Peretz, J. Mevet, J. Duchateau, J.P. Pamaey, Letters to the Editor, British Journal of Rheumatology, 1992, Vol., 31, pp281-282

28. Olmsted L., Schrauzer Gerhard N., Flores-Acre Manuel, Jim Dowd, Selenium Supplementation of Symptomatic Human Immunodeficiency Virus Infected Patients, Biological Trace Element Research, 1989, Vol. 20, 59S-65S

29. Howard T. Petrie, Lynell W. Klassen, H. David Kay, Selenium and the Immune Response: 1. Modulation of Alloreactive Human Lymphocyte Functions in Vitro, Journal of Leukocyte Biology, 1989, Vol. 45, 207S-214S

30. M. K. Baum et al., High Risk of HIV-Related Mortality Is Associated With Selenium Deficiency, Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 15, pp 370-374, 1997

31. Larry C. Clark, Effects of Selenium Supplementation for Cancer Prevention in Patients With Carcinoma of the Skin, Journal of the American Medical Association (JAMA), December 25, 1996, Vol. 276, No 24, 1957S-1963S

32. Allen Taylor, Paul F. Jacques, Esther M. Epstein, Relations among ageing, antioxidant status, and cataract, Am. J. Clin. Nutr. 1995; 62(suppl) 1439S-47S

33. Anne Peretz et al., Lymphocyte response is enhanced by supplementation of elderly subjects with selenium enriched yeast, American J. Clin. Nutr., 1991; 53: 1323 -8

34. Simin Nikbin Meydani, Dayong Wu, Michelle S. Santos, Michael G. Hayek, Antioxidants and immune response in aged persons: overview of present evidence, Am. J. Clin. Nutr. 1995; Vol. 62(suppl):1462S-76S

35. David Sandlands, Iona J. M. Jeffrey, Najib Y. Haboubi, Ian A. M. MacLennan, Joan M. Braganza, Abnormal Drug Metabolism in Chronic Pancreatitis, Gastroenterology, 1990, Vol. 98, 766S-772

36. S. Uden, D. Bilton, L. Nathan, L.P. Hunt, C. Main & J.M. Braganza, Antioxidant therapy for recurrent pancreatitis: placebo-controlled trial, Aliment. Pharmacol. Therap., 1990, Vol. 4, 357S-371S

37. J.M. Braganza, A. Thomas and A. Robinson, Antioxidants to treat chronic pancreatitis in childhood? International Journal of Pancreatology, 1988, Vol. 3, 209S-216S

38. Nigel G. Stephens, Ann Parsons, Peter M. Schofield, Frank Kelly, Kevin Cheeseman, Malcolm J. Mitchinson, Morris J. Brown, Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS), The Lancet, 1996, Vol. 347, 781S-786S

39. Jukka T. Salonen, Kari Seppänen. Marjatta Kantola, Sirpa Suntioinen, Heikki Korpela, Interactions of serum copper, selenium and low density lipoprotein cholesterol in atherogenesis, British Medical Journal, 1991, Vol. 302 pp756-759