Selenium

[Guest guest]

Below is a description (kinda lengthy!) of the status of selenium these days in

fighting cancer. Of course it was prepared by a company who manufactures

selenium compounds for that purpose, but there is some good info here

nonetheless.

I've read elsewhere that many studies indicate selenium is useful in prevention.

Here they talk about its therapeutic applications.

Not sure whether links below will still work after the copy and pasting routine

done here. If anyone is interested, contact me and I will forward the original

email as an attachment. It will probably work that way.

- Art

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Welcome To PharmaSe, Inc. and Eburon Organics, USA, Inc. We bring innovation to

Selenium Nutritional Supplements and to 35 Years of Nutrition Research involving

Selenium. Read on and then contact us!

New Product Evaluation Checklist for SeMC

Se-Methylselenocysteine

1. Description of product or technology (including novel features):

Se-Methylselenocysteine (SeMCTM) is a potent carcinostatic non-protein amino

acid naturally made by garlic, onions, leeks, ramps, broccoli, Astragalus and

likely other plants.

2. Safety Data:

The toxicity of SeMCTM as tested in rats is similar to or less than the toxicity

of L-selenomethionine the most widely marketed selenium supplement as Se-yeast

or L-selenomethionine. The National Cancer Institute has approved a $5 million

dollar toxicity trial of SeMCTM in animals. (Results in abstract form reports

that the NOAEL for male rats is 1.0 mg/kg/day, 28-Day Oral Toxicity Study of

Se-Methylselenocysteine in Rats, W.D et al, Society of Toxicology,

Nashville, TN March, 2002.) Our understanding is that all animal toxicology has

now been completed and an IND, Investigation New Drug, application is to be

filed by the NCI to the FDA in early 2003. PharmaSe, Inc supplied all the SeMCTM

to the NCI sponsored research.

3. Potential Claims and Substantiation:

The literature and recent human research has established selenium as a potent

anticarcinogen. The evidence for this effect in humans on human lung, prostate

and colorectal cancer was published in JAMA. A recent article on prostate cancer

in The Journal of the National Cancer Institute reports consumption of Allium

plants, those plants that make SeMCTM , significantly reduced this cancer in

Chinese men. See the following link.

(http://www.newsday.com/news/health/nyhspros06q2994037nov06.emailstory)

Animal data on cancer protection is extensive and an understanding of the

underlying chemistry is emerging. SeMCTM is the most effective anticarcinogen of

all the natural selenium supplements tested in animals. See the references

below, especially the one by Whanger. Abstracts can be viewed at pubmed. New!

The FDA has approved a labeling claim for selenium and its anti-cancer effects.

Go to www.fda.gov.

4: Regulatory Status in US, Major European Markets

SeMCTM has received food supplement approval (DESHEA regulations) from the US

Food and Drug (FDA) Administration in February 2002 for adult supplementation at

200 ug Se/day. PharmaSe, Inc originally submitted the FDA application in October

1999 and SeMC was approved for 100 ug Se/day supplementation in 2000. Selenium

supplements in Europe usually contain 100 ug Se.

5. Patents/Patent Fillings:

European Patents and US Patents are pending for both the synthesis and use of

SeMCTM as a food supplement for humans and pets.

6. Physical Properties of Material:

Two forms of the supplement are available, one in the free L-amino acid form and

one in the HCL form. The free amino acid has the higher percentage of selenium

by weight (43.4%). SeMCTM is produced as the L-amino acid. It is stable, off

white to yellowish in color depending on form with a characteristic " selenium "

odor much like L-selenomethionine. Its melting point as the free amino acid is

171 degrees Celsius. It is homogeneous (100% pure) by chiral HPLC analysis.

Approximate Cost of the Ingredient/Product.

NEW! PharmaSe, Inc is pleased to now offer an SeMC trit, 0.5% Se (5000 ppm Se)

in anhydrous dicalcium phosphate. We will ship the trit to your facility by

FedEx Ground FOB. The price for 1-15 kgs is $237.50/kg, 16- 25 kgs is $224.50/kg

and over 25 kgs $209.50/kg FOB by FedEx Ground. Additional discount for larger

purchases (need not be purchased now).

The present cost is $10,000.00 for one kilogram Pure SeMC (discounts for more

than a single kg order) for the free amino acid, 43.4% selenium by weight. SeMC

selenium cost for 100; 200 ug Se dosages is approximately US $0.20.

The effective protective cost for similar selenium cancer protection from

selenomethionine would between $15.00-24.00. PharmaSe, Inc can supply custom,

packaged formulations, trit or bulk material in commercial quantities. Always

compare costs by calculating your final cost per ug of Se. One kg of SeMC

contains 434,000,000 ug Se. Please supply your interests and formulation in

confidence for a quotation.

NEW TOO! We will formulate tablets or capsules with L-selenomethionine, SeMC and

other nutrients on a custom basis and deliver to you. Call with your request for

a quote. 2000 to 2 million capsules!

Timing of Commercial Availability:

Commercial amounts of the SeMCTM free L-amino acid are available right now for

your own product formulation or formulation by PharmaSe, Inc for you own label.

Shipment for the concentrate is made to your facility at no additional cost by

FedEx air within 24- 48 hrs of your order. SeMC trit is shipped FOB by FedEx

ground. Allow 5-7 days delivery depending on day of shipment and distance.

Additional descriptive information on our selenium products and SeMCTM is

attached along with references to the " Selenium Supplements backed by Science "

TM. PharmaSe, Inc will be pleased to send you copies of any of the references.

Links to Selenium Products

Links to Selenium Products

Selenium SeMC TM Products Online

www.nutri.com/selenium

www.lef.org/newshop/items/item00567.html

www.lowen.co.nz/

orders@...__________________________________________

Links to Selenium Information

USDA Announces SeMC TM Reduces Colon Cancer

http://www.ars.usda.gov/is/AR/archive/jun00/colon0600.htm

Search for More Information on SeMC

www.google.com enter methylselenocysteine, or selenium and cancer or Select

Trial, or selenomethionine

Questions about Selenium or SeMC specifically or to Contact us:

pharmase@...

Ph 806-786-8349

L- Se-METHYLSELENOCYSTEINE: The Story behind The Science

L-Se-methylselenocysteine, SeMCTM, a naturally occurring selenoamino acid which

is synthesized by Allium plants including garlic, onions, broccoli and species

of the genus Astragalus is now available on a commercial basis from PharmaSe,

Inc. Extracts of selenium-enriched garlic have shown that SeMCTM is the active

ingredient in the chemoprevention of mammary cancer and may be the active

ingredient in the protection of men from prostate cancer as reported in the

Journal of the National Cancer Institute. SeMCTM metabolism has been studied in

animals and the chemoprevention effect of SeMCTM is presently believed to occur

due to the generation of monomethylated selenium species by endogenous enzymes

(see Nutrition and Cancer Volume 40, 2001). Monomethylated selenium species have

been shown to generate superoxide and induce apoptosis to cancer cells in

culture. Unlike L-selenomethionine, which is incorporated into proteins in place

of methionine, SeMCTM is not incorporated into any

proteins thereby being fully bioavailable for chemoprevention and the synthesis

of selenium containing enzymes such as glutathione peroxidase. Preliminary

animal data indicates that SeMCTM is less toxic than L-selenomethionine when

included in diets which may be related to the accumulation of L-selenomethionine

in tissues. PharmaSe, Inc has a European Patent and U.S. Patents pending for a

novel synthesis of L-SeMCTM and its exclusive use as a dietary supplement for

humans and domestic animals.

Research Quantities of Unit Price/Unit

L-Se-methylselenocysteine* 10 mg $30.00

SeMCTM 50 mg $65.00

L-Selenomethionine 100 mg $100.00

Selenodiglutathione 1000mg $500.00

Methylseleninic acid (up to 20 gms)

*Analysis by HPLC Chromatography, Chiral GC-MS, Titration, and Melting Point

Carboxypolyselenocyanate (for attachment to antibodies and other molecules,

generates superoxide in the presence of thiols like GSH, Now Available Fall

2002) CALL! 806-786-8349

Seleno-dihydrotestosterone ( a drug for experimental prostate cancer research )

NOW Available CALL! 806-786-8349

Gamma-glutamyl-Se-methylselenocysteine (NOW Available ) Call for information

(~75% of selenium in garlic is this dipeptide)

Reference: Dong, Y., Lisk, D., Block E. and Ip, C., Characterization of the

Biological Activity of Gamma-Glutamyl-Se-methylselenocysteine: A Novel,

Naturally Occurring Anticancer Agent from Garlic. Cancer Res: 61,2923-2928,

2001.

Special Selenium Compounds Synthesized by Request, Please Call! 806-786-8349

PharmaSe, Inc.

3416 Knoxville Ave.

Lubbock, TX 79413

PH: 806-786-8349 E-mail: pharmase@...

Terms: Net 30 days in US funds. Shipping costs and taxes (where applicable) are

not included.. 50% deposit required on orders of 25 or more grams for research.

For Research and Human Supplementation as a Selenium Food Supplement as per the

Nutritional Supplement Regulations of the FDA.

References Publications

For the most up to date references go to www.ncbi.nlm.nih.gov and check PubMed

then search keyword: methylselenocysteine or methylseleninic acid for references

to SeMCTM

For Reviews with references on Selenium and Cancer go to email pharmase@...

May (Part1) and October (Part 2) Bulletins of the STDA by Spallholz, 2001 and

request copies by email.

Delineation of the Molecular Basis for Selenium-Induced Growth Arrest in Human

Prostate Cancer Cells by (Methylselenol) Oligonucleotide Array. Y. Dong, H.

Zhang, L.Hawthorn, H.E Ganther and C. Ip. Cancer Research, 63, 52-59, 2003.

Se-Methylselenocysteine (SeMC). M. Rae. Advances in Orthomolecular Research, 2,

5-13, 2003. (Review with 65 references)

Selenocompounds in Plants and Animals and Their Biological Significance. P. D.

Whanger. Journal of The American College of Nutrition, 21,223-232, 2002.

Selenium-enriched Broccoli Decreases Intestinal Tumorigenesis in Multiple

Intestinal Neoplasia in Mice. C.D. ,H. Zeng and J.W. Finley. Journal of

Nutrition 132,307-309, 2002.

Allium Vegetables and the Risk of Prostate Cancer. A.D. Hsing, A.P. Chokkalingam

et al. J. National Cancer Institute. 94, 1648-1651, 2002.

Se-methylselenocysteine Induces Apoptosis through Capase Activation and Bax

Cleavage Mediated by Calpin in SKOV-3 Ovarian Cancer Cells. J.K. Yeo, et al.

Cancer Letters, 182, 83-92, 2002.

Intracellular Glutathione is a Cofactor in Methylseleninic Acid-Induced

Apoptotic Cell Death of Human Hepatoma HEPG2 Cells. H.M. Shen and C.O. Ong. Free

Radical Biology and Medicine, 33, 552-561, 2002.

New Concepts in Selenium Chemoprevention. C. Ip, Y. Dong and H.E. Ganther.

Cancer Metastasis Reviews. 21, 281-289, 2002.

Dimethyldiselenide and Methylseleninic Acid Generate Superoxide in an In Vitro

Chemiluminescence Assay: Implications for the Anticarcinogenic Activity of

L-Selenomethionine and L-Se-methlyselenocysteine. J.E. Spallholz, B.J. Shriver

and T.W. Reid. Nutrition and Cancer 40, 31-34, 2001.

Bioactivation of Chemopreventive Selenocysteine Se-conjugates and related Amino

Acids by Amino Acid Oxidases Novel Route of Metabolism of Selenoamino Acids. M.

Rooseboom et al. Chemical Research and Toxicology, 14, 995-1005, 2001.

Se-Methylselenocysteine; A New Compound for the Treatment of Breast Cancer. D.

Medina, H. . H. Ganther and C. Ip. Nutrition and Cancer, 40,34-41, 2001.

Se-methylselenocysteine Induces Apoptosis Mediated by Reactive Oxygen Species in

HL-60 Cells. U. Jung et al. Free Radical Biology and Medicine, 31,479-489, 2001.

Selenium(Se) From High-Selenium Broccoli is Utilized Differently Than selenite,

Selenate and Selenomethionine, but is More Effective in Inhibiting Colon

Carcinogenesis. J.W. Finley and C.D. . Biofactors. 14, 191-196, 2001.

Preventing and Treating Cancer with Selenium in the New Millenium. J.E.

Spallholz, B. Shriver, L.M. Boylan and T.R. Reid Proceedings of the Seventh

Internation Symposium on Selenium in Biology and Medicine. Venice, Italy, 2000.

Selenium From High-Selenium Broccoli Protects Rats from Colon Cancer. J.W.

Findley, C.D. and Y. Feng. Journal of Nutrition 103, 2384-2389, 2000.

In Vitro and In Vivo Studies of Methylseleninic Acid: Evidence That a

Monomethylated Selenium Metabolite is Critical for Cancer Prevention.

C. Ip, H.J. Thompon, Z. Zhu, and H.E. Ganther. Cancer Research, 60, 2882-2886,

2000.

Chemical Speciation Influences Comparative Activity of Selenium-Enriched Garlic

and Yeast in Mammary Cancer Prevention. C. Ip, M. Birringer, E. Block, M.

Kotrebai, J.F. Tyson, P.C. Uden and D.J. Lisk. Journal of Agriculture and Food

Chemistry, 5. 2000.

Selenium Metabolism, Selenoproteins and Mechanisms of Cancer Prevention:

Compexities with Thioredoxin Reductase. H.E.Ganther. Cancinogenesis 20.

1657-1666, 1999

Selenium-induced Inhibitionof Angiogenesis in Mammary Cancer at Chemopreventive

Levels of (Dietary) Intake. C. Jiang,W.Jiang, Ip,C., Ganther, H. and Lu,I.

Molecular Carcinogenesis. 26,213-225, 1999.

The Retention and Distribution by Healthy Young men of Stable Isotopes of

Selenium Consumed as Selenite, Selenate or Hydroponically Grown Broccoli are

Dependent on the Chemical Form. J. FINDLEY Journal of Nutrition

129,865-871,1999.

Growing Alliums And Brassicas In Selenium- Enriched Soils Increases Their

Anticarcinogenic Potential. Medical Hypothesis. 53, 232-235, 1999.

Selenium from Broccoli is Metabolized Differently Than Se From Selenite,

Selenate or Selenomethionine. J. Findley. Journal of Agricultural and Food

Chemistry. 46,3702-3707, 1998.

Chemopreventive Agents: Selenium. G.F. Combes and W.P. Grey. Pharmacological

Therapy 79, 179-192, 1998

Lessons from Basic Research in Selenium and Cancer Prevention. C. Ip. Journal of

Nutrition 128, 1845-1854, 1998.

Should Selenium Enriched Vegetables be Consumed For the Prevention of Cancer?

P.D. Whanger, J.L. Green and J.A. . Proceedings of the Sixth International

Symposium on the Uses of Selenium and Tellurium. 57-61, 1998. sdale, AZ

Novel strategies in Selenium Cancer Chemoprevention Research. C. Ip and H.E.

Ganther. In, Selenium in Biology and Human Health, R.F. Burk, Ed. Chapter 9,

pp170-180. Springer-Verlag, Publisher New York. 1998,

Study of Prediagnostic Selenium Level in Toenails and the Risk of Advanced

Prostate Cancer. K. Yoshizawa, W.C. Willet, S.L. , S.J. Stampfer, D.

Spiegelman, E.B. Rimm and E. Giovannucci. Journal of the National Cancer

Institute 90, 1219-1224, 1998.

Chemical Transformations of Selenium in Living Organisms. Improved Forms of

Selenium for Cancer Prevention. H.E. Ganther and J.R. Lawrence. Tetrahedron 53,

12299-12310,1997.

DIETARY SELENIUM: TIME TO ACT-LOW BIOAVALIBILITY IN BRITIAN AND EUROPE COULD BE

CONTRIBUTING TO CANCERS, CARDIOVASCULAR DISEASE AND SUBFERTILITY. M.P. RAYMAN

BRITISH MEDICAL JOURNAL 314,387-388,1997.

Speciation of Selenoamino acids and Organoselenium compounds in

Selenium-enriched Yeast using High-performance Liquid Chromatography-inductively

Coupled Plasma Mass Spectrometry./ S.M. Bird, P.C. Uden, J.F. Tyson, E. Block

and E. Denoyer. J. Analytical Atomic Spectrophotometry. 12, 785-788, 1997.

Effects of Selenium Supplementation for Cancer Prevention in Patients with

Carcinoma of the Skin. L.C. et al. Journal of the American Medical

Association. 276, 1957-1963, 1996.

Effect of an Aqueous Extract of Selenium-Enriched Garlic on in vitro and in vivo

efficacy in Cancer Prevention. J. Lu, H. Pei, C. Ip, D.J. Lisk, H. Ganther and

H. J. . Carcinogenesis 17, 1903-1907, 1995.

Efficacy of Cancer Prevention by High-Selenium Garlic is Primarily Dependent on

the Action of Selenium. Carcinogenesis 16,2649-2652,1995

Allium Chemistry: Identification of Selenoaminoacids in Ordinary and

Selenium-enriched garlis, onion, and broccoli using Gas Chromatography with

Atomic Emission Detection. X.J. Cai, E. Block, P.C. Uden, Z. Zhang, B. D.

Quimbly, and J.J. Sullivan. Journal of Agricultural Chemistry. 43, 1754-1757,

1995.

Characterization of Tissue Profiles and Anicarcinogenic Responses in Rats Fed

Natural Sources of Selenium-Enriched Products. C. Ip and J. Lisk.

Carcinogenesis. 15, 573. 1994.

Enrichment of Selenium in Allium Vegetables for Cancer Prevention. C.P. Ip and

D.J. Lisk. Carcinogenesis 15, 1881-1885, 1994.

Enrichment of Selenium in Allium Vegetables for Cancer Prevention. Ibid.

Carcinogenesis 9,1881-1885,1994a.

Novel Strategies in Selenium Cancer Chemoprevention Research. Ip,C. and Ganther,

H.E. in Selenium in Biology and Human Health R.F. Burk, Ed. Chapter 9.

Springer-Verlag, New York 171-180. 1994.

Effect of Methylated Forms of Selenium on Cell Viability and the Induction of

DNA Strand Breaks.A.C. , H.J. , P.J. Schedin, N.W. Gibson, and

H.E. Ganther. Biochemical Pharamacology 43, 1137-1141, 1992.

Comparison of Selenium ans Sulfur Analogs in Cancer Prevention. C. Ip and H.E.

Ganther. Carcinogenesis 13, 1167-1170, 1992.

Mammary Cancer Prevention by Regular Garlic and Selenium-Enriched Garlic. C.Ip,

D.J. Lisk and G.S. Stoewsand. Nutrition and Cancer 17, 279-286, 1992.

Chemical Form of Selenium, Critical Metabolites, and Cancer Prevention

C. Ip, C. . R.M. Budnick and H. Ganther. Cancer Research 51,595-600,1991.

Activity of Methylated Forms of Selenium in Cancer Prevention. C. Ip and H.E.

Ganther Cancer Research, 50, 1206-1211,1990.

The Metabolism of Selenomethionine, Se-methylselenocysteine. their Selenonium

Derivatives, and Trimethylselenonium in the Rat. S. J. , R.J. Kraus and

H.E. Ganther. Archives of Biochemistry and Biophysics 251, 77-86, 1986b.

Interaction of Vitamin C and Selenium Supplementation in the Modification of

Mammary Carcinogenesis in the Rat. C. Ip Journal National Cancer Institute 77,

299-303, 1986.

Oxidation-Reduction Reactions of Organoselenium Compounds. I. Mechanism of

Reaction between Seleninic Acids and Thiols. Journal of the American Chemical

Society. 100,5094-5102,1978.

Biosynthesis of Se-methylselenocysteine and S-methylcysteine in Astragalus

bisulcatus. D.M. Chen, S.N. Nigam and W.B. McConnell. Canadian J. of

Biochemistry 48,1278-1283, 1970.

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Other Products Available From PharmaSe, Inc

Methylseleninic Acid, CH3SeOOH, (The likely active metabolite from SeMC,

Selenomethionine and Se-garlic)

L-Selenomethionine USP