Methylselenocysteine: The Super Selenium

by James South, M.A.

Selenium is an essential trace mineral, with a recently set RDA (Recommended Dietary Allowance) of 55 mcg.1 Selenium is known to be essential to activate various key enzymes, such as the antioxidant glutathione peroxidase, the metabolic enzyme thioredoxin reductase, and the thyroid-hormone-activating enzyme iodothyronine deiodinase.2

Although selenium is essential for life and health, it is also a potentially toxic mineral. Selenium expert Dr. R. Passwater notes “…organic forms of selenium [such as selenomethionine] are toxic at levels in the vicinity of 3,500 micrograms (3.5 milligrams) daily. Inorganic forms of selenium [such as sodium selenite/selenate] may be toxic at one-third that level.”3 Passwater notes, however, that many Japanese average 600 mcg daily from their diet, and Greenlanders may ingest as much as 1,300 mcg daily, without apparent ill effects.3

Selenium: The Anticancer Mineral
A connection between selenium intake and cancer has been known for decades. In 1969 Dr. R. Shamberger reported that his cancer patients averaged selenium blood levels only 60 to 80 percent as high as non-cancer patients.4

Shamberger and Frost found U.S. breast cancer rates were low in areas where selenium crop levels were high, and high where selenium crop levels were low.5 Shamberger and Frost also showed soil selenium levels (which dictate food selenium levels) were inversely connected to cancer death rates. Low selenium soil led to 516 deaths per 100,000 people; medium selenium soil led to 450; high selenium soil led to 430; and very high selenium soil correlated with 392 cancer deaths per 100,000.6

Schrauzer and colleagues found that annual selenium intake was strongly inversely correlated with breast cancer deaths in 27 countries studied, with the lowest selenium-intake countries (including the United States) having the highest breast cancer death rates, and the highest selenium-intake countries having the lowest death rate.7

A host of animal studies has also shown selenium to experimentally reduce cancer incidence. Harr and colleagues gave four groups of mice a carcinogen (FAA) for 210 days. Group I had no selenium added to its diet. Group II had 0.1 PPM (parts per million) added to its diet; Group III received an extra 0.5 PPM and Group IV had 2.5 PPM selenium added.8

After 210 days, 80 percent of Group I and II mice developed cancer; 10 percent of Group III had cancer; and only 3 percent of Group IV (highest selenium) developed cancer.

Schrauzer and Ishmael were able to reduce breast cancer incidence in female mice spontaneously prone to develop breast cancer from 82 percent in the control mice to 10 percent in the mice given 2 PPM selenium in their drinking water.9

Selenium vs. Cancer: Toxicity Concerns
The experimental animal cancer studies raised a major concern: the most powerful selenium anticancer effects often occurred at doses not far below the potentially toxic doses. This led researchers to study the biochemistry of selenium’s anticancer action in more detail, in an attempt to surmount the potential toxicity problem.

In the early years of selenium-cancer research, it was assumed that selenium provided anticancer protection through enhancing cell and liver antioxidant defenses (glutathione peroxidase) or through promoting enhanced detoxification of environmental carcinogens (glutathione S-transferase).10 Yet research from New Zealand in 1999 indicated that the selenoprotein enzymes were typically saturated (activity maximized) at dietary intakes of only 90 mcg selenium per day, far below optimal anticancer doses.11 A landmark U.S. study by L. Clark and colleagues found that a 200 mcg daily supplement of selenium from yeast given for four years or more led to a significant reduction in cancer deaths and incidence of prostate, lung and colorectal cancer compared to placebo, with prostate cancer levels reduced more than 60 percent.12,13 The diet provided an average 85 mcg of selenium, enough to saturate selenoprotein enzymes without further supplementation. Clearly other selenium effects than optimizing selenoprotein enzymes were at work.

Selenium: One Mineral, Many Forms
Throughout the 1980s and ’90s researchers discovered that different forms of selenium had different effects in the body. Inorganic forms, such as selenite/selenate, were more effective at fighting cancer than the commonly used organic form, selenomethionine, yet selenomethionine was more effective at increasing selenium tissue levels and glutathione peroxidase activity.14,15

By 1998 a major selenium/cancer researcher, Clement Ip, was able to explain the different metabolic pathways taken by selenite/selenate and selenomethionine. 16 Because cells cannot distinguish selenomethionine from the essential amino acid methionine, some selenomethionine became incorporated into general body proteins, increasing tissue selenium levels.


Yet the selenomethionine general proteins have no anticancer activity. Selenite/selenate are more frequently metabolized to the toxic metabolite hydrogen selenide (H2Se). Hydrogen selenide does have anticancer effects,17 but it is more toxic than selenomethionine.3 Its primary mode of killing cancer cells (and at high levels, normal cells as well) is through a process called “necrosis.”17,18

In necrotic cell death, cells disintegrate in a way that ruptures the cells’ DNA and membranes, and this may trigger an inflammatory reaction which can spread to nearby cells. Necrosis is a messy and toxic way to kill unwanted cells (i.e., cancer cells). Since far less selenomethionine ends up as hydrogen selenide, it is both less toxic, but also less anticancer then selenite/selenate.

Methylselenocysteine (MSC)
Selenium anticancer research of the past 15 years has focused heavily on a novel form of selenium: MSC. A relatively simple organic selenium compound, MSC is formed naturally in various plants, including garlic, wild leeks, onions and broccoli grown on high selenium soil,19 and methylselenocysteine rich foods have shown good anticancer activity, without excess tissue accumulation or toxicity.20

Methylselenocysteine is easily converted to methylselenol (Fig. 1) by an enzyme, beta-lyase, widely distributed in the body.2 Methylselenol has been shown to be an effective anticancer form of selenium,2,21 that kills cancer cells through a process of “programmed suicide,” called “apoptosis.” Apoptosis is a generally controlled, orderly, careful process of cellular self-destruction that can be triggered by various stimuli, including methylselenol.2

Cancer cells killed by apoptosis don’t leave a messy residue to trigger inflammation and spread cell death, as occurs in necrosis. Methylselenol is also known to inhibit angiogenesis in beginning cancer tumors.17 Angiogenesis, the creation of new blood vessels, is necessary for cancer cells to grow into a tumor, because cancer cells need a far greater blood supply than normal cells to survive.17

Methylselenocysteine: The Nontoxic Anticancer Selenium
Once methylselenol is formed from MSC, it is soon transformed into dimethylselenide, which is rapidly excreted in the breath.2 Any dimethylselenide not so excreted is converted to trimethylselenonium, which is thoroughly excreted in the urine.2

Thus, since MSC goes directly into the methylated selenium pathway, it cannot easily build up to toxic levels in the body. And because it is directly converted in cells to the preferred apoptotic selenium form methylselenol, methylselenocysteine has a powerful and safe anticancer effect.2,17,21

As Medina and colleagues concluded: “[Selenium] methylselenocysteine … holds promise as a true second-generation selenium chemoprevention [of cancer] compound because of its superior in vivo efficacy, virtually nonexistent toxicity, low body accumulation, and simple formulation.”2 Methylselenocysteine represents the safest and most effective anticancer form of selenium available today.

Methylselenocysteine: Safe Use
In their cancer prevention trial, Clark and colleagues found selenium (as high selenium yeast) safe at both 200 and 400 mcg/day levels, even when taken for years.1 Various peoples around the world routinely get 400 to 600 mcg selenium daily from their diet without ill effect, although Americans and Europeans typically get 100 mcg selenium or less from their daily diet.

Therefore, without knowledgeable medical supervision, selenium supplement intake, even in the form of safe methylselenocysteine, should be limited to 200 to 400 mcg daily for maximum safety. Nutritionally-oriented physicians may use as much as 900 to 2,000 mcg selenium daily as part of a comprehensive cancer treatment protocol.22

References
1. Comb, G. Impact of selenium and cancer prevention findings on the nutrition-health paradigm. Nutr Cancer 2001, 40:6-11.
2. Medina, D. et al. Se-methylselenocysteine: A new compound for chemoprevention of breast cancer. Nutr Cancer 2001, 40:12-17.
3. Passwater, R. Selenium Against Cancer and AIDS. New Canaan CT: Keats, 1996:47-48.
4. Passwater, R. Selenium as Food and Medicine. New Canaan CT: Keats, 1980:18.
5. 4 op. cit., 18-19.
6. 4 op. cit., 20.
7. 4 op. cit., 21, 23.
8. 4 op. cit., 28-29.
9. 4 op. cit., 30-31.
10. 4 op. cit., 37-41.
11. Duffield, A. et al. An estimation of selenium requirements for New Zealanders. Am J Clin Nutr 1999, 70:896-903.
12. Clark, L. et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol 1998, 81:730-34.
13. Clark, L. et al. The nutritional prevention of cancer with selenium 1983-1993: a randomized clinical trial. JAMA 1996, 276:1957-63.
14.Davis, C. et al. The chemical form of selenium influences 3,2’-dimethyl-4-aminobiphenyl-DNA adduct formation in rat colon. J Nutr 1999, 129:63-69.
15. Ip, C. and Hayes, C. Tissue selenium levels in selenium-supplemented rats and their relevance in mammary cancer prevention. Carcinogenesis 1989, 10:921-25.
16. Ip, C. Lessons from basic research in selenium and cancer prevention. J Nutr 1998, 128:1845-54.
17. Lu, J. and Jiang, C. Antiangiogenic activity of selenium in cancer chemoprevention: metabolite-specific effects. Nutr Cancer 2001, 40:64-73.
18. Hetts, S. To die or not to die: an overview of apoptosis and its role in disease. JAMA 1998, 279:300-07.
19. Whanger, P. Selenocompounds in plants and animals and their biological significance. J Am Coll Nutr 2002, 21:223-32.
20. Ip, C. and Lisk, D. Characterization of selenium profiles and anticarcinogenic responses in rats fed natural sources of selenium-rich products. Carcinogenesis 1994, 15:573-76.
21.Ip, C. et al. In vitro and in vivo studies of methylseleninic acid: evidence that a monomethylated selenium metabolite is critical for cancer chemoprevention. Cancer Res 2000, 60:2882-86.
22. 4 op. cit., 42-43.

The information in this article is not intended to provide personal medical advice, which should be obtained from a medical professional, and has not been approved by the U.S. FDA.

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