Cautionary Tale / Eat Selenium

[Travis]

Plant foods appear to have much less selenomethionine than eggs total, per mass, yet have a much higher selenomethionine/selenocysteine ratio. They also have less methionine total, perhaps making the selenomethionine/methionine ratio higher.

Khanam, Anjum. "Bioaccessibility of selenium, selenomethionine and selenocysteine from foods and influence of heat processing on the same." Food chemistry (2016)​

 

[Ulysses]

View attachment 8431

Plant foods appear to have much less selenomethionine than eggs total, per mass, yet have a much higher selenomethionine/selenocysteine ratio. They also have less methionine total, perhaps making the selenomethionine/methionine ratio higher.

Khanam, Anjum. "Bioaccessibility of selenium, selenomethionine and selenocysteine from foods and influence of heat processing on the same." Food chemistry (2016)​

Can I take this to mean that selenomethionine and selenocysteine are the only, or at least the only significant, forms of dietary selenium? I see that they're measuring for "selenium" in the third column of that chart on the last page, but is this selenium bioavailable, or does it have to be bound with a protein?

 

[Travis]

Can I take this to mean that selenomethionine and selenocysteine are the only, or at least the only significant, forms of dietary selenium? I see that they're measuring for "selenium" in the third column of that chart on the last page, but is this selenium bioavailable, or does it have to be bound with a protein?

Honestly, I don't think inorganic selenium even has a biological role. As far as I know: selenium is necessary only for selenoenzmes (i.e. glutathionine peroxidase, thyroxine deiodinase), and all selenoenzymes contain selenomethionine or selenocysteine. Catalytic metals like Zn²⁺ and Fe²⁺ exist noncovalently bound to histidine in the case of of the zinc finger, and inside porphyrin in the case of the ubiquitous heme. I believe copper also has a noncovalent role, and nothing really seems analogous to selenium. Iodide forms a noncovalent bond with tyrosine to form thyroxine, but I⁻ is a halide and not really comparable. I know that organic selenium makes inorganic selenium unnecessary, but not exactly sure whether or not the body can produce seleno‐methionine/cysteine from the bare selenide ion (Se²⁻). If I had to make a guess, I would say no; but one of us will find out pretty soon for certain (this is interesting).

 

[Ulysses]

Honestly, I don't think inorganic selenium even has a biological role. As far as I know: selenium is necessary only for selenoenzmes (i.e. glutathionine peroxidase, thyroxine deiodinase), and all selenoenzymes contain selenomethionine or selenocysteine. Catalytic metals like Zn²⁺ and Fe²⁺ exist noncovalently bound to histidine in the case of of the zinc finger, and inside porphyrin in the case of the ubiquitous heme. I believe copper also has a noncovalent role, and nothing really seems analogous to selenium. Iodide forms a noncovalent bond with tyrosine to form thyroxine, but I⁻ is a halide and not really comparable. I know that organic selenium makes inorganic selenium unnecessary, but not exactly sure whether or not the body can produce seleno‐methionine/cysteine from the bare selenide ion (Se²⁻). If I had to make a guess, I would say no; but one of us will find out pretty soon for certain (this is interesting).

Check out the thread "how to reverse soft tissue calcification." I posted a paper there about minerals in water, by the French hydrologist L.C. Vincent. His contention is that no inorganic minerals have a biological role.

 

[Amazoniac]

They make no distinction between selenium ions, selenocysteine, and selenomethione, the last of which has consistently been shown to reduce cancer. Lumping this in with inorganic selenium would of course scatter the strong correlations seen with this form only, which stems from its ability to compete with methonine. The amino acid selenomethionine can be incorporated into proteins seemingly just as well as methionine, yet unlike the latter it will not form a polyamine. This is most likely the prime mechanism of action for the carcinostatic effects seen with selenomethionine supplementation, which the author takes as synonymous with selenium—missing the point entirely.

If glutathionine peroxidase is upregulated in cancer then you shouldn't necessarily implicate selenium; this enzyme can be induced by multiple things, the most common being the redox balance. The relative increase in any one amino acid doesn't necessarily increase the rate of synthesis of proteins which contain it, and inorganic cofactor–ions don't necessarily increase the synthesis of enzymes which use them. Glutathione peroxidase is a symptom of dysregulated redox balance, I think the authors of that study need to show in rats that either selenium or selenomethione will cause diabetes—and make explicit which one they're using.

Travisord, the first link is based on a selenomethionine study.

This is from the second:

"Selenomethionine is the only Se compound which can be incorporated unspecifically into other proteins instead of its sulphur analogue methionine. Excess Se in the organism is removed in the form of the di- and trimethylated Se compounds dimethylselenide and trimethyl selenonium. After the first methylation step from hydrogen selenide to methylselenol, a spontaneous oxidation to methylselenenic acid can take place. Methylselenol can also be liberated from selenomethionine by methionine-g-lyase. Both methylselenol and methylselenenic acid possess a high reactivity towards thiols [46-48]. In the presence of oxygen, high concentrations of hydrogenselenide, which again may be derived from the reduction of the inorganic Se compounds selenite and selenate, can produce elementary Se and superoxide radicals [48]. In conclusion, current knowledge of Se metabolism and functional selenoproteins suggests that Se exerts its physiological functions via the activity of functional selenoproteins only within a very narrow range of supplementation. Long-term Se intake beyond the recommendations carries the risk of serious pro-oxidative damage to various organs due to the loss of GPx activity."

"The much weaker insulin-mimicking and anti-diabetic effects of selenite and selenomethionine may be explained by their particular metabolism. Compared to selenate, selenite already reacts during its absorptions with thiol compounds, such as GSH, to form selenodiglutathione (GSSeSG) or proteins forming selenotrisulphides (RSSeSR). Thus, selenite-derived Se metabolites delivered to tissues are GSSeSG, RSSeSR or hydrogen selenide (H2Se). A hypothetical pathway by which orally-administered selenite can at least influence the activity of PTP1B involves the formation of methylselenenic acid (MeSeOH) from methylselenol (MeSeH), which can be produced by the methylation of hydrogen selenide (H2Se), obtained from the complete reduction of selenite [47,48]. Methylselenenic (MeSeOH) acid may modify the active site cysteine from PTP1B and redound to inactive glutathionylated PTP1B by the release of methylselenol (MeSeH) in the presence of glutathione [141] (Figure 4B). A similar modification of PTP1B can be assumed to occur with selenomethionine, since methylselenol can be released from selenomethionine by methionine-g-lyase and oxidized to MeSeOH [47,48,141] (Figure 4C)."

An equitable However!
"The hypothetical inhibition of PTP1B by methylselenol derived from oral selenite and selenomethionine seems to be less effective."

"In addition to GPxs, which already reach plateau activity with the recommended dietary Se amounts, a slight supranutritive Se supplementation may contribute to a further deglutathionylation and therefore activation of PTP1B [156]. The underlying mechanisms with regard to this aspect, e.g. changes in thiols, thioredoxins or glutaredoxins, remain to be investigated. Activated PTP1B (I) dephosphorylates the insulin receptor b sub-unit and IRS1 [178180] and (II) stimulates the lipogenic pathway [181184]. This on the one hand leads to a permanent inhibition of the insulin signal and to a permanent activation of the lipogenic pathway on the other hand. Therefore, the insulin secretion hypothesis (see Figure 2) [82] combined with the PTP1B activation hypothesis provides plausible explanations for the early development of insulin resistance and obesity due to permanent Se supplemention (Figure 5), as practised in the cancer prevention trials."​

If I'm not wrong, people consume about 50mcg of selenium from diet, then 250mcg total with a selenomethionine supplement. This form is capable of elevating all markers of selenium. For it to be incorporated as protein there has to be an excess, and this sustained mild excess can be responsible for the first pro-oxidant effects which can be subtle (so no signs of toxicity right away) but become more evident in the long-term. What do you think?

 

[Travis]

That last paragraph sounds like speculation: they had listed only one source for their 'may contribute to...' sentence, yet had listed two or three citations for most of other statements they'd made. This could just be a continuation of the classical bias of unpatented drugs—which has been going on for hundreds of years; the tone of methylglyoxal speak had slowly morphed since the '60s despite its efficacy, and lapachol had been maligned for its dubiously vitamin K inhibition.

But if true, it sounds as if they are incriminating the inorganic selenium species and not selenomethionine. Of course the selenium atom can be released, but this isn't quantitative; and higher therapeutic index would be achieved with selenomethionine. The inorganic selenium ion bridges two glutathione molecules, links them together (S–Se–S), and this can just be explained by the natural affinity of selenium for sulfur; I think you could expect mercury to do something similar, as it binds thiols even more strongly.

I think we should check out the citation #156 of that article, to see if there is any real foundation for this. And even if there was, selenomethionine is going to do this much less because it doesn't always release its selenium atom.

 

[Amazoniac]

That last paragraph sounds like speculation: they had listed only one source for their 'may contribute to...' sentence, yet had listed two or three citations for most of other statements they'd made. This could just be a continuation of the classical bias of unpatented drugs—which has been going on for hundreds of years; the tone of methylglyoxal speak had slowly morphed since the '60s despite its efficacy, and lapachol had been maligned for its dubiously vitamin K inhibition.

But if true, it sounds as if they are incriminating the inorganic selenium species and not selenomethionine. Of course the selenium atom can be released, but this isn't quantitative; and higher therapeutic index would be achieved with selenomethionine. The inorganic selenium ion bridges two glutathione molecules, links them together (S–Se–S), and this can just be explained by the natural affinity of selenium for sulfur; I think you could expect mercury to do something similar, as it binds thiols even more strongly.

I think we should check out the citation #156 of that article, to see if there is any real foundation for this. And even if there was, selenomethionine is going to do this much less because it doesn't always release its selenium atom.

Pompadourable, there's one thing that I only realized now: you need to restore oxidation in cancer. Perhaps that pro-oxidant effect is good for the same reasons that increased methylglyoxal is beneficial, which in turn (not as coincidence) is elevated and involved in diabetes damage: it's depleting to the defenses when it becomes a chronic stressor. Györgyizord mentioned that methylglyoxal is safe as long as is kept more or less balanced with glutathione. It always comes down to gbolduev's balance. Remember those bars from the other thread? Lowering oxidation out of precaution in this condition will be unfruitful, I think one way to deal with this is increasing the regeneration of glutathione. If on one iwanttobecomeyou hand a brutal requirement for oxidation.. oxidizes it, by increasing its raygeneration you are able to keep a constant balance and provide what's needed for restoration while coachme minimizing harm.

My interpretation is that in cancer some more selenium can be helpful indeed, and people should aim for that slightly pro-oxidant effect while doing everything possible to protect themselves from the stress. On the other hand, for health maintenance it's not the safest thing to do because you can get all those protective effects from selenium with lower doses and without the unnecessary stress.

The reactivity with thiols occurs with quinones as well. There are people who think it's fine to take up to 45mg of supplemental menatetrenone, but in my opinion it's not; it's about the minimum dose that maximizes the benefit. When in excess it should stress the glutathione system. I know there will be an argument that herbivores consume massive amounts of phylloquinone so it can't be unsafe. The only problem is that people supplement K2 alone, whereas in plants there's ample nutritional support, which includes what's needed to maintain balance, supporting glutathione regeneration and protecting from the oxidative stress. Imagine how much nutrition herbivores get from those leaves..

 

[Travis]

Pompadourable, there's one thing that I only realized now: you need to restore oxidation in cancer. Perhaps that pro-oxidant effect is good for the same reasons that increased methylglyoxal is beneficial, which in turn (not as coincidence) is elevated and involved in diabetes damage: it's depleting to the defenses when it becomes a chronic stressor. Györgyizord mentioned that methylglyoxal is safe as long as is kept more or less balanced with glutathione. It always comes down to gbolduev's balance. Remember those bars from the other thread? Lowering oxidation out of precaution in this condition will be unfruitful, I think one way to deal with this is increasing the regeneration of glutathione. If on one iwanttobecomeyou hand a brutal requirement for oxidation.. oxidizes it, by increasing its raygeneration you are able to keep a constant balance and provide what's needed for restoration while coachme minimizing harm.

My interpretation is that in cancer some more selenium can be helpful indeed, and people should aim for that slightly pro-oxidant effect while doing everything possible to protect themselves from the stress. On the other hand, for health maintenance it's not the safest thing to do because you can get all those protective effects from selenium with lower doses and without the unnecessary stress.

The reactivity with thiols occurs with quinones as well. There are people who think it's fine to take up to 45mg of supplemental menatetrenone, but in my opinion it's not; it's about the minimum dose that maximizes the benefit. When in excess it should stress the glutathione system. I know there will be an argument that herbivores consume massive amounts of phylloquinone so it can't be unsafe. The only problem is that people supplement K2 alone, whereas in plants there's ample nutritional support, which includes what's needed to maintain balance, supporting glutathione regeneration and protecting from the oxidative stress. Imagine how much nutrition herbivores get from those leaves..

I was thinking about methylgloxal after I had made that comment, but you'd brought it up first. However, Thornalley explains the anticancer effect of methylglyoxal simply on the basis of its ability to bind with glutathione—inactivating it; he does not elaborate on why glutathione itself would enhance proliliferation. So with decreased glutathione, you could expect an increase in methylglyoxal—which could actually do its main work in glutathionine‐independent ways: (1) It could form a Schiff base with polyamines, thereby inactivating them (Koch Mechanism?): Or, (2) it could transform arginine residues inside the NADH‐binding sites (used for binding NADH's phosphate bridge) found within nearly every glycolytic enzyme ⟶ into imidazolone ⟶ abrogating its cofactor binding ability and reducing glycolysis in an intuitive, negative‐feedback manner (The Travis Mechanism). If the Koch mechanism were primary, then selenomethionine would still be more effective since it's more direct; this molecule inhibits the very synthesis of polyamines by acting as a methionine proxy, capable of being incorporated into structural proteins and enzymes yet incapable of forming polyamines.

So I guess if inorganic selenium atoms disable glutathione, the increase in methylgloxal could act to reduce glycolysis. Thornally had proven a few years ago that methylgloxal modifies a transcription factor (mSin3A), reducing the replication of mRNA for vascular endothelial growth factor. Due to its reactivity and high‐selectivity for arginine side chains of proteins, this isn't hard to believe. In fact, Thornalley had actually proved that an arginine side‐chain in transcription factor (mSin3A) had been cyclicized to imidazalone in the classic methylglyoxal–arginine reaction. So any transcription factor in the cells nucleus with an arginine‐containing DNA‐binding domain could be rightly suspected as being methylglyoxal‐modifiable, especially if it transcribes for glycolytic genes.

Yao & Thornalley "High Glucose Increases Angiopoietin-2 Transcription in Microvascular Endothelial Cells through Methylglyoxal Modification of mSin3A." The Journal of Biological Chemistry (2007)​

 

[Obi-wan]

Amazonomaniac and Travisord have been going round and round on selenomethionine as Travisord distinguishes between organic and in-organic. I have read many articles indicating 200-800 mg of organic is still a safe level.

Although selenium is an essential trace element, it is toxic if taken in excess. Exceeding the Tolerable Upper Intake Level of 400 micrograms per day can lead to selenosis.[104] This 400 µg Tolerable Upper Intake Level is based primarily on a 1986 study of five Chinese patients who exhibited overt signs of selenosis and a follow up study on the same five people in 1992.[105] The 1992 study actually found the maximum safe dietary Se intake to be approximately 800 micrograms per day (15 micrograms per kilogram body weight), but suggested 400 micrograms per day to avoid creating an imbalance of nutrients in the diet and to accord with data from other countries.[106 -Wikipedia

By the way, Travisord, Manuka Honey seems to have a good concentration of Methylglyoxal!

Is Manuka Honey Even Healthier than Normal Raw Honey?
MGO Manuka Honey. What is Methylglyoxal?

 

[Braveheart]

Amazonomaniac and Travisord have been going round and round on selenomethionine as Travisord distinguishes between organic and in-organic. I have read many articles indicating 200-800 mg of organic is still a safe level.

Although selenium is an essential trace element, it is toxic if taken in excess. Exceeding the Tolerable Upper Intake Level of 400 micrograms per day can lead to selenosis.[104] This 400 µg Tolerable Upper Intake Level is based primarily on a 1986 study of five Chinese patients who exhibited overt signs of selenosis and a follow up study on the same five people in 1992.[105] The 1992 study actually found the maximum safe dietary Se intake to be approximately 800 micrograms per day (15 micrograms per kilogram body weight), but suggested 400 micrograms per day to avoid creating an imbalance of nutrients in the diet and to accord with data from other countries.[106 -Wikipedia

By the way, Travisord, Manuka Honey seems to have a good concentration of Methylglyoxal!

Is Manuka Honey Even Healthier than Normal Raw Honey?
MGO Manuka Honey. What is Methylglyoxal?

Thank you for this post re selenium....

 

[Travis]

Amazonomaniac and Travisord have been going round and round on selenomethionine as Travisord distinguishes between organic and in-organic. I have read many articles indicating 200-800 mg of organic is still a safe level.

Although selenium is an essential trace element, it is toxic if taken in excess. Exceeding the Tolerable Upper Intake Level of 400 micrograms per day can lead to selenosis.[104] This 400 µg Tolerable Upper Intake Level is based primarily on a 1986 study of five Chinese patients who exhibited overt signs of selenosis and a follow up study on the same five people in 1992.[105] The 1992 study actually found the maximum safe dietary Se intake to be approximately 800 micrograms per day (15 micrograms per kilogram body weight), but suggested 400 micrograms per day to avoid creating an imbalance of nutrients in the diet and to accord with data from other countries.[106 -Wikipedia

Not distinguishing between selenomethionine and selenocysteine is tantamount to failing to make the distinction between ammonia and lysine, and calling them both 'nitrogen.' But as a micronutrient, it's common to dose selenomethionine in terms of its selenium content—a practice I take less issue with, although it promotes the idea of the equivalency between species. The problem I see is using the old literature on selenium toxicity & requirements to extrapolate those of selenomethionine, or even saying anything useful about it for that matter. Selenomethionine is a structural amino acid which is essential in this form only, meaning the continual conflation of the two makes about as much sense as calling cysteine simply 'sulfur'—and looking at toxicity studies on sulfuric acid to set its limit.

By the way, Travisord, Manuka Honey seems to have a good concentration of Methylglyoxal!

Is Manuka Honey Even Healthier than Normal Raw Honey?
MGO Manuka Honey. What is Methylglyoxal?

Nice. That honey would be awesome for throat cancer, although the sucrose could be a liability. This could make a nice addition to pau d' arco.

 

[Obi-wan]

@haidut should come up with a product that includes;

1. Selenomethionine
2. Methylglyoxal
3. Stearic acid
4 Pau d' Arco
This would be a blockbuster combo. He could call it SelenoMethyStericArco...the force would be very strong...

 

[Regina]

@haidut should come up with a product that includes;

1. Selenomethionine
2. Methylglyoxal
3. Stearic acid
4 Pau d' Arco
This would be a blockbuster combo. He could call it SelenoMethyStericArco...the force would be very strong...

or CancerBan

 

[Amazoniac]

Neoplasnon. Don't worry, I'll be in court supporting you.

 

[Obi-wan]

Polyaminenon.

5. L-threonine also

 

[Amazoniac]

Here's another one in favor of caution. It's a great review that supports the assumption that if selenium has an useful role in cancer, it comes associated with its pro-oxidant effects. Travisord, you posted a study on colon cancer, but it was in vitro if I'm not wrong. They claim that there's no specificity, you can't control where the excess of selenomethionine is going to be spilling, which is why the other authors above mentioned that perhaps encapsulating and delivering the selenium to the colon cancer region (just like curcumin) is a reasonable approach. All in all, one thing is for sure: a slight excess has pro-oxidant action, and this is unnecessary stress for maintenance. And now it raises the question if it's indeed good for cancer since the data is conflicting and there wasn't anything exceptional happening in trials. Supplementing 200mcg of selenomethionine will give you 250mcg or more when added to dietary intake, is this sufficient to stress and insufficient to make a difference? I don't know.

The Epidemiology of Selenium and Human Cancer - ScienceDirect

"the amount and activity of antioxidant selenoproteins, particularly glutathione peroxidases and plasma selenoprotein P, have been frequently used as indirect indicators of selenium intake, and their low levels have been frequently interpreted as a consequence and a biomarker of selenium deficiency (Fairweather-Tait et al., 2011; Jablonska & Vinceti, 2015; Labunskyy et al., 2014; Vinceti et al., 2009). However, this approach overlooks the fact that selenoprotein levels and activity increase as a compensatory response to oxidative stress, and therefore, several stressors with pro-oxidant activity, including high amounts of some selenium species, may upregulate selenoproteins (as well as other antioxidant enzymes) thanks to this mechanism (Hafeman, Sunde, & Hoekstra, 1974; Jablonska & Vinceti, 2015; Touat-Hamici et al., 2014; Vinceti et al., 2009). In addition, no clear relation between selenoprotein activity per se and health outcomes has been established so far in epidemiologic studies. These complex relations between selenium exposure and selenoprotein activity may explain why some regulatory agencies have not adopted a proteomic approach based on maximal upregulation of selenoprotein levels by ingested selenium when setting the dietary reference values for this element (Jablonska & Vinceti, 2015; Vinceti et al., 2017)."

"With specific reference to cancer, interest in a possible etiological role of selenium was first sparked by laboratory animal studies, suggesting the ability of selenium to enhance cancer growth (Nelson, Fitzhugh, & Calvery, 1943; Schroeder & Mitchener, 1972; Seifter, Ehrich, Hudyma, & Mueller, 1946) and later to counteract it (Clayton & Baumann, 1949; Shamberger & Rudolph, 1966). Similarly, ambiguous effects have been observed in more recent studies, which have reported that forms of selenium may enhance carcinogenesis (Birt et al., 1988; Chen et al., 2000; National Toxicology Program, 2011; Novoselov et al., 2005; Su, Tang, Tang, & Gao, 2005; Woutersen, Appel, & Van Garderen-Hoetmer, 1999), reduce it (Guo, Hsia, Hsiung, & Chen, 2015; INCHEM, 1987; Nakahara et al., 2013; Steinbrenner, Speckmann, & Sies, 2013; Wang, Sun, Tan, Wu, & Zhang, 2014; Wrobel, Wolff, Xiao, Power, & Toborek, 2016; Yang, Jia, Chen, Yang, & Li, 2012), or exert ambivalent effects through the selenoproteins (Brigelius-Flohe & Kipp, 2016; Hatfield, Yoo, Carlson, & Gladyshev, 2009; Kasaikina et al., 2013; Varlamova & Cheremushkina, 2017)."
Davezord, remember our talk about references? Words spoke louder than words.

"For decades, controversies regarding selenium have abounded, with claims of health benefits met with counterclaims of harm. An atmosphere of selenophobia, or fear of the health effects of selenium, in the early 1970s (Frost, 1972) gave way to a culture of selenophilia focused on the health benefits of selenium in the late 1980s (Casey, 1988). Driving the selenophilia side of the debate has been the fascinating possibility that changes of just a few μg/day in dietary intake of selenium may modify the risk of cancer."

"Smoking, for example, is a source of selenium exposure, but it also paradoxically leads to lower levels of selenium in blood, possibly due to an interaction with cadmium ( Jossa et al., 1991; Vinceti, Grill, et al., 2015)."

"The SELECT was conducted as a response to the apparent prostate cancer risk reduction findings of the NPC trial and of a trial of vitamin E (The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group, 1994), and findings from other trials examining a combination of vitamin E and selenium and other antioxidant substances (Lippman et al., 2009). This trial, a major effort by groups of oncology investigators and supported by the US National Cancer Institute, is for its size, cost (over 114 million US $), and soundness of scientific design not only the most important trial for selenium but also one of the most important trials ever implemented in the field of nutritional epidemiology and cancer chemoprevention (Goodman et al., 2013; Lippman et al., 2005)."

"The trials have consistently shown that selenium administration, in the form of 200 μg/day of organic selenium exclusively or predominantly as selenomethionine, with the exception of 250 μg/day of inorganic selenium in the Polish trial, does not reduce the risk of overall cancer or of major cancer types (Table 1). This conclusion is also reached when performing summary meta-analyses of these trials, as reported in Fig. 3."

"As shown in Fig. 3, summary estimates did not show evidence of any beneficial effect of selenium supplementation on cancer risk when looking at all cancers (Fig. 3A) and major cancer types such as colorectal cancer, melanoma and nonmelanoma skin cancer, and lung, breast, bladder, and prostate cancers (Fig. 3B–H). Limiting the analysis to the RCTs with the best methodological quality, these results were confirmed and suggested if anything a potential excess risk for breast and lung cancer and for melanoma. In a single study in patients with a history of resected lung cancer (Karp et al., 2013), selenium supplementation was also unexpectedly associated with a statistically unstable increase of some cancers such as hepatobiliary cancer, though the small number of cases made it difficult to evaluate the results."

"Subjects in the lowest baseline selenium status tertile in the NBT trial (Algotar et al., 2013) did not show a prostate cancer reduction despite being comparable (Table IV of that paper and Fig. 2) with the two NPC trial lowest and middle baseline selenium tertiles, which showed strong reductions in all cancer and prostate cancer incidence (Duffield-Lillico, Dalkin, et al., 2003; Duffield-Lillico et al., 2002)."
Simply correcting a deficiency?

"Overall, despite the heterogeneity of the study populations, the results of RCTs are consistent in ruling out a beneficial effect of selenium supplementation, further confirming the SELECT results. This is particularly true when limiting the analysis to the high-quality, low-bias studies (Fig. 3). Therefore, it is now clear that selenium intakes of around 250 μg/day [what you get from diet + supplement] or above have no effect on cancer risk compared with lower amounts, and they might also have adverse effects on the risk of cancer or other chronic diseases, contrary to previous claims about the possible benefits of supranutritional selenium intakes (Rayman, 2002)."

As part of a therapy:
"The mechanisms underlying the anticancer and antiproliferative properties of selenium compounds are not well established and are still under active investigation. They encompass a spectrum of effects including pro-oxidant and proteomic activities, which ultimately induce apoptosis, necrosis, and paraptosis (Bao et al., 2015; Fernandes & Gandin, 2015; Zhao et al., 2016). Therefore, the potential use of intermediate to high doses of selenium species in cancer therapy and more generally in human disease appears to be driven by its toxicological properties (Forceville, 2013; Jablonska & Vinceti, 2015; Nogueira & Rocha, 2011), and selenium compounds when used in this context must be considered drugs and tested as such in appropriate animal and human studies."

"Results of these trials indicate that raising exposure of organic selenium to supranutritional levels of about 300 μg/day is not effective in reducing cancer risk and may even increase it, and it also appears to increase the incidence of type 2 diabetes. As far as lower amounts of selenium intake (falling in the nutritional range) and their relation with cancer risk are concerned, no evidence from high-quality trials is available and no conclusion can be drawn from observational studies due to their methodological limitations, such as unmeasured confounding and exposure misclassification."

 

[Travis]

All there authors are talking about 'selenium,' but I've said repeatedly that only selenomethionine inhibits polyamine formation. There is a classic study (prospective) on selenomethionine and prostate cancer that had yielded a massive 70% reduction.

And the first quote makes me laugh, and reminds me of HIV research. Taking high levels of gluthatione peroxidase as a marker for selenium status is silly, and basically guarantees that selenium adequacy will often be conflated with 'oxidative stress' by some of them (as long as they are under the impression that 'high selenium' increases glutathione peroxidase levels, and not oxidative stress.)

Selenium research is so sloppy.

 

[Amazoniac]

The majority of studies in humanoids use selenomethionine or selenium-enriched yeast (which is 60-85% selenomethionine).

"preliminary report [NPC trial] has always attracted more interest than the final reports, as indicated by a February 2017 Google Scholar search conducted by our group which showed over 3000 hits for the preliminary 1996 report, 532 hits for the 2002 report, and even fewer (272) for the final report addressing the primary outcome. The report documented a sharp decrease in overall cancer incidence (39%) and mortality (50%) as well as in incidence of lung, colorectal, and prostate cancer (Clark et al., 1996). Prostate cancer had a decreased incidence of 65% compared to the placebo group, yielding a hazard ratio (HR) of 0.35 (95%CI 0.18–0.65). In contrast, there was little evidence for any effect of selenium supplementation on the primary outcome of nonmelanoma skin cancer incidence.

In contrast to this preliminary report, the final study results published in 2002–2003 were mixed and raised some important concerns (Table 1). On the positive side, there continued to be evidence of decreased prostate and colorectal cancer risk, and evidence of decreased risk for all cancers and lung cancer (Duffield-Lillico et al., 2002;Reid et al., 2002). However, there was an excess risk, though statistically imprecise, for breast cancer and for melanoma, bladder, and lymphatic malignancies. Further analyses concerning the prostate cancer endpoint showed a weak inverse relation between baseline plasma selenium levels in placebo-treated participants, but an unexpected direct association between baseline plasma selenium levels and subsequent prostate cancer incidence in selenium-treated subjects (Dalkin et al., 2001).

Furthermore, the primary outcome of the trial, the incidence of nonmelanoma skin cancer, showed an excess incidence of the disease in selenium-treated subjects (Duffield-Lillico, Slate, et al., 2003), contradicting the original hypothesis that prompted the trial. An excess risk of glaucoma was also found among selenium-treated subjects, though the results were not published in a peer-reviewed article (Marshall, Reid, & Lillico, 2002). This prompted an observational study that also found this association (Bruhn, Stamer, Herrygers, Levine, & Noecker, 2009).

Another major source of concern was raised by Stranges et al. in their secondary analysis of the NPC cohort regarding a condition thus far not associated with selenium intake, type 2 diabetes (Stranges et al., 2007). In this study, published a decade after completion of the trial, the investigators found an increased risk of diabetes in selenium-treated subjects with suggestion of a dose–response relationship according to baseline selenium status.

In addition to these sources of concern for adverse effects of selenium, a serious methodological issue was discovered shortly after the publication of the final results of the trial. The authors revealed in their 2003 report (Duffield-Lillico, Dalkin, et al., 2003) that there had been a severe detection bias, with a lower tendency to be biopsied in the selenium arm compared to the placebo arm (14% vs 35%). This bias greatly undermines the reliability of the trial results at least with regard to the prostate cancer results. It is unclear if and how it affected other cancer endpoints. Taking into account a recently published study on factors influencing prostate biopsy rates in selenium and vitamin E cancer prevention trial (SELECT) and another trial (Tangen et al., 2016), it might be hypothesized that also the increase in diabetes incidence associated with selenium supplementation in NPC may have induced a lower biopsy rate in these subjects, thus contributing to the occurrence of this detection bias."

"Financial support to this study was provided by Lega Italiana per la Lotta contro i Tumori (LILT), Reggio Emilia Section, and Associazione Sostegno Oncologia Ematologia Pediatrica (ASEOP) of Modena (to Dr. Vinceti); the National Institute of Health Grant No. NIH CA016042 (to Dr. Crespi)."

 

[Amazoniac]

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[Amazoniac]

Mineral Supplements - Would You Be Interested In Any Of The Following? (was reading the thread again and came accross this post)