Cautionary Tale / Eat Selenium

[Travis]

Okay; I'll admit that nearly any selenium species tested—be it selenite, selenate, methylselenol, dimethylselenide, L-selenomethionine, D-selenomethionine, selenocysteine, methylselenocysteine, etc.—inhibits proliferation of cancer cells in vitro and tumors in vivo to some degree, but L-selenomethionine seems to be the most effective gram for gram. Nearly every selenium species seems have a different mechanism of action and many have been formally proposed. I had concentrated on the polyamine pathway for L-selenomethionine inhibition explicitly because it is intuitive, biochemically-plausible, and has been proven to occur.⁽¹⁾ It has been known since the '60s that polyamines bind dNA⁽²⁾, and shortly thereafter they've been shown to catalyze dNA replication via PCR—an aqueous system using only enzymes, nucleotides, and heat (polyamines being optional).⁽³⁾ Later investigations had revealed that spermine lowers the energy barrier from the B-dNA configuration to the Z-dNA configuration,⁽⁴⁾ literally transforming the normal right-handed helix into one left-handed. Polyamines also have an increased affinity for 'CpG islands,' areas relatively-rich in 5-methylctyosine that also tend to be housekeeping genes.⁽⁵⁾ Polyamines so reliably catalyze dNA replication that they can rightly be considered a small-molecule transcription factor.

Thomas Baine's doctoral dissertation goes a long way towards understanding the enigmatic effects of selenium on cancer cells.⁽⁶⁾ While aiming to elucidate the primary mechanism of organic selenium species, Doctor Baines had analyzed the effects of selenomethionine and methylselenocysteine on polyamines and prostaglandin E₂. As reliable cancer cell proliferents: these two molecules seem a logical focus and Dr. Baines had previously been familiar with selenomethionine's polyamine inhibition; after all, he had co-authored the Redman article (not that Redman article, the other Redman article).⁽⁷⁾ He had given rats low parts per million doses in their food―

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It is important to give selenomethionine in food and not water, or you could end-up with results like this:⁽⁸⁾

Doctor Niall Corcoran, a urologist from Australia, had given eight groups or rats eight different selenium species in their drinking water. Upon seeing the results, he trumpets 'inorganic selenium' (sodium selenide) as being the most effective selenium species. What Doctor Corcoran failed to consider, however, is the very low solubility of selenomethionine:⁽⁹⁾

'Solubilities: The solubilities of methionine and of selenomethionine in water at 30°C and pH 7.0 are 0.386 M and 0.108 M, respectively. The fact that selenomethionine is only about one-third as soluble as methionine suggests that the side chain of selenomethionine is more hydrophobic than that of methionine.' ―Shepherd​

Methionine has a density of 1.34g/cm³ yet selenomethionine weights 49.3% more. Although Corcoran's flask could initially hold 3·ppm of selenomethionine in solution—as reported—it could potentially form a density gradient over time, depending of course on the time passed between mixing and mouse-administration. Accurate solubilities of selenomethionine do not seem to be commonly reported, and even Sigma–Aldrich lazily uses methionine's solubility to represent that of selenomethionine—as seen here and here—despite it being over three times less.⁽⁹⁾ Although the bottom of Corcoran's volumetric flask most certainly had 3·ppm of selenomethionine, and probably much more, the concentration actually poured in the mouses tongue-activated ball-bearing water dispenser could have been much lower. Since all other studies I've read show selenomethionine to be much more active than selenide, I think it's fair to conclude that the results reported by Doctor Niall Corcoran—a urologist from Australia—had been confounded by water solubility considerations.

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...and had found the expected cancer reductions. In isolated human cells, selenomethionine had caused reduced cyclooxygenase-2 protein levels after six days despite invariable mRNA levels (in HT-29 cells). Prostaglandin E₂ was correspondingly reduced, and these results were so significant that he'd decided to focus on it.

'The decrease in PGE2 levels correlate well with the growth inhibition seen during the time course.' ―Baines​

Yet he doesn't explain it, despite a large proportion of his 146-page dissertation being devoted to the 'discussion.' However, cyclooxygenase-2 does have a methionine in it's catalytic domain at position #131,⁽¹⁰⁾ and a six-day lag period is consistent with enzyme turnover & new protein synthesis.

click to embiggen

Although superoxide or oxygen are commonly assumed to be the other substrate besides arachidonate, detailed studies reveal that peroxynitrite is actually responsible.⁽¹²⁾ Peroxynitrite (ONOO⁻) is formed from the spontaneous interaction of superoxide (Ȯ₂⁻) with nitric oxide (ṄO), and is generally considered the most damaging reactive nitrogen species known. Inducible nitric oxide synthase (iNOS) reliably increases prostaglandin formation, and nitric oxide seems to be why. Peroxynitrite is perhaps known best for its tyrosine adduct, yet it has been shown to interact with lysine and methionine.⁽¹³⁾ Lysine-294 sits at the top of cyclooxygenase's heme ring, while (Se)methionine-131 sits on the bottom:⁽¹¹⁾

Cytochrome C peroxidase is a heme protein with a core iron atom axially-ligated on the underside by a thiol, a cysteine in this case.⁽¹⁴⁾ Since demethylated methionine is also a thiol, as homocysteine, I think it's reasonable to assume that cyclooxygenase's heme iron is complexed in the same way. The homocysteine of cyclooxygenase-2 could be situtated in a way analogous to the thiol–Fe²⁺ interaction of cytochrome C peroxidase (left), and could perhaps be better visualized by considering how cobalamin's central cobalt is complexed (right).

Perhaps heme enzymes normally axially-ligated through methionine exhibit a reduced activity when substituted by selenomethionine? This is not a radical proposal, and mutagenic studies have shown selenoenzymes to have vastly different kinetic rates than their sulfur analogues. Although formate dehydrogenase is not a heme protein, replacing its selenocysteine with plain cysteine results in a 311-fold reduced activity:⁽¹⁵⁾

Since tRNA and ribosomes cannot differentiate between selenoamino acids and those sulfur-based, some cyclooxygenase-2 must be occasionally-formed with selenomethionine-131. This would of course occur much more frequently upon supplementation, and could potentially lead to reduced heme binding and/or differential catalytic activities. This would of course happen over the course of a few days, and could perhaps explain the long-term reductions of prostaglandin E₂ observed by Baines.

[1] Redman, C. "Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells." Carcinogenesis (1997)
[2] Hirschman, S. "Interaction of spermine and DNA." Biopolymers (1967)
[3] Fiedorow, P. "The influence of polyamines on polymerase chain reaction (PCR)." Acta biochimica Polonica (1997)
[4] Thomas, T. "Polyamine-induced B-DNA to Z-DNA conformational transition of a plasmid DNA with (dG-dC) n insert." Journal of Biological Chemistry (1991)
[5] Antequera, F. "Number of CpG islands and genes in human and mouse." Proceedings of the National Academy of Sciences (1993)
[6] Baines, A. "The mechanism of action of the anticancer effects of selenomethionine on colon cancer." (2001).
[7] Redman, C. "Inhibitory effect of selenomethionine on the growth of three selected human tumor cell lines." Cancer letters (1998)
[8] Corcoran, N. "Inorganic selenium retards progression of experimental hormone refractory prostate cancer." The Journal of urology (2004)
[9] Shepherd, L. "Some chemical and biochemical properties of selenomethionine." Canadian journal of biochemistry (1969)
[10] Smith, W. "Cyclooxygenases: structural, cellular, and molecular biology." Annual review of biochemistry (2000)
[11] Gupta, K. "The 2.0 Å resolution crystal structure of prostaglandin H₂ synthase-1: structural insights into an unusual peroxidase." Journal of molecular biology (2004)
[12] Salvemini, D. "Nitric oxide activates cyclooxygenase enzymes." Proceedings of the National Academy of Sciences (1993)
[13] Tien, M. "Peroxynitrite-mediated modification of proteins at physiological carbon dioxide concentration." Proceedings of the National Academy of Sciences (1999)
[14] Perera, R. "Neutral thiol as a proximal ligand to ferrous heme iron." Proceedings of the National Academy of Sciences (2003)
[15] Axley, M. "Catalytic properties of an Escherichia coli formate dehydrogenase mutant in which sulfur replaces selenium." PNAS (1991)​

 

[Amazoniac]

Guru, thank you as alvvays for such a detailed post.

nearly any selenium species tested—be it selenite, selenate, methylselenol, dimethylselenide, L-selenomethionine, D-selenomethionine, selenocysteine, methylselenocysteine, etc.—inhibits proliferation of cancer cells in vitro and tumors in vivo to some degree, but L-selenomethionine seems to be the most effective gram for gram

Makes sense. Do you think the focus should be on selenium or selenomethionine? Because both provide benefits, but a reasonable therapeutic dose will vary depending on where the main benefit is coming from.

Selenium weights more than sulfur right? What about volume of the whole molecule? A difference in density might do the affectings on the shape of the proteids.

 

[Travis]

Guru, thank you as alvvays for such a detailed post.

Makes sense. Do you think the focus should be on selenium or selenomethionine? Because both provide benefits, but a reasonable therapeutic dose will vary depending on where the main benefit is coming from.

Selenium weights more than sulfur right? What about volume of the whole molecule? A difference in density might do the affectings on the shape of the proteids.

I started thinking that methionine would outnumber selenomethionine about 100∶1 at the more generous dietary intakes, meaning that the number of cyclooxygenenase enzymes made with selenomethionine would probably be insignificant. Since we do have 'selenoproteins,' the fate of selenocysteine can be controlled by the cell—yet the 'common idea' is that selenomethionine is incorporated willy-nilly into enzymes. Since L-selenomethioinine works at such low concentrations, I think you'd be forced to assume that it's either: (1) a high-affinity enzyme inhibitor, or (2) there exists a transcription factor in the nucleus that responds to selenium.

The Japanese have relatively-high tissue concentrations of selenomethionine; the Australians the least.

 

[Travis]

Makes sense. Do you think the focus should be on selenium or selenomethionine? Because both provide benefits, but a reasonable therapeutic dose will vary depending on where the main benefit is coming from.

I think it depends on the person because they have different pharmacokinetics. It has been shown that selenomethionine is four times more effective than selenide for preventing pancreatic degeneration in chicks,⁽¹⁾ perhaps indicating that the pancreatic membranes are highly lipophilic and largely-exclude the water-soluble selenide (or perhaps selenide gets absorbed to far-up the digestive tract; selenomethionine further down). Selenide does seem to reach many body locations quicker, but since the prostate has such a high methionine requirement—for polyamine synthesis—selenomethionine would likely be the better choice for reaching that.

Selenium weights more than sulfur right? What about volume of the whole molecule? A difference in density might do the affectings on the shape of the proteids.

The mass certainly helps determine solubility and pharmacokinetic considerations, but its activity is probably better understood by its valency. The electron configuration of sulfur is [Ne]·3s²·3p⁴ and that of selenium is [Ar]·4s²·3d¹⁰·4p⁴, the latter having 'd-shell' electrons that make glutathionine peroxidase activity possible:

It is the activity of glutathione peroxidase that is ultimately responsible for the reductions in cyclooxygenase noted by Baines. This is would occur after about six days, as observed, and is actually a straightforward mechanism. This does however involve a slight paradigm shift: You are invited to see hydrogen peroxide as a 'second messenger,' inducible by cytokines (INFγ), and every bit as important as cyclic-AMP and inositol triphosphate. This is not an original proposal, and many biochemists now view hydrogen peroxide in this way.⁽²⁾

It has been consistently observed many times over that selenium inhibits NF-κB transcription.⁽³⁾ This transcription factor is responsible for replicating dNA encoding i-NOS and cyclooxygenase-2, which has its response element at position #765. Nuclear factor kappa (NF-κB) is composed of dimers each having a cysteine at position #62, facing the dNA binding site and also eachother.⁽⁸⁾ It is the global 'redox status' that makes or breaks these disulfide bridges, and that is how NF-κB is activated.

Redox-active transcription is not an entirely new observation. Normally residing in the cell nucleus is p53, a protein transcription factor having internal disulfide bonds. Upon an electron-rich redox state the disulfide bonds of p53 will be reduced, thereby splitting the disulfide and 'springing open' the transcription factor ⟶ subsequent caspase transcription, dNA fragmentation, and apoptosis. Nuclear factor kappa is our cytosolic redox sensor—where it normally resides bound to IκB—and even has a direct analogue in bacteria: Escherichia coli has a redox-active transcription factor called: 'hydrogen peroxide-inducible genes activator (OxyR).' Upon exposure to hydrogen peroxide (H₂O₂), this protein's cysteine residues at #199 and #208 are oxidized forming two water molecules and a disulfide bridge:⁽⁵⁾

Cys¹⁹⁹–SH + H₂O₂ + HS–Cys²⁰⁸ ⟶ ⟶ ⟶ Cys¹⁹⁹–S–S–Cys²⁰⁸ + HOH + HOH​

The oxidized form is more compact and has a slightly different electrophoretic mobility in polyacrylamide gel. This would be expected to be less water-soluble, giving it another property promoting nuclear migration:

'We showed previously that the OxyR-regulated oxyS gene is induced within 1 min after cells are treated with 200 mM hydrogen peroxide.' ―Åslund

'Under all of these conditions, between 0.05 and 0.2 mM hydrogen peroxide was required to oxidize 50% of the OxyR protein within 30 sec, illustrating the exquisite hydrogen peroxide sensitivity of OxyR' ―Åslund​

Glutathionine peroxidase lowers cytosolic hydrogen peroxide levels by reducing it, forming two water molecules and oxidizing glutathione in the process. This enzyme also reduces leukotrienes in a manner completely independent of NF-κB, perhaps by reducing the amount of spontaneously-formed lipid peroxides.⁽⁶⁾ As a selenoenzyme, supplemental selenium taken in nearly any form will predictably increase: glutathionine peroxidase enzyme levels in the cytosol, glutathione peroxidase activity, and oxidized glutathionine concentrations after about six days.⁽⁶⁾ This is the exact same time period that had elapsed before Baines had noticed a reduction in cyclooxygenase mRNA in HCA-7 cells.⁽⁷⁾

'On the other hand. In the HCA-7 cells, there were significant decreases in RNA levels in the treated groups throughout the study, with the most significant effects occurring at day 4 and 6. This correlated well with the decreased COX-2 protein expression and prostaglandin levels observed at the latter timepoints.' ―Baines​

Essentially any form of selenium should increase glutathioine peroxidase activity, leading to reductions in: the cytosolic H₂O₂ concentration, NF-κB thiol oxidation, NF-κB gene transcription, cyclooxygenase mRNA, cyclooxygenase proper, and prostanglandins E & D after about six days. However, selenomethionine will do that while also inhibiting polyamine synthesis in the meantime.⁽⁹⁾

[1] Cantor, A. "Efficacy of selenium in selenium compounds and feedstuffs for prevention of pancreatic fibrosis in chicks." The Journal of Nutrition (1975)
[2] Rhee, S. "Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins." Current opinion in cell biology (2005)
[3] Maehira, F. "Selenium regulates transcription factor NF-κB activation during the acute phase reaction." Clinica chimica acta (2003)
[4] Ueno, M. "Thioredoxin-dependent redox regulation of p53-mediated p21 activation." Journal of Biological Chemistry (1999)
[5] Åslund, F. "Regulation of the OxyR transcription factor by hydrogen peroxide and the cellular thiol—disulfide status." PNAS (1999)
[6] Weitzel, F. "Selenoenzymes regulate the activity of leukocyte 5-lipoxygenase via the peroxide tone." Journal of Biological Chemistry (1993)
[7] Baines, A. "The mechanism of action of the anticancer effects of selenomethionine on colon cancer." (2001).
[8] Müller, C. "Structure of the NF-κB p50 homodimer bound to DNA." Nature (1995)
[9] Redman, C. "Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells." Carcinogenesis (1997)​

 

[Travis]

Nuclear factor kappa (NF-κB) is almost certainly a hydrogen peroxide sensor, responding to it with the formation of an internal disulfide bond. This peroxide-induced event naturally creates a more compact, electronically neutral, and lipid soluble form giving NF-κB a greater propensity for the nucleus while also separating it from its binding protein (IκB). There are studies that convincingly prove this, one of which follows:

Schmidt, K. "The roles of hydrogen peroxide and superoxide as messengers in the activation of transcription factor NF-κB." Chemistry & biology (1995)​

Kerstin Schmidt had used dNA vectors encoding catalase, and heme enzyme that decreases intracellular H₂O₂ by sequential reduction—ultimately forming H₂O and O₂. This enzyme is similar to glutathionine peroxidase in function, yet doesn't rely on selenium or glutathione to achieve its end. She had also used dNA vectors that encode for superoxide dismutase, an zinc/copper-dependent enzyme that converts superoxide (Ȯ₂⁻) into hydrogen peroxide (H₂O₂). She had observed, quite predictably, that cells overexpressing catalase had attenuated levels of cytosolic H₂O₂ and those overexpressing superoxide dismutase had exhibited the converse:

Nuclear factor kappa (NF-κB) transcribes for cyclooxygenase-2 and inducible-nitric oxide synthase, among other things, and certain cytokines are known to stimulate its activity. Tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β) are known to do this, and the former cytokine had been used the stimulate the cells in this study. By fractioning the cells after TNFα-stimulation and quantifying gene-binding propensity of nuclear factor kappa via ³²PO₄-labeled oligonucleotides having the NF-κB binding domain—which emit radioactivity that can be visualized—it had been plainly shown that cells expressing catalase had an attenuated response to TNFα.

The cell overexpressing superoxide dismutase had shown the opposite response. These observations—along with the use of a catalse inhibitor—all indicate that hydrogen peroxide induces activation of NF-κB . . . and also that TNFα signals via hydrogen peroxide. If hydrogen peroxide concentrations are considered: the enzyme catalase is equivalent to glutathionine peroxidase, implying that selenium should likewise reduce hydrogen peroxide concentrations and NF-κB activity. This is actually what has been observed, rather consistently, and the H₂O₂ ⟶ *NF-κB* pathway is surely why.

'It is not yet clear how H₂O₂ ultimately triggers the removal of IκB from NF-κB in the cytoplasm. It has been suggested that H₂O₂ may act by three distinct mechanisms: lipid peroxidation, calcium mobilization and/or generation of glutathionedisulfide (GSSG), a mild oxidant which modifies cysteine residues in proteins. [?]' ―Schmidt​

It has also been suggested (#124) that an internal disulfide is formed between NF-κB dimers. This is consistent with the known effects of hydrogen peroxide on thiols, the location of thiols in NF-κB, the demonstrated importance of cysteine #62 of NF-κB, and the effect H₂O₂ has on the analogous E. coli enzyme called 'hydrogen peroxide-inducible genes activator (OxyR).' Although Dr. Schmidt mentions this particular enzyme and cites an article about it—the one proving that H₂O₂-induced disulfide formation occurs—she obviously hadn't bothered to read it since she brings calcium into this [?].

'The selectivity of NF-KB for H,O, is not without precedent.The bacterial transcription factor oxyR is also specifically activated by H₂O₂ [45].' ―Schmidt​

Cytosolic hydrogen peroxide is elevated by cytokines (TNFα; IL-1β) and is capable of inducing gene expression through at least one transcription factor (NF-κB). These two observations, viewed together, elevate H₂O₂ to 'second messenger status'—placing it in the same class as cyclic-AMP and inositol triphosphate. Nuclear factor kappa (NF-κB) transcribes for the inducible forms of cyclooxgenase and nitric oxide synthase, enzymes which create additional prostaglandins and nitric oxide. This is ostensibly done with the intent of detoxifying superoxide: Nitric oxide (ṄO) adds to superoxide (Ȯ₂⁻) forming peroxynitrite (ONOO⁻), which is the second substrate for cycloxygenase besides arachidonic acid. Peroxynitrite add to arachidonic acid under the direction of cyclooxygenase to form the endoperoxide bridge of prostaglandin H₂,⁽¹⁾ a process that makes prostaglandin formation appear somewhat like 'a detoxification procedure for superoxide'—or perhaps a Ȯ₂⁻ lipid-storage device—with their genetic and neurotransmitter functions appearing only later in evolution.

Prostalandin H₂:

​

Despite their apparently-innocuous intent, prostaglandins can be harmful. However! most prostaglandin-pathology is caused by the 2-series prostaglandins derived from arachidonic acid, a membrane lipid synthesized strictly from ω−6 fatty acids (arachidonic acid ≈ elongated & desaturated linoleic acid). The 3-series prostaglandins derived from eicosapentaenoic acid (EPA) are far less problematic, and considering the historical diet of humans you'd have to assume that 2-series prostaglandins are actaully unnatural. So perhaps it is better to view this process more as 'linoleic causing cancer' and not so much as 'cyclooxygenase causing cancer,' which is a natural enzyme ostensibly trying to protect the cell from oxidative stress.

[1] Salvemini, D. "Nitric oxide activates cyclooxygenase enzymes." Proceedings of the National Academy of Sciences (1993)​

 

[Travis]

I pieced it together one study at a time, but I found one yesterday that proves the entire pathway:

Zamamiri-Davis, F. "Nuclear factor-κB mediates over-expression of cyclooxygenase-2 during activation of RAW 264.7 macrophages in selenium deficiency." Free Radical Biology and Medicine (2002)​

 

[Amazoniac]

@Travis, I was actually getting paid to say those things. I realized that the amount which I had in mind, to supplement 50-70 mcg, is the average that you need to complement healthy people's diets. In a stressed states, the needs must be higher, but I still think it's not as high as you believe. In reality you don't, Sabinsa does and you comply. I know it.

Then it occurred to me that Abram of the Hoffers was taking an extreme amount of selenium daily and there had to be an explanation for him not feeling adverse effects owa time. Then I remembered your comments about selenomethionine being able to replace methionid in the body, therefore it's also a methyl donor.

The guy was known for his insane doses of niacin. And so niacin supplementation should be helpful in preventing problems from selenium excess.

- Methylated niacin derivatives in plasma and urine after an oral dose of nicotinamide given to subjects fed a low-methionine diet
- NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink (I guess it's useful if you restrict dietary methionid and prevent muscle breaking the downs as a therapy)

 

[Amazoniac]

Marco* has been determined in figuring out this issue. More from him:
- Risk of Chronic Low-Dose Selenium Overexposure in Humans: Insights From Epidemiology and Biochemistry : Reviews on Environmental Health
- Friend or Foe? The Current Epidemiologic Evidence on Selenium and Human Cancer Risk
- https://link.springer.com/article/10.1007/s10654-018-0422-8
- Diet composition and serum levels of selenium species: A cross-sectional study - ScienceDirect
*Associazione Sostegno Oncologia Ematologia Pediatrica (ASEOP) of Modena (M. Vinceti)

Non-Marco:
- Redox regulation of protein kinase C by selenometabolites and selenoprotein thioredoxin reductase limits cancer prevention by selenium - ScienceDirect

@Mito, have you searched for 'high serum selenium'? Most are just associations but often with something bad. If it got elevated in response to a problem (and not to supplementation), it must not be good to try to normalize it.

 

[Mito]

Marco* has been determined in figuring out this issue. More from him:
- Risk of Chronic Low-Dose Selenium Overexposure in Humans: Insights From Epidemiology and Biochemistry : Reviews on Environmental Health
- Friend or Foe? The Current Epidemiologic Evidence on Selenium and Human Cancer Risk
- https://link.springer.com/article/10.1007/s10654-018-0422-8
- Diet composition and serum levels of selenium species: A cross-sectional study - ScienceDirect
*Associazione Sostegno Oncologia Ematologia Pediatrica (ASEOP) of Modena (M. Vinceti)

Non-Marco:
- Redox regulation of protein kinase C by selenometabolites and selenoprotein thioredoxin reductase limits cancer prevention by selenium - ScienceDirect

@Mito, have you searched for 'high serum selenium'? Most are just associations but often with something bad. If it got elevated in response to a problem (and not to supplementation), it must not be good to try to normalize it.

I’ll probably reduce supplementation and retest at some point. Masterjohn thinks the sweet spot is 120. Methylation issues might cause selenium to accumulate but I need to read more about that.

 

[Johnathan5544]

There is a study on the selenium content, and seleno species in beef kidneys. Best I recall it averaged around 200mcg per 100g, and half of it was selenocysteine in the form of glutathione peroxidase. I would like to see a study showing the selenocysteine content of brazil nuts but have not been able to find one.

 

[Amazoniac]

- Heart failure secondary to selenium deficiency, reversible after supplementation
- Chest Pain: Differentiating Cardiac from Noncardiac Causes

 

[Johnathan5544]

Sci-Hub | Determination of selenocysteine and selenomethionine in edible animal tissues by 2D size-exclusion reversed-phase HPLC-ICP MS following carbamidomethylation and proteolytic extraction | 10.1007/s00216-008-1883-5

Determination of selenocysteine and selenomethionine in edible animal tissues by 2D size-exclusion reversed-phase HPLC-ICP MS following carbamidomethylation and proteolytic extraction

Lamb kidneys have 450-590mcg selenium per 100g, and 90% of it is selenocysteine which is more important than selenomethioneine.

Looks like kidneys beat brazil nuts because of the form the selenium is in.

 

[Amazoniac]

Most of the data is on selenium glycinate complexes. It is selenium bound up with a carrier protein called glycine. It is easy to absorb, no big toxicity issues, very effective.

It's embarassing to admit, but that was actually a sponsored post.

Selenium-Enriched Foods Are More Effective at Increasing Glutathione Peroxidase (GPx) Activity Compared with Selenomethionine: A Meta-Analysis
"Recent results have shown that selenium glycinate (an inorganic form of selenium) increased GPx activity in men [78]."

 

[TeaRex14]

Typically someone can get enough selenium from just nutrient dense foods (i.e liver, eggs, milk, oysters, clams, red meat, etc.). However if you're already deficient you might want to take a supplemental dose. Paul Jaminet of the PHD protocol notes that selenium has a cumulative affect, and that supplementing only one time a week is probably sufficient if you're also eating nutrient dense foods.

 

[Amazoniac]

supplementing only one time

@chrismturner89 - Increasing the dose and decreasing the frequency is a good move if you're still having issues with selenium supplements.

 

[Amazoniac]

Selenium, ultraviolet radiation and the skin

"[..]in common with many other anti-oxidants, if Se is not taken as part of a balanced diet the free radical energy that selenocompounds absorb cannot be dispersed to adjacent antioxidants of lower free energy."

"Seleno-compounds do not absorb significantly in the UVB/UVA wavelengths (Fig. 3) and to achieve maximum protection from UV-induced cell death, SM [selenomethionine] or SS [sodium selenide] must be added to the cells at least 12 h before UV exposure, suggesting that incorporation into selenoproteins is necessary for protection.15,6"

"By increasing the cells' ability to breakdown peroxides, Se counteracts many [] deleterious processes. For example UVB-induced accumulation of lipid peroxides in keratinocytes is decreased by 82% if the cells are pre-treated with 50 nm SM before irradiation with 200 J/m2 UVB.16 Similarly, lipid peroxidation is prevented in fibroblasts19 by pre-supplementation with Se."

"[..]it has been shown by Rafferty et al. that SM and selenite both inhibit the UVB-induction of IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-a in a dose-dependent manner.16,20 For example, pretreatment of human keratinocytes with 50 nm SM 24 h prior to irradiation with 200 J/m2 completely abolishes the fourfold UVB induction of IL-6 mRNA. Selenium also prevents the UV-induced oxidative damage to DNA which is manifested by the accumulation of 8-OHG.16"

"Nitroxide species are produced following UVB treatment of skin and keratinocytes in culture and skin and one of the most destructive free radicals, peroxynitrite (ONOO-) is formed when nitric oxide combines with superoxide radicals. Peroxynitrite can damage both proteins and DNA. This DNA damage -- single strand breakage -- can be prevented by Se.25 Also, SM protects against nitration reactions which can damage both DNA and protein and GPX protects against peroxynitrite-mediated oxidation reactions.26"

"Se has potential as an agent to protect against UV-induced skin cancers. First, it prevents oxidative DNA damage caused by UV (although failing to prevent dimer formation, which is the principal carcinogenic photoproduct). Second, it prevents the production of inflammatory and immunosuppressive cytokines which impair immune responses following UV exposure. Third, Se boosts both cellular and humoral immunity. Finally, selenodiglutathione appears to inhibit the growth of various types of tumour cells and actually triggers their apoptosis.30 As discussed earlier, both Se dietary supplements and topical application of Se reduced dramatically the induction and growth of UVB-induced skin tumours in mice.3±5 It remains to be seen if this protective effect operates in humans. However, topical application of SM seems to protect human skin from UV-induced damage; in Burke's studies the UVB dose necessary to achieve 1 minimal erythema dose in humans was increased by 30%.31"​

@haidut

 

[Amazoniac]

- Selenium and Autoimmune Diseases: A Review Article
- Selenium, Selenoproteins, and Immunity

 

[LeeLemonoil]

Dietary Selenium in Immune Mechanisms During an Enteric Bacterial Infection (OR12-08-19). - PubMed - NCBI

 

[Amazoniac]

- The Vitamins: Fundamental Aspects in Nutrition and Health - Gerald F. Combs and James P. McClung

"Vitamin B6 is essential for the utilization of selenium (Se) from the major dietary form, selenomethionine, after that Se is transferred to selenohomocysteine. PalP is a cofactor for two enzymes, selenocysteine ß-lyase and selenocysteine γ-lyase, which catalyze the elimination of the Se from selenohomocysteine to yield hydrogen selenide (H2Se). Selenide is the obligate precursor for the incorporation of Se into selenoproteins in the form of selenocysteinyl residues produced during translation.[23]"

[23] "These include the Se-dependent glutathione peroxidases and thioredoxin reductases, which have antioxidant functions; the iodothyronine 5′-deiodinases, which are involved in thyroid hormone metabolism; selenophosphate synthase, which is involved in selenoprotein synthesis; selenoproteins P and W, which are major selenoproteins in plasma and muscle, respectively; and at least a dozen other proteins."​

 

[Amazoniac]

- Modern nutrition in health and disease (978-1-60547-461-8)

"A novel compound, called selenoneine, has selenium bound to the imidazole ring of modified histidine and is the major form of selenium in liver and blood of tuna (19). The low bioavailability of the selenium in tuna may result from this form or from complexation with mercury (14), but this issue needs further investigation."​