Cautionary Tale / Eat Selenium

[Tenacity]

@Amazoniac from what I understand about the above selenium suppresses the metabolic rate. Might this be why selenium improves my acne? I remember Peat saying that milk is often blamed for causing acne because the nutrients in milk raise the metabolic rate, making one use up anti-acne nutrients like vitamin A. Could selenium feasibly do the opposite?

EDIT: I suppose I should make it clear that it's not a selenium supplement that helps my acne, but shellfish (I assume it's the selenium in the shellfish, I could be wrong though).

EDIT2:

“Chronic inflammatory disorders are normally associated with a decrease in selenium status, and cross-sectional case–control studies have suggested that patients with inflammatory disorders such as cystic fibrosis (247), acne (246), and inflammatory bowel disease (268) may have a lower selenium status than healthy controls. Therefore, supplementation with selenium could possibly alleviate some of the symptoms of such disorders through increasing antioxidant activity and suppressing inflammatory conditions. Unlike the potential preventative benefits of selenium seen for other health issues, most of the research surrounding inflammatory disorders has been focused on supplementation as an alternative therapy, or treatment, for patients.”

I guess I'm on the right track...

 

[Amazoniac]

@Amazoniac from what I understand about the above selenium suppresses the metabolic rate. Might this be why selenium improves my acne? I remember Peat saying that milk is often blamed for causing acne because the nutrients in milk raise the metabolic rate, making one use up anti-acne nutrients like vitamin A. Could selenium feasibly do the opposite?

EDIT: I suppose I should make it clear that it's not a selenium supplement that helps my acne, but shellfish (I assume it's the selenium in the shellfish, I could be wrong though).

EDIT2:



I guess I'm on the right track...

I think that it's the opposite, constant supplementation increases thyroid hormone activity, affecting humanoids with not enough iodine reserves, and by not being able to keep up, they end up worsen their condition.
From the second one:
"[..]selenium deficiency seems to mitigate the severity of hypothyroidism in iodine-deficient cretins. The iodine intake of these subjects could be too poor to allow a sufficient thyroid hormone synthesis in case of normal selenium status and deiodinase activities."
The first study wasn't too clear for them because in normal people it's more difficult to perceive the effects.

However, they also mentioned that organs are affected in different ways. The part that caught your attention was related to thyroid hormone in the thyroid.
"[..]in the intrathyroid model, as demonstrated in experimental rats in vivo, selenium supplementation corrects thyroid glutathione peroxidase deficiency and decreases serum T4 presumably by diminishing the availability of hydrogen peroxide substrate for T4 synthesis; furthermore, consonant with the decreased T4, serum TSH is enhanced (12). In the extra-thyroid model, also demonstrated in rats, selenium supplementation increases the conversion rate of T4 to T3 which should induce a decrease in in serum TSH level (13); both mechanisms lead to a decrease of serum T4 in case of selenium supplementation. The combination of both mechanism could explain why in normal subjects serum TSH remained stable after selenium supplementation."

And that when there's a selenium deficiency, hydrogen peroxide is more available, which can explain those effects:
"Golstein et al. (1988) showed increased serum T4 and T3 values in selenium deficient rats and proposed that selenium deficiency through an increased availability of H2O2, required by the thyroperoxidase for thyroid hormone production, increases iodide organification in the thyroid gland."

If you don't eat pboyodized salt, I would be more careful with supplementation because natural foods are usually relatively balanced, and supplementing one or the other alone can be tricky.

My skin also improves with selenium..

 

[Amazoniac]

I think we have to consider what the selenium atom is bound to. Like free iron, copper, and zinc, free selenium appears‐redox active; but when carbon‐linked to methionine or cysteine, selenium is a different animal. In plants and Asians, there seems to be no limit to how much protein‐incorporated methionine can safely be replaced by Se‐methionine. And since S‐adenosylmethionine is required for polyamine synthesis, having Se‐adenosylmethionine in the cell inhibits this. Due to the disparity between inorganic selenium species and selenium amino acids, extrapolating toxicity data between the two could appear unrealistic.

Plants can have both inorganic selenium and amino acid selenium, but this varies by species and soil. When measured by flame spectroscopy, it is impossible to tell which is which. For this reason, old toxicity data on selenium in plants should be viewed with caution; any article which does not distinguish between organic selenium should perhaps be considered crude.

Selenomethionine is actually considered an essential amino acid, and selenocysteine has recently been classified as the '21st amino acid.'

Dear bro.. melained,

This might interest you:
https://chrismasterjohnphd.com/2017...manage-your-selenium-status-and-how-to-do-it/

In general, across the board, we could say that toenail selenium and hair selenium, platelet, red blood cell, plasma, serum, whole blood, whatever body tissue it is, that body tissue’s physiological needs are going to rise and then plateau once nutritional status is met for its physiological needs if the form is not selenomethionine. If the form is selenomethionine, then body tissues, whether it’s hair or nails or blood or some fraction of blood, are going to rise linearly with exposure not according to the physiological need for nutritional status, but simply according to whatever was in the diet. And the reason is that if you look, for example, at progressive increase in hair selenium content with increasing selenomethionine intakes, eventually what you’re seeing is just the random incorporation of selenomethionine into the methionine pool that would be in those proteins otherwise. So selenium levels and tissues aren’t in and of themselves markers of nutritional status unless we can show that one or more of them strongly correlate as a reliable proxy for a physiologically important functional marker like a glutathione peroxidase or selenoprotein P.

Selenoprotein P’s physiological function is to transport selenium. So we would expect it to be very specific and because it’s made in the liver and because the liver does not conserve selenium very well in deficiency, it’s a very good candidate for something that would be sensitive. We could say very similar things about glutathione peroxidase. However, glutathione peroxidase is critical to defense against cellular damage. Selenoprotein P is transporting extra selenium. You always need to protect yourself against oxidative damage. You don’t need to transport extra selenium when you don’t have any extra selenium to get anywhere.

the cancer studies suggested that the ideal blood levels of selenium for cancer prevention may be around 120 micrograms per liter, and the diabetes research suggested that 140 may increase the risk of diabetes. I think it’s probably safe and maybe beneficial to push those levels up to 120 micrograms per milliliter, but I think pushing it any higher than that is really flirting with the line of increasing the risk of cancer and diabetes, and I think on all of these things, the evidence is very mediocre, whether it’s going to do anything one way or the other. So I don’t think that you should be paranoid about a value that’s 120 or 140 micrograms per liter. I just don’t think anyone should purposefully push it that high, and if it gets that high and you’re taking a supplement, I think you can certainly eliminate the supplement.

I would take no more than a hundred micrograms supplement [!!! But not so much of a coincidence because I remember reading the same studies when I was trying to figure out a reasonable dose] because almost certainly you’re getting 20 micrograms in your diet. The supplement alone at a hundred micrograms per day would more than normalize your selenoprotein P status and it would probably push you into the range that we can suspect maybe maximize protection against cancer. So I really don’t think anyone should be taking 200 micrograms per day of selenomethionine. All of this subject of course to the caveat that if you have some kind of unusual persistently low blood level of selenium, then maybe in your individualized case you may need a higher dose.

From that link:
Methods of assessment of selenium status in humans: a systematic review

If you can spot something shaddy let me know because I'm open to change my mind.

 

[Travis]

Dear bro.. melained,

This might interest you:
https://chrismasterjohnphd.com/2017...manage-your-selenium-status-and-how-to-do-it/




From that link:
Methods of assessment of selenium status in humans: a systematic review

If you can spot something shaddy let me know because I'm open to change my mind.

Interesting study. They did show that the selenoprotein glutathione peroxidase increased in activity after selenomethionine supplementation. They also seemed to confirm my suspicion than selenium is not required in it's inorgranic form like the ions K⁺, Na⁺, Ca²⁺, Mg²⁺, Fe³⁺, Zn²⁺, and Cu²⁺, are required. Selenium appears only essential in the extent that selenomethionine and selenocysteine are needed for the catalytic activity of certain enzymes.

Such thinking could discredit Se²⁻ and SeO₄²⁻ ions as legitimate essential species, or even beneficial at all when selenomethionine is available. You could then wonder how much the recommended 'upper limit' has been influenced by historical studies on these nonessential or more toxic forms. I know many writers often fail to make the distinction, and seem to focus heavily on just the selenium atom alone. While this is sometimes necessary for bookkeeping purposes, and for brevity, this language can perhaps paint the wrong picture of selenium toxicity.

Schrauzer, Gerhard N. "Selenomethionine: a review of its nutritional significance, metabolism and toxicity." The Journal of nutrition (2000)​

'In rats fed a basal Se-deficient diet with 2 mg/g Se added as Se-met, the level of Se in muscle was 10 times that of rats fed the equivalent amount of selenite and Se-cys (27).' ―Schrauzer

'The Se contents of human skeletal muscle reflect accordingly the dietary Se-met intakes and were found to be the highest in Japanese adults (1700 ng/g), followed by Canadians (370 ng/g) and Americans (240 ng/g), with the lowest (61 ng/g) found in New Zealand adults (28).' ―Schrauzer

'Se-met is also significantly retained by brain, suggesting that it is an active form of Se for incorporation into brain proteins (30).' ―Schrauzer

'Supplemental Se-met, compared with selenite or selenate, also has differential effects on lymphocyte proliferation and other immunological variables (31,32).' ―Schrauzer​

Excess selenomethionine can become Se‐adenosylmethionine, demethylated to Se‐adenosylhomocysteine, transformed into selenocysteine, deligated . . . the selenium atom is eventually separated from selenocysteine and methylated for excretion by the liver.

'The chronic toxicity of Se-met is lower than that of selenite (46).' ―Schrauzer​

[46] Spallholz, J. E. (1987) Nutritional, chemical and toxicological evaluation of high-selenium yeast. In: Selenium in Biology and Medicine (pp. 516–529) Avi-Van Nostrand Reinhold​

And he cites an impossible to obtain book, so it's hard to tell how much less toxic selenomethionine is at a chronic intake. It's interesting to note that this is true in spite its longer half life in the body:

'Reported average whole-body half-lives of Se-met and selenite in humans were 252 and 102 d, respectively, indicating that Se-met is utilized and reutilized extensively (33,34).' ―Schrauzer​

[33] Veillon, C. (1989) Human selenite metabolism. A kinetic model. Am. J. Physiol.
[34] Swanson, C. A. (1991) Human (⁷⁴Se)selenomethionine metabolism: a kinetic model. Am. J. Clin. Nutr. ​

 

[Terma]

@Travis @Amazoniac I'm interested if we could consolidate all these views on selenium.

I originally got mine from Paul Jaminet's book several years ago (Perfect Health Diet - A diet for healing chronic disease, restoring youthful vitality, and achieving long life | Perfect Health Diet) and the takeaway matches Masterjohn's, which is simply to eat selenocysteine-rich foods.

However Jaminet's take was that selenomethionine regardless of source should be avoided because he interpreted it as interfering with normal DNA methylation and repair. This is the opposite of the uses that have been discussed here. (But he's not explicitly "pro-methylation"; he's the only author I know of who cautioned against too much B12)

Eventually I disregarded it and started taking selenomethionine at 200mcg/day because of studies on glutathione and thyroid on a different forum and because it felt better, and eventually lowered intake.

From Travis's ideas I might start taking more again, but there are these warnings about selenosis everywhere that just won't go away.

 

[Amazoniac]

@Travis @Amazoniac I'm interested if we could consolidate all these views on selenium.

I originally got mine from Paul Jaminet's book several years ago (Perfect Health Diet - A diet for healing chronic disease, restoring youthful vitality, and achieving long life | Perfect Health Diet) and the takeaway matches Masterjohn's, which is simply to eat selenocysteine-rich foods.

However Jaminet's take was that selenomethionine regardless of source should be avoided because he interpreted it as interfering with normal DNA methylation and repair. This is the opposite of the uses that have been discussed here. (But he's not explicitly "pro-methylation"; he's the only author I know of who cautioned against too much B12)

Eventually I disregarded it and started taking selenomethionine at 200mcg/day because of studies on glutathione and thyroid on a different forum and because it felt better, and eventually lowered intake.

From Travis's ideas I might start taking more again, but there are these warnings about selenosis everywhere that just won't go away.

Selenium Supplement Reccomendations?
But all those issues were addressed above (link).
- Why selenocysteine, unlike selenomethionine, is better regulated in a way that stops providing selenium when optimum level is reached.
- Why selenomethionine is preferred for supplementation.
- Why 200mcg is probably too much unless you're trying to correct a deficiency (but even then you can do it with lower doses).
- Why 50-100mcg of supplementation is all that's needed depending on dietary intake to reach about 90-120mcg in total.
1/3 of a 200mcg selenium capsule is a reasonable dose.

 

[Travis]

The Japanese have 6× higher tissue selenomethionine, and the Japanese live longer. I think the standard 200‧μg dose is plenty, and would probably be less of a dose than that obtained by switching to certain vegan diets (that is, if you buy plants from certain geographical regions). If I had some in my cabinet, I would take it. Taking more than this probably represents the crossing into 'drug territory,' which could be helpful for rapidly proliferating cancer cells. But for most people, inhibiting polyamine synthesis is not necessary or even something you could consider particularly beneficial; all cells do need polyamines to grow, and anabolic hormones such as androgens and prostaglandin E₂ increase polyamines and growth. With a lack of polyamines, the cell dies.

 

[Terma]

Selenium Supplement Reccomendations?

Oh good, I knew I couldn't be the only one who read that. Jaminet's thoughts predate a lot of posts on a lot of forums but somehow nobody read his book.

Selenium Supplement Reccomendations?
But all those issues were addressed above (link).
- Why selenocysteine, unlike selenomethionine, is better regulated in a way that stops providing selenium when optimum level is reached.
- Why selenomethionine is preferred for supplementation.
- Why 200mcg is probably too much unless you're trying to correct a deficiency (but even then you can do it with lower doses).
- Why 50-100mcg of supplementation is all that's needed depending on dietary intake to reach about 90-120mcg in total.
1/3 of a 200mcg selenium capsule is a reasonable dose.

He errs on the side of caution, nothing he wrote is definitive, and it's actually an echo of older recommendations I've seen before that probably inspired him (though he does a better job of explaining science)...

just taking as much as 200 micrograms of selenium was increasing their cancer risk. And then after that, there was a population level study that found that people who had higher levels of plasma selenium had increased risk of diabetes. So although the risk of diabetes and cancer at higher selenium levels is nowhere near conclusive, it still should provide caution in the sense that if we don’t have strong evidence that we’re going to get a benefit from pushing up our levels that much, then why would we err on the side of flirting with the line of increased risk of cancer and diabetes?

To be clear, believe it not, I have very different issues and cancer is the least of my worries at the moment. Diabetes is also fair low risk to me.

I want to use selenomethionine (or selenocysteine supplement if there was a non-methylated one, I did try a selenocysteine supplement but I don't remember the exact form) for temporary therapeutic purposes, on the order of a few months. Some people supplemented 400mcg perpetually with no apparent issues. But I wouldn't do it perpetually myself without testing or more informed opinions.

 

[Terma]

The Japanese have 6× higher tissue selenomethionine, and the Japanese live longer. I think the standard 200‧μg dose is plenty, and would probably be less of a dose than that obtained by switching to certain vegan diets (that is, if you buy plants from certain geographical regions). If I had some in my cabinet, I would take it. Taking more than this probably represents the crossing into 'drug territory,' which could be helpful for rapidly proliferating cancer cells. But for most people, inhibiting polyamine synthesis is not necessary or even something you could consider particularly beneficial; all cells do need polyamines to grow, and anabolic hormones such as androgens and prostaglandin E₂ increase polyamines and growth. With a lack of polyamines, the cell dies.

Nail on the head. Jaminet sometimes referred to Japanese's health but curiously no such reference for selenium.

 

[ddjd]

from what I understand about the above selenium suppresses the metabolic rate. Might this be why selenium improves my acne?

it stop acne because its anti estrogenic. acne is an estrogen problem

 

[Amazoniac]

@Travis - what's your opinion on this? (no sarcasm)
Selenium and Diabetes: More Bad News for Supplements | Annals of Internal Medicine | American College of Physicians

 

[Tenacity]

it stop acne because its anti estrogenic. acne is an estrogen problem

I later found out it was the manganese in mussels that helped, not the selenium. Tea and pineapple juice had similar effects.

 

[Hairfedup]

Dates are full of selenium.

 

[Amazoniac]

Dates are full of selenium.

I think those are from Middle East. It's probable that it comes down to soil.
Here they report no selenium.

 

[Amazoniac]

@Travis - what's your opinion on this? (no sarcasm)
Selenium and Diabetes: More Bad News for Supplements | Annals of Internal Medicine | American College of Physicians

@Travis - one more pending approval:

Selenium and diabetes: an enigma?

"Can additional Se promote the development of obesity and the onset of type 2 diabetes with insulin resistance?
In our opinion: Yes

Very recent results from human epidemiological studies and from Se intervention trials, including large populations, increasingly suggest that a high Se status derived from conventional nutrition or from Se intervention increases the risk of developing type II diabetes and hyperlipidemia. The results of these trials are supported by studies with rodents using GPx1 over-expression or modulation of antioxidant selenoprotein activities by manipulation of dietary Se concentration. Both approaches suggest that an excess of antioxidant selenoproteins or a permanent slight surplus of Se may contribute to the development of obesity, insulin resistance, type II diabetes and hyperlipidemia [144,151,155,157]. Two important molecular pathways underlying these undesirable effects of Se involve the tremendous increase in insulin production due to a high pancreatic GPx1 activity [82] and a high activity of the insulin antagonistic and lipogenic PTP1B [156,157] in peripheral tissues due to slightly supranutritive Se supplementation. The combination of both factors helps to explain plausibly the generation of the vicious cycle of peripheral insulin resistance and subsequently of diabesity and hyperlipidemia [82,156,157]. However, there remain a number of questions for future research to investigate the critical role of Se supplements with regard to the development of obesity, insulin resistance, diabetes and hyperlipidaemia. One approach in this direction may consist in the critical examination of the counterregulation of antioxidant selenoproteins and phase II enzymes, e.g. several glutathione-S-transferases, heme oxygenases, some aldehyde reductases and epoxide hydrolases [186-191], for which a number of beneficial effects have again been reported with regard to diabetes prevention and therapy [192-198]."

"How can Se exert opposite effects on cancer on the one hand and the development of insulin resistance, diabesity and hyperlipidemia on the other and how can this serious antagonism be balanced?

Long-term Se supplemention in the prevention of cancer has been tested in a number of larger and smaller intervention trials. However, the results of these studies are not consistent and not all cancers are positively influenced by Se supplementation. In the NPC trial [147,219] a 25% reduction of total cancers could be achieved by Se supplementation with 200 mg Se for 7.7 years. This reduction was based in particular on lower incidence rates for prostate cancer and colon cancer, whereas the incidence of nonmelanoma skin cancer and squamous cell cancers increased. The SELECT study [148] which originally planned to investigate the preventive effect of Se and vitamin E supplementation on prostate cancer incidence was early abandoned in autumn 2008 after 7 years (scheduled duration: 12 years) because Se supplementation alone and in combination with vitamin E even tended to increase prostate cancer incidence by 4 and 5%, respectively. With regard to the positive effects of Se supplementation on prostate and colon cancer a number of different and promising approaches concerning the underlying molecular mechanisms have been made. Thus, one study investigates the fact that Se (methylseleninic acid) reduces the phosphorylation of Akt/PKB at threonine 308 and serine 473 in cultured cancer cells and by these mechanisms reduces cell proliferation and differentiation [220]. According to Figure 2, dealing with pancreatic health full Akt/PKB phosphorylation is a differentiation signal in many tissues. A high Akt/PKB phosphorylation is further an indicator for insulin sensitivity, since it ultimately mediates the metabolic effects of insulin. In this context it is remarkable that in the study with GPx1 overexpressing mice, a reduced phosphorylation of Akt/PKB at exactly the threonine 308 residue and at the serine 473 residue indicated the insulin resistance of the animals [155]. Thus, at this point it must be stated that potentially the same signalling pathways contributing to a reduced proliferation and differentiation of cancer cells by Se may mediate the pro-diabetic and pro-adipogen effects of the trace element. Another investigation into the anti-carcinogenic properties in prostate cancer cells suggests that Se treatment influences the epigenetic mechanism via the reduction of DNA methylation and the increase of DNA- and histone acetylation in the promoter region of genes critical to the inhibition of tumour growth and metastasis [221]. Whereas methylation is a silencing signal for gene transcription, acetylation generally increases gene expression. In this context a similar observation could be made in the mouse trial in which pancreatic GPx1 over-expression strongly increased DNA- and histone acetylation in the PDX1 promotor region leading to a massive increase in b-cell mass and insulin production [82]. As described above for phosphorylation and signalling processes the influence of Se on DNA methylation and acetylation also impressively shows that one and the same mechanism may provide protection against cancer and increase the risk of early diabetes development. Recent results suggest that the coincidence of polymorphisms in the selenoprotein P gene and in the MnSOD gene may increase the risk of prostate cancer [222]. A reduced delivery of Se to the prostate gland leading to the subsequent reduced synthesis of antioxidant selenoproteins combined with a reduced detoxification of initially produced superoxide radicals is thought to raise the prostate cancer risk via increased oxidative stress. An influence of seleonprotein P polymorphisms was also described with regard to the protection of humans against colon cancer [223]. Generally two isoforms of seleoprotein P exist (a 50 kDa isoform and a 60 kDa isoform). Depending on the genotype and on specific polymorphisms, either the 50 kDa or the 60 kDa form dominates. The 60 kDa form seems to be more effective in supplying peripheral tissues sufficiently with Se and therefore providing the basis for the synthesis of antioxidant selenoproteins and cancer protection. In this context the observation that in case of the existence of polymorphisms forwarding the synthesis of the 50 kDa selenoprotein P isoform, Se supplementation of these patients leads to a strong increase in the favourable 60 kDa form. This opens perspectives to advise individuals with those polymorphisms to intermittently take Se supplements. That the gastrointestinal glutathione peroxidase GPx2 may play a key role in the prevention of colon cancer could be demonstrated by the ability of GPx2 to dampen the expression of cyclooxygenase 2 and microsomal prostaglandin E2 synthase-1 and therefore to reduce inflammation driven initiation of carcinogenesis by prostaglandin E2 [224]. Finally it should be mentioned that accompanying Se supplementation seems to be useful during radiotherapy of cancers, since Se increases the radiosensitivity of tumours cells [225,226]. As described in this section in certain respects permanent supranutritional Se supplementation seems therefore to influence protection from cancer and diabetes development exactly contrariwise. As stated below in our concluding remarks with regard to diabetes, the currently available data do not uniquely support the necessity of permanent supranutritive Se supply for cancer prophylaxis. This recommendation is supported by the fact that Se seems to have a certain protective effect against prostate cancer and colon cancer whereas it may increase the risk of skin cancers and squamous cell cancers [219]. In the future, modern molecular biological methods (e.g. for the detection of polymorhisms such as in selenoprotein P) may represent a helpful tool to give well-directed advice to patients to take intermittently Se supplements. A very simple approach for the prevention of colon cancer could be the encapsulation of Se into hemicellulose or other fibres which are not digestible in the small intestine. This would represent a simple tool to obtain a high local Se concentration where it is desired and to avoid it where it is not needed."

 

[Travis]

@Travis - one more pending approval:

Selenium and diabetes: an enigma?

"Can additional Se promote the development of obesity and the onset of type 2 diabetes with insulin resistance?
In our opinion: Yes

Very recent results from human epidemiological studies and from Se intervention trials, including large populations, increasingly suggest that a high Se status derived from conventional nutrition or from Se intervention increases the risk of developing type II diabetes and hyperlipidemia. The results of these trials are supported by studies with rodents using GPx1 over-expression or modulation of antioxidant selenoprotein activities by manipulation of dietary Se concentration. Both approaches suggest that an excess of antioxidant selenoproteins or a permanent slight surplus of Se may contribute to the development of obesity, insulin resistance, type II diabetes and hyperlipidemia [144,151,155,157]. Two important molecular pathways underlying these undesirable effects of Se involve the tremendous increase in insulin production due to a high pancreatic GPx1 activity [82] and a high activity of the insulin antagonistic and lipogenic PTP1B [156,157] in peripheral tissues due to slightly supranutritive Se supplementation. The combination of both factors helps to explain plausibly the generation of the vicious cycle of peripheral insulin resistance and subsequently of diabesity and hyperlipidemia [82,156,157]. However, there remain a number of questions for future research to investigate the critical role of Se supplements with regard to the development of obesity, insulin resistance, diabetes and hyperlipidaemia. One approach in this direction may consist in the critical examination of the counterregulation of antioxidant selenoproteins and phase II enzymes, e.g. several glutathione-S-transferases, heme oxygenases, some aldehyde reductases and epoxide hydrolases [186-191], for which a number of beneficial effects have again been reported with regard to diabetes prevention and therapy [192-198]."

"How can Se exert opposite effects on cancer on the one hand and the development of insulin resistance, diabesity and hyperlipidemia on the other and how can this serious antagonism be balanced?

Long-term Se supplemention in the prevention of cancer has been tested in a number of larger and smaller intervention trials. However, the results of these studies are not consistent and not all cancers are positively influenced by Se supplementation. In the NPC trial [147,219] a 25% reduction of total cancers could be achieved by Se supplementation with 200 mg Se for 7.7 years. This reduction was based in particular on lower incidence rates for prostate cancer and colon cancer, whereas the incidence of nonmelanoma skin cancer and squamous cell cancers increased. The SELECT study [148] which originally planned to investigate the preventive effect of Se and vitamin E supplementation on prostate cancer incidence was early abandoned in autumn 2008 after 7 years (scheduled duration: 12 years) because Se supplementation alone and in combination with vitamin E even tended to increase prostate cancer incidence by 4 and 5%, respectively. With regard to the positive effects of Se supplementation on prostate and colon cancer a number of different and promising approaches concerning the underlying molecular mechanisms have been made. Thus, one study investigates the fact that Se (methylseleninic acid) reduces the phosphorylation of Akt/PKB at threonine 308 and serine 473 in cultured cancer cells and by these mechanisms reduces cell proliferation and differentiation [220]. According to Figure 2, dealing with pancreatic health full Akt/PKB phosphorylation is a differentiation signal in many tissues. A high Akt/PKB phosphorylation is further an indicator for insulin sensitivity, since it ultimately mediates the metabolic effects of insulin. In this context it is remarkable that in the study with GPx1 overexpressing mice, a reduced phosphorylation of Akt/PKB at exactly the threonine 308 residue and at the serine 473 residue indicated the insulin resistance of the animals [155]. Thus, at this point it must be stated that potentially the same signalling pathways contributing to a reduced proliferation and differentiation of cancer cells by Se may mediate the pro-diabetic and pro-adipogen effects of the trace element. Another investigation into the anti-carcinogenic properties in prostate cancer cells suggests that Se treatment influences the epigenetic mechanism via the reduction of DNA methylation and the increase of DNA- and histone acetylation in the promoter region of genes critical to the inhibition of tumour growth and metastasis [221]. Whereas methylation is a silencing signal for gene transcription, acetylation generally increases gene expression. In this context a similar observation could be made in the mouse trial in which pancreatic GPx1 over-expression strongly increased DNA- and histone acetylation in the PDX1 promotor region leading to a massive increase in b-cell mass and insulin production [82]. As described above for phosphorylation and signalling processes the influence of Se on DNA methylation and acetylation also impressively shows that one and the same mechanism may provide protection against cancer and increase the risk of early diabetes development. Recent results suggest that the coincidence of polymorphisms in the selenoprotein P gene and in the MnSOD gene may increase the risk of prostate cancer [222]. A reduced delivery of Se to the prostate gland leading to the subsequent reduced synthesis of antioxidant selenoproteins combined with a reduced detoxification of initially produced superoxide radicals is thought to raise the prostate cancer risk via increased oxidative stress. An influence of seleonprotein P polymorphisms was also described with regard to the protection of humans against colon cancer [223]. Generally two isoforms of seleoprotein P exist (a 50 kDa isoform and a 60 kDa isoform). Depending on the genotype and on specific polymorphisms, either the 50 kDa or the 60 kDa form dominates. The 60 kDa form seems to be more effective in supplying peripheral tissues sufficiently with Se and therefore providing the basis for the synthesis of antioxidant selenoproteins and cancer protection. In this context the observation that in case of the existence of polymorphisms forwarding the synthesis of the 50 kDa selenoprotein P isoform, Se supplementation of these patients leads to a strong increase in the favourable 60 kDa form. This opens perspectives to advise individuals with those polymorphisms to intermittently take Se supplements. That the gastrointestinal glutathione peroxidase GPx2 may play a key role in the prevention of colon cancer could be demonstrated by the ability of GPx2 to dampen the expression of cyclooxygenase 2 and microsomal prostaglandin E2 synthase-1 and therefore to reduce inflammation driven initiation of carcinogenesis by prostaglandin E2 [224]. Finally it should be mentioned that accompanying Se supplementation seems to be useful during radiotherapy of cancers, since Se increases the radiosensitivity of tumours cells [225,226]. As described in this section in certain respects permanent supranutritional Se supplementation seems therefore to influence protection from cancer and diabetes development exactly contrariwise. As stated below in our concluding remarks with regard to diabetes, the currently available data do not uniquely support the necessity of permanent supranutritive Se supply for cancer prophylaxis. This recommendation is supported by the fact that Se seems to have a certain protective effect against prostate cancer and colon cancer whereas it may increase the risk of skin cancers and squamous cell cancers [219]. In the future, modern molecular biological methods (e.g. for the detection of polymorhisms such as in selenoprotein P) may represent a helpful tool to give well-directed advice to patients to take intermittently Se supplements. A very simple approach for the prevention of colon cancer could be the encapsulation of Se into hemicellulose or other fibres which are not digestible in the small intestine. This would represent a simple tool to obtain a high local Se concentration where it is desired and to avoid it where it is not needed."

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.

 

[Koveras]

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.

The nutritional prevention of cancer: 400 mcg per day selenium treatment.

"...selenium supplementation decreased the risk of lung, colon, prostate, and total cancers but increased the risk of nonmelanoma skin cancer. "

"The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25%; however, 400-mcg/day of Se had no effect on total cancer incidence."

"Participants were randomized, double-blinded, to [200 or 400-mcg/day] of Se in yeast or to an identical-appearing low Se yeast placebo"

"Selenomethioine was in the highest concentration, ranging from 54–62%; selenite concentrations did not exceed 1%; with the remainder of selenium in unidentified forms."

 

[Ulysses]

Oats are a good source of selenium. The one starch I've kept in my diet (boiled thoroughly, of course).

 

[Ulysses]

They make no distinction between selenium ions, selenocysteine, and selenomethione.

Is there a database somewhere that will let me check the specific molecular forms, in a given food, of micronutrients like selenium? For example, having read your comment, I would now like to know what kind of selenium is in oats. The first page of Google results is to no avail, and at any rate, I'm sick of tracking this information down piecemeal. A more efficient solution would be ideal.

 

[Travis]

Is there a database somewhere that will let me check the specific molecular forms, in a given food, of micronutrients like selenium? For example, having read your comment, I would now like to know what kind of selenium is in oats. The first page of Google results is to no avail, and at any rate, I'm sick of tracking this information down piecemeal. A more efficient solution would be ideal.

There's some good review articles which talk about it, but you might have to get familiar with sci‐hub to read them. There are many things that I'd want tabulated that aren't currently, like the Fernstrom and methionine/threonine ratios of common foods. It would be nice to have a computer programmer find out how to feed the background HTML outputs from nutritiondata.com into a program that does this (is this even possible?), but right now these things take a bit of work. I think it's unfortunate that most scientists simply measure for selenium— period. Little distinction is often made between selenomethionine and selenide (Se²⁻), which have radically different properties. Here is an explemplary article on the topic, on one food only: eggs:

Lipiec, Elżbieta. "Determination of selenomethionine, selenocysteine, and inorganic selenium in eggs by HPLC–inductively coupled plasma mass spectrometry." Analytical and bioanalytical chemistry (2010)​

Not sure if we can find a hand chart yet, but I'm curious to know. Since flame spectroscopy—a common method for determining 'minerals'—cannot tell what exactly the selenium is bound to, the more advanced high pressure liquid chromatography is used. This is cool: the molecules are first separated by chromatography and then 'flamed' into smaller pieces which are then passed through a electric field; this separates them by their mass to charge ratio. Since these fragments are small, the masses detected are always integer multiples of atoms. For instance: selenium has a mass of 78 and carbon has a mass of 12 so you can determine which fragment is which.

But I'm not sure if this has been done for every food, or whether the USDA just uses flame spectroscopy of a non‐protein aqueous fraction.

This seems to mean little without comparison to other foods, yet it highlights how selenium is distributed.