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Selenium and Diabetes/Insulin Resistance

Answered on September 12, 2014
Created March 09, 2013 at 6:26 PM

A while back I saw a user on this site (Travis Culp I believe) post the following study:

"Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial"

From the abstract: "During an average follow-up of 7.7 years (SD, 2.7), type 2 diabetes developed in 58 selenium recipients and 39 placebo recipients". "An exposure-response gradient was found across tertiles of baseline plasma selenium level, with a statistically significantly increased risk for type 2 diabetes in the highest tertile of baseline plasma selenium level".

The study found 200 ug/d of selenium significantly increase diabetes risk. The SELECT trial, another double blind RCT, noted a similar observation:

http://jama.jamanetwork.com/article.aspx?articleid=183163

Among subjects taking 200 ug/d of selenium, risk of type 2 diabetes was non-significantly higher (p=0.16, so it was close to significant).

200 ug is more than triple the RDA, so this could be a result of selenium toxicity. I guess my question is: should we be wary of excessive selenium intake? Are there factors present (or missing) in these studies that affect how the body handles selenium?

EDIT

Additional question: The form in both studies was selenomethionine. Is selenomethionine potentially a worse form of selenium?

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 12, 2013
at 12:55 PM

Here are the PHD references to selenomethionine evidence of toxicity: “suppresses DNA repair” http://pmid.us/17257432 “distorts DNA methylation” http://pmid.us/21653573 “42% fingernail damage, 24% skin fungal infections” http://pmid.us/21856002 ; And evidence that selenocysteine were not found to be toxic: http://pmid.us/15325150

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 12, 2013
at 12:51 PM

One thing I wasn't crazy about was it was intravenous, as opposed to normal digestion.

44348571d9bc70c02ac2975cc500f154

(5853)

on March 12, 2013
at 06:41 AM

I often just eat them raw in my mans salad, along with one small lamb heart :) Luckily i live in western finland where theres little more selenium in the soil due to sea. Eastern Finland is very deficient, thats why they put tons of selenium to fields.

44348571d9bc70c02ac2975cc500f154

(5853)

on March 12, 2013
at 06:34 AM

Even still, they have about 130 µg/100grams selenium. Reindeer kidneys have more than 200 µg.But they arevery hard to source. Whereas you can get lamb kidneys delivered to your doorstep twice a month. So i guess i just need to eat more of the lamb ones. I havent figured out how to make them taste amazing. But if you devil them in espelette pepper, colmans musterd powder etc, and fry them in duck fat. They are ok. You can also make a thick tomato, mushroom, beef stock for them. Or steak and kidney pie, sans the suet pastry.

Medium avatar

(39821)

on March 12, 2013
at 05:52 AM

Actually...having just looked at the paper they cited to make that conclusion, it's the total turnover in peripheral tissues, not sticking around in the serum. Also, it's the same form in most food so I'd say that's a selenium-rich red herring.

Medium avatar

(39821)

on March 12, 2013
at 05:42 AM

Oh...uh...yeah I would not ever take that. Jesus Christ.

32f5749fa6cf7adbeb0b0b031ba82b46

(41747)

on March 12, 2013
at 03:12 AM

If your soil is deficient in selenium, your lamb is also deficient in selenium. Guess the question is where is your lamb from?

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 12, 2013
at 02:15 AM

Yeah, I saw that same paper and thought the same thing as Travis. What do you make of this? "It has been reported (7) that one single intravenous dose of 200 μg L-selenomethionine can circulate in the plasma and in peripheral tissue for up to 400 days. Therefore, we assumed that it is likely that plasma concentrations of L-selenomethionine from supplements cannot reach a steady state." http://jnci.oxfordjournals.org/content/101/19/1363.long

A2c38be4c54c91a15071f82f14cac0b3

(12682)

on March 12, 2013
at 02:11 AM

Yeah, though maybe it's more common in the general population. Also, don't the bros love protein? Most of the bros I know are always saying stuff like "dood ya gotta use whey PWO to get shredded!" then they start flexing. Wait, am I interpreting the term "broscience" too literally?

Medium avatar

(39821)

on March 12, 2013
at 02:02 AM

Kinda doubt any of us are gonna have a methionine bottleneck situation unless we've subscribed to proteinphobia broscience.

A2c38be4c54c91a15071f82f14cac0b3

(12682)

on March 12, 2013
at 01:40 AM

I found some evidence re: selenomethionine being more toxic: "When methionine is limiting, a greater percentage of selenomethionine is incorporated nonspecifically into body proteins in place of methionine (see Fig. 1 ) because met-tRNA cannot distinguish between methionine and selenomethionine. In other words, the anticarcinogenic activity of selenomethionine is severely compromised in a situation in which it is preferentially compartmentalized into tissue proteins instead of entering the metabolic pathway". From this paper: http://jn.nutrition.org/content/128/11/1845.full

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 10, 2013
at 03:32 PM

FWIW, salt, water, sweating is suggested by multiple sources as a way to excrete excess minerals/metals.

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 10, 2013
at 03:32 PM

Could iodine and magnesium status also be a factor for selenium toxicity limit?

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 10, 2013
at 03:31 PM

Could the form of selenium be a factor with animal selenocysteine being less toxic than plant selenomethionine in supplements? "0.5-g high-selenium baker’s yeast tablet provided by Nutrition 21" - probably L-selenomethionine (http://www.nutrition21.com/OurProducts/Selenomax.aspx)? "selenomethionine is less useful to humans and may be toxic in ways selenocysteine is not." Perfect Health Diet (Kindle Location 5275)

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 10, 2013
at 03:31 PM

Yes, the gender connection is very interesting.

A2c38be4c54c91a15071f82f14cac0b3

(12682)

on March 10, 2013
at 01:36 AM

In this study: http://cebp.aacrjournals.org/content/11/7/630.full.pdf selenium decreased cancer risk but only in men. And in men above 1.2 ug/L cancer risk actually increased non significantly~ I'm leaning towards selenium, at least in men, being really important to get enough of and not too much of.

A2c38be4c54c91a15071f82f14cac0b3

(12682)

on March 10, 2013
at 01:14 AM

This is especially interesting to me because a number of RCT's have found reduced cancer rates in men but not women from taking selenium supplements. Clearly something about men and women is different with regards to selenium.

A2c38be4c54c91a15071f82f14cac0b3

(12682)

on March 10, 2013
at 01:13 AM

Interesting stuff. The sex specific effects of different selenium levels on glycemia in men but not women in the study you posted is very interesting because in the second study I posted only men were more likely to develop diabetes. There was no difference in women. And the first study was only on men.

800e726cb5dff569fd8edf604c3e2793

(1655)

on March 09, 2013
at 07:42 PM

"I think people assume that it's as rare as iodide often is, but that doesn't appear to be the case." -- that really depends on where you are living, or, to be more precise, where is your food grown. Some soils are rich in selenium, some are poor. You can't generalize here.

Medium avatar

(39821)

on March 09, 2013
at 07:23 PM

Love your posts as always. I can't help but picture a viking ripping kidneys out of animals and eating them. Do you have some special method to prevent them from tasting so strongly? I remember telling my grandpa about how I tried them and he said "if you don't boil them several times, you're just eating piss."

44348571d9bc70c02ac2975cc500f154

(5853)

on March 09, 2013
at 07:05 PM

I also buy potatoes that are grown in Lappland due to their great mineral content. They grow differently there cause theres 24h light during summer. Its a type of almond potato, called Lapin Puikula.

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3 Answers

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Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 09, 2013
at 10:11 PM

One observation from the first study (Effects of Long-Term Selenium Supplementation on the Incidence of Type 2 Diabetes) is the original supplement supplier was replaced in 1995, just before the study completed in 1996. Curious.

Background
The intervention agent was 200 ??g of selenium daily, supplied in a 0.5-g, high-selenium baker's yeast tablet provided by Nutrition 21 (La Jolla, California) through 1995 and by Cypress Systems (Fresno, California) thereafter.

Plasma selenium and risk of dysglycemia in an elderly French population: results from the prospective Epidemiology of Vascular Ageing Study is a more recent study that references the two in your question that attempts to add more to the conflicting data. They observed a protective effect of plasma selenium in men but not in women.

A preventive role of selenium on the risk of diabetes has been reported and ascribed to the "insulin-like" activity of selenium and the antioxidant properties of the selenoenzymes. By contrast, data from cross-sectional studies and clinical trials have suggested an adverse effect of high selenium status and selenium supplementation on type-2 diabetes risk.

It doesn't seem like a very strong study, but it might be an interesting read and it does offer an additional interpretation of the two studies in your question.

The effect of long-term selenium supplementation as a single nutrient on the incidence of type 2 diabetes was also investigated by Stranges et al. [11]. Their secondary analysis of the Nutritional Prevention of Cancer randomized trial showed a higher cumulative incidence of type 2 diabetes during 7.7 years of follow-up in participants receiving selenium (200 ??g/day as high-selenium yeast) than in those receiving placebo. Interestingly, when results were examined by tertile of baseline plasma selenium, the increased risk was only observed in the top tertile (mean baseline plasma selenium >1.54 ??mol/L). It should be noted that the median concentration of selenium in the highest tertile of our study was 1.32 ??mol/L, equivalent to their lowest tertile (??? 1.33 ??mol/L). It is of course well known that selenium intakes in France, and more generally in Europe, are considerably lower than in the United States [18,19]. Thus, it is possible that the difference between our results and those of Stranges could be partly explained by a selenium-status effect. Another point for consideration is that in this secondary analysis of the Nutritional Prevention of Cancer trial, the diabetes cases were not identified through measurement of fasting blood glucose, but were based on self-report and medical records. To our knowledge, our study is the first prospective observational study to show that healthy elderly men with baseline plasma selenium between 1.19-1.97 ??mol/L had a significantly lower risk of developing dysglycemia over a 9-year follow-up period compared to those with plasma selenium concentration below 1.00 ??mol/L. This suggests that optimal levels of selenium may reduce the risk of developing hyperglycemia or type 2 diabetes in men.

So, it seems to support some issue with supplementation vs. food source, as Travis suggested.

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 10, 2013
at 03:32 PM

Could iodine and magnesium status also be a factor for selenium toxicity limit?

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 10, 2013
at 03:31 PM

Yes, the gender connection is very interesting.

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 10, 2013
at 03:31 PM

Could the form of selenium be a factor with animal selenocysteine being less toxic than plant selenomethionine in supplements? "0.5-g high-selenium baker’s yeast tablet provided by Nutrition 21" - probably L-selenomethionine (http://www.nutrition21.com/OurProducts/Selenomax.aspx)? "selenomethionine is less useful to humans and may be toxic in ways selenocysteine is not." Perfect Health Diet (Kindle Location 5275)

A2c38be4c54c91a15071f82f14cac0b3

(12682)

on March 10, 2013
at 01:14 AM

This is especially interesting to me because a number of RCT's have found reduced cancer rates in men but not women from taking selenium supplements. Clearly something about men and women is different with regards to selenium.

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 12, 2013
at 12:51 PM

One thing I wasn't crazy about was it was intravenous, as opposed to normal digestion.

A2c38be4c54c91a15071f82f14cac0b3

(12682)

on March 12, 2013
at 01:40 AM

I found some evidence re: selenomethionine being more toxic: "When methionine is limiting, a greater percentage of selenomethionine is incorporated nonspecifically into body proteins in place of methionine (see Fig. 1 ) because met-tRNA cannot distinguish between methionine and selenomethionine. In other words, the anticarcinogenic activity of selenomethionine is severely compromised in a situation in which it is preferentially compartmentalized into tissue proteins instead of entering the metabolic pathway". From this paper: http://jn.nutrition.org/content/128/11/1845.full

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 10, 2013
at 03:32 PM

FWIW, salt, water, sweating is suggested by multiple sources as a way to excrete excess minerals/metals.

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 12, 2013
at 12:55 PM

Here are the PHD references to selenomethionine evidence of toxicity: “suppresses DNA repair” http://pmid.us/17257432 “distorts DNA methylation” http://pmid.us/21653573 “42% fingernail damage, 24% skin fungal infections” http://pmid.us/21856002 ; And evidence that selenocysteine were not found to be toxic: http://pmid.us/15325150

A2c38be4c54c91a15071f82f14cac0b3

(12682)

on March 10, 2013
at 01:13 AM

Interesting stuff. The sex specific effects of different selenium levels on glycemia in men but not women in the study you posted is very interesting because in the second study I posted only men were more likely to develop diabetes. There was no difference in women. And the first study was only on men.

A2c38be4c54c91a15071f82f14cac0b3

(12682)

on March 12, 2013
at 02:11 AM

Yeah, though maybe it's more common in the general population. Also, don't the bros love protein? Most of the bros I know are always saying stuff like "dood ya gotta use whey PWO to get shredded!" then they start flexing. Wait, am I interpreting the term "broscience" too literally?

Medium avatar

(39821)

on March 12, 2013
at 05:42 AM

Oh...uh...yeah I would not ever take that. Jesus Christ.

A2c38be4c54c91a15071f82f14cac0b3

(12682)

on March 10, 2013
at 01:36 AM

In this study: http://cebp.aacrjournals.org/content/11/7/630.full.pdf selenium decreased cancer risk but only in men. And in men above 1.2 ug/L cancer risk actually increased non significantly~ I'm leaning towards selenium, at least in men, being really important to get enough of and not too much of.

Cbdc8318738324492f2d5918868ce4c9

(1211)

on March 12, 2013
at 02:15 AM

Yeah, I saw that same paper and thought the same thing as Travis. What do you make of this? "It has been reported (7) that one single intravenous dose of 200 μg L-selenomethionine can circulate in the plasma and in peripheral tissue for up to 400 days. Therefore, we assumed that it is likely that plasma concentrations of L-selenomethionine from supplements cannot reach a steady state." http://jnci.oxfordjournals.org/content/101/19/1363.long

Medium avatar

(39821)

on March 12, 2013
at 05:52 AM

Actually...having just looked at the paper they cited to make that conclusion, it's the total turnover in peripheral tissues, not sticking around in the serum. Also, it's the same form in most food so I'd say that's a selenium-rich red herring.

Medium avatar

(39821)

on March 12, 2013
at 02:02 AM

Kinda doubt any of us are gonna have a methionine bottleneck situation unless we've subscribed to proteinphobia broscience.

4
44348571d9bc70c02ac2975cc500f154

(5853)

on March 09, 2013
at 07:00 PM

I live in Finland and eat plenty of lamb kidneys just cause our soil is very selenium poor. Kidneys are best source of minerals. I often eat brazil nuts too but i prefer meats and offal. :) Richest local source of selenium in the country are actually reindeer kidneys.

Medium avatar

(39821)

on March 09, 2013
at 07:23 PM

Love your posts as always. I can't help but picture a viking ripping kidneys out of animals and eating them. Do you have some special method to prevent them from tasting so strongly? I remember telling my grandpa about how I tried them and he said "if you don't boil them several times, you're just eating piss."

44348571d9bc70c02ac2975cc500f154

(5853)

on March 09, 2013
at 07:05 PM

I also buy potatoes that are grown in Lappland due to their great mineral content. They grow differently there cause theres 24h light during summer. Its a type of almond potato, called Lapin Puikula.

32f5749fa6cf7adbeb0b0b031ba82b46

(41747)

on March 12, 2013
at 03:12 AM

If your soil is deficient in selenium, your lamb is also deficient in selenium. Guess the question is where is your lamb from?

44348571d9bc70c02ac2975cc500f154

(5853)

on March 12, 2013
at 06:41 AM

I often just eat them raw in my mans salad, along with one small lamb heart :) Luckily i live in western finland where theres little more selenium in the soil due to sea. Eastern Finland is very deficient, thats why they put tons of selenium to fields.

44348571d9bc70c02ac2975cc500f154

(5853)

on March 12, 2013
at 06:34 AM

Even still, they have about 130 µg/100grams selenium. Reindeer kidneys have more than 200 µg.But they arevery hard to source. Whereas you can get lamb kidneys delivered to your doorstep twice a month. So i guess i just need to eat more of the lamb ones. I havent figured out how to make them taste amazing. But if you devil them in espelette pepper, colmans musterd powder etc, and fry them in duck fat. They are ok. You can also make a thick tomato, mushroom, beef stock for them. Or steak and kidney pie, sans the suet pastry.

3
Medium avatar

on March 09, 2013
at 06:49 PM

200mcg is a pretty standard dose sold as supplements. It's difficult to tell if it's the selenomethione form or if it's the total amount that's causing that (or if it's just an anomaly and totally unrelated). I kind of doubt it's selenium itself since, at least on paper, I ate 200-something mcg yesterday with no seafood. I'd be quite surprised if there were a positive between seafood and diabetes: http://www.sciencedirect.com/science/article/pii/S1262363607700800 Like most minerals, our

I'm also leery of radium-rich Brazil nuts eaten frequently, for what it's worth. I suspect that a balanced diet comprised of various nutritious foods will supply sufficient selenium. I think people assume that it's as rare as iodide often is, but that doesn't appear to be the case. If I lived in an area like New Zealand, which is known to be low in it, I would be a bit more concerned though.

800e726cb5dff569fd8edf604c3e2793

(1655)

on March 09, 2013
at 07:42 PM

"I think people assume that it's as rare as iodide often is, but that doesn't appear to be the case." -- that really depends on where you are living, or, to be more precise, where is your food grown. Some soils are rich in selenium, some are poor. You can't generalize here.

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