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Selenium

Summary

Links Between Selenium and Diabetes/Obesity

The Details

About Selenium



Summary

Links Between Selenium and Diabetes/Obesity

Dozens of peer-reviewed studies published in scientific journals have examined the relationship between selenium and diabetes or obesity.

High levels of selenium may increase the risk of type 2 diabetes, while lack of sufficient selenium may also promote diabetes.

A systematic review and meta-analysis of 5 studies found a positive association between selenium levels and type 2 diabetes in populations with both relatively low levels and high levels of selenium (Wang et al. 2016). Another review and meta-analysis found an association between selenium levels and type 2 diabetes over a range of exposure levels (Vinceti et al. 2018). A meta-analysis of 20 studies also found that higher selenium levels were associated with a higher risk of type 2 diabetes (Kim et al. 2019). However, a systematic review of 16 studies found that while observational studies usually showed positive associations between diabetes and selenium, the randomized controlled trials did not (Kohler et al. 2018).

Selenium supplements should be avoided unless deficient, especially in the U.S., or in people with adequate selenium levels. Supplementation of people who already have adequate intake with additional selenium might increase their risk of type 2 diabetes (Rayman, 2012). While selenium is an essential mineral, its toxic effects are now being found at lower levels than previously thought (Jablonska and Vinceti 2015).


The Details

About Selenium

Selenium is an essential trace element, but it can also be toxic at high doses. Most Americans have high levels of selenium intake as compared to people in some other countries, due to the higher levels of selenium in U.S. soils as well as the use of dietary supplements containing selenium (Laclaustra et al. 2009). High levels of selenium have been found in streams subject to mountaintop mining and valley fills in central Appalachia. In some streams, selenium has bioaccumulated to four times the toxic level in the food chain, a level that can cause harm in fish and birds. Groundwater wells are also affected, and state advisories are in effect for consumption of fish due to high selenium levels (Palmer et al. 2010). There is a high prevalence of diabetes in many counties in central Appalachia (Centers for Disease Control and Prevention 2009).

Type 2 Diabetes

Longitudinal Studies in Humans

Higher Selenium Levels Are Associated With an Increased Risk of Type 2 Diabetes

selenium

The blue bars on each graph show the percentage of people with that level of selenium in their bodies; most people in this U.S. study have moderate levels. The solid black lines show the risk of type 2 diabetes in A, differences in fasting glucose levels in B, and HbA1c levels in C. The gray shading show the 95% confidence levels. You can see that as selenium levels increase, the risk of diabetes increases and then flattens out at higher levels.
The strongest evidence for the ability for environmental exposures to contribute to the development of diabetes comes from longitudinal studies. These are studies that take place over a period of time, where the exposure is measured before the disease develops.

One prospective study from France found that elderly men with higher selenium levels had a lower risk of later developing type 2 diabetes or impaired fasting glucose (there was no association in women) (Akbaraly et al. 2010). A long-term study found that higher toenail levels of selenium were associated with a lower risk of type 2 diabetes in U.S. adults, at dietary levels of intake (Park et al. 2012). A study of Spanish adults found an association between selenium levels and type 2 diabetes, as well as an interaction with genes (Galan-Chilet et al. 2017). A study of Chinese seniors found that higher selenium levels were associated with a higher risk of type 2 diabetes (Yuan et al. 2018).

However, a study of elderly Swedish men found no association between selenium levels and the development of type 2 diabetes, beta cell function, or insulin resistance 20 years later (Gao et al. 2014). Neither did an Italian study-- it found no association between toenail selenium levels in women and risk of type 2 diabetes 16 years later (Vinceti et al. 2015).

A study from China found that those with higher selenium levels had higher post-meal glucose levels, as well as a higher risk of metabolic syndrome (Fang et al. 2019).

Cross-Sectional Studies in Humans

Cross-sectional studies are studies that measure exposure and disease at one point in time. These provide weaker evidence than longitudinal studies, since the disease may potentially affect the exposure, and not vice versa.

Laclaustra et al. (2009) found that in U.S. adults exposed to normal selenium levels, the prevalence of diabetes increased with increasing levels of selenium. Fasting glucose levels and hemoglobin A1C levels (a measure of long-term glucose control) increased with increasing selenium levels as well. Another U.S. study from an earlier time period also found selenium levels to be positively associated with diabetes (Bleys et al. 2007), as did one from more recent years (Moon et al. 2019).
 
A study of elderly Taiwanese found that higher selenium levels were associated with higher fasting glucose (as well as higher triglycerides and cholesterol) (Yang et al. 2010). Another study from Taiwan found high selenium levels were associated with diabetes, independent of obesity and insulin resistance (Lu et al. 2016). In Chinese adults, dietary selenium intake was associated with type 2 diabetes (Wei et al. 2015). Also in Chinese adults, blood levels of selenium were associated with metabolic syndrome and higher fasting blood sugar levels (Yuan et al. 2015), and with type 2 diabetes (Zhang et al. 2019). 

In countries with lower selenium levels, including Singapore and France, studies have generally not found associations between selenium and diabetes or glucose levels (Laclaustra et al. 2009).

A study of older adults in China found that higher selenium levels were associated with higher triglycerides, LDL (the "bad" cholesterol), fasting blood glucose, post-meal blood glucose, higher average blood glucose levels (HbA1c), higher insulin resistance, as well as NAFLD (non-alcoholic fatty liver disease) (Yang et al. 2016). Another study of older adults from China also found that selenium levels were associated with diabetes, high glucose levels, and insulin resistance (Su et al. 2016). A third study from China found that relatively high selenium levels were associated with elevated fasting blood glucose levels and impaired fasting glucose in men (Li et al. 2018). An addition Chinese study found that those with either high or low selenium levels had impaired glucose regulation (Luo et al. 2019).

In Malaysia, a study of adults newly diagnosed with type 2 diabetes found that body fat measures were lower in those with lower selenium levels. However, there was no difference in selenium levels between the people with our without type 2 diabetes (Othman et al. 2017). 

Clinical Trials of Selenium Supplementation

Since selenium is an essential element, it is sometimes found in dietary supplements. Interestingly, two trials of selenium supplementation suggest that selenium may increase the risk of type 2 diabetes. A randomized, double-blind, placebo-controlled study from the Eastern U.S. found that selenium supplementation may increase the risk of developing type 2 diabetes (Stranges et al. 2007). Another large, randomized, double-blind, placebo-controlled study, aimed to determine whether selenium (and/or vitamin E) supplements could prevent prostate and other cancers. It found instead that those who took selenium supplements alone had higher rates of type 2 diabetes (although the increased risk was not significant). The study was discontinued early. It was conducted in the U.S., Canada, and Puerto Rico (Lippman et al. 2009). Other trials, also for cancer, also found that selenium supplements increased the risk of type 2 diabetes (Kohler et al. 2018Thompson et al. 2016).

On the other hand, randomized, double-blind, placebo-controlled trials, from the western U.S., did not find any increase in diabetes risk or glucose levels with selenium supplementation in men at risk of or with prostate cancer (Algotar et al. 2013; Algotar et al. 2010). An Arizona trial found selenium supplementation did not affect beta cell function or insulin resistance (Jacobs et al. 2019). A study from Poland found that selenium supplementation improved HbA1c levels, but not fasting glucose levels (Jablonska et al. 2016). In contrast, a trial from Denmark found that selenium supplementation did not improve HbA1c levels after 2 years (Stranges et al. 2018).

A meta-analysis of four randomized controlled trials found that selenium supplementation did not find a preventative effect (or any statistically significant effect); if anything, there was a slight increased risk (not significant). The authors state, "Our findings do not support the routine application of selenium supplementation for type 2 diabetes prevention in Caucasians" (Mao et al. 2014). However, another meta-analysis, of five randomized controlled trials in people with metabolic diseases found that selenium supplementation reduced insulin levels and increased insulin sensitivity. It did not, however, affect fasting glucose levels, insulin resistance (by a different measure than insulin sensitivity), or lipid/cholesterol levels (Tabrizi et al. 2017). 

The fact that some trials have shown an increased risk of type 2 diabetes with selenium supplementation has raised concern about the use of supplements in people who are not selenium deficient. Selenium is often added to multivitamins, but "Based on current evidence, the indiscriminate use of selenium supplements in individuals and populations with adequate-to-high selenium status cannot be justified and may increase [type 2 diabetes] risk" (Rayman and Stranges, 2013). Long-term selenium supplementation is also associated with an increased risk of mortality in general (Rayman et al. 2018).

Selenium Supplementation Trials in People with Diabetes

A systematic review of 4 randomized controlled trials of selenium supplementation in people with diabetes found that supplements reduced fasting insulin levels, insulin resistance, and beta cell function, but that these studies did not evaluate other measures of interest, like diabetes complications or mortality. The authors conclude, "there is no evidence to support the effectiveness of selenium supplementation" in people with type 2 diabetes (Stróżyk et al. 2019).

A Iranian trial of selenium supplementation in people with diabetic nephropathy found that it had beneficial effects on insulin resistance, insulin levels, and beta cell function (Bahmani et al. 2016a), as well as markers of inflammation and oxidative stress (Bahmani et al. 2016b). Another Iranian trial of selenium supplementation in people with diabetes and coronary heart disease also found that it had beneficial effects in insulin resistance, insulin levels, and beta cell function (Farrokhian et al. 2016).

Insulin Resistance, Body Weight, and Metabolic Syndrome

U.S. adults with higher selenium levels had a lower BMI than those with lower levels (Zhong et al. 2018).

Spanish adults with higher selenium levels had higher total cholesterol and LDL ("bad") cholesterol levels, which are components of the metabolic syndrome (González-Estecha et al. 2017).

European women (without diabetes) who had higher levels of selenium in their blood were more likely to have metabolic syndrome than women with lower levels. There was no association in men (Arnaud et al. 2012).

Canadian adults with higher selenium intake (measured via a food questionnaire) had lower insulin resistance, except when the level becomes too high, the beneficial effect disappears (Wang et al. 2017).

Obese Korean adults with more insulin resistance had lower selenium levels in their hair than those with higher levels, perhaps indicating a mineral deficiency (Kim and Song, 2014). Obese children in Poland tended to have lower selenium levels in their blood, also perhaps indicating a mineral deficiency (Błażewicz et al. 2015); similarly, adults with low dietary intake of selenium had the highest body mass index (BMI) in another study (Wang et al. 2016). Chinese children with low selenium levels also had a higher risk of obesity (Xu et al. 2018).

In Taiwan, selenium levels were positively correlated with waist circumference, systolic blood pressure, triglycerides, fasting glucose, and insulin resistance in women, but only with fasting glucose and insulin resistance in men. Overall, metabolic syndrome was associated with increased selenium levels, especially in women (Lu et al. 2019).

Chinese men with metabolic syndrome has significantly higher blood concentrations of selenium (and other heavy metals) than those who were healthy (Guo et al. 2019).

A review of metabolic syndrome and selenium found that high levels may increase the risk of metabolic syndrome. In people with adequate selenium levels, supplementation can increase the risk of high blood pressure, high total cholesterol, and high LDL ("bad") cholesterol (Gharipour et al. 2017).

Laboratory Studies: Diabetes/Obesity

With the confusing human data, laboratory studies may help illuminate what is going on. While selenium is an essential trace element, and necessary up to a certain level-- even helping to prevent diabetes and insulin resistance-- at too-high levels it can induce insulin resistance in rats (Wang et al. 2014). In animals with low levels of selenium, supplements are helpful for improving glucose intolerance (Ueno et al. 2018). A review of the laboratory evidence finds that while earlier studies found selenium to act like insulin and help prevent diabetes, recent studies (both animal and human) have shown that prolonged, high intake of selenium can cause insulin resistance and/or diabetes in mice, rats, and pigs (Zhou et al. 2013). Even fish, exposed to selenium in water, have higher glucose levels than unexposed fish (Kim and Kang, 2014). In mice, long-term selenium supplements reduced glucose levels at first, but then increased insulin levels and led to fatty liver disease and other harmful effects (Wang et al. 2014). In rats, high levels of selenium supplementation caused insulin resistance (Stahel et al. 2017).

A mouse study suggests mechanisms by which high-dose selenium may affect the risk of diabetes. It found that selenium led to higher insulin resistance, higher insulin levels, and increased glucose tolerance via oxidative stress (Zhou et al. 2015). The effects of selenium related to insulin resistance also may vary by diet (Wang et al. 2016). A high-fructose diet in lab animal mothers, for example, affects the levels of selenium and induces metabolic disorders in offspring (Ojeda et al. 2016). Selenium causes higher blood glucose levels in conjunction with a high-fat diet in animals (Murano et al. 2018). The effects of selenium supplements also vary by baseline selenium levels in animals (Febiyanto et al. 2018).

Exposure During Development

Female rats fed were fed a low-selenium or high-selenium diet while pregnant and lactating. A few months after birth, the offspring exposed to a high-selenium diet developed high insulin levels, insulin resistance, and glucose intolerance, as compared to the deficient rats (Zeng et al. 2012). Other studies find that both high- and low-selenium diets cause metabolic disorders, including insulin resistance, in mother rats and their offspring (Ojeda et al. 2018). The female lambs of pregnant sheep given selenium had higher birth weight, more fat storage and body weight later on, and selenium also affected their glucose tolerance (Vonnahme et al. 2010). These studies show the potential for selenium exposure to affect development of the offspring later in life.

Type 1 Diabetes and Autoimmunity

A study from China finds that people with type 1 have lower levels of selenium in their blood (Zhou et al. 2018). A review finds that people with autoimmune diseases have lower selenium levels of selenium, and that sufficient selenium levels contribute to the management of complications of autoimmune diseases and even improved survival in patients with autoimmune diseases (Sahebari et al. 2018).

Gestational Diabetes

In the same study as above, the female rats who were fed a high-selenium diet developed high insulin levels, insulin resistance, and glucose intolerance while pregnant (similar to gestational diabetes in humans), as compared to the deficient rats (Zeng et al. 2012). This is a somewhat surprising result, considering that some human studies have found lower selenium levels in women with gestational diabetes, and a higher risk of gestational diabetes in women with inadequate selenium intake (Kong et al. 2016Mariath et al. 2011; Askari et al. 2015). Again, however, it may be that certain levels of selenium are protective against diabetes, while excess selenium can be harmful.

Diabetes Management and Complications

In Chinese adults with type 2 diabetes, over 6 years of follow up, zinc and selenium levels were associated with a lower risk of developing cardiovascular disease (Long et al. 2019). Also in Chinese adults, those with higher selenium intake had a higher risk of non-alcoholic fatty liver disease (NAFLD) (Wu et al. 2019).

Selenium Nanoparticles

Selenium nanoparticles-- note that nanoparticles often have different properties than the chemicals themselves-- may be able to prevent diabetic nephropathy (kidney disease) in rats (Kumar et al. 2014). They also show general anti-diabetic effects, e.g., preserving pancreatic beta cells (Ahmed et al. 2017) and lowering blood glucose levels (Al-Quraishy et al. 2015).

References

To download or see a list of all the references cited on this page, see the collection Selenium and diabetes/obesity in PubMed.