Selenium

The Details

Reviews

Reviews show that selenium has a U-shaped relationship with diabetes. At low doses (selenium deficiency), there is an increased risk of diabetes. At high doses (above recommended levels) there is also an increased risk (Casanova and Monleon, 2023; Pyrzynska and Sentkowska, 2023).

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). An updated meta-analysis by the same authors also agrees that high selenium levels increase the risk of type 2 diabetes (Vinceti et al. 2021). 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). A meta-analysis of 12 randomized, controlled trials on selenium supplementation found that supplementation led to lower beta cell function but did not affect most other glycemic measurements (Mahdavi Gorabi et al. 2019). Another review notes that high levels of selenium carry an increased risk of type 2 diabetes but lower risk of complications in diabetes, and selenium deficiency with gestational diabetes (Demircan et al. 2024).

A review found that studies that measured blood selenium levels found a link between high levels and an increased risk of type 2 diabetes. Those that measured dietary intake are less clear (Alharithy and Alafif, 2023).

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 cholesterol (Gharipour et al. 2017).

A review of rodent studies found that selenium supplementation increased blood glucose levels in health animals (Ferreira et al. 2022).

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 those with higher selenium levels had a higher risk of diabetes (Bleys et al. 2007), as did others from more recent years (Liao et al. 2020; Lin and Shen, 2020; Ma et al. 2024; Moon et al. 2019; Zhang et al. 2023). U.S. adults without diabetes who had higher selenium levels had higher fasting glucose, HbA1c (long-term glucose), and insulin levels, all precursors of type 2 diabetes (Yang et al. 2022). 

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, higher blood levels of selenium were associated with an increased risk of metabolic syndrome and higher fasting blood sugar levels (Liu et al. 2020; Yuan et al. 2015), and with an increased risk of type 2 diabetes (Lv et al. 2020; 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 additional Chinese study found that those with either high or low selenium levels had impaired glucose regulation (Luo et al. 2019). Higher selenium intake has also been associated with a higher risk of type 2 diabetes in Chinese adults (Siddiqi et al. 2020). And higher selenium levels in soil are associated with a higher risk of type 2 diabetes in Chinese adults as well (Wang et al. 2020).

In China, Higher toenail selenium levels were associated with increased insulin resistance risk in meat eaters whose dietary Se intake was above 60 μg/d, but not in vegetarians (Gu et al. 2020).

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). 

A large study found that "genetically predicted" selenium levels were linked to a higher risk of type 2 diabetes (Rath et al. 2021).

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. 2018; Thompson 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). A Greek trial also found beneficial effects on glucose control (Karalis et al. 2019).

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). They also had higher triglycerides and total and LDL cholesterol levels, and lower HDL ("good") cholesterol levels (Huang et al. 2019; Li et al. 2023).

Spanish adults with higher selenium levels had higher total cholesterol and LDL 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).

Korean adults with obesity and more insulin resistance had lower selenium levels in their hair than those with higher levels, perhaps indicating a mineral deficiency (Kim and Song, 2014). Polish children with obesity 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).

In Thailand, selenium levels were linked to obesity (as well as type 2 diabetes) (Wongdokmai et al. 2021).

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). Similarly, low levels of selenium can be harmful; in pigs, selenium deficiency reduced insulin and glucagon levels and decreased the number of islets in the pancreas (Li et al. 2020). In mice, selenium deficiency also reduced insulin secretion (Carmean et al. 2021).

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).

Some researchers are using rodents to try to figure out the optimal level of selenium, not too much to cause diabetes but not too little either (Huang et al. 2021).

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). Another rat study, however, found beneficial effects of selenium in offspring, and no evidence of increased insulin resistance (Laureano-Melo et al. 2020). Maternal selenium deficiency during gestation causes lower glucose concentrations in fetuses, and reduced fetal weight in mice (Hofstee et al. 2019). 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). People with genetically higher selenium levels have a lower risk of some autoimmune diseases but not others (Ye et al. 2021).

In mice, selenium supplementation is linked to disturbances in the gut barrier and intestinal inflammation (Zhai et al. 2019), which in turn are linked to type 1 diabetes development (see the Diet and the Gut page).

Gestational Diabetes

A review of 12 studies found that selenium levels were lower among women with gestational diabetes in comparison to those without; however, after the correction of the reporting bias, the result was no longer statistically significant (Hamdan et al. 2022). Another review of 14 studies found that lower levels of selenium were associated with an increased risk of gestational diabetes, in Asia and Africa (Yan et al. 2022).

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 (Hofstee et al. 2020; Kong et al. 2016; Liu et al. 2023; Mariath et al. 2011; Askari et al. 2015; Xu et al. 2022). Again, however, it may be that certain levels of selenium are protective against diabetes, while excess selenium can be harmful.

A trial of selenium supplementation in women with gestational diabetes in Iran found no benefits on glucose control (Sadat Najib et al. 2020).

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). U.S. adults with higher selenium levels also had a higher risk of NAFLD (Wang et al. 2021).

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).