Oxidative stress may be one of the worst threats to kidney health. Selenium is an essential micronutrient that plays a significant role in protecting the body from oxidative stress. Selenium is also important for thyroid hormone metabolism, it reduces the risk of certain cancers, and it is protective against heart disease. In this blog, I will discuss selenium and kidney health and whether this mineral should be on your list of kidney supplements. Is selenium good for kidney disease?

Selenium, the micromineral

Selenium is classified as a trace mineral because it is typically needed in small doses to exert its biological effects. Unlike other trace minerals, though, selenium does not act as a cofactor of various enzymes or proteins. Instead, it is incorporated in the essential structure of various proteins called selenoproteins.  There are about 20 known selenium-containing proteins in humans. Glutathione peroxidases (GPX) are some of the most important selenoproteins.

As mentioned earlier, selenium helps protect the body from oxidative stress. But what is oxidative stress? Free radicals, which cause oxidative stress, are a normal byproduct of daily living that happens in our cells. You might think of these as waste products. They need to be neutralized (or “reduced”) by antioxidant enzymes so that the cell stays healthy.

When free radicals build up and aren’t handled properly, they can damage enzymes, cells, and tissues. Oxidative stress has been identified as a root cause of many diseases, including heart disease, Alzheimer’s, Parkinson’s, chronic kidney disease, and many more. A nutrient like selenium that prevents free radical buildup can help to repair cells and tissues, and improve diseases of oxidative stress.


Glutathione, the master antioxidant

Selenium is crucial to the functioning of the antioxidant glutathione. Glutathione is a substance made of three amino acids (cysteine, glycine, and glutamic acid). Glutathione helps to recycle other antioxidants. On top of that, GSH has other functions such as metabolism, cell signaling, and protein interactions that can also mediate defense against oxidants. It helps the body get rid of heavy metals and a long list of toxins.

Glutathione is present in the cells in two forms: reduced (GSH) and oxidized (GSSG). The cycling between GSH and GSSG is what makes glutathione a major antioxidant. Simply put, when GSH is exposed to an oxidant it gets oxidized to GSSG by an enzyme called glutathione peroxidase. GSSG is, then, recycled back into GSH by an enzyme called glutathione reductase (see figure.)

The enzyme glutathione peroxidase is a selenoprotein that mediates the oxidation of GSH to GSSG. Selenium is an integral component of this enzyme. Selenium is, therefore, crucial for the body’s antioxidant ability.

Selenium deficiency and absorption

Selenium is primarily absorbed in the small intestines by active transport via a sodium pump, the means by which sodium ions are transferred across a cell membrane. Selenium in food exists in two forms: inorganic and organic (bound to methionine, called selenomethionine, or cysteine, called selenocysteine). Dietary selenium is absorbed efficiently. But the retention of organic forms of selenium in the body is higher than that of the inorganic forms.

Food sources of selenium include Brazil nuts, seafood, and organ meats. In fact, two Brazil nuts have more than the daily requirements of selenium.

Selenium intakes and serum concentrations in the US vary by region because of differences in the amounts of selenium in the soil. Aging, smoking, and alcohol consumption affect selenium absorption. Men tend to consume more selenium and have slightly higher serum selenium concentrations than women.

Selenium deficiency is not common. However, insufficient selenium levels may predispose people with additional stressors to be at higher risk of certain illnesses. Selenium status can be measured in serum. Normal levels are 70-150 ng/mL. Studies have shown that increasing serum selenium levels were associated with decreased mortality up to a level of 130 ng/mL.

 

Selenium and kidney disease

The kidneys and the thyroid gland have the highest concentration of selenium in the body. It turns out that the kidney proximal tubule cells have glutathione peroxidase near their basement membranes. This indicates that glutathione activity is necessary for that region due to high oxidative stress. This is probably because these cells are actively engaged in handling various toxins and in the reabsorption of amino acids, glucose, mineral salts, and other things the body wants to hold onto and recycle.

In addition, selenium levels have been found to be decreased in patients with chronic kidney disease (CKD). Selenium deficiency was also found to cause acute kidney injury in animal models. This was believed to be due to oxidative stress and mitochondrial dysfunction.

Studies have shown that using selenium as a kidney support supplement protects the kidneys from ischemic injuries, which occur when the kidneys are deprived of sufficient oxygen. Selenium supplementation also leads to reduced oxidative stress and inflammation in the kidneys.  Supplementing selenium and CoQ10 in elderly patients with CKD and selenium deficiency was found to improve renal function. The dose of selenium that was used was 200 mcg per day.

On top of that, a small human study found that supplementing selenium in an amount as high as 700 mcg daily was not only safe, but it also improved the glomerular filtration rate over a period of six weeks. It was thought that selenium plays a role in regulating the kidney blood vessels. Supplementation at these high levels should be done under the supervision of a healthcare provider.

Finally, selenium deficiency is associated with cardiovascular disease and cancer, leading to an increased burden of comorbidities in patients with kidney disease.

Selenium and heavy metal toxicity

As we saw, selenium is incorporated in many enzymes and proteins that have antioxidant properties. That is why it plays an important role in protecting against the toxicity of heavy metals. In fact, selenium has been found to decrease the toxicity of arsenic and cadmium on the kidneys. This is thought to be due to selenium’s role in transforming these toxins into non-toxic forms. It is also related to the antioxidant activity of selenium-containing enzymes. Selenium was also found to protect the kidneys from the toxicity of mercury.




Selenium toxicity

Chronic high intake of selenium can be associated with health problems. The first sign of excessive selenium is garlic breath odor and a metallic taste in the mouth. Selenosis (selenium poisoning) is characterized by hair and nail loss, mottled teeth, GI symptoms, fatigue, and irritability.

Are You Selenium Deficient?

Measuring oxidative stress in patients with CKD can be accomplished by various methods. One of our favorites is measuring the GSH:GSSG ratio. The ratio of GSH to GSSG gives an idea about exposure to oxidative stress. In healthy cells, this ratio is more than 100 but it drops to less than 10 in cells that are exposed to oxidative stress. However, this test is not widely available.

An alternative method to assessing oxidative stress is by measuring the damage caused by free radicals. This damage can be measured in protein, lipid, or DNA. Urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) is a test that measures the oxidation of DNA. High levels are associated with increased oxidative stress. This test is commercially available.

Patients who have a low GSH:GSSG ratio or high urinary 8-OHdG can have their selenium serum level measured. We aim for a level of 100-130 ng/mL. Those who have low selenium can benefit from supplementation and follow-up measurement in three-six months.

Once again, we emphasize the need to take high-quality supplements to improve kidney function.  Acute selenium toxicity has been reported due to the ingestion of an over-the-counter liquid supplement containing 200 times the labeled amount of selenium.

Ideally, once target serum levels are reached, the patient can maintain adequate selenium intake through a plant-dominant diet rich in phytonutrients.

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The bottom line

Selenium deficiency is linked to oxidative stress and inflammation, two processes that damage the kidneys. This is why adequate selenium status is essential for kidney health. Patients with kidney disease should aim for 200 mcg of selenium daily either through high-quality supplements or diet. This can be easily accomplished by eating only two Brazil nuts a day.