Selenium and Toxic Metals and the Ageing Kidney

In individuals older than 50-60 years, the kidneys’ glomerular filtration rate decreases with increasing age. The glomerular filtration rate is a measure of how well your kidneys are working. In your kidneys, there are tiny filters (called glomeruli) that remove waste and excess fluid from the blood.

Jan Aaseth
Jan Aaseth is a Norwegian physician and professor who has done extensive research in endocrinology, toxicology, and medical biochemistry. Here we summarize his review of the relationship between selenium status, heavy metal toxicity, and the kidneys.

Exposure to toxic metals – mercury, cadmium, lead – can be detrimental to kidneys of normal adults. Accordingly, exposure to toxic metals can affect individuals with reduced glomerular filtration rates even more adversely.

Professor Jan Aaseth and a team of researchers have reviewed the available research data. Their findings show the following relationships [Aaseth 2021]:

Elderly Individuals More Susceptible to Toxic Metal Exposure

Healthy elderly individuals are capable, for the most part, of maintaining normal kidney function. However, especially after the age of 70 years, physiological changes occur in the kidneys.

The ageing kidneys lose some of their functional reserve. As the functional reserve is lost, the kidneys have a reduced capacity to respond to exposures to toxic metals in the environment and reduced capacity to eliminate toxicants [Aaseth 2021].

Ageing and the Decline of Protective Antioxidant Enzymes

Aaseth et al cite studies that indicate that ageing is associated with a declining expression of the following antioxidant enzymes [Aaseth 2021]:

  • the superoxide dismutases
  • the catalase enzymes
  • the selenium-dependent glutathione peroxidases

The reduced protective activity of these enzymes against the oxidative damage caused by harmful free radicals can lead to further increases in oxidative stress and cellular ageing. It is a vicious circle.

Exposure to mercury, cadmium, or lead, even on a low-grade scale, has been shown to affect anti-oxidative enzyme systems adversely. Exposure to toxic metals can promote age-related organ changes, especially in the kidneys [Aaseth 2021].

Ageing Related to Oxidative Stress

Aaseth et al note that ageing appears to be associated with increased levels of oxidative stress, defined as an imbalance between harmful free radicals (reactive oxygen species, for the most part) and protective antioxidants. This imbalance in the cells is characterized by increased free radical production and/or by decreased efficacy of antioxidants in scavenging the free radicals [Aaseth 2021].

Selenium Related to Enhanced Antioxidant Activity

Selenium supplementation has been shown to increase the cells’ antioxidant enzyme activity and to enhance the cells’ antioxidant capacity. In particular, selenium supplementation is associated with increased antioxidant enzyme activity, e.g., the activity of selenium-dependent antioxidant glutathione peroxidase enzymes [Aaseth 2021].

The selenoenzyme GPX-3 (glutathione peroxidase–3) is formed in the kidneys and is found accumulated in the membrane surrounding the renal proximal tubules. Selenium supplementation is associated with an increase in serum GPX3 concentration [Aaseth 2021].

Selenium Supplementation and Reduced Oxidative Stress in Elderly Swedish Citizens

Data from the KiSel-10 Study, a randomized controlled study of an elderly Swedish population (average age: 78 years; range 70-88 years) has showed a statistically significant association between low selenium status (67.1 mcg/L or lower) and age-related reduction in renal function [Alehagen 2021].

  • The KiSel-10 study participants received 200 mcg/day organic selenium and 2 times 100 mg Coenzyme Q10 or matching placebos for four years.
  • The combined supplementation was associated with significantly improved kidney function as compared with the placebo supplementation.
  • The KiSel-10 research team attributed the improvement of kidney
    function to the optimized function of antioxidant selenoenzymes such as
    the glutathione peroxidases and the thioredoxin reductases.

Warning: Aaseth et al note that supra-nutritional intakes of selenium above about 300 mcg/day may have pro-oxidative effects and may be associated with increased risk of type 2 diabetes [Aaseth 2021].

N.B. The selenium researcher Prof. Lutz Schomburg, Berlin, Germany, has explained that the association between higher selenium status and increased diabetes risk most probably results from diabetes causing increased selenoprotein P synthesis and elevated selenium concentrations in the blood rather than the other way around [Schomburg 2020].

Low Selenium Status and Advanced Kidney Disease

Other research has shown the following relationships [Aaseth 2021]:

  • Patients with advanced renal disease commonly have low serum selenium [Aaseth 2021].
  • Patients on hemodialysis have low serum selenium levels, probably because of diminished selenium retention caused by chronic oxidative stress.
  • End-stage renal disease patients with low serum selenium values (less than 63 mcg/L) have shown an increased mortality risk, as compared to patients with normal or high selenium (above 118 mcg/L).
Conclusion: Optimal Selenium Status Needed for Healthy Kidney Function
  • Mercury, lead, and cadmium exposure are toxic.
  • Mercury, lead, and cadmium can be bound and detoxified by selenium
  • Administration of selenium to individuals exposed to mercury has been shown to reduce the severity of mercury’s toxic effects.
  • Available research data have shown a clear association between the incidence and severity of kidney disease and exposure to mercury, lead, and cadmium [Aaseth 2021].
  • Given that mercury, lead, and cadmium are prevalent in the environment and given that these metals have toxic effects, we need more research into the protective role of selenium compounds [Aaseth 2021].

Aaseth J, Alexander J, Alehagen U, Tinkov A, Skalny A, Larsson A, Crisponi G, Nurchi VM. The Aging Kidney-As Influenced by Heavy Metal Exposure and Selenium Supplementation. Biomolecules. 2021 Jul 22;11(8):1078.

Alehagen, U.; Aaseth, J.; Alexander, J.; Brismar, K.; Larsson, A. Selenium and Coenzyme Q10 supplementation improves renal function in elderly deficient in selenium: observational results and results from a subgroup analysis of a prospective randomised double-blind placebo-controlled trial. Nutrients. 2020;12:3780.

Schomburg L. The other view: the trace element selenium as a micronutrient in thyroid disease, diabetes, and beyond. Hormones (Athens). 2020 Mar;19(1):15-24.

The information presented in this review article is not intended as medical advice and should not be used as such.

30 May 2022

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