Recent advances in clinical studies of selenium supplementation in radiotherapy

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Abstract

Background

Radiotherapy is one of the most important and common therapies for cancer patients. Selenium has been shown to be capable of reducing the side effects of radiotherapy because selenoproteins have anti-oxidative functions against reactive oxygen species that are induced by the radiation. They also function in DNA-repair and cytokine control.

Purpose

We explored the benefits and risks of selenium supplementation in radiotherapy in our previous review to establish guidelines. In the current study, we expanded the search to cover recent advances in clinical studies of selenium supplementation in radiotherapy.

Methods

We conducted an initial screening in the PubMed using the MeSH terms and keywords “selenium”, “radiation”, “therapy”, and “radiotherapy” using the same methodology applied in our previous review. We identified 121 articles published between January 2013 and December 2019. We then identified eight articles (six studies) on selenium and radiotherapy by excluding 113 articles.

Results

In selenium supplementation studies, selenium doses of 300−500 μg/day with duration of 10 days to 6 months were used. Selenium supplementation improved the selenium nutritional conditions of the patients and reduced the side effects of radiotherapy. Selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported.

Conclusion

The results of our previous and current reviews showed that selenium supplementation offers specific benefits for several cancer types treated with radiotherapy. Here, we suggest a new guideline for selenium supplementation in radiotherapy. We recommend determining the selenium status of the patients before radiotherapy, and in cases of deficiency (<100 μg/L serum selenium level), selenium supplement can be beneficial.

Introduction

Radiotherapy is an essential cancer treatment and contributes to the cure or palliation of many cancer patients [1]. Approximately 50 % of patients who are diagnosed with cancer receive radiotherapy during the course of treatment [2]. However, irradiation causes many side effects because of normal tissue injury [3]. These short- and long-term side effects limit treatment tolerability and negatively affect quality of life of the patients [4], and thus it is important to reduce the side effects of radiotherapy [5].

Ionizing radiation results in the immediate generation of reactive oxygen species (ROS). ROS elevate oxidative stress in the cell and cause rapid protein modifications and damage to DNA, RNA, and cell membranes, which causes cell death and tissue damage [5].

In humans, there are 25 selenoproteins with selenocysteine at the active site [6,7]. Glutathione peroxidases (GPxs) are selenoproteins and have strong activities in the reduction of ROS in most tissues [8]. Selenium also exhibits roles in DNA-repair and cytokine control [9].

There is a good association between GPx activities and plasma selenium levels up to 70–100 μg/L, which correlates with selenium intake and reflects short-term changes in the selenium state [9,10]. Therefore, optimizing selenoprotein activities with supplementation has been considered beneficial in the course of treatment [[11], [12], [13]].

In our previous review [14], 16 clinical studies on the supplementation of selenium in radiotherapy between 1987 and 2012 were identified in PubMed. We concluded that selenium supplementation increased the blood selenium levels, improved quality of life, and prevented or reduced the side effects of radiotherapy, and did not reduce the effectiveness of radiotherapy or cause any toxicity. To establish guidelines for selenium supplementation in radiotherapy, we assessed the benefits and risks that were associated with selenium supplementation in radiotherapy through the recent advances in clinical studies.

Section snippets

Material and methods

A flowchart showing our literature search is presented in Fig. 1, applying the same methodology used in our previous review [14]. Briefly, we conducted an initial screening in PubMed using Medical Subject Headings (MeSH) terms and the keywords “selenium”, “radiation”, and “therapy”. The detailed keyword search was as follows: (“selenium” [MeSH Terms] OR “selenium” [All Fields]) AND (“radiotherapy” [Subheading] OR “radiotherapy” [All Fields] OR (“radiation” [All Fields] AND “therapy” [All

Clinical studies on selenium and radiotherapy between 2013 and 2019

Table 1 lists the six studies on selenium and radiotherapy in clinical studies. This table shows the references, number of patients, study designs, types of cancer/disease, radiotherapy delivery methods, supplementation forms, administration doses, samples, measurement methods and mean selenium levels of the studies.

Outlines of studies

The studies were conducted worldwide, including in European and Asian countries, between 2013 and 2018. Studies 4 and 5 included two articles about the same patients. In total, 426

Clinical studies on selenium and radiotherapy between 1987 and 2019

We summarized six clinical studies including three observational studies and three selenium supplementation studies with radiotherapy that were conducted between 2013 and 2019, following our previous review, which summarized 16 clinical studies including 10 observational studies and six selenium supplementation studies from 1987 to 2013 [14]. In our two reviews, there were 22 clinical studies of selenium observation or supplementation and radiotherapy, and 1729 patients were included. The

Conclusion

The results of the current review strongly support the conclusion of our previous review [14] that selenium supplementation with sodium selenite at oral doses ranging 200–500 μg daily increase the blood selenium level, improve quality of life, and prevent or reduce the side effects of radiotherapy, and do not reduce the effectiveness of radiotherapy or cause toxicity. In cancer patients, selenium levels tend to be low and these levels are substantially decreased by recent radiotherapy, sepsis,

Declaration of Competing Interest

The authors report no declarations of interest.

Acknowledgments

This review is based on the materials presented at the International Society for Trace Element Research in Humans (ISTERH 2019) in Bali, Indonesia (September 22-26, 2019). We really appreciate the prompt response by R. Muecke, et al., [12] to our previous review that leads us to the current conclusion.

References (37)

  • M.P. Rayman

    Selenium and human health

    Lancet

    (2012)
  • M.P. Rayman et al.

    Effect of long-term selenium supplementation on mortality: results from a multiple-dose, randomised controlled trial

    Free Radic. Biol. Med.

    (2018)
  • R. Hurst et al.

    Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial

    Am. J. Clin. Nutr.

    (2010)
  • D.E. Citrin

    Recent developments in radiotherapy

    N. Engl. J. Med.

    (2017)
  • G.V. Kryukov et al.

    Characterization of mammalian selenoproteomes

    Science

    (2003)
  • S.J. Hosseinimehr

    The protective effects of trace elements against side effects induced by ionizing radiation

    Radiat. Oncol. J.

    (2015)
  • R. Muecke et al.

    Selenium or No selenium- that is the question in tumor patients: a new controversy

    Integr. Cancer Ther.

    (2010)
  • U. Gröber et al.

    Micronutrients in oncological intervention

    Nutrients

    (2016)
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