Recent advances in clinical studies of selenium supplementation in radiotherapy
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)
- et al.
Evidence-based estimates of the demand for radiotherapy
Clin. Oncol.
(2015) - et al.
Estimating the demand for radiotherapy from the evidence: a review of changes from 2003 to 2012
Radiother. Oncol.
(2014) - et al.
Molecular mechanisms of late normal tissue injury
Semin. Radiat. Oncol.
(2007) - et al.
Mechanisms of normal tissue injury from irradiation
Semin. Radiat. Oncol.
(2017) The importance of selenium to human health
Lancet
(2000)- et al.
Effectiveness of selenium supplements in a low selenium area of China
Am. J. Clin. Nutr.
(2005) - et al.
Pre and post radiotherapy serum oxidant/antioxidant status in breast cancer patients: Impact of age, BMI and clinical stage of the disease
Rep. Pract. Oncol. Radiother.
(2016) - et al.
Protein and micronutrient deficiencies in patients with radiation cystitis and outcome after hyperbaric oxygen therapy
Clin. Nutr. ESPEN
(2018) - et al.
Serum levels of selenium in patients with brain metastases from non-small cell lung cancer before and after radiotherapy
Cancer/Radiothérapie
(2012) - et al.
Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology
Int. J. Radiat. Oncol. Biol. Phys.
(2010)
Selenium and human health
Lancet
Effect of long-term selenium supplementation on mortality: results from a multiple-dose, randomised controlled trial
Free Radic. Biol. Med.
Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial
Am. J. Clin. Nutr.
Recent developments in radiotherapy
N. Engl. J. Med.
Characterization of mammalian selenoproteomes
Science
The protective effects of trace elements against side effects induced by ionizing radiation
Radiat. Oncol. J.
Selenium or No selenium- that is the question in tumor patients: a new controversy
Integr. Cancer Ther.
Micronutrients in oncological intervention
Nutrients
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