Selenium

What Is It?

Selenium, or Se, is a naturally found nonmetal$^{1}$ in rocks and soil, usually chemically combined with sulfide, silver, copper, lead, or nickel minerals$^{2}$. Its radioactive form is additionally used in diagnostic medicine, and the natural element holds a wide array of other applications including pigment production, preparation of pharmaceuticals and antidandruff shampoos, the rubber industry, and electronics$^{2}$. While it may be toxic at high levels$^{3}$, it is an essential trace element (a mineral found in living tissues in small quantities). Selenium is also the only trace element that is genetically encoded to be integrated into proteins as selenocysteine (the 21st amino acid)$^{4}$, which is a natural component of detoxifying enzymes such as glutathione peroxidase and other selenoproteins$^{3}$. Selenium also plays a crucial role in reproduction, thyroid gland function, DNA production, and immunity$^{5}$. Furthermore, through its integration into proteins responsible for fighting oxidative DNA damage as well as a role in bolstering immune responses, selenium has been implicated as a cancer-preventative nutrient, showing associations with reduced risk of prostate, colon, and lung cancer$^{6}$.

What Are Its Other Names?

As selenium is simply an element, it is usually referred to as just selenium, or Se. It may also be referred to as elemental selenium, gray selenium, selenium dust, colloidal selenium, or Selen$^{7}$. However, selenium exists in both inorganic and organic compound forms which will be discussed in the section below. Thus, it may be referred to in this article using the names of its different forms.

What Are Its Forms?

Selenium exists in two forms – inorganic and organic. The inorganic forms include sodium selenite, or Se(IV), and sodium selenate, or Se(VI). They accumulate in plants via selenium-rich soil$^{8}$, and we ultimately ingest inorganic Se in the form of vegetables. The organic forms include selenomethionine (SeMet), selenocysteine (SeCys, the 21st amino acid), Se-methylselenocysteine (SeMeSeCys), γ-glutamyl-Se-methylselenocysteine (γ-glutamyl-SeMeSeCys), and Methylselenol (MeSeH). The former three are amino acids, the fourth is a dipeptide, and the latter is an important selenium metabolite that plays a critical role in cancer prevention$^{9}$, as will be discussed in the “How Does It Work?”section. Furthermore, selenium is often available in multivitamin or mineral supplement form, and is commonly found as selenomethionine in selenium-enriched yeast which are grown in high-selenium media$^{5}$.

What Foods Have It?

The richest food sources of selenium are Brazil nuts, seafood, and organ meats. It is also found in muscle meats, dairy products, and grains. The table below summarizes the data on selenium in commonly consumed foods, as recorded by the U.S. Department of Agricultural Research Service (ARS)$^{5}$.

* The WHO stresses that doses beyond 400 µg per day are not safe for daily consumption, as symptoms of selenosis, as discussed in the “What Are Its Main Drawbacks?” section, begin to set in at high doses. Note that 100 grams of Brazil nuts provide significantly greater quantities of selenium than the safe daily dosage limit, and 100 grams of yellowfin tuna exceeds the daily recommended value (DV) for adults and children above the age of 14, which is 55 micrograms$^{5}$ (µg). Care must be taken to not over-consume these food items, although intermittent consumption of tuna remains within safe limits. Note that selenium is found predominantly as inorganic selenite or selenate and organic selenomethionine or selenocysteine$^{5}$. The human body absorbs more than 90% of Se from selenomethionine$^{10}$, but only 50% from selenite$^{11}$. Thus, bioavailability of Se, meaning the proportion of Se that will reach target tissues and exert its effects, will vary depending on the form it is ingested as. This is also affected by malabsorption due to infection with HIV$^{12}$ , as well as use of dialysis machines due to kidney disease$^{13}$.

What Are Its Main Benefits?

Selenium deficiency affects 0.5-1 billion people worldwide and has been linked to a variety of disorders of the immune, cardiovascular, endocrine, and musculoskeletal system$^{9}$. Studies have also linked selenium consumption to reduced cancer risk, although the data is conflicting and further research is needed to definitively confirm the association. This section will discuss the various health benefits investigated with respect to selenium consumption. Regulating Inflammation Selenium has been found to regulate unwanted immune responses and manage chronic inflammation$^{14}$. One study showed that plasma selenium levels were associated with a reduced incidence of the clinical signs of systemic inflammatory response syndrome (SIRS) such as pneumonia and organ system failure$^{15}$, and supplementation with 1000 μg daily for 14 days was found to mitigate mortality from SIRS$^{16}$. Immune Modulation Selenoproteins have been demonstrated to inhibit non-specific immune system activity as well as stimulate the activity of cells that play key roles in immunity$^{8}$. Selenium stimulates the following immune cells: helper T cells, which are essential to the adaptive immune response; cytotoxic T cells, which target virally-infected or cancerous cells, also as part of the adaptive immune response; and natural killer (NK) cells, which are innate immune cells also responsible for eliminating virally-infected or cancerous cells$^{17,18}$. This occurs at low doses and leads to improved pathogen clearance abilities. At high doses, however, immune responses are dampened, potentially assisting with the reduced morbidity of autoimmune diseases observed with selenium intake. For instance, one study found that selenium yeast supplementation in patients with Hashimoto’s thyroiditis, an autoimmune disease involving the thyroid gland, led to an increase in activity of regulatory T cells (Tregs), which can mitigate the activity of autoantibodies attacking self-tissues and essentially dampen excessive immune responses$^{19}$. Thyroid Function Selenium has been established as an essential micronutrient in the upkeep of thyroid gland function$^{5,9}$. As selenocysteine, it is part of the active site of iodothyronine deiodinase, which converts thyroxine (T4) to triiodothyronine (T3), the thyroid hormone responsible for metabolic control, growth support, brain maturation during prenatal development, and female reproductive function$^{20}$. The thyroid is the organ with the highest concentration of selenium in adults$^{21}$, and aside from its involvement in hormone metabolism, selenium also contributes to the protection of the thyroid from reactive oxygen species (ROS) produced during thyroid hormone production, via its integration in the enzyme glutathione peroxidase (which helps degrade ROS). Selenium deficiency has been linked to hypothyroidism$^{22}$ – in fact, it was proposed as a factor linked to the incidence of myxedematous endemic cretinism, a condition described in Zaire characterized by developmental problems, hypothyroidism, and intellectual disability$^{23}$. Furthermore, selenium intake has been associated with better outcomes in patients with autoimmune thyroiditis$^{24,25}$, through the mechanisms described previously. Prevention of Cardiovascular Disease & Keshan Disease Selenium consumption has been definitively linked with decreased incidence of Keshan disease and other disorders of the cardiovascular system. Keshan disease is a form of dilated cardiomyopathy diagnosed only in selenium-deficient children and is the only human disease that has been definitively associated with selenium deficiency$^{26}$. Low selenium intake or low blood and hair concentrations of selenium combined with infection or other body stressors can lead to the development of this disease. Furthermore, selenium has been linked with a decreased risk of developing cardiovascular disease – in fact, selenium deficiency was linked with higher incidence of myocardial infarctions (heart attacks), heart failure, coronary heart disease, and atherosclerosis$^{27}$. Prevention of Kashin-Beck Disease & Muscle Disorders Selenium has also been associated with reduced risk of Kashin-Beck disease and has been similarly implicated in the upkeep of skeletal muscle health. Kashin-Beck disease is an osteochondropathy (disease of the cartilage) endemic to low-selenium areas in northeastern-southwestern China$^{28}$, affecting predominantly pre-adolescent or adolescent individuals. It is associated with low dietary selenium. On another note, skeletal muscle represents a major site of selenium storage$^{29}$, and selenium deficiency has been linked to skeletal muscle disorders characterized by pain, weakness, and fatigue$^{30}$. This was explained by lower glutathione peroxidase activity, and patient conditions improved in response to selenium administration$^{31}$. Cancer Prevention Several epidemiological and clinical studies have emphasized the role that low dietary levels of selenium play in preventing numerous cancers, including prostate, lung, and colon cancers. Sodium selenite, L-selenomethionine, and Se-methylselenocysteine have been identified as forms of selenium that can exert cancer-preventative effects$^{17}$. Increased selenium levels have been associated with decreased cancer diagnoses, including, lung, prostate, and colon cancer$^{6}$. Reduced plasma selenium content was observed in such cancer patients$^{32}$, and it additionally predicted a higher risk of thyroid cancer$^{9}$. Note that while selenium exerts cancer-preventing effects as an antioxidant via selenoproteins combatting ROS formation at low levels, it is a pro-oxidant at high levels$^{17}$, with the potential to act as either a cancer-promoting agent or, in a controlled setting, a cancer-treating agent. Furthermore, different forms of selenium exhibit different levels of activity – for instance, while L-selenomethionine shows no cancer-preventative activity, selenized yeast, containing methyl-selenocysteine, has been demonstrated to be an effective cancer-preventative agent$^{33}$. Cancer Treatment Selenium has additionally been implicated as a cancer-treating agent at high doses in controlled settings. At high levels, selenium acts as a pro-oxidant, inducing the production of reactive oxygen species (ROS) that can stimulate apoptosis (programmed cell death) in cancer cells$^{17}$. It has thus been harnessed as a cancer-treating agent, although relatively few studies have researched this. In one study, patients with different types of leukemia were treated with high doses of selenocystine (an average dose 100 mg/day was administered for 10-57 days) and displayed significant drops in tumor cell counts alongside increased sensitivity to other forms of cancer treatment such as 6-mercaptopurine$^{34}$. While such high doses led to symptoms of gastrointestinal upset and alopecia, they were reversible and no clear damage to the liver or kidneys was observed. Furthermore, in one randomized controlled trial, 25 women with cervical intraepithelial neoplasia were supplemented with 200 µg of selenium daily for 6 months. This resulted in 88% of women experiencing a regression of their condition, as opposed to 56% in the placebo group$^{35}$. The treatment group also exhibited significant improvements in plasma antioxidant capacity (measured by higher levels of the antioxidant glutathione). Aside from directly treating cancer, selenium has also been observed to improve general health outcomes in conjunction with existing cancer therapies. Selenium was found to reduce intracranial pressure in 76% of brain tumor patients enrolled in one study$^{36}$, and in another study, sodium selenite administration was inversely correlated with the development of edema in patients undergoing surgery for oral tumors.

What Are Its Main Drawbacks?

High levels of dietary selenium have been shown in numerous studies to lead to selenosis, reduced thyroid function, cancer development, and type II diabetes mellitus. It is incredibly important to be mindful not to over-consume foods high in selenium, as discussed in the “What Foods Have It?” section, to avoid the development of associated adverse effects. High levels of selenium, upwards of 850 µg daily, may lead to selenosis, and 400 µg has been proposed to be an upper limit of safe consumption$^{37}$. Selenium toxicity manifests itself in the form of breathing difficulties, tremors, kidney failure, and myocardial infarctions, in addition to brittle hair and nails and disorders of the nervous system$^{12}$. In fact, selenium has an incredibly narrow safe range of consumption – it is necessary for human biological function at low levels, but toxic at high doses$^{38}$. Note that inorganic forms exhibit higher toxicity than organic forms of selenium. Organic forms are more easily excreted from the body, whereas inorganic forms may produce damaging free radicals$^{4}$. Furthermore, patients on hemodialysis are at increased risk of selenium deficiency due to removal of the element through dialysis as well as low diet intake from dietary restrictions due to their condition$^{13}$. Patients with HIV also suffer from malabsorption and diarrhea, leading to low bioavailability of ingested selenium to exert its necessary functions on tissues$^{12}$. Particularly high levels of selenium were additionally associated with reduced triiodothyronine (T3) levels, diminished function of natural killer immune cells, and liver damage$^{39}$. In fact, selenium toxicity may contribute to cancer (as opposed to lower levels of selenium consumption, which has demonstrated a cancer-preventative effect), potentially due to the production of free radicals causing DNA damage as well as damage to the integrity of proteins responsible for DNA repair$^{40}$, as seen in yeast cell cultures. In some randomized controlled trials, selenium supplementation was associated with higher risk of high-grade prostate cancer, dermatitis, alopecia, and type II diabetes mellitus (T2DM)$^{38}$.

How Does It Work?

Selenium exerts both cancer-preventative and cancer-treating effects through both anti-oxidative mechanisms at low levels and pro-oxidative mechanisms at high-levels. It protects against heavy metals, acts to synergistically enhance the tumor-fighting properties of chemotherapeutics, and activates caspases involved in programmed cell death, thereby inhibiting malignant cell growth.

What Are Its Mechanisms of Action?

Cancer-Preventative

1. Combatting Oxidative Stress: Selenium integrates itself into proteins that act to combat oxidative stress and prevent DNA damage and subsequent development of malignant cells. Healthy cells are normally in a state of redox balance whereby reductive and oxidative processes effectively counter one another. However, when the rate of reduction is unable to cope with the rate of oxidation in the body, oxidative stress occurs, and this can contribute to DNA and protein damage conducive to malignant cell development$^{41}$. Selenium is an integral component to the major selenoprotein glutathione peroxidase (GPx), which plays a key role in combatting the formation of ROS and subsequent DNA damage$^{3}$. Humans have 5 selenoprotein glutathione peroxidases$^{3}$, which specifically protect against the oxidation of lipid membranes$^{42}$ by reducing hydrogen peroxide (an important ROS) using reduced glutathione. While selenoproteins directly counter oxidative stress, others mediate the regeneration of vitamins C & E and coenzyme Q10, all of which are antioxidants capable of protecting cells from oxidative damage$^{43}$.
2. Activation of Tumor Suppressor Proteins: Some selenoproteins act to either directly suppress tumor development or enhance the activity of tumor suppressor proteins and further reduce the risk of cancer development. TR1, a selenoprotein, is an important redox regulator that regulates the redox state of thioredoxin, an important player in the cell’s antioxidant defense system. TR1 has been established as an activator of p53, a tumor suppressor protein$^{44}$. In fact, in mice lacking TR1 in liver cells, tumor formation was enhanced dramatically by chemical carcinogens, compared to control$^{45}$. However, TR1 has also been found at high levels in cancer cells, and removal of TR1 in lung cancer cells led to a reduction in tumor progression$^{46}$. Tumor Suppression via Selenoprotein 15 Selenoprotein 15, or Sep15, is proposed to be an oxidoreductase regulated by endoplasmic reticulum (ER) stress. It functions to form a complex with UDP-glucose:glycoprotein glucosyltransferase, or UGT, and subsequently contribute to protein quality control$^{3}$. It has been strongly implicated as having a role in tumor suppression$^{3}$. Lung cancer patients were found to have diminished Sep15 expression$^{47}$, and a similar reduction was found in malignant lung, breast, prostate, and liver tissues$^{48}$. Note however that Sep15 was found to be highly expressed in colon cancer cell lines – its redox properties might be harnessed to protect cancer cells and promote their growth. Thus, the effect that this selenoprotein has on cells may be dependent on a variety of factors that are yet to be elucidated.
3. Protection Against Heavy Metals and Chemical Carcinogens: Selenoproteins have been shown to bind to heavy metals in the body and thereby prevent them from exerting carcinogenic effects. Heavy metals include arsenic, cadmium, chromium, and nickel and have been classified as group 1 carcinogens$^{49}$. Human exposure often occurs through environmental contamination, as electronic waste disposal leads to heavy metal contamination via erosion of contaminated soils into water sources$^{50}$. They disrupt tumor suppressor proteins and DNA damage repair processes$^{49}$ as well as cause oxidative damage in cells$^{51}$, providing optimal conditions for malignant cell development. Selenoprotein P (SEPP1) can chelate, or bind to, heavy metals, forming nontoxic selenium-metal complexes and preventing them from transforming tissues$^{9}$. On another note, selenium-enriched garlic fed to rats was shown to enhance the transcription of genes encoding phase II xenobiotic enzymes (such as glutathione-S-transferase and UDP-glucuronyltransferase), which detoxify chemical carcinogens$^{52}$.
4. Induction of Cancer Cell Death: Selenium has been shown to induce cancer cell death by selectively activating apoptosis (programmed cell death) in these cells. Selenium dioxide and selenite, but not selenate, were found to induce apoptosis in human oral squamous carcinoma cells$^{53}$. In this study, researchers found that treatment with 100 μM selenium dioxide or sodium selenite for 72 hours led to caspase-3-like and caspase-9-like activation of apoptosis$^{53}$. Caspases are proteins that, once cleaved and activated, kickstart the process of programmed cell death, which is particularly important in the elimination of mutant cells in the body$^{54}$. Furthermore, at medium to high micromolar concentrations, Se-methylselenocysteine (MSC) has been shown to inhibit the proliferation of human oral squamous carcinoma, lung carcinoma, and breast carcinoma cells. It triggered the activity of the pro-apoptotic caspases 3, 8, and 9, and the proportion of apoptotic cells was increased with selenium treatment$^{55}$.
5. Inhibition of Cancer Cell Proliferation: Selenium has demonstrated the ability to inhibit the capacity of cancer cells to divide and spread through a variety of mechanisms. Selenium treatment was shown to inhibit the expression of vascular endothelial growth factor and exhibited antiangiogenic effects$^{55}$, meaning it prevented malignant cells from invading into nearby tissues$^{56}$ and developing a blood vessel system for nourishment$^{57}$, respectively. Reduced levels of phosphorylated Akt, which promotes cell growth and proliferation$^{58}$, were also observed with selenite and MSC treatment of cancer cell lines$^{55}$. Furthermore, administered selenium compounds are metabolized in the body to methylselenol, which exerts the most potent anticancer effects in the body$^{59}$. In one study, methylselenol was shown to inhibit cancer cell growth by upregulating cyclin-dependent kinase inhibitor 1C, which inhibits the cyclin-dependent kinases (proteins) responsible for driving forward cell proliferation. It also inhibits the ERK1/2 pathway responsible for cell proliferation and arrests cells in the G1 phase of the cell cycle, preventing mitosis and thereby inhibiting malignant cell growth and invasion$^{59}$.

Cancer-Treating

1. Inducing Oxidative Stress: At high levels, selenium can generate oxidative stress, a property that can be harnessed to destroy cancer cells. It is important to understand that while malignant cells may be borne out of oxidative damage occurring in healthy cells (in fact, they exhibit relatively high basal levels of ROS), they have a lower tolerance for additional oxidative damage than healthy cells do$^{60}$. This vulnerability can be harnessed in cancer-fighting therapeutics, and selenium’s ability to produce ROS at high doses renders it a potent cancer-treating agent. In one study, sodium selenite was introduced to human larynx epithelioma cancer cells (Hep-2) and caused oxidative stress, subsequently suppressing DNA synthesis and triggering DNA damage. This activated the tumor-suppressive p53 protein pathway as well as the p38 pathway which led to apoptosis (programmed cell death) of these cancer cells$^{61}$.
2. Synergistic Effects with Chemotherapies: Selenium can additionally enhance the cancer-fighting ability of chemotherapeutic drugs. Organic selenium has been shown to enhance the tumor-fighting effects of the chemotherapeutic compounds irinotecan (in colon carcinoma tissue) and tamoxifen (in breast cancer tissue) in a dose-dependent manner$^{62}$. Additionally, selenium was shown to selectively protect non-cancerous tissues against the toxicity induced by chemotherapeutics. This means that upon selenium administration, chemotherapeutic drugs were toxic only to cancer cells, and not healthy ones.

What Are Typical Doses and Durations?

Dosage

*RDA= recommended dietary allowances (µg) The World Health Organization (WHO) recommends a dose of 26-35 µg/daily for necessary biological functions, whereas the National Institute of Health recommends a daily value of 55 µg daily for individuals above the age of 14 years$^{5}$. A maximum dose of 400 µg was also stressed by the WHO to avoid the development of selenosis. For cancer-prevention and other purposes, low levels of selenium are necessary to exert beneficial biological effects. On the other hand, for cancer-treating purposes, higher levels may be utilized, but only in a controlled clinical setting. For instance, one study investigated the administration of 200 µg of selenium as selenized yeast for 6 months and found that the dose was well-tolerated and contributed to improved metabolic profiles and tumor status in patients with cervical intraepithelial neoplasia$^{35}$. Duration Considering the necessity of low levels of selenium in the diet, lifelong ingestion of this micronutrient at the recommended dosage is essential to the maintenance of thyroid, skeletal muscle, and immune function. A high-dose 1000 µg was investigated for 14 days in the previously mentioned study on systemic inflammation and exhibited no side-effects$^{16}$, but considering the WHO’s upper limit on selenium consumption, this would not be sustainable dose for daily intake, and is only safe in controlled environments and for short periods of time. Two randomized controlled trials assessed the safety of selenium at different doses and durations. One investigated it in patients with chronic lymphocytic leukaemia and solid malignancies and found that 400 μg per day of sodium selenite, seleno-L-methionine, or Se-methylselenocysteine for 8 weeks is safe in cancer patients, but higher doses are likely needed to activate pharmacological effects$^{63}$. The second trial was conducted for 12 months in patients with prostate cancer and found that doses above 400 mg/day can likely be given for extended periods without serious toxicity, although toxic effects were seen in patients given 3200 mg of selenium per day$^{64}$.

Summary of Data

Cancer Prevention A total of 38 randomized clinical trials that investigated selenium as a cancer-preventative nutrient were identified on PubMed. The data from the trials is summarized below.

📄 Detailed Selenium (administered alone for cancer prevention) human clinical trial study notes analyzed by Anticancer.ca

A total of 5 randomized clinical trials that investigated selenium in conjunction with vitamin E as a cancer-preventative nutrient combination were identified on PubMed. The data from the trials is summarized below.

📄 Detailed Selenium (administered with vitamin E for cancer prevention) human clinical trial study notes analyzed by Anticancer.ca

A total of 2 randomized clinical trials that investigated selenium in conjunction with vitamin E and vitamin C as a cancer-preventative nutrient combination were identified on PubMed. The data from the trials is summarized below.

📄 Detailed Selenium (administered with vitamins C & E for cancer prevention) human clinical trial study notes analyzed by Anticancer.ca

A total of 1 randomized clinical trial that investigated selenium in conjunction with lycopene as a cancer-preventative nutrient combination was identified on PubMed. The data from the trial is summarized below.

📄 Detailed Selenium (administered with lycopene for cancer prevention) human clinical trial study notes analyzed by Anticancer.ca

A total of 1 randomized clinical trial that investigated selenium in conjunction with probiotic supplements as a cancer-preventative combination was identified on PubMed. The data from the trial is summarized below.

📄 Detailed Selenium (administered with probiotics for cancer prevention) human clinical trial study notes analyzed by Anticancer.ca

A total of 1 randomized clinical trial that investigated selenium in conjunction with allitridum as a cancer-preventative combination was identified on PubMed. The data from the trial is summarized below.

📄 Detailed Selenium (administered with allitridum for cancer prevention) human clinical trial study notes analyzed by Anticancer.ca

A total of 18 randomized clinical trials that investigated selenium in conjunction with a combination of several other nutrients, including vitamins and minerals, for cancer prevention were identified on PubMed. The data from the trials is summarized below.

📄 Detailed Selenium (administered with other nutrients for cancer prevention) human clinical trial study notes analyzed by Anticancer.ca

Cancer Treatment A total of 22 randomized clinical trials and 3 follow-ups that investigated selenium as a cancer-therapeutic agent were identified on PubMed. The data from the trials is summarized below.

📄 Detailed Selenium (administered for cancer therapy) human clinical trial study notes analyzed by Anticancer.ca

A total of 3 randomized clinical trials that investigated selenium in conjunction with vitamin E as a cancer-therapeutic nutrient combination were identified on PubMed. The data from the trials is summarized below.

📄 Detailed Selenium (administered with vitamin E for cancer therapy) human clinical trial study notes analyzed by Anticancer.ca

A total of 2 randomized clinical trials that investigated selenium in conjunction with vitamin E and vitamin C as a cancer-therapeutic nutrient combination were identified on PubMed. The data from the trials is summarized below.

📄 Detailed Selenium (administered with vitamins C & E for cancer therapy) human clinical trial study notes analyzed by Anticancer.ca

A total of 1 randomized clinical trial that investigated selenium in conjunction with silymarin as a cancer-therapeutic nutrient combination was identified on PubMed. The data from the trial is summarized below.

📄 Detailed Selenium (administered with silymarin for cancer therapy) human clinical trial study notes analyzed by Anticancer.ca

A total of 1 randomized clinical trial that investigated selenium in conjunction with zinc as a cancer-therapeutic nutrient combination was identified on PubMed. The data from the trial is summarized below.

📄 Detailed Selenium (administered with zinc for cancer therapy) human clinical trial study notes analyzed by Anticancer.ca

A total of 1 randomized clinical trial that investigated selenium in conjunction with vitamin C, vitamin E, β-carotene, and zinc as a cancer-therapeutic nutrient combination was identified on the PubMed database. The data from the trial is summarized below.

📄 Detailed Selenium (administered with several other nutrients for cancer therapy) human clinical trial study notes analyzed by Anticancer.ca

A total of 2 randomized clinical trials that investigated the tolerance of selenium as a cancer-therapeutic nutrient were identified on the PubMed database. The data from the trials is summarized below.

📄 Detailed Selenium (tested for tolerance as a cancer therapy) human clinical trial study notes analyzed by Anticancer.ca

References

1. selenium atom (CHEBI:27568).ChEBI https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:27568.
2. Selenium | Toxic Substances | Toxic Substance Portal | ATSDR.Center for Disease Control and Preventionhttps://wwwn.cdc.gov/TSP/substances/ToxSubstance.aspx?toxid=28.
3. Hatfield, D. L., Tsuji, P. A., Carlson, B. A. & Gladyshev, V. N. Selenium and selenocysteine: roles in cancer, health, and development.Trends in Biochemical Sciences39, 112–120 (2014).
4. Giuseppe Genchi, Graziantonio Lauria, Alessia Catalano, Maria Stefania Sinicropi, & Alessia Carocci. Biological Activity of Selenium and Its Impact on Human Health - PubMed.Int J Mol Sci 24, 2633 (2023).
5. Office of Dietary Supplements - Selenium.https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/ (2021).
6. Larry C. Clark, Gerald F. Combs, & Bruce W. Turnbull. Effects of Selenium Supplementation for Cancer Prevention in Patients With Carcinoma of the Skin: A Randomized Controlled Trial | JAMA | JAMA Network.JAMA 276, 1957–1963 (1996).
7. PubChem. Selenium.https://pubchem.ncbi.nlm.nih.gov/compound/6326970.
8. Hariharan, S. & Dharmaraj, S. Selenium and selenoproteins: it’s role in regulation of inflammation - PubMed.Inflammopharmacology 28, 667–695 (2020).
9. Kieliszek, M. & Błażejak, S. Current Knowledge on the Importance of Selenium in Food for Living Organisms: A Review - PubMed.Molecules 21, 609 (2016).
10. Selenium.https://go.drugbank.com/drugs/DB11135.
11. Institute of Medicine (US) Panel on Dietary Antioxidants and Related Compounds. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids - PubMed. National Academies Press (US) (2000) doi:10.17226/9810.
12. Office of Dietary Supplements - Selenium.https://ods.od.nih.gov/factsheets/Selenium-Consumer/ (2021).
13. Marcello Tonelliet al.Trace elements in hemodialysis patients: a systematic review and meta-analysis - PMC. BMC Med 7, (2009).
14. Zhi Huang, Aaron H. Rose, & Peter R. Hoffmann. The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities - PMC.Antioxid Redox Signal16, 705–743 (2012).
15. Xavie Forcevilleet al. Selenium, systemic immune response syndrome, sepsis, and out... : Critical Care Medicine. Critical Care Medicine 26, 1536–1544 (1998).
16. Angstwurm, M. W. A.et al.Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med 35, 118–126 (2007).
17. Razaghi, A., Poorebrahim, M., Sarhan, D. & Björnstedt, M. Selenium stimulates the antitumour immunity: Insights to future research.Eur J Cancer 155, 256–267 (2021).
18. Leonidas H. Duntas & Salvatore Benvenga. Selenium: an element for life | Endocrine.Endocrine 48, 765–775 (2014).
19. Effect of selenium on thyroid autoimmunity and regulatory T cells in patients with Hashimoto’s thyroiditis: A prospective randomized‐controlled trial - PMC.Clin Transl Sci14, 1390–1402 (2021).
20. Shahid, M. A., Ashraf, M. A. & Sharma, S. Physiology, Thyroid Hormone. inStatPearls(StatPearls Publishing, 2023).
21. Ventura, M., Melo, M. & Carrilho, F. Selenium and Thyroid Disease: From Pathophysiology to Treatment.Int J Endocrinol 2017, 1297658 (2017).
22. Fordyce, F. M. Selenium Deficiency and Toxicity in the Environment | SpringerLink. inEssentials of Medical Geology375–416 (2012).
23. Goyens, P., Golstein, J., Nsombola, B., Vis, H. & Dumont, J. E. Selenium deficiency as a possible factor in the pathogenesis of myxoedematous endemic cretinism - PubMed.Acta Endocrinol (Copenh)114, 497–502 (1987).
24. Gärtner, R., Gasnier, B. C. H., Dietrich, J. W., Krebs, B. & Angstwurm, M. W. A. Selenium Supplementation in Patients with Autoimmune Thyroiditis Decreases Thyroid Peroxidase Antibodies Concentrations.The Journal of Clinical Endocrinology & Metabolism87, 1687–1691 (2002).
25. Turker, O., Kumanlioglu, K., Karapolat, I. & Dogan, I. Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses in: Journal of Endocrinology Volume 190 Issue 1 ().Journal of Endocrinology190, 151–156 (2006).
26. Observations on effect of sodium selenite in prevention of Keshan disease.Chin Med J (Engl)92, 471–476 (1979).
27. Briana K. Shimada, Naghum Alfulaij, & Lucia A. Seale. The Impact of Selenium Deficiency on Cardiovascular Function - PMC.Int J Mol Sci22, 10713 (2021).
28. Pedrero, Z. & Madrid, Y. Novel approaches for selenium speciation in foodstuffs and biological specimens: A review.Analytica Chimica Acta634, 135–152 (2009).
29. Pascual, A. & Aranda, A. Thyroid hormone receptors, cell growth and differentiation.Biochim Biophys Acta1830, 3908–3916 (2013).
30. Chariot, P. & Bignani, O. Skeletal muscle disorders associated with selenium deficiency in humans.Muscle Nerve27, 662–668 (2003).
31. Rederstorff, M., Krol, A. & Lescure, A. Understanding the importance of selenium and selenoproteins in muscle function - PMC.Cel Mol Life Sci63, 52–59 (2005).
32. Wasowicz, W., Gromadzinska, J., Rydzynski, K. & Tomczak, J. Selenium status of low-selenium area residents: Polish experience.Toxicology Letters 137, 95–101 (2003).
33. Aseel O. Rataan, Sean M. Geary, Yousef Zakharia, Youcef M. Rustum, & Aliasger K. Salem. Potential Role of Selenium in the Treatment of Cancer and Viral Infections - PMC.Int J Mol Sci 23, 2215.
34. Selenius, M., Rundlöf, A.-K., Olm, E., Fernandes, A. P. & Björnstedt, M. Selenium and the Selenoprotein Thioredoxin Reductase in the Prevention, Treatment and Diagnostics of Cancer.Antioxidants & redox signaling 12, 867–880 (2010).
35. Karamali, M., Nourgostar, S., Zamani, A., Vahedpoor, Z. & Asemi, Z. The favourable effects of long-term selenium supplementation on regression of cervical tissues and metabolic profiles of patients with cervical intraepithelial neoplasia: a randomised, double-blind, placebo-controlled trial.Br J Nutr 114, 2039–2045 (2015).
36. Zimmermann, T.et al.Reduction of postoperative lymphedema after oral tumor surgery with sodium selenite. Biol Trace Elem Res 106, 193–203 (2005).
37. G Yang & R Zhou. Further observations on the human maximum safe dietary selenium intake in a seleniferous area of China - PubMed.J Trace Elem Electrolytes Health Dis8, 159–165 (1994).
38. Marco Vincetiet al. Selenium for preventing cancer - PubMed. Cochrane Database Syst Rev 1, (2018).
39. Miguel Navarro-Alarcon & Carmen Cabrera-Vique. Selenium in food and the human body: a review - PubMed.Sci Total Environ400, 115–141 (2008).
40. Lucia Letavayová, Danusa Vlasáková, Julian E Spallholz, Jela Brozmanová, & Miroslav Chovanec. Toxicity and mutagenicity of selenium compounds in Saccharomyces cerevisiae - PubMed.Mutat Res638, 1–10 (2008).
41. Halliwell, B. Biochemistry of oxidative stress.Biochemical Society Transactions 35, 1147–1150 (2007).
42. Jovanović, I. B.et al. Effects of Different Amounts of Supplemental Selenium and Vitamin E on the Incidence of Retained Placenta, Selenium, Malondialdehyde, and Thyronines Status in Cows Treated with Prostaglandin F2α for the Induction of Parturition. J Vet Med 2013, 867453 (2013).
43. Hatfield, D. L., Yoo, M.-H., Carlson, B. A. & Gladyshev, V. N. Selenoproteins that function in cancer prevention and promotion.Biochimica et Biophysica Acta (BBA) - General Subjects1790, 1541–1545 (2009).
44. Urig, S. & Becker, K. On the potential of thioredoxin reductase inhibitors for cancer therapy.Seminars in Cancer Biology16, 452–465 (2006).
45. Carlson, B. A.et al.Thioredoxin reductase 1 protects against chemically induced hepatocarcinogenesis via control of cellular redox homeostasis. Carcinogenesis 33, 1806–1813 (2012).
46. Min-Hyuk Yoo, Xue-Ming Xu, Bradley A. Carlson, Vadim N. Gladyshev, & Dolph L. Hatfield. Thioredoxin Reductase 1 Deficiency Reverses Tumor Phenotype and Tumorigenicity of Lung Carcinoma Cells*.Journal of Biological Chemistry281, 13005–13008 (2006).
47. E Jablonska, J Gromadzinska, & W Sobala,et al.. Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism.Eur J Nutr 47, 47–54 (2008).
48. D.L. Hatfield. Selenium: Its Molecular Biology and Role in Human Health | SpringerLink. in 345–354 (Springer Science+Business Media, 2001).
49. Hyun Soo Kim, Yeo Jin Kim, & Young Rok Seo. An Overview of Carcinogenic Heavy Metal: Molecular Toxicity Mechanism and Prevention - PMC.J Cancer Prev20, 232–240 (2015).
50. Tchounwou, P. B., Yedjou, C. G., Patlolla, A. K. & Sutton, D. J. Heavy Metals Toxicity and the Environment - PMC.101, 133–164 (2012).
51. Ercal, N., Gurer-Orhan, H. & Aykin-Burns, N. Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage - PubMed.Curr Top Med Chem1, 529–539 (2001).
52. Ip, C. & Lisk, D. J. Modulation of phase I and phase II xenobiotic-metabolizing enzymes by selenium-enriched garlic in rats - PubMed.Nutr Cancer28, 184–188 (1997).
53. Takahashi, M., Sato, T., Shinohara, F., Echigo, S. & Rikiishi, H. Possible role of glutathione in mitochondrial apoptosis of human oral squamous cell carcinoma caused by inorganic selenium compounds.International Journal of Oncology27, 489–495 (2005).
54. McIlwain, D. R., Berger, T. & Mak, T. W. Caspase Functions in Cell Death and Disease - PMC.Cold Spring Harb Perspect Biol5, (2013).
55. Suzuki, M., Endo, M., Shinohara, F., Echigo, S. & Rikiishi, H. Differential apoptotic response of human cancer cells to organoselenium compounds | Cancer Chemotherapy and Pharmacology.Cancer Chemother Pharmacol66, 475–484 (2009).
56. Yang, Y. & Cao, Y. The impact of VEGF on cancer metastasis and systemic disease - ScienceDirect.Seminars in Cancer Biology86, 251–261 (2022).
57. Nishida, N., Yano, H., Nishida, T., Kamura, T. & Kojiro, M. Angiogenesis in Cancer.Vasc Health Risk Manag2, 213–219 (2006).
58. Abeyrathna, P. & Su, Y. The Critical Role of Akt in Cardiovascular Function - PMC.Vascul Pharmacol.74, 38–48 (2015).
59. Zeng, H., Wu, M. & Botnen, J. H. Methylselenol, a selenium metabolite, induces cell cycle arrest in G1 phase and apoptosis via the extracellular-regulated kinase 1/2 pathway and other cancer signaling genes.J Nutr139, 1613–1618 (2009).
60. Wondrak, G. T. Redox-Directed Cancer Therapeutics: Molecular Mechanisms and Opportunities - PMC.Antioxid Redox Signal11, 3013–3069 (2009).
61. Rudolf, E., Rudolf, K. & Cervinka, M. Selenium activates p53 and p38 pathways and induces caspase-independent cell death in cervical cancer cells.Cell Biol Toxicol24, 123–141 (2008).
62. Zengshan Liet al.Combination of methylselenocysteine with tamoxifen inhibits MCF-7 breast cancer xenografts in nude mice through elevated apoptosis and reduced angiogenesis | Breast Cancer Research and Treatment. Breast Cancer Res Treat 118, 33–43 (2009).
63. Evans, S. O., Jacobson, G. M., Goodman, H. J. B., Bird, S. & Jameson, M. B. Comparative Safety and Pharmacokinetic Evaluation of Three Oral Selenium Compounds in Cancer Patients.Biol Trace Elem Res189, 395–404 (2019).
64. Reid, M. E.et al.A report of high-dose selenium supplementation: response and toxicities. J Trace Elem Med Biol 18, 69–74 (2004).

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• Selenium
• What Is It?
• What Are Its Other Names?
• What Are Its Forms?
• What Foods Have It?
• What Are Its Main Benefits?
• What Are Its Main Drawbacks?
• How Does It Work?
• What Are Its Mechanisms of Action?
• What Are Typical Doses and Durations?
• Summary of Data
• References
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