Use of Selenium Concentration in Whole Blood, Serum, Toenails, or Urine as a Surrogate Measure of Selenium Intake

ᮀ Our work in dogs has revealed a U-shaped dose response between selenium status and prostatic DNA damage that remarkably parallels the relationship between dietary selenium and prostate cancer risk in men, suggesting that more selenium is not necessarily better. Herein, we extend this canine work to show that the selenium dose that minimizes prostatic DNA damage also maximizes apoptosis-a cancer-suppressing death switch used by prostatic epithelial cells. These provocative findings suggest a new line of thinking about how selenium can reduce cancer risk. Mid-range selenium status (.67-.92 ppm in toenails) favors a process we call "homeostatic housecleaning"-an upregulated apoptosis that preferentially purges damaged prostatic cells. Also, the U-shaped relationship provides valuable insight into stratifying individuals as selenium-responsive or seleniumrefractory, based upon the likelihood of reducing their cancer risk by additional selenium. By studying elderly dogs, the only non-human animal model of spontaneous prostate cancer, we have established a robust experimental approach bridging the gap between laboratory and human studies that can help to define the optimal doses of cancer preventives for large-scale human trials. Moreover, our observations bring much needed clarity to the null results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and set a new research priority: testing whether men with low, suboptimal selenium levels less than 0.8 ppm in toenails can achieve cancer risk reduction through daily supplementation.

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“…This simple conversion ratio yielded results similar to the algorithmic approach described by Longnecker et al (1996).…”

Section: Discussionmentioning

confidence: 56%

Defining the Optimal Selenium Dose for Prostate Cancer Risk Reduction: Insights from the U-Shaped Relationship between Selenium Status, DNA Damage, and Apoptosis

et al. 2009

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“…Overall, a wide range of reproducibility was observed for these electrolytes; ranges of ICCs were 0.29-0.71 for potassium (21-25, 27, 28), 0.64-0.77 for calcium (24,25,27), and 0.49-0.56 for magnesium (25,27) in these previous studies. Reports regarding other urinary markers such as iodine, chloride, and selenium have been sporadic, and none of these urinary markers showed an ICC ,0.4 (21,22,29,30), below which indicates poor reproducibility (31). The current analysis, for the first time to our knowledge, further illustrated that the excretion of sulfate, uric acid, and citrate had fair to excellent reproducibility in 24-h urine samples (31).…”

Section: Discussionmentioning

confidence: 99%

Reproducibility of urinary biomarkers in multiple 24-h urine samples

Sun¹,

Bertrand²,

Franke³

et al. 2017

The American Journal of Clinical Nutrition

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Background: Limited knowledge regarding the reproducibility of biomarkers in 24-h urine samples has hindered the collection and use of the samples in epidemiologic studies. Objective: We aimed to evaluate the reproducibility of various markers in repeat 24-h urine samples. Design: We calculated intraclass correlation coefficients (ICCs) of biomarkers measured in 24-h urine samples that were collected in 3168 participants in the NHS (Nurses' Health Study), NHSII (Nurses' Health Study II), and Health Professionals Follow-Up Study. Results: In 742 women with 4 samples each collected over the course of 1 y, ICCs for sodium were 0.32 in the NHS and 0.34 in the NHSII. In 2439 men and women with 2 samples each collected over 1 wk to $1 mo, the ICCs ranged from 0.33 to 0.68 for sodium at various intervals between collections. The urinary excretion of potassium, calcium, magnesium, phosphate, sulfate, and other urinary markers showed generally higher reproducibility (ICCs .0.4). In 47 women with two 24-h urine samples, ICCs ranged from 0.15 (catechin) to 0.75 (enterolactone) for polyphenol metabolites. For phthalates, ICCs were generally #0.26 except for monobenzyl phthalate (ICC: 0.55), whereas the ICC was 0.39 for bisphenol A (BPA). We further estimated that, for the large majority of the biomarkers, the mean of three 24-h urine samples could provide a correlation of $0.8 with true long-term urinary excretion. Conclusions: These data suggest that the urinary excretion of various biomarkers, such as minerals, electrolytes, most polyphenols, and BPA, is reasonably reproducible in 24-h urine samples that are collected within a few days or #1 y. Our findings show that three 24-h samples are sufficient for the measurement of long-term exposure status in epidemiologic studies.Am J Clin Nutr 2017;105:159-68.

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“…Further, selenium measures based on nail samples have been shown to reflect selenium intake integrated over the previous 6 -12 months and can be used to rank subjects according to long-term dietary selenium intake (Longnecker et al, 1996). Moreover, a single measure has shown moderate reliability over a 6-year period, with a correlation coefficient of 0.48 (Garland et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

A case–control study of selenium in nails and prostate cancer risk in British men

et al. 2004

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In view of the experimental evidence suggesting that the micronutrient selenium reduces prostate cancer risk, we investigated the association between the selenium level in fingernails, a measure of long-term selenium intake, and prostate cancer risk in a case -control study among 656 British men, conducted in 1989British men, conducted in -1992. Nail clippings were taken at the time of recruitment and selenium concentration, measured using neutron activation techniques, was successfully assayed for 300 case -control pairs and varied six-fold among the controls (0.59 p.p.m.; interquartile range, 0.50 -0.71 p.p.m.). Nail selenium concentration was not significantly associated with prostate cancer risk: men in the highest quartile of nail selenium had a slightly increased risk compared with men in the lowest quartile (OR 1.24, 95 CI, 0.73 -2.10); for advanced prostate cancer, men in the highest quartile had a slightly reduced risk compared with men in the lowest quartile (OR 0.78, 95% CI, Selenium is an essential trace element found largely in grains, fish and meat products and has been shown to have antioxidant and other potentially anticarcinogenic properties (Combs and Gray, 1998). Experimental evidence indicates that selenium supplementation can reduce the incidence of viral and chemically induced tumours in animals (Vernie, 1984), including prostate cancer cell lines (Menter et al, 2000).The selenium content in foods varies widely between regions (Levander, 1987) because it is largely determined by the amount of selenium in the soil. Ecological data suggest that regional cancer mortality rates in the United States are inversely correlated with the selenium concentration in plants (Clark et al, 1991), and a randomised controlled trial among skin cancer patients found selenium supplementation of 200 mg day À1 to be associated with a significant 63% reduction in prostate cancer incidence (Clark et al, 1996;Duffield-Lillico et al, 2002). However, little is known about the relationship between the selenium status and prostate cancer risk in the general population.The aim of this study is to investigate the association between nail selenium concentration, a marker of long-term intake, and prostate cancer risk. A subsidiary aim is to examine whether factors that may influence selenium status, such as smoking (Hunter et al, 1990), vitamin E intake (Diplock, 1978) or the aggressiveness of disease at the time of recruitment (Yoshizawa et al, 1998;Goodman et al, 2001) modify the association between selenium concentration and prostate cancer risk. SUBJECTS AND METHODSA population-based case -control study of the association between diet and prostate cancer was established in Britain, between 1989 and 1992, and included 328 men with incident prostate cancer and 328 population-based controls (Key et al, 1997). The study was restricted to white men under the age of 75 years who could speak English and who were well enough to complete a diet interview and give a reasonable history. Identification of cases was by searching a...

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Use of Selenium Concentration in Whole Blood, Serum, Toenails, or Urine as a Surrogate Measure of Selenium Intake

Cited by 186 publications

References 16 publications

Defining the Optimal Selenium Dose for Prostate Cancer Risk Reduction: Insights from the U-Shaped Relationship between Selenium Status, DNA Damage, and Apoptosis

Defining the Optimal Selenium Dose for Prostate Cancer Risk Reduction: Insights from the U-Shaped Relationship between Selenium Status, DNA Damage, and Apoptosis

Reproducibility of urinary biomarkers in multiple 24-h urine samples

A case–control study of selenium in nails and prostate cancer risk in British men

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