29.10: Questions Remain (25b.10)
- Page ID
- 117331
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Understanding of Se, the most recently recognized essential nutrient, continues to grow. It has become clear that consequences of Se deprivation are typically sub-clinical in nature, requiring other precipitating factors (deficiencies of vitamin E, iodine and/or protein; exposure to viruses, or carcinogens) to reveal physiological effects of sub-optimal expression of selenoenzymes. It is also apparent that supranutritional intakes of Se, at which selenoenzymes are fully expressed, can be beneficial. These facts raise three pressing questions:
- Can Se prevent cancer in humans? The clinical significance of Se in cancer prevention remains a subject of debate. The nine randomized clinical trials conducted to date have yielded inconsistent results. Systematic reviews have found that Se may be effective in preventing cancer in individuals of low to adequate, but not high, Se status; and a U-shaped dose-response relationship has been proposed (Chiang et al., 2009). These conclusions are weakened by the fact that several trials have not followed robust protocols, and none has been conducted in recent years or in cohorts with individuals of both marginal and adequate Se status.
- What is the window of safety for Se? While it is clear that very high levels of exposure are required to produce selenosis, resolving the question of whether supranutritional intakes of Se can increase T2D risk remains unclear. Clarifying that will call for well controlled trials with subjects randomized by T2D risk factors (high BMI, elevated fasting glucose) and followed with unequivocal diagnostic indicators (fasting glucose, HbA1c, oral glucose tolerance). Until then, there would appear to be no justification for any healthy adult, regardless of his/her baseline Se status, to consume more than 100µg Se/day.
- Who Can Benefit from Se? This is the ultimate question. It is clear that supplementation of adults with basal Se intakes < 50µg/d will increase selenoenzyme expression, and that the magnitude of those increases will depend on the extent to which baseline plasma Se levels were below about 90ng/mL. That individuals with plasma Se levels less than about 120ng/mL may also benefit from increased Se intakes is suggested from results of the NPC Trial in which supplemental Se reduced cancer risk among adults with plasma Se levels in the range of80–120ng/mL. This suggests that individuals with plasma Se levels in that range may benefit from cancer protection unrelated to selenoenzyme expression. If so, many adults may benefit from increased Se intakes: some to maximize selenoprotein expression, others to reduce cancer risks.