title: Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults.
abstract: Mortality resulting from influenza (flu) virus infections occurs primarily in the elderly through declining immunity. Studies in mice have suggested beneficial effects of selenium (Se) supplementation on immunity to flu but similar evidence is lacking in humans. A dietary intervention study was therefore designed to test the effects of Se-supplementation on a variety of parameters of anti-flu immunity in healthy subjects aged 50-64 years.
  
  
  
  A 12-week randomized, double-blinded, placebo-controlled clinical trial (ClinicalTrials.govNCT00279812) was undertaken in six groups of individuals with plasma Se levels <110 ng/mL. Four groups were given daily capsules of yeast enriched with 0 μg Se/day (SeY-0/d; n = 20), 50 μg Se/d (SeY-50/d; n = 18), 100 μg Se/d (SeY-100/d; n = 21) or 200 μg Se/d (SeY-200/d; n = 23). Two groups were given onion-containing meals with either <1 μg Se/d (SeO-0/d; n = 17) or 50 μg Se/d (SeO-50/d; n = 18). Flu vaccine was administrated at week 10 and immune parameters were assessed until week 12.
  
  
  
  Primary study endpoints were changes in cellular and humoral immune responses. Supplementation with SeY and SeO affected different aspects of cellular immunity. SeY increased Tctx-ADCC cell counts in blood (214%, SeY-100/d) before flu vaccination and a dose-dependent increase in T cell proliferation (500%, SeY-50/100/200/d), IL-8 (169%, SeY-100/d) and IL-10 (317%, SeY-200/d) secretion after in vivo flu challenge. Positive effects were contrasted by lower granzyme B content of CD8 cells (55%, SeY-200/d). SeO (Se 50 μg/d) also enhanced T cell proliferation after vaccination (650%), IFN-γ (289%), and IL-8 secretion (139%), granzyme (209%) and perforin (190%) content of CD8 cells but inhibited TNF-α synthesis (42%). Onion on its own reduced the number of NKT cells in blood (38%). These effects were determined by comparison to group-specific baseline yeast or onion control groups. Mucosal flu-specific antibody responses were unaffected by Se-supplementation.
  
  
  
  Se-supplementation in healthy human adults with marginal Se status resulted in both beneficial and detrimental effects on cellular immunity to flu that was affected by the form of Se, supplemental dose and delivery matrix. These observations call for a thorough evaluation of the risks and benefits associated with Se-supplementation.
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK. Electronic address: kamal.ivory@ifr.ac.uk.
authors.forename: Kamal
authors.initials: K
authors.lastname: Ivory
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK. Electronic address: elenaprieto0102@gmail.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Prieto
authors.affiliation: Food and Health Program, Institute of Food Research, Norwich, UK. Electronic address: caroline.spinks@ifr.ac.uk.
authors.forename: Caroline
authors.initials: C
authors.lastname: Spinks
authors.affiliation: Food and Health Program, Institute of Food Research, Norwich, UK. Electronic address: charlotte.armah@ifr.ac.uk.
authors.forename: Charlotte N
authors.initials: CN
authors.lastname: Armah
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK. Electronic address: Andrew.Goldson@ifr.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Goldson
authors.affiliation: Analytical Science Unit, Institute of Food Research, Norwich, UK.
authors.forename: Jack R
authors.initials: JR
authors.lastname: Dainty
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK. Electronic address: claudio.nicoletti@ifr.ac.uk.
authors.forename: Claudio
authors.initials: C
authors.lastname: Nicoletti
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D015992:Body Mass Index; D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood; D004032:Diet; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007070:Immunoglobulin A / Q000032:analysis; D007136:Immunoglobulins / Q000097:blood; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000737:chemistry; D012643:Selenium / Q000008:administration & dosage* / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007070:Immunoglobulin A; D007136:Immunoglobulins; D007252:Influenza Vaccines; D012643:Selenium
keywords: Cellular immunity; Food supplements; Humoral immunity; Influenza; Selenium