Natural killer cell cytotoxicity is not regulated by folic acid in vitro

Nutrition. 2013 May;29(5):772-6. doi: 10.1016/j.nut.2012.10.006. Epub 2013 Jan 10.


Objectives: Folate supplementation may be associated with an increased risk of developing several types of cancer and a derangement of immune function. Among the latter, Natural killer (NK) cells are involved in non-MHC-restricted natural immunity against malignant target cells. Abnormalities in NK cell number or function have been associated with a higher cancer risk. The aim of this study was to study in vitro the possible effect of different concentrations of 5-methyltetrahydrofolic acid (5-MTHF) or folic acid on NK cell cytotoxic function, and expression of the stimulatory and inhibitory receptors KIRDL4, KIRDL3, and NKG2D.

Methods: Volunteer-derived peripheral mononuclear cells (PBMC) and highly enriched NK cells (95% CD56+ CD16+) were grown in folic acid free-RPMI 1640, supplemented either with folic acid or 5-MTHF (15-100 nM) during 72 h to 96 h.

Results: No differences in the cytolytic activity of PBMC and enriched NK cells were observed. After 96 h of in vitro culture without folate or supplemented with FA or 5-MTHF (30 or 100 nM), there were no changes in the percentage of HPNK receptor-positive cells.

Conclusions: Our data indicate that a high dose of 5-MTHF or folic acid does not influence NK cell function in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD56 Antigen / metabolism
  • Cytotoxicity, Immunologic / drug effects*
  • Dietary Supplements
  • Female
  • Folic Acid / immunology
  • Folic Acid / metabolism
  • Folic Acid / pharmacology*
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Receptors, IgG / metabolism
  • Receptors, Natural Killer Cell / metabolism*
  • Tetrahydrofolates / immunology
  • Tetrahydrofolates / metabolism
  • Tetrahydrofolates / pharmacology
  • Vitamin B Complex / immunology
  • Vitamin B Complex / metabolism
  • Vitamin B Complex / pharmacology*


  • CD56 Antigen
  • Receptors, IgG
  • Receptors, Natural Killer Cell
  • Tetrahydrofolates
  • Vitamin B Complex
  • Folic Acid
  • 5-methyltetrahydrofolate