title: Folic acid and creatine improve the firmness of human skin in vivo.
abstract: BACKGROUND
  The decrease in firmness is a hallmark of skin aging. Accelerated by chronic sun exposure, fundamental changes occur within the dermal extracellular matrix over the years, mainly impairing the collagenous network.
  
  
  OBJECTIVE
  Based on the qualitative and quantitative assessment of skin firmness, in vitro and in vivo studies were carried out to elucidate the effects of topical folic acid and creatine to counteract this age-dependent reduction in the amount of collagen.
  
  
  METHODS
  Topical application of a commercially available formulation containing folic acid and creatine was performed to study effects on skin firmness in vivo using cutometric analysis. Imaging and quantification of collagen density were carried out using multiphoton laser scanning microscopy (MPLSM). To investigate the effects of these compounds on collagen gene expression, procollagen synthesis, and collagen fibril organization, complementary in vitro studies on cultured fibroblast-populated collagen gels were carried out.
  
  
  RESULTS
  The underlying structural changes in the collagen network of young and aged sun-exposed facial skin in vivo were visualized by MPLSM. Topical application of a folic acid- and creatine-containing formulation significantly improved firmness of mature skin in vivo. Treatment of fibroblast-populated dermal equivalents with folic acid and creatine increased collagen gene expression and procollagen levels and improved collagen fiber density, suggesting that the in vivo effects are based on the overall improvement of the collagen metabolism.
  
  
  CONCLUSIONS
  Employing MPLSM, dermal changes occurring in photo-aged human skin were visualized in an unprecedented manner and correlated to a loss of firmness. Treatment of aged skin with a topical formulation containing folic acid and creatine counteracted this age-dependent decline by exerting sustained effects on collagen metabolism. Our results support previous findings on the efficacy of these actives.
authors.affiliation: Research & Development, Skin Research, Beiersdorf AG, Hamburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Fischer
authors.forename: Volker
authors.initials: V
authors.lastname: Achterberg
authors.forename: Annette
authors.initials: A
authors.lastname: März
authors.forename: Stefan
authors.initials: S
authors.lastname: Puschmann
authors.forename: Christian-Dennis
authors.initials: CD
authors.lastname: Rahn
authors.forename: Vivien
authors.initials: V
authors.lastname: Lutz
authors.forename: Andrea
authors.initials: A
authors.lastname: Krüger
authors.forename: Helge
authors.initials: H
authors.lastname: Schwengler
authors.forename: Sören
authors.initials: S
authors.lastname: Jaspers
authors.forename: Urte
authors.initials: U
authors.lastname: Koop
authors.forename: Thomas
authors.initials: T
authors.lastname: Blatt
authors.forename: Horst
authors.initials: H
authors.lastname: Wenck
authors.forename: Stefan
authors.initials: S
authors.lastname: Gallinat
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000494:pharmacology*; D004548:Elasticity / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005492:Folic Acid / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008853:Microscopy / Q000379:methods; D008875:Middle Aged; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000648:ultrastructure; D015595:Skin Aging / Q000187:drug effects*; D013472:Sunlight / Q000009:adverse effects; D014803:Vitamin B Complex / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D011347:Procollagen; D012333:RNA, Messenger; D014803:Vitamin B Complex; D003094:Collagen; D005492:Folic Acid; D003404:Creatinine