Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial

Signe Holm Nielsen; Samra Sardar; Anne Sofie Siebuhr; Annette Schlemmer; Erik Berg Schmidt; Anne-Christine Bay-Jensen; Morten A Karsdal; Jeppe Hagstrup Christensen; Salome Kristensen

doi:10.1007/s00296-021-04861-z

Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial

Signe Holm Nielsen, Samra Sardar, Anne Sofie Siebuhr, Annette Schlemmer, Erik Berg Schmidt, Anne-Christine Bay-Jensen, Morten A Karsdal, Jeppe Hagstrup Christensen, Salome Kristensen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

9 Citations (Scopus)

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013-Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1.

Original language	English
Journal	Rheumatology International
Volume	41
Issue	6
Pages (from-to)	1065-1077
Number of pages	13
ISSN	0172-8172
DOIs	https://doi.org/10.1007/s00296-021-04861-z
Publication status	Published - Jun 2021
Externally published	Yes

Keywords

Adult
Arthritis, Psoriatic/drug therapy
Biomarkers/metabolism
Double-Blind Method
Extracellular Matrix Proteins/drug effects
Fatty Acids, Omega-3/administration & dosage
Female
Humans
Male
Middle Aged

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10.1007/s00296-021-04861-zLicence: CC BY

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Holm Nielsen, S., Sardar, S., Siebuhr, A. S., Schlemmer, A., Schmidt, E. B., Bay-Jensen, A.-C., Karsdal, M. A., Christensen, J. H., & Kristensen, S. (2021). Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial. Rheumatology International, 41(6), 1065-1077. https://doi.org/10.1007/s00296-021-04861-z

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title = "Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial",

abstract = "Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013-Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1.",

keywords = "Adult, Arthritis, Psoriatic/drug therapy, Biomarkers/metabolism, Double-Blind Method, Extracellular Matrix Proteins/drug effects, Fatty Acids, Omega-3/administration & dosage, Female, Humans, Male, Middle Aged",

author = "{Holm Nielsen}, Signe and Samra Sardar and Siebuhr, {Anne Sofie} and Annette Schlemmer and Schmidt, {Erik Berg} and Anne-Christine Bay-Jensen and Karsdal, {Morten A} and Christensen, {Jeppe Hagstrup} and Salome Kristensen",

year = "2021",

month = jun,

doi = "10.1007/s00296-021-04861-z",

language = "English",

volume = "41",

pages = "1065--1077",

journal = "Rheumatology International",

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Holm Nielsen, S, Sardar, S, Siebuhr, AS, Schlemmer, A, Schmidt, EB, Bay-Jensen, A-C, Karsdal, MA, Christensen, JH & Kristensen, S 2021, 'Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial', Rheumatology International, vol. 41, no. 6, pp. 1065-1077. https://doi.org/10.1007/s00296-021-04861-z

Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial. / Holm Nielsen, Signe; Sardar, Samra; Siebuhr, Anne Sofie et al.
In: Rheumatology International, Vol. 41, No. 6, 06.2021, p. 1065-1077.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis

T2 - a randomized, double-blind, placebo-controlled trial

AU - Holm Nielsen, Signe

AU - Sardar, Samra

AU - Siebuhr, Anne Sofie

AU - Schlemmer, Annette

AU - Schmidt, Erik Berg

AU - Bay-Jensen, Anne-Christine

AU - Karsdal, Morten A

AU - Christensen, Jeppe Hagstrup

AU - Kristensen, Salome

PY - 2021/6

Y1 - 2021/6

N2 - Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013-Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1.

AB - Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013-Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1.

KW - Adult

KW - Arthritis, Psoriatic/drug therapy

KW - Biomarkers/metabolism

KW - Double-Blind Method

KW - Extracellular Matrix Proteins/drug effects

KW - Fatty Acids, Omega-3/administration & dosage

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

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U2 - 10.1007/s00296-021-04861-z

DO - 10.1007/s00296-021-04861-z

M3 - Journal article

C2 - 33885930

SN - 0172-8172

VL - 41

SP - 1065

EP - 1077

JO - Rheumatology International

JF - Rheumatology International

IS - 6

ER -

Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial

Abstract

Keywords

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