Low Dietary c9t11‐Conjugated Linoleic Acid Intake from Dairy Fat or Supplements Reduces Inflammation in Collagen‐Induced Arthritis

Abstract

Dietary cis-9,trans-11 (c9t11) conjugated linoleic acid (CLA) fed at 0.5 % w/w was previously shown to attenuate inflammation in the murine collagen-induced (CA) arthritis model, and growing evidence implicates c9t11-CLA as a major anti-inflammatory component of dairy fat. To understand c9t11-CLA's contribution to dairy fat's anti-inflammatory action, the minimum amount of dietary c9t11-CLA needed to reduce inflammation must be determined. This study had two objectives: (1) determine the minimum dietary anti-inflammatory c9t11-CLA intake level in the CA model, and (2) compare this to anti-inflammatory effects of dairy fat (non-enriched, naturally c9t11-CLA-enriched, or c9t11-CLA-supplemented). Mice received the following dietary fat treatments (w/w) post arthritis onset: corn oil (6 % CO), 0.125, 0.25, 0.375, and 0.5 % c9t11-CLA, control butter (6 % CB), c9t11-enriched butter (6 % EB), or c9t11-CLA-supplemented butter (6 % SB, containing 0.2 % c9t11-CLA). Paw arthritic severity and pad swelling were scored and measured, respectively, over an 84-day study period. All c9t11-CLA and butter diets decreased the arthritic score (25-51 %, P < 0.01) and paw swelling (8-11 %, P < 0.01). Throughout the study, plasma tumor necrosis factor (TNFα) was elevated in CO-fed arthritic mice compared to non-arthritic (NA) mice but was reduced in 0.5 % c9t11-CLA- and EB-fed mice. Interleukin-1β and IL-6 were increased in arthritic CO-fed mice compared to NA mice but were reduced in 0.5 % c9t11-CLA- and EB-fed mice through day 42. In conclusion, 0.125 % c9t11-CLA reduced clinical arthritis as effectively as higher doses, and decreased arthritis in CB-fed mice suggested that the minimal anti-inflammatory levels of c9t11-CLA might be below 0.125 %.

Conjugated Linoleic Acid Isomers Trans‐10, Cis‐12 and Cis‐9, Trans‐11 Prevent Collagen‐Induced Arthritis in a Direct Comparison

“…In mice that developed arthritis, CLAc9t11 treatment had no effect on disease severity compared to CO, supporting the results seen in Muhlenbeck et al (Muhlenbeck et al, 2017). In this study, CLAt10c12 had a significant antiinflammatory effect on CAS and paw thickness one week after disease onset compared to CLAc9t11 and CO treatments suggesting additional anti-inflammatory benefit beyond incidence prevention; although, it is predicted that CLAc9t11 would also decrease arthritis severity with more time post disease onset (Huebner et al, 2010(Huebner et al, , 2016Olson et al, 2017). A significant increase in IL-2, IFNγ, TNFα, and IL-10 was observed in arthritic paw tissue compared to shams supporting CA as a Th1-mediated disease (Luross and Williams, 2001;Mauri et al, 1996).…”

“…Future work would be benefited by measurement of paw cytokines along with paw fatty‐acid contents and oxylipins, ideally from the same specimen, to understand the relationship between dietary fatty‐acid changes and tissue‐specific outcomes on inflammation. The effect of reduced dietary LNA intake on reduced hepatic LNA abundance in CLA‐fed groups is possible; however, this and previous feeding trials suggest that similar dietary fat replacement with CLAc9t11 does not significantly reduce hepatic LNA over 4, 10, or 12 weeks (Huebner et al, ; Muhlenbeck et al, ).…”

“…As CLAc9t11 is naturally abundant and can be enriched up to 6% in dairy fat (Shingfield et al, ), the practical intake of an effective preventative CLAc9t11 dose for humans should be further investigated. Human intake of 0.5% (w/w of diet) CLAc9t11 from naturally enriched sources is impractical (estimated at >150 g dairy fat per day); however, dietary intake less than 0.5% per day was previously effective over time in reducing arthritic inflammation in the CA model (Huebner et al, ). A dose–response experiment investigating the preventative effects of CLAc9t11 on CA would be necessary to determine the practicality of obtaining preventative amounts through consumption of animal fats, including dairy.…”

“…Paws were collected from arthritic mice one week after arthritis onset and from sham mice at the end of the study period (63 days after primary immunization). Bars represent means + standard error of the mean (SEM) day); however, dietary intake less than 0.5% per day was previously effective over time in reducing arthritic inflammation in the CA model (Huebner et al, 2016). A doseresponse experiment investigating the preventative effects of CLAc9t11 on CA would be necessary to determine the practicality of obtaining preventative amounts through consumption of animal fats, including dairy.…”

“…To decrease the need for potentially harmful and costly pharmaceuticals, dietary interventions for IMID are being explored. Using the murine collagen induced arthritis (CA) model, dietary mixed‐isomer conjugated linoleic acid (CLA) and the individual CLA isomers, trans ‐10 cis ‐12 (t10c12) and cis ‐9 , trans ‐11 (c9t11), have been shown to reduce inflammation compared to a corn oil (CO) control diet when provided after the onset of arthritis (Huebner et al, , , ; Olson et al, ). Furthermore, CLAc9t11 treatment at 0.5% of the diet was equivalent to a 1.5 mg/kg/day dose of celecoxib, a cyclooxygenase (COX)‐2 inhibitor commonly prescribed as an anti‐inflammatory (Olson et al, ).…”