High habitual dietary α-linolenic acid intake is associated with decreased plasma soluble interleukin-6 receptor concentrations in male twins
High habitual dietary α-linolenic acid intake is associated with decreased plasma soluble interleukin-6 receptor concentrations in male twins
Year: 2010
Authors: Dai, J. Ziegler, T.R. Bostick, R.M. Manatunga, A.K. Jones, D.P. Goldberg, J. Miller, A. et.al.
Publication Name: Am. J. Clin. Nutr.
Publication Details: Volume 92; Pages 177 – 185.
Abstract:
Alpha-linolenic acid (ALA) is associated with a low risk of cardiovascular disease; however, the underlying mechanism is not completely known. The objective was to examine whether habitual dietary ALA intake is associated with plasma concentrations of inflammatory biomarkers after control for shared genetic and common environmental factors. We cross sectionally studied 353 middle-aged male twins. Habitual diet was assessed with the Willett food frequency questionnaire. Fasting plasma concentrations of interleukin-6 (IL-6) and its soluble receptor (sIL-6R), high-sensitivity C-reactive protein (hsCRP), and tumor necrosis factor-a (TNF-a) were measured. Linear mixed-effect regression analysis was used to partition the overall association into within and between pair associations. A 1g increment in habitual dietary ALA intake was associated with 11.0% lower concentrations of sIL-6R (P = 0.004) but not of IL-6 (P = 0.31), TNF-a (P = 0.16), or hsCRP (P = 0.36) after adjustment for energy intake, nutritional factors, known cardiovascular disease risk factors, and medications. After further control for shared genetic and common environmental factors by comparison of brothers within a twin pair, a twin with a 1-g higher ALA intake was likely to have 10.9% (95% CI: 3.7%, 17.6%; P = 0.004) lower sIL-6R concentrations than his co-twin with a low intake, whereas ALA intake was not significantly associated with plasma concentrations of IL-6, TNF-a, or hsCRP. These results were validated by using 1000 bootstrap samples. Habitual dietary ALA intake is inversely associated with plasma sIL-6R concentrations independent of shared genetic and common environmental influences. Lowering sIL-6R may be a mechanism underlying the cardioprotective properties of habitual dietary ALA. (Authors abstract)
Dietary a-linolenic acid (ALA) has been suggested to be protective against cardiovascular diseases (CVDs). ALA could suppress arachidonic acid cascade-related inflammation through a reduction in the production of arachidonic acid from linoleic acid. Interleukin-6 (IL-6) plays a role in arachidonic acid cascade-related inflammation through its receptor. IL-6 binds to the IL-6 receptor [either the membranebound (mIL-6R) or the soluble receptor (sIL-6R)] to form a complex that leads to the cellular response to IL-6 through the signal transduction of glycoprotein 130 (gp 130). sIL-6R may be central in the IL-6 inflammatory action through the arachidonic acid cascade, which could be inhibited by ALA. The primary aim of this study was to examine the association between habitual dietary ALA intake and plasma concentrations of IL-6 and sIL-6R. The association of ALA intake with plasma concentrations of tumor necrosis factor-a (TNF-a), an inflammatory factor that up-regulates IL-6, which, in turn, stimulates the production of C-reactive protein (CRP) in the liver was assessed. A sample of monozygotic and dizygotic middle-aged male twins reared in the same family to account for familial and genetic confounding was used. A strong inverse within pair association of habitual dietary ALA intake with plasma sIL-6R concentrations, independent of a wide range of known CVD risk factors in this middle-aged male twin cohort was noted: a 1 g higher habitual dietary ALA intake was significantly associated with an 11.0% (95% CI: 3.8%, 17.7%) lower plasma concentration of sIL-6R. The association persisted when twins within a monozygotic pair were compared. These findings indicate that the association between habitual dietary ALA and sIL-6R is independent of shared genes and common environment. A strong between pair association between habitual dietary ALA intake and plasma sIL-6R concentrations with a magnitude and direction similar to the within pair association was reported. The association between habitual dietary ALA intake and plasma sIL-6R concentrations has rarely been examined. A statistically significant association was not found between habitual dietary ALA intake and plasma concentrations of IL-6, TNF-a, and CRP. These associations have been inconsistent in various studies and further work is needed. The possible underlying biochemical mechanism through which habitual dietary ALA lowers sIL-6R is unclear but may reduce sIL-6R shedding by decreasing arachidonic acid concentrations. The findings support the hypothesis that sIL-6R is a novel biomarker for the cellular inflammatory response to dietary ALA. These results are relevant from a clinical and public health standpoint, because a 1.0 g increase in daily dietary ALA intake is easily achievable. The data support the potential importance of increasing dietary ALA in the habitual diet to prevent CVD. (Editors comments)
Dietary a-linolenic acid (ALA) has been suggested to be protective against cardiovascular diseases (CVDs). ALA could suppress arachidonic acid cascade-related inflammation through a reduction in the production of arachidonic acid from linoleic acid. Interleukin-6 (IL-6) plays a role in arachidonic acid cascade-related inflammation through its receptor. IL-6 binds to the IL-6 receptor [either the membranebound (mIL-6R) or the soluble receptor (sIL-6R)] to form a complex that leads to the cellular response to IL-6 through the signal transduction of glycoprotein 130 (gp 130). sIL-6R may be central in the IL-6 inflammatory action through the arachidonic acid cascade, which could be inhibited by ALA. The primary aim of this study was to examine the association between habitual dietary ALA intake and plasma concentrations of IL-6 and sIL-6R. The association of ALA intake with plasma concentrations of tumor necrosis factor-a (TNF-a), an inflammatory factor that up-regulates IL-6, which, in turn, stimulates the production of C-reactive protein (CRP) in the liver was assessed. A sample of monozygotic and dizygotic middle-aged male twins reared in the same family to account for familial and genetic confounding was used. A strong inverse within pair association of habitual dietary ALA intake with plasma sIL-6R concentrations, independent of a wide range of known CVD risk factors in this middle-aged male twin cohort was noted: a 1 g higher habitual dietary ALA intake was significantly associated with an 11.0% (95% CI: 3.8%, 17.7%) lower plasma concentration of sIL-6R. The association persisted when twins within a monozygotic pair were compared. These findings indicate that the association between habitual dietary ALA and sIL-6R is independent of shared genes and common environment. A strong between pair association between habitual dietary ALA intake and plasma sIL-6R concentrations with a magnitude and direction similar to the within pair association was reported. The association between habitual dietary ALA intake and plasma sIL-6R concentrations has rarely been examined. A statistically significant association was not found between habitual dietary ALA intake and plasma concentrations of IL-6, TNF-a, and CRP. These associations have been inconsistent in various studies and further work is needed. The possible underlying biochemical mechanism through which habitual dietary ALA lowers sIL-6R is unclear but may reduce sIL-6R shedding by decreasing arachidonic acid concentrations. The findings support the hypothesis that sIL-6R is a novel biomarker for the cellular inflammatory response to dietary ALA. These results are relevant from a clinical and public health standpoint, because a 1.0 g increase in daily dietary ALA intake is easily achievable. The data support the potential importance of increasing dietary ALA in the habitual diet to prevent CVD. (Editors comments)
