Abstract
PurposePrimarily, to investigate the effect of high intake of cod (lean fish) or salmon (fatty fish) on serum concentration of total neopterin, a marker of cellular immune activation that is associated with cardiovascular disease. Second, to investigate effects of high cod/salmon intake on antioxidant vitamins and elements essential for activity of antioxidant enzymes.MethodsIn this randomised clinical trial, 63 participants with overweight/obesity consumed 750 g/week of either Atlantic cod (N = 22) or Atlantic salmon (N = 22) or were instructed to continue their normal eating habits but avoid fish intake (Control group, N = 19) for 8 weeks. Food intake was recorded, and fasting serum were collected at baseline and endpoint.ResultsSerum total neopterin concentration was reduced in the Cod group (median change − 2.65 (25th, 75th percentiles − 3.68, − 0.45) nmol/l, P = 0.018) but not in the Salmon group (median change 0.00 (25th, 75th percentiles − 4.15, 3.05) nmol/l, P = 0.59) when compared with the Control group after 8 weeks. The estimated daily intake of selenium, iron, magnesium and zinc were similar between all groups. Increased serum concentration of selenium was observed only after cod intake when compared to the Control group (P = 0.017). Changes in serum concentrations of copper, iron, magnesium, all-trans retinol, α-tocopherol and γ-tocopherol were similar between the groups.ConclusionA high intake of cod, but not of salmon, lowered serum total neopterin concentration when compared to the Control group.Clinical trial registrationThis trial was registered at clinicaltrials.gov as NCT02350595
Highlights
Chronic low-grade inflammation is a common feature in obesity, and is suggested to be an important element in the development of obesity-related co-morbidities includingNorway 4 Department of Clinical Science, University of Bergen, 5021 Bergen, Norway 5 Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, 5021 Bergen, Norway insulin resistance and diabetes mellitus type 2 [1,2,3]
The cytokine interferon-γ (IFNγ), produced by activated T cells, induces the metabolism of 7,8-dihydroneopterin from guanosine triphosphate in monocyte-derived macrophages during immune activation [4]. 7,8-dihydroneopterin is a potent radical scavenger and antioxidant, and its conversion to neopterin through non-enzymatic oxidation depends on the oxidative status of the individual; the combined measurement of 7,8-dihydroneopterin and neopterin provide a sensitive measure for cellular immune activation [4]
IFNγ is an important trigger for the production of reactive oxygen species in macrophages [5], neopterin may be an indicator of oxidative stress due to immune activation [6], and circulating neopterin concentration has been shown to be inversely correlated with the concentrations of antioxidant enzyme cofactor selenium [7] and antioxidant vitamins ascorbic acid and α-tocopherol [8] in the circulation
Summary
Elevated neopterin concentration, measured either as neopterin or as the sum of 7,8-dihydroneopterin and neopterin (total neopterin), in circulation is reported in patients with chronic peripheral arterial disease [9]. Circulating neopterin is associated with adverse prognosis in patients with stable angina pectoris [11] and increased risk of inpatient hospital diagnosis of atrial fibrillation [12], and is an independent predictor of all-cause and cardiovascular mortality in individuals with or without stable coronary artery disease [13]. High BMI, adiposity and elevated plasma glucose are associated with higher circulating concentration of neopterin in healthy adults, suggesting that moderate immune stimulation plays a role in the development of insulin resistance [14, 15]. It is of great importance that a reduction in neopterin concentration of only 1–2 nmol/l, especially in the lower concentration area, has been associated with lower risk for acute coronary events in elderly adults without pre-existing coronary heart disease [16]
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