Marginal Zinc Deficiency Alters Essential Fatty Acid Metabolism in Healthy Men

Abstract

Background: Rice biofortification with Zinc (Zn) can improve the Zn status of rice-consuming populations. However, the metabolic impact in humans consuming Zn-biofortified rice is unknown.

Objectives: To determine the effects of Zn-biofortified rice on lipid metabolism in normolipidemic men.

Methods: The men consumed a rice-based diet containing 6 mg Zn/d and 1.5 g phytate (phytate/Zn ratio = 44) for 2 wk followed by a 10-mg Zn/d diet without phytate for 4 wk. An ad libitum diet supplemented with 25 mg Zn/d was then fed for 3 wk. Fasting blood samples were taken at baseline and at the end of each metabolic period for measuring plasma zinc, glucose, insulin, triglyceride (TG), LDL and HDL cholesterol, fatty acids, oxylipins, and fatty acid desaturase activities. Statistical differences were assessed by linear mixed model.

Results: Fatty acid desaturase (FADS) 1 activity decreased by 29.1% (P = 0.007) when the 6-mg Zn/d diet was consumed for 2 wk. This change was associated with significant decreases in HDL and LDL cholesterol. The alterations in FADS1, HDL cholesterol, and TG remained unchanged when Zn intakes were increased to 10 mg/d for 4 wk. Supplementation with 25 mg Zn/d for 3 wk normalized these metabolic changes and significantly increased LDL cholesterol at the end of this metabolic period compared with baseline. FADS1 activity was inversely correlated with FADS2 (rmcorr = -0.52; P = 0.001) and TG (rmcorr = -0.55; P = 0.001) at all time points.

Conclusions: A low-zinc, high-phytate rice-based diet reduced plasma HDL cholesterol concentrations and altered fatty acid profiles in healthy men within 2 wk. Consuming 10 mg Zn/d without phytate for 4 wk did not improve the lipid profiles, but a 25-mg Zn/d supplement corrects these alterations in lipid metabolism within 3 wk.

Keywords: HDL cholesterol; LDL cholesterol; fatty acid desaturase; fatty acid metabolism; lipids; oxylipins; phytate; zinc; zinc biofortification.

FIGURE 1

Study design. Eighteen healthy men aged 19–45 y with BMI 18–30 kg/m² participated in the study. The study consisted of a 3-d run-in period to acclimate the participants to the control diet, after which baseline blood samples were collected. The men then consumed a controlled diet providing 6 mg zinc (Zn)/d for 2 wk that was fortified with 1.5 g sodium phytate/d to induce a marginal Zn depletion (MP1). Between weeks 2 and 6, dietary Zn was increased to 10 mg Zn/d for 4 wk by adding 4 mg exogenous Zn sulfate to rice consumed daily. No exogenous phytate was provided during this period (MP2). During weeks 7 through 9, participants consumed an ad libitum diet with 25 mg/d supplemental Zn citrate for 3 wk. Blood samples were taken at the end of each MP. One participant missed a time point at the end of MP1, and another missed at the end of MP2. All participants completed the study. MP, metabolic period.

FIGURE 2

Modest changes in dietary zinc (Zn) intake alter fatty acid desaturase activities in 18 men at baseline and at the end of each metabolic phases with varying dietary Zn. Stearoyl-CoA desaturase 1 (SCD1) and fatty acid desaturase 1 and 2 (FADS1 and FADS2) activities were estimated from total plasma fatty acids at the end of each metabolic period. (A, B) SCD1 and FADS2 activities trended higher during the first 2 metabolic phases. (C) FADS1 activity significantly decreased following the 6-mg/d Zn intake period. Changes in FADS1 and FADS2 activities normalized to baseline following supplementation with 25 mg/d Zn citrate. Values are mean ± SEM. Sample sizes were n = 18, n = 17, n = 17, and n = 18 for baseline, MP1, MP2, and MP3 time points, respectively. Missing data were omitted from analysis. Means without common letter differ, P < 0.05. MP, metabolic period.

FIGURE 3

Oxylipin changes in 18 men at baseline and at the end of each metabolic phase with varying dietary zinc (Zn). (A) Volcano plot of log₂ fold change (Log2FC) in 49 oxylipins detected at the end of 6 mg Zn/d for 2-wk intake period. (B) Volcano plot of oxylipin change due to increasing Zn intake from 6 mg Zn/d for 2 wk to 10 mg Zn/d for 4 wk. Results show that 14(15)-epoxy-eicosatetraenoic acid [14(15)-EpETE] trended lower with reduced Zn intake (panel A; P < 0.1). 8,9-Epoxyeicosatrienoic acid [8(9)-EpETrE] and 11,12-epoxyeicosatrienoic acid [11(12)-EpETrE], which are products of arachidonic acid oxidation by P450 pathways, also trended lower (panel A; P < 0.1). A modest increase in dietary Zn intake from 6 mg Zn/d for 2 wk to 10 mg Zn/d for 4 wk significantly elevated plasma 14(15)-EpETE (panel B). (C, D) The effects of dietary Zn modulation on plasma concentrations of EPA-derived 14(15)-EpETE and 11(12)-EpETE. Results show significant dose-dependent increases in these compounds with a higher Zn intake. Values are mean ± SEM and units are nmol/L. Means without common letter differ, P < 0.05.

FIGURE 4

Repeated-measures correlations between stearoyl-CoA desaturase 1 (SCD1), fatty acid desaturase 1 (FADS1), and fatty acid desaturase 2 (FADS2) activities measured in 18 men at baseline and at the end of each metabolic phases with varying dietary zinc (Zn). Repeated-measures correlations between FADS1, FADS2, and SCD1 activity z scores at baseline and at the end of each metabolic phases were assessed using repeated-measures correlation analysis (R_mcorr). Common regression slope, which is association shared among individuals, and the 95% CI of these estimates are plotted. MP, metabolic period.

FIGURE 5

Repeated-measures correlations between enzyme activity, triglyceride (TG), and HDL cholesterol z scores calculated at baseline and at the end of each metabolic phases in 18 men. Repeated-measures correlation analysis was performed to determine the common within-individual associations between fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and stearoyl-CoA desaturase 1 (SCD1) activity z scores and fasting TG and HDL cholesterol z scores in 18 participants. Estimation of the common regression slope and 95% CI, with P values shown.