Is the omega-3 index a valid marker of intestinal membrane phospholipid EPA+DHA content?

Abstract

Despite numerous studies investigating n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation and inflammatory bowel diseases (IBD), the extent to which dietary n-3 LCPUFAs incorporate in gastrointestinal (GI) tissues and correlate with red blood cell (RBC) n-3 LCPUFA content is unknown. In this study, mice were fed three diets with increasing percent of energy (%en) derived from eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA). Dietary levels reflected recommended intakes of fish/fish oil by the American Heart Association. We analyzed the FA composition of phospholipids extracted from RBCs, plasma, and GI tissues. We observed that the 0.1%en EPA+DHA diet was sufficient to significantly increase the omega-3 index (RBC EPA+DHA) after 5 week feeding. The baseline EPA levels were 0.2-0.6% across all tissues increasing to 1.6-4.3% in the highest EPA+DHA diet; these changes resulted in absolute increases of 1.4-3.9% EPA across tissues. The baseline DHA levels were 2.2-5.9% across all tissues increasing to 5.8-10.5% in the highest EPA+DHA diet; these changes resulted in absolute increases of 3.2-5.7% DHA across tissues. These increases in EPA and DHA across all tissues resulted in strong (r>0.91) and significant (P<0.001) linear correlations between the omega-3 index and plasma/GI tissue EPA+DHA content, suggesting that the omega-3 index reflects the relative amounts of EPA+DHA in GI tissues. These data demonstrate that the GI tissues are highly responsive to dietary LCPUFA supplementation and that the omega-3 index can serve as a valid biomarker for assessing dietary EPA+DHA incorporation into GI tissues.

Keywords: Biomarker; Colon; Fatty acids; Intestine; Omega-3; Red blood cell.

Copyright © 2014 Elsevier Ltd. All rights reserved.

Figures

Figure 1. Correlations between the omega-3 index of red blood cell and the EPA+DHA of plasma or gastrointestinal tract tissues from mice fed diets with increasing EPA+DHA

(A) The omega-3 index from mice fed AIN-93G diet with either 0.0%en EPA+DHA, 0.1%en EPA+DHA, 0.675%en EPA+DHA, or 1.8%en EPA+DHA (n = 6/group). A one-way ANOVA and a Tukey’s post-hoc were used to assess differences in the tissue-specific EPA+DHA compared to each other. Differing letters denote statistical significance at P < 0.05. (B–E) The omega-3 index in RBC phospholipids correlated to the EPA+DHA of plasma (B), stomach (C), small intestine (D), cecum (E), and colon (F) phospholipids. A Pearson correlation was used to test for linear correlation between the aforementioned tissues (n=24).

Figure 2. Comparison of EPA content in phospholipid fatty acids from blood and gastrointestinal tissues mice fed diets with increasing EPA+DHA

(A–D) Fold Change in EPA content over the control group in phospholipid fatty acids from gastrointestinal tissues correlated to EPA content in phospholipid fatty acids from red blood cells: (A) Stomach, (B) Small Intestine (C) Cecum, (D) Colon. Data from the tissues of mice fed experimental diets containing EPA+DHA-enriched fish oil were normalized to the 0.0%en EPA+DHA diet group to assess fold changes in EPA content of phospholipids. A Pearson correlation was used to test linear correlation between gastrointestinal tissue EPA fold change and RBC EPA fold change (n = 18). (E–F) The EPA content from phospholipid fatty acids across blood and gastrointestinal tissues from mice fed either the control (E) or 1.8%en EPA+DHA diet (F) (n = 6/group). A one-way ANOVA and a Tukey’s post-hoc were used to assess differences in EPA content comparing all tissues to each other. Differing letters denote statistical significance at P < 0.05.

Figure 3. Comparison of DHA content in phospholipid fatty acids from blood and gastrointestinal tissues from mice fed diets with increasing EPA+DHA

(A–D) Fold Change in DHA content over the control group in phospholipid fatty acids from gastrointestinal tissues correlated to DHA content in phospholipid fatty acids from red blood cells: (A) Stomach, (B) Small Intestine (C) Cecum, (D) Colon. Data from the tissues of mice fed experimental diets containing EPA+DHA-enriched fish oil were normalized to the control group to assess fold changes in DHA content of phospholipids. A Pearson correlation was used to test linear correlation between gastrointestinal tissue DHA fold change and RBC DHA fold change (n = 18). (E–F) The DHA content from phospholipid fatty acids across blood and gastrointestinal tissues from mice fed either the control (E) or 1.8%en EPA+DHA diet (F) (n = 6/group). A one-way ANOVA and a Tukey’s post-hoc were used to assess differences in DHA content comparing all tissues to each other. Differing letters denote statistical significance at P < 0.05.

Figure 4. Comparison of AA content in phospholipid fatty acids from blood and gastrointestinal tissues from mice fed diets with increasing EPA+DHA

(A–D) Fold Change in AA content over the control group in phospholipid fatty acids from gastrointestinal tissues correlated to AA content in phospholipid fatty acids from red blood cells: (A) Stomach, (B) Small Intestine (C) Cecum, (D) Colon. Data from the tissues of mice fed experimental diets containing EPA+DHA-enriched fish oil were normalized to the control group to assess fold changes in AA content of phospholipids. A Pearson correlation was used to test linear correlation between gastrointestinal tissue AA fold change and RBC AA fold change (n = 18). (E–F) The AA content from phospholipid fatty acids across blood and gastrointestinal tissues from mice fed either the control (E) or 1.8%en EPA+DHA diet (F) (n = 6/group). A one-way ANOVA and a Tukey’s post-hoc were used to assess differences in AA content comparing all tissues to each other. Differing letters denote statistical significance at P < 0.05.