Docosahexaenoic acid in the treatment of rheumatoid arthritis: A double-blind, placebo-controlled, randomized cross-over study with microalgae vs. sunflower oil.

The potential of fish or fish oil as supplier for eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) for reducing cardiovascular risk factors and supporting therapy of chronic inflammatory diseases, has been investigated intensively, but our knowledge about the physiological effects of the individual compounds EPA and DHA are limited. STUDY DESIGN: In this double-blind pilot study, thirty-eight patients with defined RA were allocated to consume foods enriched with microalgae oil from Schizochytrium sp. (2.1 g DHA/d) or sunflower oil (placebo) for 10 weeks (cross-over), maintaining the regular RA medication during the study. RESULTS: In contrast to placebo, the daily consumption of DHA led to a decline in the sum of tender and swollen joints (68/66) from 13.9 ± 7.4 to 9.9 ± 7.0 (p = 0.010), total DAS28 from 4.3 ± 1.0 to 3.9 ± 1.2 (p = 0.072), and ultrasound score (US-7) from 15.1 ± 9.5 to 12.4 ± 7.0 (p = 0.160). The consumption of placebo products caused an increase of the n-6 PUFA linoleic acid and arachidonic acid (AA) in erythrocyte lipids (EL, p < 0.05). The amount of DHA was doubled in EL of DHA-supplemented patients and the ratios of AA/EPA and AA/DHA dropped significantly. We speculate that the production of pro-inflammatory/non-resolving AA-derived eicosanoids might decrease in relation to anti-inflammatory/pro-resolving DHA- and EPA-derived lipid mediators. In fact, plasma concentrations of AA-derived thromboxane B2 and the capacity of blood to convert AA to the pro-inflammatory 5-lipoxygenase product 5-hydroxyeicosatetraenoic acid were significantly reduced, while levels of the DHA-derived maresin/resolvin precursors 14-/17-hydroxydocosahexaenoic acid significantly increased due to DHA supplementation. CONCLUSION: The study shows for the first time that supplemented microalgae DHA ameliorates disease activity in patients with RA along with a shift in the balance of AA- and DHA-derived lipid mediators towards an anti-inflammatory/pro-resolving state.

In vitro-fermented raw and roasted walnuts induce expression of CAT and GSTT2 genes, growth inhibition, and apoptosis in LT97 colon adenoma cells.

Walnuts are rich in bioactive compounds such as polyunsaturated fatty acids, polyphenols, and dietary fiber. Therefore, the consumption of walnuts can contribute to a healthy diet and may reduce the risk for colon cancer. Heat treatment like roasting may change the chemical composition of walnuts and therefore their chemopreventive properties. Therefore, the hypothesis of the present study is that different roasting conditions (RCs) alter the chemopreventive effects of walnuts. Thus, the aim of the present study was to investigate whether different RCs (RC1=139.7°C/25 min, RC2=154.5°C/20 min, and RC3=185.5°C/25 min) alter the chemopreventive effects of walnuts. Raw and roasted walnuts were subjected to in vitro digestion and fermentation. After treatment of LT97 colon adenoma cells with fermentation supernatants (FSs), expression of CAT, SOD2, GPx1, GSTP1, and GSTT2 genes as well as cell growth and apoptosis was examined. In comparison to the fermentation blank control, walnut FS particularly increased mRNA levels of CAT 1.7-fold and GSTT2 3.1-fold, whereas GPx1 levels were significantly decreased 0.6-fold. Walnut FS decreased growth of adenoma cells in a time- and dose-dependent manner. In particular, higher concentrations of walnut FS (5%) significantly increased the number of early apoptotic cells 2.0-fold and induced caspase-3 activity 6.8-fold compared with the blank control. The roasting process had no direct impact on the observed effects. In sum, our results indicate that walnuts exhibit chemopreventive effects regarding the risk for colon cancer development by inducing expression of genes involved in detoxification (CAT, GSTT2) and by inducing growth inhibition and apoptosis in colon adenoma cells unaffected by moderate roasting.

The human ABCG4 gene is regulated by oxysterols and retinoids in monocyte-derived macrophages.

Here we report the induction of gene expression of ABCG4, a member of the ABC transporter subfamily G, from human macrophages by oxysterols and retinoids, agonists of the nuclear receptors LXR and RXR. The cloned ABCG4 transcript has a size of 3.5 kb and contains an open reading frame which encodes a polypeptide of 646 amino acids. Structurally, the putative ABC transporter protein consists of a nucleotide binding fold followed by a cluster of six transmembrane-spanning domains and thus conforms to the group of half-size ABC transporters. Among the human ABC transporter subfamily G members the novel transporter shows highest protein sequence homology and identity to ABCG1 (84 and 72%, respectively). Analysis of the genomic organization demonstrates that the ABCG4 gene is composed of at least 14 exons which extend across a region of 12.6 kb in size on chromosome 11q23.3. Based on its structural features and an LXR/RXR-responsive regulation similar to the cellular lipid export protein ABCA1, we conclude that ABCG4 may be involved in macrophage lipid homeostasis.