Evidence that soyasaponin Bb retards disease progression in a murine model of polycystic kidney disease

Evidence that soyasaponin Bb retards disease progression in a murine model of polycystic kidney disease.BackgroundWe reported a lessened cyst growth in the pcy mouse model of polycystic kidney disease (PKD) when mice were fed a soy protein isolate (SPI)–based diet and hypothesized that the soyasaponins may be associated with this therapeutic effect. The effects of feeding a saponin-enriched alcohol extract (SEAE) from SPI, an isoflavone- and saponin-enriched soy supplement (Novasoy 400®), or a 99.5% pure soyasaponin Bb powder on cyst growth are reported here.MethodsThe therapeutic effects of the soyasaponins were studied in 60-day-old male pcy mice in two separate, 90-day feeding trials. In the first study, mice were fed either a casein-based (control) diet, a diet in which SPI replaced the casein or the control diet supplemented with SEAE. In the second study, mice were fed the control diet unsupplemented or supplemented with either a soyasaponin- and isoflavone-enriched soy product (Novasoy 400®) or a 99.5% pure soyasaponin Bb powder.ResultsIn study 1, kidney weight, water content, and plasma creatinine and urea levels were markedly reduced in the SEAE-fed animals compared to tissues from the control group; likewise, mice fed the SPI-based diet showed a decreased plasma creatinine, but only a slightly reduced plasma urea. In study 2, kidney weight, water content, plasma creatinine and urea levels were significantly reduced in mice fed the soyasaponin Bb powder and the Novasoy-400® supplement, compared to controls.ConclusionSoyasaponin Bb can impede kidney enlargement and cyst growth in the pcy mouse model of PKD. Further studies are needed to determine its most effective dose and mechanism of action

Dietary Docosahexaenoic Acid and Arachidonic Acid in Early Life:What Is the Best Evidence for Policymakers?

Background: A wealth of information on the functional roles of docosahexaenoic acid (DHA) and arachidonic acid (ARA) from cellular, animal, and human studies is available. Yet, there remains a lack of cohesion in policymaking for recommended dietary intakes of DHA and ARA in early life. This is predominantly driven by inconsistent findings from a relatively small number of randomised clinical trials (RCTs), which vary in design, methodology, and outcome measures, all of which were conducted in high-income countries. It is proposed that this selective evidence base may not fully represent the biological importance of DHA and ARA during early and later life and the aim of this paper is to consider a more inclusive and pragmatic approach to evidence assessment of DHA and ARA requirements in infants and young children, which will allow policymaking to reflect the marked diversity of need worldwide. Summary: Data from clinical RCTs is considered in the context of the extensive evidence from experimental, animal and human observational studies. Although the RCT data shows evidence of beneficial effects on visual function and in specific cognitive domains, early methodological approaches do not reflect current thinking and this undermines the strength of evidence. An outline of a framework for an inclusive and pragmatic approach to policy development on dietary DHA and ARA in early life is described. Conclusion: High-quality RCTs that will determine long-term health outcomes in appropriate real-world settings need to be undertaken. In the meantime, a collective pragmatic approach to evidence assessment, may allow public health policymakers to make comprehensive reasoned judgements on the merits, costs, and expediency of dietary DHA and ARA interventions

Oral docosapentaenoic acid (22:5n-3) is differentially incorporated into phospholipid pools and differentially metabolized to eicosapentaenoic acid in tissues from young rats,” Lipids,

Abstract The present study assessed the effect of oral supplementation with docosapentaenoic acid (DPA, on the levels of serum and tissue lipid classes and their fatty acid compositions including individual phospholipid types in rat liver, heart, and kidney. Sprague-Dawley rats received daily oral gavage over 10 days as corn oil without (controls) or with purified DPA in free fatty acid form (21.2 mg/day). The DPA group exhibited significantly lower serum lipid concentrations. The concentrations in lmol/100 g serum or lmol/g tissue of DPA in the total lipid (TL) were higher by 2.3-, 2.4-, 10.9-, and 5.1-fold in the DPA group of serum, liver, heart, and kidney, respectively, with the phospholipids (PL) being the major DPA reservoir (45.2-52.1% of the DPA in the TL). No significant differences in DHA (22:6n-3) amounts in TL appeared. The highest relative mol% values as DPA were in heart tissue (means of 11.1% in PL and 16.2% in phosphatidylinositol) and lowest in kidney. The EPA (20:5n-3) concentrations were markedly higher in the DPA group and most pronounced in the kidney (5.1 times higher in the TL as compared to controls) relative to liver and heart yielding an estimated apparent % conversion of DPA to EPA of 67% and EPA:DPA ratios reaching 5.74 in kidney phosphatidylethanolamine. The serum lipid-lowering potential of dietary DPA and its impact in the kidney with the derived EPA warrants investigation

305 N-3 Polyunsaturated fatty acids alter expression of fibrotic and hypertrophic genes in a dog model of atrial cardiomyopathy

Omega-3 polyunsaturated fatty acids (PUFAs) may reduce vulnerability to atrial fibrillation (AF). The mechanism underlying this effect is unknown. A genome wide approach was used to identify gene expression profiles involved in a new model of vulnerability to AF, and determine whether they were altered by PUFA therapy. Thirty-six dogs were randomized into 3 groups of 12. Two groups were paced using simultaneous atrial and ventricular pacing (SAVP) at 220 bpm for 14 days to induce atrial enlargement, fibrosis and susceptibility to AF. One group was supplemented with oral PUFAs (850 mg/day) for 21 days, commencing 7 days before the start of pacing (SAVP-PUFAs); the other received no PUFAs (SAVP-No PUFAs). The final group was unpaced, unsupplemented and served as controls (CTRL). Atrial tissue from left appendages was sampled at the end of the protocol. PUFA supplementation caused a 24% increase in tissue phospholipid PUFA concentration. Gene expression was analyzed via microarray. Results were confirmed with QT-RT-PCR and histology. SAVP-No PUFAs dogs had significantly increased mRNA levels of MHCα, elevated levels of other proremodeling genes Akt, EGF, TIMP1, JAM3 and CD99, and significantly decreased levels of fibrosis inhibiting Smad6. PUFA supplementation was associated with significant down-regulation of Akt, EGF, TIMP1, MHCα, CD99 and lower JAM3 levels. PUFAs reversed the 34% increase in myocyte cross sectional area caused by pacing. PUFAs appear to attenuate, at the genetic level, adverse remodeling in response to mechanical stress

Correlation of omega-3 levels in serum phospholipid from 2053 human blood samples with key fatty acid ratios

<p>Abstract</p> <p>Background</p> <p>This research was conducted to explore the relationships between the levels of omega-3 fatty acids in serum phospholipid and key fatty acid ratios including potential cut-offs for risk factor assessment with respect to coronary heart disease and fatal ischemic heart disease.</p> <p>Methods</p> <p>Blood samples (n = 2053) were obtained from free-living subjects in North America and processed for determining the levels of total fatty acids in serum phospholipid as omega-3 fatty acids including EPA (eicosapentaenoic acid, 20:5 n-3) and DHA (docosahexaenoic acid, 22:6 n-3) by combined thin-layer and gas-liquid chromatographic analyses. The omega-3 levels were correlated with selected omega-6: omega-3 ratios including AA (arachidonic acid, 20:4n-6): EPA and AA:(EPA+DHA). Based on previously-published levels of omega-3 fatty acids considered to be in a 'lower risk' category for heart disease and related fatality, 'lower risk' categories for selected fatty acid ratios were estimated.</p> <p>Results</p> <p>Strong inverse correlations between the summed total of omega-3 fatty acids in serum phospholipid and all four ratios (omega-6:omega-3 (n-6:n-3), AA:EPA, AA:DHA, and AA:(EPA+DHA)) were found with the most potent correlation being with the omega-6:omega-3 ratio (R²= 0.96). The strongest inverse relation for the EPA+DHA levels in serum phospholipid was found with the omega-6: omega-3 ratio (R²= 0.94) followed closely by the AA:(EPA+DHA) ratio at R²= 0.88. It was estimated that 95% of the subjects would be in the 'lower risk' category for coronary heart disease (based on total omega-3 ≥ 7.2%) with omega-6:omega-3 ratios <4.5 and AA:(EPA+DHA) ratios <1.4. The corresponding ratio cut-offs for a 'lower risk' category for fatal ischemic heart disease (EPA+DHA ≥ 4.6%) were estimated at < 5.8 and < 2.1, respectively.</p> <p>Conclusions</p> <p>Strong inverse correlations between the levels of omega-3 fatty acids in serum (or plasma) phospholipid and omega-6: omega-3 ratios are apparent based on this large database of 2053 samples. Certain fatty acid ratios may aid in cardiovascular disease-related risk assessment if/when complete profiles are not available.</p