α-Tocopherol Stereoisomer Profiles in Matched Human Maternal and Umbilical Cord Plasma.

BACKGROUND: α-Tocopherol (αT) is essential for fetal development. One study has shown that the human placenta preferentially transfers the natural stereoisomer, RRR-αT. But prenatal supplements generally contain synthetic αT (S-αT). OBJECTIVES: We aimed to determine if umbilical cord plasma is enriched for RRR-αT in racially diverse neonates from both uncomplicated and complicated pregnancies and if cord RRR-αT enrichment is impacted by maternal αT stereoisomer profile. METHODS: We measured αT and αT stereoisomers in plasma from a randomly selected subset of 66 predominantly black and Hispanic maternal-fetal pairs from the Camden Study involving control (n = 28) and complicated pregnancies (n = 38). We collected maternal plasma at study entry (week 16 gestation; w16) and week 28 gestation (w28) and cord plasma at birth. RESULTS: RRR-αT was the predominant stereoisomer in all maternal and cord plasma samples, but S-αT stereoisomers were found in most samples and comprised a high percentage of αT in some maternal-neonate pairs. Cord plasma had a higher percentage RRR-αT (P < 0.05) and lower percentage S-αT (P < 0.0001) than w28 plasma. Pregnancy status did not impact maternal or cord plasma concentrations of αT, RRR-αT, or S-αT; except plasma from complicated pregnancies was higher in S-αT at w28 than at w16 (P < 0.05). Maternal w28 αT did not correlate with cord αT. However, both maternal w28 αT and S-αT positively correlated with both cord S-αT (r = 0.340, P = 0.0049; r = 0.538, P < 0.00001) and percentage S-αT (r = 0.399, P = 0.001; r = 0.786, P < 0.00001) but negatively correlated with cord percentage RRR-αT (r = -0.399, P = 0.0009; r = -0.786, P < 0.00001). CONCLUSIONS: The proportion of RRR-αT was higher in cord compared with maternal plasma in both uncomplicated and complicated pregnancies. Our data suggest that maternal S-αT raises cord S-αT and decreases the proportion of RRR-αT in the neonatal circulation. Because the bioactivities of RRR-αT and S-αT differ, this warrants future research to determine the importance of our observations to neonatal αT status.

Early Enteral Administration of a Complex Lipid Emulsion Supplement Prevents Postnatal Deficits in Docosahexaenoic and Arachidonic Acids and Increases Tissue Accretion of Lipophilic Nutrients in Preterm Piglets.

BACKGROUND: Preterm delivery and current nutrition strategies result in deficiencies of critical long-chain fatty acids (FAs) and lipophilic nutrients, increasing the risk of preterm morbidities. We sought to determine the efficacy of preventing postnatal deficits in FAs and lipophilic nutrients using an enteral concentrated lipid supplement in preterm piglets. METHODS: Preterm piglets were fed a baseline diet devoid of arachidonic acid (AA) and docosahexaenoic acid (DHA) and randomized to enteral supplementation as follows: (1) Intralipid (IL), (2) complex lipid supplement 1 (CLS1) with an AA:DHA ratio of 0.25, or (3) CLS2 with an AA:DHA ratio of 1.2. On day 8, plasma and tissue levels of FAs and lipophilic nutrients were measured and ileum histology performed. RESULTS: Plasma DHA levels decreased in the IL group by day 2. In contrast, DHA increased by day 2 compared with birth levels in both CLS1 and CLS2 groups. The IL and CLS1 groups demonstrated a continued decline in AA levels during the 8-day protocol, whereas AA levels in the CLS2 group on day 8 were comparable to birth levels. Preserving AA levels in the CLS2 group was associated with greater ileal villus height and muscular layer thickness. Lipophilic nutrients were effectively absorbed in plasma and tissues. CONCLUSIONS: Enteral administration of CLS1 and CLS2 demonstrated similar increases in DHA levels compared with birth levels. Only CLS2 maintained AA birth levels. Providing a concentrated complex lipid emulsion with an AA:DHA ratio > 1 is important in preventing postnatal AA deficits.

Mono- and diglycerides improve lutein absorption in healthy adults: a randomised, double-blind, cross-over, single-dose study.

With the association between increased carotenoid intake and lower risk of chronic diseases, the absorption of lutein from the diet becomes an important factor in its delivery and physiological action. The primary objective of this study was to gain an understanding of how a new formulation technology (mixture of mono- and diglycerides (MDG)), affected lutein absorption. Subjects (n 24) were randomised in a cross-over, double-blind study to receive a single dose of 6 mg lutein (FloraGLO 20 %) provided as capsules containing either high-oleic safflower (SAF) oil or a MDG oil. Subjects receiving a single dose of lutein in MDG showed a significantly greater change from baseline (0 h) to 4, 6, 8, 12, 24, 48 and 336 h (P<0·05) and baseline adjusted AUC for plasma lutein at 48 and 336 h (P<0·001) as compared with subjects given lutein in SAF. Analysis of the 48 h absorption kinetics of lutein showed that the time to peak level of lutein (12 h) was the same for SAF and MDG groups, but the change in plasma lutein at 12 and 48 h were 129 and 320 % higher, respectively, for MDG compared with SAF. This difference continued as the adjusted AUC 0-48 and 0-336 h for the MDG group was 232 and 900 % higher, respectively, v. SAF. The study data show that by changing the lipid that is combined with a lutein supplement results in significant increases in lutein absorption in healthy adults.

Nutritional immunomodulation in critically ill children with acute lung injury: feasibility and impact on circulating biomarkers.

OBJECTIVE: Respiratory failure caused by acute lung injury or acute respiratory distress syndrome is associated with significant morbidity in children. Enteral nutrition enriched with eicosapentaenoic acid, γ-linolenic acid and antioxidants (eicosapentaenoic acid + γ-linolenic acid) can safely modulate plasma phospholipid fatty acid profiles, reduce inflammation, and improve clinical outcomes in adults. There is little information regarding the use of enteral eicosapentaenoic acid + γ-linolenic acid to modulate plasma phospholipid fatty acid profiles in children. We sought to determine if continuous feeding of enteral nutrition containing eicosapentaenoic acid, γ-linolenic acid, and antioxidants was feasible in critically ill children with acute lung injury or acute respiratory distress syndrome. We further evaluated the impact of such an approach on the alteration of plasma phospholipid fatty acid concentrations. DESIGN: Prospective, blinded, randomized, controlled, multicenter trial. SETTING: PICU. PATIENTS: Twenty-six critically ill children (age 6.2 ± 0.9 yr, PaO2/FIO2 185 ± 15) with the diagnosis of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS: Mechanically ventilated children received either eicosapentaenoic acid + γ-linolenic acid or a standard pediatric enteral formula. Clinical, biochemical, plasma fatty acid, and safety data were assessed at baseline, study days 4 and 7. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no significant differences in the two study groups. Both groups met enteral feeding goals within 30 hrs and had similar caloric delivery. There were no differences in formula tolerance as measured by serum chemistries, liver and renal function, and hematology studies after 7 days of feeding either eicosapentaenoic acid + γ-linolenic acid or pediatric enteral formula. On study day 4 and 7, plasma phospholipid fatty acid profiles in the eicosapentaenoic acid + γ-linolenic acid group showed a significant increase in anti-inflammatory circulating markers. CONCLUSIONS: Providing enteral nutrition with eicosapentaenoic acid + γ-linolenic acid to critically ill children with lung injury was feasible and caloric goals were met within 30 hrs. This feeding protocol effectively modulated plasma phospholipid fatty acid concentrations to reflect an anti-inflammatory profile. This study provides data to inform future outcome studies using enteral eicosapentaenoic acid + γ-linolenic acid in children with lung injury.

Comparison of growth, serum biochemistries and n-6 fatty acid metabolism in rats fed diets supplemented with high-gamma-linolenic acid safflower oil or borage oil for 90 days.

Recently, steps have been taken to further developments toward increasing gamma-linolenic acid (GLA) concentration and lowering costs in plant seed oils using transgenic technology. Through identification and expression of a fungal delta-6 desaturase gene in the high linoleic acid safflower plant, the seeds from this genetic transformation produce oil with >40% GLA (high GLA safflower oil (HGSO)). The aim of the study was to compare the effects of feeding HGSO to a generally recognized as safe source of GLA, borage oil, in a 90 day safety study in rats. Weanling male and female Sprague-Dawley rats were fed a semi-synthetic, fat free, pelleted diet (AIN93G) supplemented with a 10% (wt/wt) oil blend containing HGSO or borage oil, with equivalent GLA levels. Results demonstrated that feeding diets containing HGSO or borage oil for 90 days had similar biologic effects with regard to growth characteristics, body composition, behavior, organ weight and histology, and parameters of hematology and serum biochemistries in both sexes. Metabolism of the primary n-6 fatty acids in plasma and organ phospholipids was similar, despite minor changes in females. We conclude that HGSO is biologically equivalent to borage oil and provides a safe alternative source of GLA in the diet.

The effects of an oral supplement enriched with fish oil, prebiotics, and antioxidants on nutrition status in Crohn's disease patients.

BACKGROUND: Research in the treatment of Crohn's disease (CD) supports anti-inflammatory benefits of n-3 fatty acids from fish oil, prebiotics, and antioxidants. A nutritionally balanced inflammatory bowel disease nutrition formula (IBDNF) enriched with these compounds has the potential to improve nutrition status and disease activity in CD. METHODS: This is an open-label pilot study investigating the effects of IBDNF on nutrition status in CD patients. Twenty-eight patients with active CD on stable medication were asked to consume 16 oz of IBDNF/d for 4 months. Nutrition status was assessed with dual-energy X-ray absorptiometry scans and serum micronutrient levels. Disease activity and quality of life were measured using the Crohn's Disease Activity Index (CDAI) and the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: Twenty patients completed the final visit. After 4 months, there was a significant decrease in plasma phospholipid levels of arachidonic acid with increases in eicosapentaenoic acid (EPA) and docosahexaenoic acid. Ten patients had a final EPA concentration of >2%. There was improvement in fat-free and fat mass in patients with final EPA >2% (P = .014 and P = .05). Vitamin D (25-OH) levels improved in all patients (18.5-25.9 ng/mL, P < .001). Those with EPA >2% had significantly lower CDAI (116 ± 94.5 vs 261.8 ± 86.5; P = .005) and higher IBDQ (179.1 ± 26.6 vs 114.6 ± 35.9, P < .001) compared to those with EPA <2%. CONCLUSIONS: IBDNF has the potential to deposit fat-free and fat mass, improve vitamin D status, and improve quality of life in CD patients.

Attenuation of proteolysis and muscle wasting by curcumin c3 complex in MAC16 colon tumour-bearing mice.

Muscle wasting or cachexia is caused by accelerated muscle protein breakdown via the ubiquitin-proteasome complex. We investigated the effect of curcumin c3 complex (curcumin c3) on attenuation of muscle proteolysis using in vitro and in vivo models. Our in vitro data indicate that curcumin c3 as low as 0.50 microg/ml was very effective in significantly inhibiting (30 %; P < 0.05) tyrosine release from human skeletal muscle cells, which reached a maximum level of inhibition of 60 % (P < 0.05) at 2.5 microg/ml. Curcumin c3 at 2.5 microg/ml also inhibited chymotrypsin-like 20S proteasome activity in these cells by 25 % (P < 0.05). For in vivo studies, we induced progressive muscle wasting in mice by implanting the MAC16 colon tumour. The in vivo data indicate that low doses of curcumin c3 (100 mg/kg body weight) was able to prevent weight loss in mice bearing MAC16 tumours whereas higher doses of curcumin c3 (250 mg/kg body weight) resulted in approximately 25 % (P < 0.05) weight gain as compared with the placebo-treated animals. Additionally, the effect of curcumin c3 on preventing and/or reversing cachexia was also evident by gains in the weight of the gastrocnemius muscle (30-58 %; P < 0.05) and with the increased size of the muscle fibres (30-65 %; P < 0.05). Furthermore, curcumin inhibited proteasome complex activity and variably reduced expression of muscle-specific ubiquitin ligases: atrogin-1/muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MURF-1). In conclusion, oral curcumin c3 results in the prevention and reversal of weight loss. The data imply that curcumin c3 may be an effective adjuvant therapy against cachexia.

Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse.

Diets rich in monounsaturated fatty acids (MUFA) are recommended for individuals with type 2 diabetes mellitus (T2DM). The American Heart Association recommends increasing intakes of n-3 polyunsaturated fatty acids (PUFA) to reduce the risk of vascular disease in high-risk individuals; however, the long-term effects of these bioactive fatty acids on glucose metabolism in insulin resistance are controversial. The present studies were conducted to evaluate the effects of diets rich in both MUFA and alpha linolenic acid (C18:3n-3, ALA), eicosapentaenoic acid (C20:5n-3, EPA), or docosahexaenoic acid (C22:6n-3, DHA), on glycemic control and other parameters related to vascular health in a mouse model of T2DM and insulin resistance. Male ob/ob mice (n = 15 per treatment) were fed 1 of 4 lipid-modified formula diets (LFDs) for 4 weeks: (1) MUFA control, (2) ALA blend, (3) EPA blend, and (4) DHA blend. A portion of a MUFA-rich lipid blend in the control LFD was replaced with 11% to 14% energy as n-3 PUFA. After 4 weeks, plasma glucose response to a standard meal (1.5 g carbohydrate/kg body weight) and insulin challenge (2 U/kg body weight, IP) was assessed, and samples were collected for analysis of glucose, insulin, and lipids. Vascular reactivity of isolated aortic rings was assessed in an identical follow-up study. The results showed that insulin-resistant mice fed an LFD with EPA and/or DHA blends had significantly (P < .05) lower triglycerides and free fatty acids, but insulin sensitivity and fasting plasma glucose were not improved. However, mice fed with the ALA blend had significantly improved insulin sensitivity when compared to those fed with other LFD (P < .05). Animals fed an LFD with n-3 PUFA from marine or plant sources showed significantly improved vascular responses as compared with the MUFA-rich LFD (E(max), P < .05) and ob/ob reference mice consuming chow (E(max) and pEC(50), P < .05). In summary, long-term consumption of LFD with n-3 PUFAs improved blood lipids and vascular function in an animal model of insulin resistance and T2DM; however, only MUFA-rich LFD with ALA also improved both insulin sensitivity and glycemic responses. Further studies of MUFA-rich LFD with ALA with individuals who have T2DM are warranted.

Green tea polyphenols modulate secretion of urokinase plasminogen activator (uPA) and inhibit invasive behavior of breast cancer cells.

Many epidemiological studies have suggested that consumption of green tea may decrease the risk of cancer. The chemopreventive effect of green tea polyphenols (GTP) has been demonstrated through the inhibition of cell proliferation and angiogenesis in cell culture and animal models of breast cancer. Metastasis of breast cancer is the major reason for the high mortality of breast cancer patients and is directly linked to the invasive behavior of breast cancer cells. Cancer metastasis consists of several interdependent processes including cancer cell adhesion, cancer cell migration, and invasion of cancer cells. In this study, we evaluated the effect of GTP on human breast cancer cells, and we show that in addition to inhibiting cell growth, GTP also suppressed the invasive behavior of MDA-MB-231 cells. These anti-invasive effects of GTP were the result of the inhibition of constitutively active transcription factors AP-1 and NF-kappaB, which further suppressed secretion of urokinase plasminogen activator (uPA) from breast cancer cells. Based on these results, it can be hypothesized that GTP treatment resulted in the inhibition of formation of signaling complexes responsible for cell adhesion and migration (uPA, uPA receptor, vitronectin, integrin receptor) and cell invasion (uPA, uPA receptor). Our results indicate that GTP may contribute to the anticancer effects of green tea by inhibiting the invasive behavior of cancer cells.

An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: a randomized, controlled trial.

BACKGROUND & AIMS: N-3 fatty acids from fish oil, antioxidants, and short-chain fatty acids (SCFAs) produced during the fermentation of soluble fiber may attenuate inflammation associated with ulcerative colitis (UC). We assessed the efficacy of a nutritionally balanced oral supplement enriched with fish oil, fructooligosaccharides, gum arabic, vitamin E, vitamin C, and selenium on disease activity and medication use in adults with mild to moderate UC. METHODS: A total of 121 patients with UC and a disease activity index (DAI) from 3-9 on a 12-point scale were block randomized for extent of disease and smoking status. In addition to their usual diet, patients consumed 18 oz of the oral supplement or a carbohydrate-based placebo formula each day for 6 months. Clinical and histologic responses were assessed at 3 and 6 months or at the final visit. A change in average prednisone use between groups was tested by using a linear mixed-effects model. RESULTS: Eighty-six patients completed the study. Baseline characteristics were not different between groups except for a higher total DAI score in the oral supplement group (7.3 +/- 1.3; n = 36) compared with the placebo group (6.2 +/- 2.0; n = 50) ( P < .05). Both groups showed significant and similar degree of improvement at 6 months in DAI (-2.5 for oral supplement and -2.8 for placebo) and histologic index (-1.9 for oral supplement vs. -2.0 for placebo). Both intent-to-treat and completed patients given oral supplement had a significantly greater rate of decrease in the dose of prednisone required to control clinical symptoms over 6 months as compared with the placebo group ( P < .001). CONCLUSIONS: The improvement in clinical response combined with a decreased requirement for corticosteroids suggest that this enriched oral supplement can be a useful adjuvant therapy in patients with UC.

Effect of long-term dietary supplementation of high-gamma-linolenic canola oil versus borage oil on growth, hematology, serum biochemistry, and N-6 fatty acid metabolism in rats.

Dietary supplementation of a high-gamma-linolenic acid canola oil (HGCO) containing approximately 36% (w/w) of gamma-linolenic acid (GLA, 18:3n-6) from the seeds of a genetically transformed canola strain, was assessed for its long-term biological effects. Growing Sprague-Dawley rats (n = 30) were fed a purified AIN93G diet containing 5, 10, or 15% (w/w) of HGCO as the fat source. For comparison, a separate group of rats (n = 10) was given the diet containing 15% (w/w) of borage oil (BO), which contained 22% (w/w) of GLA. After 12 weeks of feeding, the growth, relative organ weights, hematology, and serum biochemistry were found to be similar among rats fed the 5, 10, and 15% HGCO diets. The GLA levels in plasma and liver phospholipids (PL) were also similar. However, the levels of GLA in peripheral tissues (muscle PL and adipose triacylglycerols) were significantly higher in rats fed the 10 and 15% HGCO diets than those fed the 5% HGCO diet. When the above biologic parameters were compared between the 15% HGCO and 15% BO dietary groups, there were no significant differences except for lower final body weights and higher tissue levels of GLA, dihomo-gamma-linolenic acid (20:3n-6) and arachidonic acid (20:4n-6) in the 15% HGCO dietary group as compared with the 15% BO dietary group. This is due to a higher GLA content and possibly a more favorable stereospecific distribution of GLA in HGCO. Overall, long-term (12-week) feeding with diets containing up to 15% HGCO resulted in no adverse effects on growth, organ weight, hematology and serum biochemistry as compared to the diet containing 15% BO, suggesting that HGCO may be a safe alternative source of GLA.

Effects of high-gamma-linolenic acid canola oil compared with borage oil on reproduction, growth, and brain and behavioral development in mice.

Previous research in rats and mice has suggested that gamma-linolenic acid (GLA) derived from borage oil (BO: 23% GLA) may be an appropriate source for increasing levels of long-chain n-6 FA in the developing brain. Recently, transgenic technology has made available a highly enriched GLA seed oil from the canola plant (HGCO: 36% GLA). The first objective of this study was to compare the effects of diets containing equal levels of GLA (23%) from either BO or HGCO on reproduction, pup development, and pup brain FA composition in mice. The second objective was to compare the effects of the HGCO diluted to 23% GLA (GLA-23) with those of undiluted HGCO containing 36% GLA (GLA-36). The diets were fed to the dams prior to conception and throughout pregnancy and lactation, as well as to the pups after weaning. The behavioral development of the pups was measured 12 d after birth, and anxiety in the adult male offspring was assessed using the plus maze. The findings show that despite equivalent levels of GLA, GLA-23 differed from BO in that it reduced pup body weight and was associated with a slight increase in neonatal pup attrition. However, there were no significant effects on pup behavioral development or on performance in the plus maze. An increase in dietary GLA resulted in an increase in brain 20:4n-6 and 22:4n-6, with a corresponding decrease in 22:6n-3. Again, despite their similar levels of GLA, these effects tended to be larger in GLA-23 than in BO. In comparison with GLA-23, GLA-36 had larger effects on growth and brain FA composition but no differences with respect to effects on reproduction and behavioral development. These findings suggest that the HGCO can be used as an alternative source of GLA.

Supplementation with 3 compositionally different tocotrienol supplements does not improve cardiovascular disease risk factors in men and women with hypercholesterolemia.

BACKGROUND: Tocotrienols have been reported to lower LDL-cholesterol and fasting glucose concentrations and to have potent antioxidant effects, but the results are contradictory. OBJECTIVE: The objective was to study the relative effect of tocotrienol supplements of different compositions (mixed alpha- plus gamma-, high gamma-, or P25-complex tocotrienol) on blood lipids, fasting blood glucose, and the excretion of 8-iso-prostaglandin F(2alpha), a measure of oxidative stress, in healthy hypercholesterolemic men and women. DESIGN: This was a double-blind, randomized, parallel-design study in which subjects (n = 67 men and women) consumed 1 of 3 commercially available tocotrienol supplements or a safflower oil placebo for 28 d. Blood and urine samples were obtained before and after the 28-d supplementation phase for analysis of fasting blood lipids, glucose, tocotrienols and tocopherols, and 8-iso-prostaglandin F(2alpha). RESULTS: Overall, serum tocotrienols were increased in subjects who consumed tocotrienols, which showed that the putatively active components were absorbed. No significant differences in mean lipid or glucose concentrations were observed among the 4 treatment groups at the end of the 28-d supplementation phase. However, when the values were expressed as a percentage change from the concentrations during the presupplementation run-in phase, LDL cholesterol increased slightly (7 +/- 2%) but significantly (P < 0.05) in the group consuming the mixed alpha- plus gamma-tocotrienol supplement when compared with LDL cholesterol in the group consuming the P25-complex tocotrienol. Neither mean concentrations nor the percentage change in 8-iso-prostaglandin F(2alpha) differed significantly among treatments. CONCLUSION: Supplementation with 200 mg tocotrienols/d from 3 commercially available sources has no beneficial effect on key cardiovascular disease risk factors in highly compliant adults with elevated blood lipid concentrations.

Intestinal absorption and lymphatic transport of a high gamma-linolenic acid canola oil in lymph fistula Sprague-Dawley rats.

A new canola strain capable of producing >30% gamma-linolenic acid [GLA, 18:3(n-6)] in the seed oil has been developed in our laboratories. This study compares the intestinal absorption and lymphatic transport of this newly developed high GLA content canola oil (HGCO) with traditional GLA-rich borage oil (BO) using a lymph fistula rat model. To assess the extent that 1 mL of GLA in the supplemented oil was absorbed and transported, the fatty acid compositions of triglycerides in mesenteric lymph were compared over a 24-h collection period. The digestion, uptake and lymphatic transport of HGCO and the normal physiologic changes associated with fat absorption (e.g., lymph flow and an increase in lymphatic endogenous lipids outputs, triglycerides, cholesterol and phospholipids) were similar in the HGCO-and the BO-fed rats. The original differences in gamma-linolenic acid content in HGCO and BO were preserved in the fatty acid composition of the rats' lymph lipid. We conclude that the HGCO derived from the genetically modified canola plant is absorbed and transported into lymph similarly to BO.