Dietary Flaxseed Supplementation Research Articles

239 Effect of dietary flaxseed supplementation on folliculo-endocrine, superovulatory response, embryo quality, and pregnancy rate in Sahiwal cows

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

The effect of dietary flaxseed supplementation on sperm fatty acid composition, semen quality attributes and some blood parameters in Kurdish ram

دانه کتان منبع غنی از اسید آلفا لینولنیک (امگا3) با خاصیت آنتی اکسیدانی بالا ‌می‌باشد، که ‌می‌تواند در سنتز هورمون‌های جنسی و بهبود کیفیت اسپرم در گونه‌های مختلف نقش داشته باشد. مطالعه حاضر اثرات دانه کتان بر خصوصیات کمی و کیفی اسپرم و برخی پارامترهای خونی را بررسی ‌می‌کند. در این تحقیق که در مدت 12 هفته اجرا گردید 15 راس قوچ نژاد کردی انتخاب و به صورت تصادفی به سه گروه تقسیم شدند. گروه شاهد دریافت کننده جیره پایه و گروه دوم که شامل جیره پایه و 5 درصد دانه کتان و گروه سوم محتوی جیره پایه و 10 درصد دانه بود. نتایج نشان داد که غلظت اسپرم، نسبت اسپرم زنده، تحرک کل و عملکرد غشای پلاسما در تیمار 10 درصد دانه کتان در مقایسه با سایر گروه‌ها بیشتر بود (P<0.05). دانه کتان باعث افزایش درصد اسپرم با آکروزوم نرمال شد (P<0.01). با این حال، درصد اسپرم‌های غیر طبیعی پس از دریافت 10 درصد دانه کتان و در پایان هفته 12 در مقایسه با سایر گروه‌های مربوطه کاهش یافت (P<0.05). نتایج نشان داد که مکمل دانه کتان بر قطر بیضه اثری نداشت اما غلظت تستوسترون پلاسما را در گروه 10 درصد نسبت به گروه شاهد افزایش داد (P <0.05). اثر افزودن مکمل دانه کتان، اثر زمان و اثر متقابل آنها بر فعالیت آنزیم گلوتاتیون پراکسیداز معنی دارنبود. جیره 10 درصد کتان موجب افزایش معنی داری اسید چرب DHA (دوکوزاهگزاانوئیک DHA=Docosahexaenoic acid) در چربی اسپرم شد (P<0.05). نسبت اسیدهای چرب امگا سه به شش افزایش یافته و نیز نسبت اسیدهای چرب اشباع به اسیدهای چرب با چند باند مضاعف در گروه 10 درصد در مقایسه با سایر گروه‌ها کاهش یافت (P<0.05). نتایج نشان داد که افزودن 10 درصد دانه کتان به جیره پایه قوچ‌های کردی در خارج از فصل تولید مثل ‌می‌تواند سبب بهبود کمی و کیفی شاخص‌های ازریابی اسپرم و در نهایت بهبود باروری آنها گردد.

Cardioprotective Effects of Dietary Flaxseed Post-Infarction Are Associated with Changes in MicroRNA Expression.

MicroRNAs (miRNAs/miRs) such as miR-1, miR-133a, miR-133b, miR-135a, and miR-29b play a key role in many cardiac pathological remodeling processes, including apoptosis, fibrosis, and arrhythmias, after a myocardial infarction (MI). Dietary flaxseed has demonstrated a protective effect against an MI. The present study was carried out to test the hypothesis that dietary flaxseed supplementation before and after an MI regulates the expression of above-mentioned miRNAs to produce its cardioprotective effect. Animals were randomized after inducing MI by coronary artery ligation into: (a) sham MI with normal chow, (b) MI with normal chow, and (c–e) MI supplemented with either 10% milled flaxseed, or 4.4% flax oil enriched in alpha-linolenic acid (ALA), or 0.44% flax lignan secoisolariciresinol diglucoside. The feeding protocol consisted of 2 weeks before and 8 weeks after the surgery. Dietary flax oil supplementation selectively upregulated the cardiac expression of miR-133a, miR-135a, and miR-29b. The levels of collagen I expression were reduced in the flax oil group. We conclude that miR-133a, miR-135a, and miR-29b are sensitive to dietary flax oil, likely due to its rich ALA content. The cardioprotective effect of flaxseed in an MI could be due to modulation of these miRNAs.

Abstract B35: Dietary flaxseed supplementation in ovarian cancer: Elucidating the molecular actions of its biologically derived active compounds

Abstract The goal of our study is to elucidate the anti-ovarian cancer molecular mechanisms promoted by a flaxseed-supplemented diet in the laying hen. A flaxseed-supplemented diet generates a myriad of biologically active compounds that work synergistically to attack ovarian tumors. Our laboratory has demonstrated that flaxseed diet reduces the occurrence and severity of ovarian cancer in laying hen—the only spontaneous animal model for ovarian cancer. Flax diet in chicken induces the CYP1A1 pathway of estrogen metabolism increasing production of 2-hydroxy and 2-methoxy metabolites. 2-methoxyestradiol (2ME) is produced by the Catechol-O-Methyl transferase (COMT) enzyme from 2-hydroxyestradiol—a pathway that reduces estrogen toxicity, which is protective against ovarian cancer. Flaxseed is also a rich source of omega-3 fatty acids, mostly a-linoleic acid (ALA), which is converted into docosahexaenoic acid (DHA) in the gut. We have recently shown that flaxseed diet induces apoptosis and inhibits angiogenesis in the chicken ovarian tumors. 2ME promotes apoptosis and inhibits angiogenesis via activation of p38-MAPK; DHA has potent antiangiogenic and anti-inflammatory actions, however not dependent on the p38-MAPK pathway. To further investigate the molecular mechanisms of the antiangiogenic actions of flax diet, a qRT-PCR array analyzing 84 key genes involved in angiogenesis was performed. Nine key genes were significantly downregulated with flax diet. These genes are involved in hypoxia-induced endothelial cell migration, proliferation, differentiation, and lymphangiogenesis. Using human ovarian cancer cells, DNA damage was studied by TUNEL staining; DNA content and cell cycle progression were studied by PI staining and flow cytometry; apoptosis was measured by cleavage of caspase-3 by Western blot. 2ME treatment induced phosphorylation at ser139 of histone H2A (gH2Ax), a known marker for dsDNA breaks, along with phosphorylation at ser10 of histone H3 (pHH3) and ser14 of histone H2B (pHH2B). 2ME is known to bind at/near the colchicine binding site of the growing microtubules and therefore arresting cells at G2/M phase. 2ME effects were equivalent in ERa positive and negative human ovarian cancer cells. Also, the selective GPR30 agonist and antagonist, G1 and G15, did not modulate the effects of 2ME. Therefore, the anticancer actions of 2ME are not dependent on or mediated through the estrogen receptors. (NIH RO1AT005295) Citation Format: Purab Pal, Karen Hales, Dale Buchanan Hales. Dietary flaxseed supplementation in ovarian cancer: Elucidating the molecular actions of its biologically derived active compounds [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B35.

Flaxseed Consumption Inhibits Chemically Induced Lung Tumorigenesis and Modulates Expression of Phase II Enzymes and Inflammatory Cytokines in A/J Mice

Flaxseed consumption is associated with reduced oxidative stress and inflammation in lung injury models and has shown anticancer effects for breast and prostate tissues. However, the chemopreventive potential of flaxseed remains unexplored for lung cancer. In this study, we investigated the effect of flaxseed on tobacco smoke carcinogen (NNK)-induced lung tumorigenesis in an A/J mouse model. Mice exposed to NNK were fed a control diet or a 10% flaxseed-supplemented diet for 26 weeks. Flaxseed-fed mice showed reduced lung tumor incidence (78%) and multiplicity, with an average of 2.7 ± 2.3 surface lung tumor nodules and 1.0 ± 0.9 H&E cross-section nodules per lung compared with the control group, which had 100% tumor incidence and an average of 10.2 ± 5.7 surface lung tumor nodules and 3.9 ± 2.6 H&E cross-section nodules per lung. Furthermore, flaxseed-fed mice had a lower incidence of adenocarcinomas compared with control-fed mice. Western blotting performed on normal lung tissues showed flaxseed suppressed phosphorylation (activation) of p-AKT, p-ERK, and p-JNK kinases. RNA-Seq data obtained from normal lung and lung tumors of control and flaxseed-fed mice suggested that flaxseed intake resulted in differential expression of genes involved in inflammation-mediated cytokine signaling (IL1, 6, 8, 9, and 12α), xenobiotic metabolism (several CYPs, GSTs, and UGTs), and signaling pathways (AKT and MAPK) involved in tumor cell proliferation. Together, our results indicate that dietary flaxseed supplementation may be an effective chemoprevention strategy for chemically induced lung carcinogenesis by altering signaling pathways, inflammation, and oxidative stress. Cancer Prev Res; 11(1); 27-37. ©2017 AACR.

Performance and egg quality of laying hens fed flaxseed: highlights on n-3 fatty acids, cholesterol, lignans and isoflavones

Flaxseed is a rich source of α-linolenic acid and phytoestrogens, mainly lignans, whose metabolites (enterodiol and enterolactone) can affect estrogen functions. The present study evaluated the influence of dietary flaxseed supplementation on reproductive performance and egg characteristics (fatty acids, cholesterol, lignans and isoflavones) of 40 Hy-Line hens (20/group) fed for 23 weeks a control diet or the same diet supplemented with 10% of extruded flaxseed. The flaxseed diet had approximately three times the content of lignans (2608.54 ng/g) as the control diet, mainly secoisolariciresinol diglucoside (1534.24 v. 494.72 ng/g). When compared with the control group, hens fed flaxseed showed a similar deposition rate (72.0% v. 73.9%) and egg yield. Furthermore, there was no effect of flaxseed on the main chemical composition of the egg and on its cholesterol content. Estradiol was higher in the plasma of the control group (1419.00 v. 1077.01 pg/ml) probably due to the effect of flaxseed on phytoestrogen metabolites. The plasma lignans were higher in hens fed flaxseed, whereas isoflavones were lower, mainly due to the lower equol value (50.52 v. 71.01 ng/ml). A similar trend was shown in eggs: the flaxseed group had higher level of enterodiol and enterolactone, whereas the equol was lower (198.31 v. 142.02 ng/g yolk). Secoisolariciresinol was the main lignan in eggs of the flaxseed group and its concentration was three times higher then control eggs. Flaxseed also improved the n-3 long-chain polyunsaturated fatty acids of eggs (3.25 v. 0.92 mg/g egg), mainly DHA, however, its oxidative status (thiobarbituric reactive substances) was negatively affected. In conclusion, 10% dietary flaxseed did not affect the productive performance of hens or the yolk cholesterol concentration, whereas the lignans and n-3 polyunsaturated fatty acid content of eggs improved. Further details on the competition between the different dietary phytoestrogens and their metabolites (estrogen, equol, enterodiol and enterolactone) should be investigated.

Quality of buffalo milk as affected by dietary protein level and flaxseed supplementation

The aim of the present research was to evaluate the effects of protein level and flaxseed supplementation on the yield and quality of buffalo milk. In particular, the fatty acid profile of milk from buffalo cows subjected to different diets has been investigated. A 2×3 factorial design was tested with buffalo cows receiving 2 dietary crude protein (CP) and 3 flaxseed (FS) supplementation levels. Treatments were (1) low dietary CP level [12% of dry matter (DM)] and no flaxseed supplementation (LP); (2) low dietary CP level (12% of DM) and low flaxseed supplementation (500g/d) (LPFS500); (3) low dietary CP level (12% of DM) and moderate flaxseed supplementation (1,000g/d) (LPFS1000); (4) moderate dietary CP level (15% of DM) and no flaxseed supplementation (MP); (5) moderate dietary CP level (15% of DM) and low flaxseed supplementation (500g/d) (MPFS500); and (6) moderate dietary CP level (15% of DM) and moderate flaxseed supplementation (1,000g/d) (MPFS1000). Milk protein and casein were affected by flaxseed supplementation being higher in MP, intermediate in LP, and lower in flaxseed-supplemented diets. However, the results from the present study highlighted that low protein diets sustained milk yield, protein, and casein synthesis in milk when whole flaxseed was administered. Short-chain fatty acids, in particular C8:0 and C10:0, were the lowest in milk from buffalo cows fed the highest level of flaxseed supplementation. Medium-chain fatty acids were the lowest in FS1000, intermediate in FS500, and the highest in the HP and LP groups. Long-chain fatty acids were the highest in FS1000, intermediate in FS500 groups, and the lowest in milk from buffalo receiving no flaxseed supplementation. Protein level of the diet influenced the percentage of C18:0, which was higher in MP than LP groups. Total conjugated linoleic acid content evidenced the same trend of long-chain fatty acids, with an increase of about 7% in FL500 and of 22% in FL1000 than the control. Apart from protein level of the diet, atherogenic index, thrombogenic index, and n-6/n-3 were the lowest in FS1000 groups; thrombogenic index and n-6/n-3 were intermediate in milk from animals receiving FS500. Nutritional value of the acidic profile in buffalo milk is influenced by flaxseed supplementation, and its improvement reflects the level of dietary flaxseed supplementation.

Fatty acid profile of milk and Cacioricotta cheese from Italian Simmental cows as affected by dietary flaxseed supplementation

The study aimed to determine the effects of adding flaxseed to the diet on the fatty acid profile of the milk of Italian Simmental cows and on the Cacioricotta cheese thereby produced. The experiment involved 24 Italian Simmental cows divided into 2 groups of 12 animals according to the diet fed: a control diet (CO) with no flaxseed supplementation, and a diet supplemented with whole flaxseed (FS). Milk yield and composition was not significantly changed by diet, whereas saturated fatty acids, monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) were increased by flaxseed supplementation. Cows fed flaxseed showed higher percentages of long-chain fatty acids: in particular, linolenic acids, mainly represented by C18:3n-3, and n-3 series were higher in the FS group than in the CO group. The percentage of MUFA was higher by about 12% in FS than in CO, mainly due to the contribution of C18:1 cis-9. The percentage of conjugated linoleic acid (CLA) in milk was not significantly changed by flaxseed supplementation. Furthermore, atherogenic and thrombogenic indices were lower by about 30 and 16%, respectively, in the FS group compared with the CO group. The fatty acid profile of Cacioricotta cheese produced using Italian Simmental cow milk showed higher levels of MUFA, PUFA, and n-3, and improved atherogenic and thrombogenic indices in FS than in CO, confirming the ability to transfer beneficial molecules from milk into cheese. In particular, cheese-making technology contributed to the increased CLA content in Cacioricotta cheese.

Flaxseed Suppressed Prostatic Epithelial Proliferation in a Rat Model of Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH), a disease occurring frequently among elderly males, is a slow progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. Dietary factors may influence the prostate and exert an influence on prostatic growth and disease. The current study was undertaken to investigate the protective effect of dietary flaxseed supplementation against testosterone-induced prostatic hyperplasia in male rats. Forty male Wistar rats were divided into 5 groups: (1) untreated control; (2) treatment with testosterone propionate (TP) to induce prostate enlargement; (3) TP-treated group fed a diet containing 5% milled flaxseed; (4) TP-treated group fed a diet containing 10% milled flaxseed; and (5) TP-treated group fed a diet containing 20 ppm finasteride. Treatment with TP significantly increased the absolute and relative weights of different prostatic lobes, serum testosterone (T), and testosterone/estradiol ratio, as well as prostatic vascular endothelial growth factor (VEGF) expression, RNA synthesis per cell, and epithelial cell proliferation, detected as Ki67 labeling. Histopathological examination did not reveal marked differences in acinar morphology in ventral prostate, whereas morphometric analysis showed significantly increased epithelial cell height. Co-administration of flaxseed or finasteride with TP significantly reduced prostatic VEFG, epithelial cell proliferation, and RNA/DNA ratio, along with a significant increase in serum T and testosterone/estradiol ratio compared with TP-only-treated rats. Our results indicate that flaxseed, similar to the 5α-reductase inhibitor finasteride, blocked TP-induced prostate enlargement in a rat model of BPH, likely through suppression of prostatic VEFG and cellular proliferation.

Flaxseed in Pediatric Hyperlipidemia

Nonpharmacological management of hypercholesterolemia in children is challenging with few available options. OBJECTIVES To determine the safety and efficacy of dietary flaxseed supplementation in the management of hypercholesterolemia in children. DESIGN Four-week placebo-controlled, blinded, randomized clinical trial. Specialized dyslipidemia clinic at a tertiary pediatric care center. PARTICIPANTS Thirty-two participants aged 8 to 18 years with low-density lipoprotein cholesterol from 135 mg/dL (3.5 mmol/L) to less than 193 mg/dL (5.0 mmol/L). The intervention group ate 2 muffins and 1 slice of bread daily containing ground flaxseed (30 g flaxseed total). The control group ate muffins and bread substituted with whole-wheat flour. MAIN OUTCOME AND MEASURE Attributable change in fasting lipid profile. RESULTS Dietary flaxseed supplementation resulted in an attributable decrease of -7.35 mg/dL (-0.19 mmol/L) in high-density lipoprotein cholesterol (95% CI, -3.09 to -11.60 mg/dL[-0.08 to -0.30 mmol/L]; relative: -15%, 95% CI, -24% to -6%; P = .001), an increase of 29.23 mg/dL (+0.33 mmol/L) in triglycerides (95% CI, 4.43 to 53.14 mg/dL [+0.05 to +0.60 mmol/L]; relative: +26%, 95% CI, +4% to +48%; P = .02), and an increase of +4.88 g/d in dietary polyunsaturated fat intake (95% CI, +0.22 to +9.53; relative: +76%, 95% CI, +3% to +148%; P = .04). Flaxseed had no attributable effects on total cholesterol (-8.51 mg/dL [-0.22 mmol/L]; 95% CI, -21.66 to 4.25 mg/dL [-0.56 to +0.11 mmol/L]; relative: -4%, 95% CI, -10% to +2%; P = .20), low-density lipoprotein cholesterol (-6.96 mg/dL [-0.18 mmol/L]; 95% CI, -16.63 to 2.71 mg/dL [-0.43 to +0.07 mmol/L]; relative: -5%, 95% CI, -12% to +2%; P = .15), body mass index z score (+0.002; 95% CI, -0.147 to +0.150; relative: +0%, 95% CI, -12% to +12%; P = .30), or total caloric intake (+117 kcal; 95% CI, -243 to +479; relative: +8%, 95% CI, -17% to +33%; P = .52). An attributable change in total and low-density lipoprotein cholesterol failed to exclude a potential benefit of flaxseed supplementation based on a prespecified minimum clinically important reduction of 10%. No concerns were noted regarding safety. The use of dietary flaxseed supplementation, while safe, was associated with adverse changes in the lipid profile of children with hypercholesterolemia, although a potential benefit of low-density lipoprotein cholesterol lowering could not be excluded. The use of flaxseed supplementation in children with hypercholesterolemia might not be a viable option for lipid management in this population. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01007344.

Influence of defatted flaxseed diet on insulin sensitivity, vascular permeability and lipid profile in a rat model of type 2 diabetes mellitus

The impact of flaxseed (FSD) intake, a rich source of alpha linolenic acid (ALA), fiber and lignans, on the cardiovascular system is well documented. However, mechanisms by which flaxseed improve cardiovascular health are not clear. The aim of this study was to investigate the effects of dietary flaxseed on vascular permeability and endothelial function in streptozotocin-induced type 2 diabetes in rats. Type 2 diabetes mellitus (T2DM) was induced in male Sprague-Dawley rats by intraperitoneal injection of streptozotocin (35 mg/kg body weight) after short term feeding of high fructose diet. Diabetic rats were divided into three groups, one group fed standard diet, second group fed standard diet supplemented with defatted flaxseed powder (FSD), and third group received Metformin (200 mg/kg BW (body weight)) for 8 weeks. Fasting serum concentrations of glucose (FPG), insulin, vascular endothelial growth factor (VEGF), nitric oxide (NO), uric acid (UA) and lipid profile were measured. Vascular permeability index (VPI) was assessed at the end of experiment by quantifying the extravasation of albumin-bound Evans blue (EB) dye in the heart. Dietary FSD supplementation is comparable to Metformin in modulating blood lipid profiles, insulin and FPG levels. FSD intake was associated with significant reductions in serum insulin (-66%), glucose (-68%), VEGF levels (-66.8%) and UA (-63%), and NO (-37.5%) as compared to diabetic group without FSD supplementation. There were also improvements in lipid profile, vascular permeability index (VPI), insulin resistance and atherogenic indices in diabetic rats supplemented with flaxseed. These results suggest that dietary FSD supplementation may reduce the incidence of diabetic vascular complications through improvement of insulin sensitivity, vascular permeability and lipid profile. Key words: Diabetes mellitus, cardiovascular diseases, vascular permeability, endothelial dysfunction, insulin resistance, vascular endothelial growth factor, nitric oxide.

Dietary flaxseed supplementation improves endothelial function in the mesenteric arterial bed

Abstract The aim of this study was to evaluate the influence of flaxseed diet supplementation on endothelial function in the mesenteric arterial bed of rats. Twenty-four rats were divided into 3 groups: Control Group (CG; 10% protein; 5% fiber; 7% lipid); Flaxseed Group (FG, supplemented with 25% flaxseed; 10% protein; 7% fiber; 11% lipid); and Modified Control Group (MCG; 10% protein; 7% fiber; 11% lipid). The blood was obtained by cardiac puncture (after 180 days) and the serum was separated for lipid profile analyses. The vasodilator effect of acetylcholine (1–100 pmol) was evaluated in the preconstricted isolated rat vascular bed. FG showed a 47% increase in HDL-C, a 22% reduction in LDL-C, a 23% reduction in triacylglycerols, and an increased ( p

Omega-3-enriched broiler meat: 3. Fatty acid distribution between triacylglycerol and phospholipid classes

Consumers are becoming more aware of the effect of the food they eat on their health. One of the ways they hope to reduce their risk of cardiovascular disease is by consuming more foods enriched with n-3 polyunsaturated fatty acids (PUFA). Due to the high content of α-linolenic acid (LNA), dietary flaxseed is a good source for increasing n-3 PUFA in poultry meat. A study was conducted with 2 primary objectives: to establish the distribution of n-3 PUFA between tria-cylglycerol (TAG) and phospholipid of broiler chicken breast and thigh meat and to determine the duration of dietary flaxseed supplementation required to ensure a level of n-3 PUFA of 300 mg per 100 g of meat necessary to label meat as a source of n-3 PUFA. This experiment was conducted as a 2 × 8 factorial, with 2 dietary levels of ground flaxseed (10 and 17%) and 8 durations of dietary flaxseed before processing [0 (control), 4, 8, 12, 16, 20, 24, and 35 d]. A total of 128 Ross × Ross 308 mixed-sex broilers were evaluated to 35 d of age. Breast and thigh meat fatty acid composition was analyzed on duplicate samples of ground meat pooled from 8 birds per treatment. Broken-stick analysis was used to estimate the duration required to achieve 300 mg of n-3 PUFA per 100 g of breast meat. Results clearly indicated that LNA was mainly deposited in the TAG fraction of both breast and thigh meat. Enriching the chicken breast meat with 300 mg of n-3 PUFA per 100 g of meat was achieved in 11.3 and 26.2 d with a 17 and 10% level of flaxseed in diet, respectively. Although a significant increase of n-3 long-chain PUFA (20:5n-3, 22:5n-3, and 22:6n-3) was found in the phospholipid and TAG fraction of both tissues, the concentration of these functional components was low. More than 95% of n-3 PUFA enrichment was due to LNA.

Flaxseed Reduces Total and LDL Cholesterol Concentrations in Native American Postmenopausal Women

The objective of the study was to investigate the extent to which the daily incorporation of approximately 30 g of flaxseed, a rich source of lignans, omega-3 fatty acids, and fiber, for a period of 3 months into the diet of Native American postmenopausal women positively affects their lipid profiles. Fifty-five mild to moderately hypercholesterolemic (> or =5.1 to < or =9.8 mmol/L) Native American postmenopausal women were randomly assigned to control (A), flaxseed (B) or flaxseed + additional oat bran fiber (C) groups. Overnight fasting venous blood was collected at baseline and at the end of the treatment period to analyze lipid parameters. Dietary flaxseed supplementation lowered total cholesterol and low-density lipoprotein cholesterol (LDL-C) by approximately 7% and 10%, respectively. However, the levels of high-density lipoprotein (HDL) and triglyceride remained unaltered. No changes were observed in other clinical and hematological parameters. The results of the present study indicate that Native American postmenopausal women benefit from regular consumption of flaxseed by reducing their risk of cardiovascular disease as seen from lowered LDL-C and total cholesterol levels.

Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma

Patients with metastatic skin disease in malignant melanoma can be difficult to treat effectively, often requiring repeated treatments with different modalities in an attempt to control their disease. Treatment of nonsurgically resectable melanoma deposits is unsatisfactory, as they are often multiple and recurring. Anecdotal evidence from individual use of imiquimod in superficial metastases and intralesional interleukin (IL)-2 in subcutaneous deposits suggests that the combination may be more effective in bulky subcutaneous disease. To investigate the combination of topical imiquimod and, for selected lesions, intralesional IL-2, to treat a small cohort of patients with accessible melanoma metastases resistant to other treatments. Thirteen patients were recruited: all had evidence of multiple cutaneous and/or subcutaneous metastases. Imiquimod was applied to the metastases on a daily basis for 4 weeks, before the introduction of intralesional IL-2. This was injected up to three times a week, into selected lesions, with 0.1 mL injected per lesion at a concentration of 3.6 MIU mL(-1), a total of 1 mL being given at each session. The treated lesions were assessed individually at intervals of 3 months. Thirteen patients were treated, with 10 being eligible for assessment. In total, 182 lesions were treated: 137 purely cutaneous lesions and 41 subcutaneous lesions. Overall, a clinical response was seen in 92 lesions (50.5%) with 74 (40.7%) of these being a complete response (CR) with 91% of the CRs being in the cutaneous lesions. New lesions did appear during the treatment course; however, patients with cutaneous disease experienced a marked slowing of the appearance of new cutaneous lesions. No cutaneous lesions that responded reappeared on cessation of treatment. The combination of imiquimod and IL-2 is effective in controlling this mixed cutaneous and subcutaneous disease, and is well tolerated. Imiquimod alone is often enough to elicit a response in purely cutaneous lesions. The addition of intralesional IL-2 increases the response rates in subcutaneous lesions, and in otherwise refractory cutaneous lesions.

Dietary Flaxseed Supplementation Ameliorates Inflammation and Oxidative Tissue Damage in Experimental Models of Acute Lung Injury in Mice

Flaxseed (FS) is a nutritional supplement with high concentrations of (n-3) fatty acids and lignans that have anti-inflammatory and antioxidant properties. The use of FS in the prevention or treatment of acute lung disease is unknown. In this study, we evaluated diets with high FS content in experimental murine models of acute lung injury and inflammation. The kinetics of lignan accumulation in blood, following 10% FS supplementation, was determined using liquid chromatography tandem mass spectrometry. Mice were fed isocaloric control and 10% FS-supplemented diets for at least 3 wk and challenged by hyperoxia (80% oxygen), intratracheal instillation of lipopolysaccharide, or acid aspiration. Bronchoalveolar lavage was evaluated for white blood cells, neutrophils, and proteins after a 24 h postintratracheal challenge of hydrochloric acid or lipopolysaccharide, or after 6 d of hyperoxia. Lung lipid peroxidation was assessed by tissue malondialdehyde concentrations. The plasma concentrations of the FS lignans, enterodiol and enterolactone, were stable after mice had eaten the diets for 2 wk. Following hyperoxia and acid aspiration, bronchoalveolar lavage neutrophils decreased in FS-supplemented mice (P = 0.012 and P = 0.027, respectively), whereas overall alveolar white blood cell influx tended to be lower (P = 0.11). In contrast, neither lung injury nor inflammation was ameliorated by FS following lipopolysaccharide instillation. Lung malondialdehyde levels were lower in hyperoxic mice than in unchallenged mice (P = 0.0001), and decreased with FS treatment following acid aspiration (P = 0.011). Dietary FS decreased lung inflammation and lipid peroxidation, suggesting a protective role against pro-oxidant-induced tissue damage in vivo.

The effect of dietary flaxseed supplementation on organic anion and osmolyte content and excretion in rat polycystic kidney disease

Progression of chronic renal failure in the Han:SPRD-cy rat polycystic kidney disease is associated with renal depletion of citric acid cycle metabolites and betaine. Amelioration of this disease by a soy protein diet is associated with retention of citric acid cycle anions, despite increased excretion, and preservation of tissue levels of betaine. As we have recently found that modest dietary supplementation with flaxseed preserves renal function and reduces histologic injury in the Han:SPRD-cy rat, we undertook a high-resolution 1H NMR spectroscopic study of urine and renal tissue extracts from Han:SPRD-cy rats to explore the renal biochemical consequences of a flaxseed diet. There was no significant dietary effect upon organic anion, methylamine, or osmolyte excretion in healthy animals. There was increased citrate excretion in Han:SPRD-cy rats fed flaxseed. Urinary ammonium excretion did not differ, suggesting that the observed increase in citrate excretion was not due to an alkaline effect of diet. Tissue extract studies revealed that disease amelioration was associated with tissue retention of succinate and betaine. Amelioration of Han:SPRD-cy rat polycystic kidney disease by diet is associated with alteration in the handling of citric acid cycle metabolites. Betaine may have a metabolic role in the reduction of chronic renal injury.Key words: 1H NMR spectroscopy, polycystic kidney disease, rat, flaxseed.

Dietary flaxseed supplementation and experimental metastasis of melanoma cells in mice

The present study investigated the effect of dietary supplementation of flaxseed, the richest source of lignans, on experimental metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Mice were fed a basal diet or the basal diet supplemented with 2.5, 5 or 10% flaxseed for 2 weeks before and after the intravenous injection of 0.75×10 5 melanoma cells. At necropsy, the number of tumors that developed in the lungs was counted, the cross-sectional area of tumors was measured and the volumes of tumors were calculated. The median number of tumors in mice fed the 2.5, 5 and 10% flaxseed-supplemented diets was 32, 54 and 63% lower than that of the controls, respectively. The addition of flaxseed to the diet also caused a dose-dependent decrease in the tumor cross-sectional area and the tumor volume. These results provide the first experimental evidence that flaxseed reduces metastasis and inhibits the growth of the metastatic secondary tumors in animals. It is concluded that flaxseed may be a useful nutritional adjuvant to prevent metastasis in cancer patients.

The effect of dietary flaxseed supplementation on organic anion and osmolyte content and excretion in rat polycystic kidney disease.

Progression of chronic renal failure in the Han:SPRD-cy rat polycystic kidney disease is associated with renal depletion of citric acid cycle metabolites and betaine. Amelioration of this disease by a soy protein diet is associated with retention of citric acid cycle anions, despite increased excretion, and preservation of tissue levels of betaine. As we have recently found that modest dietary supplementation with flaxseed preserves renal function and reduces histologic injury in the Han:SPRD-cy rat, we undertook a high-resolution 1H NMR spectroscopic study of urine and renal tissue extracts from Han:SPRD-cy rats to explore the renal biochemical consequences of a flaxseed diet. There was no significant dietary effect upon organic anion, methylamine, or osmolyte excretion in healthy animals. There was increased citrate excretion in Han:SPRD-cy rats fed flaxseed. Urinary ammonium excretion did not differ, suggesting that the observed increase in citrate excretion was not due to an alkaline effect of diet. Tissue extract studies revealed that disease amelioration was associated with tissue retention of succinate and betaine. Amelioration of Han:SPRD-cy rat polycystic kidney disease by diet is associated with alteration in the handling of citric acid cycle metabolites. Betaine may have a metabolic role in the reduction of chronic renal injury.