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Biomedical subjects

B J Holub

Publications and source records attributed to B J Holub.

At least 19 recordsLinked to original sources

Very high concentrations of n-3 fatty acids in peri- and postmenopausal Inuit women from Greenland.

OBJECTIVES: The objectives of this study were to examine the profile of relative concentrations in plasma phospholipids of n-3 fatty acids among peri- and postmenopausal Inuit women living in Greenland and to verify their relationships with ischemic heart disease risk factors and more particularly, with concentrations of plasma triacylglycerols. STUDY DESIGN: This study was part of a survey conducted in 2000, which aimed to assess the prevalence of osteoporosis and the associated risk factors among peri- and postmenopausal Greenland Inuit women. METHODS: The study population consisted of 153 women aged 49-69 years (mean +/- SD: 55.3 +/- 4.4 y) randomly selected. Data were obtained through an interview (questionnaire on lifestyle habits, medical history etc) and a clinical session (physiologic and anthropologic measurements). Plasma samples were used to measure the fatty acid composition of plasma phospholipids. RESULTS: The mean body mass index of women was 27.9 +/- 6.1. Seventy-five percent were smokers and 9% were currently on hormone replacement therapy. Relative concentrations of total n-3 fatty acids were very high (13.8%, 95% CI: 13.1-14.6), with docosahexanoic and eicosapentanoic acids accounting for 4.7% and 7.2%, respectively. The ratio of n-3:n-6 fatty acids was 0.67. n-3 fatty acids were inversely correlated to triacylglycerols. CONCLUSION: These data show that peri- and post-menopausal Greenland Inuit women have very high plasma concentrations of n-3 fatty acids that protect them from ischemic heart disease.

Aged↗

Effect of combinations of fish meal and feather meal on milk fatty acid content and nitrogen utilization in dairy cows.

The effect of supplemental fishmeal in combination with feathermeal at two different proportions in the diet on milk docosahexaenoic acid (DHA) content was investigated. Recently, benefits to human health have been attributed to the consumption of this fatty acid, which is normally present in marine lipids. Six Holstein cows past peak lactation were used in a Latin square design with a 2 x 3 factorial arrangement of treatments. Fish- and feathermeals were prepared as pellets at 4:1 and 1:4 combinations and offered at 3.75, 11.75, and 27% of the diet. The supplements were top-dressed onto a basal diet based on corn silage that was progressively replaced by supplement. Nitrogen balance measures were made during the experiment because of the wide range in crude protein content of experimental diets. Milk protein content increased with level of supplementation in the diet reflecting the protein quality of the supplements used. There was overall higher milk DHA content when cows consumed the supplement containing more fishmeal than feather meal. Milk DHA content increased in a quadratic fashion, as more of either supplement was included in the diet. Apparent transfer efficiency of DHA from diet to milk declined with increasing amount of DHA in the diet. Results from this experiment suggest that transfer of docosahexaenoic acid from diet to milk may depend on diet composition and quantity present in the diet.

Animals↗

n-3 Fatty acids and cardiovascular disease risk factors among the Inuit of Nunavik.

BACKGROUND: Inuit traditionally consume large amounts of marine foods rich in n-3 fatty acids. Evidence exists that n-3 fatty acids have beneficial effects on key risk factors for cardiovascular disease. OBJECTIVE: Our goal was to verify the relation between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among the Inuit of Nunavik, Canada. DESIGN: The study population consisted of 426 Inuit aged 18-74 y who participated in a 1992 health survey. Data were obtained through home interviews and clinical visits. Plasma samples were analyzed for phospholipid fatty acid composition. RESULTS: Expressed as the percentage of total fatty acids, geometric mean concentrations of EPA, DHA, and their combination in plasma phospholipids were 1.99%, 4.52%, and 6.83%, respectively. n-3 Fatty acids were positively associated with HDL-cholesterol concentrations and inversely associated with triacylglycerol concentrations and the ratio of total to HDL cholesterol. In contrast, concentrations of total cholesterol, LDL cholesterol, and plasma glucose increased as n-3 fatty acid concentrations increased. There were no significant associations between n-3 fatty acids and diastolic and systolic blood pressure and plasma insulin. CONCLUSIONS: Consumption of marine products, the main source of EPA and DHA, appears to beneficially affect some cardiovascular disease risk factors. The traditional Inuit diet, which is rich in n-3 fatty acids, is probably responsible for the low mortality rate from ischemic heart disease in this population.

Adult↗

Relations between n-3 fatty acid status and cardiovascular disease risk factors among Quebecers.

BACKGROUND: Epidemiologic evidence shows an inverse relation between fish consumption and death from ischemic heart disease. This beneficial effect is attributed to n-3 fatty acids. OBJECTIVES: The purpose of this study was to examine the association between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among Quebecers. DESIGN: The study population consisted of 1460 subjects aged 18-74 y who participated in the 1990 Quebec Heart Health and Nutrition Survey. Data were obtained through home interviews and clinic visits. RESULTS: Expressed as the percentage of total fatty acids in plasma phospholipids, the geometric means of EPA, DHA, and their combination were 0.47%, 1.19%, and 1.70%, respectively. Concentrations of n-3 fatty acids were positively associated with fish intake. We found positive associations between EPA and total cholesterol, LDL cholesterol, HDL cholesterol, plasma glucose, and systolic and diastolic blood pressure. We found positive associations between DHA and total cholesterol, the ratio of total to HDL cholesterol, triacylglycerols, systolic blood pressure, and plasma glucose and insulin. We also found positive associations between the ratio of EPA to arachidonic acid and total cholesterol, HDL cholesterol, and systolic blood pressure and a negative association with the ratio of total to HDL cholesterol. CONCLUSIONS: Our results indicate that concentrations of EPA and DHA in plasma phospholipids reflected Quebecer fish consumption. Results also show that EPA and the ratio of EPA to arachidonic acid can positively influence HDL-cholesterol concentrations.

Adult↗

Suppressive effects of fish oil on mesangial cell proliferation in vitro and in vivo.

BACKGROUND: Mesangial cell proliferation is a characteristic feature of IgA nephropathy and many other forms of glomerulonephritis. Recent clinical studies have shown that dietary fish oil supplementation retards renal disease progression in patients with IgA nephropathy. The mechanism by which this effect occurs is unknown. METHODS: The anti-Thy 1.1 (ATS) model of mesangial proliferative glomerulonephritis was employed to test the hypothesis that dietary fish oil supplementation reduces mesangial cell proliferation following acute injury. Subcultured rat mesangial cells were used to determine the in vitro effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the primary components of fish oil, on proliferation. RESULTS: Following antithymocyte serum (ATS) administration, proteinuria was significantly decreased in animals treated with fish oil compared with sesame oil-treated controls. In ATS rats given fish oil, there was less mesangial cell and matrix expansion, mesangiolysis, or basement membrane disruption (delta% = -40%). ATS rats receiving fish oil had less glomerular cell proliferation (PCNA-delta% = -50%) and a reduction of alpha-smooth muscle actin expression (delta% = -27%) by mesangial cells. In subcultured rat mesangial cells, DHA, but not EPA, significantly inhibited proliferation. CONCLUSIONS: Fish oil inhibits mesangial cell activation and proliferation in ATS glomerulonephritis, reduces proteinuria, and decreases histologic evidence of glomerular damage. In vitro, the antiproliferative effects of fish oil are more likely related to the action of DHA. We suggest that orally administered fish oil, or purified DHA, may have a suppressive effect in acute phases or relapses of glomerulopathies by inhibiting activation and proliferation of mesangial cells.

Animals↗

Effect of a fish-oil concentrate on serum lipids in postmenopausal women receiving and not receiving hormone replacement therapy in a placebo-controlled, double-blind trial.

BACKGROUND: n-3 Fatty acid supplementation lowered serum triacylglycerol concentrations in studies in which most of the subjects were male. The effects of n-3 fatty acid supplementation in postmenopausal women receiving and not receiving hormone replacement therapy (HRT) have received little attention. OBJECTIVE: We sought to determine the effects of a fish-oil-derived n-3 fatty acid concentrate on serum lipid and lipoprotein risk factors for cardiovascular disease in postmenopausal women receiving and not receiving HRT, with an emphasis on serum triacylglycerol concentrations and the ratio of triacylglycerol to HDL cholesterol. DESIGN: Postmenopausal women (n = 36) were grouped according to exogenous hormone use and were randomly allocated to receive 8 capsules/d of either placebo oil (control) or n-3 fatty acid-enriched oil (supplement). The supplement provided 2.4 g eicosapentaenoic acid (EPA) plus 1.6 g docosahexaenoic acid (DHA) daily. Serum lipids and the fatty acid composition of serum phospholipids were determined on days 0 and 28. RESULTS: Supplementation with n-3 fatty acids was associated with 26% lower serum triacylglycerol concentrations (P < 0.0001), a 28% lower overall ratio of serum triacylglycerol to HDL cholesterol (P < 0.01), and markedly greater EPA and DHA concentrations in serum phospholipids (P < 0.05). CONCLUSIONS: These results show that supplementation with a fish-oil-derived concentrate can favorably influence selected cardiovascular disease risk factors, particularly by achieving marked reductions in serum triacylglycerol concentrations and triacylglycerol:HDL cholesterol in postmenopausal women receiving and not receiving HRT. This approach could potentially reduce the risk of coronary heart disease by 27% in postmenopausal women.

Adult↗

Effect of supplementation with dietary seal oil on selected cardiovascular risk factors and hemostatic variables in healthy male subjects.

The average daily consumption of seal oil by the Inuit people is approximately 8-9 g, yet there is very little information on the effect of seal oil consumption on cardiovascular disease risk factors. In this study, 19 healthy, normocholesterolemic subjects consumed 20 g of encapsulated seal oil containing eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3), and docosapentaenoic acid (DPA; 22:5n-3) or 20 g of vegetable oil (control) per day for 42 days. Levels of selected cardiovascular and thrombotic risk factors as well as fatty acid profiles of serum phospholipid and nonesterified fatty acid (NEFA) were determined. EPA levels in serum phospholipid and NEFA increased by 4.3- and 2.7-fold, respectively, in the seal oil supplemented group. DHA levels rose 1.5- and 2.1-fold, respectively, and DPA levels rose 0.5- and 0.7-fold, respectively. Arachidonic acid (AA) levels dropped by 26% in both serum phospholipid and serum NEFA. There was a significant decrease in the ratio of n-6 to n-3 fatty acids in serum phospholipid from 7.2 to 2.1 and a significant increase in the ratio of EPA/AA in NEFA. Ingestion of seal oil raised the coagulant inhibitor, protein C, values by 7% and decreased plasma fibrinogen by 18%. No alterations in other hemostatic variables, including plasma activity of Factors VII, VIII, IX, and X and antithrombin, or in the concentrations of von Willebrand Factor, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose, Apo A-1, or lipoprotein(a) were observed in either group. Other risk factors for cardiovascular disease, including hematocrit, white blood cell count, plasma viscosity, systolic and diastolic blood pressures, heart rate, and platelet aggregation after stimulation with ADP or collagen did not change. Our results indicate that seal oil supplementation in healthy, normocholesterolemic subjects decreased the n-6/n-3 ratio and increased EPA, DHA, and DPA and the ratio of EPA/AA and DHA/AA in the serum phospholipid and NEFA, while exhibiting a modest beneficial effect on fibrinogen and protein C levels.

Adult↗

Docosahexaenoic acid and docosapentanoic acid incorporation into human platelets after 24 and 72 hours: inhibitory effects on platelet reactivity.

Short-term in vitro platelet membrane lipid enrichment studies and feeding trials of human subjects with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown a decreased reactivity in the platelet response to collagen. In this study, exogenous albumin-bound n-3 polyunsaturated fatty acids (PUFAs), namely EPA, DHA and docosapentanoic acid (DPA) were added to platelet suspensions and maintained at 22 degrees C for 24 and 72 hours. Subsequently, the aggregation response to agonist stimulation and the morphological appearance of the platelets were evaluated. A significant enrichment of platelet phospholipids (PL) in n-3 fatty acids occurred upon incubation with n-3 PUFAs in vitro, which was accompanied by a decrease in the aggregation response to collagen and preservation of platelet morphology compared with non-supplemented control platelet preparations. The inhibitory effect of the n-3 PUFAs appeared to be surface mediated in the case of DHA and DPA because the platelet response to agonist returned when the fatty acids were removed by washing. The platelet aggregation response after storage at 22 degrees C was also evaluated in platelet suspensions collected from healthy individuals before and after 42 days of dietary supplementation with seal oil, rich in DPA and DHA. Unlike the in vitro supplementation, in vivo modification and enrichment of platelet PLs by ingestion of seal oil did not appear to improve platelet function during storage relative to the placebo group.

Journal Article↗

Effect of dietary soy protein and genistein on disease progression in mice with polycystic kidney disease.

The effects of feeding a soy protein isolate or genistein, an isoflavonoid present in soy protein, on cyst development were examined in the DBA/2FG-pcy (pcy) mouse, an accepted animal model of polycystic kidney disease, before the appearance of clinical symptoms. In study 1, 60-day-old male pcy mice were evenly divided into two groups and fed semipurified diets, based on casein or a soy protein isolate (15 g protein/100 g diet) for 90 days. In study 2, the animals were fed a casein-based diet (25 g casein/100 g diet) with or without genistein (0.05 g/100 g diet) for 60 days. In study 1, total kidney weight and kidney weight relative to body weight were significantly reduced (by 24% to 25%) in the animals fed the soy protein-based diet, relative to the casein-fed group, as was kidney water content (by 38%). In addition, mean cyst volume, as measured by morphometry, were lower (by 25%) in kidneys from the soy protein-fed group. No differences were found between these two groups with respect to final body weight, plasma creatinine, and protein content; however, plasma urea values were significantly lower in the soy protein-fed animals. Genistein supplementation of a casein-based diet in study 2 did not reduce the renal enlargement and cyst development associated with progression of polycystic kidney disease. These results suggest that soy protein is effective in retarding cyst development in the pcy mouse and that this beneficial effect may be unrelated to its genistein content.

Animals↗

Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects.

The purpose of this double-blind study was to investigate the influence of adding a quercetin-containing supplement to the diet on plasma quercetin status, serum/platelet fatty acid levels and risk factors for heart disease. Healthy men and women with cholesterol levels of 4.0-7.2 mmol/L, consumed four capsules daily of either a quercetin-containing supplement (1.0 g quercetin/d) or rice flour placebo for 28 d. Quercetin intakes were approximately 50-fold greater than the dietary intakes associated with lower coronary heart disease mortality on the basis of epidemiologic studies. Subjects consuming quercetin-containing capsules had plasma quercetin concentrations approximately 23-fold higher than those of subjects consuming the control capsules. Quercetin supplementation did not modify serum total, LDL or HDL cholesterol or triglyceride levels. There were also no alterations of other cardiovascular disease or thrombogenic risk factors, including platelet aggregation, platelet thromboxane B2 production, blood pressure or resting heart rate. Furthermore, there was no effect on the levels of (n-6) or (n-3) polyunsaturated fatty acids in serum or platelet phospholipids. In conclusion, supplementation with quercetin-containing capsules markedly enhanced the plasma quercetin concentration but had no effect on other cardiovascular or thrombogenic risk factors.

Adult↗

Effect of supplementation with different doses of DHA on the levels of circulating DHA as non-esterified fatty acid in subjects of Asian Indian background.

There is evidence to indicate that the high rates of coronary heart disease and myocardial infarction amongst Indians of Asian descent may be partly related to circulating nonesterified fatty acids (NEFA). As docosahexaenoic acid (DHA,22:6n-3) in NEFA form has been found to exhibit anti-platelet aggregatory and anti-arrhythmic potential in vitro, the effect of supplementary DHA was examined in healthy subjects of Asian Indian background. Furthermore, time- and dose-dependent changes in absolute levels of DHA as NEFA or phospholipid (PL) were compared. The subjects consumed 8 capsules daily of placebo (DHA-free) or low DHA (0.75 g/day)or high DHA (1.50 g/day) over 6 wks. Fasting blood samples were drawn at days 0, 21, and 42 for analysis of serum lipid/lipoprotein composition. No significant effect of DHA supplementation on the levels of serum lipid/lipoproteins (including Lp[a]) or blood pressure was found. However, the DHA level in serum phospholipid rose by 167% overall with low-dose supplementation (from 2.4-6.4 mol%) but only by an additional 23% upon doubling the dose from 0.75 g to 1.50 g/day. Furthermore, after 6 weeks of supplementation with 0.75 g or 1.5 g DHA/day, absolute concentrations of DHA as PL were not significantly different from the corresponding 3-week values. Interestingly, the absolute concentrations of serum DHA as NEFA showed a marked rise with low-dose supplementation (by 212% overall, from 2.4 to 7.5 microM) and a further 70% rise (to 12.7 microM) upon doubling the supplementation from 0.75 to 1.50 g/day. As well, the 6-week concentrations (DHA-NEFA) were significantly different than the corresponding 3-week values at both dose levels. Elevation of circulating DHA-NEFA levels via DHA supplementation, as shown herein, to concentrations that exhibit anti-thrombotic and anti-arrhythmic potential in vitro needs to be extended to trials where clinical end-points are determined.

Arrhythmias, Cardiac↗

Elevated levels and altered fatty acid composition of plasma lysophosphatidylcholine(lysoPC) in ovarian cancer patients.

Lysophosphatidylcholine (lysoPC), a product of phosphatidylcholine (PC) hydrolysis via phospholipase A activity, has been proposed to activate cells from a number of lineages. Here, we demonstrate that lysoPC levels are significantly elevated (by 43% overall, relative to normal controls) in the plasma of ovarian cancer patients. This does not appear to be common to all cancers as 5 out of 6 leukemia patients tested had markedly lower (less than one-half of normal) plasma lysoPC. In the plasma of ovarian cancer patients, the percentages of palmitoyl- and stearoyl-lysoPC species were significantly higher, whereas oleoyl and particularly linoleoyl-lysoPC were significantly lower than in control subjects. The molar ratios of lysoPC/PC and palmitoyl-lysoPC/linoleoyl-lysoPC were also significantly elevated in the plasma of ovarian cancer patients compared with those of control subjects. Furthermore, the calculated value of plasma (lysoPC/ PC) x (palmitoyl-lysoPC/linoleoyl-lysoPC) was markedly higher in patients compared with controls.

Adult↗

Dietary docosahexaenoic acid as a source of eicosapentaenoic acid in vegetarians and omnivores.

The utilization of dietary docosahexaenoic acid (DHA; 22:6n-3) as a source of eicosapentaenoic acid (EPA; 20:5n-3) via retroconversion was investigated in both vegetarians and omnivores. For this purpose, an EPA-free preparation of DHA was given as a daily supplement (1.62 g DHA) over a period of 6 wk. The dietary supplement provided for a marked increase in DHA levels in both serum phospholipid (from 2.1 to 7.1 mol% in vegetarians and 2.2 to 7.6 mol% in omnivores) and platelet phospholipid (from 1.1 to 3.4 mol% in vegetarians and 1.4 to 3.9 mol% in omnivores). EPA levels rose to a significant but much lesser extent, while 20:4n-6, 22:5n-6, and 22:5n-3 all decreased. Based on the serum phospholipid data, the retroconversion of DHA to EPA in vivo was estimated to be 9.4% overall with no significant difference between omnivores and vegetarians.

Adult↗

Effect of garlic and fish-oil supplementation on serum lipid and lipoprotein concentrations in hypercholesterolemic men.

This study examined the effects of garlic and fish-oil supplementation (alone and in combination) on fasting serum lipids and lipoproteins in hypercholesterolemic subjects. After an initial run-in phase, 50 male subjects with moderate hypercholesterolemia were randomly assigned for 12 wk to one of four groups: 1) 900 mg garlic placebo/d + 12 g oil placebo/d; 2) 900 mg garlic/d + 12 g oil placebo/d; 3) 900 mg garlic placebo/d + 12 g fish oil/d, providing 3.6 g n-3 fatty acids/d; and 4) 900 mg garlic/d + 12 g fish oil/d. In the placebo group, mean serum total cholesterol, low-density-lipoprotein cholesterol (LDL-C), and triacylglycerols were not significantly changed in relation to baseline. Mean group total cholesterol concentrations were significantly lower with garlic+fish oil (-12.2%) and with garlic (-11.5%) after 12 wk but not with fish oil alone. Mean LDL-C concentrations were reduced with garlic+fish oil (-9.5%) and with garlic (-14.2%) but were raised with fish oil (+8.5%). Mean triacylglycerol concentrations were reduced with garlic+fish oil (-34.3%) and fish oil alone (-37.3%). The garlic groups (with and without fish oil) had significantly lower ratios of total cholesterol to high-density-lipoprotein cholesterol (HDL-C) and LDL-C to HDL-C. In summary, garlic supplementation significantly decreased both total cholesterol and LDL-C whereas fish-oil supplementation significantly decreased triacylglycerol concentrations and increased LDL-C concentrations in hypercholesterolemic men. The combination of garlic and fish oil reversed the moderate fish-oil-induced rise in LDL-C. Coadministration of garlic with fish oil was well-tolerated and had a beneficial effect on serum lipid and lipoprotein concentrations by providing a combined lowering of total cholesterol, LDL-C, and triacylglycerol concentrations as well as the ratios of total cholesterol to HDL-C and LDL-C to HDL-C.

Adult↗

Effects of fish meal in beef cattle diets on growth performance, carcass characteristics, and fatty acid composition of longissimus muscle.

We investigated the effects of fish meal (FM) in beef cattle diets on growth performance, carcass characteristics, and fatty acid (FA) composition of longissimus muscle in 63 yearling steers (335 +/- 23 kg). High-moisture corn and alfalfa silage diets were supplemented with either a corn gluten/blood meal mixture or FM at 10% of the diet. Fish meal contained (as-is basis) 5.87 g/kg eicosapentaenoic acid (EPA) and 9.84 g/kg docosahexaenoic acid (DHA). Seven strategies were developed to feed either a control diet (no FM) or diets containing 5 or 10% FM with FM fed for either 56, 112, or 168 d before slaughter. Average daily gain and feed efficiency were not affected (P > .10) by FM feeding but DMI decreased. Within FM diets, cattle fed 5% FM consumed more (P < .01) DM and gained more (P < .02) than cattle fed 10% FM. Carcass traits were not affected (P > .05) by feeding strategy except for fatter (P < .05) and lower (P < .06) yielding carcasses in cattle fed 5 vs 10% FM diets. Fish meal feeding increased (P < .01) concentrations of (n-3) FA, including EPA and DHA, and decreased (P < .05) concentrations of arachidonic acid. Increasing the amount of dietary FM further increased (P < .01) concentrations of EPA and DHA and decreased (P < .05) concentrations of (n-6) FA. We estimate that a 114-g steak from cattle fed 10% FM would supply 35 to 90% of the current average daily intake of EPA and DHA in North America. The results indicate that FM may have a role in niche marketing of beef provided that eating quality is not compromised.

Animals↗