Lupin kernel fibre-enriched foods beneficially modify serum lipids in men

Objective: To examine the effect of a diet containing a novel legume food ingredient, Australian sweet lupin (Lupinus angustifolius) kernel fibre (LKFibre), compared to a control diet without the addition of LKFibre, on serum lipids in men.

Design: Randomized crossover dietary intervention study.

Setting: Melbourne, Australia — Free-living men.

Subjects: A total of 38 healthy males between the ages of 24 and 64 y completed the intervention.

Intervention: Subjects consumed an LKFibre and a control diet for 1 month each. Both diets had the same background menus with seven additional experimental foods that either contained LKFibre or did not. Depending on energy intake, the LKFibre diet was designed to contain an additional 17 to 30 g/day fibre beyond that of the control diet.

Results: Compared to the control diet, the LKFibre diet reduced total cholesterol (TC) (meanplusminuss.e.m.; 4.5plusminus1.7%; P=0.001), low-density lipoprotein cholesterol (LDL-C) (5.4plusminus2.2%; P=0.001), TC: high-density lipoprotein cholesterol (HDL-C) (3.0plusminus2.0%; P=0.006) and LDL-C:HDL-C (3.8plusminus2.6%; P=0.003). No effects on HDL-C, triacylglycerols, glucose or insulin were observed.

Conclusions: Addition of LKFibre to the diet provided favourable changes to some serum lipid measures in men, which, combined with its high palatability, suggest this novel ingredient may be useful in the dietary reduction of coronary heart disease risk.

Dietary counseling to increase natural folate intake: a ransomized placebo-controlled trial in free-living subjects to assess effects on serum folate and plasma total homocysteine.

BACKGROUND: The association between vascular disease and elevated plasma total homocysteine (tHcy) concentrations is caused, in part, by inadequate intakes of dietary folate. Increasing folate intake either through supplements or foods naturally rich in folates has been shown to decrease tHcy concentrations. OBJECTIVE: The aim of this study was to determine whether a similar reduction in tHcy was possible in free-living persons receiving dietary counseling. DESIGN: The study included a 4-wk placebo-controlled dietary intervention trial in which participants consumed either unfortified breakfast cereal (control group) or an extra 350 micro g folate derived from food/d (dietary group). Serum folate and tHcy concentrations in both groups were measured before and after the intervention period, and the concentrations in the dietary group were also measured 17 wk after the intervention period. RESULTS: During the 4-wk intervention, mean dietary folate intake in the dietary group increased from 263 (95% CI: 225, 307) to 618 micro g/d (535, 714), resulting in a mean increase in serum folate of 37% (15%, 63%) and a decrease in tHcy from 12.0 (10.9, 13.3) to 11.3 micro mol/L (10.2, 12.5). A further decrease in tHcy occurred in the dietary group during follow-up, with a final tHcy concentration of 9.7 micro mol/L (8.8, 10.8). CONCLUSIONS: Increasing natural folate intake improved folate status and decreased tHcy concentrations to an extent that may significantly reduce the risk of vascular disease. Dietary modification may have advantages over folic acid fortification because the altered food-consumption patterns lead to increased intakes of several vitamins and minerals and decreased intakes of saturated fatty acids.

Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial.

Objective: To determine the minimum effective dose of folic acid required to appreciably increase serum folate and to produce a significant reduction in plasma total homocysteine (tHcy).

Design: Double-blind, randomised placebo-controlled intervention trial.

Setting: Community-based project in a New Zealand city.

Subjects: Seventy free living men and women with tHcy10 µmol/l. Mean age (range) was 58 (29-90) y.

Interventions: Daily consumption over 4 weeks of 20 g breakfast cereal either unfortified (placebo) or fortified with 100, 200 or 300 µg folic acid. Dietary intake was determined by weighed diet records and consumption of commercially fortified products was avoided.

Main outcome measures: Plasma tHcy and serum folate concentrations.

Results: Average serum folate concentrations (95% CI) increased significantly in the treatment groups relative to the control group by 28(9-51)%, 60(37-87)% and 79(51-114)% for supplementation with 100, 200 and 300 µg folic acid, respectively. A reduction in tHcy was observed, being 16(8-22)%, 12(4-18)% and 17(9-24)% in the three treatment groups, respectively.

Conclusions: A regular intake of as little as 100 µg folic acid per day was sufficient to lower tHcy in persons at the upper end of the normal range for tHcy. Low-level fortification may also be appropriate for lowering the risk of neural tube defects given that, when aggregated from all sources, the total intake of folic acid may be sufficiently high to adequately improve the folate status of young women.

Exercise increases serum Hsp72 in humans

Recent evidence suggests that heat shock proteins (Hsps) may have an important systemic role as a signal to activate the immune system. Since acute exercise is known to induce Hsp72 (the inducible form of the 70-kDa family of Hsp) in a variety of tissues including contracting skeletal muscle, we hypothesized that such exercise would result in the release of Hsp72 from stressed cells into the blood. Six humans (5 males, 1 female) ran on a treadmill for 60 minutes at a workload corresponding to 70% of their peak oxygen consumption. Blood was sampled from a forearm vein at rest (R), 30 minutes during exercise, immediately postexercise (60 minutes), and 2, 8, and 24 hours after exercise. These samples were analyzed for serum Hsp72 protein. In addition, plasma creatine kinase (CK) was measured at these time points as a crude marker of muscle damage. With the exception of the sample collected at 30 minutes, muscle biopsies (n = 5 males) were also obtained from the vastus lateralis at the time of blood sampling and analyzed for Hsp72 gene and protein expression. Serum Hsp72 protein increased from rest, both during and after exercise (0.13 0.10 vs 0.87 ± 0.24 and 1.02 ± 0.41 ng/mL at rest, 30 and 60 minutes, respectively, P < 0.05, mean SE). In addition, plasma CK was elevated (P < 0.05) 8 hours postexercise. Skeletal muscle Hsp72 mRNA expression increased 6.5-fold (P < 0.05) from rest 2 hours postexercise, and although there was a tendency for Hsp72 protein expression to be elevated 2 and 8 hours following exercise compared with rest, results were not statistically significant. The increase in serum Hsp72 preceded any increase in Hsp72 gene or protein expression in contracting muscle, suggesting that Hsp72 was released from other tissues or organs. This study is the first to demonstrate that acute exercise can increase Hsp72 in the peripheral circulation, suggesting that during stress these proteins may indeed have a systemic role.

Serum vitamin D and falls in older women in residential care in Australia

Objectives: To determine the prevalence of vitamin D deficiency in older people in residential care and the influence that the level of vitamin D may have on their incidence of falls.

Design: Prospective cohort.

Setting: Residential care facilities for older people in several states of Australia.

Participants: Six hundred sixty-seven women in low-level care and 952 women in high-level care, mean age 83.7 years.

Measurements: Serum 25-hydroxyvitamin D (25D) levels and recognized risk factors for falls including current medication use, a history of previous fractures, weight, tibial length (as a surrogate for height), cognitive function, walking ability, and frequency of going outdoors were determined. The women in low-level care and high-level care were followed for an average of 145 and 168 days, respectively. Falls were recorded prospectively in diaries completed monthly by residential care staff.

Results: Vitamin D deficiency (defined as a serum 25D level below 25 nmol/L) was present in 144 (22%) women in low-level care and 428 (45%) in high-level care. After excluding 358 bed-bound residents and adjusting for weight, cognitive status, psychotropic drug use, previous Colles fracture, and the presence of wandering behavior, log serum 25D level remained independently associated with time to first fall. The adjusted hazards ratio was 0.74 (95% confidence interval=0.59–0.94; P=.01), implying a 20% reduction in the risk of falling with a doubling of the vitamin D level.

Conclusion: Vitamin D deficiency is common in residential care in Australia. A low level of serum vitamin D is an independent predictor of incident falls.

Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the third national health and nutrition examination survey

OBJECTIVE— To determine the association between serum 25-hydroxyvitamin D (25OHD) and diabetes risk and whether it varies by ethnicity.
RESEARCH DESIGN AND METHODS— We performed an analysis of data from participants who attended the morning examination of the Third National Health and Nutrition Examination Survey (1988–1994), a cross-sectional survey of a nationally representative sample of the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic blacks, and 1,726 Mexican Americans) aged ≥20 years with fasting and/or 2-h plasma glucose and serum insulin measurements.
RESULTS— Adjusting for sex, age, BMI, leisure activity, and quarter of year, ethnicityspecific odds ratios (ORs) for diabetes (fasting glucose ≥7.0 mmol/l) varied inversely across quartiles of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11– 0.60] for non-Hispanic whites and 0.17 [0.08–0.37] for Mexican Americans) in the highest vitamin D quartile (25OHD ≥81.0 nmol/l) compared with the lowest 25OHD (≥43.9 nmol/l). This inverse association
was not observed in non-Hispanic blacks. Homeostasis model assessment of insulin resistance (loge) was inversely associated with serum 25OHD in Mexican Americans (P ≥ 0.0024) and non-Hispanic whites (P≥0.058) but not non-Hispanic blacks (P≥0.93), adjusting for confounders.
CONCLUSIONS— These results show an inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans. The lack of an inverse association in non-Hispanic blacks may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.

Evaluation of brief dietary questions to estimate vegetable and fruit consumption - using serum carotenoids and red-cell folate

Objective To evaluate responses to self-administered brief questions regarding consumption of vegetables and fruit by comparison with blood levels of serum carotenoids and red-cell folate.

Design A cross-sectional study in which participants reported their usual intake of fruit and vegetables in servings per day, and serum levels of five carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin and lycopene) and red-cell folate were measured. Serum carotenoid levels were determined by high-performance liquid chromatography, and red-cell folate by an automated immunoassay system.

Settings and subjects Between October and December 2000, a sample of 1598 adults aged 25 years and over, from six randomly selected urban centres in Queensland, Australia, were examined as part of a national study conducted to determine the prevalence of diabetes and associated cardiovascular risk factors.

Results Statistically significant (P<0.01) associations with vegetable and fruit intake (categorised into groups: ≤1 serving, 2–3 servings and ≥4 servings per day) were observed for α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin and red-cell folate. The mean level of these carotenoids and of red-cell folate increased with increasing frequency of reported servings of vegetables and fruit, both before and after adjusting for potential confounding factors. A significant association with lycopene was observed only for vegetable intake before adjusting for confounders.

Conclusions These data indicate that brief questions may be a simple and valuable tool for monitoring vegetable and fruit intake in this population.

Adiponectin in umbillcal cord blood is inversely related to low-density lipoprotein cholesteril but not ethnicity

Context: Adiponectin is a recognized protective risk marker for cardiovascular disease in adults and is associated with an optimal lipid profile. The role of adiponectin at birth is not well understood, and its relationship with the neonatal lipid profile is unknown. Because ethnic disparities in cardiovascular risk have been attributed to low adiponectin and its associated low high-density lipoprotein cholesterol (HDL-C), investigation at birth may help determine the etiology of these risk patterns.

Objective: Our objective was to investigate the relationship between neonatal adiponectin and lipid profile at birth in two ethnic groups in cord blood.

Design, Setting, and Participants: Seventy-four healthy mothers and their newborns of South Asian and White European origin were studied in this cross-sectional study at St. Mary’s Hospital, Manchester, United Kingdom.

Main Outcome Measures: Serum adiponectin, total cholesterol, HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were measured in umbilical venous blood at birth and in maternal blood collected at 28 wk gestation.

Results: Cord adiponectin was significantly inversely associated with cord LDL-C (r = –0.32; P = 0.005) but not HDL-C. In a multiple regression analysis, cord LDL-C remained the most significant association of cord adiponectin (ß = –0.13; P < 0.001). We did not find any significant ethnic differences in cord adiponectin or lipids with the exception of triglycerides, which were significantly lower in South Asian newborns (P < 0.05).

Conclusion: This is the first report of an inverse relationship between cord adiponectin and LDL-C at birth. In contrast to adult studies, we found no significant association between adiponectin and HDL-C in cord blood. Our results and the strong independent association between adiponectin and HDL-C observed in adult studies suggest a role for adiponectin in lipid metabolism. Ethnic differences in adiponectin may arise after birth.

Long-term effect of calcium-vitamin D3 fortified milk on blood pressure and serum lipid concenstrations in healthy older men

Background/Objectives:
Some epidemiological and clinical studies have shown that increased dairy consumption or calcium and/or vitamin D supplementation can have a beneficial effect on blood pressure, and lipid and lipoprotein concentrations. The aim of this study was to assess the long-term effects of calcium-vitamin D3 fortified milk on blood pressure and lipid-lipoprotein concentrations in community-dwelling older men.

Subjects/Methods:
This is a substudy of a 2-year randomized controlled trial in which 167 men aged >50 years were assigned to receive either 400 ml per day of reduced fat (approx1%) milk fortified with approximately 1000 mg of calcium and 800 IU of vitamin D3 or to a control group receiving no additional fortified milk. Weight, blood pressure, lipid and lipoprotein concentrations were measured every 6 months. Participants on lipid-lowering (n=32) or antihypertensive medication (n=39) were included, but those who commenced, increased or decreased their medication throughout the intervention were excluded (n=27).

Results:
In the 140 men included in this study (milk, n=73; control, n=67), there were no significant effects of the calcium-vitamin D3 fortified milk on weight, systolic or diastolic blood pressure, total cholesterol, high-density lipoprotein or low-density lipoprotein cholesterol or triglyceride concentrations at any time throughout the intervention. Similar results were observed after excluding men taking antihypertensive or lipid-lowering medication or limiting the analysis to those with baseline calcium intakes <1000 mg per day and/or with hypovitaminosis D (25(OH)D <75 nmol/l).

Conclusions:
Supplementation with reduced-fat calcium-vitamin D3 fortified milk did not have a beneficial (nor detrimental) effect on blood pressure, lipid or lipoprotein concentrations in healthy community-dwelling older men.

Interrelations between ceruloplasmin and Fe status during human pregnancy

It is well established that Fe and ceruloplasmin interact in animals and in in vitro models. However, Fe-mediated regulation of ceruloplasmin has never been investigated in humans. In an observational study, 53 pregnant women aged 19-39 yr (29.8±0.7 yr, mean ± SEM) were recruited at the Aberdeen Antenatal Clinic, Aberdeen Maternity Hospital, UK. All requirements for local ethical committees were followed. Venous blood samples were taken from each woman at 34 wk gestation for measurement of Fe status and ceruloplasmin. Various parameters were used to test for Fe status. The most sensitive one appeared to be soluble transferrin receptor, which increased with parity. In the population studied, there was no relationship between hemoglobin or ferritin and serum ceruloplasmin. However, using soluble transferrin receptor (sTfR) levels, we were able to demonstrate an inverse linear relationship (r=0.37, p=0.021, n=41) between Fe status and ceruloplasmin. Fe supplementation, number of previous pregnancies, and smoking habits did not affect this relationship. Our data support in vitro results showing regulation of ceruloplasmin by Fe and also suggest that the interactions between Fe and ceruloplasmin should be considered when Fe supplementation is given.

Computer-assisted image analysis of liver collagen: relationship to Ishak scoring and hepatic venous pressure gradient

Histopathological scoring of disease stage uses descriptive categories without measuring the amount of fibrosis. Collagen, the major component of fibrous tissue, can be quantified by computer-assisted digital image analysis (DIA) using histological sections. We determined relationships between DIA, Ishak stage, and hepatic venous pressure gradient (HVPG) reflecting severity of fibrosis. One hundred fifteen patients with hepatitis C virus (HCV) who had undergone transplantation had 250 consecutive transjugular liver biopsies combined with HVPG (median length, 22 mm; median total portal tracts, 12), evaluated using the Ishak system and stained with Sirus red for DIA. Liver collagen was expressed as collagen proportionate area (CPA). Median CPA was 6% (0.2-45), correlating with Ishak stage (stage 6 range, 13%-45%), and with HVPG (r = 0.62; P < 0.001). Median CPA was 4.1% when HVPG was less than 6 mm Hg and 13.8% when HVPG was 6 mm Hg or more (P < 0.0001) and 6% when HVPG was less than 10 mm Hg and 17.3% when HVPG was 10 mm Hg or higher (P < 0.0001). Only CPA, not Ishak stage/grade, was independently associated by logistic regression, with HVPG of 6 mm Hg or more [odds ratio, 1.206; 95% confidence interval (CI), 1.094-1.331; P < 0.001], or HVPG of 10 mm Hg or more (odds ratio, 1.105; 95% CI, 1.026-1.191; P = 0.009). CPA increased by 50% (3.6%) compared with 20% in HVPG (1 mm Hg) in 38 patients with repeated biopsies. Conclusion: CPA assessed by DIA correlated with Ishak stage scores and HVPG measured contemporaneously. CPA was a better histological correlate with HVPG than Ishak stage, had a greater numerical change when HVPG was low, and resulted in further quantitation of fibrosis in cirrhosis.

Implementation of a management guideline aimed at minimizing the severity of primary graft dysfunction after lung transplant

Objective
Primary graft dysfunction, a severe form of lung injury that occurs in the first 72 hours after lung transplant, is associated with morbidity and mortality. We sought to assess the impact of an evidence-based guideline as a protocol for respiratory and hemodynamic management.

Methods
Preoperative and postoperative data for patients treated per the guideline (n = 56) were compared with those of a historical control group (n = 53). Patient data such as ratio of arterial Po2 to inspired oxygen fraction, central venous pressure, cumulative fluid balance, vasopressor dose, and serum urea and creatinine were measured and documented at specific times. Primary outcome was severity of primary graft dysfunction within the first 72 hours.

Results
Primary graft dysfunction grade was progressively lower in patients treated after introduction of the guideline (P = .01). Lower postoperative fluid balances (P = .01) and vasopressor doses (P = .007) were seen, with no associated renal dysfunction. There were no differences in duration of mechanical ventilation or mortality. Nonadherence to the guideline occurred in 10 cases (18%).

Conclusions
Implementation of an evidence-based guideline for managing respiratory and hemodynamic status is feasible and safe and was associated with reduction in severity of primary graft dysfunction. Further studies are required to determine whether such a guideline would lead to a consistent reduction in severity of primary graft dysfunction at other institutions. Creation of a protocol for postoperative care provides a template for further studies of novel therapies or management strategies for primary graft dysfunction.