In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development.

In humans, sexual differentiation of the external genitalia is established at 7-12 weeks post conception (wpc). During this period, maintaining the appropriate intrauterine hormone environment is critical. In contrast to other species, this regulation extends to the human fetal adrenal cortex, as evidenced by the virilization that is associated with various forms of congenital adrenal hyperplasia. The mechanism underlying these clinical findings has remained elusive. Here we show that the human fetal adrenal cortex synthesized cortisol much earlier than previously documented, an effect associated with transient expression of the orphan nuclear receptor nerve growth factor IB-like (NGFI-B) and its regulatory target, the steroidogenic enzyme type 2 3beta-hydroxysteroid dehydrogenase (HSD3B2). This cortisol biosynthesis was maximal at 8-9 wpc under the regulation of ACTH. Negative feedback was apparent at the anterior pituitary corticotrophs. ACTH also stimulated the adrenal gland to secrete androstenedione and testosterone. In concert, these data promote a distinctive mechanism for normal human development whereby cortisol production, determined by transient NGFI-B and HSD3B2 expression, provides feedback at the anterior pituitary to modulate androgen biosynthesis and safeguard normal female sexual differentiation.

Who are sexual offenders? A survey of pre-trial psychiatric reports.

Sexual offending is a serious and growing problem in our society. The aim of the study was to investigate the main characteristics of people charged with sexual offences who presented before the criminal courts. The survey was conducted retrospectively between August 2001 and August 2006 on pre-trial court reports stored in a computer database shared by forensic psychiatrists using The Grange consulting rooms in West Yorkshire. A data collection form was used to gather the characteristics of sexual offenders. The data collected was analysed using descriptive statistics. Our survey revealed the following results. Out of 78 cases evaluated, the commonest sexual offence was against children (68.8%). Thirty-two per cent of those with paedophilic behaviour had a history of childhood sexual abuse. Rape was alleged as the main sexual offence in 27.27% cases. Substance abuse (30.76%) and sexual motivation (42.30%) were the predominant motives for offending behaviour. Low rates of sexual fantasy and sadistic behaviour (8.97%) in our sample could be due to the non-disclosure by sexual offenders. Mental disorder was observed in 7.69% cases. Significant personality factors were observed in 14.10% of the sample. A sexual offending treatment programme was recommended in 57.69% cases. A very high risk of re-offending was recorded in 32.25% cases. Of the total sample, 93.50% were deemed fit to plead.

Variants in the human insulin gene that affect pre-mRNA splicing: is -23HphI a functional single nucleotide polymorphism at IDDM2?

Predisposition to type 1 diabetes and juvenile obesity is influenced by the susceptibility locus IDDM2 that includes the insulin gene (INS). Although the risk conferred by IDDM2 has been attributed to a minisatellite upstream of INS, intragenic variants have not been ruled out. We examined whether INS polymorphisms affect pre-mRNA splicing and proinsulin secretion using minigene reporter assays. We show that IVS1-6A/T (-23HphI+/-) is a key INS variant that influences alternative splicing of intron 1 through differential recognition of its 3' splice site. The A allele resulted in an increased production of mature transcripts with a long 5' leader in several cell lines, and the extended mRNAs generated more proinsulin in culture supernatants than natural transcripts. The longer mRNAs were significantly overrepresented among beta-cell-expressed sequenced tags containing the A allele as compared with those with T alleles. In addition, we show that a rare insertion/deletion polymorphism IVS1+5insTTGC (IVS-69), which is exclusively present in Africans, activated a downstream cryptic 5' splice site, extending the 5' leader by 30 bp. These results indicate that -23HphI and IVS-69 are the most important INS variants affecting pre-mRNA splicing and suggest that -23HphI+/- is a common functional single nucleotide polymorphism at IDDM2.

Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome.

OBJECTIVE: Enhancement of negative feedback control of the HPA axis in patients with chronic fatigue syndrome (CFS) has been reported using the low dose dexamethasone suppression test. We have developed the use of prednisolone (5mg) as a more physiologically appropriate alternative to dexamethasone in the investigation of mild degrees of glucocorticoid resistance or supersensitivity. The objective of the study was to use this test to look for alterations in negative feedback control of the HPA axis in CFS patients. METHODS: Fifteen patients with CFS were recruited after fulfilling strict criteria including the absence of comorbid psychiatric diagnosis. They collected urine between 0900 and 1800h and saliva at 0900h pre-prednisolone. At midnight, they took prednisolone (5mg) orally and then collected urine and saliva at the same intervals the following day. RESULTS: Salivary cortisol was lower in CFS subjects pre-prednisolone than controls. Urinary cortisol metabolites were lower in CFS subjects pre-prednisolone, but did not reach significance. Both measures were significantly lower in CFS subjects post-dose. Mean percentage suppression of both salivary cortisol and urinary cortisol metabolites was significantly higher in CFS compared to controls. CONCLUSION: There is enhanced sensitivity of the HPA axis to negative feedback in CFS as demonstrated using the prednisolone suppression test. This provides further evidence of alterations in the control of the HPA axis in patients with established CFS.

Cushing's syndrome in women with polycystic ovaries and hyperandrogenism.

BACKGROUND: A 41-year-old woman presented to an endocrinology-gynecology clinic having been diagnosed 7 years earlier with polycystic ovarian syndrome on account of hirsutism, subfertility, greasy skin, acne and multiple ovarian cysts. Ovulation induction had led to a successful pregnancy. Subfertility recurred, however, and persisted alongside a new diagnosis of hypertension and progressive weight gain. Upon examination, the patient was hypertensive with facial plethora, rounded facies and violaceous abdominal striae. INVESTIGATIONS: Low-dose dexamethasone test, bedtime salivary and 24-h urinary free cortisol estimations, CT scan of the abdomen, and serum hormone and gonadotropin analyses. DIAGNOSIS: Cushing's syndrome due to a right adrenocortical adenoma. MANAGEMENT: The patient underwent laparoscopic right adrenalectomy, which led to resolution of all symptoms, signs and biochemical abnormalities.

Assessment of subtle changes in glucocorticoid negative feedback using prednisolone: comparison of salivary free cortisol and urinary cortisol metabolites as endpoints.

BACKGROUND: Prednisolone is better than dexamethasone to probe subtle changes in HPA axis sensitivity but cortisol assay as an endpoint risks cross-reaction with prednisolone. We compared capillary gas chromatography, which distinguishes urinary cortisol and prednisolone metabolites, and salivary cortisol immunoassay. METHODS: Twenty adult volunteers (10 m) collected urine for consecutive 3 h periods and saliva at 3 h intervals from 2100 for 24 h, took prednisolone (5 mg) at midnight and continued collecting until 2100. RESULTS: Suppression of urine cortisol metabolites began at 0600 and ceased after 1800. The lowest CV was obtained for the period 0900-1800: mean suppression was 56 +/- 7% for males and 55 +/- 9% for females. Suppression of salivary cortisol was only consistently seen at 0900: mean suppression was 41 +/- 5% in males and 47 +/- 9% in females. Chromatography revealed significant cross reactivity of prednisolone in saliva at 0300 and 0600, but not by 0900. Suppression of salivary cortisol and urinary cortisol metabolites was not correlated for either gender. CONCLUSION: Both urinary cortisol metabolite and salivary cortisol assay following administration of 5 mg prednisolone have potential for investigation of changed HPA axis negative feedback, based on a convenient pre- and post-dose urinary collection between 0900 and 1800 and salivary sampling at 0900.

Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome.

OBJECTIVE: The aim of this study was to obtain comprehensive information on basal hypothalamic-pituitary-adrenal (HPA) axis activity in chronic fatigue syndrome (CFS) patients who were not affected by medication or comorbid psychiatric disorder likely to influence the HPA axis. METHOD: Steroid analysis of urine collections from 0600 to 2100 h at 3-h intervals in CFS patients and in controls. RESULTS: Urinary free cortisol and cortisone concentrations showed a significant normal diurnal rhythm, but levels were lower across the cycle in CFS. In contrast, while urinary cortisol metabolites also showed a normal diurnal rhythm, levels were not significantly different between the CFS and controls at any time. Derived metabolite ratios were similar in both groups. CONCLUSION: This study provides further evidence for reduced basal HPA axis function in patients with CFS, based on lower free cortisol and cortisone levels, but this is not corroborated by cortisol metabolite data. The difference between these measures cannot be explained by an altered timing of the diurnal rhythm.

Is there a gender difference in the associations of birthweight and adult hypothalamic-pituitary-adrenal axis activity?

OBJECTIVE: Increased hypothalamic-pituitary-adrenal (HPA) axis activity in men of low birthweight may be an important link between early life and the adult metabolic syndrome. In animal models females are more sensitive than males to HPA axis programming, but whether gender influences susceptibility in humans is unknown. DESIGN: Birth cohort study. METHODS: We studied 106 women aged 67-78 years, from Hertfordshire, UK, in whom birthweight was recorded. Negative feedback sensitivity was assessed by an overnight low-dose (0.25 mg) dexa-methasone suppression test, and adrenal sensitivity by a low-dose (1 microg) ACTH(1 - 24) stimulation test. Cortisol and its metabolites were analysed in a 24 h urine collection. Data were compared with previously published identical measurements in 205 men aged 66-77 years from the same cohort. RESULTS: In women, plasma cortisol levels after dexamethasone were lower (P < 0.0001) and peak cortisol following ACTH(1 - 24) were higher (P < 0.0001) than in men, suggesting a more responsive HPA axis. As in men, women with lower birthweight had enhanced plasma cortisol responses to ACTH(1 - 24) (P = 0.05 for trend) but no difference in plasma cortisol after dexamethasone or in urinary cortisol metabolite excretion. The strength of the association in women was not different from that in men; a 1 lb decrease in birthweight was associated with an incremental rise in cortisol of 12.6 nmol/l (95% confidence interval (CI) 1.4, 23.8) in men, P = 0.03, and 14.8 nmol/l (95% CI -0.4, 29.9) in women, P = 0.05 (P = 0.82 for birthweight x gender interaction). In a combined analysis of men and women adjusted for gender (n = 302), a 1 lb decrease in birthweight was associated with a 13.4 nmol/l (95% CI 4.5, 22.4) greater incremental rise in plasma cortisol, P = 0.003. CONCLUSIONS: Associations between lower birthweight and increased HPA axis activity are similar in men and women, supporting the hypothesis that HPA axis activation is an important mechanism underlying programming of adult disease.

Placental 11 beta-hydroxysteroid dehydrogenase-2 and fetal cortisol/cortisone shuttle in small preterm infants.

Glucocorticoids rate among the most controversial topics in today's perinatology and neonatology. Many sick preterm infants exhibit signs of adrenal insufficiency, the etiology, diagnostic criteria, and optimal treatment of which are under debate. Moreover, most of these infants are exposed to pharmacological glucocorticoid doses both in utero and after birth. In face of this, surprisingly little is known about the physiological glucocorticoid exposure before early preterm birth. This exposure is highly variable and mainly regulated by the placental enzyme 11 beta-hydroxysteroid dehydrogenase-2 (11 beta-HSD2), which converts excess cortisol (F) to inactive cortisone (E). Impaired activity of this enzyme is common in intrauterine growth restriction and preeclampsia, conditions frequently associated with early preterm birth. To identify clinical determinants associated with decreased placental 11 beta-HSD2 function, we studied 107 small preterm infants [mean birth weight, 1067 g (range, 395-2453 g); gestational age, 28.2 wk (range, 22.4-32.0 wk)] by determining their placental 11 beta-HSD2 activity rate (per milligram protein) and total activity (per placenta) as well as cord vein F and E concentrations. An E/(E+ F) ratio expresses the overall balance of the F/E shuttle. There were positive correlations between relative birth weight and placental 11 beta-HSD2 activity rate (r = 0.30; P = 0.002) and total activity (r = 0.56; P < 0.0001) as well as E/(E+ F) ratio (r = 0.27; P = 0.01) and E concentration (r = 0.32; P = 0.003). Infants with increased umbilical artery resistance had lower total placental 11 beta-HSD2 activity (P = 0.02), E/(E+ F) ratio (P = 0.04), and E concentration (P = 0.0002). Gestational age was inversely associated with placental 11 beta-HSD2 activity rate (r = -0.25; P = 0.009). We conclude that, in small preterm infants, reduced placental 11 beta-HSD2 function is associated with low relative birth weight and severe fetal distress. Whether these conditions are associated with early postnatal adrenal insufficiency or long-term cardiovascular risk remains an important issue for further study.

Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis: low birth weight and central HPA regulation.

Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as an intermediary in the association between reduced fetal growth and adult cardiovascular and metabolic diseases. Previous studies have shown that small size at birth is associated with increased fasting plasma cortisol and adrenal responsiveness to ACTH stimulation. We have extended these studies by evaluating the salivary cortisol response to awakening and plasma ACTH and cortisol responses to CRH stimulation and a dexamethasone-suppressed CRH (DEX/CRH) test in a group of low birth weight [LBW; <3.18 kg (7 lb), n = 58] and high birth weight [>3.86 kg (8.5 lb), n = 65] men aged 60-69 yr. Despite no difference in basal pituitary-adrenal activity or in their ACTH and cortisol responses to CRH, LBW men had significantly lower pituitary-adrenal responses in the DEX/CRH test. Although these findings do not explain the HPA abnormalities associated with LBW in previous studies, they provide further evidence of dysregulation of the HPA axis in people who were small at birth.

Inhibition of chronic vascular rejection by donor-specific blood transfusion is associated with a reduction in transforming growth factor-beta1 expression.

BACKGROUND: Concentric intimal thickening and the infiltration of inflammatory cells in cardiac allografts are the pathological hallmark characteristics of chronic vascular rejection (CVR), the leading cause of long-term graft failure. The precise mechanisms involved in the development and pathogenesis of CVR remain elusive. In the PVG-R23 to PVG-RT1u rat model of CVR, prior administration of a donor-specific transfusion (DST) was previously shown to prolong graft survival indefinitely and abolish the vascular lesions associated with CVR. The present study investigates in more depth the underlying mechanisms involved in the subsequent prolongation of allograft survival and inhibition of CVR by DST. METHODS: R23 heart grafts were monitored in nontransfused and transfused RT1u recipients injected 2 weeks before transplantation with 1.5 ml of R23 blood. Severity of arteriosclerosis, transplant infiltrate, transforming growth factor (TGF)-beta1 protein expression within the graft, plasma TGF-beta1 levels, class II MHC expression, tenascin protein expression, and serum alloantibody levels were measured. RESULTS: There was no significant difference in donor MHC class II, myocardial TGF-beta1, or tenascin expression between DST and non-DST-treated recipients. However, DST-pretreated recipients showed greatly reduced histological evidence of CVR and had lower titers of R23-specific IgG subclasses. Furthermore, DST-treated allograft recipients showed significant decreases in circulating TGF-beta1 levels and a reduction in TGF-beta1 and tenascin expression within coronary arteries of the allografts. CONCLUSION: The results suggested that DST inhibited CVR by altering and regulating the expression of TGF-beta1, thereby preventing the fibrogenic effects associated with TGF-beta1.

Birthsize, gestational age and adrenal function in adult life: studies of dexamethasone suppression and ACTH1-24 stimulation.

OBJECTIVE: Several studies show that low birthweight is associated with long-term alterations in the function of the hypothalamic-pituitary-adrenal axis (HPAA). We recently reported that the relationship between birthweight and fasting serum cortisol concentrations differed according to the gestational age of the babies, suggesting that both hypercortisolism and hypocortisolism could be a consequence of impaired fetal growth. We have now extended these findings by examining the relationship between birthweight, gestational age and tests of adrenal suppression and stimulation. DESIGN: Prospective birth cohort study. SUBJECTS AND METHODS: We studied 165 women (mean age 71.3 Years) born at term in Helsinki, Finland, between 1924 and 1933, whose body size and gestational age at birth were recorded. These women underwent an overnight 0.25 mg dexamethasone suppression test followed by a 1 microg ACTH(1-24) stimulation test. RESULTS: In all women combined, low birthweight was associated with lower total (P=0.03) and free (P=0.02) cortisol concentrations following dexamethasone. However, these relationships were dependent on gestational age at birth, interactions between the effects of birth size and gestational age on dexamethasone responsiveness being statistically significant. To demonstrate these interactions, we divided the study population into two groups according to gestational age. In subjects born at 40 weeks of gestation or more, low birthweight was strongly associated with enhanced dexamethasone suppression (P=0.003 for total and P=0.0004 for free cortisol), while in subjects born before 40 weeks of gestation there was no association. There was, however, no correlation between birth size and the adrenal response to ACTH(1-24). CONCLUSIONS: These findings reinforce our suggestions that events during prenatal life may lead to both up-regulation and down-regulation of the HPAA.

Predicting cardiovascular risk factors from plasma cortisol measured during oral glucose tolerance tests.

Increasing evidence suggests that activation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to the pathogenesis of the metabolic syndrome and obesity. The mechanisms are unknown but may involve alterations in the metabolic responses to feeding that interact with the HPA axis. As it is known that plasma cortisol falls during an oral glucose tolerance test (OGTT), changes in cortisol measured during an OGTT may be altered in the metabolic syndrome. We measured changes in plasma cortisol during OGTTs in a large study of 593 men and women to determine correlates of changes in cortisol with features of the metabolic syndrome and the extent to which these relationships are confounded by obesity. In men and women, higher cortisol area under the curve (AUC) during the OGTT was associated with higher glucose AUC and higher systolic blood pressure. Higher cortisol AUC was associated with reduced insulin increment in men, but higher 2-hour insulin and insulin AUC in women. However, the decline in plasma cortisol after glucose administration was poorly predictive of features of the metabolic syndrome. Obesity was associated with lower cortisol AUC but not with percentage decline in cortisol. Plasma cortisol and obesity had independent effects on plasma glucose and were the strongest predictors of plasma glucose in multiple regression analysis. Measurements of plasma cortisol during the OGTT reinforce the previously observed relationships of activation of the HPA axis in the metabolic syndrome. However, the altered HPA response to feeding does not appear to be primarily responsible for HPA activation in subjects with the metabolic syndrome.

Central hypothalamic-pituitary-adrenal activity and the metabolic syndrome: Studies using the corticotrophin-releasing hormone test.

A number of studies have suggested that the metabolic syndrome (principally, the combination of hypertension, glucose intolerance, and dyslipidemia) is associated with subtle dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis leading to raised circulating cortisol concentrations. The mechanisms underlying these observations are not known. We assessed the salivary cortisol response to awakening and pituitary-adrenal responses during a 100-microg human corticotrophin-releasing hormone (CRH) test and a dexamethasone-suppressed CRH test in a well-characterized group of 65-year-old men (n = 122). In the cohort from which this subgroup was drawn, there were associations between the components of the metabolic syndrome and 9 am cortisol concentration in line with previous studies. However, there were no significant associations between blood pressure, glucose tolerance, and lipid concentrations and the dynamic tests of HPA activity. We therefore found no evidence to suggest that exaggerated pituitary responsiveness or increased central drive to the pituitary, as determined by CRH testing, plays a part in the development of the metabolic syndrome.

Textural and Rheological Properties of Oat Beta-Glucan Gels with Varying Molecular Weight Composition.

The impact of oat ß-glucan concentration and molecular weight (MW) on gel properties was investigated. Mixed MW gels/viscous solutions at 3, 4, and 5% ß-glucan with high molecular weight (HMW):low molecular weight (LMW) ratios of 0:100, 25:75, 50:50, 75:25, and 100:0 were evaluated. The 100:0 and 50:50 gels had the lowest tan δ values. The 50:50 gels had the highest storage moduli (G'), whereas 100:0 solutions did not gel. Peak melting temperature (TP) was highest for 0:100 gels and decreased with the addition of HMW ß-glucan. Hardness, at 40% compression, increased with concentration, and 25:75 and 50:50 gels were hardest at each concentration. Ordered microstructure, apparent in 0:100 gels, diminished with HMW ß-glucan addition. Glucose addition resulted in lower tan δ values and firmer, harder gels compared to gels without glucose. Thus, the textural properties and melting profiles of ß-glucan gels can be manipulated by adjusting the ratios of molecular weight fractions or addition of sugar for different applications.

Ovarian 11ß-hydroxysteroid dehydrogenase (11ßHSD) activity is suppressed in women with anovulatory polycystic ovary syndrome (PCOS): apparent role for ovarian androgens.

CONTEXT: Altered hepatic cortisol-cortisone metabolism by type 1 11ß-hydroxysteroid dehydrogenase (11ßHSD1) has previously been linked with polycystic ovary (PCO) syndrome (PCOS). OBJECTIVES: Our objectives were to establish whether ovarian 11ßHSD activities are also altered in PCOS and to determine whether any changes in ovarian cortisol metabolism might reflect exposure to elevated concentrations of insulin or androgens. DESIGN: Cortisol and cortisone concentrations were measured in follicular fluid aspirated from size-matched follicles dissected from normal, ovulatory, and anovulatory PCOs. Human granulosa-lutein cells, recovered during oocyte retrieval for assisted conception, were maintained in primary culture for 4 days, after which 11ßHSD1 activities were measured as the net oxidation of [(3)H]cortisol (100 nmol/L) in the absence and presence of insulin (100 nmol/L) with or without metformin (1 µmol/L) or a range of androgens/oxy-androgen metabolites (0.01-10 µmol/L). RESULTS: Intrafollicular cortisol to cortisone ratios were elevated in anovulatory PCOs (2.1 ± 0.4, P < .05, n = 13) but did not differ between follicles from ovulatory PCOs (1.6 ± 0.1, n = 24) and normal ovaries (1.2 ± 0.1, n = 14). 11ßHSD1 activities were lower in granulosa-lutein cells recovered from patients with PCOS compared with all other causes of infertility (median = 5.8 vs 14.9 pmol cortisone/4 h, respectively; P < .05). Cortisol oxidation was unaffected by insulin with or without metformin, dehydroepiandrosterone, and androstenedione, but was inhibited in a concentration-dependent manner by testosterone, 11ß-hydroxyandrostenedione, and 7α- and 7ß-hydroxy-dehydroepiandrosterone (P < .01). CONCLUSIONS: There is decreased inactivation of cortisol in follicles from anovulatory PCOS. This may reflect inhibition of 11ßHSD1 by androgens and their 7/11-oxy-metabolites, local concentrations of which are increased in PCOS, and may contribute to the block to folliculogenesis seen in PCOS.

Processing affects the physicochemical properties of beta-glucan in oat bran cereal.

The tendency of mixed linkage oat beta-glucan to form viscous solutions is generally assumed to be related to its ability to lower serum cholesterol levels in humans. However, the association has not been clearly demonstrated. To conduct a clinical trial showing the relationship between LDL-cholesterol levels and viscosity, a series of extruded oat bran cereals were prepared in which the beta-glucan had a range of molecular weights and modified solubility. An extraction protocol using physiological enzymes at 37 degrees C was used to estimate the effect that the cereals would have on gut viscosity. By reducing the molecular weight from 1,930,000 to 251,000 g/mol, the apparent viscosity in the physiological extract dropped from 2900 to 131 mPa.s (at 30 s(-1)). Microscopic examination showed that as the extrusion conditions were made more severe, to cause depolymerization, the integrity of the cell walls was lost and beta-glucan dispersed throughout the cereal. Differences in the hardness and density of the extruded cereals were also evident as the molecular weight was reduced.

Physicochemical properties of oat ß-glucan influence its ability to reduce serum LDL cholesterol in humans: a randomized clinical trial.

BACKGROUND: Consumption of 3 g oat ß-glucan/d is considered sufficient to lower serum LDL cholesterol, but some studies have shown no effect. LDL cholesterol lowering by oat ß-glucan may depend on viscosity, which is controlled by the molecular weight (MW) and amount of oat ß-glucan solubilized in the intestine (C). OBJECTIVES: Our 2 primary objectives were to determine whether consumption of 3 g high-MW oat ß-glucan/d would reduce LDL cholesterol and whether LDL cholesterol lowering was related to the log(MW × C) of oat ß-glucan. DESIGN: In a double-blind, parallel-design, multicenter clinical trial, subjects with LDL cholesterol ≥3.0 and ≤5.0 mmol/L (n = 786 screened, n = 400 ineligible, n = 19 refused, n = 367 enrolled, and n = 345 completed) were randomly assigned to receive cereal containing wheat fiber (n = 87) or 3 g high-MW (2,210,000 g/mol, n = 86), 4 g medium-MW (850,000 g/mol, n = 67), 3 g medium-MW (530,000 g/mol, n = 64), or 4 g low-MW (210,000 g/mol, n = 63) oat ß-glucan/d (divided doses, twice daily) for 4 wk. RESULTS: LDL cholesterol was significantly less with 3 g high-MW, 4 g medium-MW, and 3 g medium-MW oat ß-glucan cereals than with the wheat-fiber cereal by 0.21 (5.5%; 95% CI: -0.11, -0.30; P = 0.002), 0.26 (6.5%; 95% CI: -0.14, -0.37; P = 0.0007), and 0.19 (4.7%; 95% CI: -0.08, -0.30; P = 0.01) mmol/L, respectively. However, the effect of 4 g low-MW oat ß-glucan/d (0.10 mmol/L) was not significant (2.3%; 95% CI: 0.02, -0.20). By analysis of covariance, log(MW × C) was a significant determinant of LDL cholesterol (P = 0.003). Treatment effects were not significantly influenced by age, sex, study center, or baseline LDL cholesterol. CONCLUSIONS: The physicochemical properties of oat ß-glucan should be considered when assessing the cholesterol-lowering ability of oat-containing products; an extruded breakfast cereal containing 3 g oat ß-glucan/d with a high-MW (2,210,000 g/mol) or a medium-MW (530,000 g/mol) lowered LDL cholesterol similarly by ≈0.2 mmol/L (5%), but efficacy was reduced by 50% when MW was reduced to 210,000 g/mol. This trial was registered at www.clinicaltrials.gov as NCT00981981.

Physicochemical properties of beta-glucan in differently processed oat foods influence glycemic response.

To assess the effect of food processing on the capacity of oat beta-glucan to attenuate postprandial glycemia, isocaloric crisp bread, granola, porridge, and pasta containing 4 g of beta-glucan as well as control products with low beta-glucan content were prepared. The physicochemical properties (viscosity, peak molecular weight (M(p)), and concentration (C)) of beta-glucan in in-vitro-digestion extracts were evaluated, and fasting and postprandial blood glucose concentrations were measured in human subjects. Porridge and granola had the highest efficacy in attenuating the peak blood glucose response (PBGR) because of their high M(p) and viscosity. beta-Glucan depolymerization in bread and pasta reduced beta-glucan bioactivity. Pastas, known to have low glycemic responses, showed the lowest PBGR. The analyses of these products with previously reported data indicated that 73% of the bioactivity in reducing PBGR can be explained by M(p) x C. Characterizing the physicochemical properties of beta-glucan in bioactive foods aids functional food development.