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Biomedical subjects

Andrew J Sinclair

Publications and source records attributed to Andrew J Sinclair.

At least 19 recordsLinked to original sources

The extent and breadth of benefits from participating in chronic disease self-management courses: a national patient-reported outcomes survey.

OBJECTIVE: To quantify the benefits that people receive from participating in self-management courses and identify subgroups that benefit most. METHODS: People with a wide range of chronic conditions attending self-management courses (N = 1341 individuals) were administered the Health Education Impact Questionnaire (heiQ). Baseline and follow-up data were collected resulting in 842 complete responses. Outcomes were categorized as substantial improvement (effect size, ES > or = 0.5), minimal/no change (ES -0.49 to 0.49) and substantial decline (ES < or = -0.5). RESULTS: On average, one third of participants reported substantial benefits at the end of a course and this ranged from 49% in the heiQ subscale Skill and technique acquisition to 27% in the heiQ subscale Health service navigation. Stratification by gender, age and education showed that younger participants were more likely to benefit, particularly young women. No further subgroup differences were observed. CONCLUSION: While the well-being of people with chronic diseases tends to decline, about one third of participants from a wide range of backgrounds show substantial improvements in a range of skills that enable them to self-manage. PRACTICE IMPLICATIONS: These data support the application of self-management courses indicating that they are a useful adjunct to usual care for a modest proportion of attendees.

Adolescent↗

Plasma phospholipid fatty acid composition as a biomarker of habitual dietary fat intake in an ethnically diverse cohort.

BACKGROUND AND AIM: As an evaluation of fatty acid intake measurement, our aim was to examine associations between diet and plasma phospholipid (PL) fatty acids, and whether these were modified by age, sex, country of birth, fasting status, use of cholesterol-lowering medication, body size, chronic disease and other lifestyle factors. METHODS AND RESULTS: Cross-sectional analysis of plasma PL fatty acid composition and dietary fatty acid intake over 12 months from a 121-item food frequency questionnaire (FFQ) in 4439 men and women aged 40-69 years, born in Australia, Greece or Italy. Crude correlation coefficients ranged from 0.18 to 0.40; and corrected correlation coefficients from 0.38 to 0.78 for total monounsaturated, polyunsaturated, n-6, n-3 fatty acids, oleic acid, linoleic acid, EPA and DHA. Weaker associations were observed for other fatty acids. The associations did not vary significantly by fasting status, use of lipid lowering medication or alcohol intake, but for some fatty acids did vary by sex, age, body mass index, country of birth, smoking and previous heart attack or diabetes. CONCLUSIONS: The FFQ provides useful information on intakes of mono- and polyunsaturated fatty acids. Correlations did not differ by fasting status, or use of lipid-lowering medication.

Adult↗

Omega 6 to omega 3 fatty acid imbalance early in life leads to persistent reductions in DHA levels in glycerophospholipids in rat hypothalamus even after long-term omega 3 fatty acid repletion.

Failure to provide omega 3 fatty acids in the perinatal period results in alterations in nerve growth factor levels, dopamine production and permanent elevations in blood pressure. The present study investigated whether changes in brain (i.e., hypothalamus) glycerophospholipid fatty acid profiles induced by a diet rich in omega 6 fatty acids and very low in alpha-linolenic acid (ALA) during pregnancy and the perinatal period could be reversed by subsequent feeding of a diet containing ALA. Female rats (6 per group) were mated and fed either a low ALA diet or a control diet containing ALA throughout pregnancy and until weaning of the pups at 3 weeks. At weaning, the pups (20 per group) remained on the diet of their mothers until 9 weeks, when half the pups were switched onto the other diet, thus generating four groups of animals. At 33 weeks, pups were killed, the hypothalamus dissected from the male rats and analysed for glycerophospholipid fatty acids. In the animals fed the diet with very little ALA and then re-fed the control diet containing high levels of ALA for 24 weeks, the DHA levels were still significantly less than the control values in PE, PS and PI fractions, by 9%, 18% and 34%, respectively. In this group, but not in the other dietary groups, ALA was detected in all glycerophospholipid classes at 0.2-1.7% of the total fatty acids. The results suggest that omega 6-3 PUFA imbalance early in life leads to irreversible changes in hypothalamic composition. The increased ALA and reduced DHA proportions in the animals re-fed ALA in later life are consistent with a dysfunction or down-regulation of the conversion of ALA to 18:4n-3 by the delta-6 desaturase.

Animals↗

A significant inverse relationship between concentrations of plasma homocysteine and phospholipid docosahexaenoic acid in healthy male subjects.

The aim of this study was to investigate the possibility of a relationship between plasma homocysteine (Hcy) and phospholipid FA (PUFA) in healthy Australian males. One hundred thirty six healthy male subjects aged 20-55 yr were recruited from the Melbourne metropolitan area. Each volunteer completed a semiquantitative food frequency questionnaire and gave a blood sample. Plasma Hcy concentrations were determined by an established HPLC method; the plasma phospholipid FA were determined by standard methods. Plasma Hcy concentration was significantly negatively correlated with plasma phospholipid concentration of the PUFA 20:5n-3 (r = -0.226, P = 0.009), 22:5n-3 (r= -0.182, P= 0.036), 22:6n-3 (r= -0.286, P= 0.001), total n-3 (r = -0.270, P = 0.002) and the ratio n-3/n-6 PUFA (r = -0.265, P = 0.002), and significantly positively correlated with 20:4n-6 (r= 0.180, P= 0.037). In the partial correlation analysis, after controlling for serum vitamin B12 and folate concentration, plasma Hcy was significantly negatively correlated with the plasma phospholipid concentration of 22:6n-3 (r = -0.205, P = 0.019), total n-3 (r = -0.182, P= 0.038) and the ratio n-3/n-6 PUFA (r= -0.174, P= 0.048). Evidence indicates that an increased concentration of n-3 PUFA in tissues has a beneficial effect on cardiovascular health. Our findings provide further evidence that increased consumption of dietary n-3 PUFA increases the concentration of n-3 PUFA in plasma phospholipid, which is associated with a protective effect on cardiovascular diseases and lower plasma Hcy levels. The mechanism that might explain the association between plasma 22:6n-3 and Hcy levels is not clear.

Diet↗

Facts on fats.

Cardiovascular disease and age-related macular degeneration (AMD) may share common risk factors in their causal pathways. Decades of research from the cardiovascular sciences on fats have led investigators to focus on specific types of fats rather than total fat as a whole. They have established that saturated and trans-unsaturated fats (trans fats) are damaging to cardiovascular health while polyunsaturated fats, particularly the marine omega 3 fatty acids appear protective. This has led to a number of studies investigating the associations of fat and AMD. Though the causal relationship between fats and AMD remain unproven, some studies suggest that an association may be present. To be able to understand and interpret the study results and their implications, an understanding of the fats in the diet is important. This review aims to give an overview of fatty acids, particularly the trans-unsaturated fatty acids, and the relevant food groups.

Dietary Fats↗

Effect of feeding systems on omega-3 fatty acids, conjugated linoleic acid and trans fatty acids in Australian beef cuts: potential impact on human health.

The influence of feeding systems on the levels of functional lipids and other fatty acid concentrations in Australian beef was examined. Rump, strip loin and blade cuts obtained from grass feeding, short-term grain feeding (80 days; STGF) and long-term grain feedlot rations (150-200 days; LTFL) were used in the present study. The typical Australian feedlot ration contains more than 50% barley and/or sorghum and balanced with whole cottonseed and protein meals were used as feed for STGF and LTFL regimens. Meat cuts from 18 cattle for each feeding regimen were trimmed of visible fat and connective tissue and then minced (300 g lean beef); replicate samples of 7 g were used for fatty acid (FA) analysis. There was a significantly higher level of total omega-3 (n-3) and long chain n-3 FA in grass-fed beef (P< 0.0001) than the grain-fed groups regardless of cut types. Cuts from STGF beef had significantly reduced levels of n-3 FA and conjugated linoleic acid (CLA) and similar levels of saturated, monounsaturated and n-6 FA compared with grass feeding (P < 0.001). Cuts from LTFL beef had higher levels of saturated, monounsaturated,n-6 FA and trans 18:1 than similar cuts from the other two groups (P<0.01), indicating that increased length of grain feeding was associated with more fat deposited in the carcass. There was a step-wise increase in trans 18:1 content from grass to STGF to LTGF, suggesting grain feeding elevates trans FA in beef, probably because of increased intake of 18:2n-6. Only grass-fed beef reached the target of more than 30mg of long chain n-3 FA/100 g muscle as recommended by Food Standard Australia and New Zealand for a food to be considered a source of omega-3 fatty acids. The proportions of trans 18:1 and n-6 FA were higher (P<0.001) for both grain-fed beef groups than grass-fed beef. Data from the present study show that grain feeding decreases functional lipid components (long chain n-3 FA and CLA) in Australian beef regardless of meat cuts, while increasing total trans 18:1 and saturated FA levels.

Animal Feed↗

Low dose supplementation with two different marine oils does not reduce pro-inflammatory eicosanoids and cytokines in vivo.

In view of the reported potential anti-inflammatory activity of the New Zealand green lipped mussel (NZGLM), we aimed to compare the effect of low dose marine oil supplementation, from mussels and fish, in reducing blood markers of inflammation. Thirty apparently healthy males and females were recruited from the general public in Melbourne, Australia to participate in a double blind, randomised, parallel intervention study. Subjects were consuming approximately 73 mg of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) daily in their background diet prior to the commencement of the intervention. Subjects were randomly assigned to consume either 2 mL/day of the NZGLM oil preparation (mixed with olive oil and dl-alpha-tocopherol) or fish oil preparation (also mixed with olive oil and dl-alpha-tocopherol) for six weeks. Two mL of the oils contained 241 mg and 181 mg of n-3 LCPUFA, respectively. Neutrophil phospholipid fatty acids, serum thromboxane B2 (TXB2), stimulated monocyte production of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNFalpha) were measured. During the intervention, the total intakes of n-3 LCPUFA from the background diet and the supplements were 199 mg/d and 173 mg/day for the NZGLM and FO groups, respectively. Following six weeks of supplementation, both groups showed a small, but significant increase in neutrophil phospholipid proportion of eicosapentaenoic acid. The NZGLM group also showed a significant increase in docosahexaenoic acid levels. There were no significant changes with time or treatment for TXB2, PGE2, IL-1 beta or TNFalpha. This study showed that low dose supplementation with n-3 LCPUFA from two different marine oil preparations showed no difference in inflammatory markers in this group of healthy individuals. Further studies are warranted including dose response trials and studies in populations with inflammatory conditions.

Adult↗

Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites.

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity. Male Sprague-Dawley rats were fed a chow diet (16% calories from fat, Con) or a diet high (53%) in Sat or PUFA for 8 wk. Insulin sensitivity was assessed by fasting plasma glucose and insulin and glucose tolerance via an oral glucose tolerance test. Muscle ceramide and diacylglycerol (DAG) levels and triacylglycerol (TAG) fatty acids were also measured. Both high-fat diets increased plasma free fatty acid levels by 30%. Compared with Con, Sat-fed rats were insulin resistant, whereas PUFA-treated rats showed improved insulin sensitivity. Sat caused a 125% increase in muscle DAG and a small increase in TAG. Although PUFA also resulted in a small increase in DAG, the excess fatty acids were primarily directed toward TAG storage (105% above Con). Ceramide content was unaffected by either high-fat diet. To examine the effects of fatty acids on cellular lipid storage and glucose uptake in vitro, rat L6 myotubes were incubated for 5 h with saturated and polyunsaturated fatty acids. After treatment of L6 myotubes with palmitate (C16:0), the ceramide and DAG content were increased by two- and fivefold, respectively, concomitant with reduced insulin-stimulated glucose uptake. In contrast, treatment of these cells with linoleate (C18:2) did not alter DAG, ceramide levels, and glucose uptake compared with controls (no added fatty acids). Both 16:0 and 18:2 treatments increased myotube TAG levels (C18:2 vs. C16:0, P < 0.05). These results indicate that increasing dietary Sat induces insulin resistance with concomitant increases in muscle DAG. Diets rich in n-6 PUFA appear to prevent insulin resistance by directing fat into TAG, rather than other lipid metabolites.

Animals↗

Perinatal omega-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood.

Dietary omega-3 polyunsaturated fatty acid (PUFA) influences the expression of a number of genes in the brain. Zinc transporter (ZnT) 3 has been identified as a putative transporter of zinc into synaptic vesicles of neurons and is found in brain areas such as hippocampus and cortex. Neuronal zinc is involved in the formation of amyloid plaques, a major characteristic of Alzheimer's disease. The present study evaluated the influence of dietary omega-3 PUFA on the expression of the ZnT3 gene in the brains of adult male Sprague-Dawley rats. The rats were raised and/or maintained on a control (CON) diet that contained omega-3 PUFA or a diet deficient (DEF) in omega-3 PUFA. ZnT3 gene expression was analyzed by using real-time PCR, free zinc in brain tissue was determined by zinquin staining, and total zinc concentrations in plasma and cerebrospinal fluid were determined by atomic absorption spectrophotometry. Compared with CON-raised animals, DEF-raised animals had increased expression of ZnT3 in the brain that was associated with an increased level of free zinc in the hippocampus. In addition, compared with CON-raised animals, DEF-raised animals had decreased plasma zinc level. No difference in cerebrospinal fluid zinc level was observed. The results suggest that overexpression of ZnT3 due to a perinatal omega-3 PUFA deficiency caused abnormal zinc metabolism in the brain. Conceivably, the influence of dietary omega-3 PUFA on brain zinc metabolism could explain the observation made in population studies that the consumption of fish is associated with a reduced risk of dementia and Alzheimer's disease.

Animals↗

Gas chromatography-chemical ionization-mass spectrometric fatty acid analysis of a commercial supercritical carbon dioxide lipid extract from New Zealand green-lipped mussel (Perna canaliculus).

Supercritical fluid extracts of New Zealand green-lipped mussels (NZGLM) have been suggested to have therapeutic properties related to their oil components. The large number of minor FA in NZGLM extract was characterized by a GC-CIMS/MS method that excels at identification of double-bond positions in FAME. The extract contained five major lipid classes: sterol esters, TAG, FFA, sterols, and polar lipids. The total FA content of the lipid extract was 0.664 g/mL. Fifty-three unsaturated FA (UFA) were fully identified, of which 37 were PUFA, and a further 21 UFA were detected for which concentrations were too low for assignment of double-bond positions. There were 17 saturated FA, with 14:0, 16:0, and 18:0 present in the greatest concentration. The 10 n-3 PUFA detected included 20:5n-3 and 22:6n-3, the two main n-3 FA; n-3 PUFA at low concentrations were 18:3, 18:4, 20:3, 20:4, 21:5, 22:5, 24:6, and 28:8. There were 43 UFA from the n-4, n-5, n-6, n-7, n-8, n-9, n-10, n-1 families, with 16:2n-4, 16:1n-5, 18:1n-5, 18:2n-6, 20:4n-6, 16:1n-7, 20:1n-7, 16:1n-9, 18:1 n-9, and 20:1 n-9 being the most abundant. In general, we estimated that FAME concentrations greater than 0.05% (w/w) were sufficient to assign double-bond positions. In total, 91 FA were detected in an extract of the NZGLM, whereas previous studies of fresh flesh from the NZGLM had reported identification of 42 FA. These data demonstrate a remarkable diversity of NZGLM FA.

Animals↗

Lean meat and heart health.

The general health message to the public about meat consumption is both confusing and misleading. It is stated that meat is not good for health because meat is rich in fat and cholesterol and high intakes are associated with increased blood cholesterol levels and coronary heart disease (CHD). This paper reviewed 54 studies from the literature in relation to red meat consumption and CHD risk factors. Substantial evidence from recent studies shows that lean red meat trimmed of visible fat does not raise total blood cholesterol and LDL-cholesterol levels. Dietary intake of total and saturated fat mainly comes from fast foods, snack foods, oils, spreads, other processed foods and the visible fat of meat, rather than lean meat. In fact, lean red meat is low in saturated fat, and if consumed in a diet low in SFA is associated with reductions in LDL-cholesterol in both healthy and hypercholesterolemia subjects. Lean red meat consumption has no effect on in vivo and ex vivo production of thromboxane and prostacyclin or the activity of haemostatic factors. Lean red meat is also a good source of protein, omega-3 fatty acids, vitamin B12, niacin, zinc and iron. In conclusion, lean red meat, trimmed of visible fat, which is consumed in a diet low in saturated fat does not increase cardiovascular risk factors (plasma cholesterol levels or thrombotic risk factors).

Cardiovascular Diseases↗

Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression.

Polyunsaturated fatty acids (PUFA) are essential structural components of the central nervous system. Their role in controlling learning and memory has been well documented. A nutrigenomic approach with high-density microarrays was used to reveal brain gene-expression changes in response to different PUFA-enriched diets in rats. In aged rats fed throughout life with PUFA-enriched diets, genes with altered expressions included transthyretin, alpha-synuclein, and calmodulins, which play important roles in synaptic plasticity and learning. The effect of perinatal omega-3 PUFA supply on gene expression later in life also was studied. Several genes showed similar changes in expression in rats fed omega-3-deficient diets in the perinatal period, regardless of whether they or their mothers were fed omega-3 PUFA-sufficient diets after giving birth. In this experiment, among the down-regulated genes were a kainate glutamate receptor and a DEAD-box polypeptide. Among the up-regulated genes were a chemokine-like factor, a tumor necrosis factor receptor, and cytochrome c. The possible involvement of the genes with altered expression attributable to different diets in different brain regions in young and aged rats and the possible mode of regulatory action of PUFA also are discussed. We conclude that PUFA-enriched diets lead to significant changes in expression of several genes in the central nervous tissue, and these effects appear to be mainly independent of their effects on membrane composition. The direct effects of PUFA on transcriptional modulators, the downstream developmentally and tissue-specifically activated elements might be one of the clues to understanding the beneficial effects of the omega-3 PUFA on the nervous system.

Animals↗

Immune function and adjustment style: do they predict survival in breast cancer?

The aim of this study was to investigate the role of immune status and psychosocial factors in survival from early breast cancer (N=61). Baseline assessments included lymphocyte number and function, natural killer cell activity (NKA), plasma cortisol and prolactin level. Psychosocial measures included anxiety, depression and mental adjustment to cancer and social support. Length of follow-up was 6.1-7.9 years with 14 (23%) breast cancer deaths. In Cox proportional hazards models adjusting for lymph node status two parameters predicted longer survival, low NKA (HR 29 per LLU, p=0.003) and minimizing the illness adjustment (HR 0.64 per scale point, p=0.012). These data provide little evidence for a psychoneuroimmunological mechanism in the survival from breast cancer. While this study is limited due to small sample size, and therefore the possibility of inflated estimates, longer survival in those minimizing the illness is a finding consistent with recent studies; however, the counter-intuitive finding that high NKA predicts shorter survival may be a marker for current disease or response to treatments.

Adaptation, Psychological↗

Does perinatal omega-3 polyunsaturated fatty acid deficiency increase appetite signaling?

OBJECTIVE: To investigate the effect of maternal dietary omega-3 polyunsaturated fatty acid (PUFA) deficiency and repletion on food appetite signaling. RESEARCH METHODS AND PROCEDURES: Sprague-Dawley rat dams were maintained on diets either supplemented with (CON) or deficient in (DEF) omega-3 PUFA. All offspring were raised on the maternal diet until weaning. After weaning, two groups remained on the respective maternal diet (CON and DEF groups), whereas a third group, born of dams fed the DEF diet, were switched to the CON diet (REC). Experiments on food intake began when the male rats reached 16 weeks of age. Food intake was stimulated either by a period of food restriction, by blocking glucose utilization (by 2-deoxyglucose injection), or by blocking beta-oxidation of fatty acids (by beta-mercaptoacetate injection). RESULTS: DEF animals consumed more than CON animals in response to all stimuli, with the greatest difference (1.9-fold) demonstrated following administration of 2-deoxyglucose. REC animals also consumed more than CON animals in response to food restriction and 2-deoxyglucose but not to beta-mercaptoacetate. DISCUSSION: These findings indicate that supply of omega-3 PUFA, particularly during the perinatal period, plays a role in the normal development of mechanisms controlling food intake, especially glucoprivic (i.e. reduced glucose availability) appetite signaling. Dietary repletion of omega-3 PUFA from 3 weeks of age restored intake responses to fatty acid metabolite signaling but did not reverse those in response to food restriction or glucoprivic stimuli.

Animals↗

Alpha-linolenic acid and the risk of prostate cancer. What is the evidence?

PURPOSE: Several studies have examined the association between polyunsaturated fatty acids and prostate cancer risk. We evaluated the evidence on the association between the essential polyunsaturated fatty acid, known as alpha-linolenic acid, and the risk of prostate cancer in humans. MATERIALS AND METHODS: We comprehensively reviewed published studies on the association between alpha-linolenic acid and the risk of prostate cancer using MEDLINE. RESULTS: A number of studies have shown a positive association between dietary, plasma or red blood cell levels of alpha-linolenic acid and prostate cancer. Other studies have demonstrated either no association or a negative association. The limitations of these studies include the assumption that dietary or plasma alpha-linolenic acid levels are positively associated with prostate tissue alpha-linolenic acid levels, and measurement errors of dietary, plasma and red blood cell alpha-linolenic acid levels. CONCLUSIONS: More research is needed in this area before it can be concluded that there is an association between alpha-linolenic acid and prostate cancer.

Biomedical Research↗

Mask-dependent attentional cuing effects in visual signal detection: the psychometric function for contrast.

A spatial-cuing paradigm was used to test the hypothesis of Carrasco, Penpeci-Talgar, and Eckstein (2000) that the mask-dependent cuing effects found in visual signal detection by Smith (2000a) were caused by submaximal activation of the transient-orienting system. Mask-dependent cuing was found with a range of stimulus contrasts with pure peripheral cues and with the mixed central-peripheral cues of Smith (2000a), contrary to the predictions of the submaximal activation hypothesis. The use of a pedestal detection task to control spatial uncertainty showed that the cuing effect was due to signal enhancement. A model of mask-dependent cuing is described, which assumes that attention affects the rate of information accumulation from the display and that masks limit the visual persistence of the stimulus. The model correctly predicts differential mask dependencies in sensitivity for detection and discrimination and the associated patterns of response times.

Adolescent↗