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The effects of conjugated linoleic acid supplementation on lipid profile in adults: A systematic review and dose-response meta-analysis.
Asbaghi, O, Ashtary-Larky, D, Naseri, K, Saadati, S, Zamani, M, Rezaei Kelishadi, M, Nadery, M, Doaei, S, Haghighat, N
Frontiers in nutrition. 2022;9:953012
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Elevated fats circulating in the blood has been shown to be a predictor for heart disease. Conjugated linoleic acid (CLA) is a type of fat that is found in the milk and meat of animals such as cows, sheep and goats. Although classed as a fat, when taken in a supplemental form, some studies have shown it to decrease circulating fats whereas others have shown no beneficial effects. This systematic review and meta-analysis of 56 randomised control trials aimed to explore the effects of CLA on circulating blood profiles. The results showed that CLA increased levels of cholesterols, which may contribute to heart disease, but also increased cholesterol which may help to prevent heart disease. It was concluded that CLA supplementation has little effect on fats in the blood. This study could be used by healthcare professionals to understand that there may be little utility in recommending a supplemental CLA for the management of heart disease.
Abstract
BACKGROUND The findings of trials investigating the effect of conjugated linoleic acid (CLA) administration on lipid profile are controversial. This meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of CLA supplementation on lipid profile. METHODS Two authors independently searched electronic databases including PubMed, Web of Science, and Scopus until March 2022, in order to find relevant RCTs. The random effects model was used to evaluate the mean and standard deviation. RESULTS In total, 56 RCTs with 73 effect sizes met the inclusion criteria and were eligible for the meta-analysis. CLA supplementation significantly alter triglycerides (TG) (WMD: 1.76; 95% CI: -1.65, 5.19), total cholesterols (TC) (WMD: 0.86; 95% CI: -0.42, 2.26), low-density lipoprotein cholesterols (LDL-C) (WMD: 0.49; 95% CI: -0.75, 2.74), apolipoprotein A (WMD: -3.15; 95% CI: -16.12, 9.81), and apolipoprotein B (WMD: -0.73; 95% CI: -9.87, 8.41) concentrations. However, CLA supplementation significantly increased the density lipoprotein cholesterol (HDL-C) (WMD: -0.40; 95% CI: -0.72, -0.07) concentrations. CONCLUSION CLA supplementation significantly improved HDL-C concentrations, however, increased concentrations of TG, TC, LDL-C, apolipoprotein A, and apolipoprotein B. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022331100.
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Association between Mediterranean Diet and Fatty Liver in Women with Overweight and Obesity.
Leone, A, Bertoli, S, Bedogni, G, Vignati, L, Pellizzari, M, Battezzati, A
Nutrients. 2022;14(18)
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Non-alcoholic fatty liver disease (NAFLD) is a condition resulting from excessive lipid accumulation in the liver in individuals with low alcohol consumption. Obesity is an established risk factor for the development of NAFLD, and 50% to 75% of people with obesity also have NAFLD. The aim of this study was to evaluate the association between Mediterranean diet and non-invasive indices of fatty liver in a large sample of women with overweight and obesity. This study is a cross-sectional study of 2967 consecutive women with overweight and obesity. Results show that higher adherence to the Mediterranean diet was associated with lower indices of fatty liver in women with overweight and obesity (particularly obese women than in women who are overweight). Authors conclude that women with obesity, especially during the premenopausal period, may benefit more from following a Mediterranean-style diet.
Abstract
Obesity is a risk factor for NAFLD. However, not all people with obesity have an excessive intrahepatic fat content. Adherence to a high-quality dietary pattern may also promote liver health in obesity. A cross-sectional study of 2967 women with overweight and obesity was carried out to assess the association between a Mediterranean diet and fatty liver. All women underwent clinical examination, anthropometric measurements, blood sampling, ultrasound measurements of abdominal visceral and subcutaneous fat, and assessment of adherence to the Mediterranean diet using the 14-item MEDAS questionnaire. Fatty liver index (FLI), NAFLD fatty liver steatosis (NAFLD-FLS) and hepatic steatosis index (HSI) were calculated. In women with obesity, the MEDAS score was inversely associated with FLI (β = -0.60, 95% CI: -1.04, -0.16, p = 0.008), NAFLD-FLS (β = -0.092, 95% CI: -0.134, -0.049, p < 0.001) and HSI (β = -0.17, 95% CI: -0.30, -0.04, p = 0.011). Stronger associations were observed in premenopausal women with obesity. Mediterranean diet was inversely associated with NAFLD-FLS in women with overweight, independently of menopausal status. In conclusion, Mediterranean diet is associated with a better liver status in women with overweight and obesity. This may have a public health impact and be useful in drafting nutritional guidelines for NAFLD.
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Efficacy of a 2-Month Very Low-Calorie Ketogenic Diet (VLCKD) Compared to a Standard Low-Calorie Diet in Reducing Visceral and Liver Fat Accumulation in Patients With Obesity.
Cunha, GM, Guzman, G, Correa De Mello, LL, Trein, B, Spina, L, Bussade, I, Marques Prata, J, Sajoux, I, Countinho, W
Frontiers in endocrinology. 2020;11:607
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Excess fat in the liver, known as non-alcoholic fatty liver disease (NAFLD), has been shown to increase the risk of chronic diseases such as type 2 diabetes. Standard treatment regimens consist of low-calorie (LC) diets and exercise, however these may be ineffective at reversing fat accumulation in the liver. A very low-calorie ketogenic diet (VLCKD) has been proposed as an alternative treatment for NAFLD. This randomised control pilot study of 39 individuals with obesity aimed to compare LC diet and VLCKD on fat accumulation and indicators for NAFLD for two months. The results showed greater weight loss, abdominal fat reduction, liver fat reduction and improvements in liver function with VLCKD compared to the LC diet. Cholesterol was significantly reduced by both diets. However liver stiffness remained unchanged. The authors concluded that VLCKD was more successful at reducing liver fat and abdominal fat accumulation than current standard therapy and has the potential to improve NAFLD. Health care professionals could use this study to improve liver and abdominal fat loss in patients with obesity to improve NAFLD, when standard therapy has been inadequate.
Abstract
Background: Currently the treatment of non-alcoholic fatty liver disease (NAFLD) is based on weight loss through lifestyle changes, such as exercise combined with calorie-restricted dieting. Objectives: To assess the effects of a commercially available weight loss program based on a very low-calorie ketogenic diet (VLCKD) on visceral adipose tissue (VAT) and liver fat content compared to a standard low-calorie (LC) diet. As a secondary aim, we evaluated the effect on liver stiffness measurements. Methods: Open, randomized controlled, prospective pilot study. Patients were randomized and treated either with an LC or a VLCKD and received orientation and encouragement to physical activity equally for both groups. VAT, liver fat fraction, and liver stiffness were measured at baseline and after 2 months of treatment using magnetic resonance imaging. Paired t-tests were used for comparison of continuous variables between visits and unpaired test between groups. Categorical variables were compared using the χ2-test. Pearson correlation was used to assess the association between VAT, anthropometric measures, and hepatic fat fraction. A significance level of the results was established at p < 0.05. Results: Thirty-nine patients (20 with VLCKD and 19 with LC) were evaluated at baseline and 2 months of intervention. Relative weight loss at 2 months was -9.59 ± 2.87% in the VLCKD group and -1.87 ± 2.4% in the LC group (p < 0.001). Mean reductions in VAT were -32.0 cm2 for VLCKD group and -12.58 cm2 for LC group (p < 0.05). Reductions in liver fat fraction were significantly more pronounced in the VLCKD group than in the LC group (4.77 vs. 0.79%; p < 0.005). Conclusion: Patients undergoing a VLCKD achieved superior weight loss, with significant VAT and liver fat fraction reductions when compared to the standard LC diet. The weight loss and rapid mobilization of liver fat demonstrated with VLCKD could serve as an effective alternative for the treatment of NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04322110.
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Protective effect of probiotics in patients with non-alcoholic fatty liver disease.
Cai, GS, Su, H, Zhang, J
Medicine. 2020;99(32):e21464
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Non-alcoholic fatty liver disease (NAFLD) is common in people with obesity and is characterised by high amounts of fat stored in the liver. Diet and exercise are the standard treatments, however recent studies have indicated that the gut microbiota may have an important role. This randomised control trial of 140 patients with NAFLD, aimed to assess the effect of probiotics when added to standard therapy for 3 months. The results showed that although gut microbiota, some aspects of liver function, blood lipids and blood sugars were all improved in individuals on standard therapy, there were additional improvements in those on standard therapy plus probiotics. It was concluded that although standard therapy alone is adequate to improve NAFLD, probiotics plus standard therapy was superior to standard therapy alone and effective in treatment of NAFLD. This study could be used by health professionals to justify the addition of probiotics to standard therapy to further improve NAFLD outcomes.
Abstract
To investigate the effects of probiotics on liver function, glucose and lipids metabolism, and hepatic fatty deposition in patients with non-alcoholic fatty liver disease (NAFLD).Totally 140 NAFLD cases diagnosed in our hospital from March 2017 to March 2019 were randomly divided into the observation group and control group, 70 cases in each. The control group received the diet and exercise therapy, while the observation group received oral probiotics based on the control group, and the intervention in 2 groups lasted for 3 months. The indexes of liver function, glucose and lipids metabolism, NAFLD activity score (NAS), and conditions of fecal flora in 2 groups were compared before and after the treatment.Before the treatment, there were no significant differences on alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamine transferase (GGT), total bilirubin (TBIL), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR), NAFLD activity score (NAS), and conditions of fecal flora in 2 groups (P > .05). After the treatment, ALT, AST, GGT, TC, TG, HOMA-IR, NAS, and conditions of fecal flora in the observation group were better than those in the control group, and the observation group was better after treatment than before. All these above differences were statistically significant (P < .05).Probiotics can improve some liver functions, glucose and lipids metabolism, hepatic fatty deposition in patients with NAFLD, which will enhance the therapeutic effects of NAFLD.
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Very Low-Calorie Ketogenic Diet: A Safe and Effective Tool for Weight Loss in Patients With Obesity and Mild Kidney Failure.
Bruci, A, Tuccinardi, D, Tozzi, R, Balena, A, Santucci, S, Frontani, R, Mariani, S, Basciani, S, Spera, G, Gnessi, L, et al
Nutrients. 2020;12(2)
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Very low-calorie ketogenic diets (VLCKD) may be an effective way to lose weight. However, the high amount of protein they contain may harm the kidneys, especially in those who already have impaired kidney function. This observational study of 92 obese men and women aimed to evaluate the effect of VLCKD on weight loss in individuals with mild kidney failure, compared to healthy individuals. A VLCKD diet resulted in significantly decreased BMI and body weight, due to a decrease in fat mass and slight decrease in muscle mass. Improvements were seen in blood pressure, indicators for diabetes and cholesterol levels. No changes to kidney or liver function were apparent and only a few minor adverse events were reported. Interestingly a small percentage of individuals with mildly impaired kidney function reported improvements in their condition. It was concluded that VLCKD is a safe and effective way to lose weight in patients with obesity and mild kidney disease. This study could be used by healthcare professionals to consider recommending a VLCKD to patients who are obese and have mild kidney disease.
Abstract
Very low-calorie ketogenic diets (VLCKD) are an effective and increasingly used tool for weight loss. Traditionally considered high protein, ketogenic diets are often looked at with concern by clinicians due to the potential harm they pose to kidney function. We herein evaluated the efficacy and safety of a VLCKD in patients with obesity and mild kidney failure. A prospective observational real-life study was conducted on ninety-two patients following a VLCKD for approximately 3 months. Thirty-eight had mild kidney failure and fifty-four had no renal condition and were therefore designated as control. Anthropometric parameters, bioelectrical impedance and biochemistry data were collected before and at the end of the dietary intervention. The average weight loss was nearly 20% of initial weight, with a significant reduction in fat mass. We report an improvement of metabolic parameters and no clinically relevant variation regarding liver and kidney function. Upon stratification based on kidney function, no differences in the efficacy and safety outcomes were found. Interestingly, 27.7% of patients with mild renal failure reported normalization of glomerular filtrate after dietary intervention. We conclude that, when conducted under the supervision of healthcare professionals, a VLCKD is an effective and safe treatment for weight loss in patients with obesity, including those affected by mild kidney failure.
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Effects of Some Food Components on Non-Alcoholic Fatty Liver Disease Severity: Results from a Cross-Sectional Study.
Mirizzi, A, Franco, I, Leone, CM, Bonfiglio, C, Cozzolongo, R, Notarnicola, M, Giannuzzi, V, Tutino, V, De Nunzio, V, Bruno, I, et al
Nutrients. 2019;11(11)
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Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic (liver) fat accumulation. Lifestyle interventions are the only known effective treatment for NAFLD. The aim of this study was to estimate associations between the consumption of some food group components with the grade of severity in NAFLD subjects. The study is a cross-sectional nutritional randomised clinical trial, which enrolled 136 subjects (79 males) with moderate or severe NAFLD. Results showed that some food group components were associated with a lower or a higher risk of developing severe NAFLD, and that, within the same food group, some components with a protective or promoter action are present. Authors conclude that their findings could help to elaborate personalised dietary counselling to treat NAFLD.
Abstract
Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) observed in Western countries is due to the concurrent epidemics of overweight/obesity and associated metabolic complications, both recognized risk factors. A Western dietary pattern has been associated with weight gain and obesity, and more recently with NAFLD. Methods: This is a baseline cross-sectional analysis of 136 subjects (79 males) enrolled consecutively in the NUTRIATT (NUTRItion and Ac-TiviTy) study. Study subjects had moderate or severe NAFLD diagnosed by using Fibroscan-CAP. Food Frequency Questionnaire was used to obtain information about food intake. Statistical analysis included descriptive statistics and a multivariable logistic regression model. Results: The mean age was 49.58 (±10.18) with a mean BMI of 33.41 (±4.74). A significant inverse relationship was revealed between winter ice-cream intake and NAFLD severity (O.R. 0.65, 95% C.I. 0.95-0.99); chickpeas intake and NAFLD severity (O.R. 0.57, 95% C.I. 0.34-0.97), and not industrial aged-cheeses type (O.R. 0.85, 95% C.I. 0.74-0.98). A statistically significant positive association also emerged between rabbit meat (O.R. 1.23, 95% C.I. 1.01-1.49), industrial type aged cheeses (O.R. 1.17, 95% C.I. 1.01-1.35), milk-based desserts (no winter ice cream) (O.R. 1.11, 95% C.I. 1.01-1.21), fats (O.R. 1.12, 95% C.I. 1.01-1.25), and NAFLD severity. Conclusion: The fresh foods from non-intensive farming and high legume intake that characterize the Mediterranean diet would seem to be beneficial for patients with NAFLD.
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Effects of krill oil and lean and fatty fish on cardiovascular risk markers: a randomised controlled trial.
Rundblad, A, Holven, KB, Bruheim, I, Myhrstad, MC, Ulven, SM
Journal of nutritional science. 2018;7:e3
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Fish consumption and supplementation with omega-3 rich fish oil has been shown to reduce the risk of cardiovascular disease. Krill oil is becoming a popular choice of fish oil for supplementation however few studies have investigated its health benefits. This small (n=36) double blind, randomised controlled trial aimed to assess the different impacts of 8-week consumption of either: krill oil supplements (4g oil daily); 3 fish meals per week (2 oily fish, one lean fish); or placebo of sunflower oil (4g oil daily), on cardiovascular risk markers. The results showed significant positive changes to blood glucose, lipids, phospholipids and cholesterol markers for the krill oil group, compared to the fish group and placebo. Vitamin D levels increased significantly in the fish consumption group compared to krill oil and placebo. Plasma levels of omega-3 fatty acids increased for both the krill oil group and fish consumption group. The authors conclude that krill oil supplementation and fish consumption both have positive health effects in relation to cardiovascular disease and larger studies of longer duration are needed.
Abstract
Fish consumption and supplementation with n-3 fatty acids reduce CVD risk. Krill oil is an alternative source of marine n-3 fatty acids and few studies have investigated its health effects. Thus, we compared krill oil supplementation with the intake of fish with similar amounts of n-3 fatty acids on different cardiovascular risk markers. In an 8-week randomised parallel study, thirty-six healthy subjects aged 18-70 years with fasting serum TAG between 1·3 and 4·0 mmol/l were randomised to receive either fish, krill oil or control oil. In the fish group, subjects consumed lean and fatty fish, according to dietary guidelines. The krill and control group received eight capsules per d containing 4 g oil per d. The weekly intake of marine n-3 fatty acids from fish given in the fish group and from krill oil in the krill group were 4103 and 4654 mg, respectively. Fasting serum TAG did not change between the groups. The level of total lipids (P = 0·007), phospholipids (P = 0·015), cholesterol (P = 0·009), cholesteryl esters (P = 0·022) and non-esterified cholesterol (P = 0·002) in the smallest VLDL subclass increased significantly in response to krill oil supplementation. Blood glucose decreased significantly (P = 0·024) in the krill group and vitamin D increased significantly in the fish group (P = 0·024). Furthermore, plasma levels of marine n-3 fatty acids increased significantly in the fish and krill groups compared with the control (all P ≤ 0·0003). In conclusion, supplementation with krill oil and intake of fish result in health-beneficial effects. Although only krill oil reduced fasting glucose, fish provide health-beneficial nutrients, including vitamin D.
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Silymarin in the prevention and treatment of liver diseases and primary liver cancer.
Féher, J, Lengyel, G
Current pharmaceutical biotechnology. 2012;13(1):210-7
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Non-alcoholic fatty liver disease (NAFLD) is a recognised health problem with no convincing interventions to date. This randomised trial aimed to examine the efficacy of silymarin plus vitamin E in the treatment of NAFLD. 36 patients were randomized to either group Ι or group ΙΙ. Group Ι was treated with 2 tablets of silymarin plus vitamin E per day, hypocaloric diet and exercise. Group ΙΙ was treated only with a hypocaloric diet. Study duration was 3 months for both groups. Diagnosis of NAFLD was confirmed for all participants by liver biopsy. Patients in group Ι showed significant decrease in anthropometric measurements. Both groups experienced reductions in markers of NAFLD, however in group I, these reductions were independent of weight loss, whereas in group II, those who failed to lose 5% of body weight didn’t show a change in biochemical markers. Authors conclude that intervention with silymarin plus vitamin E, alone or along with other treatments, can help NAFLD patients who fail to lose weight with diet.
Abstract
In chronic liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver diseases, drug- and chemical-induced hepatic toxicity), the antioxidant medicines such as silymarin can have beneficial effect. Liver cirrhosis, non-alcoholic fatty liver and steatohepatitis are risk factors for hepatocellular carcinoma (HCC). Insulin resistance and oxidative stress are the major pathogenetic mechanisms leading the hepatic cell injury in these patients. The silymarin exerts membrane-stabilizing and antioxidant activity, it promotes hepatocyte regeneration; furthermore it reduces the inflammatory reaction, and inhibits the fibrogenesis in the liver. These results have been established by experimental and clinical trials. According to open studies the long-term administration of silymarin significantly increased survival time of patients with alcohol induced liver cirrhosis. Based on the results of studies using methods of molecular biology, silymarin can significantly reduce tumor cell proliferation, angiogenesis as well as insulin resistance. Furthermore, it exerts an anti-atherosclerotic effect, and suppresses tumor necrosis factor-alpha-induced protein production and mRNA expression due to adhesion molecules. The chemopreventive effect of silymarin on HCC has been established in several studies using in vitro and in vivo methods; it can exert a beneficial effect on the balance of cell survival and apoptosis by interfering cytokines. In addition to this, anti-inflammatory activity and inhibitory effect of silymarin on the development of metastases have also been detected. In some neoplastic diseases silymarin can be administered as adjuvant therapy as well.
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Randomised controlled trial of effect of fruit and vegetable consumption on plasma concentrations of lipids and antioxidants.
Zino, S, Skeaff, M, Williams, S, Mann, J
BMJ (Clinical research ed.). 1997;314(7097):1787-91
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Previous studies have suggested that people with high intake of fruit and vegetables or plasma antioxidant levels have a reduced risk of cancer and cardiovascular disease. There is limited data concerning the extent to which increased intake of fruit and vegetables, opposed to antioxidant supplementation, correlate with antioxidant plasma concentration levels. he aim of this trial was to examine whether advice to increase fruit and vegetable consumption affect the plasma concentrations of antioxidants, total and low-density lipoprotein (LDL). Eighty-seven subjects with normal lipid profiles who ate three of fewer servings of fruit and vegetables a day were included and the intervention group was asked to consume eight servings of fruit and vegetables a day for eight weeks. he findings of this study showed that plasma concentrations of vitamin C, alpha-carotene and beta-carotene, factors associated with reduced cancer risk, increased in parallel with increased fruit and vegetable intake in the intervention group. More specific dietary advice may be required to modify the levels of lipoprotein and vitamin E.
Abstract
OBJECTIVES To determine the extent to which plasma antioxidant concentrations in people with habitual low intake of fruit and vegetables respond to increased intakes of these foods. To examine whether advice to increase fruit and vegetables will result in reduction of concentrations of total and low density lipoprotein cholesterol. DESIGN Randomised controlled trial in which intervention and control groups were followed up for eight weeks. The intervention group was asked to consume eight servings of fruit and vegetables a day. SETTING Dunedin, New Zealand. SUBJECTS Eighty seven subjects with normal lipid concentrations who ate three or fewer servings of fruit and vegetables daily. MAIN OUTCOME MEASURES Plasma concentrations of vitamin C, retinol, alpha and beta carotene, alpha tocopherol, lipids, and lipoproteins. Dietary intake assessed with diet records over four days. RESULTS The mean plasma vitamin C, alpha carotene, and beta carotene concentrations increased in parallel with increased dietary intake of fruit and vegetables in the intervention group. Concentrations of retinol, alpha tocopherol, lipids, and lipoproteins remained unchanged despite some increase in dietary vitamin E and a small reduction in saturated fat intake. CONCLUSIONS Following a recommendation to increase fruit and vegetable consumption produces change in plasma concentrations of vitamin C, alpha carotene, and beta carotene likely to reduce incidence of cancer. More specific dietary advice to modify fat intake may be necessary to reduce the risk of cardiovascular disease mediated by lipoprotein and vitamin E.
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Partial purification and characterization of extrinsic pathway inhibitor (the factor Xa-dependent plasma inhibitor of factor VIIa/tissue factor).
Warn-Cramer, BJ, Maki, SL, Zivelin, A, Rapaport, SI
Thrombosis research. 1987;48(1):11-22
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Green tea (GT) consumption has been associated with the prevention and control of type 2 diabetes, cardiovascular and metabolic disease as well as having a positive effect on body weight and composition. However, the polyphenols in GT have been shown to interact with mineral distribution within the body and those minerals have been shown to be deficient in obesity. Studies to measure mineral status in obese subjects supplementing with GT have been inconclusive and this study aimed to measure the serum concentrations of minerals (calcium, copper, iron, zinc, magnesium), body mass index, total antioxidant status (TAS), lipid profile and glucose concentration. 46 obese patients were randomised into 2 groups, one group were supplemented with 279mg of green tea extract (GTE) and 208mg of the polyphenol epigallocatechin-3-gallate (EGCG) and the other group were issued with a placebo for 3 months. The study concluded that GTE improved Zn and Mg, however decreased levels of FE. The results confirmed a positive effect on body mass, lipid profile, glucose and TAS. It was concluded that more studies are required on a larger population over a longer period of time.
Abstract
We report a procedure to purify partially from plasma (approximately 1200 fold) the factor Xa-dependent inhibitor of factor VIIa/tissue factor (i.e., the extrinsic pathway inhibitor or EPI) and describe some of its properties. An assay for EPI was developed based upon inhibition of factor VIIa/tissue factor induced release of activation peptide from tritiated factor IX by a test sample in the presence but not in the absence of factor Xa. Approximately 50% of the total EPI activity in plasma was found in the lipoprotein fraction, which was used as the starting material for purification. Total lipoproteins (isolated by density ultracentrifugation) were delipidated and the urea soluble apoproteins gel filtered on Sephacryl S-200. The inhibitory activity co-eluted with the major protein peak, which primarily contained apoprotein A-I. Inhibitory activity was separated from apoprotein A-I by anion-exchange chromatography on Q-Sepharose and was further resolved from higher and lower molecular weight contaminating proteins by polypreparative disc gel electrophoresis in the presence of 0.1% SDS. Functional inhibitory activity eluted from the polypreparative disc gel in two discrete pools of different molecular weights (approximately 34,000 and approximately 43,000 D). Apoprotein E was identified by immunological techniques as the major protein present in both of these pools. However, incubation with a monospecific polyclonal antibody to human apoprotein E did not decrease EPI activity either in plasma or in the partially purified polypreparative disc gel fractions. A rabbit antiserum was prepared against material from the polypreparative disc gel. The IgG fraction neutralized approximately 95% of the total inhibitory activity present in plasma. Therefore, EPI in the lipoprotein fraction and in the non-lipoprotein fraction of plasma appears to be antigenically similar.