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1.  Fish-oil esters of plant sterols differ from vegetable-oil sterol esters in triglycerides lowering, carotenoid bioavailability and impact on plasminogen activator inhibitor-1 (PAI-1) concentrations in hypercholesterolemic subjects 
Consumption of plant sterol (PS) esters lower low-density lipoprotein (LDL)-cholesterol levels by suppressing intestinal absorption of cholesterol. Commercially available PS are mainly esterified to omega-6 fatty acid (FA), such as sunflower oil (SO) FA. Emerging trends include using other sources such as olive oil (OO) or omega-3 FA from fish oil (FO), known to exert potent hypotriglyceridemic effects. Our objective was to compare the actions of different FA esterified to PS on blood lipids, carotenoid bioavailability as well as inflammatory and coagulation markers.
Twenty-one moderately overweight, hypercholesterolemic subjects consumed experimental isoenergetic diets enriched with OO (70% of fat), each lasting 28-day and separated by 4-week washout periods, using a randomized crossover design. Diets were supplemented with three PS esters preparations, PS-FO, PS-SO, or PS-OO. All PS treatments contained an equivalent of 1.7 PS g/d, and the PS-FO provided a total of 5.4 g/d FO FA (eicosapentaenoic and docosahexaenoic acids).
There were no differences between PS-containing diet effects on total cholesterol, LDL-cholesterol, or high-density lipoprotein (HDL)-cholesterol levels. However, PS-FO consumption resulted in markedly lower (P < 0.0001) fasting and postprandial triglyceride concentrations compared with PS-SO and PS-OO. These treatments affected plasma β-carotene (P = 0.0169) and retinol (P = 0.0244), but not tocopherol (P = 0.2108) concentrations. Consumption of PS-FO resulted in higher β-carotene (P = 0.0139) and retinol (P = 0.0425) levels than PS-SO and PS-OO, respectively. Plasma TNF-α, IL-6, C-reactive protein, prostate specific antigen, and fibrinogen concentrations were unaffected by the PS-interventions. In contrast, plasminogen activator inhibitor 1 (PAI-1) concentrations were lower (P = 0.0282) in the PS-FO-fed than the PS-SO, but not the PS-OO (P = 0.7487) groups.
Our findings suggest that, in hypercholesterolemic subjects consuming an OO-based diet, PS-FO results in lowered blood triglyceride and PAI-1 concentrations, and higher fat-soluble vitamin levels in comparison to the vegetable oil FA esters of PS (PS-SO and PS-OO). Thus, PS-FO may offer hyperlipidemic subjects a more comprehensive lipid lowering approach while reducing the potential risk of decreased plasma carotenoid concentrations.
PMCID: PMC2194675  PMID: 17961204
2.  A Dose-Response Study of the Effects of Dietary Cholesterol on Fasting and Postprandial Lipid and Lipoprotein Metabolism in Healthy Young Men 
Arteriosclerosis and Thrombosis  1994;14(4):576-586.
Despite many previous studies, controversy remains concerning the effects of dietary cholesterol on plasma cholesterol concentrations. In addition, the focus of previous studies has been fasting lipid and lipoprotein concentrations; there are no published studies with postprandial measurements. We studied the effects of four levels of dietary cholesterol intake on fasting lipid, lipoprotein, and apoprotein levels, as well as postprandial lipid levels, in a group of young, healthy men who were otherwise eating a low-fat, American Heart Association step 1 diet. Twenty young, healthy men completed a randomized, four-way crossover design study to test the effects of an American Heart Association step 1 diet containing 0, 1, 2, or 4 eggs per day. Dietary cholesterol ranged from 128 to 858 mg cholesterol per day. Each diet was eaten for 8 weeks, with a break between diets. Three fasting blood samples were obtained at the end of each diet period. In addition, blood samples were obtained just before and 2, 4, and 6 hours after ingestion of a standard lunch containing the various amounts of egg cholesterol. We also obtained blood 4 and 8 hours after the subjects ingested a standard, high-fat formula. Fasting plasma total cholesterol concentrations increased by 1.47 mg/dL (0.038 mmol/L) for every 100 mg dietary cholesterol added to the diet (P <.001). Low-density lipoprotein (LDL) cholesterol increased in parallel. Responsiveness varied but appeared to be normally distributed. Fasting plasma apoprotein B concentrations increased approximately 10% between the 0- and 4-egg diets and were correlated with changes in total and LDL cholesterol concentrations. Although there was a trend toward a greater response in men with an apoprotein E4 allele, this was not statistically significant. Fasting plasma cholesteryl ester transfer protein levels were higher only on the 4-egg diet, and changes in cholesteryl ester transfer protein levels between the 0- and 4-egg diets correlated with changes in total and LDL cholesterol. There were no differences in the postlunch or post-fat-formula responses of plasma lipids across the diets. Incubation of the 4-hour postlunch serum with J774 macrophages did not affect cell cholesteryl ester content at any level of dietary cholesterol. Cellular free cholesterol levels were slightly higher on each of the egg-containing diets versus the 0-egg diet. In summary, increases in dietary cholesterol resulted in linear increases in fasting total and LDL cholesterol in young, healthy men. The increases were less than expected based on previous studies, and this may have been due to the low saturated fat content of the background diet and/or the young age of the study group. Dietary cholesterol had no effect on postprandial plasma lipids either in response to the varying doses of cholesterol or after a standard high-fat meal. Increasing dietary cholesterol did not appear to result in an increased atherogenic potential of postprandial serum, as assessed by effects on cultured macrophages.
PMCID: PMC3292202  PMID: 8148356
diet; cholesterol; plasma; LDL; apoprotein B; apoprotein E; cholesteryl ester transfer protein; postprandial; macrophages
3.  Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet 
Annals of internal medicine  2010;153(3):147-157.
Previous studies comparing low-carbohydrate and low-fat diets have not included a comprehensive behavioral treatment, resulting in suboptimal weight loss.
To evaluate the effects of 2-year treatment with a low-carbohydrate or low-fat diet, each of which was combined with a comprehensive lifestyle modification program.
Randomized parallel-group trial. ( registration number: NCT00143936)
3 academic medical centers.
307 participants with a mean age of 45.5 years (SD, 9.7 years) and mean body mass index of 36.1 kg/m2 (SD, 3.5 kg/m2).
A low-carbohydrate diet, which consisted of limited carbohydrate intake (20 g/d for 3 months) in the form of low–glycemic index vegetables with unrestricted consumption of fat and protein. After 3 months, participants in the low-carbohydrate diet group increased their carbohydrate intake (5 g/d per wk) until a stable and desired weight was achieved. A low-fat diet consisted of limited energy intake (1200 to 1800 kcal/d; ≤30% calories from fat). Both diets were combined with comprehensive behavioral treatment.
Weight at 2 years was the primary outcome. Secondary measures included weight at 3, 6, and 12 months and serum lipid concentrations, blood pressure, urinary ketones, symptoms, bone mineral density, and body composition throughout the study.
Weight loss was approximately 11 kg (11%) at 1 year and 7 kg (7%) at 2 years. There were no differences in weight, body composition, or bone mineral density between the groups at any time point. During the first 6 months, the low-carbohydrate diet group had greater reductions in diastolic blood pressure, triglyceride levels, and very-low-density lipoprotein cholesterol levels, lesser reductions in low-density lipoprotein cholesterol levels, and more adverse symptoms than did the low-fat diet group. The low-carbohydrate diet group had greater increases in high-density lipoprotein cholesterol levels at all time points, approximating a 23% increase at 2 years.
Intensive behavioral treatment was provided, patients with dyslipidemia and diabetes were excluded, and attrition at 2 years was high.
Successful weight loss can be achieved with either a low-fat or low-carbohydrate diet when coupled with behavioral treatment. A low-carbohydrate diet is associated with favorable changes in cardiovascular disease risk factors at 2 years.
Primary Funding Source
National Institutes of Health.
PMCID: PMC2949959  PMID: 20679559
4.  The effect of ghee (clarified butter) on serum lipid levels and microsomal lipid peroxidation 
Ayu  2010;31(2):134-140.
Ghee, also known as clarified butter, has been utilized for thousands of years in Ayurveda as a therapeutic agent. In ancient India, ghee was the preferred cooking oil. In the last several decades, ghee has been implicated in the increased prevalence of coronary artery disease (CAD) in Asian Indians due to its content of saturated fatty acids and cholesterol and, in heated ghee, cholesterol oxidation products. Our previous research on Sprague-Dawley outbred rats, which serve as a model for the general population, showed no effect of 5 and 10% ghee-supplemented diets on serum cholesterol and triglycerides. However, in Fischer inbred rats, which serve as a model for genetic predisposition to diseases, results of our previous research showed an increase in serum total cholesterol and triglyceride levels when fed a 10% ghee-supplemented diet. In the present study, we investigated the effect of 10% dietary ghee on microsomal lipid peroxidation, as well as serum lipid levels in Fischer inbred rats to assess the effect of ghee on free radical mediated processes that are implicated in many chronic diseases including cardiovascular disease. Results showed that 10% dietary ghee fed for 4 weeks did not have any significant effect on levels of serum total cholesterol, but did increase triglyceride levels in Fischer inbred rats. Ghee at a level of 10% in the diet did not increase liver microsomal lipid peroxidation or liver microsomal lipid peroxide levels. Animal studies have demonstrated many beneficial effects of ghee, including dose-dependent decreases in serum total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides; decreased liver total cholesterol, triglycerides, and cholesterol esters; and a lower level of nonenzymatic-induced lipid peroxidation in liver homogenate. Similar results were seen with heated (oxidized) ghee which contains cholesterol oxidation products. A preliminary clinical study showed that high doses of medicated ghee decreased serum cholesterol, triglycerides, phospholipids, and cholesterol esters in psoriasis patients. A study on a rural population in India revealed a significantly lower prevalence of coronary heart disease in men who consumed higher amounts of ghee. Research on Maharishi Amrit Kalash-4 (MAK-4), an Ayurvedic herbal mixture containing ghee, showed no effect on levels of serum cholesterol, high density lipoprotein (HDL), LDL, or triglycerides in hyperlipidemic patients who ingested MAK-4 for 18 weeks. MAK-4 inhibited the oxidation of LDL in these patients. The data available in the literature do not support a conclusion of harmful effects of the moderate consumption of ghee in the general population. Factors that may be involved in the rise of CAD in Asian Indians include the increased use of vanaspati (vegetable ghee) which contains 40% trans fatty acids, psychosocial stress, insulin resistance, and altered dietary patterns. Research findings in the literature support the beneficial effects of ghee outlined in the ancient Ayurvedic texts and the therapeutic use of ghee for thousands of years in the Ayurvedic system of medicine.
PMCID: PMC3215354  PMID: 22131700
Anhydrous milk fat; cholesterol; clarified butter; coronary artery disease; ghee; lipid peroxidation; vanaspati; vegetable ghee.
5.  A High Legume Low Glycemic Index Diet Improves Serum Lipid Profiles in Men 
Lipids  2010;45(9):765-775.
Clinical studies have shown that fiber consumption facilitates weight loss and improves lipid profiles; however, the beneficial effects of high fermentable fiber low glycemic index (GI) diets under conditions of weight maintenance are unclear. In the Legume Inflammation Feeding Experiment, a randomized controlled cross-over feeding study, 64 middle-aged men who had undergone colonoscopies within the previous 2 years received both a healthy American (HA) diet (no legume consumption, fiber consumption = 9 g/1,000 kcal, and GI = 69) and a legume enriched (1.5 servings/1,000 kcal), high fiber (21 g/1,000 kcal), low GI (GI = 38) diet (LG) in random order. Diets were isocaloric and controlled for macronutrients including saturated fat; they were consumed each for 4 weeks with a 2–4 week break separating dietary treatments. Compared to the HA diet, the LG diet led to greater declines in both fasting serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (P <0.001 and P <0.01, respectively). Insulin-resistant (IR) subjects had greater reductions in high density lipoprotein cholesterol (HDL-C; P <0.01), and triglycerides (TAG)/HDL-C (P = 0.02) after the LG diet, compared to the HA diet. Insulin-sensitive (IS) subjects had greater reductions in TC (P <0.001), LDL-C (P <0.01), TC/HDL-C (P <0.01), and LDL-C/HDL-C (P = 0.02) after the LG diet, compared to the HA diet. In conclusion, a high legume, high fiber, low GI diet improves serum lipid profiles in men, compared to a healthy American diet. However, IR individuals do not achieve the full benefits of the same diet on cardiovascular disease (CVD) lipid risk factors.
PMCID: PMC3461593  PMID: 20734238
Legume intake; Lipids; Insulin resistance
6.  Effects of Ficus carica paste on constipation induced by a high-protein feed and movement restriction in beagles 
Laboratory Animal Research  2011;27(4):275-281.
Constipation is one of the most common functional digestive complaints worldwide. We investigated the laxative effects of figs (Ficus carica L) in a beagle model of constipation induced by high protein diet and movement restriction. The experiments were consecutively conducted over 9 weeks divided into 3 periods of 3 weeks each. All 15 beagles were subjected to a non-treatment (control) period, a constipation induction period, and a fig paste treatment period. We administered fig paste (12 g/kg daily, by gavage) for 3 weeks following a 3-week period of constipation induction in dogs. Segmental colonic transit time (CTT) was measured by counting radiopaque markers (Kolomark) using a radiograph performed every 6 h after feeding Kolomark capsules, until capsules were no longer observed. Fig paste significantly increased fecal quantity in constipated dogs, and segmental CTT was also reduced following fig paste administration. There were no significant differences in feed intake, water intake, body weight, or blood test results, between the constipation and fig paste administration periods. Our results demonstrate that fig is an effective treatment for constipation in beagles. Specifically, stool weight increased and segmental CTT decreased. Fig pastes may be useful as a complementary medicine in humans suffering from chronic constipation.
PMCID: PMC3251757  PMID: 22232635
Constipation; fig paste; segmental colonic transit time; Kolomark; beagle dog
7.  Effective lipid lowering diets including lean meat 
The plasma lipid and lipoprotein responses to two modified isoenergetic diets including meat were studied in 15 free living men with hyperlipidaemia (mean plasma cholesterol and triglyceride concentrations 8·1 and 3·4 mmol/l). A reference diet (diet A, 42% energy from fat, ratio of polyunsaturated to saturated fatty acids (P:S ratio) 0·2) was compared with a fat reduced diet (diet B, 35% energy from fat, P:S ratio 0·5) and with a further fat modified diet supplemented with fibre (diet C, 27% energy from fat, P:S ratio 1·0). Daily intake of meat and meat products (180 g/day) was the same in each dietary period; that in diet A had a fat content typical of the average British diet, whereas that in diets B and C was based on very lean meat and meat products. During consumption of diet B the plasma cholesterol concentration fell by 8·6% and low density lipoprotein cholesterol by 11%. During consumption of diet C plasma cholesterol fell by 18·5% and low density lipoprotein cholesterol by 23·8%. Triglyceride and high density lipoprotein cholesterol concentrations and body weight did not change appreciably during the study.
A modified diet including a moderate amount of lean meat and meat products is compatible with a reduced lipoprotein mediated risk of atherosclerotic heart disease.
PMCID: PMC2544768  PMID: 3124899
8.  Effects of Increasing Dietary Polyunsaturated Fatty Acids Within the Guidelines of the AHA Step 1 Diet on Plasma Lipid and Lipoprotein Levels in Normal Males 
Arteriosclerosis and Thrombosis  1994;14(6):892-901.
We attempted to ascertain the effects of polyunsaturated fatty acids by conducting two studies in normal young men, in which monounsaturated fats were replaced by polyunsaturated fats within the guidelines of the American Heart Association step 1 diet. Study A employed a randomized parallel design in which subjects first consumed an average American diet (AAD) containing 37% of calories as fat (saturated fat, 16% calories; monounsaturated fat, 14% calories; and polyunsaturated fat, 7% calories). After 3 weeks, one third of the subjects continued with the AAD, one third switched to a step 1 diet in which total fat calories were reduced to 30% by replacing saturated fat with carbohydrate, and one third switched to a polyunsaturated fat-enriched (Poly) diet with the same 30% fat calories and a reduction of monounsaturated fat from 14% to 8% and an increase of polyunsaturated fat from 7% to 13% of calories. The randomized period lasted 6 weeks. Total and low-density lipoprotein (LDL) cholesterol levels on the step 1 and Poly diets were reduced compared with levels on the AAD (P < .001). Total and LDL cholesterol did not differ between the step 1 and Poly diets, although comparison between the two diets is limited by the small study groups. Serum apolipoprotein (apo) B levels fell on the Poly diet compared with the AAD. Total high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol levels were not significantly affected by the diets. Postprandial lipid and lipoprotein concentrations did not significantly differ either. In study B, a randomized crossover design was used in which all subjects ate the step 1 and Poly diets for 5 weeks each with a 4-day break between diets. In the eight subjects studied, the values for fasting plasma total, LDL, and HDL cholesterol; triglycerides; apoB; and apoA-I were essentially identical at the end of each diet period. Postprandial triglyceride areas obtained after ingestion of a large, standard fat load were also the same. Finally, LDL apoB and HDL apoA-I turnovers were unaffected by replacement of monounsaturates with polyunsaturates. In summary our results indicate that modest exchanges of monounsaturated for polyunsaturated fats do not significantly affect LDL or HDL levels or metabolism, which supports the view that reducing saturated fats is the key to lowering total and LDL cholesterol.
PMCID: PMC3275914  PMID: 8199179
plasma lipids; lipoproteins; dietary fatty acids; LDL; HDL; saturated fat; monounsaturated fat; polyunsaturated fat
9.  Effects of hazelnuts consumption on fasting blood sugar and lipoproteins in patients with type 2 diabetes 
Previous studies have demonstrated that nuts consumption have beneficial effects on serum lipid profiles in hyperlipidemic or normolipidemic subjects. However, similar studies in diabetes field are quite rare. So, we aimed to investigate the effects of hazelnut consumption on fasting blood sugar (FBS) and lipid profiles in patients with type 2 Diabetes.
Materials and Methods:
An 8-week controlled randomized parallel study in patients with type 2 diabetes. Fifty eligible volunteers were assigned to either the control or intervention groups. 10% of total daily calorie intake was replaced with hazelnuts in intervention group. Blood samples were collected from fasting patients at the start and at the end of the study.
After 8 weeks, there were significant differences in high-density lipoprotein-cholesterol (HDL-C) concentrations between two groups, using analyses of covariance (P = 0.009), which was due to the larger HDL-C reduction in control group (P = 0.003). Although, Hazelnut group achieved greater reduction in triglyceride (TG) concentrations than control group, these changes were not statistically significant. Neither between-group changes nor within-group changes were significant for FBS, total cholesterol (TC), TG, and low-density lipoprotein-cholesterol (LDL-C) levels.
Results of this study indicated that incorporation of hazelnuts into diet can prevent reduction of HDL-C concentrations in patients with type 2 diabetes, but had no effect on FBS or other lipid profile indices.
PMCID: PMC3793377  PMID: 24124429
Fasting blood sugar; hazelnuts; lipid profile; type 2 diabetes
10.  Effects of High vs Low Glycemic Index of Dietary Carbohydrate on Cardiovascular Disease Risk Factors and Insulin Sensitivity 
JAMA  2014;312(23):2531-2541.
Foods that have similar carbohydrate content can differ in the amount they raise blood glucose. The effects of this property, called the glycemic index, on risk factors for cardiovascular disease and diabetes are not well understood.
To determine the effect of glycemic index and amount of total dietary carbohydrate on risk factors for cardiovascular disease and diabetes.
Randomized crossover-controlled feeding trial conducted in research units in academic medical centers, in which 163 overweight adults (systolic blood pressure, 120–159 mm Hg) were given 4 complete diets that contained all of their meals, snacks, and calorie-containing beverages, each for 5 weeks, and completed at least 2 study diets. The first participant was enrolled April 1, 2008; the last participant finished December 22, 2010. For any pair of the 4 diets, there were 135 to 150 participants contributing at least 1 primary outcome measure.
(1) A high–glycemic index (65% on the glucose scale), high-carbohydrate diet (58% energy); (2) a low–glycemic index (40%), high-carbohydrate diet; (3) a high–glycemic index, low-carbohydrate diet (40% energy); and (4) a low–glycemic index, low-carbohydrate diet. Each diet was based on a healthful DASH-type diet.
The 5 primary outcomes were insulin sensitivity, determined from the areas under the curves of glucose and insulin levels during an oral glucose tolerance test; levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides; and systolic blood pressure.
At high dietary carbohydrate content, the low– compared with high–glycemic index level decreased insulin sensitivity from 8.9 to 7.1 units (−20%, P = .002); increased LDL cholesterol from 139 to 147 mg/dL (6%, P ≤ .001); and did not affect levels of HDL cholesterol, triglycerides, or blood pressure. At low carbohydrate content, the low– compared with high–glycemic index level did not affect the outcomes except for decreasing triglycerides from 91 to 86 mg/dL (−5%, P = .02). In the primary diet contrast, the low–glycemic index, low-carbohydrate diet, compared with the high–glycemic index, high-carbohydrate diet, did not affect insulin sensitivity, systolic blood pressure, LDL cholesterol, or HDL cholesterol but did lower triglycerides from 111 to 86 mg/dL (−23%, P ≤ .001).
In this 5-week controlled feeding study, diets with low glycemic index of dietary carbohydrate, compared with high glycemic index of dietary carbohydrate, did not result in improvements in insulin sensitivity, lipid levels, or systolic blood pressure. In the context of an overall DASH-type diet, using glycemic index to select specific foods may not improve cardiovascular risk factors or insulin resistance.
TRIAL REGISTRATION Identifier: NCT00608049
PMCID: PMC4370345  PMID: 25514303
11.  Long-term effects of a ketogenic diet in obese patients 
Although various studies have examined the short-term effects of a ketogenic diet in reducing weight in obese patients, its long-term effects on various physical and biochemical parameters are not known.
To determine the effects of a 24-week ketogenic diet (consisting of 30 g carbohydrate, 1 g/kg body weight protein, 20% saturated fat, and 80% polyunsaturated and monounsaturated fat) in obese patients.
In the present study, 83 obese patients (39 men and 44 women) with a body mass index greater than 35 kg/m2, and high glucose and cholesterol levels were selected. The body weight, body mass index, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, fasting blood sugar, urea and creatinine levels were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored after eight, 16 and 24 weeks of treatment.
The weight and body mass index of the patients decreased significantly (P<0.0001). The level of total cholesterol decreased from week 1 to week 24. HDL cholesterol levels significantly increased, whereas LDL cholesterol levels significantly decreased after treatment. The level of triglycerides decreased significantly following 24 weeks of treatment. The level of blood glucose significantly decreased. The changes in the level of urea and creatinine were not statistically significant.
The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.
PMCID: PMC2716748  PMID: 19641727
Diet; Ketosis; Obesity
12.  Diet-induced metabolic hamster model of nonalcoholic fatty liver disease 
Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology.
Experiments were planned to develop a diet-induced Bio F1B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O.
In this study, we established a diet-induced Bio F1B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed with a high-fat/high cholesterol diet, as compared to animals fed with the control diet.
Our study established that hamsters fed with a high-fat/high-cholesterol diet developed fatty liver and mild diabetes. Bio F1B hamsters fed with a high-fat/high-cholesterol diet may thus be a good animal model for research on the treatment of diet-induced metabolic syndrome complicated by nonalcoholic fatty liver disease.
PMCID: PMC3131800  PMID: 21760736
fatty liver disease; in vivo model; diet; atherogenic index; obesity
13.  Camel milk ameliorates steatohepatitis, insulin resistance and lipid peroxidation in experimental non-alcoholic fatty liver disease 
Camel milk (CM) is gaining increasing recognition due to its beneficial effects in the control and prevention of multiple health problems. The current study aimed to investigate the effects of CM on the hepatic biochemical and cellular alterations induced by a high-fat, cholesterol-rich diet (HCD), specifically, non-alcoholic fatty liver disease (NAFLD).
Seventy male Wistar rats were divided into four groups: the Control (C) Group fed a standard diet; the Control + camel milk (CCM) Group fed a standard diet and CM, the Cholesterol (Ch) Group fed a HCD with no CM, and the Cholesterol + camel milk (ChM) Group fed a HCD and CM. The following parameters were investigated in the studied groups; basal, weekly random and final fasting blood glucose levels, intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT), serum insulin, serum lipids, liver functions, lipid peroxidation products, the antioxidant activity of catalase (CAT) and the levels of reduced glutathione (GSH). In addition, HOMA-IR as an index of insulin resistance (IR) and the histopathology of the hepatic tissue were assessed.
The Ch Group developed features similar to those of non-alcoholic steatohepatitis (NASH), characterized by hepatic steatosis; inflammatory cellular infiltration in liver tissue; altered liver functions; and increased total cholesterol, triglycerides, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, atherogenic index (AI), blood glucose, IR, and malondialdehyde (MDA) levels. Additionally, feeding the HCD to animals in the Ch Group decreased CAT activity and the GSH and high-density lipoprotein (HDL) cholesterol levels. Camel milk intake for eight weeks decreased hepatic fat accumulation and inflammatory cellular infiltration, preserved liver function, increased the GSH levels and CAT activity, decreased the MDA levels, and ameliorated the changes in the lipid profile, AI, and IR in animals from the ChM Group.
CM has a unique composition that is rich in minerals; vitamins, insulin and insulin-like protein, and it increased HDL-cholesterol and ameliorated the biochemical and cellular features of NAFLD in rats that received a HCD. The antioxidant effect of CM is a likely mechanism for the altered metabolism and absorption of HCD in the presence of CM. Regular consumption of CM could provide a natural way to protect against NAFLD induced by a high-fat diet.
PMCID: PMC3852981  PMID: 24119413
Camel milk; Non-alcoholic fatty liver disease; Steatohepatitis; High-fat diet; Insulin resistance; Hyperlipidemia; Oxidative stress; Rats
14.  Body weight status and cardiovascular risk factors in adults by frequency of candy consumption 
Nutrition Journal  2013;12:53.
Limited information is available regarding the impact of candy consumption on health. The purpose of this study was to investigate associations between typical frequency of candy consumption and body weight status and select cardiovascular risk factors among adults in the United States.
Using data collected in the 2003–2006 National Health and Nutrition Examination Surveys (NHANES), adults were categorized as infrequent (≤ 3 eating occasions [EO]/month), moderate (> 3 EO/month and ≤ 3.5 EO/week), or frequent (> 3.5 EO/week) candy consumers based on the combined frequency of chocolate and other candy consumption over the previous 12 months. Weight and adiposity status were analyzed using logistic regression models, and blood pressure, lipids, and insulin sensitivity were analyzed using linear regression models. Models were adjusted for age, sex and race/ethnicity, and also for additional covariates with potential associations with the outcomes. Appropriate statistical weights were used to yield results generalizable to the US population.
Frequency of candy consumption was not associated with the risk of obesity, overweight/obesity, elevated waist circumference, elevated skinfold thickness, blood pressure, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol, triglycerides, or insulin resistance. Increased frequency of candy consumption was associated with higher energy intakes and higher energy adjusted intakes of carbohydrates, total sugars and added sugars, total fat, saturated fatty acids and monounsaturated fatty acids (p < 0.05), and lower adjusted intakes of protein and cholesterol (p < 0.001).
Increased frequency of candy consumption among adults in the United States was not associated with objective measures of adiposity or select cardiovascular risk factors, despite associated dietary differences. Given the cross-sectional study design, however, it cannot be concluded that candy consumption does not cause obesity or untoward levels of cardiovascular risk markers. The lack of an association between frequency of candy consumption and cardiovascular risk factors could be due to reduced intake of candy among the overweight due to dieting or a health professional’s recommendations. Additionally, it is important to note that the analysis was based on frequency of candy consumption and not amount of candy consumed. Longitudinal studies are needed to confirm the lack of associations between frequency of candy consumption and cardiovascular risk factors.
PMCID: PMC3644488  PMID: 23631725
Candy; Confectionery; NHANES; Adults; Obesity; Cardiovascular risk factors
15.  High-density lipoprotein concentrations increase after stopping smoking. 
Concentrations of plasma lipoproteins in 10 men who were habitual smokers were monitored for six weeks after they stopped smoking and related to changes in diet and body weight. The energy intake increased by 10% (p less than 0.05) owing to a higher consumption of carbohydrates and fat, and body weight increased by 2% (p less than 0.01). Plasma triglyceride, cholesterol, and low-density lipoprotein cholesterol concentrations did not change significantly. The most prominent finding was a rapid and pronounced increased in high-density lipoprotein concentrations. From comparatively low values (mean 0.82 mmol/1) they rose by 29% (p less than 0.01) within two weeks and remained at this value throughout the observation period. In three subjects who resumed smoking after the end of the study they again fell to initial values six weeks later. The initial increase in concentration could be accounted for mainly by an increase in the esterified fraction and only to a lesser extent in the free cholesterol fraction. The changes in concentrations were accompanied by similar but less pronounced rises in high-density lipoprotein phospholipid and in apolipoprotein AI concentrations (p less than 0.01), whereas high-density lipoprotein phospholipid and in apolipoprotein AI concentration (p less than 0.01), whereas high-density lipoprotein triglyceride concentrations did not change significantly. These findings confirm and extend those of earlier cross-sectional studies which showed low concentrations of high-density lipoproteins in cigarette smokers, A significant correlation between the rise in high-density lipoprotein cholesterol concentrations and the increase in fat consumption after stopping smoking indicate that the changes in high-density lipoprotein concentrations may be partly due to nutritional factors.
PMCID: PMC1498412  PMID: 6805587
16.  Maternal diet rich in saturated fats has deleterious effects on plasma lipids of mice 
High dietary fat intake has been reported to cause an alteration in lipid metabolism that is associated with an increased risk of cardiovascular disease. In the present study, an animal model was used to evaluate the effects of feeding diets rich in different fatty acids to mothers during pregnancy and lactation, and the effects of the maternal diet on parameters of lipid metabolism in adult offspring. The interaction between the offspring’s own diet and the programming due to the maternal diet was also evaluated.
Female C57BL/6 mice were fed a high-fat diet (20% fat [weight to weight]) rich in either saturated fatty acids (SFA) or polyunsaturated fatty acids (PUFA) for two weeks before mating, during pregnancy and until weaning. The offspring were divided into two groups; each group was fed a high-fat diet enriched in either SFA or PUFA for eight weeks after weaning. The groups were designated as SFA/SFA (diet of the mother/diet of the offspring), SFA/PUFA, PUFA/PUFA and PUFA/SFA. Blood and tissues were collected at the end of the eight-week feeding period after an overnight fast.
The plasma total cholesterol and low density lipoprotein cholesterol concentrations were significantly higher in the SFA/SFA group than in all other groups, whereas the PUFA/PUFA group had the lowest total cholesterol and low density lipoprotein cholesterol concentrations. Plasma high density lipoprotein cholesterol concentrations were significantly higher in the PUFA/SFA group than in the PUFA/PUFA and SFA/PUFA groups, whereas plasma triglyceride concentrations were not different among the groups.
The data suggest that high maternal dietary fat intake during pregnancy affects lipid metabolism in the adult offspring. However, it appears that the offspring’s own diet is also important in maintaining the regulation of lipid metabolism.
PMCID: PMC2274858  PMID: 18651049
Atherosclerosis; Diet; Fetal programming; Lipid metabolism; Polyunsaturated fats; Predictive adaptive responses
17.  Antihypertensive effect of diet compared with drug treatment in obese men with mild hypertension. 
BMJ : British Medical Journal  1989;299(6697):480-485.
OBJECTIVE--To determine whether dietary treatment has a similar antihypertensive effect to conventional drug treatment while being superior to drugs in improving serum lipid concentrations in obese men with mild hypertension. DESIGN--Six week run in period followed by randomisation to either diet or drug treatment groups for one year. SETTING--Outpatient clinic in city hospital. PATIENTS--61 Men aged 40-69 years, body mass index greater than or equal to 26, diastolic blood pressure 90-104 mm Hg when untreated. Exclusion criteria were signs of organ damage secondary to hypertension and diseases that might have interfered with compliance or with interpretation of results. INTERVENTIONS--Dietary treatment was based on weight reduction, restriction of sodium, and decrease of excess alcohol intake (defined as greater than or equal to 250 g alcohol per week). Drug treatment used a stepped care approach with atenolol as drug of first choice. MAIN OUTCOME MEASURES--Diastolic blood pressure less than 90 mm Hg; absolute reductions in blood pressure and serum lipid concentrations. RESULTS--Mean body weight decreased 7.6 kg in the diet group and increased 0.9 kg in the drug treatment group (p less than 0.0001), and mean sodium excretion decreased 42 and 10 mmol/24 h respectively (p = 0.019). There was no difference in reported alcohol intake. Mean systolic blood pressure decreased 4 mm Hg in the diet group and 16 mm Hg in the drug group (p = 0.003) and diastolic blood pressure 3 and 11 mm Hg respectively (p = 0.002). Diastolic blood pressure of 90 mm Hg was attained by 29% of the diet group (nine men) and 73% (22) of those receiving drug treatment (mean difference 44%, 95% confidence interval 21 to 67%, p = 0.001). Dietary treatment produced decreases in mean serum concentrations of total and low density lipoprotein cholesterol as well as triglycerides and an increase in high density lipoprotein cholesterol concentration. In the drug treatment group the changes were in the opposite direction, and the groups differed significantly in all but total cholesterol. CONCLUSIONS--Dietary treatment was inferior to conventional drug treatment in controlling mild hypertension but superior in lowering serum concentrations of lipids.
PMCID: PMC1837358  PMID: 2507028
18.  Efficacy of aerobic exercise and a prudent diet for improving selected lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials 
BMC Medicine  2011;9:74.
Studies addressing the effects of aerobic exercise and a prudent diet on lipid and lipoprotein concentrations in adults have reached conflicting conclusions. The purpose of this study was to determine the effects of aerobic exercise combined with a prudent diet on lipid and lipoprotein concentrations in adults.
Studies were located by searching nine electronic databases, cross-referencing, and expert review. Two independent reviewers selected studies that met the following criteria: (1) randomized controlled trials, (2) aerobic exercise combined with diet recommendations (saturated/trans fat intake less than 10% of total calories and cholesterol less than 300 mg/day and/or fiber intake ≥25 g/day in women and ≥35 grams per day in men), (3) intervention ≥4 weeks, (4) humans ≥18 years of age, (5) published studies, including dissertations and Master's theses, (6) studies published in any language, (7) studies published between January 1, 1955 and May 1, 2009, (8) assessment of one or more of the following lipid and lipoprotein concentrations: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), ratio of TC to HDL-C, non-HDL-C, low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Two reviewers independently extracted all data. Random-effects models that account for heterogeneity and 95% confidence intervals were used to pool findings.
Of the 1,401 citations reviewed, six studies representing 16 groups (8 intervention, 8 control) and up to 559 men and women (282 intervention, 277 control) met the criteria for analysis. Statistically significant intervention minus control reductions were found for TC (-15.5 mg/dl, 95% CI, -20.3 to -10.7), TC:HDL-C (-0.4 mg/dl, 95% CI, -0.7 to -0.2), LDL-C (-9.2 mg/dl, 95% CI, -12.7 to -5.8) and TG (-10.6 mg/dl, 95% CI, -17.2 to -4.0) but not HDL-C (-0.5 mg/dl, 95% CI, -4.0 to 3.1). Changes were equivalent to reductions of 7.5%, 6.6%, 7.2% and 18.2% respectively, for TC, TC:HDL-C, LDL-C and TG. Because of missing variance statistics, non-HDL-C was excluded.
Aerobic exercise combined with a prudent diet is highly efficacious for improving TC, TC:HDL-C, LDL-C and TG, but not HDL-C concentrations, in adults. However, additional studies are needed, including effectiveness studies using intention-to-treat analysis.
PMCID: PMC3141539  PMID: 21676220
19.  Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia 
Higher intake of monounsaturated fat may raise high-density lipoprotein (HDL) cholesterol without raising low-density lipoprotein (LDL) cholesterol. We tested whether increasing the monounsaturated fat content of a diet proven effective for lowering LDL cholesterol (dietary portfolio) also modified other risk factors for cardiovascular disease, specifically by increasing HDL cholesterol, lowering serum triglyceride and further reducing the ratio of total to HDL cholesterol.
Twenty-four patients with hyperlipidemia consumed a therapeutic diet very low in saturated fat for one month and were then randomly assigned to a dietary portfolio low or high in monounsaturated fatty acid for another month. We supplied participants’ food for the two-month period. Calorie intake was based on Harris–Benedict estimates for energy requirements.
For patients who consumed the dietary portfolio high in monounsaturated fat, HDL cholesterol rose, whereas for those consuming the dietary portfolio low in monounsaturated fat, HDL cholesterol did not change. The 12.5% treatment difference was significant (0.12 mmol/L, 95% confidence interval [CI] 0.05 to 0.21, p = 0.003). The ratio of total to HDL cholesterol was reduced by 6.5% with the diet high in monounsaturated fat relative to the diet low in monounsaturated fat (−0.28, 95% CI −0.59 to −0.04, p = 0.025). Patients consuming the diet high in monounsaturated fat also had significantly higher concentrations of apolipoprotein AI, and their C-reactive protein was significantly lower. No treatment differences were seen for triglycerides, other lipids or body weight, and mean weight loss was similar for the diets high in monounsaturated fat (−0.8 kg) and low in monounsaturated fat (−1.2 kg).
Monounsaturated fat increased the effectiveness of a cholesterol-lowering dietary portfolio, despite statin-like reductions in LDL cholesterol. The potential benefits for cardiovascular risk were achieved through increases in HDL cholesterol, further reductions in the ratio of total to HDL cholesterol and reductions in C-reactive protein. ( trial register no. NCT00430430.)
PMCID: PMC3001502  PMID: 21041432
20.  Effect of tomato consumption on high-density lipoprotein cholesterol level: a randomized, single-blinded, controlled clinical trial 
Epidemiologic evidence suggests that tomato-based products could reduce the risk of cardiovascular diseases. One of the main cardiovascular risk factors is low levels of high-density lipoprotein cholesterol (HDL-C). This study aimed to prospectively evaluate the effect of tomato consumption on HDL-C levels.
Subject and methods
We conducted a randomized, single-blinded, controlled clinical trial. We screened 432 subjects with a complete lipid profile. Those individuals with low HDL-C (men <40 mg/dL and women <50 mg/dL) but normal triglyceride levels (<150 mg/dL) were included. Selected participants completed a 2-week run-in period on an isocaloric diet and then were randomized to receive 300 g of cucumber (control group) or two uncooked Roma tomatoes a day for 4 weeks.
A total of 50 individuals (women = 41; 82%) with a mean age of 42 ± 15.5 years and a mean body mass index of 27.6 ± 5.0 kg/m2 completed the study. A significant increase in HDL-C levels was observed in the tomato group (from 36.5 ± 7.5 mg/dL to 41.6 ± 6.9 mg/dL, P < 0.0001 versus the control group). After stratification by gender, the difference in HDL-C levels was only significant in women. The mean HDL-C increase was 5.0 ± 2.8 mg/dL (range 1–12 mg/dL). Twenty patients (40%) finished the study with levels >40 mg/dL. A linear regression model that adjusted for those parameters that impact HDL-C levels (age, gender, waist-to-hip ratio, body mass index, fasting triglyceride concentration, simple sugars, alcohol, physical activity, and omega-3 consumption) showed an independent association between tomato consumption and the increase in HDL-C (r2 = 0.69; P < 0.0001).
Raw tomato consumption produced a favorable effect on HDL-C levels in overweight women.
PMCID: PMC3735277  PMID: 23935376
lycopene; hypoalphalipoproteinemia; dyslipidemia; overweight; cardiovascular diseases
21.  Murine Fig4 is dispensable for muscle development but required for muscle function 
Skeletal Muscle  2013;3:21.
Phosphatidylinositol phosphates (PIPs) are low-abundance phospholipids that participate in a range of cellular processes, including cell migration and membrane traffic. PIP levels and subcellular distribution are regulated by a series of lipid kinases and phosphatases. In skeletal muscle, PIPs and their enzymatic regulators serve critically important functions exemplified by mutations of the PIP phosphatase MTM1 in myotubular myopathy (MTM), a severe muscle disease characterized by impaired muscle structure and abnormal excitation–contraction coupling. FIG4 functions as a PIP phosphatase that participates in both the synthesis and breakdown of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Mutation of FIG4 results in a severe neurodegenerative disorder in mice and a progressive peripheral polyneuropathy in humans. The effect of FIG4 mutation on skeletal muscle has yet to be examined.
Herein we characterize the impact of FIG4 on skeletal muscle development and function using the spontaneously occurring mouse mutant pale tremor (plt), a mouse line with a loss of function mutation in Fig4.
In plt mice, we characterized abnormalities in skeletal muscle, including reduced muscle size and specific force generation. We also uncovered ultrastructural abnormalities and increased programmed cell death. Conversely, we detected no structural or functional abnormalities to suggest impairment of excitation–contraction coupling, a process previously shown to be influenced by PI(3,5)P2 levels. Conditional rescue of Fig4 mutation in neurons prevented overt muscle weakness and the development of obvious muscle abnormalities, suggesting that the changes observed in the plt mice were primarily related to denervation of skeletal muscle. On the basis of the ability of reduced FIG4 levels to rescue aspects of Mtmr2-dependent neuropathy, we evaluated the effect of Fig4 haploinsufficiency on the myopathy of Mtm1-knockout mice. Male mice with a compound Fig4+/−/Mtm1–/Y genotype displayed no improvements in muscle histology, muscle size or overall survival, indicating that FIG4 reduction does not ameliorate the Mtm1-knockout phenotype.
Overall, these data indicate that loss of Fig4 impairs skeletal muscle function but does not significantly affect its structural development.
PMCID: PMC3844516  PMID: 24004519
Autophagy; Congenital myopathies; FIG4; MTM1; Phosphatidylinositol
22.  Exchanging carbohydrate or protein for fat improves lipid-related cardiovascular risk profile in overweight men and women when consumed ad libitum 
Journal of Investigative Medicine  2010;58(5):711-719.
The impact of low-fat diets on the plasma lipoprotein profile is incompletely understood. We conducted two 16-week dietary studies to compare the effects of a moderate fat (mod-FAT) baseline diet with isocaloric and ad libitum low-fat diets rich in either carbohydrates (high-CHO, n=16) or protein (high-PRO, n=19) on plasma lipids, post-heparin lipase activities, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP). Switching from the mod-FAT to the isocaloric high-CHO diet lowered plasma HDL-cholesterol concentrations (p<0.001) and tended to increase triglyceride levels (p=0.087). Cholesterol content in the larger, buoyant LDL-fractions decreased while those of the VLDL, IDL, and smaller, denser LDL-fractions tended to increase. These changes were largely reversed when subjects lost weight by consuming this high-CHO diet ad libitum. Switching from the mod-FAT diet to the isocaloric high-PRO diet did not increase cholesterol content in the small dense LDL-fraction, and led to decreases in both LDL- and HDL-cholesterol in plasma (p<0.001 for both). Consumption of the high-PRO ad libitum diet accompanied by weight loss did not change plasma lipids further, except for a shift of cholesterol from dense LDL fractions to more buoyant LDL fractions. CETP concentrations decreased with high-CHO feeding, whereas CETP concentrations and hepatic lipase and PLTP activities all decreased during high-PRO feeding. Both high-CHO and high-PRO diets improve plasma lipid-related risk of cardiovascular disease when consumed ad libitum.
PMCID: PMC3390239  PMID: 20305576
Fat; carbohydrate; protein; lipoproteins; lipids; cardiovascular disease
23.  Impact of daily Chlorella consumption on serum lipid and carotenoid profiles in mildly hypercholesterolemic adults: a double-blinded, randomized, placebo-controlled study 
Nutrition Journal  2014;13:57.
High level of serum cholesterol is considered to be a major risk factor for cardiovascular disease (CVD). A double-blinded, randomized, placebo-controlled trial was performed to test the hypothesis that a daily intake of Chlorella may improve serum lipid profile through enhancement of serum carotenoid concentration in mildly hypercholesterolemic subjects.
Eligible subjects (n = 63) were randomized to either Chlorella (5 g/day) or placebo for a double-blinded trial with a 2-week lead-in period and a 4-week intervention period. Serum triglycerides, total cholesterol, lipoproteins, apolipoproteins and carotenoids were assessed at the beginning and the end of the trial.
Compared with the control group, the Chlorella group exhibited remarkable changes in total cholesterol (Chlorella −1.6%; placebo 0.03%; P = 0.036), triglycerides (Chlorella −10.3%; placebo 11.9%; P = 0.002), lutein/zeaxanthin (Chlorella 89.6%; placebo −1.7%; P < 0.0001), and α-carotene (Chlorella 163.6%; placebo 15%; P < 0.0001). Improvement of serum lipids was supported by significant reductions of very low-density lipoprotein cholesterol (Chlorella −11%; placebo 11.8%; P = 0.006), apolipoprotein B (Chlorella −1.5%; placebo 1.7%; P = 0.044), non high-density lipoprotein (Chlorella −2.6%; placebo −0.5%; P = 0.032), and high-density lipoprotein/triglycerides (Chlorella 4.0%; placebo −9.5%; P = 0.023), suggesting an inhibitory effect of Chlorella on the intestinal absorption of dietary and endogenous lipids. Further, the changes of serum lipids appeared to be associated with the changes of serum carotenoids.
Daily consumption of Chlorella supplements provided the potential of health benefits reducing serum lipid risk factors, mainly triglycerides and total cholesterol, in mildly hypercholesterolemic subjects. The effect was related to carotenoid consumption.
Trial registration
WHO International Clinical Trials Registry Platform KCT0000259.
PMCID: PMC4066283  PMID: 24920270
Chlorella; Serum lipid; Carotenoids; Human
24.  Physiological Role of a Multigrain Diet in Metabolic Regulations of Lipid and Antioxidant Profiles in Hypercholesteremic Rats 
Journal of Pharmacopuncture  2014;17(2):34-40.
The objective of the present study was to investigate the lipid and the antioxidant regulatory potential of a multigrain diet in laboratory animals with reference to lipid profiles, tissue lipid peroxidation and antioxidant status.
Two types of diets, with or without addition of cholesterol, were used in the study – a commercial diet and a formulated multigrain diet (with Sorghum vulgare, Avena sativa, Pennisetum typhoideum, Oryza sativa, Eleusine coracana and Zea mays grains). After a 10-week period of feeding the diets to albino rats the plasma, liver and fecal lipid profiles and the hepatic and renal antioxidant status of the animals that were fed the commercial and the formulated diets (with and without cholesterol addition) were assessed.
The commercial diet supplemented with cholesterol elevated the levels of plasma total lipids, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C), as well as the atherogenic index (AI). The high-density lipoprotein cholesterol (HDL-C) content and the antioxidant profiles (total ascorbic acid, superoxide dismutase, catalase, glutathione peroxidase reduced glutathione) declined along with increases in lipid peroxidation. The formulated diet (with and without addition of cholesterol) was found to be more efficient than the commercial diet in controlling plasma, hepatic and fecal lipid profiles, as well as hepatic and renal lipid peroxidation and antioxidant status, than of the hypercholesteremic animals.
The multigrain diet used in the present study is effective in countering the hyperlipidemia and oxidative stress caused by high cholesterol intake.
PMCID: PMC4331993  PMID: 25780697
enzymatic antioxidants; fecal lipids; lipid metabolism; multigrain; non-enzymatic antioxidants; oxidative stress
25.  Primary Prevention of Gestational Diabetes Mellitus and Large-for-Gestational-Age Newborns by Lifestyle Counseling: A Cluster-Randomized Controlled Trial 
PLoS Medicine  2011;8(5):e1001036.
In a cluster-randomized trial, Riitta Luoto and colleagues find that counseling on diet and activity can reduce the birthweight of babies born to women at risk of developing gestational diabetes mellitus (GDM), but fail to find an effect on GDM.
Our objective was to examine whether gestational diabetes mellitus (GDM) or newborns' high birthweight can be prevented by lifestyle counseling in pregnant women at high risk of GDM.
Method and Findings
We conducted a cluster-randomized trial, the NELLI study, in 14 municipalities in Finland, where 2,271 women were screened by oral glucose tolerance test (OGTT) at 8–12 wk gestation. Euglycemic (n = 399) women with at least one GDM risk factor (body mass index [BMI] ≥25 kg/m2, glucose intolerance or newborn's macrosomia (≥4,500 g) in any earlier pregnancy, family history of diabetes, age ≥40 y) were included. The intervention included individual intensified counseling on physical activity and diet and weight gain at five antenatal visits. Primary outcomes were incidence of GDM as assessed by OGTT (maternal outcome) and newborns' birthweight adjusted for gestational age (neonatal outcome). Secondary outcomes were maternal weight gain and the need for insulin treatment during pregnancy. Adherence to the intervention was evaluated on the basis of changes in physical activity (weekly metabolic equivalent task (MET) minutes) and diet (intake of total fat, saturated and polyunsaturated fatty acids, saccharose, and fiber). Multilevel analyses took into account cluster, maternity clinic, and nurse level influences in addition to age, education, parity, and prepregnancy BMI. 15.8% (34/216) of women in the intervention group and 12.4% (22/179) in the usual care group developed GDM (absolute effect size 1.36, 95% confidence interval [CI] 0.71–2.62, p = 0.36). Neonatal birthweight was lower in the intervention than in the usual care group (absolute effect size −133 g, 95% CI −231 to −35, p = 0.008) as was proportion of large-for-gestational-age (LGA) newborns (26/216, 12.1% versus 34/179, 19.7%, p = 0.042). Women in the intervention group increased their intake of dietary fiber (adjusted coefficient 1.83, 95% CI 0.30–3.25, p = 0.023) and polyunsaturated fatty acids (adjusted coefficient 0.37, 95% CI 0.16–0.57, p<0.001), decreased their intake of saturated fatty acids (adjusted coefficient −0.63, 95% CI −1.12 to −0.15, p = 0.01) and intake of saccharose (adjusted coefficient −0.83, 95% CI −1.55 to −0.11, p  =  0.023), and had a tendency to a smaller decrease in MET minutes/week for at least moderate intensity activity (adjusted coefficient 91, 95% CI −37 to 219, p = 0.17) than women in the usual care group. In subgroup analysis, adherent women in the intervention group (n = 55/229) had decreased risk of GDM (27.3% versus 33.0%, p = 0.43) and LGA newborns (7.3% versus 19.5%, p = 0.03) compared to women in the usual care group.
The intervention was effective in controlling birthweight of the newborns, but failed to have an effect on maternal GDM.
Trial registration
Current Controlled Trials ISRCTN33885819
Please see later in the article for the Editors' Summary
Editors' Summary
Gestational diabetes mellitus (GDM) is diabetes that is first diagnosed during pregnancy. Like other types of diabetes, it is characterized by high levels of sugar (glucose) in the blood. Blood-sugar levels are normally controlled by insulin, a hormone that the pancreas releases when blood-sugar levels rise after meals. Hormonal changes during pregnancy and the baby's growth demands increase a pregnant woman's insulin needs and, if her pancreas cannot make enough insulin, GDM develops. Risk factors for GDM, which occurs in 2%–14% of pregnant women, include a high body-mass index (a measure of body fat), excessive weight gain or low physical activity during pregnancy, high dietary intake of polyunsaturated fats, glucose intolerance (an indicator of diabetes) or the birth of a large baby in a previous pregnancy, and a family history of diabetes. GDM is associated with an increased rate of cesarean sections, induced deliveries, birth complications, and large-for-gestational-age (LGA) babies (gestation is the time during which the baby develops within the mother). GDM, which can often be controlled by diet and exercise, usually disappears after pregnancy but increases a woman's subsequent risk of developing diabetes.
Why Was This Study Done?
Although lifestyle changes can be used to control GDM, it is not known whether similar changes can prevent GDM developing (“primary prevention”). In this cluster-randomized controlled trial, the researchers investigate whether individual intensified counseling on physical activity, diet, and weight gain integrated into routine maternity care visits can prevent the development of GDM and the occurrence of LGA babies among newborns. In a cluster-randomized controlled trial, groups of patients rather than individual patients are randomly assigned to receive alternative interventions, and the outcomes in different “clusters” are compared. In this trial, each cluster is a municipality in the Pirkanmaa region of Finland.
What Did the Researchers Do and Find?
The researchers enrolled 399 women, each of whom had a normal blood glucose level at 8–12 weeks gestation but at least one risk factor for GDM. Women in the intervention municipalities received intensified counseling on physical activity at 8–12 weeks' gestation, dietary counseling at 16–18 weeks' gestation, and further physical activity and dietary counseling at each subsequent antenatal visits. Women in the control municipalities received some dietary but little physical activity counseling as part of their usual care. 23.3% and 20.2% of women in the intervention and usual care groups, respectively, developed GDM, a nonstatistically significant difference (that is, a difference that could have occurred by chance). However, the average birthweight and the proportion of LGA babies were both significantly lower in the intervention group than in the usual care group. Food frequency questionnaires completed by the women indicated that, on average, those in the intervention group increased their intake of dietary fiber and polyunsaturated fatty acids and decreased their intake of saturated fatty acids and sucrose as instructed during counseling, The amount of moderate physical activity also tended to decrease less as pregnancy proceeded in the intervention group than in usual care group. Finally, compared to the usual care group, significantly fewer of the 24% of women in the intervention group who actually met dietary and physical activity targets (“adherent” women) developed GDM.
What Do These Findings Mean?
These findings indicate that intensified counseling on diet and physical activity is effective in controlling the birthweight of babies born to women at risk of developing GDM and encourages at least some of them to alter their lifestyle. However, the findings fail to show that the intervention reduces the risk of GDM because of the limited power of the study. The power of a study—the probability that it will achieve a statistically significant result—depends on the study's size and on the likely effect size of the intervention. Before starting this study, the researchers calculated that they would need 420 participants to see a statistically significant difference between the groups if their intervention reduced GDM incidence by 40%. This estimated effect size was probably optimistic and therefore the study lacked power. Nevertheless, the analyses performed among adherent women suggest that lifestyle changes might be a way to prevent GDM and so larger studies should now be undertaken to test this potential primary prevention intervention.
Additional Information
Please access these Web sites via the online version of this summary at
The US National Institute of Diabetes and Digestive and Kidney Diseases provides information for patients on diabetes and on gestational diabetes (in English and Spanish)
The UK National Health Service Choices website also provides information for patients on diabetes and on gestational diabetes, including links to other useful resources
The MedlinePlus Encyclopedia has pages on diabetes and on gestational diabetes; MedlinePlus provides links to additional resources on diabetes and on gestational diabetes (in English and Spanish)
More information on this trial of primary prevention of GDM is available
PMCID: PMC3096610  PMID: 21610860

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