Association of dietary patterns and risk of cardiovascular disease events in the MASHAD cohort study.

BACKGROUND: Cardiovascular disease (CVD) is the principal cause of mortality and disability in Iranian adults. We aimed to evaluate the relationship between dietary patterns and CVD incidence in a large sample of adults in northeastern Iran. METHODS: The present study comprised a prospective study of 5706 CVD-free men and women aged 35-65 years who participated in a cohort study. All of the participants were followed up for a 6-year period. Dietary patterns were derived from a 65-item validated food frequency questionnaire and the factor analysis method was used to determine dietary patterns. RESULTS: We identified two major dietary patterns: (i) a Balanced dietary pattern (a high intake of green leafy vegetables, other vegetables, fruits, dairy products, red meats, poultry, seafoods, legumes and nuts, as well as a low intake of sugar) and (ii) a Western dietary pattern (a high intake of sugar, tea, egg, snacks, fast foods, potato, carbonated beverages, pickled foods, organs meat and butter) by factor analysis. The hazard ratio (HR) and 95% confidence intervals (CIs) of total CVD in the highest versus lowest tertiles of the Balanced pattern were 1.29 (95% CI = 0.67-2.47; P = 0.44). The HR and 95% CIs of CVD in the highest versus lowest tertiles of Western pattern were 2.21 (95% CI = 1.08-4.45; P = 0.03). CONCLUSIONS: During the 6-year follow-up, we found that adherence to a Balanced dietary pattern was not significantly associated with CVD events. However, adherence to a Western dietary pattern was associated with a significantly increased risk of CVD events and its associated risk.

The effect of electro-acupuncture on pro-oxidant antioxidant balance values in overweight and obese subjects: a randomized controlled trial study.

Objective To undertake a randomized controlled trial in 196 obese subjects to examine the effect of electro-acupuncture on serum pro-oxidant antioxidant balance (PAB) values. Methods Subjects received authentic acupuncture (cases) or sham acupuncture (controls) for 6 weeks in combination with a low-calorie diet. In the following 6 weeks, they received the low-calorie diet alone. Serum PAB was measured at baseline, and 6 and 12 weeks later. Results We found that serum PAB values decreased significantly in the group receiving the authentic acupuncture compared to the sham treatment (p<0.001) at week 6, and whilst serum PAB increased significantly (p<0.05) in the second phase of the study, a significant difference between two groups remained at 12 weeks (p<0.05). Conclusions Electro-acupuncture in combination with a low-calorie diet was more effective at reducing serum PAB values in obese subjects compared to diet alone. Further work is required to determine the mechanism by which electro-acupuncture has this effect.

Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer.

The most important biological function of exosomes is their possible use as biomarkers in clinical diagnosis. Compared with biomarkers identified in conventional specimens such as serum or urine, exosomal biomarkers provide the highest amount of sensitivity and specificity, which can be attributed to their excellent stability. Exosomes, which harbor different types of proteins, nucleic acids and lipids, are present in almost all bodily fluids. The molecular constituents of exosomes, especially exosomal proteins and microRNAs (miRNAs), are promising as biomarkers in clinical diagnosis. This discovery that exosomes also contain messenger RNAs and miRNAs shows that they could be carriers of genetic information. Although the majority of RNAs found in exosomes are degraded RNA fragments with a length of <200 nucleotides, some full-length RNAs might be present that may affect protein production in the recipient cell. In addition, exosomal miRNAs have been found to be associated with certain diseases. Several studies have pointed out miRNA contents of circulating exosomes that are similar to those of originating cancer cells. In this review, the recent advances in circulating exosomal miRNAs as biomarkers in gastrointestinal cancers are discussed. These studies indicated that miRNAs can be detected in exosomes isolated from body fluids such as saliva, which suggests potential advantages of using exosomal miRNAs as noninvasive novel biomarkers.

Serum hs-CRP varies with dietary cholesterol, but not dietary fatty acid intake in individuals free of any history of cardiovascular disease.

The objective of this study was to investigate whether serum high-sensitivity C-reactive protein (hs-CRP) concentration varies with dietary fatty acid intake in Iranian adults free of any history of cardiovascular disease (CVD). This cross-sectional study involved 8105 adults (3142 men) aged 35-65 years. Dietary intake was assessed using 24-h dietary recalls. The relationship between anthropometric, cardiometabolic risk factors and dietary data and serum hs-CRP was assessed using SPSS software. Median crude dietary saturated fat decreased across hs-CRP quarters (P =0.009 for linear trend), whereas energy-adjusted total fat (P =0.017), trans-fat (P =0.016), monounsaturated fatty acids (P =0.030) and cholesterol (P =0.005) monotonically increased, with some evidence of statistical interactions by gender. In conclusion, serum hs-CRP concentrations were associated with some components of dietary fatty acid intake in our population of individuals without CVD, suggesting that dietary fat intake could be associated with subclinical inflammation.

Locked nucleic acid anti-miR-21 inhibits cell growth and invasive behaviors of a colorectal adenocarcinoma cell line: LNA-anti-miR as a novel approach.

Colorectal cancer (CRC) is the third leading cause of cancer-related death and has an extremely poor prognosis. Dysregulation of microRNAs (miRNAs) has been shown to be involved in the pathogenesis and progression of many malignancies. Recent data suggest that microRNA-21 (miR-21) is significantly elevated in different types of cancer, especially colon adenocarcinoma. Against this background, locked nucleic acid (LNA)-modified oligonucleotides have recently been suggested as a novel approach for targeting miRNAs as antisense-based gene silencing. The aim of the current study was to explore the functional role of LNA-anti-miR-21 in a colon adenocarcinoma LS174T cell line. LS174T cells were transfected with LNA-anti-miR-21 for 24, 48 and 72 h. Quantitative real-time reverse transcriptase-PCR (qRT-PCR) was performed to assess miR-21 expression by LNA-anti-miR-21. The viability of the cells was evaluated by MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay and Annexin V/propidium iodide staining assay was used to detect apoptosis. Moreover, invasive behavior of the cells was evaluated before and after therapy by transwell assay. LNA-anti-miR-21 was successfully transfected in human LS174T cells and suppressed the endogenous miR-21. LNA-anti-miR-21 inhibited the cells' growth followed by induction of apoptosis. LNA-anti-miR-21 (50 pmol/µl) reduced the invasive behaviors of LS174T cells after 24 h, compared with untreated cells and scrambled LNA-transfected cells. However, this effect was more pronounced after 72 h. Our findings suggest the therapeutic potential of LNA-anti-miR-21 in a colon adenocarcinoma for targeting miR-21 expression. Further studies are warranted to investigate the molecular mechanisms underlying this novel inhibitor in colorectal cancer to establish its potential value for treatment of CRC patients with high miR-21 expression.

Serum high-sensitivity C-reactive protein as a biomarker in patients with metabolic syndrome: evidence-based study with 7284 subjects.

BACKGROUND/OBJECTIVES: Metabolic syndrome (MetS) is characterized by abdominal obesity, dyslipidemia, hypertension and glucose intolerance, and is associated with an increased risk of developing cardiovascular disease (CVD), diabetes mellitus and related diseases. Circulating levels of inflammatory markers such as C-reactive-protein (CRP) have reported to be associated with CVD. Against this background, the prevalence of MetS is increasing globally, and thus predictive biomarkers are required for identification of MetS patients at an increased risk. Here we explored the value of CRP as a biomarker in 7284 subjects and also investigated which features of MetS have the greatest association with the hs-CRP level. SUBJECTS/METHODS: The subjects were recruited from the Mashhad stroke and heart atherosclerotic disorder study. Anthropometric factors and biochemical parameters (for example, high-sensitivity CRP (hs-CRP), high-density lipoprotein/low-density lipoprotein, triglycerides (TGs) and fasting blood glucose (FBG)) were determined. Univariate and multivariate analyses were conducted to evaluate the association of hs-CRP and MetS. RESULTS: Our results illustrated that the concentration of serum hs-CRP increased progressively with the number of MetS components, and subjects who fulfilled the criteria of MetS for waist circumference, TGs, blood pressure and FBG were found to have hs-CRP of 0.53, 0.38, 0.34 and 0.71 mg/l, respectively, higher than matched-subjects. Importantly, FBG had the greatest association with hs-CRP concentration. CONCLUSIONS: Our data demonstrate the significant association between MetS components with hs-CRP, indicating that this association was cumulative by increasing the number of the defining features of MetS, supporting further studies to explore the value of emerging marker as a novel method for detecting individuals at high risk of developing MetS.

Comparative measurement of ghrelin, leptin, adiponectin, EGF and IGF-1 in breast milk of mothers with overweight/obese and normal-weight infants.

BACKGROUND/OBJECTIVES: Obese infants are more susceptible to develop adulthood obesity and its related comorbidities. Previous studies have shown the presence of hormones and growth factors in maternal breast milk that may influence infant adiposity. The aim of this study was to investigate differences in concentrations of three hormones and two growth factors in the breast milk of mothers with obese and non-obese infants. SUBJECTS/METHODS: In this cross-sectional study, 40 mothers with overweight or obese infants (weight for length percentile >97) and 40 age-matched mothers with normal-weight infant (-10 < weight for length percentile < 85) who were between 2 and 5 months of age were enrolled. Anthropometric indices of infants and mothers were measured by routine methods. Breast milk concentrations of ghrelin and adiponectin, leptin, epithelial growth factor (EGF) and insulin-like growth factor-1 (IGF-1) were measured using enzyme-linked immunosorbent assay methods. RESULTS: The mean breast milk concentration of ghrelin was higher in mothers with normal-weight infants, 137.50 pg/ml, than in mothers with obese infants, 132.00 pg/ml (P=0.001). This was also true regarding the concentration of EGF in mothers with (0/04 ng/ml) and without (0/038 ng/ml) normal-weight infants (P=0.01). No significant differences were observed in concentrations of leptin, adiponectin and IGF-1 between two groups (P > 0.05). There was also a significant positive correlation between EGF and ghrelin in both groups. CONCLUSIONS: This study revealed that there was a correlation between ghrelin and EGF level in breast milk of mothers with obese and non-obese infants, suggesting a possible regulatory effect of these two hormones on weight in infants.

Association between serum trace element concentrations and the disease activity of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex, incompletely understood, etiology. Several genetic and environmental factors are suspected to be involved in its aetiology. Oxidative stress may be implicated in the pathogenesis of SLE and may be affected by trace element status. Zinc (Zn), copper (Cu) and selenium (Se) are essential components of several anti-oxidative enzymes and are also involved in several immune functions. The current study aimed to assess the relationship between serum concentrations of these trace elements and the clinical disease activity of SLE assessed using the SLE disease activity index (SLEDAI). Serum concentrations of albumin (Alb) (p = 0.001), Se (p = 0.001), Zn (p = 0.001) and the Zn to Cu ratio (Zn/Cu R) (p = 0.001) were lower in patients with SLE than the age- and sex-matched healthy controls. However, only Alb (p = 0.001) and Cu (p = 0.03) were negatively correlated with disease activity, which was supported by regression analysis. In summary, lower serum values of Alb, Zn, Se and Zn/Cu R were found in SLE patients compared with healthy controls; however, in addition to serum Alb concentrations, serum Cu concentrations were also negatively correlated with lupus disease activity.

Dietary intake of patients with angiographically defined coronary artery disease and that of healthy controls in Iran.

OBJECTIVE: The aim of this study was to investigate the relationship between dietary intake and biomarkers of cardiovascular risk in individuals with and without angiographically defined coronary artery disease. SUBJECTS/METHODS: Coronary angiography was undertaken in 445 individuals who were divided into those with significant disease (>50% occlusion) (Angio+ (n=273)) and those with <50% coronary artery occlusion (Angio- (n=172)). Apparently healthy, non-symptomatic individuals (n=443) were considered as the control group. Dietary intake was assessed using a 24-h dietary recall method and dietary analysis was performed using Diet Plan 6 software. RESULTS: Concentrations of starch, saturated fatty acids, polyunsaturated fatty acids, magnesium, iron and copper in the control group were less than those in the other groups (P<0.05), but after adjusting for total energy intake these differences were no longer apparent. The mean intake of protein, cholesterol, phosphorus, zinc, zinc/copper ratio, selenium, iodine, carotene, vitamin E, niacin, pantothene and pyridoxine was less in the control group compared with the other two groups (P<0.05), and the mean of sugar, fiber, transfatty acids, manganese, folate and vitamin C was higher in the control group than in other groups (P<0.05). Lipid profile values between the three groups did not differ significantly. CONCLUSIONS: These results indicate that the amount of intake of various nutrients can be considered as an independent risk factor for CAD. Further research on the relationship between CAD and nutrient intake, especially intake of essential micronutrients, is needed.

MET as a potential target for the treatment of upper gastrointestinal cancers: characterization of novel c-Met inhibitors from bench to bedside.

The receptor tyrosine kinase mesenchymal-epithelial transition factor (c-Met) plays a pivotal role in regulation of cell proliferation and migration. Abnormal expression of c-Met has been associated with poor prognosis in several cancer types, including upper gastrointestinal malignancies. Moreover, c-Met interaction with multiple signalling pathways involved in tumor growth and invasive/metastatic phenotype has gained substantial attention in the last few years, suggesting the therapeutic potential of this target. This has led to the development and evaluation of a number of c-Met inhibitors. Here we describe the critical role of the HGF/c-Met pathway in cancer, as well as the preclinical and clinical investigations on c-Met inhibitors in solid tumors, with particular emphasis on recent findings with small-molecule inhibitors in gastrointestinal cancers. Clinical trials with several of these novel inhibitors have been encouraging and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung cancers with ALK-rearrangement. There are accumulating evidences on the therapeutic potential of this and other c-Met inhibitors for the treatment of other malignancies, such as gastric and pancreatic cancers. These inhibitors might be used in combination with chemotherapy as well as with other biological agents, in order to overcome different resistance mechanisms. However, further studies are needed to identify determinants of the activity of c-Met inhibitors, through the analysis of genetic and environmental alterations affecting c-Met and parallel pro-cancer pathways. These studies will be critical to improve the efficacy and selectivity of current and future anticancer strategies targeting c-Met.

Association between Malnutrition and Depression in Elderly People in Razavi Khorasan: A Population Based-Study in Iran.

BACKGROUND: To determine the prevalence of malnutrition and depression in free-living elderly people and their relationships (If any) in Razavi Khorasan, Iran 2007. METHODS: To evaluate nutritional status, we used Mini Nutritional Assessment (MNA) method in free-living elderly people (n=1565 using cluster sampling, 720 males and 845 females, aged≥ 60 yr) and their relationship to Socio Economic Conditions (SECs). Based on the final scores, our patients were classified into three groups: score 17-23.5 (at risk for malnutrition), score less than 17 (with malnutrition), and score 24-30 (well nourished). To determine the mood status (here depression), we used Geriatric Depression Score (GDS). According to this score our participants turned out to be in two distinct groups: depressed (score ≥8) and non-depressed (score < 8). RESULTS: From the total subjects entered the study (1495), 22.07% were depressed and 11.5% and 44% were malnourished or at risk of malnutrition respectively. In depressed group, the prevalence of malnutrition was 14.5% (48 out of 330) and the prevalence of "at risk of malnutrition" was 45.8%, whereas the prevalence of malnutrition and at risk of malnutrition in non-depressed population were 10.6% and 43.3% respectively. From the aforementioned information we have concluded that there is a significant statistical difference between the prevalence of malnutrition in depressed and non-depressed individuals (P= 0.047). CONCLUSIONS: With respect to the high rate of vegetative symptoms in elderly depressed individuals, malnutrition would have a higher prevalence in the depressed people.

Coronary artery disease and its risk factors status in iran: a review.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of mortality, morbidity, and disability in the world. The high prevalence and morbidity associated with CAD in Iran is one of the most pressing health problems. METHODS: We have reviewed the status of CAD and prevalence of its traditional and novel risk factors based on the published papers in recent years that may have an impact on the rate of CAD in Iran. Evaluation of current impact of metabolic syndrome in Iran was the other aim of this review, as it contributes to pathogenesis of coronary artery disease. We reviewed all PubMed indexed related studies. Some evidences from national articles which were published by the Ministry Of Health and Medical Education Research Council Certified Medical Journals of Islamic Republic of Iran were also included. RESULTS: The prevalence of CAD, coronary risk factors and metabolic syndrome in Iran is higher than Western countries and similar to some Middle East countries. There are limited data with regard to novel coronary risk factors in Iran. CONCLUSION: Primary and secondary prevention of CAD including life style modifications and dietary interventions strongly recommended in Iranian population.

Selenium supplementation and premature (pre-labour) rupture of membranes: a randomised double-blind placebo-controlled trial.

The aim was to determine if selenium supplementation during pregnancy reduces the occurrence of premature (pre-labour) rupture of membranes (PROM). A total of 166 primigravid pregnant women in the first trimester of pregnancy, were randomised to receive 100 microg of selenium (n = 83, drop-outs = 22) or a placebo (n = 83, drop-outs = 19) per day until delivery. The incidence of PROM, as well as serum selenium concentrations were evaluated at baseline and at the end of the study. Supplementation with selenium was associated with a significant increase in mean serum selenium concentration at term (p < 0.001). In contrast, mean serum selenium concentration remained unchanged in the control group (p > 0.05). The incidence of PROM was significantly lower in the selenium group (n = 8, 13.1%) than in the control group (n = 22, 34.4%) (p < 0.01). Our findings indicate that selenium supplementation (100 microg/day) in pregnant women effectively reduces the incidence of PROM.

Prevalence of obesity and its association with socioeconomic factors in elderly Iranians from Razavi-Khorasan province.

There are few data regarding the prevalence of obesity and its socioeconomic determinants among elderly individuals, particularly in Iran. We wished to determine the prevalence of overweight and obesity in free-living elderly people and the relationship to nutritional and socioeconomic factors in the Razavi-Khorasan province of Iran. Free-living elderly persons (917 males/1045 females), aged > or =60 years, were recruited using cluster sampling. Overweight and obesity were evaluated using body mass index (BMI) and subjects were categorized as thin (BMI <18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (> or =30 kg/m2). The association between the prevalence of overweight or obesity with socioeconomic and demographic factors, including gender, place of residence, literacy, type of living, source of income, use of supplements during the past 3 months, and employment status, was examined using regression analysis. The distribution of BMI values indicated that 13, 46.5, 28.9, and 11.7% of the total population were thin, normal, overweight, and obese, respectively. The prevalence of central obesity was higher among Iranian women than men (63.1 vs. 18.6%, respectively). Regression analysis results indicated that gender (p < 0.001), place of residence (p < 0.001), literacy (p = 0.01), and source of income (p < 0.001) were significantly associated with the incidence of overweight or obesity. This study showed that 40.6% of elderly subjects were overweight or obese. Results reinforce the need to plan strategies for primary prevention of this fast-growing public health problem.

The potential role of heat shock proteins in cardiovascular disease: evidence from in vitro and in vivo studies.

The heat shock proteins (HSPs) are highly conserved families of proteins expressed by a number of cell types following exposure to stressful environmental conditions. These conditions include several known risk factors for cardiovascular disease. A number of the HSPs have been shown to be molecular chaperones that are involved in the refolding of other damaged protein molecules. Over the past two decades there has been an increasing interest in the relationship between HSPs and cardiovascular disease, and particularly whether an autoimmune response may be implicated. The fact that microorganisms also produce HSPs, and that these are homologous to human HSPs has given rise to concept of molecular mimicry. While most of the past studies have focused on HSP 65 and 70, there has been recent interest and investigations of the possible role of the smaller HSPs, such as HSP27, in atherogenesis. Furthermore, the possibility that autoimmunity may be mediating the deleterious effects of HSPs has led some investigators to explore tolerization as a potential therapeutic approach.

The relationship between established coronary risk factors and serum copper and zinc concentrations in a large Persian cohort.

INTRODUCTION: The relationship between demographic and biochemical characteristics, including several established coronary risk factors, and serum copper and zinc was assessed in a large Iranian population sample. MATERIALS AND METHODS: A group of 2233 individuals, 15-65 years of age [1106 (49.5%) males and 1127 (50.5%) females] was recruited from residents of the Greater Khorasan province in northeast of Iran. Demographic data were collected using questionnaires. Coronary risk factors were determined using standard protocols, and trace elements were measured in serum using atomic absorption spectroscopy. RESULTS: Degree of glucose tolerance and smoking habit were not associated with serum zinc and copper levels. Serum copper levels were significantly higher in obese and hypertensive than in normal subjects (p<0.001). In the whole group and for the female subgroup, serum zinc (p<0.01) and copper (p<0.001) were both significantly lower in individuals with normal versus high levels of low-density lipoprotein cholesterol. A strong positive correlation was found between serum copper and body mass index (BMI) (r=0.85, p<0.001). Weaker positive associations were found between serum copper and calculated 10 years' coronary risk (r=0.11, p<0.001). Serum zinc/copper ratio was strongly inversely associated with calculated 10 years' coronary risk (r=-0.10, p<0.001). The partial Eta squared (PES) values for factors determining serum zinc were hypertension (0.007, p=0.01) and BMI (0.004, p=0.01); and for serum copper, they were gender (0.02, p=0.001), hypertension (0.004, p=0.009), and 10 years' coronary risk for men (0.003, p=0.03) and women (0.002, p=0.07). CONCLUSION: Significant associations between serum trace element concentrations and several coronary risk factors, including calculated 10 years' coronary risk scores, were found.

Prevalence of type 2 diabetes mellitus in Iran and its relationship with gender, urbanisation, education, marital status and occupation.

INTRODUCTION: We investigated the prevalence of type 2 diabetes mellitus and its relationship between gender, urbanisation, education, marital status and occupation in the Iranian population. METHODS: A total of 3,778 men and women aged between 15 and 64 years were recruited by using a cluster-stratified sampling method from Khorasan province, northeast Iran. Using an interviewer-administrated questionnaire, demographical data including gender, urbanisation, education, marital status and occupation was collected. Anthropometrical and biochemical measurements were taken for each subject. Associations of type 2 diabetes mellitus and other variables were tested for significance. RESULTS: The prevalence of diabetes mellitus (defined as fasting blood sugar equal to or more than 126 mg/dL) was 5.5 percent, and the prevalence in men and women was 5.1 percent and 5.8 percent, respectively, with a significantly higher prevalence among urban dwellers (seven percent) compared to that of the rural subgroup (three percent, p-value is less than 0.001). Diabetes mellitus was found to be most prevalent among the older age group (age more than 60 years, 10.9 percent), those who were retired (14.4 percent), and illiterate (6.1 percent, p-value is less than 0.001). Marital status was not significantly related to diabetes mellitus (p-value equals 0.09). CONCLUSION: The prevalence of diabetes mellitus is related to some sociodemographical factors within the Iranian population. Thus the preventive strategies should be based on the affective factors. The urbanisation of the population with the migration of people from rural to urban areas may account in part for the increasing prevalence of type 2 diabetes mellitus in Iran.

Natural honey and cardiovascular risk factors; effects on blood glucose, cholesterol, triacylglycerole, CRP, and body weight compared with sucrose.

It has been found that honey ameliorates cardiovascular risk factors in healthy individuals and in patients with elevated risk factors. The present study investigated the effect of natural honey on total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triacylglycerole, C-reactive protein (CRP), fasting blood glucose (FBG), and body weight in overweight individuals. There were 55 patients, overweight or obese, who were randomly recruited into the study and assigned into two groups: control group (17 subjects) and experimental group (38 subjects). Patients in the control group received 70 g of sucrose daily for a maximum of 30 days and patients in the experimental group received 70 g of natural honey for the same period. In the control and experimental groups, body weight, body mass index, body fat weight, total cholesterol, LDL-C, HDL-C, triacylglycerole, FBG, and CRP were measured before treatment and at day 31 after the commencement of treatment. Results showed that honey caused a mild reduction in body weight (1.3%) and body fat (1.1%). Honey reduced total cholesterol (3%), LDL-C (5.8), triacylglycerole (11%), FBG (4.2%), and CRP (3.2%), and increased HDL-C (3.3%) in subjects with normal values, while in patients with elevated variables, honey caused reduction in total cholesterol by 3.3%, LDL-C by 4.3%, triacylglycerole by 19%, and CRP by 3.3% (p < 0.05). It is our conclusion that consumption of natural honey reduces cardiovascular risk factors, particularly in subjects with elevated risk factors, and it does not increase body weight in overweight or obese subjects.