Adequacy of Nutrients Intake among Jordanian Pregnant Women in Comparison to Dietary Reference Intakes.

OBJECTIVE: Maternal nutrition is considered an important pillar in the pregnancy outcomes for both mother and infant. A mother's malnutrition and inadequate nutrient intake is associated with many undesirable pregnancy outcomes. Hence, assessing the nutritional status of the mother in the early stages of the pregnancy and preventing any inadequacy can preclude many health problems for both mother and infant. Therefore, this study aimed to assess the adequacy of nutrient intakes among Jordanian pregnant women as compared to their corresponding dietary reference intakes (DRIs). METHODS: This cross-sectional study was conducted at a major University Hospital in Jordan. Three hundred pregnant women were invited to participate in the study and 286 agreed to participate. Fifty pregnant women were enrolled at week 9, then 96 pregnant women were at week 20 and 137 pregnant women were at week 30 of pregnancy. The participants completed the interview-based demographic questionnaire, pregnancy physical activity questionnaire, and quantitative food frequency questionnaire (FFQ). RESULTS: The mean energy intake was 2768.9 ± 767.8 kcal/day and it was significantly higher in the 3rd trimester (p < 0.05). Women in the 3rd trimester consumed significantly more protein, carbohydrates, and sugar than women in the 1st and 2nd trimesters (p < 0.05). The pregnant women in the 3rd trimester consumed more sodium than women in the 1st and 2nd trimesters (p < 0.05). The vitamin K intake was significantly (p = 0.045) lower in the 2nd trimester than the 1st and 3rd trimesters. The calcium intake was significantly higher in the 3rd trimester than the 1st and 2nd trimesters (p = 0.021). The total micronutrient (vitamins B1, B2, B3, B6, B12, and D, calcium, and iron) intakes derived from dietary supplements and food sources throughout the 3 trimesters was significantly higher in the 3rd trimester than the 1st and 2nd trimesters (p < 0.05). The vitamin D, calcium, and iron intakes had the most significant increases between the 1st and 3rd trimesters (p < 0.001), while folic acid intake was significantly higher in the 1st trimester than the 2nd and 3rd trimester (p < 0.001). Most women exceeded the tolerable upper intake level (UL) for sodium in all trimesters, while 82% of women exceeded the UL of folic acid in the 1st trimester and from the supplement, not the diet. CONCLUSION: While the intake of some nutrients from food alone remains below the DRIs in the diets of pregnant women, the intake of other nutrients is above the UL. Raising the awareness of pregnant women about their diet and how a supplement intake can reduce the risk of inadequate intake for many micronutrients and improve their pregnancy outcomes is of great importance.

A high weekly dose of cholecalciferol and calcium supplement enhances weight loss and improves health biomarkers in obese women.

Obesity, a chronic condition associated with several life-threatening diseases, affects a significant proportion of the global population and has long been associated with vitamin D deficiency. The prevalence of both obesity and vitamin D deficiency has increased dramatically in Jordan in recent decades, especially among women. Few studies in Jordan and the surrounding area address this issue. In this study, we hypothesize that calcium and vitamin D have beneficial effects on weight reduction and metabolic profile in obese women. The objective of this study is to examine the effect of vitamin D3 and calcium supplementation on anthropometric measurements and some blood metabolites. Forty-five obese female subjects with vitamin D deficiency were recruited by a dietitian and randomly assigned to the same weight loss diet in addition to the following treatments (4 groups): control (CON), no prescribed supplements; vitamin D3 (Diet/D), given a high weekly dose of cholecalciferol (50 000 IU/subject/week); calcium (Diet/Ca), given 1200 mg/dL calcium/subject/day; vitamin D3 plus Ca (Diet/Ca/D), given cholecalciferol (50 000 IU/subject/week) and calcium (1200 mg/dL calcium/subject/day). Results revealed that after 3 months of supplementation, the Diet/Ca/D group subjects experienced a significant reduction (P ≤ .05) in weight (10.49 kg), BMI (4.61 ± 2 kg/m2), waist circumference (11.41 ± 8.9 cm), body fat percentage (2.43 ± 1.7%), FBG (25.81 ± 11.4 mg/dL), PTH (27.58 ± 8.9 pg/mL), cholesterol (0.56 ± 0.2 mmol/L), and triglycerides (0.53 ± 0.21 mmol/L) when compared to the Diet/Ca and the CON groups. Interestingly, however, the CON group showed a significant increase in serum PTH concentration (9.51 ± 3.8 pg/mL, P ≤ .05). Based on these results, a combined Ca and vitamin D3 supplement appears to enhance weight loss and improve some of the blood metabolic profiles in obese women subjected to a weight loss diet, thus supporting our study hypothesis.

Fast Foods, Sweets and Beverage Consumption and Risk of Colorectal Cancer: A Case-Control Study in Jordan

Background: The effects of consuming fast foods, sweets and beverages on the development of colorectal cancer (CRC) are unclear. The aim of this case-control study was to assess possible associations between the consumption of different fast foods, sweets and beverages and CRC risk in a Jordanian population. Methods: Two hundred and twenty diagnosed CRC cases and 281 controls were enrolled. Diet history was obtained using a validated quantitative questionnaire. Results: Consumption of some types of fast food, and particularly falafel, was associated with an increased risk of developing CRC. Elevated risk was found for potato and corn chips with an AOR of 4.36 (95%CI: 1.24-15.28) for daily consumption and 3.33 (95%CI: 1.00-11.11) for ≥5 servings/week. Consuming 1-2 or >5 servings per week of fried potatoes or 2-3 servings per week of chicken in sandwiches also increased the risk while exposure to fresh tomato juice and hot pepper sauce on a monthly basis appeared to exert a protective effect. Conclusions: Consumption of fried fast food items was significantly linked with an increased risk of developing CRC in Jordan.

Dietary patterns and colorectal cancer.

BACKGROUND & AIMS: Dietary pattern and lifestyle have been reported to be important risk factors in the development of colorectal cancer (CRC). However, the mechanism of action of dietary factors in CRC disease is unclear. The aim of this study is the examination of several dietary choices and their potential association with the risk of developing CRC. METHODS: Dietary data was collected from 220 subjects who were previously diagnosed with CRC, and 281 control subjects (matched by age, gender, occupation and marital status). The data was collected between January 2010 and December 2012, using interview-based questionnaires. Multivariate logistic regression was used to estimate the relationship between dietary choices and risk of developing colorectal cancer. RESULTS: Factor analysis revealed three major dietary patterns. The first pattern we identified as the "Healthy Pattern", the second was identified as "High Sugar/High Tea Pattern" and the third as "Western Pattern". In the Healthy Pattern group we found a 10.54% variation in food intake, while the intake variation was 11.64% in the Western Pattern. After adjusting for confounding factors, the Western Pattern food choice was found to be significantly associated with an increased risk of developing CRC (OR = 1.88; 95% CI = 1.12-3.16). The results for the Healthy and High-Sugar/High Tea Patterns showed a decrease, but the statistic was not significant for the risk of CRC development. CONCLUSION: The Western Pattern of dietary choice was directly associated with CRC. The association between the dietary food choice in the Healthy and High-Sugar/High Tea Patterns and colorectal cancer needs further study in our Jordanian population.

Fast foods perception among adolescents by gender and weight status.

BACKGROUND: Fast food restaurants have become widespread in both developed and developing countries due to nutritional and economic transitions. The frequency of fast food intake is relatively high among adolescents; however, fast food consumption is positively associated with total energy intake and obesity in adolescents. OBJECTIVE: This study aimed to examine the perception of Jordanian adolescents towards fast foods relative to gender and obesity. METHODS: A cross-sectional survey was conducted on 400 boys and 395 girls, aged 15-18 years. The adolescents completed a validated questionnaire to measure the perception of adolescents towards fast foods during the year 2013-2014. Weight and height were measured. Numbers who were non-overweight, overweight, and obese were calculated for each age and sex using the International Obesity Task Force (IOTF) standard. RESULTS: The majority of participants perceived foods which are eaten as sandwiches as fast foods. A significant difference between boy and girl adolescents was reported regarding perception of French fries ( p < 0.012), fried chicken ( p < 0.001), fattayer ( p < 0.001), foul (boiled broad beans) sandwich ( p < 0.001), falafel sandwich ( p < 0.044) and fried eggs sandwich ( p < 0.001) as fast foods. Girls were significantly more enthusiastic than boys to consider cuscusi plate ( p < 0.001), rice dishes ( p < 0.002), Chinese foods ( p < 0.001), Indian foods ( p < 0.010), Mexican foods ( p < 0.011), and Italian foods ( p < 0.004) as non-fast foods. The difference between obese and non-obese regarding the perception of fast foods was only significant among boy participants. Western or non-Arab foods, food prepared fast and eaten fast in self-service outlets, and food rich in calories were significantly perceived as fast food by Jordanian adolescents ( p < 0.05). CONCLUSIONS: The perception of foods as fast foods or non-fast foods was significantly different between both genders as well as in obese and non-obese male Jordanian adolescents.

Association between mass media and body weight concern among Jordanian adolescents' residents of Amman: the role of gender and obesity.

OBJECTIVES: Body image in the mass media promotes an unrealistic picture of body shape that leads to body dissatisfaction among adolescentsQuery. Therefore, the study presented in this paper aimed to assess the association between mass media and adolescents' weight concerns and perceptions of body weight and shape. METHODS: A cross-sectional survey was conducted on school adolescents aged between 15 and 18 years during the academic year 2013-2014. Multistage stratified sampling method was used. The number of participants in the study was 795 students: 400 boys and 395 girls. RESULTS: All participants have a common behavior in rarely reading magazines, but they spend more than 2 h in watching television or less than 3 h using the internet. However, most of obese/non-obese adolescents, boys or girls, have shown high influence (p < 0.05) of reading magazines on the subject of dieting to lose weight. CONCLUSION: While obese students read more magazines on dieting to lose weight, other mass media did not show the same results on weight concerns and body shape among Jordanian adolescents.

Consumption of Whole Grains, Refined Cereals, and Legumes and Its Association With Colorectal Cancer Among Jordanians.

Background The role of whole grains, refined cereals, and legumes in preventing or initiating colorectal cancer (CRC) is still uncertain. The aim of this study is to examine the possible association between the consumption of whole grains, refined cereals, and legumes and the risk of developing CRC among Jordanian population. Methods A validated food frequency questionnaire was used to collect dietary data with regard to intake of whole grains, refined cereals, and legumes. A total of 220 diagnosed CRC participants and 281 CRC-free control participants matched by age, gender, occupation, and marital status were recruited. Logistic regression was used to estimate the odds of developing CRC in relation to the consumption of different types of whole grains, refined cereals, and legumes. Results The odds ratio (OR) for developing CRC among cases consumed refined wheat bread at all meals was 3.1 compared with controls (95% CI: 1.2-7.9, P-Trend = 0.001); whereas the OR associated with whole wheat bread was 0.44 (95% CI: 0.22-0.92, P-Trend = 0.001). The statistical evaluation for daily consumption of rice suggested a direct association with the risk of developing CRC, OR = 3.0 (95% CI: 0.27-33.4, P-Trend = 0.020). Weekly consumption of macaroni was associated with CRC with OR of 2.4 (95% CI: 1.1-5.3, P-Trend = 0.001). The consumption of corn, bulgur, lentils, and peas suggested a protective trend, although the trend was not statistically significant. Conclusion This study provides additional indicators of the protective role of whole grains and suggests a direct association between consumption of refined grains and higher possibility for developing CRC.

Macro- and micronutrients consumption and the risk for colorectal cancer among Jordanians.

OBJECTIVE: Diet and lifestyle have been reported to be important risk factors for the development of colorectal cancer (CRC). However, the association between total energy and nutrient intake and the risk of developing CRC has not been clearly explained. The aim of our study is to examine the relationship between total energy intake and other nutrients and the development of CRC in the Jordanian population. RESEARCH METHODS AND PROCEDURES: Dietary data was collected from 169 subjects who were previously diagnosed with CRC, and 248 control subjects (matched by age, gender, occupation and marital status). These control subjects were healthy and disease free. Data was collected between January 2010 and December 2012, using interview-based questionnaires. Logistic regression was used to evaluate the association between quartiles of total energy, macro- and micronutrient intakes with the risk of developing CRC in our study population. RESULTS: Total energy intake was associated with a higher risk of developing CRC (OR = 2.60 for the highest versus lowest quartile of intake; 95% CI: 1.21-5.56, p-trend = 0.03). Intakes of protein (OR = 3.62, 95% CI: 1.63-8.05, p-trend = 0.002), carbohydrates (OR = 1.41, 95% CI: 0.67-2.99, p-trend = 0.043), and percentage of energy from fat (OR = 2.10, 95% CI: 0.38-11.70, p-trend = 0.009) significantly increased the risk for the development of CRC. Saturated fat, dietary cholesterol and sodium intake showed a significant association with the risk of developing CRC (OR = 5.23, 95% CI: 2.33-11.76; OR = 2.48, 95% CI: 1.18-5.21; and OR = 3.42, 95% CI: 1.59-7.38, respectively), while vitamin E and caffeine intake were indicative of a protective effect against the development of CRC, OR = 0.002 (95% CI: 0.0003-0.011) and 0.023 (95%CI: 0.008-0.067), respectively. CONCLUSION: Our results suggest an increased risk for the development of CRC in subjects with high dietary intake of energy, protein, saturated fat, cholesterol, and sodium, and diets high in vitamin E and caffeine were suggestive of a protective effect against the risk of developing CRC. IMPACT: This is the first study in Jordan to suggest that it may be possible to reduce CRC risk by adjusting the intake of some macro-and micronutrients.

Food groups and the risk of colorectal cancer: results from a Jordanian case-control study.

The role of diet in colorectal cancer (CRC) in Jordan has not been studied previously. This study aimed at examining the association between food groups (including grains, fruits, vegetables, milk, and meat and legumes) and CRC risk in Jordan. We compared intakes of the different food groups among CRC patients (n=167) and matched controls (n=240) by age, sex, occupation, and marital status. A validated food frequency questionnaire was used to collect dietary data. Logistic regression was used to evaluate the association of quartiles of intakes of the different food groups with CRC risk. In addition, the association of selected food items with CRC risk was examined. Odds ratios (ORs) for the fourth versus the first quartile of intake were 2.92 [95% confidence interval (CI): 1.40-6.08] for grains, 1.66 (95% CI: 0.81-3.40) for vegetables, 0.55 (95% CI: 0.26-1.16) for fruits, 0.96 (95% CI: 0.46-1.97) for milk, and 1.43 (95% CI: 0.68-2.98) for meat and legumes. In a comparison of the highest with the lowest weekly frequency of consumption, there was a direct association between the risk of CRC and the frequency of consumption of chicken (OR=2.52, 95% CI: 1.33-4.77). An increase in risk was observed with increased consumption of white bread (OR=3.13, 95% CI: 1.18-9.25), whereas consumption of whole bread was associated with a decreased risk for CRC (OR=0.32, 95% CI: 0.12-0.84). Our results support a role of diet in CRC. Direct associations were found for grains, white bread, and chicken, whereas an inverse relation was reported for whole bread.

Fruit and vegetable intake among Jordanians: results from a case-control study of colorectal cancer.

BACKGROUND: Diets that include fruits and vegetables have been suggested as one way to reduce the risk of developing colorectal cancer (CRC); however, the association between consuming fruits and vegetables and CRC risk is not clear. The objective of the present study is to compare fruit and vegetable intake between 2 groups of Jordanians and further investigate this possible relationship. METHODS: A history of fruit and vegetable consumption was obtained from 220 people with CRC and 281 healthy controls, all of whom were from Jordan. Both groups were matched for age, sex, occupation, and marital status. Fruit and vegetable consumption was quantified for the previous 12 months in both groups. RESULTS: Total vegetable intake was associated with the risk of developing CRC. Consuming 5 servings of vegetables a day decreased the risk of developing CRC when compared with no more than 1 serving a day (odds ratio [OR] = 0.23; 95% confidence interval [CI]: 0.55-0.97). A significant direct relationship between CRC risk and consuming cauliflower and cabbage was found; however, no association was found for raw or cooked leafy vegetable and other vegetable types. Consuming several types of fruits also revealed no association with risk of CRC, although an increased intake of dates and figs was associated with a reduced risk of developing CRC. The ORs for the highest intake of servings compared with the lowest intake were 0.48 (95% CI: 0.27-0.87; P = .004) for dates and 0.604 (95% CI: 0.35-1.06; P = .003) for figs. CONCLUSIONS: Consuming fruits and vegetables did not significantly correlate with a lowered incidence of CRC. However, a trend of protection was detected for several types of fruits and vegetables.

Nutrient intake and lifestyle factors by diabetes status of Circassians and Chechans in Jordan.

OBJECTIVES: Diabetes is one of the most prevalent diseases in Jordan. However, little is known about nutrient intakes of minority groups in Jordan with and without diabetes. Our study aimed to examine if the intake of energy, macronutrients and some micronutrients differed between normal and diabetic adults among Circassians and Chechans in Jordan. DESIGN, SETTING, PARTICIPANTS: This cross-sectional study was conducted among 437 Circassians (160 males and 277 females) and 355 Chechans (119 males and 236 females) aged > or = 18 years. They were recruited from the Chechan and Circassian communities living in Jordan. MAIN OUTCOME MEASURES: A participant was defined as affected by type 2 diabetes mellitus if diagnosis was known to patient or if his or her condition complied with the American Diabetes Association definition. One 24-hour dietary recall for each participant was collected by face-to-face interview. RESULTS: Most of the measured anthropometric and biochemical parameters showed a significant difference between normal individuals and those with impaired fasting glucose or diabetes. Intakes of nutrients involved in the pathogenesis of diabetes including protein, fat and fiber did not differ between stratified participants according to blood glucose status for both Circassians and Chechans. CONCLUSIONS: Intake of nutrients did not differ in participants with normal blood glucose from those who had impaired fasting glucose or diabetes in the two studied populations. These two populations may need genetic studies to identify the risk factors other than dietary and lifestyle factors for type 2 diabetes.

Prevalence of food insecurity among women in northern Jordan.

Food insecurity--not having sufficient quantities of good-quality foods--is inversely related to physical and mental health and directly related to poor dietary intake. The objectives of this research were to (a) measure the prevalence of food insecurity among women in northern Jordan, (b) study the socioeconomic factors associated with an increased risk of food insecurity, and (c) investigate the relationship between household food insecurity and women's reported body-weight. This cross-sectional study was conducted using an interview-based questionnaire. In total, 500 women were interviewed in the waiting rooms of the outpatient clinics of two major public hospitals in northern Jordan. Food insecurity was assessed using the short form of the U.S. food security survey module. The prevalence of food insecurity was 32.4%. Income below the poverty-line, illiteracy, unemployment, rented housing, and woman heading the household were among the socioeconomic factors that increased the probability of food insecurity. No evidence was found to support the relationship between obesity and food insecurity. Except grains, food-insecure women with hunger had lower intake of all food-groups. This study demonstrated that the problem of food insecurity is present in Jordan. Food-insecure women with hunger are at a risk of malnutrition. Interventions that target reduction of the factors associated with food insecurity are necessary.

Inhibition of the formation of advanced glycation end products by thymoquinone.

The inhibitory activity of thymoquinone, a major quinone from black seeds (Nigella sativa) against the formation of advanced glycation end products was studied using the hemoglobin-δ-gluconolactone, human serum albumin-glucose, and the N-acetyl-glycyl-lysine methyl ester-ribose assays. A comparison was made with the inhibitory activity of aminoguanidine. The cytotoxicity of thymoquinone was studied by the release of lactate dehydrogenase from platelets and the levels of plasma thiols. At 20µM, thymoquinone inhibited 39% of hemoglobin glycation, 82% of post-Amadori glycation products, reduced methyglyoxal-mediated human serum albumin glycation by 68%, inhibited 78% of late glycation end products. Aminoguanidine at 10mM was less effective than thymoquinone. The IC50 for thymoquinone and aminoguanidine were 7.2µM and 1.25mM, respectively. Thymoquinone at 20-50µM was not toxic to platelet lactate dehydrogenase and plasma thiols. The potential of thymoquinone in food applications is discussed.

Gestational nutrition improves outcomes of vaginal deliveries in Jordan: an epidemiologic screening.

Adequate and balanced nutrition during gestation is essential for achieving healthy pregnancy outcomes. This retrospective survey tested the hypothesis that maternal nutrition (macronutrients intake, micronutrients intake, and weight gain) during gestation will impact gestational outcomes (gestational age, birth weight, and labor spontaneity). The objectives of this study were to test the impact of macronutrients and micronutrients consumed during gestation, pregestational weight and weight gain during gestation on gestational age, birth weight, and labor spontaneity among Jordanian women. Study participants (n = 700) were recruited from a women's hospital in northern Jordan. Data were collected using structured interviews. Dietary determinants examined in the study included daily intake of macronutrients (energy, carbohydrate, protein, fat, and n-3 and n-6 fatty acids) and micronutrients (zinc, calcium, folate, vitamin C, vitamin A, and vitamin B6), pregestational body mass index, total weight gain, and weight gain pattern during pregnancy. Dietary data were obtained from a semiquantitative food frequency questionnaire. Mean (SEM) daily intakes of energy, carbohydrate, and protein were 10894 (138) Kj, 320 (3.8) g, and 90 (0.95) g, respectively; with fat contributing 36% of total energy. Average daily energy and carbohydrate intake during pregnancy were related negatively to gestational age (P < .05). Pregestational body mass index was associated positively with gestational age and birth weight (P < .05). Intakes of vitamin A and calcium had significant relationships with birth weight. Daily intakes of zinc, calcium, vitamin B6, and n-3 and n-6 fatty acids were associated with labor spontaneity. Dietary factors consumed during pregnancy are associated with pregnancy outcomes.

Developing a food exchange list for Middle Eastern appetizers and desserts commonly consumed in Jordan.

AIM: This study was conducted to develop a meal-planning exchange list for Middle Eastern foods commonly included in the Jordanian cuisine. Forty types of appetizers and another 40 types of desserts were selected; with five different recipes for each item. Recipes were collected from different housewives and Arabic cookbooks. Ingredients' weight and dish net weight were recorded based on an average recipe, and dishes were prepared accordingly. Dishes were proximately analyzed following the AOAC procedures. Proximate analysis was compared to the WHO-food composition tables (FCT) for the use in the Middle East, and with food analysis software (ESHA). RESULTS: Significant correlations (P < 0.001) were found between macronutrient content obtained from proximate analysis and those obtained from ESHA. The correlation coefficients (r) were 0.92 for carbohydrate, 0.86 for protein, and 0.86 for fat. Strong correlations were also detected between proximate analysis FCT for carbohydrate (r=0.91, P<0.001) and protein (r=0.81; P<0.001) contents. However, this significant correlation was not found as strong, yet significant for fat (r=0. 62, P<0.001). CONCLUSION: A valid exchange system for traditional desserts and appetizers is now available and ready to be used by dietitians and health care providers in Jordan and Arab World.

Assessment of nutritional status among ESRD patients in Jordanian hospitals.

OBJECTIVE: Our objective was to assess nutritional status and compare quality of treatment among hemodialysis patients in public and private hospitals in Jordan. DESIGN: We utilized a cross-sectional survey. SETTING: Our setting involved hospital hemodialysis units. PATIENTS: This study was undertaken in five large Jordanian hospitals between 2004 and 2005. One hundred and eighty participants diagnosed with end-stage renal failure (ESRD) were enrolled. These participants (91 women and 89 men) who underwent hemodialysis treatment were recruited using a convenience sampling technique. Data from participants who received hemodialysis treatment in public hospital settings were compared with equivalent data from participants treated in private hospital settings. MAIN OUTCOME MEASURES: Subjective global assessment (SGA), anthropometry, and biochemical measurements were used as evaluative tools. RESULTS: In the anthropometric measurement of triceps skinfold thickness (TSF), we found a statistically significant difference (P < .05) between participants treated in the two hospital settings. In addition, approximately 62% of all participants, regardless of treatment site, were found to be moderately to severely malnourished. Anthropometric measurements showed some significant increase between prehemodialysis and posthemodialysis weight and body mass index in private hospitals; this was not unexpected. There were no statistically significant differences in the measured mean levels of eight different biochemical parameters, with the exception of plasma phosphorus and sodium levels. CONCLUSIONS: The prevalence of malnutrition and the quality of treatment in our two groups of participants were similar.

Hypoxia inducible factor pathways as targets for functional foods.

The etiology of most chronic angiogenic diseases such as rheumatoid arthritis, atherosclerosis, diabetes complications, and cancer includes the presence of pockets of hypoxic cells growing behind aerobic cells and away from blood vessels. Hypoxic cells are the result of uncontrolled growth and insufficient vascularization and have undergone a shift from aerobic to anaerobic metabolism. Cells respond to hypoxia by stimulating the expression of hypoxia inducible factor (HIF), which is critical for survival under hypoxic conditions and in embryogenesis. HIF is a heterodimer consisting of the O2-regulated subunit, HIF-1alpha, and the constitutively expressed aryl hydrocarbon receptor nuclear translocator, HIF-1beta. Under hypoxic conditions, HIF-1alpha is stable, accumulates, and migrates to the nucleus where it binds to HIF-1beta to form the complex (HIF-1alpha + HIF-1beta). Transcription is initiated by the binding of the complex (HIF-1alpha + HIF-1beta) to hypoxia responsive elements (HREs). The complex [(HIF-1alpha + HIF-1beta) + HREs] stimulates the expression of genes involved in angiogenesis, anaerobic metabolism, vascular permeability, and inflammation. Experimental and clinical evidence show that these hypoxic cells are the most aggressive and difficult angiogenic disease cells to treat and are a major reason for antiangiogenic and conventional treatment failure. Hypoxia occurs in early stages of disease development (before metastasis), activates angiogenesis, and stimulates vascular remodeling. HIF-1alpha has also been identified under aerobic conditions in certain types of cancer. This review summarizes the role of hypoxia in some chronic degenerative angiogenic diseases and discusses potential functional foods to target the HIF-1alpha pathways under hypoxic and normoxic conditions. It is reported that dietary quinones, semiquinones, phenolics, vitamins, amino acids, isoprenoids, and vasoactive compounds can down-regulate the HIF-1 pathways and therefore the expression of several proangiogenic factors. Considering the lack of efficiency or the side effects of synthetic antiangiogenic drugs at clinical trials, down-regulation of hypoxia-induced angiogenesis by use of naturally occurring functional foods may provide an effective means of prevention.

In vitro anti-proliferative activities of ellagic acid.

The potential cytotoxic and anti-proliferative activities of ellagic acid (a naturally occurring bioactive compound in berries, grapes, and nuts) was evaluated using human umbilical vein endothelial cells (HUVEC), normal human lung fibroblast cells HEL 299, Caco-2 colon, MCF-7 breast, Hs 578T breast, and DU 145 human prostatic cancer cells. Ellagic acid at concentration in the range 10-100 micromol/L did not affect the viability of normal fibroblast cells during a 24-hour incubation. An increase in adenosine triphosphate (ATP) bioluminescence of approximately 18-21% was observed in normal cells incubated with ellagic acid. In contrast, ellagic acid at 1-100 micromol/L dose-dependently inhibited HUVEC tube formation and proliferation on a reconstituted extracellular matrix and showed strong anti-proliferative activity against the colon, breast, and prostatic cancer cell lines investigated. The most sensitive cells were the Caco-2, and the most resistant were the breast cancer cells. Ellagic acid induced cancer cell death by apoptosis as shown by the microscopic examination of cell gross morphology. Ellagic acid induced reduced cancer cell viability as shown by decreased ATP levels of the cancer cells. After 24 hours incubation of 100 micromol/L of ellagic acid with Caco-2, MCF-7, Hs 578T, and DU 145 cancer cells, ellagic acid suppressed fetal bovine serum (FBS) stimulation of cell migration. The apoptosis induction was accompanied by a decreased in the levels of pro-matrix metalloproteinase-2 (pro-MMP-2 or gelatinase A), pro-matrix metalloproteinase-9 (pro-MMP-9 or gelatinase B), and vascular endothelial growth factor (VEGF(165)) in conditioned media. The results suggest that ellagic acid expressed a selective cytotoxicity and anti-proliferative activity, and induced apoptosis in Caco-2, MCF-7, Hs 578T, and DU 145 cancer cells without any toxic effect on the viability of normal human lung fibroblast cells. It was also observed that the mechanism of apoptosis induction in ellagic acid-treated cancer cells was associated with decreased ATP production, which is crucial for the viability of cancer cells.

Inhibition of matrix metalloproteinase-1 activity by the soybean Bowman-Birk inhibitor.

Inductively coupled plasma analysis of soybean Bowman-Birk inhibitor (BBI) indicated that BBI was a metalloprotein which contained magnesium, calcium, and zinc at 0.40, 0.43 and 0.008 atom/mol BBI, respectively. Heparin-enhanced gelatin zymography, quenched fluorescence substrate hydrolysis analysis, and the Biotrak assay of the interaction of BBI with the matrix metalloproteinase-1 (MMP-1) demonstrated that demineralized BBI at 30 nM inhibited MMP-1 activity whereas mineralized BBI was inhibitory at 115 nM.

In vitro inhibition of the activation of Pro-matrix Metalloproteinase 1 (Pro-MMP-1) and Pro-matrix metalloproteinase 9 (Pro-MMP-9) by rice and soybean Bowman-Birk inhibitors.

The in vitro inhibitory activity of the rice Bowman-Birk inhibitor (rBBI) or soybean Bowman-Birk inhibitor (sBBI) against trypsin-catalyzed activation of pro-matrix metalloproteinase 1 or 9 (pro-MMP-1 or pro-MMP-9), respectively, was investigated using electrophoresis with silver staining, heparin-enhanced zymography, biotinylated gelatin, Biotrak assay, and fluorescence quenched substrate hydrolysis. rBBI at concentrations of 0.08-0.352 mg/mL dose-dependently inhibited the in vitro activation of 45 microg/mL pro-MMP-1 by trypsin. Heparin-enhanced zymography analysis of pro-MMP-1, trypsin-activated MMP-1, and a mixture of pro-MMP-1-trypsin-rBBI showed clear zones associated with trypsin-activated MMP-1 and the absence of clear zones in lanes containing pro-MMP-1 or a mixture of pro-MMP-1, trypsin, and rBBI. The results of the Biotrak assay also indicated that rBBI dose-dependently suppressed the activation of pro-MMP-1 by trypsin. sBBI dose-dependently inhibited the activation of 100 microg/mL of pro-MMP-9 by trypsin. Biotinylated gelatin assays demonstrated that pro-MMP-9 or pro-MMP-9 in the presence of trypsin and BBI did not hydrolyze gelatin, whereas p-aminophenylmercury acetate (APMA)-activated MMP-9 and trypsin-activated MMP-9 caused significant hydrolysis of gelatin. Quenched fluorescence substrate hydrolysis for total MMP activity showed that pro-MMP-1 or pro-MMP-9 did not hydrolyze the substrate Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2; active MMP-1 or MMP-9 hydrolyzed the substrate, but lower substrate hydrolysis was obtained when pro-MMP-1 or pro-MMP-9 was incubated with trypsin in the presence of increasing concentrations of rBBI. The results are discussed in light of the role of MMP-1 and MMP-9 in the process of angiogenesis and the potential of rBBI or sBBI as a functional food ingredient.