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By X. Zarkos. Monterey Institute of International Studies.

Neither the prospective studies nor the three large intervention trials reported aspects of colonic function (Alberts et al cheap 20mg tadalis sx otc erectile dysfunction test yourself. It is possible that bulkier stools or faster transit through the colon reduce the risk of bowel cancer (Cummings et al purchase tadalis sx online pills impotence vitamins supplements. In addition order tadalis sx 20 mg online impotence support group, posi- tive benefits of fiber with respect to colon cancer may not occur until Dietary Fiber intake is sufficiently high; for example, greater than the median 32 g/d for the highest quintile in The Health Professionals Follow-Up Study of men (Giovannucci et al. Infor- mation is lacking on the role of Functional Fibers in the incidence of colon cancer because of the lack of intake data on specific Functional Fibers col- lected in epidemiological studies. Most animal studies on fiber and colon cancer, however, have used what could be termed Functional Fibers (Jacobs, 1986). Because evidence available is either too conflicting or inadequately understood, a recommended intake level based on the prevention of colon cancer cannot be set. Dietary Fiber and Protection Against Breast Cancer A growing number of studies have reported on the relationship of Dietary Fiber intake and breast cancer incidence, and the strongest case can be made for cereal consumption rather than consumption of Dietary Fiber per se (for an excellent review see Gerber [1998]). Between-country studies, such as England versus Wales (Ingram, 1981), southern Italy versus northern Italy versus the United States (Taioli et al. However, starchy root, vegetable, and fruit intakes were not related to breast cancer risk for either diet. Prospective Studies There have been at least two prospective studies relating Dietary Fiber intake to breast cancer incidence in the United States and both found no significant association (Graham et al. A Canadian study showed a significant protective trend for the intake of cereals, with borderline significance for Dietary Fiber (Rohan et al. Verhoeven and coworkers (1997) investigated the relationship between Dietary Fiber intake and breast cancer risk in The Netherlands Cohort Study. This prospective cohort study showed no evidence that a high intake of Dietary Fiber decreased the risk of breast cancer. Case-Control Studies Eight of eleven reported case-control studies showed a protective effect of Dietary Fiber against breast cancer (Baghurst and Rohan, 1994; De Stefani et al. For studies that showed this protection, the range of the odds ratio or relative risk was 0. Intervention Studies Most intervention studies on fiber and breast cancer have examined fiber intake and plasma or urinary indicators of estrogen (e. Since certain breast cancers are hormone dependent, the con- cept is that fiber may be protective by decreasing estrogen concentrations. Rose and coworkers (1991) provided three groups of premenopausal women with a minimum of 30 g/d of Dietary Fiber from wheat, oats, or corn. After 2 months, wheat bran was shown to decrease plasma estrone and estradiol concentrations, but oats and corn were not effective. Bagga and coworkers (1995) provided 12 premenopausal women a very low fat diet (10 percent of energy) that provided 25 to 35 g/d of Dietary Fiber. After 2 months there were significant decreases in serum estradiol and estrone concentrations, with no effects on ovulation. In a separate study, the same researchers again provided a low fat (20 per- cent of energy), high fiber (40 g of Dietary Fiber) diet to premenopausal African-American women and observed reduced concentrations of serum estradiol and estrone sulfate when compared with a typical Western diet (Woods et al. Mechanisms A variety of different mechanisms have been proposed as to how fiber might protect against breast cancer, but the primary hypothesis is through decreasing serum estrogen concentrations. Fiber can reduce the entero- hepatic circulation of estrogen by binding unconjugated estrogens in the gastrointestinal tract (Shultz and Howie, 1986), making them unavailable for absorption (Gorbach and Goldin, 1987). Goldin and coworkers (1982) reported decreased plasma concentrations of estrone and increased fecal excretion of estrogens with increasing fecal weight. Alternatively, certain fibers can modify the colonic microflora to produce bacteria with low deconjugating activity (Rose, 1990), and deconjugated estrogens are reabsorbed. Another related hypothesis is that fiber speeds up transit through the colon, thus allowing less time for bacterial deconjugation. In fact, Petrakis and King (1981) noted abnormal cells in the mammary fluid of severely constipated women. Also, fiber sources contain phytoestrogens, which may compete with endogenous estrogens and act as antagonists (Lee et al. Finally, one report showed that Dietary Fiber intake was negatively correlated with total body fat mass, intra-abdominal adipose tissue, and subcutaneous abdominal adipose tissue in 135 men and 214 women (Larson et al. Since estrogen synthesis can occur in lipid stores, a decreased lipid mass should result in decreased synthesis. In addition to decreasing serum estrogen concentrations, fiber may be protective by adsorbing carcinogens or speeding their transit through the colon and providing less opportunity for their absorption. Carcinogens known to be related to breast cancer that may be affected include hetero- cyclic amines (Ito et al. Summary There are no reports on the role of Functional Fibers in the risk of breast cancer. Because of the lack of evidence to support a role of Dietary Fiber in preventing breast cancer, this clinical endpoint cannot be used to set a recommended intake level. Dietary Fiber and Other Cancers Although the preponderance of the literature on fiber intake and cancer involves colon cancer and breast cancer, several studies have shown decreased risk for other types of cancer. Because Dietary Fiber has been shown to decrease serum estrogen concentrations, some researchers have hypothesized a protective effect against hormone-related cancers such as endometrial, ovarian, and prostate. Studies on Dietary Fiber intake and endo- metrial cancer have shown both significant and nonsignificant decreases in risk (Barbone et al. In addition, studies have shown a decreased risk in ovarian cancer with a high intake of Dietary Fiber (McCann et al. However, no significant associations have been observed between Dietary Fiber intake and risk of prostate cancer (Andersson et al. Although interesting to note, this literature is in its infancy and cannot be used to set a recommended intake level for Dietary Fiber. Dietary Fiber and Functional Fiber and Glucose Tolerance, Insulin Response, and Amelioration of Diabetes Epidemiological Studies Epidemiological evidence suggests that intake of certain fibers may delay glucose uptake and attenuate the insulin response, thus providing a protective effect against diabetes. Evidence for the protective effect of Dietary Fiber intake against type 2 diabetes comes from several prospective studies that have reported on the relationship between food intake and type 2 diabetes (Colditz et al. One study examined the relationship between specific dietary patterns and risk of type 2 diabetes in a cohort of 42,759 men, while controlling for major known risk factors (Salmerón et al. The results suggest that diets with a high glycemic load and low cereal fiber content are positively associated with risk of type 2 diabetes, indepen- dent of other currently known risk factors (Figure 7-1). In a second study, diet and risk of type 2 diabetes in a cohort of 65,173 women were evalu- ated (Salmerón et al. Of particular importance is that this combination resulted in a relative risk of 2. In theory, the hypothesis as to how Dietary Fiber may be protective against type 2 diabetes is that it attenuates the glucose response and decreases insulin concentrations. This theory is supported by results from the Zutphen Elderly Study, where a negative relationship was observed between Dietary Fiber intake and insulin concentrations (Feskens et al. Intervention Studies In some clinical intervention trials ranging from 2 to 17 weeks, con- sumption of Dietary Fiber was shown to decrease insulin requirements in type 2 diabetics (Anderson et al.

Guidelines for evaluation of systematic reviews Were the question and methods clearly stated and were comprehensive search methods used to locate relevant studies? In meta-analysis discount tadalis sx online american express erectile dysfunction drugs least side effects, the process of article selection and analysis should proceed by a preset protocol 20 mg tadalis sx discount erectile dysfunction drugs. By not changing the process in mid-analysis the author’s bias and retrospective bias are minimized tadalis sx 20 mg free shipping what causes erectile dysfunction yahoo. This means that the definitions of outcome and predictor or therapy variables of the analysis are not changed in Meta-analysis and systematic reviews 369 mid-stream. The research question must be clearly defined, including a defined patient population and clear and consistent definitions of the disease, interven- tions, and outcomes. A carefully defined search strategy must be used to detect and prevent publi- cation bias. This bias occurs because trials with positive results and those with large sample sizes are more likely to be published. The bibliographies of all relevant articles found should be hand searched to find any misclassified articles that were missed in the origi- nal search. The authors must cite where they looked and should be exhaustive in look- ing for unpublished studies. Not using foreign studies may introduce bias since some foreign studies are published in English-language journals while others may be missed. The authors should also contact the authors of all the studies found and ask them about other researchers working in the area who may have unpublished studies available. Also, the National Library of Medicine and the National Institutes of Health in the United States have an online repository of clinical tri- als called www. Were explicit methods used to determine which articles to include in the review and were the selection and assessment of the methodologic quality of the primary studies reproducible and free from bias? Objective selection of articles for the meta-analysis should be clearly laid out and include inclusion and exclusion criteria. This includes a clearly defined research and abstraction method and a scoring system for assessing the quality of the included studies. The publication status may sug- gest stronger studies in that those that were never published or only published in abstract form may be significantly deficient in methodological areas. A well-designed obser- vational study with appropriate safeguards to prevent or minimize bias and con- founding, will also give very strong results. The methods of meta-analysis include ranking or grading the quality of the evidence. The study sites and patient populations of the individual studies may limit generalizability of the meta-analysis. We will discuss issues of how to judge homogeneity and combine heterogeneous studies. Independent review of the methods section looks at inclusion and exclusion criteria, coding, and replication issues. There must be accurate and objective abstraction of the data, ideally done by blinded abstracters. Two abstracters should gather the data independently and the author should check for inter- rater agreement. The methods and results sections should be disguised to pre- vent reviewers from discovering the source of the research. Once this has been established, a single coder can code all the remaining study results. Were the differences in individual study results adequately explained and were the results of the primary studies combined appropriately? Testing for heterogeneity of the stud- ies is done to determine if the studies are qualitatively similar enough to com- bine. The tests for heterogeneity include the Mantel–Haentszel chi-squared test, the Breslow–Day test, and the Q statistic by the DerSimonian and Laird method. However, the absence of statistical significance does not mean homogeneity and may only be present due to low power of the statistical test for heterogeneity. The presence of heterogeneity among the studies analyzed will result in erro- neous interpretation of the statistical results. If the studies are very heteroge- neous, one strategy for analyzing them is to remove the study with most extreme or outlier results and recalculate the statistic. If the statistic is no longer statisti- cally significant, it can be assumed that the outlier study was responsible for all or most of the heterogeneity. That study should then be examined more closely to determine what about the study design might have caused the observed extreme result. This could be due to differences in the population studied or systematic bias in the conduct of the study. Analysis and aggregation of the data can be done in several ways, but should consider sample sizes and magnitude of effects. A simple vote count in which the number of studies with positive results is directly compared with the number of studies with negative results is not an acceptable method since neither effect Meta-analysis and systematic reviews 371 size nor sample size are considered. Pooled analysis or lumped data add numer- ators and denominators of each study together to produce a new result. This is better than a vote count, but still not acceptable since that process ignores the confidence intervals for each study and allows errors to multiply in the process of adding the results. Simple combination of P values is not acceptable because this does not consider the direction of the effect or magnitude of the effect size. Weighted outcomes compare small and large studies, analyze them as equals, and then weight the results by the sample size. This involves adjusting each out- come by a value that accounts for the sample size and degree of variation. Con- fidence intervals should be applied to the mean results of each study evaluated. Aggregate study and control-group means and confidence intervals can then be calculated. Subgroups should be analyzed where appropriate, recognizing the potential for making a Type I error. There are two standard measures for evaluat- ing the results of a meta-analysis: the odds ratio and the effect size. The odds ratio can be calculated for each study showing whether the intervention increases or decreases the odds of a favorable outcome. These can then be combined statistically and the 95% confidence intervals calculated for all the odds ratios. If the data are skewed, it is better to use median rather than mean of the data to cal- culate the effect size, but this requires the use of other, more complex statistical methods to accomplish the analysis. The statistical analytic procedures usually employed in systematic reviews are far too complex to discuss here. However, there are important distinctions between the methods used in the presence and in the absence of heterogene- ity of the results of the studies, which the reader should be aware of.

Although the major sources of monounsaturated fatty acids (animal fat and vegetable oils) are not required to supply essential nutrients best tadalis sx 20mg relative impotence judiciary, very low intakes of monounsaturated fatty acids would require increased intakes of other types of fatty acids to achieve recommended fat intakes buy tadalis sx amex erectile dysfunction causes cures. Consequently purchase tadalis sx discount erectile dysfunction treatment urologist, intakes of saturated and n-6 polyunsaturated fatty acids would probably exceed a desirable level of intake (see “n-6 Poly- unsaturated Fatty Acids” and Chapter 8). High n-9 Monounsaturated Fatty Acid Diets There are limited data on the adverse health effects from consuming high levels of n-9 monounsaturated fatty acids (see Chapter 8, “Tolerable Upper Intake Levels”). Acceptable Macronutrient Distribution Range n-9 Monounsaturated fatty acids are not essential in the diet, and the evidence relating low and high intakes of monounsaturated fatty acids and chronic disease is limited. Many populations of the world, such as in Crete and Japan, have low total intakes of n-6 polyunsaturated fatty acids (e. However, high intakes of n-6 polyunsaturated fats have been associated with blood lipid profiles (e. An inverse association between linoleic acid intake and risk of coronary death was observed in several prospective studies (Arntzenius et al. Controlled trials have examined the effects of sub- stituting n-6 fatty acids in the diet to replace carbohydrate or saturated fatty acids (Mensink et al. Risk of Diabetes A number of epidemiological studies have been conducted to ascer- tain whether the quality of fat can affect the risk for diabetes. An inverse relationship was reported for vegetable fats and polyunsaturated fats and risk of diabetes (Colditz et al. One study reported a positive association between 2-hour glucose concentrations and polyunsaturated fatty acid intake (Mooy et al. A review of epidemiological studies on this relationship concluded that higher intakes of polyunsaturated fats could be beneficial in reducing the risk for diabetes (Hu et al. Risk of Nutrient Inadequacy Dietary n-6 polyunsaturated fatty acids have been reported to contrib- ute approximately 5 to 7 percent of total energy intake of adults (Allison et al. Oxidation products of lipids and proteins are found in athero- sclerotic plaque and in macrophage foam cells. Risk of Inflammatory Disorders There has been significant interest in the use of dietary n-6 fatty acids to modulate inflammatory response. The ∆6 desaturase enzyme is the initial step in desaturation of linoleic acid to arachidonic acid (see Figure 8-1). Epidemiological studies, however, suggest that n-6 polyunsaturated fatty acids are not associated (or have an inverse relationship) with cancer. Howe and coworkers (1990) analyzed 12 case- control studies conducted prior to 1990 and determined that the relative risk of breast cancer for an increment of 45 g of polyunsaturated fat per day was only 1. More recent case-control and prospective studies fur- ther support the minimal effect of n-6 polyunsaturated fatty acids on breast cancer risk (Männistö et al. A similar relation- ship has been reported for linoleic acid intake and prostate cancer (Giovannucci et al. The range of intake of polyunsaturated fat was sufficiently large in these combined studies to comfortably conclude that the epidemiological evi- dence largely contradicts the animal studies; at least to date, no association between polyunsaturated fat, mainly n-6 fatty acids, and risk of breast cancer has been detected. Furthermore, in a review of the literature and meta-analyses of case-controlled and prospective epidemiological studies, Zock and Katan (1998) concluded that it was unlikely that high intakes of linoleic acid substantially raise the risk of breast, colorectal, or prostate cancer. Risk of Nutrient Excess High intakes of linoleic acid can inhibit the formation of long-chain n-3 polyunsaturated fatty acids from α-linolenic acid, which are precursors to the important eicosanoids (see Chapter 8). Many of the epidemiological studies used fish or fish oil intake as a surrogate for n-3 polyunsaturated fatty acid intake. The amounts of n-3 fatty acids vary greatly in fish, however, and unless the amounts of n-3 fatty acids are known, any conclusions are open to question. Furthermore, other components in fish may have effects that are similar to n-3 fatty acids and therefore may confound the results. A similar result was found in Rotterdam that compared older people who ate fish with those who did not (Kromhout et al. In the Physicians’ Health Study, eating fish once per week decreased the relative risk of sudden cardiac death by 52 percent compared with eating fish less than once per month (Albert et al. In this study, although dietary total n-3 fatty acid intake correlated inversely with total mortality, no effect on total myocardial infarction, nonsudden cardiac death, or total cardiovascular mortality was observed. After adjustment for classical risk factors, the reduction was only 32 percent and no longer significant. There are fewer data with regard to the effects of fish and n-3 poly- unsaturated fatty acids on stroke. In the Zutphen Study, consumption of more than 20 g/d of fish was associated with a decrease in the risk of stroke (Keli et al. In contrast, in the Chicago Western Electric Study and the Physicians’ Health Study, fish intake was not signifi- cantly associated with decreased stroke risk (Morris et al. Some studies, however, did not show an effect on platelet aggregation after the consumption of 4. There was a significant reduction in risk for cardiac death for the experimental group after 27 months, and a reduction after a 4-year follow-up. The extent to which these reductions in risk were due to n-3 fatty acids is uncertain. This group also expe- rienced a 20 percent reduction in all-cause mortality and a 45 percent reduction in sudden deaths compared with the control group. Vitamin E, in contrast to n-3 polyunsaturated fatty acids, had no beneficial effects on cardiovascular endpoints. A meta-analysis of 31 placebo- controlled trials estimated a mean reduction in systolic and diastolic blood pressure of 3. Further- more, a statistically significant dose–response effect occurred with the smallest reduction observed with intakes of less than 3 g/d and the largest reduction observed with intakes at 15 g/d. Because impaired heart rate variability is associated with increased arrhythmic events (Farrell et al. However, the beneficial effect was found only in men with low initial heart rate variability. Several studies have examined whether n-3 polyunsaturated fatty acids affect growth of adipose tissue. Parrish and colleagues (1990, 1991) found that rats given a high fat diet supplemented with fish oil had less fat in perirenal and epididymal fat pads and decreased adipocyte volumes compared with rats fed lard. Adipose tissue growth restriction appeared to be the result of limiting the amount of triacylglycerol in each adipose tissue cell rather than by limiting the number of cells. The researchers concluded that the rats supplemented with n-3 fatty acids demonstrated reduced oxidation of fat and increased carbo- hydrate utilization. Little data exist with respect to the specific effects of dietary n-3 polyunsaturated fatty acids on adiposity in humans; therefore, prevention of obesity cannot be considered an indicator at this time. While several studies have reported a nega- tive relationship between polyunsaturated fatty acid intake and risk of diabetes (Colditz et al. A review of the epidemiological data on this association concluded that polyunsaturated fatty acids, and possibly long- chain n-3 fatty acids, could be beneficial in reducing the risk of diabetes (Hu et al. Studies conducted in rodents have shown that administration of fish oil results in increased insulin sensitivity (Chicco et al. Substituting a proportion of the fat in a high fat diet with fish oil prevented the devel- opment of insulin resistance in rats (Storlien et al.

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