Introduction: safety and regulatory issues related to the use of macronutrient substitutes in the food supply.
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Fat facets is a Drosophila deubiquitinating enzyme required for eye development and early embryogenesis. Genetic evidence suggests that Fat facets deubiquitinates and thereby prevents the proteasomal degradation of specific substrates. The Drosophila Liquid facets protein is implicated as the critical substrate of Fat facets in the eye. A mouse homolog of Fat facets, called Fam, has been identified. The results of biochemical experiments implicate two different proteins, Af-6 and beta-catenin, as substrates for Fam. Here, the functional relationship between Fat facets and Fam is explored. We show that Fam can substitute for Fat facets in all of its essential functions in Drosophila. In addition, we tested the hypothesis that Canoe and Armadillo, the Drosophila homologs of Af-6 and beta-catenin, respectively, are important substrates for Fat facets in the Drosophila eye. We found no genetic evidence to support a role for either Canoe or Armadillo in the essential Fat facets pathways in Drosophila eye development. The significance of these results is discussed in light of the biochemical experiments that suggest that Af-6 and beta-catenin are substrates of Fam.
There are reasons to suspect that dietary changes through adult life may modify risk for some cancers. We examined the association of recent and past dietary habits and changes in dietary intake over time with ovarian cancer risk. Long-term nutritional assessment was performed retrospectively in 631 incident cases of invasive epithelial ovarian cancer and in 1174 matched controls (matched by age +/- 2 y, country of origin, and period of immigration) as part of a nationwide case-control study of ovarian cancer conducted between the years of 1994 and 1996 in Israel. Using a 2-step quantified Food Frequency Questionnaire, participants were first asked about their consumption of food items 1 y prior to the interview, and then whether their consumption had changed over time. The time of the change and consumption level before the change were recorded, allowing reconstruction of daily intakes for several time points. The reported mean percentage of animal fat intake decreased by 1.3% in cases but by 1.9% in controls (P for difference = 0.003). Conditional multivariate logistic regression was used to estimate odds ratios adjusted for total energy, parity, and oral contraceptive use. Substituting nonanimal fat in preference to animal fat over a relatively short term (between 2 and 7 y prior to interview) decreased the risk of ovarian cancer [OR = 0.65/100 kcal (418.4 kJ), 95% CI = 0.50 - 0.85]. Our results suggest that substitution of nonanimal for animal fat during adult life might reduce the risk of ovarian cancer, but this requires confirmation in prospective studies.
The objective of this study was to examine the effects of the intake of dietary fat upon colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. Original data records for 5,287 cases of colorectal cancer and 10,470 controls were combined. Logistic regression analysis was used to estimate odds ratios (OR) for intakes of total energy, total fat and its components, and cholesterol. Positive associations with energy intake were observed for 11 of the 13 studies. However, there was little, if any, evidence of any energy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01, 1.02, and 0.92 for quintiles of residuals of total fat intake (P trend = 0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (P trend = 0.39). The analysis suggests that, among these case-control studies, there is no energy-independent association between dietary fat intake and risk of colorectal cancer. It also suggests that simple substitution of fat by other sources of calories is unlikely to reduce meaningfully the risk of colorectal cancer.
Considering that over half of Americans will die from cardiovascular disease, the over-whelming majority of those deaths being from atherosclerosis, we need to accept and act on the vast body of information derived from investigation of coronary risk factors. Identification of persons at risk needs to be done early--when the patient is in his or her 20s or 30s--not after an infarction has occurred or an angiogram indicates a problem. Although high serum lipid levels are obviously not the only factor involved in development of atherosclerosis, their early identification is a simple, cost-effective way to start preventive care. The concept of "normal" levels of cholesterol and triglyceride must be revised, and that of "safe" levels should be adopted instead. Patients with abnormal electrophoretic patterns should not be the only target; they are only the tip of the iceberg. A typical workup in a young patient consists merely of measurement of cholesterol and triglyceride levels. Further evaluation is necessary if the levels are high or the family history suggests a problem. Lipoprotein electrophoresis and computation of the ratio of high-density lipoprotein to low-density lipoprotein are then used not just as predictors but as a guide to therapy. Basic therapy begins with a change in life-style to incorporate dietary reduction of saturated fats and cholesterol and substitution of polyunsaturated fats. Other measures such as cessation of cigarette smoking, introduction of an appropriate exercise program and, most importantly, reduction of body weight complete the game plan.(ABSTRACT TRUNCATED AT 250 WORDS)
To identify systematically the nutrient and food group intakes associated with a low-fat diet, the authors used the detailed dietary information collected from 10,306 individuals aged 32-86 years in the 1982-1984 National Health Epidemiologic Follow-up Study. Intakes of vitamin C and percentages of calories from carbohydrates, dietary fiber, poultry, low-fat dairy products, fruits, vegetables, cereals, and whole grains were markedly higher, while intakes of protein, total fat, saturated fat, oleic and linoleic acids, cholesterol, sodium, all red meats, high-fat dairy products, eggs, nuts, white bread, fried potatoes, desserts, fats, and oils were much lower in the quartile with the lowest percentage of calories from fat. These dietary patterns associated with a low-fat diet were essentially constant across strata of age, sex, race, and socioeconomic status. This study suggests that individuals on a low-fat diet substitute certain carbohydrate-rich foods such as fruits and vegetables for fat. Given these associations between low-fat diets and other dietary factors independently associated with certain cancers, these dietary factors should be considered potential confounders in studies of dietary fat and these cancers.
One hundred and ten adult out-patients entered a prospective study of the effect of dietary control of hyperlipidaemia. Seventy-nine were male and 31 female. Eighty-four patients had primary type II and 26 had primary type IV hyperlipidaemia. Cases of secondary hyperlipidaemia were excluded. Patients with type II hyperlipidaemia were treated with a diet low in saturated fat and cholesterol, with substitution of polyunsaturated fats. Additional carbohydrate and alcohol restriction was applied to patients with type IV hyperlipidaemia. Calorie restriction was prescribed for overweight patients. In type II patients, mean serum cholesterol fell from 322 to 286 mg per 100 ml, and weight from 159 to 152 lb over the first six months of treatment. In type IV patients cholesterol fell from 328 to 281 mg per 100 ml, triglycerides from 389 to 241 mg per 100 ml and weight from 166 to 156 lb over the same period. All reductions were statistically significant at the 1 per cent level. No statistical correlation was observed between reduction of weight and reduction in lipid levels. Over a three-year follow-up period no tendancy for lipid levels or weight to 'rebound' was noted. It is concluded that diet can produce a significant reduction in plasma lipid levels over six months in some hyperlipidaemic patients. Further follow-up is continuing to determine whether this effect can be maintained over the longterm.
A prospective study of the effect of dietary control of hyperlipoproteinemia (HLP) was carried out in 1,800 adult out-patients. The patients with type II A were treated with a diet low in saturated fat and cholesterol, with substitution of polyunsaturated fat. Additional carbohydrate and alcohol restriction was applied to patients with types II B, III and IV HLP. Caloric restriction was prescribed for overweighted patients. These diets were followed by sequences of stabilizing diets which were modified quarterly. After 7 years the best results were obtained for type IV (50%) followed by II B (22%). The nutritional HLP treatment, in keeping with the metabolic dependence, corrected HLP to one third of the initial sample, without improving the objective cardiovascular disturbances.
The effects of intraduodenal and dietary lipid on alertness, mood and performance in a task requiring sustained attention were investigated in two studies. The first experiment compared the effect of duodenal infusion of either 100 g/l Intralipid (8.36 kJ/min) or isotonic saline (9 g NaCl/l) in paired studies carried out on two non-consecutive days on five male volunteers. Two consecutive 3 h infusions, one of lipid, the other saline, were given blind on each day using a crossover design. Analysis of variance indicated that lipid significantly reduced alertness (P < 0.05) and affected the speed and accuracy of performance in a sustained attention task (P < 0.05). A second experiment compared the effects on eight male volunteers of two isoenergetic lunches of similar appearance, taste and protein content but differing fat and carbohydrate (CHO) contents (fat energy:CHO, 64:18 v. 7:76). Alertness was lower (P < 0.05) and responses to stimuli in a sustained attention task were slower after the high-fat meal than after the low-fat meal (P < 0.05). In conclusion, infusion of lipid into the small intestine, and the substitution of fat for carbohydrate while keeping energy and protein constant in a lunch, both cause an enhanced postprandial decline in alertness and concentration. This may be related to the presence of lipid in the small intestine.
As a consequence of an increasing awareness and findings about the technical and analytical difficulties related to the employment of triglycerides as fatty food simulants in migration testing, EU Directive 82/711/EEC on the basic rules of migration has been amended for the second time and adapted with the recent Commission Directive 97/48/EC. The major merit of this important amendment is to authorize alternative tests such as extraction tests and to allow substitute tests for the fat test with concrete indication of corresponding test conditions to be applied. As a novelty in food law compliance testing it authorizes a modified polyphenylene oxide (MPPO), well-known as Tenax, a thermostable and highly adsorptive porous polymer, as a 'solid' matrix to substitute fat simulant D at temperatures equal to or higher than 100 degrees C. In the study presented here, comparative migration testing--overall and specific--was carried out between fat simulants olive oil and 14C-labelled HB 307 and the substitute test media iso-octane, 95% ethanol and MPPO using polypropylene materials as examples at test temperatures of 100 degrees C to 120 degrees C and prescribed corresponding substitute test conditions. As a consequence, a number of conclusions were drawn which are relevant for overall and/or specific migration testing under the investigated test conditions. One of the major findings was that MPPO was generally more equivalent to the fat test than the other two substitute test media. The presence of volatile hydrocarbons in the test samples was found to play a crucial role with respect to the equivalence of the iso-octane-based substitute test. At high volatile concentrations in the test sample the iso-octane test underestimated the olive oil benchmark whereas low volatile concentrations led to satisfying equivalence. It is therefore recommended that the procedure is modified and GC-FID screening of the isooctane extract is carried out. As a logical consequence, the possibility of quantitative determination of the overall extract by GC-FID is recommendable and should be investigated in more depth. Concerning the overall migration test procedure in olive oil, the vacuum pre-conditioning at 60 degrees C should be given re-consideration to avoid the possibility of loss of volatile migrants whose determination should be within the scope of the overall migration test method itself. Finally, the specific migration related equivalence between olive oil, MPPO and iso-octane needs further investigations to clarify the net effect of strongly increased diffusion rates at the regular high temperature versus the substitute test solvent accelerated extraction effect at 60 degrees C. Stability aspects of migrants at the different test temperatures deserve further consideration.
Defective lipolysis, steatorrhea, and hypocholesterolemia characterize pancreatic insufficiency. Lipid metabolism in pancreatic insufficiency was studied by measuring serum lipoproteins, cholesterol absorption with double labels and serum plant sterols, and bile acid and cholesterol synthesis with fecal and dietary steroid analysis and cholesterol precursor sterols before and during exogenous pancreatic enzyme substitution. Baseline fecal fat, masses, bile acids and neutral steroids, and cholesterol synthesis were increased, whereas cholesterol absorption was markedly reduced. In fact, the present data suggest that sterol absorption may be disturbed more sensitively than fat absorption in pancreatic insufficiency. Enzyme substitution significantly reduced fecal fat, masses, bile acids and neutral steroids, and synthesis of cholesterol and improved cholesterol absorption in relation to serum cholesterol, although normal values were not obtained. Serum level of high-density lipoprotein cholesterol was significantly elevated by exogenous enzymes, whereas levels of cholesterol or triglycerides in other lipoproteins remained unchanged. Improved sterol absorption increased also serum levels of plant sterols and reduced levels of cholesterol precursors and cholesterol synthesis and precursor sterol-plant sterol ratios. Thus, reduced intestinal lipolysis with expanded oil phase appears to be a major reason for impaired cholesterol absorption, causing enhanced cholesterol and, consequently, bile acid synthesis and reduced serum cholesterol level. Exogenous enzyme substitution seems partly to correct these abnormalities, improvements of which can be monitored by the gas-liquid chromatographic determination of serum plant sterols or cholesterol precursor-plant sterol ratios.
Restriction of fatty foods is an effective means of reducing caloric intake and is consistent with public health goals to reduce the risk of chronic diseases. Compliance with low-fat diets is enhanced by the substitution of foods with the same organoleptic properties as fat, namely flavor, texture, and mouth-feel. Fat substitutes could replace a significant proportion of dietary fat and as such become macronutrient substitutes. The safety of these materials must be established prior to introduction into the food supply. As their use increases so will concerns about their safety. Appropriate methods of safety evaluation must be used. Traditional methods for the safety evaluation of food additives are inappropriate, since concentrations of the test materials high enough to provide a 100-fold safety factor cannot be used. An approach that recognizes the unique nature of macronutrient substitutes and includes the use of in vitro, whole-animal, and human studies and nutritional, physiological, and toxicological end points is proposed. Evaluations in humans are conducted early in this program but only when the animal data adequately support these studies. Human data will complement the animal data and may eliminate the need for some animal studies. The introduction of postmarketing surveillance will identify consumption patterns, associated adverse reactions, and potentially sensitive segments of the population and will ensure the continued safety of macronutrient substitutes.
The increasing popularity of low-fat products increases the need for a better understanding of how flavor release is affected by partial substitution of fat with hydrocolloids. Partitioning and release of aroma compounds from four pectin gels with different compositions were studied with static headspace and with a model mouth. Air/product partition coefficients determine the potential extent of aroma release, and mass transfer determines the rate at which aroma compounds are released to the vapor phase. This study showed that the gel network had large effects on the partition of aroma compounds between the gel and vapor phase. The specific properties of the aroma compounds were also of importance for the air/gel partition. Storage of the four gels showed that one of the weaker gels was influencing the concentration of aroma compounds in the headspace, probably caused by formation of a denser network over time.
OBJECTIVE: To determine the influence of central obesity and type 2 diabetes on peripheral wave reflection in Indigenous Australians. DESIGN AND METHODS: A cross-sectional study of remote Indigenous Australians with (n = 43) and without (n = 54) type 2 diabetes of similar age (47 years) and sex; using anthropometric and bioelectrical impedance measures of obesity and applanation tonometry to determine the aortic augmentation index (AI) as an index of peripheral wave reflection. RESULTS: Indices of obesity were significantly higher in the diabetic than non-diabetic participants [body mass index (BMI): 27.3 versus 24.6 kg/m, P = 0.018; waist circumference: women 101 versus 94 cm, P = 0.008, men 102 versus 91 cm, P = 0.039]. AI was negatively related to obesity: BMI (r = -0.35, P = 0.0003), weight (r = -0.44, P < 0.0005), waist circumference (r = -0.34, P = 0.0003) and fat mass (r = -0.35, P < 0.0005). There was no significant difference in AI between the groups with and without diabetes. On multiple regression analysis, 66% of the variance in AI was explained with the following significant predictors: age, heart rate, male gender, fat mass and mean arterial pressure. Similar results were obtained when weight, waist circumference or BMI were substituted for fat mass. CONCLUSION: When compared with Indigenous Australians without diabetes, those with type 2 diabetes do not have greater aortic pressure augmentation from peripheral wave reflection. However, obesity, irrespective of the index used, was related to lower peripheral wave reflection in both those with and without type 2 diabetes.
Our aim was to determine the effects of the substitution of sucrose polyester (SPE) for dietary fat in a 16-week outpatient study in 36 obese subjects with primary hypercholesterolemia. The subjects were randomized into three groups who followed a 16-week treatment period where all subjects received hypocaloric diets which provided approximately 7 kcal/lb body weight, a polyunsaturated/saturated (P/S) fat ratio of 0.9, and 180 mg cholesterol/day. The percentages of calories as fat in the 3 groups were as follows: a low fat diet group (n = 12) received 27% of dietary calories as fat, a low fat plus SPE group (n = 13) received 25% of calories as fat plus 27 g SPE/day as a bread spread and salad dressing, and a third group (placebo, n = 11) received 37% of calories as fat with a 27 g/day conventional fat placebo (bread spread and salad dressing). Mean weight loss from baseline in the 16 week treatment period was 2.6, 3.9, and 3.4% respectively in the placebo, diet, and SPE groups, p less than .05 for each group, without significant differences between the groups. There was a mean reduction of low density lipoprotein cholesterol (LDL-C) of 16% in the SPE group (p less than .05), more than twice the reductions in the placebo and diet groups, 5% and 6%, respectively. There was a mean 20% reduction in the SPE group in triglyceride and very low density lipoprotein cholesterol (p less than .05), compared to 7 and 10% reductions in the placebo and diet groups respectively. The degree of weight loss was correlated with the degree of reduction in LDL-C in the low fat diet group, and in the low fat diet group plus SPE (r = 0.59 for both groups). Without confounding by different levels of dietary cholesterol or P/S, SPE induced significant reductions in LDL-C in hypercholesterolemic obese subjects beyond the effects of weight loss alone. The effects of SPE were significantly greater than those achieved by the use of a diet which severely limited conventional dietary fat intake (to 40 g/day). SPE in the form of a bread spread and a salad dressing is a practical formulation for outpatient hypocholesterolemic low fat diets and provides the lubricity and organoleptic benefits of authentic foods without the dense caloric content of digestible fats.
The potential for achieving the NACNE target for percentage of energy derived from fat (34 per cent), resulting from the theoretical substitution of skimmed milk for high-fat milks, was investigated using the dietary records of 738 middle-aged males and females in the South Wales area. The average male in the sample could theoretically achieve the NACNE target by changing to skimmed milk providing that energy intake remained the same. In the small sample of women the average female could not reach the NACNE target. Four groups of individuals were identified: -(1) Those consuming diets providing less than 34 per cent of total energy from fat; (2) those unable to reach the NACNE target by changing to skimmed milk; (3) those who could reach the NACNE target by changing to skimmed milk even if they remained in energy deficit; (4) those who could reach the NACNE target by changing to skimmed milk providing that they made up the lost energy by eating foods free of fat. A graph is presented which would enable a trained person to assess whether substitution of skimmed for high-fat milks would result in an individual achieving the NACNE recommendation.
Six groups of rats were fed diets containing 40% (by weight) lipids, mostly as saturated fatty acids (from 78 to 90%), with a basic amount of linoleic acid (18:2) (1.9%). In four groups, 5% of the saturated fats were substituted with an oil (vegetable: corn, rapeseed; or fish: cod liver, maxepa) and in one group 0.6% of the saturated fats was replaced by eicosapentaenoic acid ethyl ester. The diets supplied different amounts of 18:2 (1.9 to 10%), 18:3 (0.2 to 1.2%), 20:5 (n--3) (eicosapentaenoic acid) (0 to 1.3%) and 22:6(n--3) (0 to 1.6%). After 3-8 months on diets, platelet aggregation, plasma and platelet cholesterol, fatty acids and incorporation of [14C]acetate and [14C]arachidonate into platelet lipids were investigated. The three diets supplying eicosapentaenoic acid (1.3%) induced an approximately 80-fold increase in this fatty acid in plasma and platelet phospholipids, mainly at the expense of arachidonic acid. This was associated with an increase of the incorporation of arachidonic acid into platelet PE and PS. The incorporation of acetate in the (n--3) fatty-acid-fed animals was markedly increased into 22:5 and 22:6(n--3) at the expense of 22:4(n--6). Platelet aggregation induced by ADP was similar in the six groups. The response to thrombin was lower in animals fed corn and maxepa oils. Collagen aggregation tended to be lower in the fish-oil groups. Platelet aggregation to collagen was significantly negatively correlated to the level of eicosapentaenoic acid in platelet phospholipids, while the aggregation to thrombin was related to the level of 20:3(n--9). In the present study in rat, the (n--3) fatty acids added in small amounts to a saturated fat diet over a period of several months induced drastic changes in platelet lipid metabolism and composition without comparable effects on platelet behaviour.
OBJECTIVE: To examine, in free-living adults eating self-selected diets, the effects on plasma cholesterol of substituting saturated fat rich foods with either n-6 polyunsaturated or monounsaturated fat rich foods while at the same time adhering to a total fat intake of 30-33% of dietary energy. DESIGN: Two randomised crossover trials. SETTING: General community. SUBJECTS: Volunteer sample of healthy free-living nutrition students at the University of Otago. Trial I, n=29; and trial II, n=42. INTERVENTIONS: In trials I and II participants were asked to follow for 2(1/2) weeks a diet high in saturated fat yet with a total fat content that conformed to nutrition recommendations (30-33% energy). During the 2(1/2) week comparison diet, saturated fat rich foods were replaced with foods rich in n-6 polyunsaturated fats (trial I) whereas in trial II the replacement foods were rich in monounsaturated fats. Participants were asked to maintain a total fat intake of 30-33% of energy on all diets. MAIN OUTCOME MEASURES: Energy and nutrient intakes, plasma triglyceride fatty acids, and plasma cholesterol. RESULTS: When replacing saturated fat with either n-6 polyunsaturated fat or monounsaturated fat, total fat intakes decreased by 2.9% energy and 5.1% energy, respectively. Replacing saturated fat with n-6 polyunsaturated fat (trial I) lowered plasma total cholesterol by 19% [from 4.87 (0.88) to 3.94 (0.92) mmol/l, mean (s.d.)], low density lipoprotein cholesterol by 22% [from 2.87 (0.75) to 2.24 (0.67) mmol/l], and high density lipoprotein cholesterol by 14% [from 1.39 (0.36) to 1.19 (0.34) mmol/l], whereas replacing saturated fat with monounsaturated fat (trial II) decreased total cholesterol by 12%, low density lipoprotein cholesterol by 15%, and high density lipoprotein cholesterol by 4%, respectively. The change in the ratio of total to high density lipoprotein cholesterol was similar during trial I and trial II. CONCLUSIONS: Young adults are very responsive to dietary-induced changes in plasma cholesterol even when an isocaloric replacement of saturated fat with n-6 polyunsaturated or monounsaturated fat is not achieved. Replacing saturated fat with either n-6 polyunsaturated or monounsaturated fat is equally efficacious at reducing the total to high density lipoprotein cholesterol ratio. SPONSORSHIP: University of Otago, Meadow Lea Ltd.