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Daily intake of multivitamins during long-term intake of olestra in men prevents declines in serum vitamins A and E but not carotenoids.

The objective of this study was to determine whether vitamin supplementation during long-term (36 wk) ingestion of olestra supplemented with vitamin E could prevent decreases in vitamin E, vitamin A, and carotenoids. This was a 36-wk study of 37 healthy males randomly assigned to consume a control diet composed of 33% energy from fat, a similar diet in which one third of the energy from fat had been replaced with olestra, or a fat-reduced (25% of energy from fat) diet. Subjects also ingested a daily multivitamin (Centrum). Serum concentrations of alpha-tocopherol, retinol, beta-carotene, lycopene, and lutein + zeaxanthin were analyzed by HPLC. Subjects eating the olestra-containing diet had substantial decreases in serum beta-carotene, lycopene, and lutein + zeaxanthin, which occurred by 12 wk; these changes were found despite correcting for serum total cholesterol or BMI. Serum beta-carotene and lycopene concentrations were below the lower limit of the reference range (<0.186 and <0.298 mumol/L, respectively) at one or more time points. The slight decline in serum alpha-tocopherol concentration, significant at 24 wk, was caused by the decline in serum cholesterol. Retinol concentrations decreased with time in all 3 groups, but were not affected by olestra. We conclude that supplementation with a multivitamin containing vitamins A and E was adequate to prevent olestra-induced decrease in serum alpha-tocopherol and retinol. Olestra-induced decreases in serum beta-carotene, lycopene, and lutein + zeaxanthin were not prevented by the vitamin supplement used in this study.

Adult↗

Long-term effects of polyacrylamide hydrogel on human breast tissue.

Polyacrylamide hydrogel is an atoxic, stable, nonresorbable sterile watery gel consisting of approximately 2.5% cross-linked polyacrylamide and nonpyrogenic water. Polyacrylamide hydrogel is widely used in ophthalmic operations, drug treatment, food packaging products, and water purification. In the former Soviet Union, polyacrylamide hydrogel has been used in plastic and aesthetic surgery for more than 10 years, and Kiev City Hospital treats approximately 300 women a year for breast augmentation using the polyacrylamide hydrogel Interfall (Contura SA, Montreux, Switzerland). Capsule shrinkage following these injections has never been observed. The authors examined breast tissue samples from a total of 27 women who had polyacrylamide hydrogel injected at Kiev City Hospital up to 8 years and 10 months earlier. Age at operation, duration of polyacrylamide hydrogel implantation, history of possible side effects to the gel injection, other intercurrent diseases, the reason for present open breast operation, and breast palpation findings before operation were in each case compared with the histological findings on samples taken from breast tissue bordering the gel. The gel presented itself as a dark violet, homogenous mass with a rounded or ragged outline in large or medium-size deposits and as elongated strands, which mimicked the extracellular matrix, in small deposits. Histological findings of the breast tissue bordering the gel showed three different patterns: large collections of gel gave rise to a thick, soft-looking cellular membrane of macrophages and foreign-body giant cells; medium-size deposits were surrounded by just a thin layer of macrophages; and small deposits were not associated with any reaction in the surrounding tissue. Projections of the cellular soft membrane, known as granulomas, were seen in six patients. The granulomas were composed of macrophages, foreign-body giant cells, lymphocytes, and blood cells. A thin layer of fibrous connective tissue was occasionally present around the foreign-body membrane, but the thick fibrous capsule, which has been described in connection with silicone implants, was completely absent. The gel changes could be correlated to neither time since gel injection nor a history of recent injury or inflammation. It is concluded that the polyacrylamide hydrogel Interfall, which has been used in the former Soviet Union, is stable over time, nondegradable, confined to the breast, and diffusion and migration resistant. When the hydrogel is injected in medium-size or large quantities a cellular foreign-body reaction occurs, but in small amounts it is capable of splitting up individual connective tissue fibers and fat cells, substituting for the extracellular connective tissue matrix without eliciting any foreign-body reaction. As far as these data are concerned, polyacrylamide hydrogel is well tolerated by the breast and does not give rise to severe fibrosis, pain, or capsule shrinkage. However, to determine safety with more certainty, a larger sample size would be necessary.

Acrylic Resins↗

Phytosterol additives increase blood pressure and promote stroke onset in salt-loaded stroke-prone spontaneously hypertensive rats.

1. To assess the effect of dietary phytosterol on stroke and the lifespan of salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP), we investigated the effects of the addition of phytosterol to soybean oil (phytosterol content: 0.3%) on stroke onset, lifespan following onset of stroke and overall lifespan compared with canola oil (phytosterol content: 0.9%). 2. Six-week-old male SHRSP were fed a test diet prepared by the addition of canola oil (CA diet), soybean oil (SO diet), soybean oil plus 0.6% phytosterol (SO + 0.06P diet) or soybean oil plus 4.5% phytosterol (SO + 0.45P diet) as a 10% fat source. 3. Systolic blood pressure (SBP) increased in the SO + 0.06P and SO + 0.45P groups compared with the SO group and the increase was dependent on the amount of phytosterol added, indicating that the addition of phytosterol to soybean oil may promote an increase in SBP in salt-loaded SHRSP. 4. The onset of stroke was shortest in the SO + 0.45P group and survival after the onset of stroke was shortest in the CA group. Consequently, the SO + 0.45P and CA groups showed marked lifespan shortening, indicating that a fivefold greater amount of phytosterol was required to produce an effect equivalent to that of canola oil. 5. Investigation of the mRNA expression of ATP-binding cassette (ABC) transporters involved in intestinal phytosterol absorption indicated significant decreases in the intestinal mRNA expression of Abcg5 and Abcg8 in SHRSP and Wistar-Kyoto rats compared with Wistar rats. 6. In conclusion, the addition of phytosterol to soybean oil elevated SBP and promoted the onset of stroke, which may cause a reduction in survival time. However, a fivefold greater amount of phytosterol was required to produce an effect that was equivalent to the survival time-shortening effect of canola oil. The significant decrease in the intestinal mRNA expression of Abcg5 and Abcg8 in SHRSP may be responsible, at least in part, for the unfavourable effects observed following the addition of phytosterol.

ATP-Binding Cassette Transporters↗

Ethanol-related changes in liver microsomes and mitochondria from the monkey, Macaca fascicularis.

Four Macaca fascicularis monkeys were maintained 1 year on a liquid diet containing 26% of calories as ethanol. Four control animals were fed a liquid diet of equivalent calories with protein, carbohydrate, and fat being substituted for ethanol calories. In liver mitochondria prepared from ethanol-fed monkeys (ethanol mitochondria), respiratory control was lowered 20% due to a decrease in state 3 respiration (28%). This was also accompanied by a 20% decrease in ADP translocation into ethanol mitochondria. The major change was a 61% decrease in cytochrome oxidase activity. The respiratory rate in the presence of uncoupler was also lowered 14%, but the decrease was not statistically significant. In contrast with our earlier observations with Macaca nemestrina, no significant ethanol-induced changes were observed in enzyme activities associated with the microsomal electron transport system, and no ethanol-elicited fatty liver was evident. The major changes in fatty acid composition of microsomal and mitochondrial phospholipids were increased amounts of palmitoleic and oleic acids, and decreased amounts of linoleic and arachidonic acids.

Animals↗

Standardization of a simplified scintigraphic methodology for the assessment of gastric emptying in a multicenter setting.

OBJECTIVE: Scintigraphy remains the gold standard to study gastric emptying. The technique is onerous and normal values vary between centers. Standardized protocols, although desirable, are not presently available. We validated a simplified scintigraphic protocol in a multicenter setting. METHODS: In 69 healthy volunteers from seven Canadian institutions, gastric emptying of a standard meal (99mTc-labeled beef liver) was assessed by scintigraphy every 10 min for 1 h, then every 20 min for the next 2 h. Gastric retention was fitted to a power exponential model, Prop(t) = (-(kappat)beta) with Prop(t) = proportion of retention at time t, either using all 13 time intervals (conventional technique) or using measurements at 0, 1, 2, and 3 h (simplified technique). RESULTS: The power exponential model yielded identical emptying curves and T 1/2 values with both techniques. Gastric emptying was more rapid in men than in women < 35 yr (p<0.01) and in younger than in older men (p<0.005). Gastric emptying was slower in women from Québec than in women from Ontario (p<0.04). Gastric retention was similar at 1, 2, and 3 h among the seven centers. Gastric emptying of a beef liver meal was slower than that of a low fat egg substitute (p<0.03). CONCLUSIONS: A simpler scintigraphic approach, using four rather than 13 samples, provides results comparable to those of the conventional technique. This simpler approach provides an economical, yet accurate, alternative to the techniques presently used and is applicable to a multicenter setting.

Adult↗

Effects of wheat bran and Olestra on objective measures of stool and subjective reports of GI symptoms.

OBJECTIVE: The aim of this study was to compare the effects of two nondigested, nonabsorbed dietary components on objective and subjective measures of gastrointestinal (GI) function. METHODS: A placebo-controlled parallel study compared the effects of wheat bran (20 g/day or 40 g/day in cereal), a well-known dietary fiber, with those of olestra (20 g or 40 g/day in potato chips), a nonabsorbed fat, on stool output, stool apparent viscosity (log peak force for extrusion [PF]), stool water content, and GI symptoms. Sixty subjects resided on a metabolic ward for 9 days: 3 days baseline and 6 days treatment. RESULTS: Compared with placebo, consumption of 20 g/day wheat bran for 6 days resulted in a rapid (within 38 h) increase in mean (+/-SE) stool output (placebo, 150 +/- 29 g/day; bran, 246 +/- 35 g/day, p < 0.05), a directional increase in mean stool water content (placebo, 81.2 +/- 0.8%; bran, 83.9 +/- 0.8%), stool water output (placebo, 159 +/- 54 g/day; bran, 238 +/- 30 g/day), and bowel movement frequency (BM/day) (placebo, 2.2 +/- 0.4; bran, 2.6 +/- 0.4), and no stool-softening effect (placebo log PF, 2.9 +/- 0.1 g; bran log PF, 2.9 +/- 0.1 g). Wheat bran 40 g/day results were not significantly different from wheat bran 20 g/day. Compared with placebo, consumption of olestra 20 g/day and 40 g/day for 6 days showed no significant difference in mean stool output (151 +/- 18 g/day and 204 +/- 28 g/day, respectively), mean BM frequency (1.8 +/- 0.2 BM/day and 2.1 +/- 0.3 BM/day, respectively), and stool water output (138 +/- 13 g/day and 184 +/- 31 g/day, respectively), a significant (p < 0.05) decrease in stool water content (75.5 +/- 1.7% and 72.6 +/- 2.2%, respectively), and either no effect on stool apparent viscosity (olestra 20 g/day, mean log PF, 3.0 +/- 0.1 g) or a gradual stool-softening effect beginning study day 6 (olestra 40 g/day, log PF, 2.7 +/- 0.1 g). None of the treatment groups showed a significant increase in GI symptoms compared with placebo. CONCLUSIONS: Consumption of wheat bran in excess of levels in a typical Western diet significantly increased stool output, but did not soften normal-viscosity stool nor result in an increase in common GI symptoms. The observed plateau effect for wheat bran at 40 g/day suggests a maximal mechanical stimulatory effect. Consumption of olestra in excess of usual snacking conditions did not result in a significant increase in stool output or common GI symptoms. At the highest level tested, olestra resulted in a gradual stool-softening effect after several days of consumption.

Adolescent↗

Effects of yo-yo diet, caloric restriction, and olestra on tissue distribution of hexachlorobenzene.

Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the environment and animal tissues. They enter the body in food and are stored in adipose tissue. Loss of body fat through caloric restriction mobilizes stored lipophilic xenobiotics and results in distribution to other tissues. We have studied the reversibility of this process in mice that followed a regimen of body weight cycling. Weight gain was followed by weight loss, a second gain, and a second loss ("yo-yo diet regimen"). We measured the distribution of orally gavaged [14C]hexachlorobenzene, which is sparingly metabolized. We found that weight cycling has different effects in different organs. Continued weight loss resulted in a threefold increase of 14C amount and concentration in the brain. After weight regain, 14C in the brain decreased but then increased again after a second weight loss. Weight loss resulted in an increase in the concentration of 14C in adipose tissue without changing the total amount in that tissue. Weight loss and regain resulted in an increase of 14C in the liver, which reflected an increase of fat in the liver. The regimen of weight gain and loss was repeated in mice gavaged with [14C]hexachlorobenzene, with one group receiving the nonabsorbable fat olestra in the diet. Combined dietary olestra and caloric restriction caused a 30-fold increase in the rate of excretion of 14C relative to an ad libitum diet or a reduced caloric diet alone. Distribution of 14C into the brain resulting from the restricted diet was reduced by 50% by dietary olestra.

Adipose Tissue↗

Intestinal alkaline phosphatase release is not associated with chylomicron formation.

Intestinal alkaline phosphatase (IAP) is one of the major sources of alkaline phosphatase in circulation. It is secreted into the intestinal lumen, serum, and lymph. After the ingestion of lipid, lymphatic alkaline phosphatase secretion increases significantly. We have found that the nonabsorbable fat olestra is unable to stimulate lymphatic alkaline phosphatase secretion. We also found that the hydrophobic surfactant Pluronic L-81, which blocks chylomicron formation, fails to inhibit this increase in lymphatic alkaline phosphatase secretion. These results suggest that it is the lipid uptake into the mucosa and/or reesterification to form triacylglycerols, but not the formation of chylomicrons, that is necessary for the stimulation of the secretion of alkaline phosphatase into the lymph.

Alkaline Phosphatase↗

Exercise prevents the accumulation of triglyceride-rich lipoproteins and their remnants seen when changing to a high-carbohydrate diet.

We tested the hypothesis that daily aerobic exercise opposes the fasting hypertriglyceridemia and exaggerated postprandial lipemia observed after substituting dietary fat with carbohydrate. Eight healthy postmenopausal women aged 51 to 66 years consumed the same high-fat mixed meal on 3 occasions: (1) after 3 days on a low-carbohydrate diet (35%, 50%, and 15% energy from carbohydrate, fat, and protein, respectively); (2) after 3 days on an isoenergetic high-carbohydrate diet (corresponding values 70%, 15%, and 15%); and (3) after 3 days on the same high-carbohydrate diet with 60 minutes of brisk walking daily. Plasma triglycerides were higher after the high-carbohydrate diet than after the low-carbohydrate diet: fasting, 1.58+/-0.19 versus 0.96+/-0.12 mmol/L, respectively; 6-hour postprandial area under concentration versus time curve, 13.74+/-1.57 versus 10.12+/-1.15 (mmol/L)xhour, respectively (both P<0.01). In the fasted and postprandial states, concentrations of apolipoproteins B-48 and B-100 in the triglyceride-rich lipoprotein fraction were significantly higher after the high-carbohydrate diet, as was the concentration of remnant-like lipoprotein particle cholesterol (a measure of lipoprotein remnants). These carbohydrate-induced increases in the number of circulating triglyceride-rich particles and their remnants were abolished when subjects had exercised daily during the high-carbohydrate diet.

3-Hydroxybutyric Acid↗

Free radical injury and liver tumor promotion.

One of the underlying mechanisms of tumor promotion both in the skin and liver involves free radical mediated injury to informational macromolecules of target cells. A choline-deficient (CD) diet, which is an efficient liver tumor promoter, induces peroxidative damage of liver cell membrane lipids. By modifying components of a CD diet, we have shown that the efficacy of the promotion is correlated with the extent of lipid peroxidation. The substitution of fats in a CD diet with predominantly polyunsaturated fat and the addition of methapyrilene to a CD diet enhances membrane lipid peroxidation and the promoting effects. An antioxidant (BHT) and hypolipidemic peroxisome proliferators (BR931 and DEHP) suppress both of these effects. Contrary to these findings, phenobarbital did not induce membrane lipid peroxidation, and its addition to a CD diet inhibited the diet-induced lipid peroxidation, though such a combination exerted a stronger promoting action. Thus, a CD diet and phenobarbital exert their promoting actions through different mechanisms. The consequence of membrane lipid peroxidation in the liver cells induced by a CD diet may be multiple. Our recent study of surface membrane insulin receptors of liver cells of rats fed a CD diet showed a decrease in number and an enhanced binding affinity leading to altered responsiveness of liver cells to insulin mediated glycogen synthesis. It is suggested that CD diet-induced lipid peroxidation leads to functional alterations of membrane receptors involved in cell growth control and may thereby exert its promoting action.

Animals↗

Nutritional control of heart disease and cancer: are different diets necessary.

Man evolved as a wild animal and his nutritional biology was adapted to wild plants and animals. That diets have been modified by trade is illustrated from the author's experience in Uganda where dramatic differences occur in the diets in the North and South of the country. Internationally, the incidence and pattern both of cardiovascular disease and cancer caries with the ecology of the regions. What is seen in miniature in Uganda is to be seen enlarged upon a world scale. In the course of agriculture we have changed the balance of nutrients offered by wild plants and animals. In particular we have substituted storage fat for structural fat whilst also changing our diet in the direction of a high refined carbohydrate food structure.

Adult↗

Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: clinical and laboratory effects.

A variety of health effects have been attributed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but little information is available on the course of a verified high-level TCDD intoxication. In this paper we describe two cases of heavy intoxication with TCDD and present a 2-year follow-up including clinical, biochemical, hematologic, endocrine, and immunologic parameters monitored in two women, 30 and 27 years of age, who suffered from chloracne due to TCDD intoxication of unknown origin. Patient 1, who had the highest TCDD level ever recorded in an individual (144,000 pg/g blood fat), developed severe generalized chloracne, whereas in the second patient, despite heavy intoxication (26,000 pg/g blood fat), only mild facial acne lesions occurred. Both patients initially experienced nonspecific gastrointestinal symptoms. In Patient 1 we observed a moderate elevation of blood lipids, leukocytosis, anemia, and secondary amenorrhoea. The laboratory parameters in Patient 2 were all normal. Despite the high TCDD levels, apart from chloracne, only few clinical and biochemical health effects were observed within the first 2 years after TCDD intoxication.

Acneiform Eruptions↗

Update on the pharmacotherapy of obesity.

OBJECTIVE: To review recent developments in the pharmacotherapy of obesity, including the agents currently approved for use in the management of obesity and those under development. DATA SOURCES: A MEDLINE search from January 1990 to July 1997 was conducted to identify English literature available on the pharmacotherapy of obesity. The search was supplemented by a review of the bibliographies of identified literature. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. When available, double-blind, placebo-controlled trials were used preferentially. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, clinical trial data regarding efficacy, adverse effects, pharmacokinetics, drug interactions, and contraindications where information was available. Study design, selected population, results, and adverse effect information were included. DATA SYNTHESIS: The anorexiants currently available or under development for the management of obesity regulate food intake and satiety via the adrenergic and/or serotonergic pathways. Clinical trials have shown a 10-15% weight loss can typically be anticipated; however, little long-term safety and efficacy data are available. Adverse events tend to be mild and self-limiting, but serious adverse events can occur. Treatment options under development include thermogenic agents, digestive inhibitors, and analogs and antagonists of hormones that regulate food intake and satiety. CONCLUSIONS: Several mechanisms to control weight are currently under investigation for the management of obesity. Since obesity is a chronic condition, further studies should be conducted to evaluate the long-term safety and efficacy of these agents and the role of combination therapy using different modalities.

Adrenergic Agents↗

Additive gastrointestinal effects with concomitant use of olestra and orlistat.

OBJECTIVE: To report a case of significant additive gastrointestinal effects with concomitant use of orlistat and an olestra-containing snack food. CASE SUMMARY: A 16-year-old African American girl with type 2 diabetes, hypercholesterolemia, and hypertension was participating in a pilot study that tested the safety and efficacy of orlistat. After 2 weeks of orlistat treatment, the patient presented to the clinic with complaints of soft, fatty/oily stools, flatus with discharge, abdominal pain, increased flatus, and fecal incontinence. On further questioning, it was determined that she was also consuming approximately 5 ounces of olestra-containing potato chips on a daily basis. The patient eliminated olestra from her diet and returned to the clinic with substantially diminished gastrointestinal adverse effects, despite continuing to take orlistat. DISCUSSION: This is the first published case describing additive gastrointestinal effects after concurrent use of orlistat and olestra. Education about the potential for serious additive gastrointestinal adverse effects is important to prevent premature and unnecessary discontinuation of orlistat therapy. Awareness of this potential interaction could be especially important for patients with underlying disease states in which severe gastrointestinal symptoms could result in significant complications. CONCLUSIONS: This case illustrates that significant gastrointestinal distress may result after olestra consumption during orlistat therapy. All patients receiving orlistat for the management of obesity should be properly educated about this potential drug-food interaction.

Adolescent↗

Effect of the moderate consumption of olestra in patients receiving long-term warfarin therapy.

We conducted a prospective, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effect of the moderate consumption of snacks containing olestra on the international normalized ratio (INR) in 40 patients receiving long-term warfarin therapy. Patients continued their warfarin regimen and were assigned to receive 1.5 servings/day (42 g) for 2 weeks of Pringles Original Flavor Fat Free Potato Crisps with Olean (12 g olestra/1.5 servings) or Pringles Original Flavor Potato Crisps (placebo group). Patients' INRs were measured weekly for 2 weeks. Thirty-six patients completed the first week of the trial. After 1 week, the mean change in the INR from baseline increased by 0.02 +/- 0.5 in the olestra group and by 0.17 +/-0.4 in the placebo group (p= 0.327). Ten patients in the olestra group and 12 in the placebo group completed the second week of the study. Mean change in the INR from baseline was similar at week 2, -0.18 +/- 0.38 and 0.09 +/- 0.53 (p=0.193), respectively. Gastrointestinal side effects (diarrhea, gas, bloating) occurred in three patients in the olestra group and five in the placebo group (p=0.3). Moderate consumption of snacks containing olestra did not significantly affect the INR (> 0.3 U) at 1 week in patients receiving long-term anticoagulation with warfarin. It does not appear that moderate consumption of these snacks would affect the INR after 2 weeks, but this must be confirmed in a larger sample with adequate power at 2 weeks.

Aged↗

Food sources, dietary behavior, and the saturated fat intake of Latino children.

BACKGROUND: Recent recommendations for Americans aged 2 and older call for a reduction in the average saturated fat intake to less than 10% of calories. METHODS: Using 24-hour dietary recalls collected from mothers of 4- to 7-year-old urban Latino children, we identified foods and dietary behavior patterns that distinguish children with higher and lower mean daily percentages of calories from saturated fat. RESULTS: Compared with children in the lowest quintile of intake, children in the highest quintile consumed more than twice as much saturated fat per day from high-fat milk products (18.5 g vs 7.8 g), mostly from whole milk. They did not consume different kinds of milk or different amounts of milk per eating occasion, but on average they consumed milk more frequently (2.8 vs 1.6 eating occasions per day). Even children in the lowest quintile, on average, exceeded the 10% of calories from saturated fat currently recommended. If low-fat (1% fat) milk had been substituted without other dietary changes, all but the highest two quintiles would have been within the recommended level. CONCLUSIONS: The substitution of low-fat for whole milk appears to be a key strategy for preschool children for achieving recommended levels of saturated fat intake.

Animals↗