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Effects of orlistat on fat-soluble vitamins in obese adolescents.

STUDY OBJECTIVES: To determine whether orlistat causes fat-soluble vitamin deficiencies in African-American and Caucasian adolescents. DESIGN: Prospective, open-label pilot study. SETTING: Warren Grant Magnuson Clinical Center of the National Institutes of Health. PATIENTS: Seventeen adolescents with body mass indexes above the 95th percentile for age, race, and gender who also had at least one obesity-related comorbid condition. INTERVENTION: Subjects received orlistat 120 mg 3 times/day and a daily multivitamin supplement containing vitamin A 5000 IU, vitamin D 400 IU, vitamin E 300 IU, and vitamin K 25 microg. MEASUREMENTS AND MAIN RESULTS: During 3-6 months of orlistat treatment, acute absorption of retinol (vitamin A) was not significantly altered, but absorption of alpha-tocopherol (vitamin E) was significantly reduced compared with baseline levels (p<0.001). Serum levels of vitamins A and E did not change significantly; however, there was a nonsignificant decrease in vitamin K. Mean vitamin D levels were significantly reduced compared with baseline (p<0.02) after 1 month of orlistat, despite multivitamin supplementation. CONCLUSION: It may be prudent to monitor vitamin D concentrations in adolescents who take orlistat, even when a multivitamin is prescribed.

Adolescent↗

Clinical and epidemiologic studies of cleft lip and palate in the Philippines.

Clinical and epidemiologic studies of defined geographic populations can serve as a means of establishing data important for genetic counseling and as a first step in identifying strategies best suited for identification of causes. Under the sponsorship of Operation Smile International, clinical, genetic, and epidemiologic studies were carried out at six sites within the Philippines between 1989 and 1996. Patients who were being evaluated for surgical repair of craniofacial anomalies (primarily clefts of the lip and palate) were briefly examined for the presence of associated anomalies, and a family history was obtained to look for the frequency of cleft lip and palate in siblings. Birth records of 47,969 newborns over an 8-year period at one hospital in Bacolod City in the province of Negros Occidental were reviewed. Medical records of infants born with clefts of the lip and/or palate and other major anomalies were reviewed and birth prevalence rates calculated. Findings include a birth prevalence of 1.94 per 1000 live births for cleft lip with/without palate in the Philippines. Recurrence rates in siblings for nonsyndromic clefts of the lip and palate were 23 per 1000 for cleft lip with or without cleft palate, and 14 per 1000 for cleft palate only. The percentage of clefts associated with multiple anomalies was 21% at birth and 6% for individuals examined during the screening process, providing evidence for a high postnatal death rate. These data provide groundwork for additional etiologic studies including segregation analysis and molecular genetic studies involving linkage or association, as well as for studies of environmental contributions to clefting such as vitamin deficiencies. Preliminary molecular analysis using an association approach is reported in a companion paper. The findings suggest a high incidence of cleft lip and palate in native-born Filipinos.

Abnormalities, Multiple↗

Transport of thyroxine in the serum of vitamin A-deficient rats.

Thyroxine (T4) transport in the serum of rats deficient in vitamin A was studied by electrophoresis after incubation of serum samples with radioactive T4. In serum from vitamin A-deficient rats, the amount of radioactivity bound to the prealbumin zone of the electrophoretograms decreased, whereas there was an increase in the amount of radioactivity bound to the albumin zone. The serum from vitamin A-deficient rats subsequently fed a normal diet (repletion experiment) had an electrophoretic pattern similar to that of normal rats. The serum fraction which bound radioactive T4 appeared in the prealbumin rather than the albumin zone. These results suggest that vitamin A deficiency causes an early change in the transport of thyroid hormones in the plasma and a new level of serum thyroxine which may be responsible for the biochemical and physiological changes which occur in vitamin A-deficient rats.

Animals↗

A vitamin profile of heroin addiction.

Circulating thiamine, riboflavin, nicotinates, folates, vitamin B12, B6, A, and carotenes of 149 heroin addicts aged 17-60 years were compared to 204 healthy subjects not using drugs or vitamins. Only 24 per cent of the addicts had no evidence of hypovitaminemia; 45 per cent and 37 per cent had vitamin B6 and folate deficit respectively, whereas deficits of thiamine, vitamin B12, riboflavin, and nicotinate were recorded for 13-19 per cent of the addict population; impaired liver function in addicts did not influence these results.

Adolescent↗

Vitamin supplementation therapy in the elderly.

Vitamin supplementation in large dosages is increasingly common in the older population. Often, such supplementation is used in an attempt to improve an individual's health status. There have been claims that the effects of vitamins halt the normal aging process or prevent and cure disease. However, several recent studies have failed to demonstrate the efficacy of vitamin supplementation in preventing several types of cancer. In moderate dosages, supplementation with vitamin E (tocopherols) shows promise as a lipid antioxidant, and may reduce the risk of coronary heart disease. However, before vitamin E becomes an accepted medical therapy, further long term studies must be undertaken to examine the safety and efficacy of such therapy. An adequate intake of vitamins should be ensured by adherence to a well balanced diet. However, the elderly are prone to circumstances that may prevent them from eating a balanced diet. In addition, there are several age-related medical conditions that may predispose individuals to dietary and vitamin deficiencies. To prevent vitamin deficiency diseases and their associated morbidity, modest vitamin supplementation may be necessary. However, supplementation should be reserved for individuals with documented deficiency or who are at risk of developing such deficiencies, especially those who are homebound or institutionalised. Vitamins taken in large dosages should be considered as drugs. These medicines, which are obtainable over-the-counter, should be carefully regulated to prevent toxicity.

Adult↗

Influences of diet and nutrition on clinical pharmacokinetics.

The human diet represents a complex and variable mixture of nutrients, many of which have the potential for altering the disposition of drugs. This review highlights progress from a number of laboratories illustrating nutrient influences on drug dispositions and actions. Emphasis is placed on nutritional effects on hepatic drug metabolism studied in humans. Data from animals have sometimes been difficult to extrapolate to humans, as illustrated by reports on the influences of starvation, dietary lipids, and ascorbic acid. From studies in healthy subjects it is now clear that a number of specific dietary factors can influence drug metabolism by the mixed function oxidase system and conjugating enzymes. These include dietary protein, cruciferous vegetables, charcoal-broiled beef containing polycyclic aromatic hydrocarbons, and methylxanthines. The effects of such dietary components have been demonstrated for only a limited number of drug substrates for these enzyme systems. Effects of food on bioavailability have been more widely studied, and depend greatly upon the type of drug. Malnutrition can be associated with variable but potentially important effects on the bioavailability, binding, hepatic metabolism, and renal clearance of drugs. In malnourished patients it is generally difficult to recognise the roles of individual nutrient deficiencies on drug disposition, and clinical predictors of altered pharmacokinetics for various drugs in such patients are not well defined. It is likely that many important interrelationships between nutrition and new or already marketed drugs remain to be recognised, and therefore warrant further research. Nutritional effects on drug metabolising enzymes also have implications for endogenous substances such as hormones and environmental toxins and carcinogens which are metabolised by the same or related enzyme systems, and for diseases likely to be related to the actions of such chemicals.

Age Factors↗

Nutrition and immunity: laboratory and clinical aspects.

It is well known that inappropriate nutrient intake accounts for the maintenance of the immunological equilibrium, in humans and animals. Vitamins, elements, lipids, proteins and nucleic acids play an important role in the regulation of cellular and humoral immune responses since single or multiple deficits of these food components have been shown to cause immune abnormalities. For instance, in the course of protein-calorie malnutrition bacterial and/or viral infections represent the major cause of death. Ageing is characterized by a decline of many immune functions, and this process is called immunosenescence. Here, we report novel findings on the inability of superantigens to activate old CD8+, natural killer and B cells, as an expression of cell amnesia. In the elderly, this lack of activation could lead to lethal effects in the case of severe staphylococcal infections. Quite interestingly, recent findings outlined some similarities between human immune deficiency virus (HIV)-1 infection and ageing in terms of immune changes. The model of HIV-infection may be useful for the interpretation of ageing mechanisms and possible therapeutical interventions. Finally, the role of nutrition in different pathological conditions and the use of medical foods for correcting of immune deficits will be described.

Aging↗

Drug metabolism under pathological and abnormal physiological states in animals and man.

The activity of microsomal drug-metabolizing enzymes is altered by several pathological or abnormal physiological states, such as changes in nutritional status, liver, heart or kidney diseases, hormonal disturbances, pregnancy, tumour-bearing state, adjuvant arthritis, changes in reticuloendothelial system and environmental factors (stress, irradiation, heavy metals). The activities of other metabolic pathways, such as glucuronidation, sulphate conjugation, acetylation and alcohol oxidation are generally affected to lesser extents. Rats are most commonly used in drug metabolism studies, and it is important to know that the activity of most of the microsomal drug-metabolizing enzymes is higher in males than in females through androgen action which is readily impaire drug-metabolizing enzymes in male rats are thus manifested by two mechanisms; one is by impairment of androgen action and the other is by depression of the basic enzymic activity. Therefore, those effects of pathological states, observed only in male rats but not in females, are generally not seen in other species of animals, including man. The effects of starvation, hyperthyroidism, adrenal insufficiency, diabetes and morphine administration are cases where changes in metabolism are due solely to impairment of androgen action. In other pathological cases, those drug-metabolizing enzymes showing sex differences are depressed more markedly in male rats than those showing no clear sex difference. The author therefore recommends the use of female rats in the evaluation of the effects of pathological states on hepatic microsomal drug-metabolizing enzymes. Generally, changes in activity of the hepatic enzymes reflect closely the changes in the rates of drug metabolism in vivo. However, the protein-binding of drugs, hepatic blood flow and renal function are also known to affect the rate of drug metabolism and excretion in vivo, and therefore changes of these factors in pathological states should also be taken into consideration.

Animals↗

Nutrient inadequacy in obese and non-obese youth.

PURPOSE: In this study, the Dietary Reference Intake standards were used to evaluate the prevalence of inadequate intakes of micronutrients in obese and non-obese youth. METHODS: Dietary intake was analyzed with a dietary history taken by a registered dietitian. The obese group (n=156) had a body mass index (BMI) above the 95th percentile for age and sex. The non-obese group (n=90) was between the tenth and 85th BMI percentiles. RESULTS: In the obese subjects, the prevalence of inadequate intakes was 81% for vitamin E and 27% for magnesium; the proportions with intakes below the Adequate Intakes (AIs) for calcium and vitamin D were 55% and 46%, respectively. The obese children consumed 124% of estimated need for energy, 32% of which came from fat. The non-obese had a similar prevalence of inadequate intakes (vitamin E, 93%; magnesium, 29%; calcium, 51%; vitamin D, 44%). They consumed 107% of estimated need for energy, and 31% of energy came from fat. For both groups, all other nutrient intakes were adequate. CONCLUSIONS: Even though children may consume an excess of energy, they may not be meeting all of their micronutrient needs.

Adolescent↗