RESUMO
A young girl, age 8.5 years, presented with profound hypercholesterolemia and early xanthomatosis, suggesting homozygous familial (or type II) hypercholesterolemia. The patient's low density lipoprotein (LDL) receptor function and parental lipoprotein profiles were determined to be normal, prompting revision of the initial diagnosis to pseudohomozygous familial hypercholesterolemia. When she subsequently presented with giant platelets, the case was presented to colleagues on an electronic mailing list. It was recommended that plasma and sterol analysis be performed, which led to a diagnosis of sitosterolemia. The presentation of profound hypercholesterolomia in childhood that ultimately is not attributed as due to homozygous or compound heterozygous defects in the LDL receptor gene has been termed pseudohomozygous familial (or type II) hypercholesterolemia (PHT2HC). Patients diagnosed with PHT2HC subsequently confirmed to have sitosterolemia have been previously reported only rarely. The challenge of achieving accurate specific diagnosis and appropriate workup for these conditions in children is discussed in the context of this rare case and review of the historical literature concerning these conditions.
Assuntos
Hipercolesterolemia/diagnóstico , Hipercolesterolemia/genética , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Enteropatias/diagnóstico , Enteropatias/genética , Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/genética , Fitosteróis/efeitos adversos , Plaquetas/citologia , Criança , Diagnóstico Diferencial , Feminino , Homozigoto , Humanos , Fitosteróis/genética , Receptores de LDL/genética , Esteróis/sangue , Resultado do Tratamento , Xantomatose/complicações , Xantomatose/genéticaRESUMO
Smith-Lemli-Opitz syndrome (SLOS) is caused by a genetic deficiency in 7-dehydrocholesterol (7-DHC) reductase (EC 1.3.1.21), the last enzyme of the cholesterol synthetic pathway. In SLOS, plasma cholesterol concentration is reduced and immediate precursor concentration (7-DHC) is elevated. Surprisingly, total sterol synthesis is reduced but HMG-CoA reductase activity, a rate-limiting enzyme in cholesterol synthesis is unaltered as judged by normal urinary excretion of mevalonic acid (MVA) (Pappu et al. J Lipid Res 43:1661-1669, 2002). These findings raise the possibility of increased diversion of MVA into the MVA shunt pathway away from sterol synthesis, by activation of the shunt pathway enzymes. To test this hypothesis, we measured the urinary excretion of 3-methylglutaconic acid (U-3MGC), a by-product of the shunt pathway, in 19 mildly to moderately severely affected SLOS subjects (ten males, nine females) receiving either a cholesterol-free or a high cholesterol diet, and in 20 age- and sex-matched controls. U-3MGC was similar in SLOS and controls, and was unaffected by dietary cholesterol intake. Further, no change in U-3MGC was observed in a subset of SLOS subjects (n = 9) receiving simvastatin. In contrast, U-MVA was reduced by cholesterol supplementation (~54%, p < 0.05) and by simvastatin (~50%, p < 0.04). There was no correlation between U-3MGC and either plasma sterol concentrations, urinary isoprenoids, or the subjects' clinical severity score. However U-3MGC was inversely correlated with age (p < 0.04) and body weight (p < 0.02), and higher in females than in males (~65%, p < 0.025). The data show that DHCR7 deficiency does not result in 3MGC accumulation in SLOS and suggest that the MVA shunt pathway is not activated in patients with the condition.
Assuntos
Colesterol/sangue , Colesterol/metabolismo , Ácido Mevalônico/metabolismo , Síndrome de Smith-Lemli-Opitz/metabolismo , Criança , Colesterol na Dieta/metabolismo , Desidrocolesteróis/sangue , Desidrocolesteróis/metabolismo , Dieta Hiperlipídica , Suplementos Nutricionais , Feminino , Glutaratos/metabolismo , Glutaratos/urina , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Masculino , Ácido Mevalônico/urina , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Sinvastatina/farmacologia , Síndrome de Smith-Lemli-Opitz/sangue , Síndrome de Smith-Lemli-Opitz/urina , Terpenos/metabolismo , Terpenos/urinaRESUMO
BACKGROUND: Carotenoids may interact differently in their absorption and transport in animals and humans. The simultaneous administration of large amounts of lutein, zeaxanthin and beta carotene would affect not only plasma values but also their concentrations in the retina and other tissues. OBJECTIVE: In this study, we investigated the transport, distribution and interactions of lutein, zeaxanthin and beta-carotene in the plasma, retina and other tissues of chicks fed supplements rich in lutein, zeaxanthin or beta-carotene. METHODS: Newly hatched male Leghorn chicks were randomly assigned to ten groups. One group provided baseline data (1-day-old group). The other groups were fed one of the following six diets for 14 or 28 days: high lutein diet; high zeaxanthin diet; three high beta-carotene supplemented diets and the control diet. Plasma and tissues including retina were analyzed for lutein and zeaxanthin and beta-carotene at baseline and at 14 and 28 days. RESULTS: All tissues had increased concentrations of lutein after the high lutein diet and had increased concentrations of zeaxanthin after the high zeaxanthin diet. After 28 days, the retinal concentrations of lutein and zeaxanthin in the chicks supplemented with lutein (27.2 mg/kg diet) and zeaxanthin (15.3 mg/kg diet) increased 128 and 116%, respectively, compared to the retinas of chicks fed the control diet (lutein 5.2 mg/kg and zeaxanthin 1.7 mg/kg). Lutein was decreased in plasma and other non-retinal tissues when the diet was supplemented with zeaxanthin; likewise, zeaxanthin was decreased in plasma and non-retinal tissues after the lutein supplement. Zeaxanthin increased in the retina after the high lutein supplement, and retinal lutein was maintained after the high zeaxanthin supplement. The high beta-carotene supplement increased the beta-carotene content of plasma and liver very little, and beta-carotene was not found in any other tissue in the chick, including the retina. More importantly, beta-carotene decreased the concentrations of both lutein and zeaxanthin in the plasma and most tissues, including the retina. CONCLUSION: High dose dietary supplementation of a single carotenoid may alter the assimilation of other carotenoids. The retina appears to have the capacity to preserve accumulation of lutein and zeaxanthin, but this capacity is diminished when intake of beta-carotene is high.
Assuntos
Luteína/administração & dosagem , Luteína/metabolismo , Xantofilas/administração & dosagem , Xantofilas/metabolismo , beta Caroteno/administração & dosagem , beta Caroteno/metabolismo , Animais , Galinhas , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais/efeitos adversos , Fígado/metabolismo , Luteína/efeitos adversos , Luteína/sangue , Masculino , Distribuição Aleatória , Retina/metabolismo , Fatores de Tempo , Xantofilas/efeitos adversos , Xantofilas/sangue , Zeaxantinas , beta Caroteno/efeitos adversos , beta Caroteno/sangueRESUMO
AIMS: To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials. METHODS AND RESULTS: We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-2891 and Brouwer et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006;295:2613-2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis (n = 1148) showed no convincing protective effect of fish oil (RR 0.90; 95% CI 0.67-1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline (0.79; 0.60-1.06) tended towards a protective effect. The pooled analysis (n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = 0.79). CONCLUSION: These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.
Assuntos
Desfibriladores Implantáveis , Ácidos Graxos Ômega-3/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Taquicardia Ventricular/terapia , Idoso , Suplementos Nutricionais , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Prevenção Secundária , Taquicardia Ventricular/mortalidade , Resultado do TratamentoRESUMO
OBJECTIVE: To test the hypothesis that there is a correlation between the ratio of plant sterols to cholesterol in plasma and dietary cholesterol absorption in children with Smith-Lemli-Opitz syndrome (SLOS), a cholesterol synthesis disorder. STUDY DESIGN: We obtained measurements of cholesterol absorption with a direct radioisotope cholesterol absorption method during 9 visits of children with SLOS. We measured plasma sterols in 22 children with SLOS and 16 control children, and we measured dietary intake of cholesterol and sitosterol (n=11 SLOS). RESULTS: The correlations of 2 plasma plant sterol ratios (sitosterol/cholesterol and campesterol/cholesterol) with direct cholesterol absorption measurement were poor (R= -0.33 and R= -0.25, respectively), significantly lower than the published correlation in adults (R=0.73; P< .02). CONCLUSIONS: Although the ratios of plant sterols to cholesterol in plasma has been used as a surrogate for cholesterol absorption in adults and children, these ratios may not accurately reflect cholesterol absorption in children with SLOS. These ratios should not be used as a surrogate for cholesterol absorption in children without further validation.
Assuntos
Colesterol na Dieta/metabolismo , Absorção Intestinal , Fitosteróis/sangue , Síndrome de Smith-Lemli-Opitz/sangue , Síndrome de Smith-Lemli-Opitz/dietoterapia , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Colesterol na Dieta/sangue , Feminino , Humanos , Lactente , Masculino , Sensibilidade e Especificidade , Sitosteroides/sangueRESUMO
Deficient cholesterol and/or excessive 7-dehydrocholesterol (7-DHC) may be responsible for the pathology of Smith-Lemli-Opitz syndrome (SLOS). Both high-cholesterol diets given to ameliorate cholesterol deficiency while decreasing 7-DHC and cholesterol-enriched diets plus simvastatin to further decrease sterol synthesis have been used as potential therapies. However, the effect of dietary cholesterol and simvastatin on cholesterol synthesis in SLOS has not been reported. Twelve subjects with SLOS enrolled in the study: Nine had received a high cholesterol diet (HI) for 3 y and three were studied after 4 wk on a low cholesterol diet (LO). Cholesterol fractional synthesis rate (FSR) was measured after oral administration of deuterium oxide, using gas chromatography isotope ratio mass spectrometry. FSR was lower in HI compared with LO (HI: 1.46 +/- 0.62%/d; LO: 4.77 +/- 0.95%/d; p < 0.001). Three HI subjects were retested after 0.8 y taking simvastatin (HI + ST). Simvastatin tended to reduce FSR and significantly decreased (p < 0.01) plasma 7-DHC compared with cholesterol supplementation alone. The study demonstrates the utility of the deuterium incorporation method to understand the effect of therapeutic interventions in SLOS. The data suggest that dietary cholesterol supplementation reduces cholesterol synthesis in SLOS and further support the rationale for the combined treatment of SLOS with a cholesterol-enriched diet and simvastatin.
Assuntos
Colesterol na Dieta/metabolismo , Colesterol/biossíntese , Sinvastatina/uso terapêutico , Síndrome de Smith-Lemli-Opitz/metabolismo , Adolescente , Anticolesterolemiantes , Criança , Pré-Escolar , Colesterol na Dieta/administração & dosagem , Desidrocolesteróis/metabolismo , Suplementos Nutricionais , Feminino , Humanos , Lactente , Masculino , Síndrome de Smith-Lemli-Opitz/dietoterapia , Síndrome de Smith-Lemli-Opitz/tratamento farmacológicoRESUMO
The relationship of plasma cholesterol-reducing interventions to emotional states, such as depression and hostility, remains a topic of debate. The present study employed a randomised, controlled design, and was conducted at a clinical research center to test the effect of dietary cholesterol-lowering on psychological symptoms. Ten women and eight men were randomly assigned to one of two counterbalanced diet cycles (low-fat versus high-fat diet; isocaloric; 6 weeks each; separated by a washout period). Analyses for repeated measures revealed that the low-fat diet significantly reduced total, LDL and HDL cholesterol, when compared with baseline and the high-fat diet. As expected, weight remained unchanged. Ratings of depression, hostility and global severity of psychological symptoms as measured by the SCL-90-R also improved significantly on the low-fat, high-complex carbohydrate diet when compared with baseline. These results suggest that plasma cholesterol-lowering in the context of a low-fat, high-complex carbohydrate diet may have a beneficial effect on psychological symptoms.
Assuntos
Agressão/efeitos dos fármacos , Anticolesterolemiantes/uso terapêutico , Depressão , Adolescente , Adulto , Anticolesterolemiantes/administração & dosagem , Feminino , Humanos , Hipercolesterolemia/dietoterapia , Hipercolesterolemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto JovemRESUMO
Carotenoids are fat-soluble antioxidants that may protect polyunsaturated fatty acids, such as n-3 fatty acids from oxidation, and are potentially important for Alzheimer's disease (AD) prevention and treatment. Fasting plasma carotenoids were measured in 36 AD subjects and 10 control subjects by HPLC. Correlations between plasma carotenoid levels, red blood cell (RBC) n-3 fatty acids, and dementia severity were examined in AD patients. Moderately severe AD patients (MMSE=16-19) had much lower plasma levels of two major carotenoids: lutein and beta-carotene, compared to mild AD patients (MMSE=24-27) or controls. Among AD patients, variables (lutein, beta-carotene, RBC docosahexaenoic acid (DHA) and LDL-cholesterol) were significantly correlated with MMSE. A lower MMSE score was associated with lower lutein, beta-carotene and RBC DHA levels, and a higher LDL-cholesterol level. These variables explained the majority of variation in dementia severity (55% of variance in MMSE). Lutein, beta-carotene and beta-cryptoxanthin were positively correlated with RBC DHA in AD patients. The association between higher carotenoids levels and DHA and higher MMSE scores, supports a protective role of both types of nutrients in AD. These findings suggest targeting multiple specific nutrients, lutein, beta-carotene, and DHA in strategies to slow the rate of cognitive decline.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Demência/diagnóstico , Ácidos Docosa-Hexaenoicos/sangue , Luteína/sangue , Estado Nutricional , beta Caroteno/sangue , Biomarcadores , Cromatografia Líquida de Alta Pressão , Jejum , Humanos , Testes Neuropsicológicos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Low dietary intakes and low plasma concentrations of lutein and zeaxanthin are associated with an increased risk of age-related macular degeneration (AMD). No studies have challenged AMD patients with a diet high in lutein and zeaxanthin. OBJECTIVE: The objective was to examine the effect of diets low or high in lutein and zeaxanthin on plasma carotenoids and their transport in AMD patients. DESIGN: Seven AMD patients and 5 control subjects were fed a low-lutein, low-zeaxanthin diet ( approximately 1.1 mg/d) for 2 wk, which was followed by a high-lutein, high-zeaxanthin diet ( approximately 11 mg/d) for 4 wk. Ten subjects continued the diet for 8 wk. Plasma and lipoprotein carotenoids were measured by HPLC. RESULTS: The high-lutein, high-zeaxanthin diet resulted in 2- to 3-fold increases in plasma concentrations of lutein and zeaxanthin and other carotenoids, except lycopene, in the AMD patients and the control subjects. With this diet, 52% of the lutein and 44% of the zeaxanthin were transported by HDL; approximately 22% of lutein and zeaxanthin was transported by LDL. Only 20-25% of alpha-carotene, beta-carotene, and lycopene was transported by HDL; 50-57% was transported by LDL. CONCLUSIONS: The AMD patients and control subjects responded similarly to a diet high in lutein and zeaxanthin; plasma carotenoid concentrations increased greatly in both groups, and the transport of carotenoids by lipoproteins was not significantly different between the groups. This finding suggests that abnormalities in the metabolism of lutein and zeaxanthin in AMD may reside in the uptake of lutein and zeaxanthin from the plasma and transport into the retina.
Assuntos
Carotenoides/sangue , Dieta , Lipoproteínas/sangue , Luteína/farmacologia , Degeneração Macular/sangue , Xantofilas/farmacologia , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico , Peso Corporal , Feminino , Humanos , Lipídeos/sangue , Luteína/sangue , Degeneração Macular/dietoterapia , Masculino , Xantofilas/sangue , ZeaxantinasRESUMO
PURPOSE: Lutein and zeaxanthin are largely transported in plasma by high-density lipoprotein (HDL). The Wisconsin hypoalpha mutant (WHAM) chicken has a recessive sex-linked mutation in the ABCA1 transporter gene that results in a severe deficiency of HDL. In this study, the transport and tissue distribution of lutein and zeaxanthin were examined in newly hatched and 28-day-old WHAM chicks compared with control chicks. METHODS: One-day-old WHAM and control chicks were randomized to be fed a high-lutein or a control diet for 28 days. The plasma and tissues were analyzed for lutein, zeaxanthin, and lipoproteins on days 1 and 28. RESULTS: The WHAM chicks had very low plasma levels of HDL cholesterol (5.3% of normal). They also had very low concentrations of lutein in the plasma and all other tissues compared with control chicks. The plasma and retina were only 9% and 6% of control levels (P < 0.01), respectively. Zeaxanthin levels were similarly low (9% of control, P < 0.01). The high-lutein diet increased the content of lutein in the plasma and tissues of control chicks (P < 0.01). In contrast, in WHAM chicks, lutein increased greatly in the plasma, liver, and heart, but little in the retina (6% of control). CONCLUSIONS: HDL deficiency in the WHAM chicks was associated with a deficiency of lutein and zeaxanthin in the tissues, especially in the retina. The high-lutein diet increased the lutein content of some tissues via LDL and VLDL transport, but retinal lutein remained very low. These data support the prime role of HDL as the specific transporter of lutein and zeaxanthin into the retina. The WHAM chick provides an excellent model for the study of the role of HDL in the retinal uptake of lutein and zeaxanthin.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , HDL-Colesterol/fisiologia , Luteína/metabolismo , Mutação , Retina/metabolismo , Xantofilas/metabolismo , Transportador 1 de Cassete de Ligação de ATP , Animais , Animais Geneticamente Modificados , Animais Recém-Nascidos , Galinhas , HDL-Colesterol/sangue , HDL-Colesterol/deficiência , Cromatografia Líquida de Alta Pressão , Dieta , Gema de Ovo/química , Fígado/metabolismo , Luteína/administração & dosagem , Miocárdio/metabolismo , Transporte Proteico , Distribuição Tecidual , Xantofilas/administração & dosagem , ZeaxantinasAssuntos
Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Sinvastatina/uso terapêutico , Quimioterapia Combinada , Ezetimiba , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/patologia , Túnica Íntima/patologia , Túnica Média/patologiaRESUMO
Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of prenatal n-3 intake on cognitive development. Other papers quantify the negative impact of prenatal exposure to MeHg on cognitive development, and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults. This paper aggregates eight randomized controlled trials (RCTs) comparing cognitive development in controls and in children who had received n-3 PUFA supplementation (seven studies of formula supplementation and one study of maternal dietary supplementation). Our analysis assigns study weights accounting for statistical precision, relevance of three endpoint domains (general intelligence, verbal ability, and motor skills) to prediction of IQ, and age at evaluation. The study estimates that increasing maternal docosahexaenoic acid (DHA) intake by 100 mg/day increases child IQ by 0.13 points. The paper notes that findings were inconsistent across the RCTs evaluated (although our findings were relatively robust to changes in the weighting scheme used). Also, for seven of the eight studies reviewed, effects are extrapolated from formula supplementation to maternal dietary intake.
Assuntos
Cognição/efeitos dos fármacos , Ácidos Graxos Ômega-3/administração & dosagem , Desenvolvimento Fetal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Fenômenos Fisiológicos da Nutrição Pré-Natal , Sistema Nervoso Central/efeitos dos fármacos , Pré-Escolar , Ácidos Docosa-Hexaenoicos/análise , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Fórmulas Infantis/química , Inteligência/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Materna , Leite Humano/química , GravidezRESUMO
Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of fish consumption on coronary heart disease (CHD) mortality and nonfatal myocardial infarction (MI). Other papers quantify stroke risk and the impacts of both prenatal MeHg exposure and maternal intake of n-3 PUFAs on cognitive development. This analysis identified articles in a recent qualitative review appropriate for the development of a dose-response relationship. Studies had to satisfy quality criteria, quantify fish intake, and report the precision of the relative risk estimates. Relative risk results were averaged, weighted proportionately by precision. CHD risks associated with MeHg exposure were reviewed qualitatively because the available literature was judged inadequate for quantitative analysis. Eight studies were identified (29 exposure groups). Our analysis estimated that consuming small quantities of fish is associated with a 17% reduction in CHD mortality risk, with each additional serving per week associated with a further reduction in this risk of 3.9%. Small quantities of fish consumption were associated with risk reductions in nonfatal MI risk by 27%, but additional fish consumption conferred no incremental benefits.
Assuntos
Doença das Coronárias/mortalidade , Alimentos Marinhos/estatística & dados numéricos , Adulto , Idoso , Animais , Doença das Coronárias/prevenção & controle , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Humanos , Masculino , Compostos de Metilmercúrio/toxicidade , Pessoa de Meia-Idade , Medição de Risco , Alimentos Marinhos/efeitos adversosRESUMO
Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of fish consumption on stroke risk. Other papers quantify coronary heart disease mortality risk and the impacts of both prenatal MeHg exposure and maternal intake of n-3 PUFAs on cognitive development. This analysis identified articles in a recent qualitative literature review that are appropriate for the development of a dose-response relationship between fish consumption and stroke risk. Studies had to satisfy quality criteria, quantify fish intake, and report the precision of the relative risk estimates. The analysis combined the relative risk results, weighting each proportionately to its precision. Six studies were identified as appropriate for inclusion in this analysis, including five prospective cohort studies and one case-control study (total of 24 exposure groups). Our analysis indicates that any fish consumption confers substantial relative risk reduction compared to no fish consumption (12% for the linear model), with the possibility that additional consumption confers incremental benefits (central estimate of 2.0% per serving per week).
Assuntos
Alimentos Marinhos/estatística & dados numéricos , Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Alimentos Marinhos/efeitos adversosRESUMO
Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish, while recommendations encourage fish consumption among the general population because of nutritional benefits. To investigate the aggregate impacts of hypothetical shifts in fish consumption, the Harvard Center for Risk Analysis convened an expert panel (see acknowledgements). Effects investigated include prenatal cognitive development, coronary heart disease mortality, and stroke. Substitution of fish with high MeHg concentrations with fish containing less MeHg among women of childbearing age yields substantial developmental benefits and few negative impacts. However, if women instead decrease fish consumption, countervailing risks substantially reduce net benefits. If other adults (mistakenly and inappropriately) also reduce their fish consumption, the net public health impact is negative. Although high compliance with recommended fish consumption patterns can improve public health, unintended shifts in consumption can lead to public health losses. Risk managers should investigate and carefully consider how populations will respond to interventions, how those responses will influence nutrient intake and contaminant exposure, and how these changes will affect aggregate public health.
Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Compostos de Metilmercúrio/toxicidade , Alimentos Marinhos/estatística & dados numéricos , Adolescente , Adulto , Animais , Sistema Nervoso Central/efeitos dos fármacos , Doença das Coronárias/mortalidade , Doença das Coronárias/prevenção & controle , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Humanos , Masculino , Modelos Biológicos , Política Nutricional , Anos de Vida Ajustados por Qualidade de Vida , Medição de Risco , Alimentos Marinhos/efeitos adversos , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Estados UnidosRESUMO
Dietary sitostanol has a hypocholesterolemic effect because it decreases the absorption of cholesterol. However, its effects on the sitostanol concentrations in the blood and tissues are relatively unknown, especially in patients with sitosterolemia and xanthomatosis. These patients hyperabsorb all sterols and fail to excrete ingested sitosterol and other plant sterols as normal people do. The goal of the present study was to examine the absorbability of dietary sitostanol in humans and animals and its potential long-term effect. Two patients with sitosterolemia were fed the margarine Benecol (McNeill Nutritionals, Ft. Washington, PA), which is enriched in sitostanol and campestanol, for 7-18 wk. Their plasma cholesterol levels decreased from 180 to 167 mg/dL and 153 to 113 mg/dL, respectively. Campesterol and sitosterol also decreased. However, their plasma sitostanol levels increased from 1.6 to 10.1 mg/dL and from 2.8 to 7.9 mg/dL, respectively. Plasma campestanol also increased. After Benecol withdrawal, the decline in plasma of both sitostanol and campestanol was very sluggish. In an animal study, two groups of rats were fed high-cholesterol diets with and without sitostanol for 4 wk. As expected, plasma and liver cholesterol levels decreased 18 and 53%, respectively. The sitostanol in plasma increased fourfold, and sitostanol increased threefold in skeletal muscle and twofold in heart muscle. Campestanol also increased significantly in both plasma and tissues. Our data indicate that dietary sitostanol and campestanol are absorbed by patients with sitosterolemia and xanthomatosis and also by rats. The absorbed plant stanols were deposited in rat tissues. Once absorbed by sitosterolemic patients, the prolonged retention of sitostanol and campestanol in plasma might increase their atherogenic potential.
Assuntos
Erros Inatos do Metabolismo/metabolismo , Fitosteróis/sangue , Sitosteroides/sangue , Xantomatose/metabolismo , Adolescente , Animais , Colesterol/sangue , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fitosteróis/farmacocinética , Fitosteróis/farmacologia , Ratos , Ratos Wistar , Sitosteroides/farmacocinética , Sitosteroides/farmacologia , Distribuição TecidualRESUMO
CONTEXT: Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. OBJECTIVE: To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. PATIENTS: Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. INTERVENTION: Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). MAIN OUTCOME MEASURES: Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. RESULTS: Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). CONCLUSION: Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.
Assuntos
Desfibriladores Implantáveis , Ácidos Graxos Ômega-3/farmacologia , Taquicardia Ventricular/terapia , Fibrilação Ventricular/terapia , Idoso , Suplementos Nutricionais , Método Duplo-Cego , Membrana Eritrocítica/metabolismo , Ácidos Graxos Ômega-3/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Análise de Sobrevida , Taquicardia Ventricular/prevenção & controle , Fibrilação Ventricular/prevenção & controleRESUMO
BACKGROUND: Flaxseed oil is a rich source of 18:3n-3 (alpha-linolenic acid, or ALA), which is ultimately converted to 22:6n-3 (docosahexaenoic acid, or DHA), a fatty acid important for the development of the infant brain and retina. OBJECTIVE: The objective of this study was to determine the effect of flaxseed oil supplementation on the breast-milk, plasma, and erythrocyte contents of DHA and other n-3 fatty acids in lactating women. DESIGN: Seven women took 20 g flaxseed oil (10.7 g ALA) daily for 4 wk. Breast-milk and blood samples were collected weekly before, during, and after supplementation and were analyzed for fatty acid composition. RESULTS: Breast milk, plasma, and erythrocyte ALA increased significantly over time (P < 0.001) and after 2 and 4 wk of supplementation (P < 0.05). Over time, 20:5n-3 (eicosapentaenoic acid, or EPA) increased significantly in breast milk (P = 0.004) and in plasma (P < 0.001). In addition, plasma EPA increased significantly (P < 0.05) after 2 and 4 wk of supplementation. There were significant increases over time in breast-milk 22:5n-3 (docosapentaenoic acid, or DPA) (P < 0.02), plasma DPA (P < 0.001), and erythrocyte DPA (P < 0.01). No significant changes were observed in breast-milk, plasma, or erythrocyte DHA contents after flaxseed oil supplementation. CONCLUSIONS: Dietary flaxseed oil increased the breast-milk, plasma, and erythrocyte contents of the n-3 fatty acids ALA, EPA, and DPA but had no effect on breast-milk, plasma, or erythrocyte DHA contents.
Assuntos
Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos/metabolismo , Lactação , Óleo de Semente do Linho/administração & dosagem , Leite Humano/química , Adulto , Dieta , Ácidos Docosa-Hexaenoicos/análise , Ácidos Graxos/sangue , Feminino , Humanos , Óleo de Semente do Linho/metabolismoRESUMO
BACKGROUND: Adequate intake of essential fatty acids (EFAs) is required for optimal development of the central nervous system and visual acuity in infants. Little information exists regarding the EFA status of vulnerable populations living in Southern regions. OBJECTIVE: We examined the adequacy of EFA status in Cuban breast-feeding mothers and their infants. DESIGN: Blood and breast-milk samples were obtained from a cross-sectional sample of mothers and term infants in Havana at 2 mo postpartum. We determined the fatty acid profiles of total lipids in breast milk, plasma, and erythrocytes and assessed infant visual acuity by using Teller acuity cards. RESULTS: Of the 56 mothers and infants examined, none showed biochemical signs of poor EFA status. Compared with values reported in the literature, mothers had an adequate EFA profile in their breast milk, plasma, and erythrocytes. The docosahexaenoic acid (DHA) concentration in breast milk was 0.43 +/- 0.26% of total fatty acids. It appeared that these breast-fed infants had an adequate dietary supply of DHA, as reflected by the mean plasma and erythrocyte DHA concentrations (2.82 +/- 0.84% and 7.41 +/- 1.16% of total fatty acids, respectively). Infant visual acuity testing showed a mean of 2.00 +/- 0.68 cycles/degree, which is within the normal range of mean binocular acuities for 2-mo-old term infants. The data did not show any relation between EFA concentrations and visual acuity. CONCLUSION: The results suggest that n-3 fatty acid deficiency and potential related deficits in early visual neural development are rare, if they exist at all, in breast-feeding women and their infants in Havana.
Assuntos
Eritrócitos/química , Ácidos Graxos Essenciais/análise , Ácidos Graxos Essenciais/sangue , Fenômenos Fisiológicos da Nutrição do Lactente , Leite Humano/química , Estado Nutricional , Adulto , Aleitamento Materno , Estudos Transversais , Cuba , Ácidos Docosa-Hexaenoicos/análise , Ácidos Docosa-Hexaenoicos/sangue , Feminino , Idade Gestacional , Humanos , Lactente , Alimentos Infantis , Lipídeos/análise , Lipídeos/sangue , Gravidez , Acuidade VisualRESUMO
BACKGROUND: An important therapeutic goal for patients with type 2 diabetes is weight loss, which improves metabolic abnormalities. Ad libitum low-fat diets cause weight loss in nondiabetic populations. Compared with diets higher in monounsaturated fat, however, eucaloric low-fat diets may increase plasma triacylglycerol concentrations and worsen glycemic control in persons with type 2 diabetes. OBJECTIVE: We investigated whether, in type 2 diabetes patients, an ad libitum low-fat diet would cause greater weight loss than would a high-monounsaturated fat diet and would do this without increasing plasma triacylglycerol concentrations or worsening glycemic control. DESIGN: Eleven patients with type 2 diabetes were randomly assigned to receive an ad libitum low-fat, high-carbohydrate diet or a high-monounsaturated fat diet, each for 6 wk. The diets offered contained 125% of the estimated energy requirement to allow self-selection of food quantity. The response variables were body weight; fasting plasma lipid, lipoprotein, glucose, glycated hemoglobin A(1c), and fructosamine concentrations; insulin sensitivity; and glucose disposal. RESULTS: Body weight decreased significantly (1.53 kg; P < 0.001) only with the low-fat diet. Plasma total, LDL-, and HDL-cholesterol concentrations tended to decrease during both diets. There were no interaction effects between diet and the lipid profile response over time. Plasma triacylglycerol concentrations, glycemic control, and insulin sensitivity did not differ significantly between the 2 diets. CONCLUSION: Contrary to expectations, the ad libitum, low-fat, high-fiber diet promoted weight loss in patients with type 2 diabetes without causing unfavorable alterations in plasma lipids or glycemic control.