Showing papers in "Journal of Nutrition in 2002"

The Clinical Importance of the Metabolite Equol—A Clue to the Effectiveness of Soy and Its Isoflavones

Abstract: Equol [7-hydroxy-3-(4'-hydroxyphenyl)-chroman] is a nonsteroidal estrogen of the isoflavone class. It is exclusively a product of intestinal bacterial metabolism of dietary isoflavones and it possesses estrogenic activity, having affinity for both estrogen receptors, ERalpha and ERbeta. Equol is superior to all other isoflavones in its antioxidant activity. It is the end product of the biotransformation of the phytoestrogen daidzein, one of the two main isoflavones found in abundance in soybeans and most soy foods. Once formed, it is relatively stable; however, equol is not produced in all healthy adults in response to dietary challenge with soy or daidzein. Several recent dietary intervention studies examining the health effects of soy isoflavones allude to the potential importance of equol by establishing that maximal clinical responses to soy protein diets are observed in people who are good "equol-producers." It is now apparent that there are two distinct subpopulations of people and that "bacterio-typing" individuals for their ability to make equol may hold the clue to the effectiveness of soy protein diets in the treatment or prevention of hormone-dependent conditions. In reviewing the history of equol, its biological properties, factors influencing its formation and clinical data, we propose a new paradigm. The clinical effectiveness of soy protein in cardiovascular, bone and menopausal health may be a function of the ability to biotransform soy isoflavones to the more potent estrogenic isoflavone, equol. The failure to distinguish those subjects who are "equol-producers" from "nonequol producers" in previous clinical studies could plausibly explain the variance in reported data on the health benefits of soy.

A Systematic Screening of Total Antioxidants in Dietary Plants

Abstract: A predominantly plant-based diet reduces the risk for development of several chronic diseases. It is often assumed that antioxidants contribute to this protection, but results from intervention trials with single antioxidants administered as supplements quite consistently do not support any benefit. Because dietary plants contain several hundred different antioxidants, it would be useful to know the total concentration of electron-donating antioxidants (i.e., reductants) in individual items. Such data might be useful in the identification of the most beneficial dietary plants. We have assessed systematically total antioxidants in a variety of dietary plants used worldwide, including various fruits, berries, vegetables, cereals, nuts and pulses. When possible, we analyzed three or more samples of dietary plants from three different geographic regions in the world. Total antioxidants was assessed by the reduction of Fe(3+) to Fe(2+) (i.e., the FRAP assay), which occurred rapidly with all reductants with half-reaction reduction potentials above that of Fe(3+)/Fe(2+). The values, therefore, expressed the corresponding concentration of electron-donating antioxidants. Our results demonstrated that there is more than a 1000-fold difference among total antioxidants in various dietary plants. Plants that contain most antioxidants included members of several families, such as Rosaceae (dog rose, sour cherry, blackberry, strawberry, raspberry), Empetraceae (crowberry), Ericaceae (blueberry), Grossulariaceae (black currant), Juglandaceae (walnut), Asteraceae (sunflower seed), Punicaceae (pomegranate) and Zingiberaceae (ginger). In a Norwegian diet, fruits, berries and cereals contributed 43.6%, 27.1% and 11.7%, respectively, of the total intake of plant antioxidants. Vegetables contributed only 8.9%. The systematic analysis presented here will facilitate research into the nutritional role of the combined effect of antioxidants in dietary plants.

Maternal Methyl Supplements in Mice Affect Epigenetic Variation and DNA Methylation of Offspring

Abstract: This study was designed to determine if maternal dietary methyl supplements increase DNA methylation and methylation-dependent epigenetic phenotypes in mammalian offspring. Female mice of two strains were fed two levels of dietary methyl supplement or control diet prior to and during pregnancy. Offspring of these mice vary in phenotype, which is epigenetically determined and affects health and 2-y survival. Phenotype and DNA methylation of a long terminal repeat (LTR) controlling expression of the agouti gene were assayed in the resulting offspring. Methyl supplements increase the level of DNA methylation in the agouti LTR and change the phenotype of offspring in the healthy, longer-lived direction. This shows that methyl supplements have strong effects on DNA methylation and phenotype and are likely to affect long-term health. Optimum dietary supplements for the health and longevity of offspring should be intensively investigated. This should lead to public policy guidance that teaches optimal, rather than minimal, dose levels of maternal supplements.

Physical Activity and Cancer Prevention: Etiologic Evidence and Biological Mechanisms

Abstract: Scientific evidence is accumulating on physical activity as a means for the primary prevention of cancer. Nearly 170 observational epidemiologic studies of physical activity and cancer risk at a number of specific cancer sites have been conducted. The evidence for decreased risk with increased physical activity is classified as convincing for breast and colon cancers, probable for prostate cancer, possible for lung and endometrial cancers and insufficient for cancers at all other sites. Despite the large number of studies conducted on physical activity and cancer, most have been hampered by incomplete assessment of physical activity and a lack of full examination of effect modification and confounding. Several plausible hypothesized biological mechanisms exist for the association between physical activity and cancer, including changes in endogenous sexual and metabolic hormone levels and growth factors, decreased obesity and central adiposity and possibly changes in immune function. Weight control may play a particularly important role because links between excess weight and increased cancer risk have been established for several sites, and central adiposity has been particularly implicated in promoting metabolic conditions amenable to carcinogenesis. Based on existing evidence, some public health organizations have issued physical activity guidelines for cancer prevention, generally recommending at least 30 min of moderate-to-vigorous intensity physical activity on > or =5 d/wk. Although most research has focused on the efficacy of physical activity in cancer prevention, evidence is increasing that exercise also influences other aspects of the cancer experience, including cancer detection, coping, rehabilitation and survival after diagnosis.

Functional Foods: Benefits, Concerns and Challenges—A Position Paper from the American Council on Science and Health

Abstract: Functional foods can be considered to be those whole, fortified, enriched or enhanced foods that provide health benefits beyond the provision of essential nutrients (e.g., vitamins and minerals), when they are consumed at efficacious levels as part of a varied diet on a regular basis. Linking the consumption of functional foods or food ingredients with health claims should be based on sound scientific evidence, with the "gold standard" being replicated, randomized, placebo-controlled, intervention trials in human subjects. However, not all foods on the market today that are claimed to be functional foods are supported by enough solid data to merit such claims. This review categorizes a variety of functional foods according to the type of evidence supporting their functionality, the strength of that evidence and the recommended intakes. Functional foods represent one of the most intensively investigated and widely promoted areas in the food and nutrition sciences today. However, it must be emphasized that these foods and ingredients are not magic bullets or panaceas for poor health habits. Diet is only one aspect of a comprehensive approach to good health.

Extent of Vitamin A Deficiency among Preschool Children and Women of Reproductive Age

Abstract: Knowledge of the extent of vitamin A (VA) deficiency (D) is critical for identifying high-risk populations and mobilizing resources for prevention. Yet, all estimates are necessarily imperfect, often based on assumptions in the absence of data. In 1995, the World Health Organization estimated 254 million children to be VA-deficient and 2.8 million to have xerophthalmia. Subsequently, estimates were changed to 75-140 million and 3.3 million, respectively. Although both sets are consistent with a problem of enormous magnitude, the discrepancies also created uncertainty. The present analysis indicates there are approximately 127 million and 4.4 million preschool children with VAD (serum retinol 6 million women develop night blindness (XN) during pregnancy annually. Roughly 45% of VA-deficient and xerophthalmic children and pregnant women with low-to-deficient VA status live in South and Southeast Asia. These regions harbor >60% of all cases of maternal XN, three fourths of whom seem to live in India. Africa accounts for 25-35% of the global cases of child and maternal VAD; about 10% of all deficient persons live in the eastern Mediterranean region, 5-15% live in the Western Pacific and approximately 5% live in the Region of the Americas. VA prophylaxis seems to be preventing the number of deficient preschool children from increasing while probably reducing rates of blindness and mortality. Greater effort is needed to assess and prevent VAD and its disorders, particularly among pregnant and lactating women.

Substituting Fish Oil with Crude Palm Oil in the Diet of Atlantic Salmon (Salmo salar) Affects Muscle Fatty Acid Composition and Hepatic Fatty Acid Metabolism

Abstract: Supplies of marine fish oils (FO) are limited and continued growth in aquaculture production dictates that substitutes must be found that do not compromise fish health and product quality. In this study the suitability of crude palm oil (PO) as a replacement for FO in diets of Atlantic salmon was investigated. Duplicate groups of Atlantic salmon post-smolts were fed four practical-type diets in which the added lipid was either 100% FO and 0% crude PO (0% PO); 75% FO and 25% PO (25% PO); 50% FO and 50% PO (50% PO); and 100% PO, for 30 wk. There were no effects of diet on growth rate or feed conversion ratio nor were any histopathological lesions found in liver, heart or muscle. Lipid deposition was greatest in fish fed 0% PO and was significantly greater than in fish fed 50% and 100% PO. Fatty acid compositions of muscle total lipid were correlated with dietary PO inclusion such that the concentrations of 16:0, 18:1(n-9), 18:2(n-6), total saturated fatty acids and total monoenoic fatty acids increased linearly with increasing dietary PO. The concentration of eicosapentaenoic acid [20:5(n-3)] was reduced significantly with increasing levels of dietary PO but the concentration of docosahexaenoic acid [22:6(n-3)] was significantly reduced only in fish fed 100% PO, compared with the other three treatments. Similar diet-induced changes were seen in liver total lipid fatty acid compositions. Hepatic fatty acid desaturation and elongation activities were approximately 10-fold greater in fish fed 100% PO than in those fed 0% PO. This study suggests that PO can be used successfully as a substitute for FO in the culture of Atlantic salmon in sea water. However, at levels of PO inclusion above 50% of dietary lipid, significant reductions in muscle 20:5(n-3), 22:6(n-3) and the (n-3):(n-6) PUFA ratio occur, resulting in reduced availability of these essential (n-3) highly unsaturated fatty acids to the consumer.

The Effects of Short-Chain Fatty Acids on Human Colon Cancer Cell Phenotype Are Associated with Histone Hyperacetylation

Abstract: The short-chain fatty acid (SCFA) butyrate is produced via anaerobic bacterial fermentation within the colon and is thought to be protective in regard to colon carcinogenesis. Although butyrate (C4) is considered the most potent of the SCFA, a variety of other SCFA also exist in the colonic lumen. Butyrate is thought to exert its cellular effects through the induction of histone hyperacetylation. We sought to determine the effects of a variety of the SCFA on colon carcinoma cell growth, differentiation and apoptosis. HT-29 or HCT-116 (wild-type and p21-deleted) cells were treated with physiologically relevant concentrations of various SCFA, and histone acetylation state was assayed by acid-urea-triton-X gel electrophoresis and immunoblotting. Growth and apoptotic effects were studied by flow cytometry, and differentiation effects were assessed using transient transfections and Northern blotting. Propionate (C3) and valerate (C5) caused growth arrest and differentiation in human colon carcinoma cells. The magnitude of their effects was associated with a lesser degree of histone hyperacetylation compared with butyrate. Acetate (C2) and caproate (C6), in contrast, did not cause histone hyperacetylation and also had no appreciable effects on cell growth or differentiation. SCFA-induced transactivation of the differentiation marker gene, intestinal alkaline phosphatase (IAP), was blocked by histone deacetylase (HDAC), further supporting the critical link between SCFA and histones. Butyrate also significantly increased apoptosis, whereas the other SCFA studied did not. The growth arrest induced by the SCFA was characterized by an increase in the expression of the p21 cell-cycle inhibitor and down-regulation of cyclin B1 (CB1). In p21-deleted HCT-116 colon cancer cells, the SCFA did not alter the rate of proliferation. These data suggest that the antiproliferative, apoptotic and differentiating properties of the various SCFA are linked to the degree of induced histone hyperacetylation. Furthermore, SCFA-mediated growth arrest in colon carcinoma cells requires the p21 gene.

Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline.

Abstract: DNA methylation influences the expression of some genes and depends upon the availability of methyl groups from S-adenosylmethionine (SAM). Dietary methyl groups derive from foods that contain methionine, one-carbon units and choline (or the choline metabolite betaine). Humans ingest ∼50 mmol of methyl groups per day; 60% of them are derived from choline. Transmethylation metabolic pathways closely interconnect choline, methionine, methyltetrahydrofolate (methyl-THF) and vitamins B-6 and B-12. The pathways intersect at the formation of methionine from homocysteine. Perturbing the metabolism of one of these pathways results in compensatory changes in the others. For example, methionine can be formed from homocysteine using methyl groups from methyl-THF, or using methyl groups from betaine that are derived from choline. Similarly, methyl-THF can be formed from one-carbon units derived from serine or from the methyl groups of choline via dimethylglycine, and choline can be synthesized de novo using methyl groups derived from methionine (via SAM). When animals and humans are deprived of choline, they use more methyl-THF to remethylate homocysteine in the liver and increase dietary folate requirements. Conversely, when they are deprived of folate, they use more methyl groups from choline, increasing the dietary requirement for choline. The availability of transgenic and knockout mice has made possible additional studies that demonstrate the interrelationship of these methyl sources. In summary, as we consider dietary requirements and possible effects on DNA methylation, it is important to realize that methionine, methyl-THF and choline can be fungible sources of methyl groups, and the design of our studies should reflect this.

Epidemiologic studies of folate and colorectal neoplasia: a review.

Abstract: Dietary folate influences DNA methylation, synthesis and repair. Aberrations in these DNA processes may enhance carcinogenesis, particularly in rapidly proliferative tissues such as the colorectal mucosa. DNA methylation abnormalities may influence the expression of cancer-related genes, and inadequate levels of folate may lead to uracil misincorporation into DNA and to chromosomal breaks. Folate deficiency enhances intestinal carcinogenesis in several animal models. An increasing number of epidemiologic studies indicate that higher intakes of folate either from dietary sources or from supplements may lower the risk of colorectal adenoma and cancer. More limited data also suggest that dietary methionine, which might also influence methylation, may have a similar protective role. High alcohol consumption, which has a strong antifolate effect, also has been related to higher risk of colorectal neoplasia. The deleterious effects of alcohol are accentuated when folate or methionine intake is low. Some evidence also suggests that the risk of colorectal neoplasia may vary according to genetic polymorphisms in methylenetetrahydrofolate reductase, an enzyme that is involved in folate metabolism. The cumulative data indicate that maintaining adequate folate levels may be important in lowering risk of colorectal cancer.

Family food insufficiency, but not low family income, is positively associated with dysthymia and suicide symptoms in adolescents

Abstract: Food insufficiency has been shown to be associated with poor health, academic and psychosocial outcomes in American children, but the relationship between food insufficiency and depressive disorders in U.S. adolescents has not been studied. Further, there are no national estimates of the prevalence of depressive disorders for U.S. adolescents, nor investigation of associations with sociodemographic characteristics using national data. Therefore, we analyzed data for 15- and 16-y-old adolescents from the Third National Health and Nutrition Examination Survey (NHANES III). Depressive disorders and suicidal symptoms were assessed using the Diagnostic Interview Schedule. Adolescents were classified as "food insufficient" if a family respondent reported that the family sometimes or often did not have enough to eat. The prevalence of depression outcomes is reported by sociodemographic characteristics. Odds ratios for associations with food insufficiency are reported, adjusted for sociodemographic factors. Overall, lifetime prevalence of major depressive disorder was 6.3% and of dysthymia, 5.4%. Almost 5% of 15- to 16-y-old adolescents reported that they had ever attempted suicide and 38.8% reported at least one suicidal symptom. Female adolescents were significantly more likely than males to have had dysthymia, any depressive disorder and all symptoms of suicide. Low income adolescents were less likely to report suicide ideation than high income adolescents, but there were no other differences by family income. Food-insufficient adolescents were significantly more likely to have had dysthymia, thoughts of death, a desire to die and have attempted suicide. There is a strong association between food insufficiency and depressive disorder and suicidal symptoms in U.S. adolescents.

Absorption and Metabolism of Anthocyanins in Elderly Women after Consumption of Elderberry or Blueberry

Abstract: The absorption and metabolism of anthocyanins (ACN) in humans was studied in four elderly women given 12 g elderberry extract (EBX) (720 mg total ACN), and six elderly women given 189 g lowbush blueberry (BB) (690 mg total ACN). The two major ACN in EBX, cyanidin-3-glucoside and cyanidin-3-sambubioside, as well as four metabolites: 1) peonidin 3-glucoside, 2) peonidin 3-sambubioside, 3) peonidin monoglucuronide, and 4) cyanidin-3-glucoside monoglucuronide were identified in urine within 4 h of consumption using HPLC-MS/MS with diode-array detector detection and retention time. Total EBX ACN excretion was 554 +/- 90 microg (mean +/- SD, n = 4) (0.077% of intake/4 h, wt/wt). In 5 of 6 women fed BB, urine samples contained ACN, which were identified as the original forms based upon comparisons to the BB food sample, which contained 24 ACN, 22 of which were identified by HPLC-MS/MS. Reasonable correlations between BB and urine proportions of the different ACN were obtained except for ACN arabinosides. Total urinary excretion during the first 6 h was 23.2 +/- 10.9 microg (mean +/- SD, n = 5) (0.004% of intake/6 h, wt/wt). Plasma ACN levels were below detection limits using 2 mL plasma in women that consumed BB. This study demonstrates for the first time that in vivo methylation of cyanidin to peonidin and glucuronide conjugate formation occurs after people consume ACN and demonstrates the low absorption and excretion of ACN compared with other flavonoids.

A Cost Constraint Alone Has Adverse Effects on Food Selection and Nutrient Density: An Analysis of Human Diets by Linear Programming

Abstract: Economic constraints may contribute to the unhealthy food choices observed among low socioeconomic groups in industrialized countries. The objective of the present study was to predict the food choices a rational individual would make to reduce his or her food budget, while retaining a diet as close as possible to the average population diet. Isoenergetic diets were modeled by linear programming. To ensure these diets were consistent with habitual food consumption patterns, departure from the average French diet was minimized and constraints that limited portion size and the amount of energy from food groups were introduced into the models. A cost constraint was introduced and progressively strengthened to assess the effect of cost on the selection of foods by the program. Strengthening the cost constraint reduced the proportion of energy contributed by fruits and vegetables, meat and dairy products and increased the proportion from cereals, sweets and added fats, a pattern similar to that observed among low socioeconomic groups. This decreased the nutritional quality of modeled diets, notably the lowest cost linear programming diets had lower vitamin C and beta-carotene densities than the mean French adult diet (i.e., <25% and 10% of the mean density, respectively). These results indicate that a simple cost constraint can decrease the nutrient densities of diets and influence food selection in ways that reproduce the food intake patterns observed among low socioeconomic groups. They suggest that economic measures will be needed to effectively improve the nutritional quality of diets consumed by these populations.

Golden Rice: Introducing the β-Carotene Biosynthesis Pathway into Rice Endosperm by Genetic Engineering to Defeat Vitamin A Deficiency

Abstract: To obtain a functioning provitamin A (beta-carotene) biosynthetic pathway in rice endosperm, we introduced in a single, combined transformation effort the cDNA coding for phytoene synthase (psy) and lycopene beta-cyclase (beta-lcy) both from Narcissus pseudonarcissus and both under the control of the endosperm-specific glutelin promoter together with a bacterial phytoene desaturase (crtI, from Erwinia uredovora under constitutive 35S promoter control). This combination covers the requirements for beta-carotene synthesis and, as hoped, yellow beta-carotene-bearing rice endosperm was obtained in the T(0)-generation. Additional experiments revealed that the presence of beta-lcy was not necessary, because psy and crtI alone were able to drive beta-carotene synthesis as well as the formation of further downstream xanthophylls. Plausible explanations for this finding are that these downstream enzymes are constitutively expressed in rice endosperm or are induced by the transformation, e.g., by enzymatically formed products. Results using N. pseudonarcissus as a model system led to the development of a hypothesis, our present working model, that trans-lycopene or a trans-lycopene derivative acts as an inductor in a kind of feedback mechanism stimulating endogenous carotenogenic genes. Various institutional arrangements for disseminating Golden Rice to research institutes in developing countries also are discussed.

Fortification: Overcoming Technical and Practical Barriers

Abstract: The main barriers to successful iron fortification are the following: 1) finding an iron compound that is adequately absorbed but causes no sensory changes to the food vehicle; and 2) overcoming the inhibitory effect on iron absorption of dietary components such as phytic acid, phenolic compounds and calcium. These barriers have been successfully overcome with some food vehicles but not with others. Iron-fortified fish sauce, soy sauce, curry powder, sugar, dried milk, infant formula and cereal based complementary foods have been demonstrated to improve iron status in targeted populations. The reasons for this success include the use of soluble iron such as ferrous sulfate, the addition of ascorbic acid as an absorption enhancer or the use of NaFeEDTA to overcome the negative effect of phytic acid. In contrast, at the present time, it is not possible to guarantee a similar successful fortification of cereal flours or salt. There is considerable doubt that the elemental iron powders currently used to fortify cereal flours are adequately absorbed, and there is an urgent need to investigate their potential for improving iron status. Better absorbed alternative compounds for cereal fortification include encapsulated ferrous sulfate and NaFeEDTA, which, unlike ferrous sulfate, do not provoke fat oxidation of cereals during storage. Encapsulated compounds also offer a possibility to fortify low grade salt without causing off-colors or iodine loss. Finally, a new and useful additional approach to ensuring adequate iron absorption from cereal based complementary foods is the complete degradation of phytic acid with added phytases or by activating native cereal phytases.

Olive Oil Phenols Are Absorbed in Humans

Abstract: Animal and in vitro studies suggest that olive oil phenols are effective antioxidants. The most abundant phenols in olive oil are the nonpolar oleuropein- and ligstroside-aglycones and the polar hydroxytyrosol and tyrosol. The aim of this study was to gain more insight into the metabolism of those phenols in humans. We measured their absorption in eight healthy ileostomy subjects. We also measured urinary excretion in the ileostomy subjects and in 12 volunteers with a colon. Subjects consumed three different supplements containing 100 mg of olive oil phenols on separate days in random order. Ileostomy subjects consumed a supplement with mainly nonpolar phenols, one with mainly polar phenols and one with the parent compound oleuropein-glycoside. Subjects with a colon consumed a supplement without phenols (placebo) instead of the supplement with oleuropein-glycoside. Ileostomy effluent and urine were collected for 24 h after supplement intake. Tyrosol and hydroxytyrosol concentrations were low (< 4 mol/100 mol of intake) in the ileostomy effluent, and no aglycones were detected. We estimated that the apparent absorption of phenols was at least 55-66% of the ingested dose. Absorption was confirmed by the excretion of tyrosol and hydroxytyrosol in urine. In ileostomy subjects, 12 mol/100 mol and in subjects with a colon, 6 mol/100 mol of the phenols from the nonpolar supplement were recovered in urine as tyrosol or hydroxytyrosol. In both subject groups, 5--6 mol/100 mol of the phenols was recovered from the polar supplement. When ileostomy subjects were given oleuropein-glycoside, 16 mol/100 mol was recovered in 24-h urine, mainly in the form of hydroxytyrosol. Thus, humans absorb a large part of ingested olive oil phenols and absorbed olive oil phenols are extensively modified in the body.

Folate status: effects on pathways of colorectal carcinogenesis

Abstract: Many epidemiologic, animal and human studies suggest that folate status modulates carcinogenesis. Although these observations have been made in a number of tissues, the data are clearly most compelling for the colorectum. The mechanism(s) by which this modulation is mediated remains ill defined. Alterations in either genome-wide or gene-specific DNA methylation and/or alterations in DNA stability, resulting from DNA strand breaks or uracil misincorporation, are leading candidates in this regard. Folate has a central role in biological methylation and nucleotide synthesis, and therefore it is not surprising that folate depletion has been observed to alter DNA methylation and diminish DNA stability. The hypothesis that these two pathways are the means by which folate modulates cancer risk is also supported by the epidemiological observation that a common polymorphism in the methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) gene differentially affects the relative risk of colon cancer depending on folate status, because MTHFR catalyzes the reaction that determines whether cellular folate is diverted into biological methylation or nucleotide synthesis. This phenomenon suggests that it is an imbalance between biological methylation and nucleotide synthesis that is responsible for folate-related carcinogenesis. The control of cell proliferation, which also is related to DNA methylation, is another candidate mechanism by which folate status modulates carcinogenesis. In cell culture studies, folate supplementation has been observed to suppress excessive cell proliferation. Understanding the mechanisms by which folate status modulates carcinogenesis is important for advancing insight into cancer biology and for facilitating those efforts to translate research in folate and carcinogenesis into effective and safe public health initiatives.

Nutrient Requirements For Preterm Infant Formulas

Abstract: Achieving appropriate growth and nutrient accretion of preterm and low birth weight (LBW) infants is often difficult during hospitalization because of metabolic and gastrointestinal immaturity and other complicating medical conditions. Advances in the care of preterm-LBW infants, including improved nutrition, have reduced mortality rates for these infants from 9.6 to 6.2% from 1983 to 1997. The Food and Drug Administration (FDA) has responsibility for ensuring the safety and nutritional quality of infant formulas based on current scientific knowledge. Consequently, under FDA contract, an ad hoc Expert Panel was convened by the Life Sciences Research Office of the American Society for Nutritional Sciences to make recommendations for the nutrient content of formulas for preterm-LBW infants based on current scientific knowledge and expert opinion. Recommendations were developed from different criteria than that used for recommendations for term infant formula. To ensure nutrient adequacy, the Panel considered intrauterine accretion rate, organ development, factorial estimates of requirements, nutrient interactions and supplemental feeding studies. Consideration was also given to long-term developmental outcome. Some recommendations were based on current use in domestic preterm formula. Included were recommendations for nutrients not required in formula for term infants such as lactose and arginine. Recommendations, examples, and sample calculations were based on a 1000 g preterm infant consuming 120 kcal/kg and 150 mL/d of an 810 kcal/L formula. A summary of recommendations for energy and 45 nutrient components of enteral formulas for preterm-LBW infants are presented. Recommendations for five nutrient:nutrient ratios are also presented. In addition, critical areas for future research on the nutritional requirements specific for preterm-LBW infants are identified.

Assessment and Control of Vitamin A Deficiency: The Annecy Accords

Abstract: Comprehensive recommendations for the assessment and control of vitamin A deficiency (VAD) were rigorously reviewed and revised by a working group and presented for discussion at the XX International Vitamin A Consultative Group meeting in Hanoi, Vietnam. These recommendations include standardized definitions of VAD and VAD disorders. VAD is defined as liver stores below 20 micro g (0.07 micro mol) of retinol per gram. VAD disorders are defined as any health and physiologic consequences attributable to VAD, whether clinically evident (xerophthalmia, anemia, growth retardation, increased infectious morbidity and mortality) or not (impaired iron mobilization, disturbed cellular differentiation and depressed immune response). An estimated 140 million preschool-aged children and at least 7.2 million pregnant women are vitamin A deficient, of whom >10 million suffer clinical complications, principally xerophthalmia but also increased mortality, each year. A maternal history of night blindness during a recent pregnancy was added to the clinical criteria for assessing vitamin A status of a population, and the serum retinol criterion for a "public health problem" was revised to 15% or more of children sampled having levels of <20 micro g/dL (0.7 micro mol/L). Clinical trials and kinetic models indicate that young children in developing countries cannot achieve normal vitamin A status from plant diets alone. Fortification, supplementation, or other means of increasing vitamin A intake are needed to correct widespread deficiency. To improve the status of young infants, the vitamin A supplements provided to mothers during their first 6 wk postpartum and to young infants during their first 6 mo of life should be doubled.

The Body of Evidence to Support a Protective Role for Lutein and Zeaxanthin in Delaying Chronic Disease. Overview

Abstract: Recent evidence introduces the possibility that lutein and zeaxanthin may protect against the development of the two common eye diseases of aging, cataract and macular degeneration. This potential and the lack of other effective means to slow the progression of macular degeneration have fueled high public interest in the health benefits of lutein and zeaxanthin and the proliferation of supplements containing them on pharmacy shelves. An understanding of the biologic consequences of limiting or supplementing with these carotenoids is only beginning to emerge. Some epidemiologic evidence supports a role in eye disease and, to a lesser extent, cancer and cardiovascular disease. However, the overall body of evidence is insufficient to conclude that increasing levels of lutein and zeaxanthin, specifically, will confer an important health benefit. Future advances in scientific research are required to gain a better understanding of the biologic mechanisms of their possible role in preventing disease. Additional research is also required to understand the effect of their consumption, independent of other nutrients in fruits and vegetables, on human health. The newly advanced ability to measure levels of lutein and zeaxanthin in the retina in vivo creates a unique opportunity to contribute some of this needed evidence.

Elevation in S-Adenosylhomocysteine and DNA Hypomethylation: Potential Epigenetic Mechanism for Homocysteine-Related Pathology

Abstract: Chronic nutritional deficiencies in folate, choline, methionine, vitamin B-6 and/or vitamin B-12 can perturb the complex regulatory network that maintains normal one-carbon metabolism and homocysteine homeostasis. Genetic polymorphisms in these pathways can act synergistically with nutritional deficiencies to accelerate metabolic pathology associated with occlusive heart disease, birth defects and dementia. A major unanswered question is whether homocysteine is causally involved in disease pathogenesis or whether homocysteinemia is simply a passive and indirect indicator of a more complex mechanism. S-Adenosylmethionine and S-adenosylhomocysteine (SAH), as the substrate and product of methyltransferase reactions, are important metabolic indicators of cellular methylation status. Chronic elevation in homocysteine levels results in parallel increases in intracellular SAH and potent product inhibition of DNA methyltransferases. SAH-mediated DNA hypomethylation and associated alterations in gene expression and chromatin structure may provide new hypotheses for pathogenesis of diseases related to homocysteinemia.

Inhibition of Carcinogenesis by Conjugated Linoleic Acid: Potential Mechanisms of Action

Abstract: Conjugated linoleic acid (CLA) is composed of positional and stereoisomers of octadecadienoate (18:2); it is found in foods derived from ruminants (beef and lamb as well as dairy products from these sources). When a mixture of isomers is fed to experimental animals, chemi- cally induced tumorigenesis of mammary, skin and colon is reduced. Importantly, many isomers of CLA are readily me- tabolized to desaturated/elongated products as well as -oxidized products, suggesting that these metabolites may be important anticancer compounds. Mechanisms of inhibition of carcinogenesis may include reduction of cell proliferation, alterations in the components of the cell cycle and induction of apoptosis. In addition, CLA modulates markers of immunity and eicosanoid formation in numer- ous species as well as lipid metabolism and gene expres- sion. It is likely that CLA exerts inhibitory properties in carcinogenesis via one or more of these pathways with some tissue specificity. This review will explore recent ad- vances in putative mechanisms of reduction of carcinogen- esis by CLA. J. Nutr. 132: 2995-2998, 2002.

Physiological Effects of Medium-Chain Triglycerides: Potential Agents in the Prevention of Obesity

Abstract: Medium chain fatty acids (MCFA) are readily oxidized in the liver. Animal and human studies have shown that the fast rate of oxidation of MCFA leads to greater energy expenditure (EE). Most animal studies have also demonstrated that the greater EE with MCFA relative to long-chain fatty acids (LCFA) results in less body weight gain and decreased size of fat depots after several months of consumption. Furthermore, both animal and human trials suggest a greater satiating effect of medium-chain triglycerides (MCT) compared with long-chain triglycerides (LCT). The aim of this review is to evaluate existing data describing the effects of MCT on EE and satiety and determine their potential efficacy as agents in the treatment of human obesity. Animal studies are summarized and human trials more systematically evaluated because the primary focus of this article is to examine the effects of MCT on human energy metabolism and satiety. Hormones including cholescytokinin, peptide YY, gastric inhibitory peptide, neurotensin and pancreatic polypeptide have been proposed to be involved in the mechanism by which MCT may induce satiety; however, the exact mechanisms have not been established. From the literature reviewed, we conclude that MCT increase energy expenditure, may result in faster satiety and facilitate weight control when included in the diet as a replacement for fats containing LCT.

Genistein Chemoprevention: Timing and Mechanisms of Action in Murine Mammary and Prostate

Abstract: We investigated the potential of genistein, the primary isoflavone of soy, to protect against breast and prostate cancers in animal models. For mammary cancer studies, Sprague-Dawley rats were fed AIN-76A diet ± 250 mg genistein/kg diet. Dimethylbenz[a]anthracene was administered by gavage at d 50 postpartum to induce mammary tumors. Mammary cancer chemoprevention was demonstrated after prepubertal and combined prepubertal and adult genistein treatments but not after prenatal- or adult-only treatments, demonstrating that the timing of exposure to genistein is important for mammary cancer chemoprevention. The cellular mechanism of action was found to be mammary gland and cell differentiation, as shown by whole-mount analysis and β-casein expression. An imprinting effect was shown for epidermal growth factor receptor expression in mammary terminal end buds. For prostate cancer studies, we used two models. The first was a chemically (N-methylnitrosourea) induced prostate cancer rat model. Genistein in the diet inhibited the development of invasive adenocarcinomas in a dose-dependent manner. The second model was a transgenic mouse model that resulted in spontaneously developing adenocarcinoma tumor of the prostate. Genistein in the diet reduced the incidence of poorly differentiated prostatic adenocarcinomas in a dose-dependent manner and down-regulated androgen receptor, estrogen receptor-a, progesterone receptor, epidermal growth factor receptor, insulin-like growth factor-1, and extracellular signal-regulated kinase-1 but not estrogen receptor-β and transforming growth factor-a mRNA expressions. We conclude that dietary genistein protects against mammary and prostate cancers by regulating specific sex steroid receptors and growth factor signaling pathways.

Child Feeding Practices Are Associated with Child Nutritional Status in Latin America: Innovative Uses of the Demographic and Health Surveys

Abstract: Data from the Demographic and Health Surveys (DHS) for 5 Latin American countries (7 data sets) were used to explore the feasibility of creating a composite feeding index and to examine the association between feeding practices and child height-for-age Z-scores (HAZ). The variables used for the index were as follows: current breast-feeding, use of complementary foods and liquids in the past 24 h, frequency of use over the past week and feeding frequency. The index was made age specific for 6- to 9-, 9- to 12- and 12- to 36-mo-old age groups, and age-specific feeding terciles were created. Bivariate analyses showed that feeding practices were strongly and significantly associated with child HAZ in all 7 data sets, especially after 12 mo of age. Differences in HAZ between child feeding terciles remained significant after controlling for potentially confounding influences, for all countries except Bolivia. Multiple regression analyses also revealed that better feeding practices were more important for children of lower, compared with higher socioeconomic status (in Colombia 1995 and Nicaragua 1998); among children of Ladino (Spanish speaking) compared with indigenous origin (in Guatemala 1995); and among children whose mothers had primary schooling compared with mothers with no schooling, or mothers with higher than primary school level (Peru 1996). The data available in DHS data sets can thus be used effectively to create a composite child feeding index and to identify vulnerable groups that could be targeted by nutrition education and behavior change interventions.

Folic Acid Intake from Fortification in United States Exceeds Predictions

Abstract: In 1996, the U.S. Food and Drug Administration issued a regulation requiring that all enriched cereal-grain products be fortified with folic acid by January 1998. An average increase in folic acid intake of 100 micro g/d was projected as a result of this fortification. The objective of the present study was to estimate the effect of this fortification on the intake of folic acid and total folate, and on the prevalence of individuals with inadequate folate intake and with high folic acid intake. We used data on food and nutrient intake from 1480 individuals who participated in the 5th and 6th examinations of the Framingham Offspring Cohort Study. Fortification was instituted during the 6th examination so that 931 participants were examined before its implementation (nonexposed) and 549 after implementation (exposed). Published data on total folate in enriched cereal-grain products were used to correct folate content in these foods to reflect fortification. Among nonsupplement users, folic acid intake increased by a mean of 190 [95% confidence interval (CI): 176, 204] micro g/d (P < 0.001) and total folate intake increased by a mean of 323 (95% CI: 296-350) micro g dietary folate equivalents (DFE)/d (P < 0.001) in the exposed participants. Similar increases were seen among supplement users exposed to fortification. The prevalence of exposed individuals with total folate intake below the estimated average requirement (320 micro g DFE/d) decreased from 48.6% (95% CI: 44.2-53.1%) before fortification to 7.0% (95% CI: 3.1-10.9%) after fortification in individuals who did not use folic acid supplements. This prevalence was approximately 1% or less for users of supplements both before and after fortification. Prevalence of individuals with folic acid intake above the upper tolerable intake level (1000 micro g folic acid/d) increased only among supplement users exposed to fortification (from 1.3 to 11.3%, P < 0.001). No changes in folic acid intake were observed over time in the nonexposed participants. By these estimations, folic acid fortification resulted in a mean increase in folic acid intake that was approximately twice as large as previously projected.

Metabolic Interactions of Alcohol and Folate

Abstract: The goals and objectives of these studies, conducted over the past 30 y, were to determine: a) how chronic alcoholism leads to folate deficiency and b) how folate deficiency contributes to the pathogenesis of alcoholic liver disease (ALD). The intestinal absorption of folic acid was decreased in binge drinking alcoholics and, prospectively, in volunteers fed alcohol with low folate diets. Monkeys fed alcohol for 2 y developed decreased hepatic folate stores, folic acid malabsorption and decreased hepatic uptake but increased urinary excretion of labeled folic acid. Micropigs fed alcohol for 1 y developed features of ALD in association with decreased translation and activity of intestinal reduced folate carrier. Another study in ethanol-fed micropigs demonstrated abnormal hepatic methionine and DNA nucleotide imbalance and increased hepatocellular apoptosis. When alcohol feeding was combined with folate deficiency, micropigs developed typical histological features of ALD in 14 wk, together with elevated plasma homocysteine levels, reduced liver S-adenosylmethionine and glutathione and increased markers for DNA and lipid oxidation. In summary, chronic alcohol exposure impairs folate absorption by inhibiting expression of the reduced folate carrier and decreasing the hepatic uptake and renal conservation of circulating folate. At the same time, folate deficiency accelerates alcohol-induced changes in hepatic methionine metabolism while promoting enhanced oxidative liver injury and the histopathology of ALD.

Supplemental Fructooligosaccharides and Mannanoligosaccharides Influence Immune Function, Ileal and Total Tract Nutrient Digestibilities, Microbial Populations and Concentrations of Protein Catabolites in the Large Bowel of Dogs

Abstract: The goal of this study was to examine whether supplemental fructooligosaccharides (FOS) and (or) mannanoligosaccharides (MOS) influenced indices of gut health of dogs. Adult female dogs (n = 4) surgically fitted with ileal cannulas were fed a dry, extruded, kibble diet twice daily. At each feeding, the following treatments were administered: 1) Control (no FOS or MOS); 2) 1 g FOS; 3) 1 g MOS; or 4) 1 g FOS + 1 g MOS. Fecal, ileal and blood samples were collected during the last 4 d of each 14-d period to measure protein catabolite concentrations, microbial populations, immune characteristics and nutrient digestibilities. Treatment means were compared using preplanned orthogonal contrasts. Dogs supplemented with MOS had lower (P = 0.05) fecal total aerobes and tended to have greater (P = 0.13) Lactobacillus populations. Ileal immunoglobulin (Ig) A concentrations were greater (P = 0.05) in dogs supplemented with FOS + MOS vs. control. Lymphocytes (% of total white blood cells) were greater (P < 0.05) in dogs supplemented with MOS. Serum IgA concentrations also tended (P = 0.13) to be greater in dogs supplemented with MOS. Dogs supplemented with FOS and FOS + MOS had lower (P < 0.05) fecal total indole and phenol concentrations. Dogs supplemented with MOS tended to have lower ileal DM (P = 0.149) and OM (P = 0.146) digestibilities vs. control. Results of this study suggest that dietary supplementation of FOS and MOS may have beneficial effects on colonic health and immune status of dogs.

Influence of the Protein Digestion Rate on Protein Turnover in Young and Elderly Subjects

Abstract: It has long been recognized that numerous dietary parameters, such as the amount and type of protein and nonprotein energy sources, affect protein metabolism. More recently, we demonstrated that the protein digestion rate is an independent factor regulating postprandial protein gain. Indeed, in young men, using a non-steady-state approach and intrinsically labeled milk protein fractions [whey protein (WP) and casein (CAS)] we showed that a slow digested dietary protein (CAS) induced a greater protein gain than a fast one (WP). The mechanisms of this gain also differed according to the protein rate of digestion. WP stimulated amino acid oxidation and protein synthesis without modifying proteolysis, whereas CAS increased amino acid oxidation and protein synthesis to a lesser extent and strongly inhibited proteolysis. These results led to the concept of "slow" and "fast" protein and were confirmed by further experiments during which the meals tested presented different digestion rates but were otherwise identical in terms of amino acid profile. We also analyzed the effects of fat and carbohydrates added to CAS and WP. Our preliminary results suggest that added nonprotein energy sources to CAS and WP attenuated the differences in both the protein digestion rate and protein gain. Finally, and in contrast to young subjects, a "fast" protein may be more beneficial than a "slow" one in elderly subjects, to limit body protein loss. However, long-term studies are needed to confirm this age-related effect.

A Ketogenic Diet Favorably Affects Serum Biomarkers for Cardiovascular Disease in Normal-Weight Men

Abstract: Very low-carbohydrate (ketogenic) diets are popular yet little is known regarding the effects on serum biomarkers for cardiovascular disease (CVD). This study examined the effects of a 6-wk ketogenic diet on fasting and postprandial serum biomarkers in 20 normal-weight, normolipidemic men. Twelve men switched from their habitual diet (17% protein, 47% carbohydrate and 32% fat) to a ketogenic diet (30% protein, 8% carbohydrate and 61% fat) and eight control subjects consumed their habitual diet for 6 wk. Fasting blood lipids, insulin, LDL particle size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin responses to a fat-rich meal were determined before and after treatment. There were significant decreases in fasting serum TAG (-33%), postprandial lipemia after a fat-rich meal (-29%), and fasting serum insulin concentrations (-34%) after men consumed the ketogenic diet. Fasting serum total and LDL cholesterol and oxidized LDL were unaffected and HDL cholesterol tended to increase with the ketogenic diet (+11.5%; P = 0.066). In subjects with a predominance of small LDL particles pattern B, there were significant increases in mean and peak LDL particle diameter and the percentage of LDL-1 after the ketogenic diet. There were no significant changes in blood lipids in the control group. To our knowledge this is the first study to document the effects of a ketogenic diet on fasting and postprandial CVD biomarkers independent of weight loss. The results suggest that a short-term ketogenic diet does not have a deleterious effect on CVD risk profile and may improve the lipid disorders characteristic of atherogenic dyslipidemia.