Search PubMed⌕ Search

Biomedical subjects

Irwin H Rosenberg

Publications and source records attributed to Irwin H Rosenberg.

At least 19 recordsLinked to original sources

Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials.

BACKGROUND: Despite their important role in cognitive function, the value of B vitamin supplementation is unknown. A systematic review of the effect of pyridoxine hydrochloride (hereinafter "vitamin B(6)"), cyanocobalamin or hydroxycobalamin (hereinafter "vitamin B(12)"), and folic acid supplementation on cognitive function was performed. METHODS: Literature search conducted in MEDLINE with supplemental articles from reviews and domain experts. We included English language randomized controlled trials of vitamins B(6) and/or B(12) and/or folic acid supplementation with cognitive function outcomes. RESULTS: Fourteen trials met our criteria; most were of low quality and limited applicability. Approximately 50 different cognitive function tests were assessed. Three trials of vitamin B(6) and 6 of vitamin B(12) found no effect overall in a variety of doses, routes of administration, and populations. One of 3 trials of folic acid found a benefit in cognitive function in people with cognitive impairment and low baseline serum folate levels. Six trials of combinations of the B vitamins all concluded that the interventions had no effect on cognitive function. Among 3 trials, those in the placebo arm had greater improvements in a small number of cognitive tests than participants receiving either folic acid or combination B-vitamin supplements. The evidence was limited by a sparsity of studies, small sample size, heterogeneity in outcomes, and a lack of studies that evaluated symptoms or clinical outcomes. CONCLUSION: The evidence does not yet provide adequate evidence of an effect of vitamin B(6) or B(12) or folic acid supplementation, alone or in combination, on cognitive function testing in people with either normal or impaired cognitive function.

Cognition↗

Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification.

BACKGROUND: Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical. OBJECTIVE: We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score < 34) in senior participants in the 1999-2002 US National Health and Nutrition Examination Survey. DESIGN: The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration < 148 pmol/L or a serum methylmalonic acid concentration > 210 nmol/L-the maximum of the reference range for serum vitamin B-12-replete participants with normal creatinine. RESULTS: After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate > 59 nmol/L (80th percentile), as opposed to < or = 59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were < 1.0 (P(interaction) < 0.05), but significantly < 1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9). CONCLUSION: In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment.

Aged↗

Challenges and opportunities in the translation of the science of vitamins.

Some 100 y after the description and naming of the first vitamin, this conference on the state-of-the-science has shown that remarkable and exciting advances have been made in our understanding of the biology, chemistry, and metabolism of vitamins, explaining their essentiality in the diet. A great deal more needs to be done in the translation of this knowledge into an understanding of the benefit of vitamin supplements to disease prevention and to health and well-being. Not only are advances in fundamental science and biology necessary, but more attention must be paid to genomics, epigenetics, behavioral science, and new techniques for evidence analysis of studies. Information relating individual vitamins or small combinations of vitamins to disease prevention is stronger than that for multivitamins, formulations that cry out for greater standardization. This large task of translating emerging science to better policy in the field of vitamin and multivitamin-mineral supplement use should occupy our attention intensively in the years to come. Issues needing more attention include the content and labeling of such products and the effects of the products on nutrient adequacy as well as in chronic degenerative disease prevention. In this quest, the development of more and better surrogate markers will be critical. Dose-response assessments of safety are badly needed for updating Tolerable Upper Intake Levels. At its best, all of these disparate types of research will require a robust interaction between the public and private sectors in a regulatory framework that supports and rewards investment in good science.

Chronic Disease↗

Hydration and cognitive function in children.

Adequate fluid intake is critical for survival. While adults are at liberty to drink fluids as wanted, children and infants are dependent upon caregivers for food and fluid. Children are at greater risk for dehydration than adults due to their higher surface-to-mass ratio. Additionally, children have different thirst sensitivities and body cooling mechanisms than adults. Children differ from adults in total body water content, and boys and girls differ in body water content with maturation. Research in young adults shows that mild dehydration corresponding to only 1% to 2% of body weight loss can lead to significant impairment in cognitive function. Dehydration in infants is associated with confusion, irritability, and lethargy; in children, it may produce decrements in cognitive performance.

Body Surface Area↗

Age-related changes in neutral sphingomyelin-specific phospholipase C activity in striatum, hippocampus, and frontal cortex: implication for sensitivity to stress and inflammation.

UNLABELLED: Previous studies show the enrichment of mammalian brain with neutral sphingomyelin-specific phospholipase C (ceramide-phosphocholine phosphodiesterase, EC 3.1.4.12; N-Sase), a key enzyme of sphingolipid metabolism and sphingolipid-induced signaling. OBJECTIVE: The objective of this study was to evaluate the membrane-associated and cytosolic N-Sase activities in the brain regions associated with behavior (striatum, hippocampus, and frontal cortex). RESULTS: Results showed higher membrane-associated N-Sase activity as compared to the N-Sase activity in the cytosolic fractions of all the evaluated brain regions. In the hippocampus, the N-Sase activity was significantly higher than in the striatum and cortex. In addition, age-related changes in the hippocampal N-Sase activities were profoundly higher than in the respective fractions isolated from the striatum and cortex. Age-related decreases in the hippocampal and striatal cytosolic N-Sase activities were accompanied by increases in the membrane N-Sase activities in those brain regions. There was a significant increase in the cortical membrane-associated N-Sase activity with age; however, to a much lesser extend than in other brain regions. The increase in the hippocampal membrane-associated N-Sase activity was accompanied by a higher expression of the inflammatory marker, interleukin-1 beta (IL-1 beta), with age. One of the important findings of the present study is the region-specific expression of heat shock protein 70 (hsp70). Frontal cortex showed lower hsp70 expression in both young and old age groups as compared to the striatal and hippocampal hsp70 levels which can contribute to the recently reported higher cortical sensitivity to oxidative stress. CONCLUSION: In conclusion (a) our results, for the first time to our knowledge, demonstrated the association between the N-Sase activity and the stress/inflammatory markers expression in the brain regions controlling behavior; (b) these findings suggest the role of N-Sase as a contributor to the increased stress and inflammatory sensitivity among the brain regions with age.

Aging↗

Interdepartmental Committee on Nutrition for National Defense surveys in Asia and Africa.

I suppose I should establish my bonafides for participation in this symposium. I did participate in 3 Interdepartmental Committee on Nutrition for National Defense (ICNND) surveys as far separated as one on the Blackfeet Indian Reservation (1) in Montana and 2 in Asia-Burma (2) and East Pakistan (3). In fact, the Blackfeet Reservation and Burma surveys were my training grounds for becoming the clinical chief for the East Pakistan survey and later the codirector. More importantly, in 1962, I followed Alan Forbes, who is much missed at this symposium, as the deputy to Arnie Schaefer at ICNND and NIH, and did have experience of an office in the Stone House on the NIH campus. There I participated in the transmutation of the ICNND to the Interdepartmental Committee on National Development and its alignment with the Office of International Research at the NIH and a repositioning within the Department of Health and Human Services. It was from this position that ICNND went on to organize some civilian surveys in the mid-1960s, including those in Central America and Panama (4), and it was from this position that the groundwork was laid for the application of ICNND techniques to the first U.S. domestic survey outside of an Indian reservation, culminating in the Ten State Nutrition Survey (5), which documented that there was hunger in America, as well as abroad.

Africa↗

Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women.

The purpose of this study was to determine skeletal muscle cutpoints for identifying elevated physical disability risk in older adults. Subjects included 4,449 older (> or = 60 years) participants from the Third National Health and Nutrition Examination Survey during 1988-1994. Physical disability was assessed by questionnaire, and bioimpedance was used to estimate skeletal muscle, which was normalized for height. Receiver operating characteristics were used to develop the skeletal muscle cutpoints associated with a high likelihood of physical disability. Odds for physical disability were compared in subjects whose measures fell above and below these cutpoints. Skeletal muscle cutpoints of 5.76-6.75 and < or =5.75 kg/m2 were selected to denote moderate and high physical disability risk in women. The corresponding values in men were 8.51-10.75 and < or =8.50 kg/m2. Compared with women with low-risk skeletal muscle values, women with moderate- and high-risk skeletal muscle values had odds for physical disability of 1.41 (95% confidence interval (CI): 0.97, 2.04) and 3.31 (95% CI: 1.91, 5.73), respectively. The corresponding odds in men were 3.65 (95% CI: 1.92, 6.94) and 4.71 (95% CI: 2.28, 9.74). This study presents skeletal muscle cutpoints for physical disability risk in older adults. Future applications of these cutpoints include the comparison of morbidity risk in older persons with normal muscle mass and those with sarcopenia, the determination and comparison of sarcopenia prevalences, and the estimation of health-care costs attributable to sarcopenia.

Activities of Daily Living↗

Relations of plasma homocysteine to left ventricular structure and function: the Framingham Heart Study.

AIMS: Hyperhomocysteinaemia is a risk factor for congestive heart failure, especially in women. We investigated if homocysteine promotes left ventricular (LV) remodelling. METHODS AND RESULTS: We examined cross-sectional relations of plasma total homocysteine to echocardiographic LV structure and function in 2697 Framingham Heart Study participants (mean age 58 years, 58% women) free of heart failure and previous myocardial infarction. Adjusting for age and height, plasma homocysteine was positively related to LV mass, wall thickness, and relative wall thickness in women (p=0.0004-0.04), but not in men (p=0.28-0.68). Adjusting additionally for other clinical covariates, the relations of plasma homocysteine to LV mass and wall thickness in women remained statistically significant, but the relation to relative wall thickness became of borderline significance (1.92 g, 0.01 cm, and 0.29% increase, respectively, for a 1-SD increase in ln[homocysteine], p=0.01-0.08). LV mass and wall thickness were higher in the fourth quartile of plasma homocysteine compared to the lower three in all models in women (p=0.0003-0.02), but not in men (p=0.25-0.78). Plasma homocysteine was not related to left atrial size or LV fractional shortening in either sex. CONCLUSION: In our community-based sample, plasma homocysteine was directly related to LV mass and wall thickness in women but not in men.

Cardiac Volume↗

Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial.

BACKGROUND: High homocysteine and low B vitamin concentrations have been linked to the risk of vascular disease, stroke, and dementia and are relatively common in older adults. OBJECTIVE: We assessed the effect of breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 on vitamin and homocysteine status. DESIGN: A randomized, double-blind trial was conducted in 189 volunteers aged 50-85 y. The subjects had no history of hypertension, anemia, asthma, cancer, or cardiovascular or digestive disease and did not regularly consume multiple or B vitamin supplements or highly fortified breakfast cereal. Subjects were randomly assigned to consume 1 cup (0.24 L) breakfast cereal fortified with 440 microg folic acid, 1.8 mg vitamin B-6, and 4.8 microg vitamin B-12 or placebo cereal for 12 wk. Blood was drawn at 0, 2, 12, and 14 wk. Methionine-loading tests were conducted at baseline and week 14. RESULTS: Final baseline-adjusted plasma homocysteine concentrations were significantly lower and B vitamin concentrations were significantly higher in the treatment group than in the placebo group (P < 0.001). The percentage of subjects with plasma folate concentrations < 11 nmol/L decreased from 2% to 0%, with vitamin B-12 concentrations < 185 pmol/L from 9% to 3%, with vitamin B-6 concentrations < 20 nmol/L from 6% to 2%, and with homocysteine concentrations > 10.4 micromol/L (women) or > 11.4 micromol/L (men) from 6.4% to 1.6%. The percentage of control subjects with values beyond these cutoff points remained nearly constant or increased. CONCLUSIONS: In this relatively healthy group of volunteers, consumption of 1 cup fortified breakfast cereal daily significantly increased B vitamin and decreased homocysteine concentrations, including post-methionine-load homocysteine concentrations.

Aged↗

Folate and brain function in the elderly.

PURPOSE OF REVIEW: Over the past several decades, folate has emerged as an important nutrient in several key conditions of concern to the elderly. Subclinical levels of folate inadequacy can have significant negative impacts on health in older individuals. RECENT FINDINGS: Serum and red blood cell folate levels are associated with depression in younger individuals, but the relationship is less clear in older people. However, folate status does predict response to antidepressant treatment in older individuals. Cognitive decline and some forms of dementia, including Alzheimer's disease, are associated with lower folate levels. Supplementation with folic acid can provide cognitive benefits in some circumstances. Folic acid supplementation is generally regarded as safe; however, there remains some concern that high levels of folic acid may exacerbate the neurological consequences of a vitamin B12 deficiency. SUMMARY: Evidence for the role of folate in depression and dementia in the aged is increasing, although there remains much about mechanisms to be determined.

Aged↗

The atherogenic effect of excess methionine intake.

Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways. Elevated plasma homocysteine (hyperhomocysteinemia) is associated with occlusive vascular disease. Whether homocysteine per se or a coincident metabolic abnormality causes vascular disease is still an open question. Animals with genetic hyperhomocysteinemia have so far not displayed atheromatous lesions. However, when methionine-rich diets are used to induce hyperhomocysteinemia, vascular pathology is often observed. Such studies have not distinguished the effects of excess dietary methionine from those of hyperhomocysteinemia. We fed apolipoprotein E-deficient mice with experimental diets designed to achieve three conditions: (i) high methionine intake with normal blood homocysteine; (ii) high methionine intake with B vitamin deficiency and hyperhomocysteinemia; and (iii) normal methionine intake with B vitamin deficiency and hyperhomocysteinemia. Mice fed methionine-rich diets had significant atheromatous pathology in the aortic arch even with normal plasma homocysteine levels, whereas mice fed B vitamin-deficient diets developed severe hyperhomocysteinemia without any increase in vascular pathology. Our findings suggest that moderate increases in methionine intake are atherogenic in susceptible mice. Although homocysteine may contribute to the effect of methionine, high plasma homocysteine was not independently atherogenic in this model. Some product of excess methionine metabolism rather than high plasma homocysteine per se may underlie the association of homocysteine with vascular disease.

Animals↗

Plasma homocysteine, hypertension incidence, and blood pressure tracking: the Framingham Heart Study.

Plasma homocysteine is cross-sectionally associated with blood pressure in large, community-based studies. It is unknown whether elevated plasma homocysteine predicts hypertension incidence. We investigated the relations of baseline plasma total homocysteine levels to hypertension incidence and blood pressure tracking in 2104 Framingham Heart Study participants (mean age, 57 years; 58% women), who were free of hypertension, myocardial infarction, heart failure, atrial fibrillation, or renal failure at baseline. Baseline mean+/-SD plasma homocysteine was 10.1+/-3.7 micromol/L. On follow-up 4 years from baseline, 360 persons (17.1%) had developed hypertension, and 878 persons (41.7%) had progressed to a higher blood pressure stage. In unadjusted analyses, a 1-SD higher log homocysteine value was associated with increased odds of developing hypertension (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.05 to 1.32) and increased odds of blood pressure progression (OR, 1.17; 95% CI, 1.07 to 1.27). The relations of plasma homocysteine to the incidence of hypertension or blood pressure progression were statistically nonsignificant in age- and sex-adjusted logistic regression models (OR, 0.98; 95% CI, 0.87 to 1.11 and OR, 1.05; 95% CI, 0.96 to 1.16, respectively) and in multivariable models adjusted for age, sex, body mass index, diabetes, interim weight change, smoking, serum creatinine, baseline blood pressure, and blood pressure category (OR, 0.92; 95% CI, 0.81 to 1.06 and OR, 1.07; 95% CI, 0.97 to 1.18, respectively). In conclusion, we found no major relation of baseline plasma homocysteine levels to hypertension incidence or longitudinal blood pressure progression in a large, community-based cohort of nonhypertensive individuals after adjustment for age, sex, and other important covariates.

Blood Pressure↗

Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction.

CONTEXT: Elevated plasma homocysteine levels are associated with increased risk of vascular disease. It is unclear whether elevated homocysteine levels are a risk factor for congestive heart failure (CHF). OBJECTIVE: To study prospectively the association between nonfasting plasma homocysteine and incidence of CHF. DESIGN, SETTING, AND PARTICIPANTS: Community-based prospective cohort study of 2491 adults (mean age 72 years, 1547 women) who participated in the Framingham Heart Study during the 1979-1982 and 1986-1990 examinations and were free of CHF or prior myocardial infarction (recognized or unrecognized) at baseline. MAIN OUTCOME MEASURE: Incidence of a first episode of CHF during an 8-year follow-up period. RESULTS: During follow-up, 156 subjects (88 women) developed CHF. In multivariable analyses controlling for established risk factors for CHF including the occurrence of myocardial infarction (recognized or unrecognized) during follow-up, plasma homocysteine levels higher than the sex-specific median value were associated with an adjusted hazards ratio for heart failure of 1.93 in women (95% confidence interval, 1.19-3.14) and 1.84 in men (95% confidence interval, 1.06-3.17). The relation of plasma homocysteine levels to CHF risk was more continuous in women than in men. In analyses restricted to participants without any manifestation of coronary heart disease at baseline, the association of plasma homocysteine levels with risk of CHF was maintained in men and women. CONCLUSIONS: An increased plasma homocysteine level independently predicts risk of the development of CHF in adults without prior myocardial infarction. Additional investigations are warranted to confirm these findings.

Aged↗

Demographics and trends in overweight and obesity in patients at time of kidney transplantation.

BACKGROUND: The epidemic of overweight and obesity is one of the most serious public health problems in the United States, although information regarding its effect on chronic kidney transplant patients is sparse. The authors describe the prevalence, demographics, and trends in overweight and obesity at the time of kidney transplantation. METHODS: Data were obtained from a national transplant database that included all kidney transplants since 1987. Body mass indices (BMI) at time of transplantation were stratified by demographic categories and year. Trends of overweight and obesity between the general population and subjects undergoing kidney transplantation were compared. Logistic regression analyses were performed to identify variables associated with increased likelihood of being obese. RESULTS: The majority (60%) of subjects at time of transplantation currently are overweight or obese. Between 1987 and 2001, the proportion of obese transplant recipients rose by 116%. The rate of increase was grossly similar to that in the general population. The likelihood of being obese increased with age, female sex, noninsulin-dependent diabetes mellitus, black race, and the more recent the transplant year. Conversely, the proportion of recipients with lower BMI fell by approximately 50%. CONCLUSIONS: Overweight and obesity are very prevalent at the time of kidney transplantation and are eclipsing protein-energy malnutrition as the more common nutritional illness. This may have profound negative effects on patient and allograft outcomes. Nephrologists may need to reexamine traditional notions of nutritional disease and therapeutic strategies to more effectively deal with this formidable challenge.

Adolescent↗

Tropical enteritis: nutritional consequences and connections with the riddle of cholera.

One of the important consequences of the infection-nutrition interaction is mediated by malabsorption associated with chronic inflammation in the intestine, enteritis. Studies made possible after development of the peroral intestinal biopsy technique in the 1950s indicated the wide prevalence of enteropathy, particularly in tropical developing countries with poor levels of sanitation. Some consider this so-called subclinical tropical malabsorption to be the base of an iceberg, whose tip is tropical sprue, a severe form of malabsorption leading to nutritional deficiency that had been reported in colonial expatriates in tropical countries for 200 y. Some of the first demonstrations of the prevalence of tropical enteritis in Asia were made in quest of the pathologic lesion of cholera, and further examination of the water and electrolyte, as well as nutrient, malabsorption in cholera led serendipitously to the discovery of the oral rehydration solution for the treatment of diarrheal disease.

Cholera↗