Showing papers in "Current Opinion in Clinical Nutrition and Metabolic Care in 2004"
TL;DR: Overall, alpha-linolenic acid appears to be a limited source of longer-chain n-3 fatty acids in man and so adequate intakes of preformed n- 3 polyunsaturated fatty acids, in particular docosahexaenoic acid, may be important for maintaining optimal tissue function.
Abstract: Purpose of review: This review critically evaluates current knowledge of [alpha]-linolenic acid metabolism in adult humans based on the findings of studies using stable isotope tracers and on increased dietary [alpha]-linolenic acid intake. The relative roles of [alpha]-linolenic acid and of longer-chain polyunsaturated fatty acids in cell structure and function are discussed together with an overview of the major metabolic fates of [alpha]-linolenic acid. The extent of partitioning towards [beta]-oxidation and carbon recycling in humans is described. The use and limitations of stable isotope tracers to estimate [alpha]-linolenic acid desaturation and elongation are discussed. A consensus view of the extent of [alpha]-linolenic acid conversion to longer-chain fatty acids in humans is presented. The extent to which increasing dietary [alpha]-linolenic acid intake alters the concentrations of longer-chain n-3 fatty acids is described. The biological and nutritional implications of these findings are discussed. Recent findings: Conversion of [alpha]-linolenic acid to eicosapentaenoic acid is limited in men and further transformation to docosahexaenoic acid is very low. A lower proportion of [alpha]-linolenic acid is used as a substrate for [beta]-oxidation in women compared with men, while the fractional conversion to longer-chain fatty acids is greater, possibly due to the regulatory effects of oestrogen. Summary: Overall, [alpha]-linolenic acid appears to be a limited source of longer-chain n-3 fatty acids in man and so adequate intakes of preformed n-3 polyunsaturated fatty acids, in particular docosahexaenoic acid, may be important for maintaining optimal tissue function. Capacity to upregulate [alpha]-linolenic acid transformation in women may be important for meeting the demands of the fetus and neonate for docosahexaenoic acid.
414 citations
TL;DR: Testosterone induces skeletal muscle hypertrophy by multiple mechanisms, including its effects in modulating the commitment of pluripotent mesenchymal cells, which lead to improved muscle strength and leg power; however, further studies are needed to determine the effects of testosterone on physical function and health-related outcomes in sarcopenia associated with aging and chronic illness.
Abstract: Purpose of reviewTo highlight recent data demonstrating direct anabolic effects of androgens on the mammalian skeletal muscle and review the mechanisms by which testosterone regulates body composition.Recent findingsTestosterone increases lean body mass and decreases fat mass in young men; the magni
386 citations
TL;DR: This review describes the literature published in the last few years concerning nutritional deficiencies after bariatric surgery as well as their etiology, incidence, treatment and prevention and gives special attention to adolescents, mainly girls at reproductive age who have a substantial risk of developing iron deficiency.
Abstract: Purpose of reviewThe number of adolescent and adult patients submitting to bariatric surgery is increasing rapidly around the world. This review describes the literature published in the last few years concerning nutritional deficiencies after bariatric surgery as well as their etiology, incidence,
319 citations
TL;DR: Sarcopenia is likely a multifactorial condition that impairs physical function and predisposes to disability and may be prevented or treated with lifestyle interventions and pharmacological treatment.
Abstract: Purpose of reviewThis review article focuses on the changes that occur in muscle with age, specifically the involuntary loss of muscle mass, strength and function, termed sarcopenia. Particular emphasis is given to the metabolic alterations that characterize sarcopenia, and to the potentially treata
303 citations
TL;DR: The new information adds pieces of evidence to the assumption that butyrate may ameliorate colonic inflammation and may be chemopreventive in carcinogenesis, and justifies the need for carefully designed clinical trials to test the benefits derived frombutyrate production.
Abstract: Purpose of reviewShort-chain fatty acids are important end products of bacterial carbohydrate fermentation in the colon. In particular, n-butyrate is thought to play a regulatory role in the maintenance of a physiological environment. Disturbances in the interplay between the microflora and the lini
238 citations
TL;DR: Factors contributing to variation in total daily energy expenditure and its primary components are reviewed, including resting metabolic rate; diet-induced thermogenesis; and activity thermogenesis, including exerciseEnergy expenditure and nonexercise activity.
Abstract: Purpose of reviewTo review factors contributing to variation in total daily energy expenditure and its primary components: (1) resting metabolic rate; (2) diet-induced thermogenesis; and (3) activity thermogenesis, including exercise energy expenditure and nonexercise activity. For each component, t
217 citations
TL;DR: In the pathogenesis of cancer anorexia, cytokines play a pivotal role influencing the imbalance of orexigenic and anorexigenic circuits that regulate the homeostatic loop of body-weight regulation, leading to cachexia.
Abstract: Purpose of reviewCancer anorexia-cachexia syndrome is observed in 80% of patients in the advanced stages of cancer and is a strong independent risk factor for mortality. Numerous cytokines produced by tumor and immune cells, interacting with the neuropeptidergic system, mediate the cachectic effect
173 citations
TL;DR: The role of proinflammatory cytokines in the development of muscular abnormalities resulting in a loss of muscle mass and function is focused on and the description of new molecular targets that might lead to new therapeutic options for the treatment of muscular atrophy is described.
Abstract: Purpose of reviewMetabolic abnormalities leading to a catabolic syndrome with progressive muscular atrophy are a common final stage of various chronic diseases. Proinflammatory cytokines have been suggested both to induce and mediate local catabolic mechanisms. This review focuses on the role of pro
171 citations
TL;DR: Preliminary evidence suggests that neither the metabolic activity of the fat-free body, nor the obligatory phase of the thermic effect of food is different between those with and without injury, and persons with chronic spinal cord injury should be encouraged to engage in increased frequency, intensity and/or duration of physical activity.
Abstract: Purpose of reviewObesity is a common secondary complication of chronic spinal cord injury and is associated with adverse metabolic sequelae. Because positive energy balance is the fundamental cause of obesity, we herein review the current knowledge pertaining to total daily energy expenditure, inclu
162 citations
TL;DR: In conclusion, clinical intervention to boost Akt signaling or modulate myostatin and NF-κB activities may prove useful in diseases associated with chronic muscle wasting and the requirement of the PI(3)K/Akt pathway in the regulation of muscle hypertrophy is confirmed.
Abstract: Purpose of review Regulation of muscle size is essential for proper development and homeostasis of adult musculature. This regulation is mediated in large part by signal transduction pathways that promote the synthesis or breakdown of skeletal muscle. PI(3)K/Akt, myostatin and NF-kappaB represent three such pathways that will be the focus of this review. Recent findings Recent reports solidify the requirement of the PI(3)K/Akt pathway in the regulation of muscle hypertrophy. In response to IGF-1, Akt activates downstream effectors, mTOR and p70S6K to stimulate protein synthesis thereby increasing the cytoplasmic compartment in muscle fibers. Tsc2 was also identified as a novel Akt target, whose phosphorylation and inactivation by Akt may lead to an increase in cell size. The mechanisms by which myostatin functions in muscle wasting was recently explored using in-vitro assays of myogenesis. Myostatin was found to repress myogenesis by inhibiting the synthesis and activity of MyoD. Paradoxically, myostatin expression is itself regulated by MyoD binding to the myostatin promoter. The NF-kappaB transcription factor also functions as a negative regulator of myogenesis by inhibiting MyoD. Chronic activation of NF-kappaB has been associated with muscle wasting, but the mechanisms by which this regulation occurs remain for the most part unknown. Summary Recent cell culture and animal studies have provided insight on the mechanisms by which Akt, myostatin, and NF-kappaB signaling pathways regulate muscle size. Clinical intervention to boost Akt signaling or modulate myostatin and NF-kappaB activities may prove useful in diseases associated with chronic muscle wasting.
162 citations
TL;DR: In adults, within the normal physical activity index range, the distribution of time spent at activities with low and moderate intensity determines the physical activity level, and high-intensity activity does not have much impact on daily energy expenditure.
Abstract: Purpose of review This is a review on the measurement of physical activity under daily life conditions. The focus is on the doubly labelled water method and accelerometry. Doubly labelled water is a gold standard and the reference for the validation of field methods to assess physical activity. Accelerometry is the most objective and precise technique to assess activity patterns in terms of frequency, duration and intensity. Applications of the two techniques are illustrated with the limits of physical activity and energy expenditure and with activity intensity as a determinant of the physical activity level. Recent findings The upper limit of the physical activity index (total energy expenditure as a multiple of basal metabolic rate) of 2.5, as derived from cross-sectional data, is confirmed by training intervention studies. Exercise training, in which total energy expenditure was measured before and at the end of the training programme, showed no increase in physical activity index when training was combined with an energy restricted diet and in elderly subjects. In children, the distribution of time spent at activities with low and high intensity determines the physical activity index while in adults moderate-intensity activities are the main determinant. Summary In adults, within the normal physical activity index range, the distribution of time spent at activities with low and moderate intensity determines the physical activity level. High-intensity activity does not have much impact on daily energy expenditure. High-intensity activity is not required to increase the activity energy expenditure.
TL;DR: It is concluded that glutamine has a beneficial effect on infectious complications and reduces hospital stay and in critically ill patients glutamine supplementation may reduce morbidity and mortality.
Abstract: Purpose of reviewThe aim of this review is to describe the clinical relevance of supplementation of glutamine from the recent literature. First, new basic research is examined and subsequently recent clinical trials and a metaanalysis are illustrated.Recent findingsGlutamine has a major impact on th
TL;DR: Dietary factors are important but still under-explored candidates in the search for environmental strategies to reduce the enormous impact of allergic diseases in modernized societies.
Abstract: Purpose of review: With escalating rates of allergic disease, it is vital to explore novel causal pathways. This review examines the evidence for a potential role of changing dietary intake of [omega]-3 polyunsaturated fatty acids in the development, treatment and prevention of allergic diseases. Recent findings: Although it is difficult to determine the contribution of altered (decreased) dietary intake of [omega]-3 polyunsaturated fatty acids to the recent rise in the incidence of allergic disease, there is growing evidence that these nutrients have antiinflammatory properties and may modulate immune responses. These fatty acids have few side effects, and may be of some benefit in established allergic diseases (such as asthma and atopic dermatitis), although these effects are not strong. Because of this limited efficacy in established disease, the focus has shifted to the potential benefits of these immune modulators in earlier life for disease prevention. Two recent preliminary reports in infants suggest that dietary [omega]-3 polyunsaturated fatty acid supplements in pregnancy or in the early postnatal period could have immunomodulatory properties and associated clinical effects, although more studies are now needed. Novel synthetic polyunsaturated fatty acids with more potent and selective antiinflammatory effects may also provide safe therapeutic and preventive strategies in the future. Summary: Dietary factors are important but still under-explored candidates in the search for environmental strategies to reduce the enormous impact of allergic diseases in modernized societies. There is an ongoing need for further research into the role of [omega]-3 polyunsaturated fatty acids in allergic disease, particularly in early life before atopy is established.
TL;DR: N-3 polyunsaturated fatty acids, usually provided as fish oil, modulate expression of a number of genes with such broad functions as DNA binding, transcriptional regulation, transport, cell adhesion, cell proliferation, and membrane localization, which may significantly modify cell function, development and/or maturation.
Abstract: Purpose of reviewThis review focuses on the effect(s) of n-3 polyunsaturated fatty acids on gene transcription as determined by data generated using cDNA microarrays. Introduced within the past decade, this methodology allows detection of the expression of thousands of genes simultaneously and, henc
TL;DR: It is reasonable to conclude that the risk exposure through physical activity is outweighed by its overall benefits, and health authorities strongly encourage participation in moderate intensity physical activity on a daily basis.
Abstract: Purpose of reviewThis article will summarize the current findings on the effects of physical activity on human health and well-being.Recent findingsPhysical activity is associated with enhanced health and reduced risk of all-cause mortality such as cardiovascular disease, hypertension, type 2 diabet
TL;DR: Until more definite data are available, although soy foods and isoflavones can not be viewed as substitutes for established anti-osteoporotic medications health professionals can feel justified in encouraging postmenopausal women concerned about bone health to incorporate soyfoods into their diet.
Abstract: Purpose of reviewOsteoporosis is a worldwide problem of immense magnitude that is expected to worsen in many countries with aging populations. Consequently, there is a need to identify ways to reduce the risk of developing this disease. This is especially true in light of clinical trial data showing
TL;DR: The occurrence of oxidative stress in critically ill patients is associated with a poor prognosis and the measurement of a cluster of assays representative of the quantification of reactive species or of antioxidants may improve the usefulness of therapeutic intervention and increase knowledge of pathophysiological alterations.
Abstract: Purpose of review Oxidative stress is caused by a higher production of reactive oxygen and reactive nitrogen species or a decrease in endogenous protective antioxidative capacity. In all types of critical illness, such as sepsis, trauma, burn injury, acute pancreatitis, liver injury, severe diabetes, acute respiratory distress syndrome, AIDS and kidney failure, the occurrence of increased oxidative stress or a reduced antioxidative status is described. Whereas in the past, reactive oxygen and reactive nitrogen species were mainly known as harmful agents, recent investigations have given a new insight into the (patho)physiological importance of these substances as powerful messenger molecules involved in gene regulation, thereby enabling the synthesis of cytokines or adhesion molecules necessary for defending inflammatory processes. As shown in this review, there are numerous possibilities for the quantification of oxidative stress. Recent findings Several investigations showed a close association of single or multiple parameters, such as total antioxidative capacity, lipid peroxidation, vitamins C and E, the activation of nuclear factor kappa B, and respiratory burst, with the patient's outcome. However, no recommendation for a single parameter to be measured can be given because the assays described do not allow the definition of an overall "antioxidative status" for patients. Summary The occurrence of oxidative stress in critically ill patients is associated with a poor prognosis. The measurement of a cluster of assays representative of the quantification of reactive species or of antioxidants may improve the usefulness of therapeutic intervention and increase knowledge of pathophysiological alterations.
TL;DR: Recent studies have led to refinements in the understanding of the urea cycle and agmatine metabolism, and the most exciting findings in the field are coming from studies indicating new roles for the arginases in various diseases.
Abstract: Purpose of review Arginine metabolism has been a topic of intense interest over the past 15-20 years, primarily with regard to the role of arginine as the nitrogen donor for nitric oxide synthesis. However, other important aspects of arginine metabolism, such as arginine transport and arginine catabolism via the arginases, arginine decarboxylase or agmatinase, have been less well studied. The purpose of this review is to highlight recent studies on the urea cycle, agmatine metabolism, and the arginases. Recent findings Recent advances include the cloning of complementary DNA encoding agmatinase, N-acetylglutamate synthetase, and proteins involved in mitochondrial arginine transport, as well as initial investigations of their regulation and tissue-specific expression. The most exciting results of studies in this area over the past year or so have indicated new roles for the arginases in health and disease, as a result of their effects on the synthesis of nitric oxide, proline, or polyamines, or on the expression of specific genes by their ability to limit the availability of free arginine. Summary Recent studies have led to refinements in our understanding of the urea cycle. Agmatine metabolism is still largely a mystery, although the isolation of cloned cDNA for agmatinase and possibly also arginine decarboxylase should stimulate much needed investigations in this area. The most exciting findings in the field are coming from studies indicating new roles for the arginases in various diseases.
TL;DR: Obesity is a common problem in the elderly, although its prevalence decreases in extreme old age, and prevention and treatment programmes have the potential to decrease the impact of diabetes, vascular disease, and other complications of obesity.
Abstract: Purpose of review: To investigate emerging data on the relationship between obesity, increased morbidity and mortality, and decreased function in the elderly. To examine what is known about the effectiveness of interventions, and how treatment might be improved.
Recent findings: Obesity is a common problem in the elderly, although its prevalence decreases in extreme old age. Decreased physical activity and decreased energy expenditure with ageing predispose to fat accumulation and fat redistribution. Reduction in muscle mass (sarcopenic obesity) is an important determinant of physical function and metabolic rate. Chronic inflammation and endocrine changes contribute to the changes in metabolism and body composition that accompany ageing, and are potential therapeutic targets. Body weight and body mass index are imperfect indicators of risk from obesity. The focus of treatment should be on reduction of intra-abdominal fat and preservation of muscle mass and strength. A number of recent studies have confirmed the effectiveness of exercise interventions in the elderly. Progressive resistance training, rather than endurance exercise, may be more effective in many cases. Reduced function and decreased quality of life accompany development of the complications of obesity such as diabetes and vascular disorders. There is considerable scope to impede the development of these complications in the elderly with lifestyle interventions.
Summary: Sarcopenic obesity, with accumulation of intra-abdominal fat, is a major determinant of health status in the elderly. As in the younger population, prevention and treatment programmes have the potential to decrease the impact of diabetes, vascular disease, and other complications of obesity.
TL;DR: Methods for a more detailed analysis of the physiological and metabolic deficits leading to falls in the elderly may provide a better understanding of frailty in general.
Abstract: Purpose of reviewThere is currently intense interest in understanding why certain elderly individuals become frail and disabled with age whereas others do not. Is frailty the result of an acceleration of normal aging processes or is it the result of chronic medical conditions that are superimposed o
TL;DR: Studies reported in the past 18 months have greatly expanded knowledge of one of the signaling pathways through which amino acids act to regulate mTOR and also the molecular interactions that mediate the interaction between m TOR and two downstream substrates, eukaryotic initiation factor 4E binding protein 1 and ribosomal protein S6 kinase.
Abstract: Purpose of reviewThe purpose of this review is to provide a summary of the current state of knowledge concerning one of the intracellular signal transduction pathways through which amino acids, and in particular leucine, regulate the initiation phase of mRNA translation. The primary focus is on a pr
TL;DR: Better training in the detection, prevention and management of fluid and electrolyte imbalance is needed to reduce common and serious morbidity associated with this problem to which the elderly are especially prone, owing to their diminished physiological reserves and increased comorbidity.
Abstract: Purpose of reviewThe intake of water and electrolytes is inseparable from the ingestion of nutrients by normal or artificial means. Recent reports have agreed in criticizing the poor standards of practice and of training in the management of fluid and electrolyte balance, resulting in a large amount
TL;DR: It is suggested that proteins and drugs that inactivate myostatin, or interfere with its binding to its receptor, may be useful for the therapy of wasting and degenerative muscle diseases and for the food industry.
Abstract: Purpose of review To review papers on myostatin published in 2003 and early 2004. Myostatin is a negative regulator of skeletal muscle mass produced in this tissue. Inactivating mutations of the myostatin gene or interaction of myostatin protein with follistatin and other inhibitory proteins induce a hypermuscular phenotype in cattle and mice; this is assumed to result from inhibition of muscle cell proliferation and DNA and protein synthesis (antianabolic effects). Myostatin also controls muscle mass in other animals, and appears to affect adipose tissue mass. Recent findings New protein interactions inhibiting myostatin that lead to double muscling, as well as the induction of hypermuscularity with myostatin antibodies, or the generation of a myostatin conditional knockout mouse, have been reported. Conversely, a transgenic mouse over-expressing myostatin and exhibiting reduced muscle mass in a gender-specific process has been obtained. In addition, novel inactivating mutations in the myostatin gene and genetic loci regulating myostatin effects, and the characterization of the myostatin gene and its effects on metabolism in fish and chicken have been described. Finally, the regulation of myostatin levels by growth hormone, glucorticoids, anabolic agents, nutritional status and exercise, the characterization of myostatin signaling pathways, and the clarification of myostatin effects on cell replication and differentiation, are other important recent findings. Summary These studies suggest that proteins and drugs that inactivate myostatin, or interfere with its binding to its receptor, may be useful for the therapy of wasting and degenerative muscle diseases and for the food industry. Other promising approaches may derive from new insights into the biochemical cascade that mediates myostatin effects, and into the role of myostatin in the regulation of fat metabolism and of heart and muscle regeneration after injury.
TL;DR: All reviews of patients with enterocutaneous fistulae reveal that the best results with the least morbidity are obtained by definitive resection and end-to-end anastomoses.
Abstract: Purpose of reviewEnterocutaneous fistulae are abnormal communications between the small or large bowel and the skin, which may be lined with epithelium or associated with intra-abdominal sepsis. Patients with high fluid and electrolyte losses are best managed in a nutrition unit by a dedicated team
TL;DR: It is demonstrated that the use of improved anatomical and physiological techniques and animal models with targeted gene modifications lead to an improved understanding of the complex role of gastrointestinal signals in the control of energy homeostasis.
Abstract: PURPOSE OF REVIEW: The control of glucose and energy homeostasis, including feeding behaviour, is tightly regulated by gut-derived peptidic and nonpeptidic endocrine mediators, autonomic nervous signals, as well as nutrients such as glucose. We will review recent findings on the role of the gastrointestinal tract innervation and of portal vein glucose sensors; we will review selected data on the action of gastrointestinally released hormones.
RECENT FINDINGS: The involvement of mechanosensory vagal afferents in postprandial meal termination has been clarified using mouse models with selective impairments of genes required for development of mechanosensory fibres. These activate central glucogen-like peptide-1/glucogen-like peptide-2 containing ascending pathways linking the visceroceptive brainstem neurons to hypothalamic nuclei. Mucosal terminals comprise the chemosensory vagal afferents responsive to postprandially released gastrointestinal hormones. The mechanism by which the hepatoportal glucose sensor stimulates glucose utilization by muscles was demonstrated, using genetically modified mice, to be insulin-independent but to require GLUT4 and AMP-kinase. This sensor is a key site of glucogen-like peptide-1 action and plays a critical role in triggering first phase insulin secretion. PeptideYY and ghrelin target intracerebral receptors as they are bidirectionally transported across the blood brain barrier. The anorectic functions of peripherally released peptideYY may however be mediated both via vagal afferents and intracerebral Y2 receptors in the brainstem and arcuate nucleus.
SUMMARY: These recent findings demonstrate that the use of improved anatomical and physiological techniques and animal models with targeted gene modifications lead to an improved understanding of the complex role of gastrointestinal signals in the control of energy homeostasis.
TL;DR: It is indicated that stress may be a significant factor in the pathogenesis of metabolic disorders, and nutritional intervention or pharmacological agents targeted at modulating stress should be investigated.
Abstract: Purpose of reviewVarious threatening stimuli, such as pain, low blood pressure, or infection, elicit a set of neuroendocrine responses that include an increased secretion of catecholamines and glucocorticoid from the adrenal gland and activation of the sympathetic nervous system. These hormonal secr
TL;DR: The identification of an antimyostatin monoclonal antibody shows the promise of myostatin as a target for muscle-wasting disorders; the antibody has already been shown to increase muscle mass in healthy older mice and muscle function in postnatal mdx mice.
Abstract: Purpose of reviewThis review discusses recent developments in myostatin research, focusing on the basic actions of myostatin on skeletal muscle, the identification of key regulatory elements of the myostatin pathway, and the promise of myostatin as a therapeutic target in muscle-related disorders.Re
TL;DR: Malnutrition is a worsening factor in chronic obstructive pulmonary disease and altitude exposure point to the importance of hypoxia in this regard, and a better understanding of the underlying mechanisms will help to find alternative therapeutic approaches.
Abstract: Purpose of review Loss of body mass and exercise intolerance are common findings in chronic obstructive pulmonary disease and are often difficult to reverse despite optimal nutritional intake. Similar findings have been reported in healthy individuals during high-altitude exposure. The role of hypoxia in modulating metabolism has been largely investigated in vitro and in animal studies. More fragmentary is the knowledge regarding hypoxia effects on in-vivo human metabolism. This paper reviews recent literature regarding the effects of chronic exposure to hypoxia on metabolism, particularly comparing chronic obstructive pulmonary disease patients with humans exposed to high altitude. Recent findings Hypoxia has important metabolic effects. Many oxygen-sensitive regulatory mechanisms work through hypoxia inducible factor 1, and recent literature regarding the hypoxic stimulus and its pathological implications deals largely with hypoxia inducible factor 1-related findings. Hypoxia inducible factor 1 is pivotal in the adaptation to chronic hypoxia: it induces gene expression for fructose-2-6-biphosphatase, an enzyme switching glucose metabolism towards glycolysis, allowing energy production in anaerobic conditions. Hypoxia inducible factor 1 is also involved in the development of anorexia because it induces the promoter of the leptin gene. Particularly important for future therapeutic implications are findings related to hypoxia inducible factor 1 polymorphism and interaction with other molecules, especially estrogens, in the clinical evolution of disease. Summary Malnutrition is a worsening factor in chronic obstructive pulmonary disease. Similarities between chronic obstructive pulmonary disease and altitude exposure point to the importance of hypoxia in this regard. A better understanding of the underlying mechanisms will help to find alternative therapeutic approaches.
TL;DR: Evidence for the role of folate in depression and dementia in the aged is increasing, although there remains much about mechanisms to be determined.
Abstract: 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.
TL;DR: A fundamental advance in our understanding of endocrine control of energy balance and body weight came with the discovery of the adipocyte-derived hormone leptin this article, which appeared to be the long-sought peripheral signal pathway from the adipose tissue to the brain.
Abstract: Purpose of reviewA fundamental advance in our understanding of endocrine control of energy balance and body weight came with the discovery of the adipocyte-derived hormone leptin. The leptin pathway appeared to be the long-sought peripheral signal pathway from the adipose tissue to the brain involve