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Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study.
Pedersen, M, Asprusten, TT, Godang, K, Leegaard, TM, Osnes, LT, Skovlund, E, Tjade, T, Øie, MG, Wyller, VBB
Brain, behavior, and immunity. 2019;75:94-100
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Chronic fatigue is defined as substantial fatigue lasting for more than six months. The main aim of this study is to investigate predictors of chronic fatigue six months after an acute Epstein-Barr virus (EBV) infection. This study includes the prospective results from the first six months of the CEBA project (chronic fatigue following acute Epstein-Barr virus infection in adolescents), which encompasses a prospective, a cross-sectional and a randomized controlled design with a total follow-up time of 21 months. A total of 200 adolescents with EBV and 70 healthy controls were included. Results indicate that fatigue six months after acute EBV infection is significantly and independently predicted by baseline clinical symptoms, functional impairments, negative emotions, verbal memory, plasma c-reactive protein (CRP) and plasma vitamin B12. On average, baseline CRP levels were significantly lower in the acute EBV infection group as compared to healthy controls. Authors conclude that development of fatigue is to a larger extent predicted by baseline variables related to symptoms and functions than to baseline variables reflecting infectious and immune processes.
Abstract
INTRODUCTION Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue and Chronic Fatigue Syndrome (CFS). This study investigated baseline predictors of chronic fatigue six months after an acute EBV infection. MATERIALS AND METHODS A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. We performed linear regression to assess possible associations between baseline predictors and fatigue (Chalder Fatigue Questionnaire total score) six months after the acute EBV infection. A total of 70 healthy controls were included for cross-sectional reference. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents). RESULTS In the final multiple linear regression model, fatigue six months after acute EBV infection was significantly and independently predicted by the following baseline variables (regression coefficient B[95% CI]): Sensory sensitivity (0.8[0.09-1.6]), pain severity (0.2[0.02-0.3]), functional impairment (1000 steps/day) (-0.3[-0.5 to -0.08]), negative emotions (anxiety) (0.4[0.2-0.6]), verbal memory (correct word recognition) (1.7[0.1-3.3]), plasma C-reactive protein (2.8[1.1-4.4] for CRP values >0.86) and plasma Vitamin B12 (-0.005[-0.01 to -0.001]). CONCLUSIONS Development of fatigue after acute EBV infection is to a larger extent predicted by baseline variables related to symptoms and functions than to baseline variables reflecting infectious and immune processes. TRIAL REGISTRATION ClinicalTrials, ID: NCT02335437, https://clinicaltrials.gov/ct2/show/NCT02335437.
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Nutrition Interventions in Rheumatoid Arthritis: The Potential Use of Plant-Based Diets. A Review.
Alwarith, J, Kahleova, H, Rembert, E, Yonas, W, Dort, S, Calcagno, M, Burgess, N, Crosby, L, Barnard, ND
Frontiers in nutrition. 2019;6:141
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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by joint pain and inflammation with both genetic and modifiable risk factors. Research suggests a plant-based diet may play a role in management and remission. The aim of this review was to summarize the associations between plant-based diet patterns and RA symptoms. Current studies indicate an association between improvements in RA symptoms with weight loss and with plant-based diets. Based on these findings, the authors conclude excess weight and diets that include animal products may exacerbate symptoms associated with RA, whereas plant-based diets may help reduce pain and inflammation in these patients. The authors suggest further research is needed to test the effectiveness of plant-based diets on patients with RA.
Abstract
Rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease, affects roughly 1% of the world's population. RA pathogenesis remains unclear, but genetic factors account for 50-60% of the risk while the remainder might be linked to modifiable factors, such as infectious diseases, tobacco smoking, gut bacteria, and nutrition. Dietary triggers may play an inciting role in the autoimmune process, and a compromised intestinal barrier may allow food components or microorganisms to enter the blood stream, triggering inflammation. In addition, excessive body weight may affect pharmacotherapy response and the likelihood of disease remission, as well as the risk of disease mortality. Evidence suggests that changes in diet might play an important role in RA management and remission. Several studies have shown improvements in RA symptoms with diets excluding animal products. Studies have also shown that dietary fiber found in these plant-based foods can improve gut bacteria composition and increase bacterial diversity in RA patients, thus reducing their inflammation and joint pain. Although some of the trigger foods in RA patients are individualized, a vegan diet helps improve symptoms by eliminating many of these foods. This review examines the potential role of a plant-based diet in mediating RA symptoms. Further research is needed to test the effectiveness of plant-based diets on joint pain, inflammation, and quality of life in patients with RA.
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Associations between Dietary Patterns and Bile Acids-Results from a Cross-Sectional Study in Vegans and Omnivores.
Trefflich, I, Marschall, HU, Giuseppe, RD, Ståhlman, M, Michalsen, A, Lampen, A, Abraham, K, Weikert, C
Nutrients. 2019;12(1)
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Colorectal cancer is associated with higher intakes of meat and lower consumption of fibre. Fibre may alter cholesterol and bile acid production and high bile acids may cause changes in the cells of the colon. Vegan diets high in fibre and low in fat may affect bile acid production and this observational study of 72 people aimed to compare bile acids in the faeces and blood of vegans and omnivores. The results showed that vegans had higher fibre and lower fat intakes, compared to omnivores, and although bile acids in the faeces were lower in vegans, blood levels were higher. Fat intake was associated with increased bile acids in the faeces whereas fibre intake was associated with lower levels. Coffee, fish, margarine, fried potatoes, bread, and processed meat were all associated with increased bile acids in the faeces and muesli was associated with lower levels. It was concluded that high fibre, low-fat intakes characteristic of vegan diets, are associated with lower bile acids in the faeces and this could impact colorectal cancer incidence. This study could be used by healthcare professionals to recommend a vegan diet high in fibre and low in saturated fat to individuals with colorectal cancer or those who are at an increased risk.
Abstract
Bile acids play an active role in fat metabolism and, in high-fat diets, elevated concentrations of fecal bile acids may be related to an increased risk of colorectal cancer. This study investigated concentrations of fecal and serum bile acids in 36 vegans and 36 omnivores. The reduced rank regression was used to identify dietary patterns associated with fecal bile acids. Dietary patterns were derived with secondary and conjugated fecal bile acids as response variables and 53 food groups as predictors. Vegans had higher fiber (p < 0.01) and lower fat (p = 0.0024) intake than omnivores. In serum, primary and glycine-conjugated bile acids were higher in vegans than in omnivores (p ≤ 0.01). All fecal bile acids were significantly lower in vegans compared to omnivores (p < 0.01). Processed meat, fried potatoes, fish, margarine, and coffee contributed most positively, whereas muesli most negatively to a dietary pattern that was directly associated with all fecal bile acids. According to the pattern, fat intake was positively and fiber intake was inversely correlated with bile acids. The findings contribute to the evidence that, in particular, animal products and fat may play a part in higher levels of fecal bile acids.
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Effect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: A randomized controlled trial.
Del Bo', C, Riso, P, Gardana, C, Brusamolino, A, Battezzati, A, Ciappellano, S
Clinical nutrition (Edinburgh, Scotland). 2019;38(2):575-583
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Vitamin B12 (cyanocobalamin) represents an important and essential water-soluble nutrient involved in the formation of erythrocytes, in the maintenance of the central nervous system, and in cognitive performance. The aim of this study was to evaluate the ability of two different doses (350ug/week vs 2000 mg/week) of sublingual supplements in improving the nutritional status of cyanocobalamin in a group of vegans and vegetarians with a marginal deficiency. Forty subjects were enrolled and randomly divided into two groups of 20 subjects each for a 12-week double-blind (participants and outcome assessors), randomised, controlled, parallel dietary intervention study. Results indicate that as a little as 350ug per week of vitamin B12 supplementation was enough to correct a marginal deficiency of cobalamin and to improve biomarkers of cobalamin status in a group of vegans and vegetarians. Authors conclude that even though vitamin B12 supplementation is important for vegetarians and vegans with a marginal deficiency, the absence of a consensus on vitamin B12 cut-off values and the high individual variability make it difficult to identify the real needs for vegans and vegetarians.
Abstract
BACKGROUND & AIMS Vegetarians and vegans are more vulnerable to vitamin B12 deficiency with severe risks of megaloblastic anemia, cognitive decline, neuropathy, and depression. An easy and simple method of supplementation consists of taking one weekly dosage of 2000 μg. However, single large oral doses of vitamin B12 are poorly absorbed. The present research evaluates the ability of two different sublingual dosages of vitamin B12 (350 μg/week vs 2000 μg/week) in improving cyanocobalamin (vitamin B12) nutritional status in vegans and vegetarians with a marginal deficiency. METHODS A 12-week randomized, double-blind, controlled, parallel intervention trial was performed. Forty subjects with marginal vitamin B12 deficiency were enrolled and randomly divided into two groups: test group Ld (low dose, 350 μg/week) and control group Hd (high dose, 2000 μg/week) vitamin B12 supplementation. Blood samples were collected at baseline and after 15, 30, 60, and 90 days from the intervention for the determination of vitamin B12, related metabolic markers, and blood cell counts. RESULTS Two-way analysis of variance showed a significant effect of time (P < 0.0001) and of time × treatment interaction (P = 0.012) on serum concentration of vitamin B12 that increased after 90-day supplementation (Ld and Hd) compared to baseline. Both the supplements increased (P < 0.0001, time effect) the levels of holotranscobalamin, succinic acid, methionine and wellness parameter, while decreased (P < 0.0001, time effect) the levels of methylmalonic acid, homocysteine and folate compared to baseline. No difference was observed between groups (Ld vs Hd). No effect was detected for vitamin B6 and blood cell count. CONCLUSIONS In our experimental conditions, both supplements were able to restore adequate serum concentrations of vitamin B12 and to improve the levels of related metabolic blood markers in subjects with a marginal deficiency. The results support the use of a sublingual dosage of 50 μg/day (350 μg/week) of cobalamin, instead of 2000 μg/week (provided as a single dose), to reach a state of nutritional adequacy of vitamin B12 in this target population. This study was registered at www.isrctn.org as ISRCTN75099618.
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Plant-Based Diets Are Associated With a Lower Risk of Incident Cardiovascular Disease, Cardiovascular Disease Mortality, and All-Cause Mortality in a General Population of Middle-Aged Adults.
Kim, H, Caulfield, LE, Garcia-Larsen, V, Steffen, LM, Coresh, J, Rebholz, CM
Journal of the American Heart Association. 2019;8(16):e012865
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Plant based diets have been associated with better health outcomes, however mixed results have been shown on their relationship with death by any cause and death due to heart disease. This cohort study of 15792 middle aged people aimed to determine if plant-based diets are associated with a lower risk of heart disease, death due to heart disease or death due to any cause and whether this was on a sliding scale depending on adherence to a healthful plant-based diet. The results showed that individuals following a plant-based diet had a 16% lower risk of heart disease, 32% lower risk of death due to heart disease and a 25% lower risk of death by any cause and individuals who followed a healthier plant-based diet were at an even lower risk of heart disease, death due to heart disease and death due to any cause. Interestingly when margarine was included in an individual’s diet, the decreased risk of heart disease was attenuated. It was concluded that higher adherence to a healthy plant-based diet was associated with a lower risk of heart disease, death due to heart disease and death by any cause. This study could be used by healthcare practitioners to recommend a plant-based diet to those at an increased risk of heart disease.
Abstract
Background Previous studies have documented the cardiometabolic health benefits of plant-based diets; however, these studies were conducted in selected study populations that had narrow generalizability. Methods and Results We used data from a community-based cohort of middle-aged adults (n=12 168) in the ARIC (Atherosclerosis Risk in Communities) study who were followed up from 1987 through 2016. Participants' diet was classified using 4 diet indexes. In the overall plant-based diet index and provegetarian diet index, higher intakes of all or selected plant foods received higher scores; in the healthy plant-based diet index, higher intakes of only the healthy plant foods received higher scores; in the less healthy plant-based diet index, higher intakes of only the less healthy plant foods received higher scores. In all indexes, higher intakes of animal foods received lower scores. Results from Cox proportional hazards models showed that participants in the highest versus lowest quintile for adherence to overall plant-based diet index or provegetarian diet had a 16%, 31% to 32%, and 18% to 25% lower risk of cardiovascular disease, cardiovascular disease mortality, and all-cause mortality, respectively, after adjusting for important confounders (all P<0.05 for trend). Higher adherence to a healthy plant-based diet index was associated with a 19% and 11% lower risk of cardiovascular disease mortality and all-cause mortality, respectively, but not incident cardiovascular disease (P<0.05 for trend). No associations were observed between the less healthy plant-based diet index and the outcomes. Conclusions Diets higher in plant foods and lower in animal foods were associated with a lower risk of cardiovascular morbidity and mortality in a general population.
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Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.
Hall, KD, Ayuketah, A, Brychta, R, Cai, H, Cassimatis, T, Chen, KY, Chung, ST, Costa, E, Courville, A, Darcey, V, et al
Cell metabolism. 2019;30(1):67-77.e3
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Diets high in ultra-processed foods have been related to several poor health outcomes and even death, possibly due to properties that make them highly palatable resulting in overeating and obesity. However, to date, there are few studies that demonstrate this relationship. This randomised control trial of 20 individuals aimed to compare the effects of an ultra-processed diet to an unprocessed diet on energy intake. The results showed that the ultra-processed diet resulted in higher energy intakes due to increased carbohydrates and fat, whereas energy intake during the unprocessed diet remained stable and this was not due to differences in pleasantness of familiarity. During the ultra-processed diet participants gained weight, and lost weight during the unprocessed phase, due to increased energy intake. It was concluded that eliminating ultra-processed foods from the diet decreases energy intake resulting in weight loss. Healthcare professionals could use this study to understand the importance of recommending a diet without ultra-processed foods to decrease overeating and improve health.
Abstract
We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, aged (mean ± SE) 31.2 ± 1.6 years and BMI = 27 ± 1.5 kg/m2. Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508 ± 106 kcal/day; p = 0.0001), with increased consumption of carbohydrate (280 ± 54 kcal/day; p < 0.0001) and fat (230 ± 53 kcal/day; p = 0.0004), but not protein (-2 ± 12 kcal/day; p = 0.85). Weight changes were highly correlated with energy intake (r = 0.8, p < 0.0001), with participants gaining 0.9 ± 0.3 kg (p = 0.009) during the ultra-processed diet and losing 0.9 ± 0.3 kg (p = 0.007) during the unprocessed diet. Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.
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Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments.
Zuo, L, Prather, ER, Stetskiv, M, Garrison, DE, Meade, JR, Peace, TI, Zhou, T
International journal of molecular sciences. 2019;20(18)
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Reactive oxygen species (ROS) are produced during normal metabolic processes or can be induced by environmental factors. High levels of ROS in the cell can lead to oxidation causing cellular damage and a subsequent increase in inflammation, which is a significant contributor to disease. Age-associated increases in such chronic, low-grade inflammation is also referred to as inflammaging. This review summarizes how inflammaging plays a role in various age-related health conditions. Described are the mechanisms of how ROS and the age-related decline in cellular turn-over and immune activation contribute to the pathology of cardiovascular disease, cancer, neurodegeneration concerning Alzheimer’s and Parkinson’s disease, diabetes and rheumatoid arthritis. Furthermore, the authors discuss potential treatments that could assist in the management of such inflammaging-related diseases. These include vaccines to stimulate immune activity, stem cell intervention, drugs like metformin, nutritional and nutraceutical supplements like zinc, vitamin E, vitamins C, D, carotenoids, polyphenols and flavonoids like resveratrol, red algae extract and melatonin. Addressed are also general dietary concepts like calorie restriction, the benefits of the Mediterranean diet or a whole foods diet, and the potential of specific plant derived compounds like baicalin and sulforaphanes. The authors also briefly highlight the importance of the gut microbiome, as a poor gut microbiota has been associated with unfavourable age-related immune alterations and overall inflammaging. This review provides a comprehensive resource, detailing the effects and mechanisms of oxidative damage and its contribution to age-related diseases, including a list of interventions to consider when navigating the impact and risks associated with inflammaging.
Abstract
It has been proposed that a chronic state of inflammation correlated with aging known as inflammaging, is implicated in multiple disease states commonly observed in the elderly population. Inflammaging is associated with over-abundance of reactive oxygen species in the cell, which can lead to oxidation and damage of cellular components, increased inflammation, and activation of cell death pathways. This review focuses on inflammaging and its contribution to various age-related diseases such as cardiovascular disease, cancer, neurodegenerative diseases, chronic obstructive pulmonary disease, diabetes, and rheumatoid arthritis. Recently published mechanistic details of the roles of reactive oxygen species in inflammaging and various diseases will also be discussed. Advancements in potential treatments to ameliorate inflammaging, oxidative stress, and consequently, reduce the morbidity of multiple disease states will be explored.
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Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target.
Sorgdrager, FJH, Naudé, PJW, Kema, IP, Nollen, EA, Deyn, PP
Frontiers in immunology. 2019;10:2565
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Inflammation is a normal physiological process activated by the immune system in response to injury or infection. As we age, the immune system changes and the balance between pro- and anti-inflammatory agents can shift. This causes a chronic inflammatory state referred to as inflammaging. The rate of inflammaging is strongly associated with age-related disability, disease and mortality. The way in which the essential amino acid tryptophan (Trp) is broken down affects inflammation. If it is converted to kynurenine (Kyn) and its metabolites, inflammation is modulated. Studies have shown that the Kyn/Trp ratio, measured in blood, is strongly associated with ageing in humans. It could therefore be a useful marker to predict the onset of age-related diseases. This review discusses the metabolism of Trp and the links to inflammation. The authors hypothesize how intervening in these pathways could impact health- and lifespan. Future studies are needed to confirm the value of Trp metabolism as a biomarker for (un)healthy ageing and as drug target for inflammaging-related disease.
Abstract
Inflammation aims to restore tissue homeostasis after injury or infection. Age-related decline of tissue homeostasis causes a physiological low-grade chronic inflammatory phenotype known as inflammaging that is involved in many age-related diseases. Activation of tryptophan (Trp) metabolism along the kynurenine (Kyn) pathway prevents hyperinflammation and induces long-term immune tolerance. Systemic Trp and Kyn levels change upon aging and in age-related diseases. Moreover, modulation of Trp metabolism can either aggravate or prevent inflammaging-related diseases. In this review, we discuss how age-related Kyn/Trp activation is necessary to control inflammaging and alters the functioning of other metabolic faiths of Trp including Kyn metabolites, microbiota-derived indoles and nicotinamide adenine dinucleotide (NAD+). We explore the potential of the Kyn/Trp ratio as a biomarker of inflammaging and discuss how intervening in Trp metabolism might extend health- and lifespan.
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Meta-inflammaging at the crossroad of geroscience.
Chen, G, Yung, R
Aging medicine (Milton (N.S.W)). 2019;2(3):157-161
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The concept of “geroscience” represents a perspective in the understanding of the molecular underpinning of aging. Currently, seven biological processes are regarded as the underpinning of the aging process. This study is a review which focused on the link between chronic low‐grade sterile inflammation prevalent in old age and obesity‐associated metabolic inflammation. Old age, particularly in elderly adults with poor physical function or frailty, is linked to a state of chronic low‐grade sterile inflammation (inflammaging) with elevated pro‐inflammatory cytokines [a general term for the immunoregulatory cytokines that favour inflammation]. Another potential source of pro‐inflammatory cytokines in aging is adipose, or fat tissue, which can be the largest organ in obese individuals. Obesity has been linked to a low‐grade sterile chronic inflammatory state, with similarities to inflammaging, and is termed “metainflammation”. Adiposity has emerged as a major source of inflammation in both diet‐ and aging‐associated obesity, which in turn is linked to most common diseases in old age.
Abstract
Geroscience posits that selected fundamental biological processes are the foundation of age-related chronic diseases and are responsible for the decline in physical and mental function in old age. Late-life chronic low-grade inflammation ("inflammaging") and altered signal transduction pathways in metabolism have been identified as two of the key themes in the aging process. Age-related changes in the immune and metabolic responses are also recognized as playing a critical pathogenic role in most common chronic medical conditions that plague the elderly. Emerging investigations emphasize the interconnectedness of the immune and metabolic responses in aging, an area of gerontological research that can be termed "meta-inflammaging."
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Dietary Fat Intake and Metabolic Syndrome in Older Adults.
Julibert, A, Bibiloni, MDM, Mateos, D, Angullo, E, Tur, JA
Nutrients. 2019;11(8)
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Metabolic syndrome (MetS) is an umbrella term for a cluster of conditions that can increase your chance of developing heart disease, type 2 diabetes and cancer. Growing evidence points to a role of the diet and nutrients in the development of MetS. This cross-sectional nutritional survey of 477 older male and female adults aimed to assess fat intake in older adults with or without MetS. The intake of many different nutrients were analysed for relationships with MetS, however of note the results showed that individuals with MetS consumed significantly higher total fat intake but lower energy, carbohydrate and fibre intake. Part of the analysis showed that hypertension is associated with lower polyunsaturated fat intake, however stomach obesity was associated with high polyunsaturated fat and vegetable fat intake. Interestingly men with MetS reported lower consumption of ready to eat meals. It was concluded that individuals with MetS are less likely to meet recommendations for fat, carbohydrate and protein consumption than those without MetS. This study could be used by clinicians to emphasise the need for individuals with MetS to consume a variety of fruits, vegetables, fish, nuts and whole grains as part of a balanced nutrient rich diet.
Abstract
BACKGROUND Metabolic Syndrome (MetS) is associated with higher rates of cardiovascular disease (CVD), type 2 diabetes mellitus, and cancer worldwide. OBJECTIVE To assess fat intake in older adults with or without MetS. DESIGN Cross-sectional nutritional survey in older adults living in the Balearic Islands (n = 477, 48% women, 55-80 years old) with no previous CVD. METHODS Assessment of fat (total fat, MUFA, PUFA, SFA, TFA, linoleic acid, α-linolenic acid, marine and non-marine ω-3 FA, animal fat and vegetable fat, cholesterol) and macronutrient intake using a validated food frequency questionnaire, and its comparison with recommendations of the US Institute of Medicine (IOM) and the Spanish Society of Community Nutrition (SENC). RESULTS Participants with MetS showed higher BMI, lower physical activity, higher total fat and MUFA intake, and lower intake of energy, carbohydrates, and fiber than participants without MetS. Men and women with MetS were below the Acceptable Macronutrient Distribution Range (AMDR) proposed by IOM for carbohydrates and above the AMDR for total fat and MUFAs, and women were below the AMDR proposed for α-linolenic acid (ALA) compared with participants without MetS. CONCLUSIONS Subjects with MetS were less likely to meet IOM and SENC recommendations for fat and macronutrient intakes as compared to non-MetS subjects.