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Trends in the contribution of greenhouse gas emissions from food and beverage purchases in Mexico: 1989–2020

Assessing the trends in dietary GHGE considering the social patterning is critical for understanding the role that food systems have played and will play in global emissions in countries of the global south. O...

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Higher oxidative balance score was associated with decreased risk of erectile dysfunction: a population-based study

Erectile dysfunction (ED) is a prevalent condition that is thought to be significantly impacted by oxidative stress. The oxidative balance score (OBS) has been built to characterize the state of antioxidant/pr...

Correction: Effect of soy isoflavone supplementation on blood pressure: a meta-analysis of randomized controlled trials

The original article was published in Nutrition Journal 2024 23 :32

National trends in nine key minerals intake (quantity and source) among U.S. adults, 1999 to march 2020

Changes in economy and dietary guidelines brought a great shock to diet quality and meal behaviors, but if these transformations have extended to minerals intake and their sources was still poorly understood. ...

Causal relationship of interleukin-6 and its receptor on sarcopenia traits using mendelian randomization

Previous research has extensively examined the role of interleukin 6 (IL-6) in sarcopenia. However, the presence of a causal relationship between IL-6, its receptor (IL-6R), and sarcopenia remains unclear.

Development and application of the Meal and Snack Assessment (MESA) quality scale for children and adolescents using item response theory

Meals differ in terms of food items and nutritional quality. The aim of the present study was to propose a scale to measure the meals quality of schoolchildren according to food processing degree, perform a pr...

Estimating effects of whole grain consumption on type 2 diabetes, colorectal cancer and cardiovascular disease: a burden of proof study

Previous studies on whole grain consumption had inconsistent findings and lacked quantitative assessments of evidence quality. Therefore, we aimed to summarize updated findings using the Burden of Proof analys...

Nonlinear relationship between oxidative balance score and hyperuricemia: analyses of NHANES 2007–2018

Limited data regarding the correlation between oxidative balance score (OBS) and hyperuricemia highlights the necessity for thorough investigations. This study aims to examine the link between OBS, which incor...

Effects of whole grains on glycemic control: a systematic review and dose-response meta-analysis of prospective cohort studies and randomized controlled trials

Whole grains have recently been promoted as beneficial to diabetes prevention. However, the evidence for the glycemic benefits of whole grains seems to conflict between the cohort studies and randomized contro...

Remnant cholesterol is an effective biomarker for predicting survival in patients with breast cancer

Breast cancer is the most common malignancy in women worldwide. The relationship between remnant cholesterol (RC) and the prognosis of patients with breast cancer has not been clearly reported. This study inve...

Epidemiological study of pediatric nutritional deficiencies: an analysis from the global burden of disease study 2019

Nutritional deficiencies (ND) continue to threaten the lives of millions of people around the world, with children being the worst hit. Nevertheless, no systematic study of the epidemiological features of chil...

Association between watching eating broadcast “Mukbang and Cookbang” and body mass index status in South Korean adolescents stratified by gender

It has been suggested that Mukbang and Cookbang, a type of eating broadcast originating from Korea and gaining popularity, may contribute to obesity. However, despite suggestions that Mukbang might contribute ...

The global diet quality score as an indicator of adequate nutrient intake and dietary quality – a nation-wide representative study

The Global Diet Quality Score (GDQS) was developed to be a simple, timely and cost-effective tool to track, simultaneously, nutritional deficiency and non-communicable disease risks from diet in diverse settin...

Development of a sustainable diet index in US adults

A transformation towards healthy diets through a sustainable food system is essential to enhance both human and planet health. Development of a valid, multidimensional, quantitative index of a sustainable diet...

Maternal vitamin D status and risk of gestational diabetes mellitus in twin pregnancies: a longitudinal twin pregnancies birth cohort study

Gestational diabetes mellitus (GDM) is a common complication of pregnancy, with significant short-term and long-term implications for both mothers and their offspring. Previous studies have indicated the poten...

Correction: Dietary intake and gastrointestinal symptoms are altered in children with Autism Spectrum Disorder: the relative contribution of autism-linked traits

The original article was published in Nutrition Journal 2024 23 :27

A late eating midpoint is associated with increased risk of diabetic kidney disease: a cross-sectional study based on NHANES 2013–2020

Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, ...

Traditional japanese diet score and the sustainable development goals by a global comparative ecological study

Reducing the environmental impact of the food supply is important for achieving Sustainable Development Goals (SDGs) worldwide. Previously, we developed the Traditional Japanese Diet Score (TJDS) and reported ...

Association between dietary magnesium intake and muscle mass among hypertensive population: evidence from the National Health and Nutrition Examination Survey

Magnesium is critical for musculoskeletal health. Hypertensive patients are at high risk for magnesium deficiency and muscle loss. This study aimed to explore the association between magnesium intake and muscl...

Adult dietary patterns with increased bean consumption are associated with greater overall shortfall nutrient intakes, lower added sugar, improved weight-related outcomes and better diet quality

Limited evidence is available that focuses on beans within American dietary patterns and health. The purpose of this study was to identify commonly consumed adult dietary patterns that included beans and compa...

Validity and reproducibility of the PERSIAN Cohort food frequency questionnaire: assessment of major dietary patterns

Dietary patterns, encompassing an overall view of individuals’ dietary intake, are suggested as a suitable means of assessing nutrition’s role in chronic disease development. The aim of this study was to evalu...

Associations of dietary patterns and longitudinal brain-volume change in Japanese community-dwelling adults: results from the national institute for longevity sciences-longitudinal study of aging

The association of dietary patterns and longitudinal changes in brain volume has rarely been investigated in Japanese individuals. We prospectively investigated this association in middle-aged and older Japane...

Association between serum 25-hydroxyvitamin D and vitamin D dietary supplementation and risk of all-cause and cardiovascular mortality among adults with hypertension

The relationship between vitamin D status and mortality among adults with hypertension remains unclear.

Effect of soy isoflavone supplementation on blood pressure: a meta-analysis of randomized controlled trials

Previous experimental studies have suggested that the consumption of soy isoflavones may have a potential impact on lowering blood pressure. Nevertheless, epidemiological studies have presented conflicting out...

The Correction to this article has been published in Nutrition Journal 2024 23 :53

The effects of L-carnitine supplementation on inflammation, oxidative stress, and clinical outcomes in critically Ill patients with sepsis: a randomized, double-blind, controlled trial

Sepsis, a life-threatening organ dysfunction caused by a host’s dysregulated response to infection with an inflammatory process, becomes a real challenge for the healthcare systems. L-carnitine (LC) has antiox...

Metabolic syndrome risk in adult coffee drinkers with the rs301 variant of the LPL gene

Metabolic syndrome (MetS), a cluster of metabolic and cardiovascular risk factors is influenced by environmental, lifestyle, and genetic factors. We explored whether coffee consumption and the rs301 variant of...

Towards objective measurements of habitual dietary intake patterns: comparing NMR metabolomics and food frequency questionnaire data in a population-based cohort

Low-quality, non-diverse diet is a main risk factor for premature death. Accurate measurement of habitual diet is challenging and there is a need for validated objective methods. Blood metabolite patterns refl...

Circulating concentrations of bile acids and prevalent chronic kidney disease among newly diagnosed type 2 diabetes: a cross-sectional study

The relationship between circulating bile acids (BAs) and kidney function among patients with type 2 diabetes is unclear. We aimed to investigate the associations of circulating concentrations of BAs, particul...

Dietary intake and gastrointestinal symptoms are altered in children with Autism Spectrum Disorder: the relative contribution of autism-linked traits

Dietary and gastrointestinal (GI) problems have been frequently reported in autism spectrum disorder (ASD). However, the relative contributions of autism-linked traits to dietary and GI problems in children wi...

The Correction to this article has been published in Nutrition Journal 2024 23 :40

The effect of bovine dairy products and their components on the incidence and natural history of infection: a systematic literature review

Dairy products and their components may impact immune function, although the current evidence base has some research gaps. As part of a larger systematic literature review of dairy products/components (includi...

Food sufficiency status and sleep outcomes in older adults: the National Health and Aging Trends Study (NHATS)

Studies investigating the relationship between food insecurity and sleep among older populations are limited. This study aimed to cross-sectionally examine the associations between food sufficiency status and ...

Effects of vitamin D supplementation on liver fibrogenic factors, vitamin D receptor and liver fibrogenic microRNAs in metabolic dysfunction-associated steatotic liver disease (MASLD) patients: an exploratory randomized clinical trial

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global metabolic problem which can lead to irreversible liver fibrosis. It has been shown that vitamin D and its receptors contribute to fi...

Validity of food and nutrient intakes assessed by a food frequency questionnaire among Chinese adults

Studies regarding the validity of the food frequency questionnaire (FFQ) and the food composition table (FCT) are limited in Asian countries. We aimed to evaluate the validity of a 64-item FFQ and different me...

Association of sugar intake from different sources with cardiovascular disease incidence in the prospective cohort of UK Biobank participants

The relation between incident cardiovascular disease (CVD) and sugar might not only depend on the quantity consumed but also on its source. This study aims to assess the association between various sources of ...

Association of dietary inflammatory index and the SARS-CoV-2 infection incidence, severity and mortality of COVID-19: a systematic review and dose-response meta-analysis

Several studies have reported the association between dietary inflammatory index (DII) and the SARS-CoV-2 infection risk, severity or mortality of COVID-19, however, the outcomes remain controversial.

Breakfast quality and its sociodemographic and psychosocial correlates among Italian children, adolescents, and adults from the Italian Nutrition & HEalth Survey (INHES) study

Breakfast quality, together with regularity of breakfast, has been suggested to be associated with cardiometabolic health advantages. We aimed to evaluate the quality of breakfast and its socioeconomic and psy...

The association between lifelines diet score (LLDS) with depression and quality of life in Iranian adolescent girls

It has been proposed that a greater degree of adherence to a healthy dietary pattern is associated with a lower risk of depression and a poor quality of life (QoL). The Lifelines diet score (LLDS) is a new, ev...

Diet in secondary prevention: the effect of dietary patterns on cardiovascular risk factors in patients with cardiovascular disease: a systematic review and network meta-analysis

Improving dietary habits is a first-line recommendation for patients with cardiovascular disease (CVD). It is unclear which dietary pattern most effectively lowers cardiovascular risk factors and what the shor...

Prognostic potential of nutritional risk screening and assessment tools in predicting survival of patients with pancreatic neoplasms: a systematic review

The nutritional evaluation of pancreatic cancer (PC) patients lacks a gold standard or scientific consensus, we aimed to summarize and systematically evaluate the prognostic value of nutritional screening and ...

40 years of adding more fructose to high fructose corn syrup than is safe, through the lens of malabsorption and altered gut health–gateways to chronic disease

Labels do not disclose the excess-free-fructose/unpaired-fructose content in foods/beverages. Objective was to estimate excess-free-fructose intake using USDA loss-adjusted-food-availability (LAFA) data (1970–...

Relationship between trajectories of dietary iron intake and risk of type 2 diabetes mellitus: evidence from a prospective cohort study

The association between dietary iron intake and the risk of type 2 diabetes mellitus (T2DM) remains inconsistent. In this study, we aimed to investigate the relationship between trajectories of dietary iron in...

Dietary pattern and precocious puberty risk in Chinese girls: a case-control study

The role of dietary intake on precocious puberty remains unclear. This study aimed to investigate the association between the amount and frequency of dietary intake and the risk of precocious puberty in Chines...

Tracking progress toward a climate-friendly public food service strategy: assessing nutritional quality and carbon footprint changes in childcare centers

Public food procurement and catering are recognized as important leverage points in promoting sustainable and healthy dietary habits. This study aimed to analyze changes in nutritional quality and carbon footp...

Avocado intake and cardiometabolic risk factors in a representative survey of Australians: a secondary analysis of the 2011–2012 national nutrition and physical activity survey

Avocados are a rich source of nutrients including monounsaturated fats, dietary fibre and phytochemicals. Higher dietary quality is reported in studies of consumers with higher avocado intakes. The present stu...

Components in downstream health promotions to reduce sugar intake among adults: a systematic review

Excessive sugar consumption is well documented as a common risk factor for many Non-Communicable Diseases (NCDs). Thus, an adequate intervention description is important to minimise research waste and improve ...

Improving economic access to healthy diets in first nations communities in high-income, colonised countries: a systematic scoping review

Affordability of healthy food is a key determinant of the diet-related health of First Nations Peoples. This systematic scoping review was commissioned by the Ngaanyatjarra Pitjantjatjara Yankunytjatjara Women...

Associations between estimation of salt intake and salt-restriction spoons and hypertension status in patients with poorly controlled hypertension: a community-based study from Huzhou City, Eastern China

As the prevalence of hypertension increases in China, it is advised to use salt-restriction spoons (SRS) as a lifestyle modification. This study aimed to examine the associations between estimated salt consump...

Potassium levels and the risk of all-cause and cardiovascular mortality among patients with cardiovascular diseases: a meta-analysis of cohort studies

Abnormal blood potassium levels are associated with an increased risk of cardiometabolic diseases and mortality in the general population; however, evidence regarding the association between dyskalemia and mor...

Combined versus independent effects of exercise training and intermittent fasting on body composition and cardiometabolic health in adults: a systematic review and meta-analysis

Exercise training (Ex) and intermittent fasting (IF) are effective for improving body composition and cardiometabolic health overweight and obese adults, but whether combining Ex and IF induces additive or syn...

Correction: Associations Between Plant-Based Dietary Patterns and Risks of Type 2 Diabetes, Cardiovascular Disease, Cancer, and Mortality – A Systematic Review and Meta-analysis

The original article was published in Nutrition Journal 2023 22 :46

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Nutrition Journal

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Current and Future Landscape of Nutritional Epidemiologic Research

• 1 Departments of Nutrition and Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
• 2 Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
• Viewpoint Improving the Quality of Dietary Research David S. Ludwig, MD, PhD; Cara B. Ebbeling, PhD; Steven B. Heymsfield, MD JAMA

The last half-century of nutrition research has expanded beyond traditional nutrition research based primarily on in vitro biochemistry, animal models, and short-term feeding studies with risk factors as the primary outcomes. Although such studies are still an integral part of nutrition research, they do not directly connect diets with long-term health and disease in humans. Dietary guidelines and recommendations, until recently, were in part based on professional opinions using extrapolations across species and experimental models and limited human evidence from cross-sectional or small feeding studies. Nutritional epidemiology, building on the experience of epidemiology in other fields of public health, has begun to provide important new information and has had substantial effects on diets globally.

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Hu FB , Willett WC. Current and Future Landscape of Nutritional Epidemiologic Research. JAMA. 2018;320(20):2073–2074. doi:10.1001/jama.2018.16166

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• v.369; 2020

Food for Thought 2020

Food and mood: how do diet and nutrition affect mental wellbeing, joseph firth.

1 Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health, Oxford Road, University of Manchester, Manchester M13 9PL, UK

2 NICM Health Research Institute, Western Sydney University, Westmead, Australia

James E Gangwisch

3 Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, USA

4 New York State Psychiatric Institute, New York, NY, USA

Alessandra Borsini

5 Section of Stress, Psychiatry and Immunology Laboratory, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, King’s College London, London, UK

Robyn E Wootton

6 School of Psychological Science, University of Bristol, Bristol, UK

7 MRC Integrative Epidemiology Unit, Oakfield House, Bristol, UK

8 NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK

Emeran A Mayer

9 G Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA

10 UCLA Microbiome Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA

Poor nutrition may be a causal factor in the experience of low mood, and improving diet may help to protect not only the physical health but also the mental health of the population, say Joseph Firth and colleagues

Key messages

• Healthy eating patterns, such as the Mediterranean diet, are associated with better mental health than “unhealthy” eating patterns, such as the Western diet
• The effects of certain foods or dietary patterns on glycaemia, immune activation, and the gut microbiome may play a role in the relationships between food and mood
• More research is needed to understand the mechanisms that link food and mental wellbeing and determine how and when nutrition can be used to improve mental health

Depression and anxiety are the most common mental health conditions worldwide, making them a leading cause of disability. 1 Even beyond diagnosed conditions, subclinical symptoms of depression and anxiety affect the wellbeing and functioning of a large proportion of the population. 2 Therefore, new approaches to managing both clinically diagnosed and subclinical depression and anxiety are needed.

In recent years, the relationships between nutrition and mental health have gained considerable interest. Indeed, epidemiological research has observed that adherence to healthy or Mediterranean dietary patterns—high consumption of fruits, vegetables, nuts, and legumes; moderate consumption of poultry, eggs, and dairy products; and only occasional consumption of red meat—is associated with a reduced risk of depression. 3 However, the nature of these relations is complicated by the clear potential for reverse causality between diet and mental health ( fig 1 ). For example, alterations in food choices or preferences in response to our temporary psychological state—such as “comfort foods” in times of low mood, or changes in appetite from stress—are common human experiences. In addition, relationships between nutrition and longstanding mental illness are compounded by barriers to maintaining a healthy diet. These barriers disproportionality affect people with mental illness and include the financial and environmental determinants of health, and even the appetite inducing effects of psychiatric medications. 4

Hypothesised relationship between diet, physical health, and mental health. The dashed line is the focus of this article.

While acknowledging the complex, multidirectional nature of the relationships between diet and mental health ( fig 1 ), in this article we focus on the ways in which certain foods and dietary patterns could affect mental health.

Mood and carbohydrates

Consumption of highly refined carbohydrates can increase the risk of obesity and diabetes. 5 Glycaemic index is a relative ranking of carbohydrate in foods according to the speed at which they are digested, absorbed, metabolised, and ultimately affect blood glucose and insulin levels. As well as the physical health risks, diets with a high glycaemic index and load (eg, diets containing high amounts of refined carbohydrates and sugars) may also have a detrimental effect on psychological wellbeing; data from longitudinal research show an association between progressively higher dietary glycaemic index and the incidence of depressive symptoms. 6 Clinical studies have also shown potential causal effects of refined carbohydrates on mood; experimental exposure to diets with a high glycaemic load in controlled settings increases depressive symptoms in healthy volunteers, with a moderately large effect. 7

Although mood itself can affect our food choices, plausible mechanisms exist by which high consumption of processed carbohydrates could increase the risk of depression and anxiety—for example, through repeated and rapid increases and decreases in blood glucose. Measures of glycaemic index and glycaemic load can be used to estimate glycaemia and insulin demand in healthy individuals after eating. 8 Thus, high dietary glycaemic load, and the resultant compensatory responses, could lower plasma glucose to concentrations that trigger the secretion of autonomic counter-regulatory hormones such as cortisol, adrenaline, growth hormone, and glucagon. 5 9 The potential effects of this response on mood have been examined in experimental human research of stepped reductions in plasma glucose concentrations conducted under laboratory conditions through glucose perfusion. These findings showed that such counter-regulatory hormones may cause changes in anxiety, irritability, and hunger. 10 In addition, observational research has found that recurrent hypoglycaemia (low blood sugar) is associated with mood disorders. 9

The hypothesis that repeated and rapid increases and decreases in blood glucose explain how consumption of refined carbohydrate could affect psychological state appears to be a good fit given the relatively fast effect of diets with a high glycaemic index or load on depressive symptoms observed in human studies. 7 However, other processes may explain the observed relationships. For instance, diets with a high glycaemic index are a risk factor for diabetes, 5 which is often a comorbid condition with depression. 4 11 While the main models of disease pathophysiology in diabetes and mental illness are separate, common abnormalities in insulin resistance, brain volume, and neurocognitive performance in both conditions support the hypothesis that these conditions have overlapping pathophysiology. 12 Furthermore, the inflammatory response to foods with a high glycaemic index 13 raises the possibility that diets with a high glycaemic index are associated with symptoms of depression through the broader connections between mental health and immune activation.

Diet, immune activation, and depression

Studies have found that sustained adherence to Mediterranean dietary patterns can reduce markers of inflammation in humans. 14 On the other hand, high calorie meals rich in saturated fat appear to stimulate immune activation. 13 15 Indeed, the inflammatory effects of a diet high in calories and saturated fat have been proposed as one mechanism through which the Western diet may have detrimental effects on brain health, including cognitive decline, hippocampal dysfunction, and damage to the blood-brain barrier. 15 Since various mental health conditions, including mood disorders, have been linked to heightened inflammation, 16 this mechanism also presents a pathway through which poor diet could increase the risk of depression. This hypothesis is supported by observational studies which have shown that people with depression score significantly higher on measures of “dietary inflammation,” 3 17 characterised by a greater consumption of foods that are associated with inflammation (eg, trans fats and refined carbohydrates) and lower intakes of nutritional foods, which are thought to have anti-inflammatory properties (eg, omega-3 fats). However, the causal roles of dietary inflammation in mental health have not yet been established.

Nonetheless, randomised controlled trials of anti-inflammatory agents (eg, cytokine inhibitors and non-steroidal anti-inflammatory drugs) have found that these agents can significantly reduce depressive symptoms. 18 Specific nutritional components (eg, polyphenols and polyunsaturated fats) and general dietary patterns (eg, consumption of a Mediterranean diet) may also have anti-inflammatory effects, 14 19 20 which raises the possibility that certain foods could relieve or prevent depressive symptoms associated with heightened inflammatory status. 21 A recent study provides preliminary support for this possibility. 20 The study shows that medications that stimulate inflammation typically induce depressive states in people treated, and that giving omega-3 fatty acids, which have anti-inflammatory properties, before the medication seems to prevent the onset of cytokine induced depression. 20

However, the complexity of the hypothesised three way relation between diet, inflammation, and depression is compounded by several important modifiers. For example, recent clinical research has observed that stressors experienced the previous day, or a personal history of major depressive disorders, may cancel out the beneficial effects of healthy food choices on inflammation and mood. 22 Furthermore, as heightened inflammation occurs in only some clinically depressed individuals, anti-inflammatory interventions may only benefit certain people characterised by an “inflammatory phenotype,” or those with comorbid inflammatory conditions. 18 Further interventional research is needed to establish if improvements in immune regulation, induced by diet, can reduce depressive symptoms in those affected by inflammatory conditions.

Brain, gut microbiome, and mood

A more recent explanation for the way in which our food may affect our mental wellbeing is the effect of dietary patterns on the gut microbiome—a broad term that refers to the trillions of microbial organisms, including bacteria, viruses, and archaea, living in the human gut. The gut microbiome interacts with the brain in bidirectional ways using neural, inflammatory, and hormonal signalling pathways. 23 The role of altered interactions between the brain and gut microbiome on mental health has been proposed on the basis of the following evidence: emotion-like behaviour in rodents changes with changes in the gut microbiome, 24 major depressive disorder in humans is associated with alterations of the gut microbiome, 25 and transfer of faecal gut microbiota from humans with depression into rodents appears to induce animal behaviours that are hypothesised to indicate depression-like states. 25 26 Such findings suggest a role of altered neuroactive microbial metabolites in depressive symptoms.

In addition to genetic factors and exposure to antibiotics, diet is a potentially modifiable determinant of the diversity, relative abundance, and functionality of the gut microbiome throughout life. For instance, the neurocognitive effects of the Western diet, and the possible mediating role of low grade systemic immune activation (as discussed above) may result from a compromised mucus layer with or without increased epithelial permeability. Such a decrease in the function of the gut barrier is sometimes referred to as a “leaky gut” and has been linked to an “unhealthy” gut microbiome resulting from a diet low in fibre and high in saturated fats, refined sugars, and artificial sweeteners. 15 23 27 Conversely, the consumption of a diet high in fibres, polyphenols, and unsaturated fatty acids (as found in a Mediterranean diet) can promote gut microbial taxa which can metabolise these food sources into anti-inflammatory metabolites, 15 28 such as short chain fatty acids, while lowering the production of secondary bile acids and p-cresol. Moreover, a recent study found that the ingestion of probiotics by healthy individuals, which theoretically target the gut microbiome, can alter the brain’s response to a task that requires emotional attention 29 and may even reduce symptoms of depression. 30 When viewed together, these studies provide promising evidence supporting a role of the gut microbiome in modulating processes that regulate emotion in the human brain. However, no causal relationship between specific microbes, or their metabolites, and complex human emotions has been established so far. Furthermore, whether changes to the gut microbiome induced by diet can affect depressive symptoms or clinical depressive disorders, and the time in which this could feasibly occur, remains to be shown.

Priorities and next steps

In moving forward within this active field of research, it is firstly important not to lose sight of the wood for the trees—that is, become too focused on the details and not pay attention to the bigger questions. Whereas discovering the anti-inflammatory properties of a single nutrient or uncovering the subtleties of interactions between the gut and the brain may shed new light on how food may influence mood, it is important not to neglect the existing knowledge on other ways diet may affect mental health. For example, the later consequences of a poor diet include obesity and diabetes, which have already been shown to be associated with poorer mental health. 11 31 32 33 A full discussion of the effect of these comorbidities is beyond the scope of our article (see fig 1 ), but it is important to acknowledge that developing public health initiatives that effectively tackle the established risk factors of physical and mental comorbidities is a priority for improving population health.

Further work is needed to improve our understanding of the complex pathways through which diet and nutrition can influence the brain. Such knowledge could lead to investigations of targeted, even personalised, interventions to improve mood, anxiety, or other symptoms through nutritional approaches. However, these possibilities are speculative at the moment, and more interventional research is needed to establish if, how, and when dietary interventions can be used to prevent mental illness or reduce symptoms in those living with such conditions. Of note, a recent large clinical trial found no significant benefits of a behavioural intervention promoting a Mediterranean diet for adults with subclinical depressive symptoms. 34 On the other hand, several recent smaller trials in individuals with current depression observed moderately large improvements from interventions based on the Mediterranean diet. 35 36 37 Such results, however, must be considered within the context of the effect of people’s expectations, particularly given that individuals’ beliefs about the quality of their food or diet may also have a marked effect on their sense of overall health and wellbeing. 38 Nonetheless, even aside from psychological effects, consideration of dietary factors within mental healthcare may help improve physical health outcomes, given the higher rates of cardiometabolic diseases observed in people with mental illness. 33

At the same time, it is important to be remember that the causes of mental illness are many and varied, and they will often present and persist independently of nutrition and diet. Thus, the increased understanding of potential connections between food and mental wellbeing should never be used to support automatic assumptions, or stigmatisation, about an individual’s dietary choices and their mental health. Indeed, such stigmatisation could be itself be a casual pathway to increasing the risk of poorer mental health. Nonetheless, a promising message for public health and clinical settings is emerging from the ongoing research. This message supports the idea that creating environments and developing measures that promote healthy, nutritious diets, while decreasing the consumption of highly processed and refined “junk” foods may provide benefits even beyond the well known effects on physical health, including improved psychological wellbeing.

Contributors and sources: JF has expertise in the interaction between physical and mental health, particularly the role of lifestyle and behavioural health factors in mental health promotion. JEG’s area of expertise is the study of the relationship between sleep duration, nutrition, psychiatric disorders, and cardiometabolic diseases. AB leads research investigating the molecular mechanisms underlying the effect of stress and inflammation on human hippocampal neurogenesis, and how nutritional components and their metabolites can prevent changes induced by those conditions. REW has expertise in genetic epidemiology approaches to examining casual relations between health behaviours and mental illness. EAM has expertise in brain and gut interactions and microbiome interactions. All authors contributed to, read, and approved the paper, and all the information was sourced from articles published in peer reviewed research journals. JF is the guarantor.

Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following: JF is supported by a University of Manchester Presidential Fellowship and a UK Research and Innovation Future Leaders Fellowship and has received support from a NICM-Blackmores Institute Fellowship. JEG served on the medical advisory board on insomnia in the cardiovascular patient population for the drug company Eisai. AB has received research funding from Johnson & Johnson for research on depression and inflammation, the UK Medical Research Council, the European Commission Horizon 2020, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and King’s College London. REW receives funding from the National Institute for Health Research Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. EAM has served on the external advisory boards of Danone, Viome, Amare, Axial Biotherapeutics, Pendulum, Ubiome, Bloom Science, Mahana Therapeutics, and APC Microbiome Ireland, and he receives royalties from Harper & Collins for his book The Mind Gut Connection. He is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, and the US Department of Defense. The views expressed are those of the authors and not necessarily those of the organisations above.

Provenance and peer review: Commissioned; externally peer reviewed.

This article is part of series commissioned by The BMJ. Open access fees are paid by Swiss Re, which had no input into the commissioning or peer review of the articles. T he BMJ thanks the series advisers, Nita Forouhi, Dariush Mozaffarian, and Anna Lartey for valuable advice and guiding selection of topics in the series.

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Global research trend and hotspot in the low FODMAP diet: a bibliometric analysis

• Cheng Xu 1 , 2 ,
• Zhen Song 2 ,
• Jing-yi Hu 1 ,
• Chong-chao Li 2 &
• Hong Shen 1  

Journal of Health, Population and Nutrition volume  43 , Article number:  63 ( 2024 ) Cite this article

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The low FODMAP diet is the most recommended dietary intervention for the clinical management of IBS symptoms.

Bibliometrics analysis provides a comprehensive perspective and direction on global research trend and hotspot in the low FODMAP diet research.

The restriction stage of the low FODMAP diet is superior to other dietary therapies for IBS in terms of symptom response, but it has a negative impact on the abundance of gut Bifidobacteria and diet quality.

Identification of biomarkers to predict response to the low FODMAP diet has become the current research hotspot.

Large, well-designed clinical research studies are needed in the future to investigate the long-term efficacy and safety of the low FODMAP diet, including FODMAP reintroduction and personalization stages.

According to national guidelines, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is a second-line therapy option for irritable bowel syndrome (IBS) and improves functional intestinal symptoms. Numerous noteworthy results have been published in this field over the past fifteen years. This study aims to analyze the global research trend and hotspot of the low FODMAP diet research, and provide a comprehensive perspective and direction for researchers.

The Science Citation Index-Expanded of the Web of Science Core Collection (WoSCC) was used to identify low FODMAP diet-related articles and reviews. Three bibliometric programs (CiteSpace, VOSviewer, Scimago Graphic) were utilized to analyze and visualize the annual publications, authors, countries, institutions, journals, citations, and keywords.

In total, 843 documents related to the low FODMAP diet research were published in 227 journals by 3,343 authors in 1,233 institutions from 59 countries. The United States, which was the most engaged nation in international collaboration, had the largest annual production and the fastest growth. The most productive organization was Monash University, and the most fruitful researcher was Gibson PR. Nutrients ranked first in terms of the number of published documents. The article “A diet low in FODMAPs reduces symptoms of irritable bowel syndrome” (Halmos EP, 2014) received the most co-citations. Keywords that appear frequently in the literature mainly involve two main aspects: the clinical efficacy evaluation and mechanism exploration of the low FODMAP diet. The term “gut microbiota” stands out as the most prominent keyword among the burst keywords that have remained prevalent till date.

The restriction stage of the low FODMAP diet is superior to other dietary therapies for IBS in terms of symptom response, but it has a negative impact on the abundance of gut Bifidobacteria and diet quality. Identification of biomarkers to predict response to the low FODMAP diet is of great interest and has become the current research hotspot.

Introduction

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) are a category of possibly poorly digested and absorbed but fermentable carbohydrates that can cause gastrointestinal discomfort in some people. Professor Gibson PR initially introduced the concept of the low FODMAP diet in 2005 for the prevention and treatment of Crohn’s disease [ 1 ], but the main focus of research quickly shifted to irritable bowel syndrome (IBS). IBS is a functional bowel disorder, mainly manifested by abdominal pain and bloating, accompanied by changes in bowel habits and/or abnormal stool characteristics [ 2 ]. The low FODMAP diet caused a short-term clinical response in 50–80% of IBS patients [ 3 ], and meta-analyses revealed that the diet was superior to other dietary therapies in terms of improving abdominal pain, bloating or distension, and bowel habits [ 4 ]. The low FODMAP diet was recommended as second-line therapy by national guidelines in United States [ 5 , 6 ] and the United Kingdom [ 7 , 8 ], and was perhaps the most evidence-based dietary intervention for IBS [ 5 ]. The low FODMAP diet is a therapeutic approach that includes an initial phase of restricting high FODMAP foods, followed by a systematic reintroduction process to evaluate an individual’s tolerance to different FODMAP categories. This step-wise approach ultimately leads to the development of a personalized diet plan tailored to each individual’s specific needs and tolerances [ 9 ].

Over the past fifteen years, there has been a significant increase in published studies on the low FODMAP diet. With such rapid growth, it becomes essential to adopt new approaches to review and interpret research trends. Bibliometrics, which combines mathematics, statistics, and philology, provides a multidimensional quantitative analysis and evaluation of literature, enabling a comprehensive understanding of the current state, potential development trend, and hotspot in a research area [ 10 , 11 ]. To date, no bibliometric analysis has been conducted to assess the global research trend and hotspot in the low FODMAP diet. This study aims to address the following research questions by providing a comprehensive analysis through the examination of pertinent data collected from previous research related to low FODMAP diet research (Table ​ 1 ).

Data collection

The Science Citation Index-Expanded of the Web of Science Core Collection (WoSCC) database was utilized for the search. Two authors independently conducted and verified all searches on July 1, 2023, to ensure accuracy and eliminate bias resulting from database upgrades. The search strategy was as follows: TS= (“FODMAP*” OR “Fermentable, poorly absorbed, short-chain carbohydrates” OR “Fermentable oligosaccharides, disaccharides, monosaccharides and polyols”). Taking into account the constant updating of the database, we conducted a secondary search on April 13, 2024 to integrate the results of recently published studies that met the criteria. The search encompassed the entire time range from the establishment of the database to April 13, 2024, and was limited to publications written in English. Articles and review articles related to the low FODMAP diet that could be correctly identified using bibliometric tools were included in the bibliometric analysis. The detailed search plan and data filtering procedure are displayed in Fig.  1 .

Flowchart for data collection and bibliometric analysis

• Bibliometric analysis

The full record and cited references of all literature obtained from WoSCC were downloaded in TXT format [ 12 ]. The TXT files were then imported into CiteSpace (V6.3 R1 Advanced), VOSviewer (V1.6.19), and Scimago Graphica (V1.0.40) for further analysis [ 13 , 14 , 15 ].

CiteSpace, VOSviewer, and Scimago Graphica are commonly used bibliometric and visualization software platforms [ 16 ]. CiteSpace is a Java program created by Professor Chaomei Chen to analyze and visualize trends and patterns in scientific publications [ 17 ]. In this study, CiteSpace was used for dual-map overlap analysis of journals, document co-citation analysis, and keyword-related analysis and visualization. VOSviewer, a Java-based bibliometric mapping application developed by Leiden University, excelled in processing extensive bibliometric maps based on network data and presenting scientific information [ 18 ]. VOSviewer was utilized for co-occurrence analysis, identifying patterns among countries, institutions, authors, journals, and keywords. Scimago Graphica is an application designed to analyze and visualize data. Scimago Graphica was used to produce collaboration and geographic distribution maps of publications.

Annual growth trend of publications

A total of 843 publications related to the low FODMAP diet were identified through our search strategy, including 474 articles (56.23%) and 369 review articles (43.77%). The annual number of publications is displayed in Fig.  2 . The number of publications in the early stage (2007–2012) remained small, with less than 10 publications per year. The subsequent four-year period (2013–2016) exhibited a steady growth pattern, with the annual publication count consistently exceeding twenty. Between 2017 and 2022, there was a considerable increase in the number of publications in this area, indicating that research on the low FODMAP diet has gained worldwide attention. However, there was a slight decline in the number of articles published in 2023. In general, judging from the fitting curve, the number of publications in this field will continue to grow steadily in the future.

The number of annual research publications and growth trend related to low FODMAP diet research

Distribution of countries and institutions

In total, 1,233 institutions from 59 different countries participated in the research of the low FODMAP diet. Table  2 lists the top 10 productive countries for scientific research. Most publications were produced in the United States (210, 24.91%), followed by Australia (155, 18.39%), the United Kingdom (120, 14.23%), Italy (105, 12.46%), and Canada (53, 6.29%). The United States had the highest annual output and the fastest growth, gradually overtaking Australia, which once maintained its leading position in the field. The United States was the most active country in international cooperation (Fig.  3 A), and Australia and the United Kingdom had the most common cooperation with the United States (Fig.  3 B and C). The top 10 productive institutions are listed in Table  2 , with Monash University (99, 11.71%) in Australia ranking first, followed by King’s College London (39, 4.63%), La Trobe University (23, 2.73%), and Guy’s and St Thomas’ NHS Foundation Trust (21, 2.49%). The cooperation between institutions is depicted in Fig.  3 D, with Monash University serving as the center of inter-institutional cooperation.

( A ) Network map of the collaboration analysis of the low FODMAP diet research among countries, export of results from VOSviewer. Each node represents a country. The size of the node is proportional to the number of documents published. The lines between nodes represent cooperation between countries. ( B ) Visualization map of international collaboration generated by Scimago Graphica. The size of the node represents the number of publications, and the color and thickness of the line represents the strength of cooperation between countries. ( C ) Map of geographical distribution of publications generated by Scimago Graphica. The size of the node represents the number of publications, and the color and thickness of the line represents the strength of cooperation between countries. ( D ) Network map of the collaboration analysis of the low FODMAP diet research among institutions, export of results from VOSviewer. Each node represents an institution. The size of the node is proportional to the number of documents published. The lines between nodes represent cooperation between institutions

Core author’s distribution and co-authorship network

In all, 3,343 authors contributed to research on the low FODMAP diet. Table S1 lists the top 10 authors in terms of publications and co-citations. The top three authors based on the number of publications were Gibson PR (65, 7.71%), Muir JG (44, 5.22%), and Whelan K (29, 3.44%). The network visualization map offers vivid details of cooperative interactions, aiding in the identification of possible partnerships (Fig.  4 A). In terms of co-citations, Staudacher HM had the most citations, reaching 909, followed by Halmos EP (711), and Gibson PR (607). Co-citation relationships occur when two publications are jointly cited by a third citation publication [ 19 ]. The network visualization of the relationship between co-cited authors is displayed in Fig.  4 B. Four of the top 10 productive authors were among the top 10 co-cited authors (Gibson PR, Staudacher HM, Biesiekierski JR, and Barrett JS).

Analysis of journals and co-cited journals

Publications related to the low FODMAP diet research were found in 227 journals. The top 10 productive journals and co-cited journals related to the low FODMAP diet research are listed in Table  3 . As shown in Fig.  4 C, Nutrients had the greatest volume with 140 documents (14.61%), followed by Neurogastroenterology and Motility (32, 3.80%), Journal of Gastroenterology and Hepatology (31, 3.68%), and Alimentary Pharmacology & Therapeutics (24, 2.85%). The frequency of co-citations, which indicates a journal’s substantial effect on a certain topic, is a key indicator of its influence. When ranked by co-citations, the top three journals were Gastroenterology (4174), American Journal of Gastroenterology (3166), and Gut (2642). The network visualization of co-cited journals is shown in Fig.  4 D. Among the top 10 co-cited journals, 40% were in the United Kingdom and 30% were in the United States. Additionally, 90% of these journals belonged to the Q1 or Q2 JCR division. The topical distribution of academic journals is depicted in the dual-map overlay of journals (Fig.  4 E). The colored paths show the citation relationships, with the citing journals on the left and the cited journals on the right. As shown, the low FODMAP diet research was mainly published in journals about “medicine, medical, clinical” subjects, and the documents cited by these studies were mostly published in journals related to “environmental, toxicology, nutrition”, “molecular, biology, genetics” or “health, nursing, medicine subjects”.

( A ) Network map of the collaboration analysis of low FODMAP diet research among core authors, export of results from VOSviewer. Each node represents an author. The size of the node is proportional to the number of documents published. ( B ) Network map of the co-cited authors related to low FODMAP diet research, export of results from VOSviewer. The size of the node is proportional to the number of citations. ( C ) Network map of the academic journals publishing low FODMAP diet research, export of results from VOSviewer. Each node represents a journal. The size of the node is proportional to the number of documents published. The colors represent the average year of publications (blue: earlier, yellow: later). ( D ) Network map of the co-cited journals publishing low FODMAP diet research, export of results from VOSviewer. The size of the node is proportional to the number of citations. ( E ) A dual-map overlap of journals publishing low FODMAP diet research, export of results from CiteSpace. The left side is the citing journal, the right side is the cited journal, and the longer transverse width of the ellipse indicates more documents in the relevant journal

Analysis of document co-citation

A total of 28,797 references were cited in the 843 included documents. Table  4 lists the top 10 highly co-cited documents related to research on the low FODMAP diet, all of which were clinical trials investigating the clinical efficacy of this therapy. The most highly co-cited document, authored by Halmos EP, received 217 citations. Among the top 10 highly co-cited documents, Halmos EP and Staudacher HM each had two documents. All of the top 10 highly co-cited documents were published in JCR Q1 or Q2 journals, with four of them published in Gastroenterology and two in Gut .

Analysis of keywords co-occurrence and topics trending

Keywords play a crucial role in revealing the primary themes of an academic publication. Fig.  5 A depicts the co-occurrence analysis of keywords, and Table S2 lists the top 20 keywords by frequency. Among the 459 keywords originating from the 843 included documents, the three most frequently used keywords were “irritable bowel syndrome” (529), “low FODMAP diet” (314), and “gastrointestinal symptoms” (216). The clustering visual analysis map delineates four principal research topics within the realm of low FODMAP diet, encompassing clinical trials, mechanisms, efficacy and safety, and efficacy comparison (Fig. 5 B).

The hierarchical cluster labeling method was employed to identify keywords most relevant to research on the low FODMAP diet. As shown in Fig.  5 C, these keywords were grouped into ten clusters, primarily focusing on evaluating the clinical efficacy (#0 irritable bowel syndrome, #3 ulcerative colitis, #4 quality of life, #6 symptoms, #7 inflammatory bowel disease) and exploring the mechanisms (#1 chronic pain, #2 nutrition, #9 gas production, #8 lactose malabsorption) of the low FODMAP diet. The clustering timeline view combines cluster analysis with time slice analysis to provide a clear depiction of the distribution and trend of keywords over time.

Keyword burst detection is a technique for detecting topics trending and current hotspot. The top 25 keywords with the strongest burst strength related to the low FODMAP diet research from 2007 to 2024 are presented in Fig.  5 D. Prior to 2012, there was a significant emergence of burst keywords such as “fructose malabsorption”, “lactose malabsorption”, and “common Australian vegetables”. Subsequently, from the period of 2013 to 2021, keywords like “gastrointestinal symptoms”, “placebo-controlled trial”, and “healthy subjects” exhibited a high burst strength. The recent burst in keywords such as “gut microbiota” (with a burst strength of 5.94), “mediterranean diet” (with a burst strength of 5.31), “disorders of gut brain interaction” (with a burst strength of 4.14), “carbohydrate diet” (with a burst strength of 4.05), and “scale” (with a burst strength of 3.16) reflects the emerging trends in the low FODMAP diet research. Among these keywords, “gut microbiota” stands out with the highest burst strength, signifying its position as the research hotspot in this field.

( A ) Temporal view of keywords co-occurrence generated by VOSviewer. Each node represents a keyword. The size of each node is proportional to the frequency of occurrence. The colors represent the average year of keyword occurrence (blue: earlier, yellow: later). ( B ) Clustering visual analysis map of keywords generated by VOSviewer. The size of each node is proportional to the frequency of occurrence. Nodes of different colors form separate clusters, each representing distinct research directions. ( C ) Timeline view of keywords co-occurrence generated by CiteSpace. Each node represents a keyword. The node size, indicative of occurrence frequency, correlates with the sum of their sizes along the yearly ring line. The links between keywords indicate co-occurrence, where deep blue signifies earlier appearances, deep red represents later ones, and overlapping colors denote occurrences in corresponding years. ( D ) Keywords with the strongest burst strength related to low FODMAP diet research during the period of 2007–2024. The burst period is represented by the red section on the blue timeline, export of results from CiteSpace

General information

The low FODMAP diet has gained significant attention in recent years within the scientific literature. This article presents the first study to utilize the bibliometric method for analyzing documents related to low FODMAP diet research, employing mathematical statistics and visual analysis to identify development trend and research hotspot based on data information.

Over the past fifteen years, there has been an increase in research related to the low FODMAP diet. Dietary therapy has become an important part of multidisciplinary intestinal disease management, evolving from a virtually non-existent position in the mid-20th century to one oriented on patient care and now plays an essential role in providing treatment [ 20 , 21 ]. Furthermore, the increasing research on the low FODMAP diet can be attributed to its value in controlling functional gastrointestinal symptoms, particularly in IBS. It is currently considered the most evidence-based dietary intervention for IBS [ 5 ], and has been recommended as a second-line herapy option for IBS [ 8 , 22 , 23 ]. The increase in studies demonstrates the prospective future for the low FODMAP diet research and requires greater focus and in-depth investigation.

The United States has emerged as the leading country in terms of publications in the field of low FODMAP diet research. This is unsurprising considering its academic funding and economic growth [ 24 ]. In addition to the United States, Australia, and the United Kingdom have published more than 100 documents related to the low FODMAP diet research, reflecting the fact that current studies are based on western dietary patterns. Among institutions, Monash University in Australia had the most publications worldwide. The study team from Monash University, a pioneer in this field, was the first to propose and develop the low FODMAP diet [ 1 ]. The United States and Australia exhibit the highest level of cooperation, which is unsurprising considering the United States’ significant output and Australia’s role as the initiator of low FODMAP diet research. The cooperation between the European region, represented by the United Kingdom, and the United States or Australia should not be ignored. In general, the research on the low FODMAP diet is a domain of global cooperation, so it is very important to strengthen institutional and international collaboration to promote the sustainable development of this field.

The number of publications represents the author’s contribution to the research field, and the number of citations reflects the author’s influence. Among the authors who contributed to the research of the low FODMAP diet from 2007 to 2024, Gibson PR from Monash University published the most documents. Gibson PR’s research team has been at the forefront of investigating the mechanisms and clinical aspects of this therapy. Staudacher HM from Deakin University is the most co-cited author in this field, focusing on researching the impact of the low FODMAP diet on gut microbiota, and relevant research literature has been widely cited [ 25 , 26 ]. Gibson PR, Staudacher HM, Biesiekierski JR, and Barrett JS are among the top 10 authors in terms of both published documents and citations, indicating their extensive scientific output and significant influence.

Analysis of journal publishing volume and journal co-citations can demonstrate their contributions to the field, and researchers can utilize these results to identify appropriate journals for submission. Among the 227 journals that have published low FODMAP diet research, Nutrients stands out with the highest number of publications, totaling 140. Nutrients is an international journal focused on nutrition and human health, and its considerable influence in the low FODMAP diet research field is noteworthy. It has emerged as a prominent platform for the dissemination of the latest and most extensive research in this area. Besides, documents published in Gastroenterology occupied the highest citation. As the official journal of the American Gastroenterological Association, Gastroenterology holds a prestigious position within the field of gastrointestinal diseases, demonstrating that some high-level and influential journals value the low FODMAP diet research. The results of the dual-map overlap of journals revealed that the majority of low FODMAP diet research was published in “medicine, medical, clinical” journals, and the cited literature was mostly published in “environmental, toxicology, nutrition”, “molecular, biology, genetics” or “health, nursing, medicine” journals, indicating that the research in this field was mainly focused on clinical trials and translational medicine research.

Knowledge base

Highly cited publications serve as indicators of the research hotspot within the field, and analyzing the cited references provides insights into the knowledge base of the field. Notably, the top 10 highly co-cited documents are all randomized controlled trials (RCTs) of the low FODMAP diet, serving as reliable reference resources for future research in this area. The first RCT of the low FODMAP diet found that after 4 weeks of restriction of fermentable carbohydrates, it significantly relieved the symptoms of IBS compared to a habitual diet [ 25 ]. Subsequent studies have consistently confirmed the efficacy of the low FODMAP diet. Most of these studies demonstrated that the low FODMAP diet had a positive effect on IBS symptoms compared to habitual diets [ 27 ], typical diets [ 28 , 29 ], a high FODMAP diet [ 30 ], or a sham diet [ 26 ], and several studies found its equivalent treatment efficacy to standard dietary advice [ 31 ] or general dietary guidelines [ 32 ]. However, the quality of evidence was rated as low due to potential bias stemming from a lack of double-blinding and inadequate reporting of suboptimal adverse events [ 4 ]. It is important to note that while the efficacy of the low FODMAP diet is considered “low quality evidence” according to GRADE criteria, it is recognized that dietary interventions rarely meet the criteria for “high quality evidence” used to evaluate pharmaceutical trials [ 33 ]. Several management guidelines have still recommended the use of this diet as a primary or secondary treatment for IBS [ 6 , 34 ].

Diet exerts a significant influence on the human gut microbiota [ 35 , 36 ], and the low FODMAP diet is no exception. Several studies among the top 10 highly co-cited documents have reported a relative reduction in total bacterial abundance due to FODMAP restriction, including a decrease in gut microbes typically linked with health, such as Bifidobacterium [ 25 , 26 , 37 ]. The first RCT of the low FODMAP diet showed a decrease in the proportion and concentration of luminal Bifidobacteria compared to a habitual diet [ 25 ]. Similarly, two other RCTs demonstrated a lower absolute abundance of Bifidobacteria in the low FODMAP diet compared to a placebo diet [ 26 , 37 ]. In contrast, another RCT did not observe a decrease in Bifidobacteria with the low FODMAP diet, but rather found an increase in the Bifidobacteriaceae family and certain species within the family Lachnospiraceae when following a high FODMAP diet [ 30 ]. The consistent finding of reduced Bifidobacteria abundance due to the low FODMAP diet raises concerns about potential adverse consequences, although the health effects of lower Bifidobacteria resulting from this diet remain unknown. In the long term, the adverse effects on luminal Bifidobacteria levels caused by FODMAP restriction can be effectively restored through FODMAP personalization [ 38 ], emphasizing the essential role played by the reintroduction and personalization stages in the low FODMAP diet [ 39 ]. However, further rigorous clinical trials are still necessary to establish the long-term efficacy and safety of the low FODMAP diet.

Research trend and hotpot

Visualized analysis of keywords reveals the evolution of high-frequency keywords and shows the development path of the low FODMAP diet. After clustering, we obtained 10 clustering labels that encompassed two primary aspects: the evaluation of clinical efficacy (#0 irritable bowel syndrome, #2 ulcerative colitis, #4 functional dyspepsia, #5 children, #6 celiac disease, #7 dietary interventions, #8 diet quality) and the exploration of mechanisms (#0 gas production, #2 colonic fermentation, #9 bifidobacteria) related to the low FODMAP diet.

Clinical research on the low FODMAP diet has mostly focused on its efficacy in IBS, which has been discussed in the previous sections. However, it is exciting to explore the potential efficacy of the low FODMAP diet for diseases other than IBS. More and more research data supported the use of the low FODMAP diet in conditions such as inflammatory bowel disease [ 40 , 41 ], functional dyspepsia [ 42 , 43 , 44 ], and celiac disease [ 45 ], etc. The low FOAMAP diet can assist in symptom management of a variety of diseases, which is thought to be related to the underlying pathological mechanism of FODMAP’s involvement in visceral hypersensitivity [ 46 ]. While encouraging, larger and more rigorously designed clinical trials evaluating the long-term effects of the low FODMAP diet are needed to evaluate its efficacy and safety in clinical practice.

The low FODMAP diet is the most recommended dietary intervention for managing of IBS symptoms, but faces challenges in dietary therapy development. In addition to its impact on gut microbiota mentioned above, the low FODMAP diet may also affect nutrition intake and diet quality. Patients with IBS were reported to have lower calcium intakes than those who followed a regular diet after following the low FODMAP diet for 4 weeks [ 25 ], as well as lower calorie, carbohydrate, and fiber intakes when compared to those following the diet recommended by the National Institute for Health and Care Excellence [ 32 ]. While the implementation of the low FODMAP diet was observed to reduce several micronutrients, most of these reductions were not significant after adjusting for energy intake, except for riboflavin [ 47 ]. An RCT of 130 individuals revealed that the low FODMAP diet had higher intakes of vitamin B 12 and selenium than the sham diet and more intakes of vitamin B 12 than a habitual diet, but decreased diet quality compared with the habitual control diet [ 48 ]. The reintroduction and personalization of FODMAP can be a solution to the nutritional deficiency that can occur with FODMAP restriction [ 49 ]. Besides, several attempts have been made to include dietary supplements to enhance the nutritional value of the diet, with specific supplements showing additional symptomatic benefits compared to FODMAP restriction alone [ 50 , 51 ]. Clinicians and dietitians should provide guidance to optimize nutrient intake, maintain diet quality and enhance patient adherence [ 52 , 53 ].

The low FODMAP diet may improve gastrointestinal symptoms through various mechanisms, and further research on mechanisms may broader its clinical application. FODMAP malabsorption leads to intestinal fermentation, gas production, and an increase in osmotic pressure, which stimulate mechano- and chemoreceptors, resulting in pain, decreased gastrointestinal motility, flatulence, and bloating [ 43 ]. However, a study using MRI showed that after consuming fermentable carbohydrates, IBS patients and healthy controls had comparable levels of gas and bowel distension, which suggested that the colonic hypersensitivity to distension, rather than the excess of gas, was the underlying cause of symptoms in IBS patients [ 54 ]. A recent finding has revealed that the low FODMAP diet can alter visceral hypersensitivity by increasing colon microcirculation perfusion and decreasing the expression of vascular endothelial-derived growth factor [ 55 ]. Another hypothesized mechanism by which FODMAPs cause gastrointestinal symptoms is related to increased histamine. It has been reported that IBS patients have increased urinary histamine levels and the low FODMAP diet can decrease histamine levels [ 30 ]. The cause of the histamine elevation has not been identified, as it may derive from dietary sources, or be produced by colonic mast cells or intestinal microbiota [ 56 ]. In addition, a decrease in the inflammatory cytokines interleukin (IL)-6 and IL-8 have been reported in IBS patients following the low FODMAP diet [ 57 ]. Therefore, the low FODMAP diet may improve gastrointestinal symptoms by regulating mucosal barrier and proinflammatory factors.

Keyword burst is regarded as a key indicator of trend and hotspot in a research field. The period prior to 2012 witnessed the burst of keywords such as “fructose malabsorption”, “lactose malabsorption”, and “common Australian vegetables”, which served as markers of the formulation and development of new concept within the field. Subsequently, spanning from 2013 to 2021, burst keywords like “gastrointestinal symptoms”, “placebo controlled trial”, and “healthy subjects” indicated a substantial surge in clinical trials performed during this timeframe to assess the effects of the low FODMAP diet. Burst keyword that has persisted until now can be regarded as the forefront of the low FODMAP diet research. The low FODMAP diet can improve the clinical condition in 50-80% of IBS patients [ 3 ]. In other words, 20–50% of individuals do not respond to the low FODMAP diet. Therefore, research on identifying biomarkers to predict response to the low FODMAP diet has become a prominent topic. Predicting responses to the low FODMAP diet based on fecal bacteria profiles is an emerging research field. The fecal microbiota has been analyzed by a “GA-map Dysbiosis Test” to create a “Dysbiosis Index” score, which provides a numerical score indicating how an individual’s bacterial composition compares to a healthy reference population, with some bacteria having higher abundance than others, including Bacteroides stercoris , Acinetobacter , Pseudomonas , and genus Desulfitispora [ 58 ]. Children with IBS who responded to the low FODMAP diet had a higher abundance of certain bacteria at baseline, such as Bacteroides , Ruminococcaceae , and Faecalibacterium prausnitzii , which are known to have great saccharolytic metabolic capacity [ 29 , 59 ]. Moreover, a recent study stratified IBS patients based on gut microbiota species and metabolic genetic characteristics, identifying two distinct microbiota profiles for IBS pathogenic-like and IBS health-like subtypes [ 60 ]. Patients with IBS pathogenic-like subtypes had a greater clinical response to the low FODMAP diet than those with IBS health-like subtypes [ 60 ]. However, a recent finding showed that the fecal microbiota did not predict response to the low FODMAP diet, and supported the distinction between the low FODMAP diet responders and non-responders based on fecal metabolites [ 61 ]. A previous study also used fecal volatile organic compounds at baseline to predict the response of IBS patients to the low FODMAP diet with 97% accuracy [ 62 ]. As a low-cost and non-invasive method, fecal volatile organic compounds profiling can be used to predict whether IBS patients would respond to the low FODMAP diet, but it still has to be verified by a large prospective cohort. The research on predictors of response to the low FODMAP diet is currently a hotspot, with preliminary evidence supporting the use of fecal microbiota or fecal metabolites. However, these methods need to be tested in larger external validation populations.

Strengths and limitations

To our knowledge, this study is the first to comprehensively summarize and analyze the knowledge base, research trend and current hotspot of the low FODMAP diet research using bibliometrics. Compared with traditional literature reviews, a bibliometric analysis based on bibliometrics tools (CiteSpace, VOSviewer, Scimago Graphic) can provide a relatively comprehensive and objective presentation of the data to better describe and visualize the research trend and hotspot. However, it is important to acknowledge that this study has inherent limitations due to the use of bibliometric analysis. First, the WOSCC database is still being updated, and some of the updated documents were not included in our study, so the results could not fully reflect the situation of the documents published in 2024. Second, the documents included in our study may not be complete. On the one hand, we only focused on data from the WoSCC database since CiteSpace can only analyze and visualize co-citation maps of data retrieved from this database. This selection was made due to the unavailability of co-citation analysis support on other significant search engines such as PubMed, Embase, and Ovid. On the other hand, due to the uniformity of data extraction, only published English literature was searched, and some bias was introduced. Nevertheless, considering the authority of the WoSCC database and the widespread use of English as the predominant international language, we consider this study still effectively portrays the overall situation in this field. Third, since citations to documents take time to accumulate, their amount does not accurately reflect the influence of the documents. Early published literature may receive more citations, while newer high-quality publications may require more time to accumulate citations.

This research is the first bibliometric analysis to summarize and visualize the development of the low FODMAP diet research, and explore the research trend and hotspot in this field. The gradual increase in published documents over the past fifteen years suggests that this field is receiving more attention from researchers. The research in this area has mainly focused on the evaluation of clinical efficacy and exploration of the mechanism of the low FODMAP diet in the treatment of IBS. The restriction stage of the low FODMAP diet is superior to other dietary therapies for IBS in terms of symptom response, but it has a detrimental influence on the abundance of gut Bifidobacteria and diet quality. Identification of biomarkers to predict response to the low FODMAP diet is of great interest and has become the current research hotspot. To provide higher levels of clinical evidence, large, well-designed clinical research studies are needed in the future to investigate the long-term efficacy and safety of the low FODMAP diet, including FODMAP reintroduction and personalization stages. We hope that this study will aid researchers in better comprehending the general trends in this field and can offer direction for further study.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols

• Irritable bowel syndrome

Web of Science Core Collection

Randomized controlled trials

Interleukin

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The study was supported by the project of Jiangsu Province Traditional Chinese medicine digestive disease medical innovation center [grant number CXZX202208].

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Cheng Xu and Hong Shen conceived and designed the study. Zhen Song and Jing-yi Hu contributed to data collection. Cheng Xu, Zhen Song and Jing-yi Hu conducted the data analysis and interpretation. Cheng Xu and Zhen Song drafted the initial manuscript. Chong-chao Li and Hong Shen revised the manuscript. All authors contributed to the article and approved the submitted version.

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Xu, C., Song, Z., Hu, Jy. et al. Global research trend and hotspot in the low FODMAP diet: a bibliometric analysis. J Health Popul Nutr 43 , 63 (2024). https://doi.org/10.1186/s41043-024-00567-7

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Optimizing clinical nutrition research: the role of adaptive and pragmatic trials

• Camila E. Orsso   ORCID: orcid.org/0000-0001-5989-0528 1 ,
• Katherine L. Ford   ORCID: orcid.org/0000-0002-8620-9360 1 , 2 ,
• Nicole Kiss   ORCID: orcid.org/0000-0002-6476-9834 3 ,
• Elaine B. Trujillo   ORCID: orcid.org/0000-0002-8480-2427 4 ,
• Colleen K. Spees 5 ,
• Jill M. Hamilton-Reeves 6 , 7 &
• Carla M. Prado   ORCID: orcid.org/0000-0002-3609-5641 1  

European Journal of Clinical Nutrition volume  77 ,  pages 1130–1142 ( 2023 ) Cite this article

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• Clinical trials
• Randomized controlled trials

Evidence-based nutritional recommendations address the health impact of suboptimal nutritional status. Efficacy randomized controlled trials (RCTs) have traditionally been the preferred method for determining the effects of nutritional interventions on health outcomes. Nevertheless, obtaining a holistic understanding of intervention efficacy and effectiveness in real-world settings is stymied by inherent constraints of efficacy RCTs. These limitations are further compounded by the complexity of nutritional interventions and the intricacies of the clinical context. Herein, we explore the advantages and limitations of alternative study designs (e.g., adaptive and pragmatic trials), which can be incorporated into RCTs to optimize the efficacy or effectiveness of interventions in clinical nutrition research. Efficacy RCTs often lack external validity due to their fixed design and restrictive eligibility criteria, leading to efficacy-effectiveness and evidence-practice gaps. Adaptive trials improve the evaluation of nutritional intervention efficacy through planned study modifications, such as recalculating sample sizes or discontinuing a study arm. Pragmatic trials are embedded within clinical practice or conducted in settings that resemble standard of care, enabling a more comprehensive assessment of intervention effectiveness. Pragmatic trials often rely on patient-oriented primary outcomes, acquire outcome data from electronic health records, and employ broader eligibility criteria. Consequently, adaptive and pragmatic trials facilitate the prompt implementation of evidence-based nutritional recommendations into clinical practice. Recognizing the limitations of efficacy RCTs and the potential advantages of alternative trial designs is essential for bridging efficacy-effectiveness and evidence-practice gaps. Ultimately, this awareness will lead to a greater number of patients benefiting from evidence-based nutritional recommendations.

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This research received no specific grant from any funding agency, commercial or not-for-profit sectors. CMP was funded by as a Campus Alberta Innovation Program Chair in Nutrition, Food, and Health. Support for time for JHR was provided by National Institutes of Health MERIT award (R37CA218118) and by the Nutrition Shared Resource through the National Cancer Institute Cancer Center support grant (P30 CA16852); the contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

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Camila E. Orsso, Katherine L. Ford & Carla M. Prado

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Katherine L. Ford

Institute for Physical Activity and Nutrition, Deakin University, Geelong, VIC, Australia

Nicole Kiss

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CEO and CMP designed research; CEO and KLF conducted literature search; CEO, KLF, and CMP contributed to writing—original draft preparation; CEO, KLF, NK, EBT, CKS, JHR, and CMP contributed to writing—review and editing. All authors have read and approved the final manuscript.

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Orsso, C.E., Ford, K.L., Kiss, N. et al. Optimizing clinical nutrition research: the role of adaptive and pragmatic trials. Eur J Clin Nutr 77 , 1130–1142 (2023). https://doi.org/10.1038/s41430-023-01330-7

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Food for thought: study links key nutrients to slower brain aging.

2 days ago · 4 min read

Food for thought: Study links key nutrients to slower brain aging

Scientists have long been studying the brain with a goal of aiding healthier aging. While much is known about risk factors for accelerated brain aging, less has been uncovered to identify ways to reduce cognitive decline.

There is evidence that nutrition matters, and a novel study from the University of Nebraska–Lincoln’s Center for Brain, Biology and Behavior and the University of Illinois at Urbana-Champaign further signals how specific nutrients may play a pivotal role in the healthy aging of the brain. The findings were published in Nature Publishing Group Aging.

The team of scientists, led by Aron Barbey, director of the Center for Brain, Biology and Behavior, with Jisheng Wu, a doctoral student at Nebraska, and Christopher Zwilling, research scientist at UIUC, performed the multimodal study — combining state-of-the-art innovations in neuroscience and nutritional science — and identified a specific nutrient profile in participants who performed better cognitively.

The cross-sectional study enrolled 100 cognitively healthy participants, aged 65-75. These participants completed a questionnaire with demographic information, along with measures of body composition and physical fitness. Blood plasma was collected following a fasting period to analyze the nutrient biomarkers. Participants also underwent cognitive assessments and MRI scans. Analysis of this large set of measures revealed two types of brain aging among the participants — accelerated and slower-than-expected. Those with slower brain aging had a distinct nutrient profile.

The beneficial nutrient blood biomarkers were a combination of fatty acids (vaccenic, gondoic, alpha linolenic, elcosapentaenoic, eicosadienoic and lignoceric acids); antioxidants and carotenoids including cis-lutein, trans-lutein and zeaxanthin; two forms of vitamin E and choline. This profile is correlated with nutrients found in the Mediterranean diet, which research has previously associated with healthy brain aging.

“We investigated specific nutrient biomarkers, such as fatty acid profiles, known in nutritional science to potentially offer health benefits. This aligns with the extensive body of research in the field demonstrating the positive health effects of the Mediterranean diet, which emphasizes foods rich in these beneficial nutrients,” said Barbey, Mildred Francis Thompson Professor of Psychology. “The present study identifies particular nutrient biomarker patterns that are promising and have favorable associations with measures of cognitive performance and brain health.”

Barbey noted that previous research on nutrition and brain aging has mostly relied on food frequency questionnaires, which are dependent on participants’ own recall. This study is one of the first and the largest to combine brain imaging, blood biomarkers and validated cognitive assessments.

“The unique aspect of our study lies in its comprehensive approach, integrating data on nutrition, cognitive function and brain imaging,” Barbey said. “This allows us to build a more robust understanding of the relationship between these factors. We move beyond simply measuring cognitive performance with traditional neuropsychological tests. Instead, we simultaneously examine brain structure, function and metabolism, demonstrating a direct link between these brain properties and cognitive abilities. Furthermore, we show that these brain properties are directly linked to diet and nutrition, as revealed by the patterns observed in nutrient biomarkers.”

The researchers will continue to explore this nutrient profile as it relates to healthy brain aging. Barbey said it’s possible, in the future, that the findings will aid in developing therapies and interventions to promote brain health.

“An important next step involves conducting randomized controlled trials. In these trials, we will isolate specific nutrients with favorable associations with cognitive function and brain health, and administer them in the form of nutraceuticals,” Barbey said. “This will allow us to definitively assess whether increasing the levels of these specific nutrient profiles reliably leads to improvements in cognitive test performance and measures of brain structure, function and metabolism.”

Barbey is also co-editing an upcoming special collection for the Journal of Nutrition, “Nutrition and the Brain — Exploring Pathways to Optimal Brain Health Through Nutrition,” which is currently inviting submissions for consideration, and articles will begin publishing next year.

“There’s immense scientific and medical interest in understanding the profound impact of nutrition on brain health,” Barbey said. “Recognizing this, the Office of Nutrition Research at the National Institutes of Health recently launched a 10-year strategic plan to significantly accelerate nutrition research. Our work directly aligns with this critical initiative, aiming to contribute valuable insights into how dietary patterns influence brain health and cognitive function.”

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Many of us can’t imagine starting the day without a cup of coffee. One reason may be that it supplies us with a jolt of caffeine, a mild stimulant to the central nervous system that quickly boosts our alertness and energy levels. [1] Of course, coffee is not the only caffeine-containing beverage. Read on to learn more about sources of caffeine, and a review of the research on this stimulant and health.

Absorption and Metabolism of Caffeine

The chemical name for the bitter white powder known as caffeine is 1,3,7 trimethylxanthine. Caffeine is absorbed within about 45 minutes after consuming, and peaks in the blood anywhere from 15 minutes to 2 hours. [2] Caffeine in beverages such as coffee, tea, and soda is quickly absorbed in the gut and dissolves in both the body’s water and fat molecules. It is able to cross into the brain. Food or food components, such as fibers, in the gut can delay how quickly caffeine in the blood peaks. Therefore, drinking your morning coffee on an empty stomach might give you a quicker energy boost than if you drank it while eating breakfast.

Caffeine is broken down mainly in the liver. It can remain in the blood anywhere from 1.5 to 9.5 hours, depending on various factors. [2] Smoking speeds up the breakdown of caffeine, whereas pregnancy and oral contraceptives can slow the breakdown. During the third trimester of pregnancy, caffeine can remain in the body for up to 15 hours. [3]

People often develop a “caffeine tolerance” when taken regularly, which can reduce its stimulant effects unless a higher amount is consumed. When suddenly stopping all caffeine, withdrawal symptoms often follow such as irritability, headache, agitation, depressed mood, and fatigue. The symptoms are strongest within a few days after stopping caffeine, but tend to subside after about one week. [3] Tapering  the amount gradually may help to reduce side effects.

Sources of Caffeine

Caffeine is naturally found in the fruit, leaves, and beans of coffee , cacao, and guarana plants. It is also added to beverages and supplements. There is a risk of drinking excess amounts of caffeinated beverages like soda and energy drinks because they are taken chilled and are easy to digest quickly in large quantities.

• Coffee. 1 cup or 8 ounces of brewed coffee contains about 95 mg caffeine. The same amount of instant coffee contains about 60 mg caffeine. Decaffeinated coffee contains about 4 mg of caffeine. Learn more about coffee .
• Espresso. 1 shot or 1.5 ounces contains about 65 mg caffeine.
• Tea. 1 cup of black tea contains about 47 mg caffeine. Green tea contains about 28 mg. Decaffeinated tea contains 2 mg, and herbal tea contains none. Learn more about tea .
• Soda. A 12-ounce can of regular or diet dark cola contains about 40 mg caffeine. The same amount of Mountain Dew contains 55 mg caffeine.
• Chocolate (cacao) . 1 ounce of dark chocolate contains about 24 mg caffeine, whereas milk chocolate contains one-quarter of that amount.
• Guarana. This is a seed from a South American plant that is processed as an extract in foods, energy drinks, and energy supplements. Guarana seeds contain about four times the amount of caffeine as that found in coffee beans. [4] Some drinks containing extracts of these seeds can contain up to 125 mg caffeine per serving.
• Energy drinks. 1 cup or 8 ounces of an energy drink contains about 85 mg caffeine. However the standard energy drink serving is 16 ounces, which doubles the caffeine to 170 mg. Energy shots are much more concentrated than the drinks; a small 2 ounce shot contains about 200 mg caffeine. Learn more about energy drinks .
• Supplements. Caffeine supplements contain about 200 mg per tablet, or the amount in 2 cups of brewed coffee.

Recommended Amounts

In the U.S., adults consume an average of 135 mg of caffeine daily, or the amount in 1.5 cups of coffee (1 cup = 8 ounces). [5] The U.S. Food and Drug Administration considers 400 milligrams (about 4 cups brewed coffee) a safe amount of caffeine for healthy adults to consume daily. However, pregnant women should limit their caffeine intake to 200 mg a day (about 2 cups brewed coffee), according to the American College of Obstetricians and Gynecologists.

The American Academy of Pediatrics suggests that children under age 12 should not consume any food or beverages with caffeine. For adolescents 12 and older, caffeine intake should be limited to no more than 100 mg daily. This is the amount in two or three 12-ounce cans of cola soda.

Caffeine and Health

Caffeine is associated with several health conditions. People have different tolerances and responses to caffeine, partly due to genetic differences. Consuming caffeine regularly, such as drinking a cup of coffee every day, can promote caffeine tolerance in some people so that the side effects from caffeine may decrease over time. Although we tend to associate caffeine most often with coffee or tea, the research below focuses mainly on the health effects of caffeine itself. Visit our features on coffee , tea , and energy drinks for more health information related to those beverages.

Caffeine can block the effects of the hormone adenosine, which is responsible for deep sleep . Caffeine binds to adenosine receptors in the brain, which not only lowers adenosine levels but also increases or decreases other hormones that affect sleep, including dopamine, serotonin, norepinephrine, and GABA. [2] Levels of melatonin, another hormone promoting sleep, can drop in the presence of caffeine as both are metabolized in the liver. Caffeine intake later in the day close to bedtime can interfere with good sleep quality. Although developing a caffeine tolerance by taking caffeine regularly over time may lower its disruptive effects, [1] those who have trouble sleeping may consider minimizing caffeine intake later in the day and before going to bed.

In sensitive individuals, caffeine can increase anxiety at doses of 400 mg or more a day (about 4 cups of brewed coffee). High amounts of caffeine may cause nervousness and speed up heart rate, symptoms that are also felt during an anxiety attack. Those who have an underlying anxiety or panic disorder are especially at risk of overstimulation when overloading on caffeine.

Caffeine stimulates the heart, increases blood flow, and increases blood pressure temporarily, particularly in people who do not usually consume caffeine. However, strong negative effects of caffeine on blood pressure have not been found in clinical trials, even in people with hypertension, and cohort studies have not found that coffee drinking is associated with a higher risk of hypertension. Studies also do not show an association of caffeine intake and atrial fibrillation (abnormal heart beat), heart disease , or stroke. [3]

Caffeine is often added to weight loss supplements to help “burn calories.” There is no evidence that caffeine causes significant weight loss. It may help to boost energy if one is feeling fatigued from restricting caloric intake, and may reduce appetite temporarily. Caffeine stimulates the sympathetic nervous system, which plays a role in suppressing hunger, enhancing satiety, and increasing the breakdown of fat cells to be used for energy. [6] Cohort studies following large groups of people suggest that a higher caffeine intake is associated with slightly lower rates of weight gain in the long term. [3] However, a fairly large amount of caffeine (equivalent to 6 cups of coffee a day) may be needed to achieve a modest increase in calorie “burn.” Additional calories obtained from cream, milk, or sweetener added to a caffeinated beverage like coffee or tea can easily negate any calorie deficit caused by caffeine.

Caffeine can cross the placenta, and both mother and fetus metabolize caffeine slowly. A high intake of caffeine by the mother can lead to prolonged high caffeine blood levels in the fetus. Reduced blood flow and oxygen levels may result, increasing the risk of miscarriage and low birth weight. [3] However, lower intakes of caffeine have not been found harmful during pregnancy when limiting intakes to no more than 200 mg a day. A review of controlled clinical studies found that caffeine intake, whether low, medium, or high doses, did not appear to increase the risk of infertility. [7]

Most studies on liver disease and caffeine have specifically examined coffee intake. Caffeinated coffee intake is associated with a lower risk of liver cancer, fibrosis, and cirrhosis. Caffeine may prevent the fibrosis (scarring) of liver tissue by blocking adenosine, which is responsible for the production of collagen that is used to build scar tissue. [3]

Studies have shown that higher coffee consumption is associated with a lower risk of gallstones. [8] Decaffeinated coffee does not show as strong a connection as caffeinated coffee. Therefore, it is likely that caffeine contributes significantly to this protective effect. The gallbladder is an organ that produces bile to help break down fats; consuming a very high fat diet requires more bile, which can strain the gallbladder and increase the risk of gallstones. It is believed that caffeine may help to stimulate contractions in the gallbladder and increase the secretion of cholecystokinin, a hormone that speeds the digestion of fats.

Caffeine may protect against Parkinson’s disease. Animal studies show a protective effect of caffeine from deterioration in the brain. [3] Prospective cohort studies show a strong association of people with higher caffeine intakes and a lower risk of developing Parkinson’s disease. [9]

Caffeine has a similar action to the medication theophylline, which is sometimes prescribed to treat asthma. They both relax the smooth muscles of the lungs and open up bronchial tubes, which can improve breathing. The optimal amount of caffeine needs more study, but the trials reviewed revealed that even a lower caffeine dose of 5 mg/kg of body weight showed benefit over a placebo. [10] Caffeine has also been used to treat breathing difficulties in premature infants. [3]

Caffeine stimulates the release of a stress hormone called epinephrine, which causes liver and muscle tissue to release its stored glucose into the bloodstream, temporarily raising blood glucose levels. However, regular caffeine intake is not associated with an increased risk of diabetes . In fact, cohort studies show that regular coffee intake is associated with a lower risk of type 2 diabetes , though the effect may be from the coffee plant compounds rather than caffeine itself, as decaffeinated coffee shows a similar protective effect. [3] Other observational studies suggest that caffeine may protect and preserve the function of beta cells in the pancreas, which are responsible for secreting insulin. [11]

Signs of Toxicity

Caffeine toxicity has been observed with intakes of 1.2 grams or more in one dose. Consuming 10-14 grams at one time is believed to be fatal. Caffeine intake up to 10 grams has caused convulsions and vomiting, but recovery is possible in about 6 hours. Side effects at lower doses of 1 gram include restlessness, irritability, nervousness, vomiting, rapid heart rate, and tremors.

Toxicity is generally not seen when drinking caffeinated beverages because a very large amount would need to be taken within a few hours to reach a toxic level (10 gm of caffeine is equal to about 100 cups of brewed coffee). Dangerous blood levels are more often seen with overuse of caffeine pills or tablets. [3]

Did You Know?

• Caffeine is not just found in food and beverages but in various medications. It is often added to analgesics (pain relievers) to provide faster and more effective relief from pain and headaches. Headache or migraine pain is accompanied by enlarged inflamed blood vessels; caffeine has the opposite effect of reducing inflammation and narrowing blood vessels, which may relieve the pain.
• Caffeine can interact with various medications. It can cause your body to break down a medication too quickly so that it loses its effectiveness. It can cause a dangerously fast heart beat and high blood pressure if taken with other stimulant medications. Sometimes a medication can slow the metabolism of caffeine in the body, which may increase the risk of jitteriness and irritability, especially if one tends to drink several caffeinated drinks throughout the day. If you drink caffeinated beverages daily, talk with your doctor about potential interactions when starting a new medication.

Energy Drinks

• Clark I, Landolt HP. Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials. Sleep medicine reviews . 2017 Feb 1;31:70-8. *Disclosure: some of HPL’s research has been supported by Novartis Foundation for Medical-Biological Research.
• Institute of Medicine (US) Committee on Military Nutrition Research. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington (DC): National Academies Press (US); 2001. 2, Pharmacology of Caffeine. Available from: https://www.ncbi.nlm.nih.gov/books/NBK223808/
• van Dam RM, Hu FB, Willett WC. Coffee, Caffeine, and Health.  NEJM .  2020 Jul 23; 383:369-378
• Moustakas D, Mezzio M, Rodriguez BR, Constable MA, Mulligan ME, Voura EB. Guarana provides additional stimulation over caffeine alone in the planarian model. PLoS One . 2015 Apr 16;10(4):e0123310.
• Drewnowski A, Rehm CD. Sources of caffeine in diets of US children and adults: trends by beverage type and purchase location. Nutrients . 2016 Mar;8(3):154.
• Harpaz E, Tamir S, Weinstein A, Weinstein Y. The effect of caffeine on energy balance. Journal of basic and clinical physiology and pharmacolog y. 2017 Jan 1;28(1):1-0.
• Bu FL, Feng X, Yang XY, Ren J, Cao HJ. Relationship between caffeine intake and infertility: a systematic review of controlled clinical studies.  BMC Womens Health . 2020;20(1):125.
• Zhang YP, Li WQ, Sun YL, Zhu RT, Wang WJ. Systematic review with meta‐analysis: coffee consumption and the risk of gallstone disease. Alimentary pharmacology & therapeutics . 2015 Sep;42(6):637-48.
• Hong CT, Chan L, Bai CH. The Effect of Caffeine on the Risk and Progression of Parkinson’s Disease: A Meta-Analysis. Nutrients . 2020 Jun;12(6):1860.
• Welsh EJ, Bara A, Barley E, Cates CJ. Caffeine for asthma.  Cochrane Database Syst Rev . 2010;2010(1):CD001112.
• Lee S, Min JY, Min KB. Caffeine and Caffeine Metabolites in Relation to Insulin Resistance and Beta Cell Function in US Adults. Nutrients . 2020 Jun;12(6):1783.

Last reviewed July 2020

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Nonlinear association of triglyceride-glucose index with hyperuricemia in US adults: a cross-sectional study

• Linjie Qiu 1   na1 ,
• Yan Ren 1   na1 ,
• Jixin Li 1   na1 ,
• Meijie Li 1 ,
• Wenjie Li 2 ,
• Lingli Qin 1 ,
• Chunhui Ning 1 ,
• Jin Zhang 1 &
• Feng Gao 1  

Lipids in Health and Disease volume  23 , Article number:  145 ( 2024 ) Cite this article

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Despite abundant evidence on the epidemiological risk factors of metabolic diseases related to hyperuricemia, there is still insufficient evidence regarding the nonlinear relationship between triglyceride-glucose (TyG) index and hyperuricemia. Thus, the purpose of this research is to clarify the nonlinear connection between TyG and hyperuricemia.

From 2011 to 2018, a cross-sectional study was carried out using data from the National Health and Nutrition Examination Survey (NHANES). This study had 8572 participants in all. TyG was computed as Ln [triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The outcome variable was hyperuricemia. The association between TyG and hyperuricemia was examined using weighted multiple logistic regression, subgroup analysis, generalized additive models, smooth fitting curves, and two-piecewise linear regression models.

In the regression model adjusting for all confounding variables, the OR (95% CI) for the association between TyG and hyperuricemia was 2.34 (1.70, 3.21). There is a nonlinear and reverse U-shaped association between TyG and hyperuricemia, with a inflection point of 9.69. The OR (95% CI) before the inflection point was 2.64 (2.12, 3.28), and after the inflection point was 0.32 (0.11, 0.98). The interaction in gender, BMI, hypertension, and diabetes analysis was statistically significant.

Additional prospective studies are required to corroborate the current findings, which indicate a strong positive connection between TyG and hyperuricemia among adults in the United States.

Introduction

Uric acid is produced when purine nucleotides are metabolized. The condition known as hyperuricemia occurs when uric acid levels rise over a certain point due to either excessive uric acid synthesis or inadequate uric acid elimination. It affects patients of all ages and genders, and its prevalence is on the rise globally [ 1 , 2 ]. Up to 2016, the global prevalence of hyperuricemia has reached 21% [ 3 ], and the prevalence of hyperuricemia varies by geographic region. For example, in South Korea, it is 11.4% [ 4 ], and a survey conducted among adults aged 18–59 in China showed a prevalence of 15% for hyperuricemia [ 5 ]. Data from the 2007–2016 National Health and Nutrition Examination Survey (NHANES) show that 14.6–20% of Americans suffer with hyperuricemia [ 6 ]. Furthermore, hyperuricemia poses a serious threat to public health as numerous epidemiological studies have confirmed that it is a significant risk factor for a number of chronic diseases, including gout, cardiovascular diseases, chronic kidney disease, hypertension, metabolic syndrome, and many others [ 7 , 8 , 9 , 10 ], posing a serious threat to public health.

Insulin resistance (IR) is a physiological and pathological process closely associated with hyperuricemia [ 8 ]. Epidemiological studies have confirmed the close association between IR and serum urate concentration [ 11 , 12 ]. High insulin levels induced by IR lead to reduced uric acid excretion and increased production, resulting in uric acid accumulation [ 13 ]. Reducing IR has been shown in studies to lower uric acid levels and lower the chance of developing gout [ 14 ]. An animal experimental study from Japan also found that insulin can promote uric acid reabsorption through urate transporter 1 and ATP-binding cassette sub-family G member 2 [ 15 ]. Additionally, a nationwide cohort study confirmed a significant association between insulin resistance and an increased risk of hyperuricemia [ 16 ]. When assessing IR, the glucose clamp method is regarded as the gold standard. However, the use of this detection technology in clinical practice is restricted because of its complexity and comparatively expensive cost. The body’s level of IR can be determined simply using the triglyceride-glucose (TyG) index [ 17 ]. The two main factors used to compute TyG are fasting triglycerides (TG) and fasting glucose (FPG). Multiple studies have confirmed its reliability in predicting various diseases related to IR [ 18 , 19 , 20 ]. TyG and hyperuricemia are significantly correlated in individuals with non-alcoholic fatty liver disease, diabetic nephropathy, and primary hypertension, according to earlier Chinese research [ 21 , 22 , 23 ]. Li et al. discovered that TyG might predict the coexistence of hypertension and hyperuricemia in the elderly population [ 24 ]. An additional cross-sectional study conducted in Northeast China examined the validity of TyG in determining the risk of hyperuricemia in people 40 years of age and older [ 25 ]. While prior research has indicated a connection between hyperuricemia and TyG index, these investigations mostly examined the Chinese population and had rather small sample sizes. The relationship between the TyG index and hyperuricemia is understudied in the US population. Wang et al. found a positive correlation between hyperuricemia and the TyG index in non-diabetic populations in the United States [ 26 ]. Furthermore, there are no reports on the relationship between the TyG index and hyperuricemia in the general adult population in the United States.

Therefore, for this cross-sectional analysis, NHANES data from 2011 to 2018 were used. This study aims to explore the relationship between TyG and adult Americans’ hyperuricemia.

Study design and population

This study made use of cross-sectional data from the National Center for Health Statistics (NCHS) 2011–2018 NHANES, a nationwide survey that used a sophisticated sampling design. The survey, conducted biennially since 1999, covers demographic, dietary, examination, laboratory, and questionnaire data [ 27 , 28 ]. All participants completed informed permission forms, and the NHANES survey procedures and detailed data are available on the official website after being approved by NCHS.

After excluding 16,539 participants under the age of 20, 247 pregnant participants, 2,440 participants with missing FPG and TG data, and 11,358 participants with missing data on uric acid BMI, blood glucose, hypertension and related covariates, the final analysis includes 8,572 participants in total (Fig.  1 ).

From chart of sample selection from the NHANES 2011–2018

Definitions of the exposure and outcome variables

Employing an automatic analyzer, blood samples from individuals fasting for at least 8 h but less than 24 h were measured for TG and FPG using enzymatic methods. The TyG can be computed using the formula Ln [TG (mg/dL) × FPG (mg/dL)/2] [ 29 ]. By using uricase and H 2 O 2 to undergo enzymatic oxidation, the concentration of uric acid in serum was determined and reported in milligrams per deciliter (mg/dL). This can be multiplied by 59.48 to get micromoles per liter (µmol/L). Serum uric acid levels ≥ 416 µmol/L (7 mg/dL) in men and ≥ 357 µmol/L (6 mg/dL) in women are classified as hyperuricemia, given the diagnostic criteria for the condition [ 30 ].

Definition of covariates

To examine the distinct link between hyperuricemia and TyG, we adjusted for potential confounding factors, including demographics, lifestyle, anthropometric measurements, laboratory examinations, and health conditions. Age, gender, race, marital status, degree of education, and the ratio of household income to poverty were the main demographic factors; lifestyle mainly encompassed smoking status, alcohol consumption, and physical activity; anthropometric measurements primarily incorporated BMI; laboratory examination data mainly included HbA1c, LDL, HDL, eGFR, and serum creatinine; health conditions comprised hypertension, diabetes, arthritis, stroke, and coronary heart disease.

According to survey findings, “Yes” indicates that a person has smoked at least 100 cigarettes in their lifetime, whereas “no” indicates that they have smoked fewer than 100 [ 31 ]. Similarly, alcohol consumption is classified as “yes” (consuming at least 12 drinks per year) or “no” (consuming fewer than 12 drinks per year) [ 32 ]. Physical activity is grouped into three categories—active, moderately active, and inactive—following the guidelines for physical activity [ 33 ]. Three categories are used to classify education levels: below high school, high school, and above high school. Parameters such as HDL, LDL, HbA1c, and serum creatinine are measured from each participant’s fasting venous blood using an automated analyzer. Conditions like high blood pressure, heart disease, stroke, and arthritis are categorized based on self-reported medical diagnosis. The three factors used to identify diabetes are a self-reported medical diagnosis, a glycosylated hemoglobin (HbA1c) of 6.5% or above, or a fasting blood glucose level of 7.0 mmol/L or higher. The widely accepted algorithm developed by the Chronic Kidney Disease Epidemiology Collaboration is used to calculate the estimated glomerular filtration rate (eGFR) [ 34 ].

Statistical analyses

Sample weights were appropriately applied in statistical analyses to account for complex sampling designs, following guidelines from the NHANES official website. All of the study population’s descriptive statistics were calculated, and the TyG index was divided into quartiles. The categorical data were reported as percentages, and the continuous variables were shown as mean ± standard deviation (SD). To examine differences between continuous and categorical data, weighted chi-square tests and weighted linear regression models were employed, respectively. In accordance with the STROBE statement [ 35 ], three distinct multivariate logistic regressions were run to investigate the relationship between TyG and hyperuricemia. While Model 2 and Model 3 adjusted for age, gender, and race, educational level, marital status, RIP, smoking, alcohol consumption, physical activity, BMI, HDL, LDL, HbA1c, serum creatinine, eGFR, hypertension, diabetes, arthritis, stroke, and coronary heart disease, Model 1 left covariates unadjusted. Relationship consistency was verified by a linear trend test, and nonlinear relationships were investigated using a Generalized Additive Model (GAM) with smooth curve fitting. In the presence of nonlinearity, a recursive algorithm identified significant turning points in the TyG and hyperuricemia relationship. Threshold effect analysis assessed differences between logistic regression models and two-part logistic regression models. Additionally, subgroup analyses and interaction tests were performed for age, gender, BMI, hypertension, diabetes, stroke, arthritis, and coronary heart disease, with adjustments for corresponding confounding factors. The results were considered credible if the interaction P -value was not significant; if it was, then likely subgroup variations were considered. EmpowerStats ( http://www.empowerstats.com ) and R (version 4.2.2) were used for all statistical analyses, with a P -value < 0.05 denoting statistical significance.

Baseline characteristics of participants

Table  1 displays the baseline attributes of the individuals in the TyG index. Compared to the lowest TyG quartile, individuals in the TyG Q4 group exhibited a tendency towards older age, male gender, Mexican American ethnicity, lower educational attainment, marital status, non-smoking behavior, lower RIP levels, lower HDL, lower eGFR, and higher prevalence of hypertension, diabetes, coronary heart disease, arthritis, stroke. Additionally, they displayed higher levels of BMI, HbA1c, FPG, TG, LDL, serum creatinine, and uric acid (all P  < 0.05). Notably, there was a significantly increased frequency of hyperuricemia ( P  < 0.05) in participants with high TyG levels.

Association between TyG and its components and hyperuricemia

Table  2 displays the relationship between TyG and its components and hyperuricemia. After adjusting for potential confounding variables (Model 3), the study found a significant positive correlation between TG and hyperuricemia (OR = 1.68, 95% CI: 1.38, 2.04). Further dividing TG into quartiles, in Model 3, participants in the highest quartile of TG had a 1.95-fold higher risk of hyperuricemia compared to those in the lowest quartile (OR: 2.95, 95% CI: 1.83, 4.75). Additionally, a significant dose-response relationship was found ( P  < 0.05). However, after adjusting for potential confounding variables (Model 3), the study did not find a significant association between FPG and hyperuricemia (OR = 1.00, 95% CI: 0.99, 1.01). Further dividing FPG into quartiles, in Model 3, participants in quartile 4 of FPG had a significantly positive correlation with hyperuricemia compared to Q1 (OR = 1.84, 95% CI: 1.14, 2.99). Our study also found a significant dose-response relationship ( P  < 0.05). Moreover, the investigation’s findings demonstrated a positive correlation between TyG and the likelihood of hyperuricemia. Variable adjustments bolstered this association, and all multivariate logistic regression models (model 1: OR = 1.70, 95% CI: 1.51,1.91; model 2: OR = 1.69, 95% CI: 1.50,1.92; model 3: OR = 2.34, 95% CI: 1.70,3.21) showed positive correlations regardless of whether confounding variables were adjusted. It’s interesting to note that a unit increase in the TyG index was linked to a 1.34-fold increase in the risk of hyperuricemia after controlling for possible confounding variables (model 3; Table  2 ). When TyG was further split into quartiles using Q1 as the reference group and different variables were taken into account in model 3, the risk of hyperuricemia was 3.85 times higher for those in the highest quartile of the TyG index than for those in the lowest quartile (OR: 4.85, 95% CI: 3.03, 7.78) (Table  2 ). Furthermore, a noteworthy dose-response correlation ( P  < 0.05) was noted.

However, the odds ratios (ORs) for Q2, Q3, and Q4 show that there might be a non-linear correlation; the 95% confidence intervals (CIs) for these three questions are 1.54 (0.98, 2.14), 2.17 (1.44, 3.25), and 4.85 (3.03, 7.78), respectively. Using GAM and smooth curve fitting, a non-linear association between TyG and hyperuricemia was found (Fig.  2 ), adding to the validity of the results. Further exploration through threshold effect analysis revealed a turning point at 9.69 (Table  3 ). Before the turning point, TyG and hyperuricemia exhibited a significant positive correlation, with an OR (95% CI) of 2.64 (2.12, 3.28). Subsequently, after the turning point, TyG and hyperuricemia showed a significant negative correlation, with an OR (95% CI) of 0.32 (0.11, 0.98) (Table  3 ). Additionally, after stratification by age and gender, our results also indicate a non-linear relationship between TyG and hyperuricemia (Figs.  3 and 4 ).

Smooth curve fitting for TyG and hyperuricemia. Non-linear relationship between TyG and hyperuricemia was detected by the generalized additive model. The solid red line represents the smooth curve fit between variables. Blue dotted lines represent the 95% CI from the fit. Adjustment factors included age, sex, race, educational level, marital status, smoking status, alcohol consumption, physical activity, BMI, RIP, LDL, HDL, HbA1c, Serum creatinine, eGFR, hypertension, diabetes, arthritis, coronary heart disease and Stroke

The association between TyG and hyperuricemia stratified by gender. Age, race, educational level, marital status, smoking status, alcohol consumption, physical activity, BMI, RIP, LDL, HDL, HbA1c, Serum creatinine, eGFR, hypertension, diabetes, arthritis, coronary heart disease and Stroke were adjusted

The association between TyG and hyperuricemia stratified by age. Gender, race, educational level, marital status, smoking status, alcohol consumption, physical activity, BMI, RIP, LDL, HDL, HbA1c, Serum creatinine, eGFR, hypertension, diabetes, arthritis, coronary heart disease and Stroke were adjusted

To further evaluate the association between TyG and hyperuricemia in various categories, we also conducted interaction tests and stratified analysis accounting for gender, age, BMI, hypertension, diabetes, coronary heart disease, arthritis, and stroke. The positive link between TyG and hyperuricemia does not appear to be influenced by age, arthritis, coronary heart disease, or stroke, according to the results of our study. However, interactions were observed in gender, BMI, diabetes, and hypertension, with particular significance in female, non-obese, non-hypertensive, and non-diabetic populations (OR: 2.98, 95% CI: 2.27, 3.92), (OR: 3.33, 95% CI: 2.56, 4.33), (OR: 2.62, 95% CI: 2.05, 3.35), (OR: 2.92, 95% CI: 2.32, 3.69) (Fig.  5 ). Therefore, we further explored the non-linear relationship between TyG and hyperuricemia through stratification. After stratification by gender, we found that their non-linear relationship still exists (Fig.  3 ). Furthermore, after stratification by BMI, hypertension, and diabetes, we still observed a non-linear association (Supplementary Figs.  1 , 2 and 3 ).

Subgroup and interaction analyses of the TyG index and hyperuricemia. Adjustment factors included age, sex, race, educational level, marital status, smoking status, alcohol consumption, physical activity, BMI, RIP, LDL, HDL, HbA1c, Serum creatinine, eGFR, hypertension, diabetes, arthritis, coronary heart disease and Stroke

Based on NHANES data from 2011 to 2018, our large-sample cross-sectional analysis demonstrates a strong correlation between elevated TyG and a higher risk of hyperuricemia. Even when categorizing the TyG into quartiles (Q1-Q4), this positive correlation persists. In the adult population in the United States, we found a non-linear association between hyperuricemia and the TyG index after applying a smooth curve. There is a segmented inhibitory effect between the TyG index and hyperuricemia, with 9.69 as a significant inflection point. Before this point, a significant increase in hyperuricemia risk was reported with the increasing TyG, and after this point, a significant decrease in hyperuricemia risk was observed with increasing TyG index. Additionally, our study presents the most detailed stratified analysis.

The TyG index and hyperuricemia had a linear positive connection, according to a prior cross-sectional study from northeastern China, with a 54.1% rise in the probability of hyperuricemia for every unit increase in the TyG [ 25 ]. A cross-sectional study conducted in Thailand also found that among Royal Thai Army members, the TyG index and hyperuricemia had a substantial positive connection that persisted regardless of the soldiers’ obesity condition [ 36 ]. Qing et al. evaluated the relationship between TyG and hyperuricemia in a cohort study involving 42,387 Chinese patients having physical exams. The findings demonstrated a favorable relationship between hyperuricemia and the TyG index [ 37 ]. These studies support our findings. In addition, our research revealed a strong positive association between TyG and hyperuricemia, with each unit rise in TyG associated with a 1.34-fold increase in the risk of hyperuricemia. It was also discovered that interactions occurred regardless of obesity, however in non-obese people this link was stronger.

In addition, after conducting subgroup analyses and interaction tests, our study found that gender, hypertension, and diabetes interacted with the relationship between TyG and hyperuricemia, especially in females, and this association was more pronounced in non-hypertensive and non-diabetic populations. Gender variations have been observed in the TyG index’s ability to detect hyperuricemia in the past, particularly in females [ 38 ], which is consistent with our study results. This may be because estrogen is a uric acid generator and is associated with complex metabolic endocrine factors, thereby affecting lipid metabolism and causing gender differences in lipid metabolism [ 39 ]. In hypertensive people with an average age of 63.81 years, a study in China demonstrated a positive connection between TyG and hyperuricemia (OR = 2.04; 95%CI: 1.87 to 2.24) [ 40 ]. An additional cross-sectional study conducted in Chinese hospitals investigated the relationship between hyperuricemia and TyG in patients with hypertension. TyG and hyperuricemia were shown to positively correlate in hypertensive individuals; this correlation was more pronounced in patients with grade 1–2 hypertension than in those with grade 3 hypertension [ 22 ]. This is consistent with the trend observed in our study. Regardless of the existence of hypertension, we discovered a favorable connection between TyG and hyperuricemia, but this correlation was more pronounced in non-hypertensive individuals. Differences in demographic characteristics and research methods may explain this discrepancy. Further research is needed to uncover these underlying factors. Through a retrospective analysis, Han et al. [ 41 ] discovered a substantial positive connection between TyG and hyperuricemia in patients with diabetes, whereas our study discovered an interaction between TyG and hyperuricemia in patients without diabetes. The observed occurrence could potentially be attributed to variations in the study population, ethnicity, and sample size. More study is required to validate these findings because there is a dearth of information regarding the connection between TyG and hyperuricemia in both diabetic and non-diabetic groups.

The mechanism of TyG in hyperuricemia is not yet clear, but the following biological mechanisms can be explained. Since TyG is computed by summing up TG and FPG, there is a strong correlation between the pathophysiology of hyperuricemia and TG and FPG levels in the human body. Abnormalities in lipid metabolism result from the breakdown of elevated quantities of TG into free fatty acids, which are then transferred to different parts of the body and speed up the breakdown of adenosine triphosphate. Lipid metabolism abnormalities cause kidney damage, reduce uric acid excretion, and consequently increase serum uric acid levels [ 42 ]. Furthermore, high TG levels inhibit insulin receptor activity and quantity on adipocytes, competing with glucose to block insulin’s ability to bind to receptors and cause IR [ 43 ]. Excessive accumulation of glucose leads to hyperglycemia, alters the expression and activity of glucose transporter proteins in tissues, and reduces insulin sensitivity [ 44 , 45 ]. Notably, with an inflection point of 9.69, our study discovered a strong segmental inhibitory effect between TyG and hyperuricemia. TyG and hyperuricemia had a substantial positive correlation up to 9.69, whereas a significant negative correlation followed after 9.69. This differs from the results reported in previous studies, and one possible reason is speculated to be racial differences. Previous correlation studies have mainly focused on Asian countries such as China and Thailand, and racial differences have been shown to affect insulin sensitivity [ 46 ]. Also differences in demographic characteristics and research methods may be potential factors. To sum up, additional pertinent research is required to validate our findings, particularly in the US population.

There are various restrictions on this study. First off, because the study is cross-sectional, we are unable to determine if TyG and hyperuricemia are causally related. The conclusions reached must be supported by further research. Second, although we included many relevant covariates and adjusted accordingly, there may still be interference from other confounding factors, such as hyperthyroidism, alcoholism, renal insufficiency, drugs, tumors, and other factors that affect uric acid levels. To substantiate the connection between hyperuricemia and the TyG index, more intervention studies ought to be carried out. Additionally, serum uric acid levels are influenced by diets rich in purines, and the data on dietary questionnaires in NHANES are very limited, so we cannot determine whether participants have a high-purine diet.

In general, hyperuricemia and the TyG index have a reverse U-shaped connection. In patients with TyG < 9.69, a higher risk of hyperuricemia is significantly correlated with a greater TyG. On the other hand, a higher TyG is substantially linked to a decreased risk of hyperuricemia in patients with TyG > 9.69. These results imply that the prevention and treatment of hyperuricemia may benefit from reducing or raising TyG levels within a specific range. Confirming the causal relationship and underlying mechanisms between them will require more investigation.

Data availability

Data is provided within the supplementary information files.

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Acknowledgements

The authors thank all team members and participants in the NHANES study.

This study was funded by the Science and Technology Innovation Project of the Chinese Academy of Traditional Chinese Medicine (CI2021A03005).

Author information

Linjie Qiu, Yan Ren and Jixin Li contributed equally to this work.

Authors and Affiliations

Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China

Linjie Qiu, Yan Ren, Jixin Li, Meijie Li, Lingli Qin, Chunhui Ning, Jin Zhang & Feng Gao

Shanxi University of Chinese Medicine, Taiyuan, Shanxi, China

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Contributions

LQ, YR, JZ, and FG drafted the manuscript and made substantial contributions to its conception and design. JL, ML and WL extracted the data used for the study from the NHANES official website, while LQ and CN were responsible for the production of photographs and tables for this study. LQ, YR, JZ, and FG were responsible for data analysis and interpretation of the results for this research. All authors have thoroughly reviewed and approved the final manuscript.

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Correspondence to Jin Zhang or Feng Gao .

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Qiu, L., Ren, Y., Li, J. et al. Nonlinear association of triglyceride-glucose index with hyperuricemia in US adults: a cross-sectional study. Lipids Health Dis 23 , 145 (2024). https://doi.org/10.1186/s12944-024-02146-5

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DOI : https://doi.org/10.1186/s12944-024-02146-5

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Watch CBS News

Limit these ultra-processed foods for longer-term health, 30-year study suggests

By Sara Moniuszko

Edited By Paula Cohen

Updated on: May 10, 2024 / 11:09 AM EDT / CBS News

New research is adding to the evidence linking  ultra-processed foods  to health concerns. The study tracked people's habits over 30 years and found those who reported eating more of certain ultra-processed foods had a slightly higher risk of death — with four categories of foods found to be the biggest culprits. 

For the study, published in The BMJ , researchers analyzed data on more than 100,000 U.S. adults with no history of cancer, cardiovascular disease or diabetes. Every four years between 1986 and 2018, the participants completed a detailed food questionnaire.

The data showed those who ate the most  ultra-processed food — about 7 servings per day — had a 4% higher risk of death by any cause, compared to participants who ate the lowest amount, a median of about 3 servings per day.

Ultra-processed foods include "packaged baked goods and snacks, fizzy drinks, sugary cereals, and ready-to-eat or heat products,"  a news release  for the study noted. "They often contain colors, emulsifiers, flavors, and other additives and are typically high in energy, added sugar, saturated fat, and salt, but lack vitamins and fiber."

Foods with the strongest associations with increased mortality, according to the study, included:

• Ready-to-eat meat, poultry and seafood-based products
• Sugary drinks
• Dairy-based desserts
• Highly processed breakfast foods

Ultra-processed food is a "very mixed group of very different foods," the lead author of the study, Mingyang Song,  told CBS News , meaning these categories can offer a helpful distinction. 

"Some of the foods actually have really beneficial ingredients like vitamins, minerals, so that's why we always recommend that people not focus too much on the (whole of) ultra-processed food, but rather the individual categories of ultra-processed food."

The research included a large number of participants over a long timespan, but it did have some limitations. As an observational study, no exact cause-and-effect conclusions can be drawn. And the participants were health professionals and predominantly White and non-Hispanic, "limiting the generalizability of our findings," the authors acknowledged.

But they wrote that the findings "provide support for limiting consumption of certain types of ultra-processed food for long term health." 

"Future studies are warranted to improve the classification of ultra-processed foods and confirm our findings in other populations," they added.

This study comes after other research published earlier this year found diets high in ultra-processed food are associated with an increased risk of 32 damaging health outcomes , including higher risk for cancer, major heart and lung conditions, gastrointestinal issues, obesity, type 2 diabetes, sleep issues, mental health disorders and early death.

Sara Moniuszko is a health and lifestyle reporter at CBSNews.com. Previously, she wrote for USA Today, where she was selected to help launch the newspaper's wellness vertical. She now covers breaking and trending news for CBS News' HealthWatch.

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