Tag: Vegetables

Ketogenic diet can be a powerful aid in treating mental illness

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For people living with serious mental illness like schizophrenia or bipolar disorder, standard treatment with antipsychotic medications can be a double-edged sword. While these drugs help regulate brain chemistry, they often cause metabolic side effects such as insulin resistance and obesity, which are distressing enough that many patients stop taking the medications.

Now, a pilot study led by Stanford Medicine researchers has found that a ketogenic diet not only restores metabolic health in these patients as they continue their medications, but it further improves their psychiatric conditions. The results, published March 27 in Psychiatry Research, suggest that a dietary intervention can be a powerful aid in treating mental illness.

It’s very promising and very encouraging that you can take back control of your illness in some way, aside from the usual standard of care.”

Shebani Sethi, MD, associate professor of psychiatry and behavioral sciences and first author of the new paper

The senior author of the paper is Laura Saslow, PhD, associate professor of health behavior and biological sciences at the University of Michigan.

Making the connection

Sethi, who is board certified in obesity and psychiatry, remembers when she first noticed the connection. As a medical student working in an obesity clinic, she saw a patient with treatment-resistant schizophrenia whose auditory hallucinations quieted on a ketogenic diet.

That prompted her to dig into the medical literature. There were only a few, decades-old case reports on using the ketogenic diet to treat schizophrenia, but there was a long track record of success in using ketogenic diets to treat epileptic seizures.

“The ketogenic diet has been proven to be effective for treatment-resistant epileptic seizures by reducing the excitability of neurons in the brain,” Sethi said. “We thought it would be worth exploring this treatment in psychiatric conditions.”

A few years later, Sethi coined the term metabolic psychiatry, a new field that approaches mental health from an energy conversion perspective.

Meat and vegetables

In the four-month pilot trial, Sethi’s team followed 21 adult participants who were diagnosed with schizophrenia or bipolar disorder, taking antipsychotic medications, and had a metabolic abnormality -; such as weight gain, insulin resistance, hypertriglyceridemia, dyslipidemia or impaired glucose tolerance. The participants were instructed to follow a ketogenic diet, with approximately 10% of the calories from carbohydrates, 30% from protein and 60% from fat. They were not told to count calories.

“The focus of eating is on whole non-processed foods including protein and non-starchy vegetables, and not restricting fats,” said Sethi, who shared keto-friendly meal ideas with the participants. They were also given keto cookbooks and access to a health coach.

The research team tracked how well the participants followed the diet through weekly measures of blood ketone levels. (Ketones are acids produced when the body breaks down fat -; instead of glucose -; for energy.) By the end of the trial, 14 patients had been fully adherent, six were semi-adherent and only one was non-adherent.

Feeling better

The participants underwent a variety of psychiatric and metabolic assessments throughout the trial.

Before the trial, 29% of the participants met the criteria for metabolic syndrome, defined as having at least three of five conditions: abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated blood pressure and elevated fasting glucose levels. After four months on a ketogenic diet, none of the participants had metabolic syndrome.

On average, the participants lost 10% of their body weight; reduced their waist circumference by 11% percent; and had lower blood pressure, body mass index, triglycerides, blood sugar levels and insulin resistance.

“We’re seeing huge changes,” Sethi said. “Even if you’re on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, the insulin resistance. I think that’s very encouraging for patients.”

The psychiatric benefits were also striking. On average, the participants improved 31% on a psychiatrist rating of mental illness known as the clinical global impressions scale, with three-quarters of the group showing clinically meaningful improvement. Overall, the participants also reported better sleep and greater life satisfaction.

“The participants reported improvements in their energy, sleep, mood and quality of life,” Sethi said. “They feel healthier and more hopeful.”

The researchers were impressed that most of the participants stuck with the diet. “We saw more benefit with the adherent group compared with the semi-adherent group, indicating a potential dose-response relationship,” Sethi said.

Alternative fuel for the brain

There is increasing evidence that psychiatric diseases such as schizophrenia and bipolar disorder stem from metabolic deficits in the brain, which affect the excitability of neurons, Sethi said.

The researchers hypothesize that just as a ketogenic diet improves the rest of the body’s metabolism, it also improves the brain’s metabolism.

“Anything that improves metabolic health in general is probably going to improve brain health anyway,” Sethi said. “But the ketogenic diet can provide ketones as an alternative fuel to glucose for a brain with energy dysfunction.”

Likely there are multiple mechanisms at work, she added, and the main purpose of the small pilot trial is to help researchers detect signals that will guide the design of larger, more robust studies.

As a physician, Sethi cares for many patients with both serious mental illness and obesity or metabolic syndrome, but few studies have focused on this undertreated population.

She is founder and director of the metabolic psychiatry clinic at Stanford Medicine

“Many of my patients suffer from both illnesses, so my desire was to see if metabolic interventions could help them,” she said. “They are seeking more help. They are looking to just feel better.”

Researchers from the University of Michigan; the University of California, San Francisco; and Duke University contributed to the study.

The study was supported by Baszucki Group Research Fund, Keun Lau Fund and the Obesity Treatment Foundation.

Source:

Journal reference:

Sethi, S., et al. (2024). Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry Research. doi.org/10.1016/j.psychres.2024.115866.

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April 1, 2024
Antioxidant-rich diets linked to lower type 2 diabetes risk, supplements less effective
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Scientists at the Karolinska Institute in Sweden have conducted a systematic review and meta-analysis to determine the relationship between dietary antioxidant intake and type 2 diabetes risk.

The study is published in the journal Advances in Nutrition.

Review: Vitamins C, E, and beta-carotene and risk of type 2 diabetes: a systematic review and meta-analysis. Image Credit: alicja neumiler / Shutterstock

Background

Type 2 diabetes is a serious metabolic disease characterized by reduced secretion or impaired functioning of insulin and subsequent increase in blood glucose level (hyperglycemia). Insulin resistance and pancreatic beta-cell dysfunction are two major hallmarks of the disease.

More than 10% of the global population is currently affected by type 2 diabetes. Its prevalence is sharply increasing worldwide mainly because of an increasing inclination towards unhealthy food habits and sedentary lifestyles.

Diet plays an important role in regulating the body’s metabolism, among various lifestyle factors. Evidence indicates that an increased adherence to healthy diets, such as the Mediterranean or DASH (Dietary Approach to Stop Hypertension), can significantly reduce the risk of type 2 diabetes. The fundamental characteristic of these diets is a higher intake of plant-based foods rich in antioxidants, including vitamins C, E, and beta-carotene.

In this systematic review and meta-analysis, scientists have assessed whether consumption of dietary vitamins C, E and beta-carotene can reduce the risk of type 2 diabetes.

Study design

The scientists searched various electronic databases to identify studies investigating the association between dietary intakes, circulating levels, or supplementation of vitamin C, E, and beta-carotene and type 2 diabetes incidence or insulin resistance/sensitivity and beta cell function in non-diabetic individuals.

The final screening led to the identification of 25 prospective observational studies and 15 randomized controlled trials. Moderate and serious risks of bias were observed in 21 and 4 observational studies, respectively. Among randomized controlled trials, 13 had a low risk of bias, and 2 had some concerns.

Important observations

The study found that moderate intakes of vitamins C, E, and beta-carotene can reduce the risk of type 2 diabetes.

Vitamin C

The meta-analysis of observational studies revealed that a vitamin C intake of up to 70 mg per day can reduce type 2 diabetes risk by 24%. However, no further risk reduction was observed for an intake higher than this level.

An inverse association was observed between dietary intake of vitamin C and insulin resistance. Vitamin C intake also showed a positive impact on beta cell function.

Vitamin E

The meta-analysis of observational studies revealed that the vitamin E intake of up to 12 mg per day can reduce the risk of type 2 diabetes by 28%. Similar to vitamin C, no further risk reduction was observed for an intake higher than this level.

The meta-analysis of randomized clinical trials revealed that vitamin E supplementation does not have any protective effect against type 2 diabetes development. However, vitamin E supplementation showed a positive impact on insulin sensitivity.

Beta-carotene

The meta-analysis of observational studies revealed that the beta-carotene intake of up to 4 mg per day can reduce the risk of type 2 diabetes by 22%. No further risk reduction was observed above this level.

The meta-analysis of randomized controlled trials revealed that beta-carotene supplementation cannot reduce the risk of type 2 diabetes. It was also observed that circulating beta-carotene can reduce insulin resistance and increase insulin sensitivity.

Study significance

This systematic review and meta-analysis found an inverse association between dietary and circulating vitamins C, E, and beta-carotene and the risk of type 2 diabetes. However, no protective efficacy of supplementation with these antioxidants has been observed against type 2 diabetes.

The robust antioxidant properties of these vitamins are mainly responsible for their anti-diabetic effects. Vitamin C is a water-soluble vitamin commonly found in fruits and vegetables. It can remove free radicals in the body’s hydrophilic compartments and regenerate vitamin E from its oxidized form.

Vitamin E is a fat-soluble vitamin commonly found in nuts, seeds, and vegetable oils. It can prevent lipid peroxidation and protect lipid parts of the body, such as cell membranes. Beta-carotene is a fat-soluble provitamin A carotenoid commonly found in fruits and vegetables. Similar to vitamin E, beta-carotene can protect lipid parts of the body from free radical-mediated damage.
Article Revisions

Mar 27 2024 – Addition of Graphical abstract illustration.
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March 26, 2024
New method paves the way for clearer dietary guidelines on brain health

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In a recent study published in the journal Frontiers in Nutrition, researchers developed a method to retrospectively harmonize data on the association between dietary patterns and cognitive health from individual studies that vary widely in the methodologies and results.

Review: Diet patterns associated with cognitive decline: methods to harmonize data from European and US cohort studies. Image Credit: Elena Eryomenko / Shutterstock

Background

A growing area of research is the association between dietary patterns and cognitive health, especially related to understanding the modifiable risk factors for dementia and other neurodegenerative diseases. Findings from various reviews and meta-analyses have found that diets rich in fruits, whole grains, and vegetables are beneficial for cognitive health.

However, findings from individual studies about dietary patterns such as the Dietary Approach to Stop Hypertension (DASH), Mediterranean, anti-inflammatory, and Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diets have been inconsistent. These inconsistencies, stemming from heterogeneity in the methods for conducting dietary and cognitive assessments, study populations, follow-up durations, and various other study parameters, have made it challenging to conclude potential dietary guidelines for cognitive health.

A proposed approach to draw inferences from these heterogeneous individual studies involves pooling individual participant data from various clinical and observational trials, similar to a meta-analysis. It differs from a meta-analysis in that the data is sought from the eligible study rather than extracted from the publication. However, a method of harmonizing the data is still required to ensure comparability and compatibility across the data.

About the study

The present study described a protocol for retrospectively harmonizing individual participant data from numerous studies from the United States (U.S.) and Europe on the association between dietary patterns and cognitive health. They also discussed the study selection criteria to address the study question and provided definitions for the outcomes and exposures of the study.

Harmonization of data

To determine the associations between dietary patterns and the incidence of cognitive decline and mild cognitive impairment, the selection criteria stipulated the inclusion of studies that examined diets representative of different populations across the U.S. and Europe, with the study design being either a clinical trial or a prospective cohort study. Only studies conducted on adults above the age of 35 who were cognitively healthy were to be included in the harmonization analysis. Sensitivity analyses were recommended to assess the interactive effects of comorbidities such as obesity, cardiovascular disease, diabetes, depression, and physical activity.

The exposures considered for the analysis comprise dietary patterns such as adaptations of the Mediterranean diet pattern, EAT-Lancet pattern, the Healthy Eating Index, or a pattern derived a posteriori from the results of a principal component analysis. Diet history, food frequency questionnaires, or data from repeat interviews would be used to determine the daily food intake scores.

The outcomes for the analysis consist of cognitive performance assessments at two time points to determine changes in cognition or the development of mild cognitive impairment. The data on dietary patterns would be harmonized into groups of foods and beverages such as dairy, vegetables, fruits, meat, candy, and sugar-sweetened beverages.

The researchers also recommended ensuring that the units used report the nutrients were converted to one unit and reported along with the number of grams in one serving of each food category. The harmonized dietary data would consist of one exposure variable for healthy dietary patterns, reported in terms of a score such as the Healthy Eating Index.

The proposed method for harmonizing individual participant data suggested that only those instruments of cognitive measures that can potentially diagnose mild cognitive impairment or measure executive function, verbal fluency, and verbal memory be included in the analysis. Additionally, the cognitive data should be harmonized using pre-statistical harmonization to categorize the cognitive tests from each study according to the cognitive abilities being examined.

Schematic study protocol to assess the association between diet patterns and cognitive decline.

Data augmentation strategies were suggested to address possible heterogeneity across factors such as administration of cognitive measurements, instrument adaptation, components, and instrument version. Furthermore, a confirmatory factor analysis will be used to test the equivalence of the cognitive measurements.

The study also discussed methods to harmonize data on confounding factors such as lifestyles, physical activity, sociodemographic factors, anthropometry, and physical activity levels. The harmonized data on dietary intake, cognitive measures, and confounding factors will then be used to determine the association between diet and cognitive health through an individual participant data meta-analysis.

Conclusions

To summarize, the study provides a method to harmonize data from numerous heterogeneous studies so that the study design can infer the association between dietary patterns and cognitive health. The application of this method and the findings will help formulate dietary guidance recommendations to improve cognitive health and prevent cognitive decline.

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March 25, 2024
Research explores the health benefits of resistant starch in plant-based diets

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In a recent review published in the journal Frontiers in Nutrition, a group of authors examined the health benefits of resistant starch (RS). It assessed the impact of food processing methods on its retention in plant-based foods, using clinical evidence and observational studies from 2010 to 2023.

Study: Harnessing the power of resistant starch: a narrative review of its health impact and processing challenges. Image Credit: Adao / Shutterstock

Background

Carbohydrates (CHO) are crucial for energy and glucose regulation in diets, with starch being a major source found in cereals, fruits, vegetables, and legumes. Starches vary in digestibility, from rapidly to slowly digestible forms, while RS evades digestion, benefiting colon health similarly to dietary fibers. Despite dietary recommendations promoting a minimum daily fiber intake to reduce chronic disease risks, actual consumption is often below suggested levels across various regions. Current global RS intake is low, underscoring a significant dietary gap. This highlights the urgent need for research into food processing techniques that can maintain or increase RS content, aiming to utilize its health advantages more effectively.

Exploring the benefits and production of RS

RS represents a critical focus in nutritional science due to its potential health benefits and the challenges associated with preserving its content through food processing. This review embarks on an in-depth exploration, drawing from a literature search across Medline, COCHRANE, and The Lens databases. RS varies in form and function and is categorized into five types, each with unique properties and sources. For instance, Resistant starch type 1 (RS1) is found in whole or partly milled grains and seeds, resisting digestion due to its physical entrapment. Resistant starch type 2 (RS2) exists in its native state in foods like uncooked potatoes and green bananas, protected by its granular structure. Resistant starch type 3 (RS3), or retrograded starch, forms when cooked starchy foods cool down, making it indigestible to enzymes. Resistant starch type 4 (RS4) is a product of chemical modification designed to resist digestion. The resistant starch (RS5) category, initially defined for starch-lipid complexes, has expanded to include other resistant complexes formed with molecules like amino acids and polyphenols.

The impact of food processing on RS

The nutritional value of RS, especially its low glycemic index and satiety-enhancing properties, can be influenced significantly by food processing methods. For example, the RS content in foods can be affected at various stages, from the type of crop grown to the methods of cooking, cooling, and storing the food. Breeding techniques that increase the amylose content of starches can lead to higher RS content post-cooking. However, milling can reduce RS content by breaking down starch’s crystalline structure. Similarly, cooking methods that involve high temperatures can decrease RS levels, whereas cooling and storage processes can retrograde starch and increase RS content.

Breeding for higher RS content

Breeding techniques focusing on a higher amylose-to-amylopectin ratio significantly elevate RS levels in foods. High-amylose wheat cultivars, for instance, have shown promising increases in RS content in bread, which translates into notable health benefits such as improved postprandial glycemia. However, there are trade-offs, as high-amylose varieties can affect the textural quality of dough and bread products.

Impact of milling and cooking

Milling processes, particularly those breaking down starch’s crystalline structure, can reduce RS content, with whole grains generally offering higher RS levels. Cooking methods, including microwave and heat-moisture treatments, significantly influence RS content. For example, microwave cooking can enhance RS levels, likely due to its unique heating method, which favors starch retrogradation. Moreover, carefully controlling the starch-to-moisture ratio and the duration and temperature of heating can further optimize RS content.

Cooling, storage, and fermentation effects

Post-cooking cooling and subsequent storage significantly impact RS content, with refrigeration after cooking notably increasing RS levels in foods like rice and bread. The type of storage, whether ambient, refrigerated, or frozen, plays a crucial role in this process. Fermentation conditions also markedly affect RS content; for instance, sourdough fermentation with specific microbial strains can increase RS levels in bread. Such fermentation strategies, alongside optimal storage conditions, offer practical avenues to enhance the RS content in foods, contributing to the broader goal of improving dietary fiber intake and associated health benefits.

Clinical evidence on the health impacts of RS

The review delves into the clinical evidence assessing RS’s effects on health outcomes, including gastrointestinal health, metabolic responses, and inflammatory markers. RS intake has been associated with several health benefits, such as improved stool quality, reduced glycemic response, and a favorable impact on gut microbiota. Furthermore, RS consumption has been linked to lower levels of inflammation and improved antioxidant capacity.

Conclusions and future directions

This narrative review underscores the significant health benefits of RS and the complex interplay between food processing methods and RS content. It highlights the need for further research to optimize processing techniques to enhance the dietary availability of RS, ultimately contributing to better health outcomes. Understanding the mechanisms behind RS’s health benefits and the influence of food processing can guide the development of nutritional recommendations and food products rich in RS, paving the way for improved public health strategies.

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March 22, 2024
How sweet drinks in childhood fatten future
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In a recent article published in the European Journal of Clinical Nutrition, researchers assessed the relationship between sweet drink consumption in early life and adiposity in adulthood.

Their results indicate that consumption of sweet beverages in early life is associated with greater adiposity and less healthy dietary patterns in adulthood, with implications for dietary interventions for young children.

Study: Early exposure to sugar sweetened beverages or fruit juice differentially influences adult adiposity. Image Credit: Dundanim / Shutterstock

Background

Sugar-sweetened beverage (SSB) consumption during childhood has been associated with higher risks of obesity. However, many studies treat carbonated drinks, fruit juices without additional sugar, and all other sweet drinks as similar.

Considering SSBs and fruit juices separately to ascertain which are associated with adverse outcomes can improve dietary interventions to reduce adult obesity. SSB consumption may also be an indicator of a calorie-rich diet, in which case removing it from the diet would not significantly reduce energy intake.

About the study

In this study, researchers set out to test the hypothesis that all sugary drinks belong to the same category in terms of their effect on adiposity outcomes. They also tested whether their influence should be considered as part of an overall dietary pattern and whether gender-based responses to beverage choices are different.

The study sample consisted of children born in Bristol, the United Kingdom, from April 1991 to December 1992. Their diet was assessed at six points when the children were two, three, four, seven, 11, and 13.

When they were two years old, their carers were asked if they had consumed cola or other carbonated drinks and fruit juices, including apple juice and squash, between 15 months and two years. They defined early exposure to a drink as consumption before the age of two.

During the following dietary assessment, their carers filled up a food frequency questionnaire to provide insights into dietary patterns, noting consumption of fatty foods, sweet-tasting foods, fruits and vegetables, and other foods such as fish, meat, and pizza.

Carers completed three-day dietary diaries when the children were four and seven, while 11 and 13-year-olds filled the diaries themselves.

Their height and weight were measured to calculate BMI. Android fat mass was measured as the abdominal fat present around the organs. The other primary outcome was their total fat mass at the age of 24.

Data analysis included hierarchical regression equations, and models were adjusted for the mother’s prenatal weight, her age when the child was born, her partner’s education and BMI, the mother’s and her partner’s occupation, and deprivation in terms of income, health deprivation, disability, employment, housing, education, training, and skills. Male and female groups were analyzed separately.

Findings

For males, cola consumption was associated with higher adiposity; individuals who did not drink apple juice had a higher BMI, on average. Drinking fruit squash but not pure fruit juice was associated with higher adiposity in females.

Researchers then explored whether the relationships they saw were due to the sweet drinks alone or the overall dietary pattern.

Children who consumed fruit squash, fizzy drinks, or cola at the age of three consumed more carbohydrates, energy, protein, non-milk extrinsic sugars, and fats but lower levels of non-starch polysaccharides. Those who consumed apple juice consumed more proteins and healthy sugars but less fat.

These associations indicate that overall dietary patterns must differ as SSBs do not contain fat or protein.

Boys who consumed fruit squash, fizzy drinks, and cola also consumed more sausages, burgers, French fries, pizza, chocolate, sweets, and meat but ate less fruit. Those who drank apple juice ate more salad, green vegetables, fruits, and fish. Similar patterns were seen for girls.

Another interesting finding was that boys who consumed cola before they turned two also consumed more energy when they were four to nine years old. Meanwhile, girls who consumed apple juice showed lower energy intake at the age of four.

Regression results indicated that diet was a predictor of body fat for males at 24 years old; consumption of root vegetables, burgers and sausages, and French fries at the age of three had a significant effect. Similar results were seen for females; additionally, those who did not consume fresh fruit or biscuits had higher fat mass.

More significant social deprivation was associated with a higher likelihood of children drinking cola and a lower likelihood of them drinking fruit juice.

Conclusions

These findings indicate that sweet beverage consumption in early life is significantly linked to health outcomes well into adulthood. The beverages children consume are affected by their family’s socioeconomic and demographic characteristics, with children from more deprived households being more likely to receive unhealthy beverages like cola and less likely to drink relatively healthier drinks such as pure fruit juice.

The study adds to a growing body of evidence that dietary patterns during early childhood significantly affect obesity risk in adulthood. Nutritional interventions to control energy intake during infancy and early childhood may be effective in curbing the issue of adult obesity.
Journal reference:

Early exposure to sugar sweetened beverages or fruit juice differentially influences adult adiposity. Benton, D., Young, H.A. European Journal of Clinical Nutrition (2024). DOI: 10.1038/s41430-024-01430-y, https://www.nature.com/articles/s41430-024-01430-y
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March 19, 2024
Mediterranean diet linked to richer gut diversity, study finds
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In a recent study published in the journal Nutrients, researchers explored how following the Mediterranean diet (MD) influences the gut microbiome of healthy individuals through a well-defined cohort study.

Their results indicate that adhering to MD increases the species diversity of microbiota, offering insights into how it can lead to measurable health benefits.

Study: Impact of the Mediterranean Diet on the Gut Microbiome of a Well-Defined Cohort of Healthy Individuals. Image Credit: Marian Weyo / Shutterstock

Background

Traditionally followed by many Mediterranean coastal communities, MD is a nutrient-rich diet dominated by whole grains, healthy fats, fruits, and vegetables with antioxidant and anti-inflammatory properties.

It has been associated with improved cardiovascular health and reductions in the risk of metabolic syndrome, neurogenerative disorders, type 2 diabetes, and some cancers. This is in contrast with diets high in refined carbohydrates and fats, which have been implicated in increases in obesity and multiple metabolic disorders.

The effect of different diets may be mediated by how they influence the gut microbiome, which plays a crucial role in disease prevention and maintaining health. Certain dietary habits and food components associated with MD may strengthen beneficial gut microbiota, as dietary diversity, fat composition, and fiber intake all leave distinct marks on microbial communities.

About the study

In this study, researchers recruited healthy volunteers (donors and relatives) from a fecal transplant clinic in Spain. Participating individuals had a body mass index (BMI) between 17 and 30, no known diseases or disorders, did not drink more than 50g of alcohol per day, and had not taken vaccines and specified medications in the three months preceding the study.

Participants were stratified by age and provided demographic information, dietary intake through a food-frequency questionnaire, and medical history. Their adherence to the MD was assessed using a dietary quality index; those receiving a score of 1-4 were classified as having ‘good’ adherence, while those scoring 5-9 had ‘medium’ adherence.

The gut microbiome was assessed by analyzing stool samples, identifying microbe species, and measuring species richness, the number of species found in a sample, and species evenness (Pielou index), which measures uniformity or similarity in the abundance of different species.

The inverse Simpson index was used to indicate richness in communities with the same evenness, while the Shannon index examined how many species lived in a given habitat and their relative abundances.

The alpha diversity, which measures species diversity within a single individual, and beta diversity, which assesses diversity differences among individuals, were also calculated. Researchers also calculated correlations between microbial abundance and nutrient intake.

Findings

Of the 60 individuals enrolled in the study, slightly over 50% were female, and the median age was 31. On average, females showed more species richness and higher values for the Pielou, inverse Simpson, and Shannon indexes.

Firmicutes, Bacteroidetes, and Actinobacteria, were the dominant phyla in males and females. Abundant genera included Bifidobacterium, Bacteroides, Faecalibacterium, Prevotella, and Blautia. While Bacteroides were abundant across all age groups, Bifidobacterium became less dominant with age.

Across all diversity indices, children showed consistently lower values than other groups. Teenagers had the highest richness values, while older adults (49 years old and above) had higher Pielou, Shannon, and inverse Simpson values. Stratifying these results by sex showed that these differences remained for males but not females, except for species evenness, which persisted for both.

The median diet adherence score for the 39 individuals who completed the food-frequency questionnaires was 5. People with good adherence had a median age of 48, while those with medium adherence were younger, with a median age of 30.

Better MD adherence was associated with having higher Bacteroides and Paraprevotella abundance, but there were no sex-based differences in alpha and beta diversity indices. Stratifying by age, the researchers found that good adherence decreased the abundance of different genera for different groups.

Correlation analysis showed that fat intake was negatively associated with the Shannon index, while non-starch polysaccharides (NSPs) and total sugars were positively associated. The Pielou index showed a negative association with red meat intake while directly correlating with total sugars and NSPs.

People with better adherence also showed differences in pathways related to bladder cancer, polycyclic aromatic hydrocarbon degradation, and vasopressin-regulated water reabsorption. They showed more enzymes related to lipid metabolism and different biosynthesis processes.

Conclusions

This study assessed MD influence on gut microbiota through a well-defined cohort based on sex and age, finding significant differences in microbial composition as well as alpha and beta diversity associated with adherence. These findings were strengthened by the identification of functional pathways and specific bacterial taxa that differed based on adherence levels.

The small sample study size may limit the generalizability of these findings; further studies using longitudinal designs and larger cohorts are needed to better understand how MD can strengthen the microbiome and boost health outcomes.
Journal reference:

Impact of the Mediterranean diet on the gut microbiome of a well-defined cohort of healthy individuals. Vázquez-Cuesta, S., García, N.L., Rodríguez-Fernández, S., Fernández-Avila, A.I., Bermejo, J., Fernández-Avilés, F., Muñoz, P., Bouza, E., Reigadas, E. Nutrients (2024). DOI: 10.3390/nu16060793, https://www.mdpi.com/2072-6643/16/6/793
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March 13, 2024
The effects of high maternal folate intake on the health outcomes of offspring

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In a recent review article published in Nutrients, researchers summarized what is known about the effects of excessive folic acid (FA) supplementation for mothers on children.

Study: Risk of Excess Maternal Folic Acid Supplementation in Offspring. Image Credit: luchschenF/Shutterstock.com

They conclude that while folate is a crucial nutrient, higher than necessary maternal FA intake may have adverse effects on their offspring.

Folate is an essential nutrient

Water-soluble vitamin B9, or folate, is needed for red blood cell (RBC) formation and to promote healthy cell growth and functioning. Doctors consider it necessary during pregnancy and lactation for fetal and placental growth, for the enlargement of the uterus, to reduce the risk of the child developing congenital disabilities in the brain and spine, and otherwise improve cardiovascular and reproductive health.

Folate can be found naturally in some foods, such as beans, peas, green leafy vegetables, and nuts. However, synthesized FA has been distributed widely in fortified food and nutrient supplements. Once consumed, it facilitates methyl group transfer among molecules, facilitating nucleotide synthesis and the metabolism of amino acids. Specifically, it is involved in methyl-donor metabolism.

Adequate FA supplementation has been associated with higher birth and placental weight and a lower risk of children being small for their gestational age and low birth weight. It also reduces the likelihood of neural tube defects (NTDs).

Continuing supplementation into the second and third trimesters has been shown to have sustained benefits for the neurocognitive development of children up to 11 years old. These included emotional intelligence, word reasoning, semantic processing, verbal-executive and motor function, attention, communication, and social competence.

Maternal deficiency of folate has been linked to numerous adverse outcomes, including elevated blood pressure and overweight in children. However, the availability of fortified foods and supplements has significantly raised folate levels in serum, RBCs, and overall, and recent studies have raised the possibility of adverse consequences of excess supplementation.

FA supplementation and ASD

Maternal intake of folate has been associated with autism spectrum disorder (ASD) incidence in addition to its neurodevelopmental benefits. A study in Norway found that FA intake starting four weeks before the pregnancy began and continuing for 12 weeks was protective against ASD.

However, a more recent study in the United States found a ‘U-shaped’ relationship between ASD risk and the frequency of maternal multivitamin supplementation. This suggests that ASD risk is highest at very low and very high levels of supplementation.

Another analysis indicates that unmetabolized folic acid (UMFA) levels in the cord blood could be positively associated with ASD risk, particularly in Black children, but further research is needed to shed light on these mechanisms.

Insights from mouse models

While well-designed mouse models can provide important information on the effects of high FA supplementation that cannot be ethically researched using human experiments, the timing and duration of supplementation, concentration of FA, how FA was administered, and the possibility of differential effects depending on the sex of the offspring must be considered.

Researchers used microarrays, Western blotting, ribonucleic acid sequencing (RNA-seq), and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to analyze the effects of FA.

Results from some studies indicate that mice exposed to an intermediate level of FA had more gene changes. In terms of sex-based differences, some genes were more affected in female mice while others were more affected in male mice, leading to differential effects in the placenta, embryonic brain, and early postnatal brain. There were also indications that FA could affect brain development early in life but lead to lasting changes in behavior into adulthood.

While maternal FA deficiency has been implicated in NTD, excess supplementation has been associated with reduced placental and embryonic weights, smaller hippocampal areas, and increased weight gain in male but not female offspring. Observed neurodevelopmental impacts included short-term memory impairment, hyperactivity-like and repetitive behavior, and increased anxiety in mouse pups.

Findings varied across studies, but there is clear evidence that excess maternal FA intake can have long-term influences on physical and behavioral outcomes. It may also be implicated in glucose metabolism and reproductive disorders, but there are no indications that there are transgenerational inheritance effects.

Conclusions

Concerns about maternal folate deficiency, but FA supplements and fortified foods are now widely available, and excess intake may have widespread effects on the central nervous system.

While there is now growing evidence of detrimental effects in addition to benefits, there is a need to translate learnings from mouse models to studies on humans and explore the sex-linked impacts. Additionally, focus should be given to new forms of FA supplementation that can mitigate the potential harms of currently available supplements.

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March 8, 2024
Nutrients like vitamin B12 and vitamin D potentially play a role in risk of multimorbidity

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In a recent study published in BMC Public Health, researchers explored potential associations between nutrient intake and multimorbidities.

Study: Nutrient intake and risk of multimorbidity: a prospective cohort study of 25,389 women. Image Credit: Saowanee K/Shutterstock.com

Background

Multimorbidity, or the presence of many chronic illnesses, is a worldwide health concern, particularly among older individuals. It raises the risk of early mortality, hospitalization, loss of physical function, depression, polypharmacy, and a decline in quality of life, inflicting a considerable cost load on healthcare systems.

Nutritional variables have a vital role in multimorbidity prevention. Unhealthy dietary habits like binge eating and excessive drinking might raise the risk. In the Netherlands, individuals with cardiometabolic multimorbidity eat more meat and snacks. Consuming fruits, vegetables, and whole grains can help reduce the risk. Mediterranean diets and increasing calcium and potassium intake are associated with decreased cardiometabolic multimorbidity. Lutein and zeaxanthin are potentially helpful nutrients. However, further study is needed to discover dietary therapies that reduce the multimorbidity burden.

About the study

In the present prospective cohort study, researchers investigated the influence of dietary intake on multimorbidity risk.

The researchers analyzed the United Kingdom Women’s Cohort Study (UKWCS) data from 25,389 females aged between 35 and 69 years. The UKWCS dataset included food intake, anthropometric parameters, socioeconomic status, lifestyle habits, and health outcomes. The participants self-reported baseline chronic diseases such as hypertension, angina, coronary artery disease, stroke, diabetes, hyperlipidemia, gallstones, large intestinal polyps, and cancer.

The team excluded non-residents of England with multiple chronic diseases at baseline and missing covariate data. They used food frequency questionnaires (FFQs) from the UK for the European Prospective Investigation into Cancer and Nutrition (EPIC) study to estimate daily energy and nutrient intakes. They assessed multimorbidity using Charlson comorbidity index (CCI) scores electronically linked to the Hospital Episode Statistics (HES) database through March 2019, using the International Classification of Diseases, tenth edition, Australian modification (ICD-10-AM) codes.

The researchers assessed dietary intake using McCance & Widdowson Food Composition (fifth edition) and Food Standards Agency guidelines, adjusting for total calorie intake by nutrient density. They performed Cox proportional hazards modeling to estimate hazard ratios (HRs) for the relationships between regular nutrient intake and multimorbidity risk. They used multinomial logistic regressions to evaluate the association in the sensitivity analysis and performed a stratified assessment, considering 60 years as the threshold for age. Study covariates included age, body mass index (BMI), educational level, marital status, ethnicity, socioeconomic status (SES), and physical activity.

Results

The mean participant age was 51 years, among whom 31% (n=7,799) developed multimorbidities over a 22-year follow-up (median). Individuals with multimorbidity had a higher BMI, lower educational levels, and higher SES status and showed an increased likelihood of being single or widowed compared to their counterparts.

Compared to the lowermost quintile, the uppermost quintile of regular calorie and protein intakes was related to 8.0% and 12% higher multimorbidity risks, respectively (hazard ratio, 1.1). Compared to the lowermost quintile, higher statistical quintiles of regular vitamin C consumption had a 10% lowered multimorbidity risk, while regular vitamin D consumption had a 10% increased multimorbidity risk. In comparison to the lowermost quintile of vitamin B12 consumption, multimorbidity risk was significantly higher in the topmost quintile (HR, 1.1). Compared with the lowermost quintile, higher quintiles of iron intake had marginally lowered multimorbidity risks.

In the sensitivity analysis, the significantly higher multimorbidity risks linearly related to higher statistical quintiles of B12 and D vitamin intakes were non-significant using multinomial logistic regressions. The team found evidence of age-modifying effects on vitamin B1 and iron intakes associated with multimorbidity risk. For iron intake, the team found an 11% to 13% lower multimorbidity risk among individuals below 60 years compared to those aged above 60 years.

Conclusions

The study findings highlighted a relationship between nutrient consumption and the risk of multimorbidity for developing preventive, diagnostic, treatment, and prognostic methods. The findings indicated that higher intakes of vitamin B12, vitamin D, protein, and energy may raise the risk of multimorbidity, but higher intakes of vitamin C may reduce it. Iron consumption was adversely linked with multimorbidity risk in women aged <60 years, while there was no such association in women aged >60 years.

The study reveals that specific nutrients, notably vitamin B12, vitamin D, protein, and energy, may influence the likelihood of multimorbidity. Researchers must further investigate the optimal nutritional consumption levels for individuals with multimorbidity, and policymakers and clinical practitioners should address individualized nutrition. Additional clinical studies are necessary to determine whether dietary treatments help improve multimorbidity. More studies are needed to draw definitive conclusions.

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March 8, 2024
Mediterranean diet and exercise reshape gut microbiome, aiding weight loss
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In a recent study published in The American Journal of Clinical Nutrition, researchers investigate the health benefits of the Mediterranean diet (MedDiet) and physical activity interventions on overweight and obese participants by measuring changes in fecal metabolomic- and gut microbiota.

Study: Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: A randomized clinical trial. Image Credit: Valentyn Volkov / Shutterstock.com

Health benefits of the MedDiet

Characterized by a high intake of healthy vegetables, legumes, fruits, whole cereals, and nuts, moderate intake of seafood, low intake of dairy products and processed meats, as well as olive oil comprising the primary fat source, the traditional MedDiet has been growing in global popularity.

Previous studies have investigated the health benefits of the MedDiet, which include significant cardiovascular disease (CVD), obesity, neurological, and all-cause mortality risk reductions as compared to suboptimal dietary patterns like the Western diet.

The high concentrations of dietary fiber and anti-inflammatory nutraceuticals in the MedDiet have also been associated with promoting and persisting beneficial gut microbiota. To date, the metabolomic consequences of these associations remain unknown.

Exploring the blood metabolome provides important insights into how gut microbiota-derived metabolites correlate with cardiometabolic diseases. Through the use of plasma metabolomics and 16S sequencing, researchers can elucidate how diet, circulating metabolites, and gut microbiota impact cardiovascular health.

Understanding the influence of dietary interventions on both gut microbial composition and metabolomic profiles can support clinical recommendations to follow the MedDiet and other healthy diets, particularly in high-risk patients. Furthermore, these data can provide foundational insights for future studies investigating the indirect effects of diet on other non-cardiovascular somatic systems.

About the study

In the present study, researchers used data from the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial to investigate the effects of one year of intensive lifestyle intervention on fecal metabolites, gut microbiota, and cardiovascular risk factors, particularly in overweight and obese patients. The study comprised 400 individuals between the ages of 55 and 75 years from Alicante, Barcelona, Reus, and Valencia who were randomly divided between the intervention group (IG) and control group (CG).

Data collection included dietary and lifestyle information obtained through the er-MedDiet questionnaire, a 17-item derivation of the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire. Blood and stool samples were also collected during baseline assessments and routine follow-up. Anthropometric measurements and demographic data were further obtained from medical and government records.

The researchers encouraged all study participants to increase their usual physical activity levels to include at least 45 minutes daily of brisk walking or an equivalent activity. All study participants were also encouraged to perform specific exercises that increase their balance, strength, and flexibility to ultimately complete 150 minutes or more of moderate-to-vigorous physical activity each week.

Changes in physical activity levels were quantified using questionnaires that assigned the metabolic equivalent of tasks (MET) min/week metrics to physical activity status and MET h/day for sedentary behaviors. The study intervention included lifestyle recommendations for physical activity and diet and in-person behavioral support from a licensed dietitian for the IG group. In contrast, CG was treated ad libitum with a regular MedDiet, which was the only intervention.

Outcomes of interest were measured using liquid chromatography-tandem mass spectrometry (LC-MS) for metabolomics identification, characterization, and quantification and 16S amplicon sequencing for gut microbiome evaluations. Linear regression models and weighted gene co-expression network analysis (WGCNA) were used to identify between-group differences and metabolomic sub-networks, respectively.

Study findings

The present study highlights the combined health benefits of a dietitian-guided MedDiet alongside physical activity compared to an ad libitum MedDiet.

Overweight and obese participants in the IG cohort exhibited a mean weight reduction of 4.2 kg and 4.4 cm lower waist circumference than their CG counterparts. The body mass index (BMI) and total energy intake estimates of the IG group were 1.5 kg/m² and 113.9 kcal lower than controls, thus explaining the 0.1% observed reductions in glycated hemoglobin values as compared to controls.

Fecal metabolomic analysis revealed a total of 532 fecal metabolites, four of which were significantly different between IG and CG following one year. These four metabolites included 4,7,10,13,16-docosapentaenoic acid (DPA) and adrenic acid, both of which decreased following the intervention, as well as oleic acid and 3-methyl-adipic acid (3-MAA), both of which increased following intervention. While preliminary analyses suggested an additional 56 metabolites of interest, these were non-significant following false discovery rate (FDR) corrections.

Network analyses grouped the 532 identified metabolites into 16 subnetworks ranging in size from Grey60 to brown. The Black, Midnight Blue, Pink, and Salmon subnetworks significantly differed between IG and CG cohorts following one year of the study.

The Black subnetwork comprised ceramides and spingosines, whereas the Midnight blue subnetwork consists of purines. The Pink subnetwork metabolites included fatty acids and carnitines, whereas the Salmon network comprised bile acids.

Compared to the CG, the IG exhibited reduced levels of the Black, Midnight Blue, and Pink subnetworks. Comparatively, the IG exhibited increased levels of the Salmon subnetwork compared to the CG.

Gut microbial analysis determined that IG Shannon and Chao1 alpha diversity indices were significantly higher than CG indices by the end of the study, with the top two axes of the principal coordinate analysis (PCoA) explaining 36% of the observed differences.

The Eubacterium hallii group exhibited a significant reduction in population size in the IG compared to the CG. A reduced abundance of Dorea was also observed but to a lesser extent than in the Eubacterium hallii group.

Conclusions

The present lifestyle intervention-based clinical trial highlights the benefits of stringent dietary supervision and physical activity engagement for at-risk overweight and obese individuals, even when compared to equal-risk subjects consuming a similarly healthy diet. The energy-reduced MedDiet and physical activity intervention in the IG, when compared with an ad libitum MedDiet for the CG, significantly reduced weight metrics, including waist circumference and BMI.

Even with similar healthy dietary patterns, the high intensity of the dietary intervention and weight-loss intervention components, such as caloric restriction and physical activity, could have significant benefits on CVD risk factors, potentially through modulation of the fecal microbiota and metabolome. Public health policies and interventions can be tailored to individual microbiome profiles, allowing for more precise and effective strategies for preventing and managing cardiometabolic diseases.”
Journal reference:

García-Gavilán, J. F., Atzeni, A., Babio, N., et al. (2024). Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: A randomized clinical trial. The American Journal of Clinical Nutrition. doi:10.1016/j.ajcnut.2024.02.021
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March 5, 2024
Increased adherence to DASH diet related to decreased probabilities of metabolic disease conditions among adolescents, particularly overweight girls

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In a recent study published in Scientific Reports, researchers evaluated the relationship between Dietary Approaches to Stop Hypertension (DASH) and metabolic health status among Iranian overweight and obese adolescents.

Study: Association of priori-defined DASH dietary pattern with metabolic health status among Iranian adolescents with overweight and obesity. Image Credit: monticello/Shutterstock.com

Background

Adolescent overweight and obesity are global health concerns associated with metabolic conditions such as hypertension, blood lipid abnormalities, impaired glucose metabolism, and insulin resistance. These diseases increase the risk of cardiovascular disease, type 2 diabetes, and early death—lifestyle variables such as food and physical exercise influence metabolic health.

Recent studies report favorable relationships between high vegetable and fruit intake and low sugary beverages and fats, implying a link between healthy diets and metabolically healthy overweight or obesity. The DASH diet, which contains more vegetables, fruits, whole grains, legumes, seeds, and low-fat-type dairy foods, has been researched in adolescents, but disputed findings call for more research.

About the study

In the present cross-sectional study, researchers explored the metabolic impact of DASH diets among overweight and obese adolescents.

The team surveyed 203 adolescents aged 12 to 18 years with overweight or obesity status, as determined by body mass index (BMI) values using the Quetelet formula. Eligible students did not follow weight-loss diets, had no endocrinal or genetic disease, and did not use vitamin or mineral supplements or medications that could alter their metabolic profiles.

The researchers obtained dietary intake data using standardized food frequency questionnaires (FFQs). They also collected data on anthropometric parameters such as circulating insulin, blood pressure, lipid profile, and fasting blood sugar. The team characterized DASH scores based on eight components, i.e., higher intake of low-fat dairy foods, whole grains, seeds, nuts, vegetables, fruits, and legumes, and lower consumption of sodium, sweetened beverages, and processed and red meats.

The team obtained blood samples from all participants for biochemical analysis. They measured insulin levels by enzyme-linked immunosorbent assays (ELISA) and ascertained metabolic health status based on insulin resistance, determined using the International Diabetes Federation (IDF) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) criteria.

The researchers assessed physical activity levels using the Physical Activity Questionnaire for Adolescents (PAQ-A) and total calorie intake using the United States Department of Agriculture (USDA) food composition database. They used multivariate logistic regression to calculate the odds ratios (ORs) for the association between DASH diets and metabolic health, adjusting for age, gender, physical activity, socioeconomic status, and total calorie intake.

Results

The mean values for age and BMI of the study participants were 14 years and 27 kg/m2, respectively. Among participants, 79 (42 girls and 37 boys, 39%) suffered from metabolically unhealthy overweight or obesity (MUO) by the IDF definition, and 62 (32 girls and 35 boys, 33%) were MUO following the IDF and HOMA-IR guidelines. Using the IDF definition, MUO prevalence in the DASH diet’s highest tertile was lower compared to the lowest statistical tertile (10 vs. 67%). Using HOMA-IR guidelines yielded similar findings (10 vs. 61%).

Individuals in the uppermost tertile of the DASH diet were more physically active, with higher HDL-c levels and lower blood pressure, fasting blood sugar, insulin, triglyceride, and HOMA-IR levels, compared to those in the lowest tertile. Confounder adjustment showed that individuals in the highest vs. lowest DASH tertile had 91% and 92% lower MUO odds using the IDF/IR (OR, 0.09) and IDF definition (OR, 0.08), respectively.

The highest vs. lowest DASH adherence was associated with decreased odds of hyperglycemia, hypertriglyceridemia, insulin resistance, and low HDL cholesterolemia, with odds ratios of 0.1, 0.3, 0.1, and 0.3, respectively. Subgroup analysis by BMI and sex indicated that the association was more robust among females (OR, 0.02) than males (OR, 0.09). The DASH diet likely improves metabolic health by lowering inflammation because of its high fiber, antioxidants, potassium, magnesium, and low salt content.

Conclusions

Overall, the study findings showed that increased adherence to the DASH diet was related to decreased probabilities of metabolic disease conditions among Iranian adolescents, particularly overweight girls. The study also found that adhering to the DASH diet reduced the risk of hypertriglyceridemia, hyperglycemia, insulin resistance, and low HDL cholesterol. Further research, including prospective surveys, could validate the study findings.

The inverse association observed between the DASH dietary pattern and the MUO category in the current study indicates that adolescents must increase the intake of health-associated DASH components, including fruits, vegetables, legumes, low-fat-type dairy foods, whole grains, seeds, and nuts while limiting the consumption of unhealthy foods such as processed and red meats, sweetened beverages, and salt to improve dietary quality and decrease the metabolic disease burden.

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March 4, 2024