-
1.
Host-diet-gut microbiome interactions influence human energy balance: a randomized clinical trial.
Corbin, KD, Carnero, EA, Dirks, B, Igudesman, D, Yi, F, Marcus, A, Davis, TL, Pratley, RE, Rittmann, BE, Krajmalnik-Brown, R, et al
Nature communications. 2023;14(1):3161
-
-
-
Free full text
Plain language summary
Composition of the human gut microbiome has been shown to be associated with chronic diseases such as obesity, however whether they have a causal effect in disease development or whether microbiota composition is a direct result of the disease is unclear. This randomised control trial of 17 individuals aimed to determine the effects of a diet designed to modulate the gut microbiome (MBD) on human energy balance compared to a typical Western style diet (WD). The MBD diet maximised fibre, resistant starch, and limited processed foods and resulted in a significant decrease in the amount of energy produced by individuals compared to the WD. It was also shown that the MBD increased the microbial composition and decreased nutrient breakdown. It was concluded that the MBD increased the amount of gut bacteria and altered the amount of energy produced by individuals on this diet. This study could be used by healthcare practitioners to understand that composition of the gut microbiome can affect the amount of energy gained from food. Diets high in fibre, starch and low in processed foods, which promote microbial diversity may help individuals to lose weight.
Abstract
The gut microbiome is emerging as a key modulator of human energy balance. Prior studies in humans lacked the environmental and dietary controls and precision required to quantitatively evaluate the contributions of the gut microbiome. Using a Microbiome Enhancer Diet (MBD) designed to deliver more dietary substrates to the colon and therefore modulate the gut microbiome, we quantified microbial and host contributions to human energy balance in a controlled feeding study with a randomized crossover design in young, healthy, weight stable males and females (NCT02939703). In a metabolic ward where the environment was strictly controlled, we measured energy intake, energy expenditure, and energy output (fecal and urinary). The primary endpoint was the within-participant difference in host metabolizable energy between experimental conditions [Control, Western Diet (WD) vs. MBD]. The secondary endpoints were enteroendocrine hormones, hunger/satiety, and food intake. Here we show that, compared to the WD, the MBD leads to an additional 116 ± 56 kcals (P < 0.0001) lost in feces daily and thus, lower metabolizable energy for the host (89.5 ± 0.73%; range 84.2-96.1% on the MBD vs. 95.4 ± 0.21%; range 94.1-97.0% on the WD; P < 0.0001) without changes in energy expenditure, hunger/satiety or food intake (P > 0.05). Microbial 16S rRNA gene copy number (a surrogate of biomass) increases (P < 0.0001), beta-diversity changes (whole genome shotgun sequencing; P = 0.02), and fermentation products increase (P < 0.01) on an MBD as compared to a WD along with significant changes in the host enteroendocrine system (P < 0.0001). The substantial interindividual variability in metabolizable energy on the MBD is explained in part by fecal SCFAs and biomass. Our results reveal the complex host-diet-microbiome interplay that modulates energy balance.
-
2.
An Energy-Reduced Mediterranean Diet, Physical Activity, and Body Composition: An Interim Subgroup Analysis of the PREDIMED-Plus Randomized Clinical Trial.
Konieczna, J, Ruiz-Canela, M, Galmes-Panades, AM, Abete, I, Babio, N, Fiol, M, Martín-Sánchez, V, Estruch, R, Vidal, J, Buil-Cosiales, P, et al
JAMA network open. 2023;6(10):e2337994
-
-
-
-
Free full text
-
Plain language summary
The Mediterranean diet (MedDiet), which focuses on whole grains, lean meat, fruits, vegetables, and low amounts of minimally processed foods has been shown in previous research to improve body composition and decrease fat storage around the middle. This randomised control trial of 1556 older adults aimed to determine the effects of combining a 30% lower energy version of the MedDiet in combination with physical exercise on body composition. After 3 years, the results showed that compared to a normal MedDiet without exercise, the lower energy version in combination with exercise improved body composition by decreasing total fat, and the fat stored around the organs and increasing muscle mass. However, benefits were more pronounced after 1 year and decreased slightly at 3 years. It was concluded that a low energy MedDiet in combination with physical activity may be able to improve the body composition of overweight and older adults with obesity. This study could be used by healthcare professionals to recommend a low energy MedDiet to older adults to promote weight loss, whilst attenuating muscle loss associated with ageing.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The addition of exercise to an energy-reduced diet, which focuses on whole grains, healthy fats, lean protein, and fruits and vegetables can emphasise positive effects on body composition in older adults.
- However, there is a loss of lean mass associated with this type of diet (contrary to author conclusions) and measures should be taken to monitor and increase protein intake to prevent or limit this loss.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
This study aimed to determine the long-term effects of an energy reduced MedDiet in combination with physical activity on body composition.
Methods
- This is a predetermined 3-year interim analysis of a 6-year single-blind, randomised control trial of 1556 individuals aged 55-75 who are overweight or obese with metabolic syndrome.
- 760 individuals on 30% energy reduced MedDiet with limited processed foods, plus 45 minutes walking 6 days per week and behavioural and motivational support. [Intervention group]
- 761 on standard MedDiet without physical activity. [Control]
Results
Within group comparisons showed that individuals in the intervention group lost (P value represents baseline vs year 3):
- Total fat mass percentage (1-year vs baseline, −1.14%; 95% CI, −1.32% to −0.96%; 3-year vs baseline, −0.52%; 95% CI, −0.71% to −0.33% P=<0.001)
- Absolute visceral fat (1-year vs baseline, −154 g; 95% CI, −191 to −116 g; 3-year vs baseline, −75.1 g, 95% CI, −115 to −35.3 g P=<0.001)
- Absolute total fat after 1 year (mean change at 1 year vs baseline, −1677 g; 95% CI, −1930 to −1424 g) but regained some at year 3 (mean change at 3 years vs baseline, −1018 g; 95% CI, −1280 to −756 g P=<0.001)
- Absolute lean mass (mean change at 1 year vs baseline −300 g; 95% CI, −439 to −162 g) with further losses at year 3 (−626 g; 95% CI, −770 to −483 g P=0.001).
Within group comparisons also showed significantly increased:
- Total lean mass percentage, which was greater at year 1 than year 3 (1-year vs baseline, 1.07%; 95%CI, 0.90%-1.25%; 3-year vs baseline, 0.47%; 95% CI, 0.29%-0.65% P=<0.001).
As a result of total fat loss and some lean mass in the intervention group, the lean:fat mass ratio improved and was unchanged in the control group (between group differences (P=<0.001).
Compared to women, men may find the MedDiet + exercise more beneficial as it was shown that body composition changes were slightly more pronounced in men.
Conclusion
An energy-reduced MedDiet plus exercise emphasised positive changes to body composition compared to standard MedDiet in older adults who are overweight or have obesity.
Clinical practice applications:
- The recommendation of a reduced energy MedDiet in combination with physical activity to older people who are overweight or obese may improve body composition.
- Although lean mass loss slowed between years 1 and 3, other practices should be employed to attenuate the loss of lean mass associated with an energy-reduced MedDiet and ageing.
Considerations for future research:
- The research has not yet concluded but when it does, it will address the incidence of cardiovascular disease along with body composition changes.
- It will also look at long-term effects of the diet to determine longevity.
- Future research could focus on how to limit lean mass loss through the possibility of changing the type of exercise that accompanies the MedDiet.
Abstract
IMPORTANCE Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. OBJECTIVE To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. DESIGN, SETTING, AND PARTICIPANTS The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. INTERVENTION Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. MAIN OUTCOMES AND MEASURES The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). RESULTS A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, -0.94% [95% CI, -1.19 to -0.69]; 3 years, -0.38% [95% CI, -0.64 to -0.12] and visceral fat storage after 1 year, -126 g [95% CI, -179 to -73.3 g]; 3 years, -70.4 g [95% CI, -126 to -15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95% CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. CONCLUSIONS AND RELEVANCE The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN89898870.
-
3.
Mediterranean and Western diet effects on Alzheimer's disease biomarkers, cerebral perfusion, and cognition in mid-life: A randomized trial.
Hoscheidt, S, Sanderlin, AH, Baker, LD, Jung, Y, Lockhart, S, Kellar, D, Whitlow, CT, Hanson, AJ, Friedman, S, Register, T, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022;18(3):457-468
-
-
-
-
Free full text
-
Plain language summary
There is a current understanding that Alzheimer’s disease (AD) development is related to a high intake of saturated fat and simple carbohydrates, which are found in abundance in the so-called Western Diet (WD). In contrast the consumption of low saturated fat and simple carbohydrates characteristic of the Mediterranean Diet (MD), has been associated with a reduced risk for the development of AD. This study aimed to look at the association of the MD and WD with AD in a more robust way using the randomised control method in 84 individuals both with and without mild memory impairment. The results showed that depending on whether an individual has mild brain impairment determines their response to the MD or WD after 4 weeks. In those without brain impairment the adoption of the WD resulted in a shift towards increasing the risk for AD development and the reverse following the MD. Whereas in those with brain impairment, the adoption of the WD was protective against the development of AD and the MD moved individuals towards worse disease outcomes. It was concluded that diet can be of importance in the prevention or progression of AD and that further studies are required to determine the possible mechanisms through which these two diets can act differentially. This study could be used by health care professionals to understand that diet can have a large impact on AD.
Expert Review
Conflicts of interest:
None
Take Home Message:
- A Med-diet may be beneficial for supporting brain health, cognitive function. metabolic health and reduce the risk of an AD pathology in middle-aged adults with normal cognitive function
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
Epidemiological studies have associated a Western diet (West-diet) with an increased risk of Alzheimer’s disease (AD) and other dementias. This study aimed to examine the impact of a Mediterranean-diet (Med-diet) versus a West-diet on AD pathology, cognition, vascular function and metabolic markers in middle aged adults with normal cognitive (NC) function compared to adults with mild cognitive impairment (MCI).
Methods
N=41 NC adult females completed the Med-diet and N=43 adult females with MCI completed the West-diet arm of this study. The average age of the participants was 56y. All participants received isocaloric diets which were either high or low in saturated fat, sodium and glycaemic index (GI) for 4 weeks. Statistical analyses were conducted per dietary arm as well as per cognitive function (NC vs MCI).
Results
- NC Participants were found to have decreased cerebro-spinal fluid (CSF) biomarkers (p=.026) following the Med-diet and increased levels following the West-diet. Whereas, cerebral perfusion increased following the med-diet and decreased after the West-diet (p=.003). These results indicate a reduced AD risk. The MCI group showed no changes to CSF or cerebral perfusion for either dietary group.
- Cognition tended to improve for the NC Med-diet and remain the same for the NC West-diet group. No changes were found for the MCI groups.
- Total cholesterol levels were increased following the West-diet and decreased following the Med-diet for both groups (p=0.0001).
- Glucose and HbA1C were unchanged in the NC group following the Med-diet, increased for the West-diet (p=.049) and decreased for the MCI group (p=<.001). whereas fasting insulin was increased in the NC Med-diet group and decreased in the MCI Med-diet (p=.0.12) and West diet groups.
Conclusion
The results of this study found that diet may modulate AD pathology, cognitive and metabolic function in middle-aged adults. A West-like diet may increase risk of AD through its effects on impairing cognitive function, reducing cerebral infusion and negatively influencing metabolic health in NC adults. Conversely, A Med-diet may promote brain function and metabolic health. However, surprisingly, in this study the results were reversed for MCI middle aged adults, the results showed improvement in metabolic and cerebrospinal fluid biomarkers for the West-diet. These results require further confirmation.
No conflicts of interest were declared.
Clinical practice applications:
- A Med-diet may be beneficial for supporting brain health, cognitive function, metabolic health and reducing the risk of an AD pathology in middle-aged adults with normal cognitive function but not for those with MCI.
Considerations for future research:
The authors acknowledged several limitations to this study.
- These results require further confirmation through longer and larger studies, particularly the surprising finding that a West-diet may confer beneficial effects on metabolic and brain health for middle-aged adults with MCI.
Abstract
INTRODUCTION Mid-life dietary patterns are associated with Alzheimer's disease (AD) risk, although few controlled trials have been conducted. METHODS Eighty-seven participants (age range: 45 to 65) with normal cognition (NC, n = 56) or mild cognitive impairment (MCI, n = 31) received isocaloric diets high or low in saturated fat, glycemic index, and sodium (Western-like/West-diet vs. Mediterranean-like/Med-diet) for 4 weeks. Diet effects on cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral perfusion were assessed to determine whether responses differed by cognitive status. RESULTS CSF amyloid beta (Aβ)42/40 ratios increased following the Med-diet, and decreased after West-diet for NC adults, whereas the MCI group showed the reverse pattern. For the MCI group, the West-diet reduced and the Med-diet increased total tau (t-tau), whereas CSF Aβ42 /t-tau ratios increased following the West-diet and decreased following the Med-diet. For NC participants, the Med-diet increased and the West-diet decreased cerebral perfusion. DISCUSSION Diet response during middle age may highlight early pathophysiological processes that increase AD risk.
-
4.
Longitudinal association of dietary carbohydrate quality with visceral fat deposition and other adiposity indicators.
Zamanillo-Campos, R, Chaplin, A, Romaguera, D, Abete, I, Salas-Salvadó, J, Martín, V, Estruch, R, Vidal, J, Ruiz-Canela, M, Babio, N, et al
Clinical nutrition (Edinburgh, Scotland). 2022;41(10):2264-2274
-
-
-
-
Free full text
Plain language summary
Abdominal obesity, measured by waist circumference, a proxy of visceral fat, is increasing at an even greater rate than overall obesity alone. Diet plays a key role in body fat accumulation; however, recent evidence also indicates that, beyond quantity, the quality of certain nutrients may have an independent effect. The aim of this study was to determine the dynamic association between changes in overall dietary carbohydrate quality and changes in objectively measured visceral and overall adiposity distribution This study is a prospective cohort study based on data collected during the first year of the PREDIMED-Plus (PREvencion con DIeta MEDiterranea Plus) randomised controlled trial. In the PREDIMED-Plus trial, a total of 6874 people were randomly allocated in a 1:1 ratio to either the intervention or control group. Results show that a carbohydrate quality index increase was associated with a decrease in regional and overall adiposity. The observed associations were mostly driven by fibre and the wholegrains/total grains ratio. Authors conclude that the promotion of fibre-rich foods, including fruits, vegetables, legumes and nuts, and the substitution of refined grains by wholegrains, may be important dietary recommendations to adopt in clinical practice to promote a healthier body composition.
Expert Review
Conflicts of interest:
None
Take Home Message:
This prospective cohort of older adults with overweight/obesity and MetS, found that improvements in dietary carbohydrate quality over one year was associated with positive changes in visceral and overall fat deposition, largely due to dietary fibre and the wholegrain/total grain ratio.
Evidence Category:
-
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
X
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Background
Obesity prevalence is increasing worldwide and is associated with a range of metabolic and cardiovascular diseases. Excess visceral fat appears with increasing age but also with unhealthy dietary patterns and lifestyle behaviours, and it contributes to chronic diseases, particularly type 2 diabetes (T2D), insulin resistance, metabolic syndrome (MetS), and cardiovascular diseases (CVD).
Aim
This study determined the association between changes in overall dietary carbohydrate quality and changes in objectively-measured visceral and overall adiposity distribution. Three repeated measurements of diet and adiposity were conducted throughout a 1-year follow-up, using a dual-energy X-ray absorptiometry (DXA) scans for body composition assessment.
The study compared an intensive weight-loss (intervention group) using an energy-reduced Mediterranean Diet (MedDiet), with physical activity (PA), and behavioural support on the prevention of CVD events, compared to usual care and dietary counselling only.
This prospective cohort study analysed a subgroup of 1476 participants (men aged 55-75 years and women aged 60-75 years) enrolled in the PREDIMED-Plus randomized controlled trial. Participants were overweight or obese (BMI>27 kg/m2 and <40 kg/m2) with no previous cardiovascular events and at least three characteristics of metabolic syndrome (MetS): hypertension, hyper-triglyceridemia, lower high-density lipoprotein (HDL) cholesterol, hyperglycemia, or central obesity.
Dietary intake was measured at baseline, 6- and 12-months using a Spanish version of the validated 143-item semi-quantitative food-frequency questionnaire, via face-to-face interviews by trained dietitian-nutritionists. Carbohydrate quality index (CQI) was calculated using four criteria: total dietary fibre, glycemic index, wholegrain/total grain carbohydrate ratio, and solid/total carbohydrate ratio.
Results
Improvements in body composition and lifestyle factors were observed compared to baseline data (both study arms combined) (p < 0.05 for all). A higher Carbohydrate Quality Index CQI (p = 0.024) was observed at both the 6 and 12 month follow-up.
A 3-point increment in CQI over 12-month follow-up was associated with a decrease in visceral fat (β 0.067 z-score, 95% CI -0.088 to -0.046, p<0.001), android-to-gynoid fat ratio* (β -0.038, 95% CI -0.059 to -0.017, p<0.001) (*calculated by dividing the fat mass (g) from the specific regions), and total fat (β -0.064, 95% CI -0.080 to -0.047, p<0.001).
Fibre intake and the ratio of whole grain/total grain showed the strongest inverse associations with all adiposity indicators. Statistically significant differences were observed over time in all CQI components. The most relevant changes were the increase in consumption of carbohydrates from whole-grains and a decrease in refined grains, and an increase in dietary fibre intake. After evaluating each CQI component separately, the study found that fibre intake and the ratio of whole grain/total grain presented the strongest and statistically significant negative associations with all adiposity indicators (all p-values <0.01).
Limitations
Due to the observational nature of the study, causality cannot be inferred. The study population is based on older people with overweight/obesity and MetS from a Mediterranean area, which can limit the generalisability of findings to the general population.
The use of self-reported dietary data is subject to measurement error, where self-reports may be affected by a tendency to respond in a manner to avoid criticism or judgement and to seek social approval.
Clinical practice applications:
Evidence has shown that the quality of dietary carbohydrates, rather than the quantity, may have a greater impact on health and overall mortality.
While visceral fat constitutes only a small proportion of total fat, the available evidence indicates that it plays an important role in certain chronic diseases, such as T2D, MetS, CVD and cancer.
Findings from this study suggest a better CQI via the manipulation of carbohydrate quality may be associated with a decrease in visceral fat, which are independent of changes in total body fat.
Considerations for future research:
Future strategies to decrease visceral fat are warranted.
Robust reference ranges are needed for the interpretation of visceral fat in clinical practice and research settings.
Abstract
BACKGROUND & AIMS The quality of dietary carbohydrates rather than total carbohydrate intake may determine the accumulation of visceral fat; however, to date, few studies have examined the impact of diet on adiposity using specific imaging techniques. Thus, the aim of this prospective study was to investigate the association between concurrent changes in carbohydrate quality index (CQI) and objectively-quantified adiposity distribution over a year. METHODS We analyzed a cohort of 1476 participants aged 55-75 years with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus randomized controlled trial. Dietary intake information was obtained at baseline, 6- and 12-months from a validated 143-item semi-quantitative food-frequency questionnaire, and CQI (range: 4 to 20) was calculated based on four dietary criteria: total dietary fibre, glycemic index, wholegrain/total grain carbohydrate ratio, and solid/total carbohydrate ratio. Overall and regional adiposity (total body fat, visceral fat and android-to-gynoid fat ratio) was quantified using dual-energy X-ray absorptiometry at all three time points. Multiple adjusted linear mixed-effects models were used to assess associations between concurrent changes in repeatedly measured CQI and adiposity over time. RESULTS After controlling for potential confounding factors, a 3-point increment in CQI over 12-month follow-up was associated with a decrease in visceral fat (β -0.067 z-score, 95% CI -0.088; -0.046, p < 0.001), android-to-gynoid fat ratio (-0.038, -0.059; -0.017, p < 0.001), and total fat (-0.064, -0.080; -0.047, p < 0.001). Fibre intake and the ratio of wholegrain/total grain showed the strongest inverse associations with all adiposity indicators. CONCLUSIONS In this prospective cohort of older adults with overweight/obesity and MetS, we found that improvements in dietary carbohydrate quality over a year were associated with concurrent favorable changes in visceral and overall fat deposition. These associations were mostly driven by dietary fibre and the wholegrain/total grain ratio. TRIAL REGISTRATION The trial was registered at the International Standard Randomized. CONTROLLED TRIAL (ISRCTN http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.
-
5.
Obesity and Sex-Related Associations With Differential Effects of Sucralose vs Sucrose on Appetite and Reward Processing: A Randomized Crossover Trial.
Yunker, AG, Alves, JM, Luo, S, Angelo, B, DeFendis, A, Pickering, TA, Monterosso, JR, Page, KA
JAMA network open. 2021;4(9):e2126313
-
-
-
Free full text
-
Plain language summary
Added sweeteners are increasingly being used in foods to maintain the sweet taste without the added calories, however the health consequences of this are still unclear. Most of the research that exists is in men of normal weight, however women and individuals with obesity have shown to have differing appetite responses. This randomised crossover trial of 74 adults aimed to determine the effect of consuming sweetener compared to sugar on brain, hormone, and appetite responses and whether these differed by sex and obesity status. The results showed that women had increased food related brain responses and consumed greater calories following ingestion of an artificially sweetened drink. In those with obesity food related brain response was also increased following sweetener consumption. Blood glucose hormone response was decreased following sweetener consumption compared to sugar consumption. It was concluded that females and individuals with obesity have differing brain activity following consumption of sweetener. This study could be used by healthcare professionals to understand that the recommendation of artificial sweeteners for weight loss in women and those who are already suffering from obesity may lead to greater calorie consumption. However further research is needed to confirm this.
Abstract
Importance: Nonnutritive sweeteners (NNSs) are used as an alternative to nutritive sweeteners to quench desire for sweets while reducing caloric intake. However, studies have shown mixed results concerning the effects of NNSs on appetite, and the associations between sex and obesity with reward and appetitive responses to NNS compared with nutritive sugar are unknown. Objective: To examine neural reactivity to different types of high-calorie food cues (ie, sweet and savory), metabolic responses, and eating behavior following consumption of sucralose (NNS) vs sucrose (nutritive sugar) among healthy young adults. Design, Setting, and Participants: In a randomized, within-participant, crossover trial including 3 separate visits, participants underwent a functional magnetic resonance imaging task measuring blood oxygen level-dependent signal in response to visual cues. For each study visit, participants arrived at the Dornsife Cognitive Neuroimaging Center of University of Southern California at approximately 8:00 am after a 12-hour overnight fast. Blood was sampled at baseline and 10, 35, and 120 minutes after participants received a drink containing sucrose, sucralose, or water to measure plasma glucose, insulin, glucagon-like peptide(7-36), acyl-ghrelin, total peptide YY, and leptin. Participants were then presented with an ad libitum meal. Participants were right-handed, nonsmokers, weight-stable for at least 3 months before the study visits, nondieters, not taking medication, and with no history of eating disorders, illicit drug use, or medical diagnoses. Data analysis was performed from March 2020 to March 2021. Interventions: Participants ingested 300-mL drinks containing either sucrose (75 g), sucralose (individually sweetness matched), or water (as a control). Main Outcomes and Measures: Primary outcomes of interest were the effects of body mass index (BMI) status and sex on blood oxygen level-dependent signal to high-calorie food cues, endocrine, and feeding responses following sucralose vs sucrose consumption. Secondary outcomes included neural, endocrine, and feeding responses following sucrose vs water and sucralose vs water (control) consumption, and cue-induced appetite ratings following sucralose vs sucrose (and vs water). Results: A total of 76 participants were randomized, but 2 dropped out, leaving 74 adults (43 women [58%]; mean [SD] age, 23.40 [3.96] years; BMI range, 19.18-40.27) who completed the study. In this crossover design, 73 participants each received water (drink 1) and sucrose (drink 2), and 72 participants received water (drink 1), sucrose (drink 2), and sucralose (drink 3). Sucrose vs sucralose was associated with greater production of circulating glucose, insulin, and glucagon-like peptide-1 and suppression of acyl-ghrelin, but no differences were found for peptide YY or leptin. BMI status by drink interactions were observed in the medial frontal cortex (MFC; P for interaction < .001) and orbitofrontal cortex (OFC; P for interaction = .002). Individuals with obesity (MFC, β, 0.60; 95% CI, 0.38 to 0.83; P < .001; OFC, β, 0.27; 95% CI, 0.11 to 0.43; P = .002), but not those with overweight (MFC, β, 0.02; 95% CI, -0.19 to 0.23; P = .87; OFC, β, -0.06; 95% CI, -0.21 to 0.09; P = .41) or healthy weight (MFC, β, -0.13; 95% CI, -0.34 to 0.07; P = .21; OFC, β, -0.08; 95% CI, -0.23 to 0.06; P = .16), exhibited greater responsivity in the MFC and OFC to savory food cues after sucralose vs sucrose. Sex by drink interactions were observed in the MFC (P for interaction = .03) and OFC (P for interaction = .03) after consumption of sucralose vs sucrose. Female participants had greater MFC and OFC responses to food cues (MFC high-calorie vs low-calorie cues, β, 0.21; 95% CI, 0.05 to 0.37; P = .01; MFC sweet vs nonfood cues, β, 0.22; 95% CI, 0.02 to 0.42; P = .03; OFC food vs nonfood cues, β, 0.12; 95% CI, 0.02 to 0.22; P = .03; and OFC sweet vs nonfood cues, β, 0.15; 95% CI, 0.03 to 0.27; P = .01), but male participants' responses did not differ (MFC high-calorie vs low-calorie cues, β, 0.01; 95% CI, -0.19 to 0.21; P = .90; MFC sweet vs nonfood cues, β, -0.04; 95% CI, -0.26 to 0.18; P = .69; OFC food vs nonfood cues, β, -0.08; 95% CI, -0.24 to 0.08; P = .32; OFC sweet vs nonfood cues, β, -0.11; 95% CI, -0.31 to 0.09; P = .31). A sex by drink interaction on total calories consumed during the buffet meal was observed (P for interaction = .03). Female participants consumed greater total calories (β, 1.73; 95% CI, 0.38 to 3.08; P = .01), whereas caloric intake did not differ in male participants (β, 0.68; 95% CI, -0.99 to 2.35; P = .42) after sucralose vs sucrose ingestion. Conclusions and Relevance: These findings suggest that female individuals and those with obesity may be particularly sensitive to disparate neural responsivity elicited by sucralose compared with sucrose consumption. Trial Registration: ClinicalTrials.gov Identifier: NCT02945475.
-
6.
Lipids activate skeletal muscle mitochondrial fission and quality control networks to induce insulin resistance in humans.
Axelrod, CL, Fealy, CE, Erickson, ML, Davuluri, G, Fujioka, H, Dantas, WS, Huang, E, Pergola, K, Mey, JT, King, WT, et al
Metabolism: clinical and experimental. 2021;121:154803
-
-
-
Free full text
-
Plain language summary
Insulin resistance is a key pathophysiological mechanism in the development and progression of type 2 diabetes. Abnormalities in lipid metabolism and ectopic lipid accumulation are known to directly contribute to the onset of insulin resistance. Authors hypothesised that lipid infusion would increase dynamin related protein 1 [a type of protein]-mediated mitochondrial fission in skeletal muscle independent of function and content, consequently reducing peripheral insulin sensitivity. The study included sedentary but otherwise healthy adults who were prospectively randomized to receive either lipid or saline infusion to isolate the direct contribution of fatty acids to skeletal muscle mitochondrial dynamics. Results show that mitochondrial fission and quality control networks are activated in response to lipid infusion which occurs independent of changes in mitochondrial content or capacity and contributes to the onset of insulin resistance in healthy humans. Authors conclude that treatments that limit lipid-induced activation of mitochondrial fission and/or quality control processes may have therapeutic value in the treatment of insulin resistance.
Abstract
BACKGROUND AND AIMS A diminution in skeletal muscle mitochondrial function due to ectopic lipid accumulation and excess nutrient intake is thought to contribute to insulin resistance and the development of type 2 diabetes. However, the functional integrity of mitochondria in insulin-resistant skeletal muscle remains highly controversial. METHODS 19 healthy adults (age:28.4 ± 1.7 years; BMI:22.7 ± 0.3 kg/m2) received an overnight intravenous infusion of lipid (20% Intralipid) or saline followed by a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity using a randomized crossover design. Skeletal muscle biopsies were obtained after the overnight lipid infusion to evaluate activation of mitochondrial dynamics proteins, ex-vivo mitochondrial membrane potential, ex-vivo oxidative phosphorylation and electron transfer capacity, and mitochondrial ultrastructure. RESULTS Overnight lipid infusion increased dynamin related protein 1 (DRP1) phosphorylation at serine 616 and PTEN-induced kinase 1 (PINK1) expression (P = 0.003 and P = 0.008, respectively) in skeletal muscle while reducing mitochondrial membrane potential (P = 0.042). The lipid infusion also increased mitochondrial-associated lipid droplet formation (P = 0.011), the number of dilated cristae, and the presence of autophagic vesicles without altering mitochondrial number or respiratory capacity. Additionally, lipid infusion suppressed peripheral glucose disposal (P = 0.004) and hepatic insulin sensitivity (P = 0.014). CONCLUSIONS These findings indicate that activation of mitochondrial fission and quality control occur early in the onset of insulin resistance in human skeletal muscle. Targeting mitochondrial dynamics and quality control represents a promising new pharmacological approach for treating insulin resistance and type 2 diabetes. CLINICAL TRIAL REGISTRATION NCT02697201, ClinicalTrials.gov.
-
7.
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.
Yoshino, M, Yoshino, J, Kayser, BD, Patti, GJ, Franczyk, MP, Mills, KF, Sindelar, M, Pietka, T, Patterson, BW, Imai, SI, et al
Science (New York, N.Y.). 2021;372(6547):1224-1229
-
-
-
Free full text
-
Plain language summary
Nicotinamide adenine dinucleotide (NAD+) is a co-substrate for NAD+-consuming enzymes that are essential in the regulation of diverse biological processes. The aim of this study was to determine the effects of nicotinamide mononucleotide (NMN) supplementation on i) body composition, ii) skeletal muscle insulin sensitivity, and insulin signalling; and iii) muscle NAD+ content and global gene expression profile. This study is a 10-week, randomized, placebo-controlled, double-blind trial in postmenopausal women with prediabetes who were overweight or obese. Twenty-five postmenopausal women with prediabetes were randomised to the placebo group (n=12) or the NMN group (n=13). Results show that 10 weeks of NMN supplementation increases muscle insulin signalling and muscle insulin sensitivity in postmenopausal women with prediabetes who are overweight or obese. Authors conclude that the precise mechanism(s) responsible for these metabolic effects and the potential metabolic benefits of NMN supplementation in other patient populations remain to be explored.
Abstract
In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT03151239).
-
8.
A Single Bout of Premeal Resistance Exercise Improves Postprandial Glucose Metabolism in Obese Men with Prediabetes.
Bittel, AJ, Bittel, DC, Mittendorfer, B, Patterson, BW, Okunade, AL, Abumrad, NA, Reeds, DN, Cade, WT
Medicine and science in sports and exercise. 2021;53(4):694-703
-
-
-
Free full text
-
Plain language summary
Prediabetes is a metabolic condition defined by elevated fasting (impaired fasting glucose) and/or postprandial (impaired glucose tolerance) plasma glucose. The aim of this study was to determine the effects of a single bout of resistance exercise on postprandial glucose metabolism following a mixed meal in obese, sedentary men with prediabetes. This study is a randomised, cross-over study design which enrolled ten participants. Participants were aged 39-62 years, obese, and demonstrated insulin resistance with compensatory increases in beta cell function. Results show that a single bout of resistance exercise performed 4.5 hours before a mixed meal (as opposed to an oral glucose tolerance test) reduced total postprandial glucose appearance, increased insulin sensitivity, and reduced the glycaemic response to a mixed meal. However, it did not have effect on glucose oxidation in obese men with prediabetes. Improvements in insulin sensitivity were complemented by reduced postprandial insulin concentration. Authors conclude that further investigation is needed to elucidate how resistance exercise affects exogenous (meal) vs endogenous postprandial glucose metabolism, and if additional bouts of exercise (i.e. training) produce superior outcomes for this population.
Abstract
INTRODUCTION Prediabetes is a major risk factor for type 2 diabetes and cardiovascular diseases. Although resistance exercise (RE) is recommended for individuals with prediabetes, the effects of RE on postprandial glucose metabolism in this population are poorly understood. Therefore, the purpose of this study was to elucidate how RE affects postprandial glucose kinetics, insulin sensitivity, beta cell function, and glucose oxidation during the subsequent meal in sedentary men with obesity and prediabetes. METHODS We studied 10 sedentary men with obesity (body mass index, 33 ± 3 kg·m-2) and prediabetes by using a randomized, cross-over study design. After an overnight fast, participants completed either a single bout of whole-body RE (seven exercises, 3 sets of 10-12 repetitions at 80% one-repetition maximum each) or an equivalent period of rest. Participants subsequently completed a mixed meal test in conjunction with an intravenous [6,6-2H2]glucose infusion to determine basal and postprandial glucose rate of appearance (Ra) and disappearance (Rd) from plasma, insulin sensitivity, and the insulinogenic index (a measure of beta cell function). Skeletal muscle biopsies were obtained 90 min postmeal to evaluate pyruvate-supported and maximal mitochondrial respiration. Whole-body carbohydrate oxidation was assessed using indirect calorimetry. RESULTS RE significantly reduced the postprandial rise in glucose Ra and plasma glucose concentration. Postprandial insulin sensitivity was significantly greater after RE, whereas postprandial plasma insulin concentration was significantly reduced. RE had no effect on the insulinogenic index, postprandial pyruvate respiration, or carbohydrate oxidation. CONCLUSION/INTERPRETATION A single bout of RE has beneficial effects on postprandial glucose metabolism in men with obesity and prediabetes by increasing postprandial insulin sensitivity, reducing the postprandial rise in glucose Ra, and reducing postprandial plasma insulin concentration.
-
9.
A Low ω-6 to ω-3 PUFA Ratio (n-6:n-3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth.
Van Name, MA, Savoye, M, Chick, JM, Galuppo, BT, Feldstein, AE, Pierpont, B, Johnson, C, Shabanova, V, Ekong, U, Valentino, PL, et al
The Journal of nutrition. 2020;150(9):2314-2321
-
-
-
Free full text
-
Plain language summary
Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of fat in the liver of people who drink very little or no alcohol. NAFLD is a common problem in children with obesity and diet is a contributory factor. Recent research has suggested that the Western diet and its high omega-6 and low omega-3 fat intakes may lead to the development of NAFLD. This quasi-experimental study of twenty children with obesity and NAFLD aimed to determine whether 12 weeks of low omega-6: omega-3 ratio diet affected liver fat content. The results showed that the diet did not affect weight loss but still significantly decreased liver fat content, with one third of the participants returning their liver fat content to normal. In lieu of weight loss, improvements were also observed in markers for liver function, diabetes and blood cholesterol. Interestingly those who carry a certain gene increasing their risk of developing NAFLD, showed greater improvements in liver fat percentage and liver function. It was concluded that in the absence of weight loss, a diet high in omega-3 and low in omega-6 improves fatty liver disease, risk factors for heart disease and has the potential to revert liver fat content to normal levels. This study could be used by healthcare professionals to recommend a low omega-6:omega-3 diet in children with obesity and NAFLD.
Abstract
BACKGROUND Recent literature suggests that the Western diet's imbalance between high ω-6 (n-6) and low ω-3 (n-3) PUFA intake contributes to fatty liver disease in obese youth. OBJECTIVES We tested whether 12 wk of a low n-6:n-3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response. METHODS In a single-arm unblinded study, obese youth 9-19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n-6:n-3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann-Whitney U test, and covariance pattern modeling were used. RESULTS Twenty obese adolescents (median age: 13.3 y; IQR: 10.5-16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time. CONCLUSIONS These data suggest that, independently of weight loss, a low n-6:n-3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype.This trial was registered at clinicaltrials.gov as NCT01556113.
-
10.
The consequences of exercise-induced weight loss on food reinforcement. A randomized controlled trial.
Flack, KD, Hays, HM, Moreland, J
PloS one. 2020;15(6):e0234692
-
-
-
Free full text
Plain language summary
Exercise is a long-standing remedy for nearly all of obesity’s comorbidities and often recommended as an economical and health-promoting option for weight loss and weight loss maintenance. The aim of this study was to investigate the effect of exercise on food reinforcement (reward-driven feeding), and to examine whether changes in body composition would be correlated with changes in food reinforcement. This study is randomized controlled trial with a total of 52 participants aged 18 to 40 years. Participants were randomly assigned to one of the three groups (six exercise sessions per week, two sessions per week, and sedentary control). Results indicate that there is great variability in individuals’ change in food reinforcement after a 12-week aerobic exercise intervention. Furthermore, those who did increase their food reinforcement were also those who lost the greatest amount of fat-free mass post-intervention. Authors conclude that preventing the loss of fat-free mass may be a valuable piece to a weight loss programme (with resistance training or dietary protein intake as adjunct therapy).
Abstract
BACKGROUND Obesity remains a primary threat to the health of most Americans, with over 66% considered overweight or obese with a body mass index (BMI) of 25 kg/m2 or greater. A common treatment option many believe to be effective, and therefore turn to, is exercise. However, the amount of weight loss from exercise training is often disappointingly less than expected with greater amounts of exercise not always promoting greater weight loss. Increases in energy intake have been prescribed as the primary reason for this lack of weight loss success with exercise. Research has mostly focused on alterations in hormonal mediators of appetite (e.g.: ghrelin, peptide YY, GLP-1, pancreatic polypeptide, and leptin) that may increase hunger and/or reduce satiety to promote greater energy intake with exercise training. A less understood mechanism that may be working to increase energy intake with exercise is reward-driven feeding, a strong predictor of energy intake and weight status but rarely analyzed in the context of exercise. DESIGN Sedentary men and women (BMI: 25-35 kg/m2, N = 52) were randomized into parallel aerobic exercise training groups partaking in either two or six exercise sessions/week, or sedentary control for 12 weeks. METHODS The reinforcing value of food was measured by an operant responding progressive ratio schedule task (the behavioral choice task) to determine how much work participants were willing to perform for access to a healthy food option relative to a less healthy food option before and after the exercise intervention. Body composition and resting energy expenditure were assessed via DXA and indirect calorimetry, respectively, at baseline and post testing. RESULTS Changes in fat-free mass predicted the change in total amount of operant responding for food (healthy and unhealthy). There were no correlations between changes in the reinforcing value of one type of food (healthy vs unhealthy) to changes in body composition. CONCLUSION In support of previous work, reductions in fat-free mass resulting from an aerobic exercise intervention aimed at weight loss plays an important role in energy balance regulation by increasing operant responding for food.