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Metabolites
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Impact of Macronutrients on Metabolism
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Impact of Macronutrients on Metabolism

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 44084

Special Issue Editor

Dr. Janine Wirth

E-Mail Website
Guest Editor
School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, Ireland
Interests: public health; nutritional epidemiology; metabolic health; protein intake; intervention studies; cohort studies; systematic reviews

Special Issue Information

Dear Colleagues,

Poor metabolic health is often captured by the metabolic syndrome, which is considered a combination of metabolic dysfunctions including unfavorable blood glucose levels, triglycerides, high-density lipoprotein cholesterol (HDL), blood pressure and abdominal obesity. It is associated with a number of chronic health conditions and is established as a risk factor for cardiovascular disease and some cancers.
In this context, diet plays an important role in primary and secondary prevention, but when it comes to the ideal distribution of macronutrients, the literature is inconclusive. A diet high in carbohydrates has frequently been associated with an increased risk of metabolic syndrome. Some studies conclude that replacing carbohydrates with any fat, particularly polyunsaturated fat, will improve metabolic functions. Positive effects are assumed for protein with increased intake.

What studies of carbohydrates, fats and protein have in common is an increasing emphasis on the role of quality and source, suggesting different metabolic responses by subgroups of macronutrients. This makes coming to an overall conclusion and the formulation of nutritional recommendations even more difficult.
The aim of this Special Issue is to elucidate the role of macronutrient intake, their combinations and interactions in the diet on the pathway to metabolic function and dysfunction. Authors are invited to submit original research or systematic reviews examining one of the following aspects:

  • Identification of pathways that explain the association between macronutrient intake and metabolic response/health (common markers of metabolic health, metabolomic approaches, metabolic disease risk)
  • Acute or chronic metabolic response after intake of certain macronutrients
  • The role of dietary macronutrient combinations and substitutions
  • The relevance of macronutrient source and quality
  • Recent findings from longitudinal studies or randomized controlled trials and systematic reviews and meta-analyses are highly appreciated and warmly welcomed.

Dr. Janine Wirth
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • carbohydrate intake
  • dietary protein
  • chronic metabolic response

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Published Papers (6 papers)

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Research

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17 pages, 3970 KiB  
Article
Rats Exposed to Excess Sucrose During a Critical Period Develop Inflammation and Express a Secretory Phenotype of Vascular Smooth Muscle Cells
by Verónica Guarner-Lans, Elizabeth Soria-Castro, Agustina Cano-Martínez, María Esther Rubio-Ruiz, Gabriela Zarco, Elizabeth Carreón-Torres, Oscar Grimaldo, Vicente Castrejón-Téllez and Israel Pérez-Torres
Metabolites 2024, 14(10), 555; https://doi.org/10.3390/metabo14100555 - 17 Oct 2024
Viewed by 708
Abstract
Background: Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Inflammation might contribute to changes during this period and could be associated with variations in the vascular smooth muscle [...] Read more.
Background: Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Inflammation might contribute to changes during this period and could be associated with variations in the vascular smooth muscle (VSMC) phenotype. Objective: We studied changes in inflammatory pathways that could underlie the expression of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP. Methods: We analyzed histological changes in the aorta and the expression of the COX-2, TLR4, iNOS, eNOS, MMP-2 and -9, and β- and α-actin, the quantities of TNF-α, IL-6, and IL-1β using ELISA, and the levels of fatty acids using gas chromatography. Results: The aortic wall presented disorganization, decellularization, and wavy elastic fibers and an increase in the lumen area. The α- and β-actin expressions were decreased, while COX-2, TLR4, TNF-α, and the activity of IL-6 were increased. Oleic acid was increased in CP in comparison to the control group. Conclusions: There is transient hypertension at the end of the CP that is accompanied by inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the development of hypertension when animals reach adulthood. Full article
(This article belongs to the Special Issue Impact of Macronutrients on Metabolism)
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13 pages, 631 KiB  
Article
Estimating Dietary Protein and Sodium Intake with Sodium Removal in Peritoneal Dialysis Patients
by Ana Bontić, Aleksandra Kezić, Jelena Pavlović, Marko Baralić, Selena Gajić, Kristina Petrovic, Vidna Karadžić Ristanović, Olga Petrović, Vera Stjepanović, Sanja Stanković and Milan Radović
Metabolites 2024, 14(8), 460; https://doi.org/10.3390/metabo14080460 - 19 Aug 2024
Viewed by 972
Abstract
An increase in dietary protein intake (DPI) carries a risk with respect to increased sodium intake, which further leads to the development of cardiovascular morbidity in peritoneal dialysis (PD) patients. Dialytic (DSR) and urinary sodium removal (USR) are potential indicators of sodium intake. [...] Read more.
An increase in dietary protein intake (DPI) carries a risk with respect to increased sodium intake, which further leads to the development of cardiovascular morbidity in peritoneal dialysis (PD) patients. Dialytic (DSR) and urinary sodium removal (USR) are potential indicators of sodium intake. In this single-center cross-sectional study with 60 prevalent PD patients, we analyze the correlation of DPI with sodium intake and the association between residual renal function (RRF) and comorbidity grade, expressed as the Davies score with sodium removal and protein metabolism indices such as normalized protein catabolic rate (nPCR) and lean body mass (LBM). The value of RRF < 2 mL/min/1.73 m2 is significantly associated with lower USR (p = 0.000) and lower %LBM (p < 0.001). The greatest USR is detected in patients with low Davies comorbidity grade (p = 0.018). Compared to patients with DPI < 0.8 g/kg/day, patients with DPI > 0.8 g/kg/day have a greater sodium intake (3.69 ± 0.71 vs. 2.94 ± 0.86; p < 0.018) and a greater nPCR (p < 0.001). Protein intake is significantly correlated with sodium intake (p = 0.041), but not with total sodium removal (TSR). A strong correlation is observed between sodium intake and TSR (p = 0.000), although single TSR values are not the same as the corresponding sodium intake values. An increasing protein intake implies the necessity to determine both sodium intake and sodium removal. Preservation of RRF has a beneficial role not just in sodium removal, but also in the increase of LBM. Full article
(This article belongs to the Special Issue Impact of Macronutrients on Metabolism)
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17 pages, 3942 KiB  
Article
Oligomalt, a New Slowly Digestible Carbohydrate, Reduces Post-Prandial Glucose and Insulin Trajectories Compared to Maltodextrin across Different Population Characteristics: Double-Blind Randomized Controlled Trials in Healthy Individuals, People with Obesity, and People with Type 2 Diabetes
by Odd Erik Johansen, Joel Neutel, Sanjay Gupta, Barbara Mariani, Gerhard Ufheil, Emilie Perrin, Andreas Rytz, Anirban Lahiry, Frederik Delodder, Jaclyn Lerea-Antes, Naomi Ocampo and Maximilian von Eynatten
Metabolites 2024, 14(8), 410; https://doi.org/10.3390/metabo14080410 - 26 Jul 2024
Viewed by 989
Abstract
We assessed the glucometabolic effects of oligomalt, a novel fully slowly digestible carbohydrate, compared with maltodextrin, in cross-over randomized controlled trials (NCT05058144; NCT05963594) involving healthy volunteers (HV), people with overweight or obesity (PwO), and people with type 2 diabetes (T2D). We tested 33 [...] Read more.
We assessed the glucometabolic effects of oligomalt, a novel fully slowly digestible carbohydrate, compared with maltodextrin, in cross-over randomized controlled trials (NCT05058144; NCT05963594) involving healthy volunteers (HV), people with overweight or obesity (PwO), and people with type 2 diabetes (T2D). We tested 33 g and/or 50 g of oligomalt/maltodextrin, which were dissolved in 300 mL of water and consumed after fasting in the morning. The primary exploratory endpoint was the incremental area under the curve (iAUC) for postprandial glucose, assessed by frequent blood sampling over 3 h. Insulin levels were also assessed. In the HV cohort, a 4 h hydrogen breath test was performed with 15 g of inulin as a positive control. Analysis was performed by a mixed model. Oligomalt elicited a lower post-prandial glucose response compared to maltodextrin in HV (50 g, n = 15 [7 women], mean age/BMI 31 years/22.6 kg/m2), in PwO (33 g and 50 g, n = 26 [10 women], age/BMI 44 years/29.9 kg/m2, mean HbA1c 5.3%), and in people with T2D (50 g, n = 22 [13 women], age/BMI 61 years/31.8 kg/m2, HbA1c 7.4%), with significant reductions observed in PwO and T2D for the 0–1 h window (HV: −19% [p = 0.149]/PwO33g-38% [p = 0.0002]/PwO50g-28% [p = 0.0027]/T2D-38% [p < 0.0001]; the 0–2 h window (HV: −17% [p = 0.311]/PwO33g-34% [p = 0.0057]/PwO50g-21% [p = 0.0415]/T2D-37% [p < 0.0001]), and the 0–3 h window (HV: −15% [p = 0.386]/PwO33g-30% [p = 0.0213]/PwO50g0−19% [p = 0.0686]/T2D−37% [p = 0.0001]). The post-prandial insulin response was significantly lower, by 38–60%, across all populations, dose, and time points, with oligomalt. In HV, the breath-hydrogen pattern was comparable between oligomalt and maltodextrin, but increased significantly with inulin. These data support the glucometabolic advantages of oligomalt over maltodextrin, hence confirming it as a healthier carbohydrate, and underscoring its full digestibility. This therefore opens up the possibility for the incorporation of oligomalt in relevant food products/matrices. Full article
(This article belongs to the Special Issue Impact of Macronutrients on Metabolism)
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12 pages, 578 KiB  
Article
Association between Protein Intake and Diabetes Complications Risk Following Incident Type 2 Diabetes: The EPIC-Potsdam Study
by Elif Inan-Eroglu, Olga Kuxhaus, Franziska Jannasch, Daniela V. Nickel and Matthias B. Schulze
Metabolites 2024, 14(3), 172; https://doi.org/10.3390/metabo14030172 - 19 Mar 2024
Viewed by 1777
Abstract
Our knowledge about the connection between protein intake and diabetes-related complications comes largely from studies among those already diagnosed with type 2 diabetes (T2D). However, there is a lack of information on whether changing protein intake after diabetes diagnosis affects complications risk. We [...] Read more.
Our knowledge about the connection between protein intake and diabetes-related complications comes largely from studies among those already diagnosed with type 2 diabetes (T2D). However, there is a lack of information on whether changing protein intake after diabetes diagnosis affects complications risk. We aimed to explore the association between protein intake (total, animal, and plant) and vascular complications in incident T2D patients considering pre-diagnosis intake and changes in intake after diagnosis. This prospective cohort study included 1064 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort who developed T2D during follow-up (physician-verified). Dietary protein intake was measured with a food frequency questionnaire at baseline and follow-up. We included physician-reported incident diabetes complications (myocardial infarction, stroke, nephropathy, and neuropathy). A total of 388 participants developed complications, 82 macrovascular complications, and 343 microvascular complications. Substituting carbohydrates with protein showed a trend towards lower complications risk, although this association was not statistically significant (hazard ratio (HR) for 5% energy (E) substitution: 0.83; 95% confidence intervals (CI): 0.60–1.14). Increasing protein intake at the expense of carbohydrates after diabetes diagnosis was not associated with total and microvascular complications (HR for 5% E change substitution: 0.98; 95% CI: 0.89–1.08 and HR for 5% E change substitution: 1.02; 95% CI: 0.92–1.14, respectively). Replacing carbohydrates with protein did not elevate the risk of diabetes complications in incident T2D cases. Full article
(This article belongs to the Special Issue Impact of Macronutrients on Metabolism)
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Review

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23 pages, 1515 KiB  
Review
The Cellular Stability Hypothesis: Evidence of Ferroptosis and Accelerated Aging-Associated Diseases as Newly Identified Nutritional Pentadecanoic Acid (C15:0) Deficiency Syndrome
by Stephanie Venn-Watson
Metabolites 2024, 14(7), 355; https://doi.org/10.3390/metabo14070355 - 23 Jun 2024
Cited by 1 | Viewed by 36147
Abstract
Ferroptosis is a newly discovered form of cell death caused by the peroxidation of fragile fatty acids in cell membranes, which combines with iron to increase reactive oxygen species and disable mitochondria. Ferroptosis has been linked to aging-related conditions, including type 2 diabetes, [...] Read more.
Ferroptosis is a newly discovered form of cell death caused by the peroxidation of fragile fatty acids in cell membranes, which combines with iron to increase reactive oxygen species and disable mitochondria. Ferroptosis has been linked to aging-related conditions, including type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). Pentadecanoic acid (C15:0), an odd-chain saturated fat, is an essential fatty acid with the primary roles of stabilizing cell membranes and repairing mitochondrial function. By doing so, C15:0 reverses the underpinnings of ferroptosis. Under the proposed “Cellular Stability Hypothesis”, evidence is provided to show that cell membranes optimally need >0.4% to 0.64% C15:0 to support long-term health and longevity. A pathophysiology of a newly identified nutritional C15:0 deficiency syndrome (“Cellular Fragility Syndrome”) is provided that demonstrates how C15:0 deficiencies (≤0.2% total circulating fatty acids) can increase susceptibilities to ferroptosis, dysmetabolic iron overload syndrome, type 2 diabetes, cardiovascular disease, and NAFLD. Further, evidence is provided that C15:0 supplementation can reverse the described C15:0 deficiency syndrome, including the key components of ferroptosis. Given the declining dietary intake of C15:0, especially among younger generations, there is a need for extensive studies to understand the potential breadth of Cellular Fragility Syndrome across populations. Full article
(This article belongs to the Special Issue Impact of Macronutrients on Metabolism)
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30 pages, 933 KiB  
Review
Adaptive Effects of Endocrine Hormones on Metabolism of Macronutrients during Fasting and Starvation: A Scoping Review
by Reza Karimi, Alina Yanovich, Fawzy Elbarbry and Anita Cleven
Metabolites 2024, 14(6), 336; https://doi.org/10.3390/metabo14060336 - 16 Jun 2024
Cited by 1 | Viewed by 2559
Abstract
Food deprivation can occur for different reasons. Fasting (<24 h duration) occurs to meet religious or well-being goals. Starvation (>1-day duration) occurs when there is intentional (hunger strike or treatment of a medical condition) or unintentional (anorexia nervosa, drought, epidemic famine, war, or [...] Read more.
Food deprivation can occur for different reasons. Fasting (<24 h duration) occurs to meet religious or well-being goals. Starvation (>1-day duration) occurs when there is intentional (hunger strike or treatment of a medical condition) or unintentional (anorexia nervosa, drought, epidemic famine, war, or natural disaster) food deprivation. A scoping review was undertaken using the PubMed database to explore 1805 abstracts and review 88 eligible full-text articles to explore the adaptive relationships that emerge between cortisol, insulin, glucagon, and thyroid hormones on the metabolic pathways of macronutrients in humans during fasting and starvation. The collected data indicate that fasting and starvation prime the human body to increase cortisol levels and decrease the insulin/glucagon ratio and triiodothyronine (T3) levels. During fasting, increased levels of cortisol and a decreased insulin/glucagon ratio enhance glycogenolysis and reduce the peripheral uptake of glucose and glycogenesis, whereas decreased T3 levels potentially reduce glycogenolysis. During starvation, increased levels of cortisol and a decreased insulin/glucagon ratio enhance lipolysis, proteolysis, fatty acid and amino acid oxidation, ketogenesis, and ureagenesis, and decreased T3 levels reduce thermogenesis. We present a potential crosstalk between T3 and the above hormones, including between T3 and leptin, to extend their adaptive roles in the metabolism of endogenous macronutrients during food deprivation. Full article
(This article belongs to the Special Issue Impact of Macronutrients on Metabolism)
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