The impacts of dietary sphingomyelin supplementation on metabolic parameters of healthy adults: a systematic review and meta-analysis of randomized controlled trials.

Background: Studies have shown that sphingomyelin (SM) and its metabolites play signaling roles in the regulation of human health. Endogenous SM is involved in metabolic syndrome (MetS), while dietary SM supplementation may maintain lipid metabolism and prevent or alleviate MetS. Therefore, we hypothesized that dietary SM supplementation is beneficial for human health. Aims: In order to examine the impacts of dietary SM on metabolic indexes in adults without MetS, we performed a meta-analysis to test our hypothesis. Methods: A comprehensive search was performed to retrieve randomized controlled trials that were conducted between 2003 and 2023 to examine the effects of dietary SM supplementation on metabolic parameters in the Cochrane Library, PubMed, Web of Science, Embase, and ClinicalTrials.gov databases. RevMan 5.4 and Stata 14.0 software were used for meta-analysis, a sensitivity analysis, the risk of bias, and the overall quality of the resulted evidence. Results: Eventually, 10 articles were included in this meta-analysis. Dietary SM supplementation did not affect the endline blood SM level. When compared to the control, SM supplementation reduced the blood total cholesterol level [MD: -12.97, 95% CI: (-14.57, -11.38), p < 0.00001], low-density lipoprotein cholesterol level [MD: -6.62, 95% CI: (-10.74, -2.49), p = 0.002], and diastolic blood pressure [MD: -3.31; 95% CI (-4.03, -2.58), p < 0.00001] in adults without MetS. The supplementation also increased high-density lipoprotein level [MD:1.41, 95% CI: (0.94, 1.88), p < 0.00001] and muscle fiber conduction velocity [MD: 95% 1.21 CI (0.53, 1.88), p = 0.0005]. The intake of SM had no effect on the blood phospholipids and lyso-phosphatidylcholine, but slightly decreased phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol concentrations. Dietary SM supplementation reduced insulin level [MD: -0.63; 95% CI (-0.96, -0.31), p = 0.0001] and HOMA-IR [MD: -0.23; 95% CI (-0.31, -0.16), p < 0.00001] without affecting blood levels of glucose and inflammatory cytokines. Conclusion: Overall, dietary SM supplementation had a protective effect on blood lipid profiles and insulin level, but had limited impacts on other metabolic parameters in adults without MetS. More clinical trials and basic research are required. Systematic review registration: PROSPERO, identifier CRD42023438460.

Probiotics supplementation during pregnancy or infancy on multiple food allergies and gut microbiota: a systematic review and meta-analysis.

CONTEXT: Probiotics show promise in preventing and managing food allergies, but the impact of supplementation during pregnancy or infancy on children's allergies and gut microbiota remains unclear. OBJECTIVE: This study aimed to assess the effects of maternal or infant probiotic supplementation on food allergy risk and explore the role of gut microbiota. DATA SOURCES: A systematic search of databases (PubMed, Cochrane Library, Embase, and Medline) identified 37 relevant studies until May 20, 2023. DATA EXTRACTION: Two independent reviewers extracted data, including probiotics intervention details, gut microbiota analysis, and food allergy information. DATA ANALYSIS: Probiotics supplementation during pregnancy and infancy reduced the risk of total food allergy (relative risk [RR], 0.79; 95% CI, 0.63-0.99), cow-milk allergy (RR, 0.51; 95% CI, 0.29-0.88), and egg allergy (RR, 0.57; 95% CI, 0.39-0.84). Infancy-only supplementation lowered cow-milk allergy risk (RR, 0.69; 95% CI, 0.49-0.96), while pregnancy-only had no discernible effect. Benefits were observed with over 2 probiotic species, and a daily increase of 1.8 × 109 colony-forming units during pregnancy and infancy correlated with a 4% reduction in food allergy risk. Children with food allergies had distinct gut microbiota profiles, evolving with age. CONCLUSIONS: Probiotics supplementation during pregnancy and infancy reduces food allergy risk and correlates with age-related changes in gut microbial composition in children. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023425988.

Dietary supplementation of water extract of Eucommia ulmoides bark improved caecal microbiota and parameters of health in white-feathered broilers.

Eucommia ulmoides has been used as a food and medicine homologue for a long time in China. We hypothesize that Eucommia ulmoides achieves its health-promoting effects via altering gut microbiota. Here, we investigated the effects of water extract of Eucommia ulmoides bark on caecal microbiota and growth performance, antioxidant activity, and immunity in white-feathered broilers treated for 42 days. A total of 108 one-day-old Cobb white-feathered broilers were randomly assigned to three treatment groups: control diet, 0.75% Eucommia ulmoides diet (EU Ⅰ) and 1.5% Eucommia ulmoides diet (EU Ⅱ). The results showed that EU Ⅱ treatment improved average body weight (ABW), thigh muscle quality and total length of intestines, and decreased the serum total triglycerides and total cholesterol (TC) (p < 0.05). Eucommia ulmoides supplementation increased serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant activities and content of immunoglobulins, and reduced levels of malondialdehyde and tumour necrosis factor-α (TNF-α) (p < 0.05). Moreover, the supplementation increased the diversity of caecal microbiota and reduced the pathogenic genera Escherichia Shigella and Helicobacter. The genera Ochrobactrum, Odoribater, Klebsiella, Enterobacter, Georgenia and Bifidobacterium were positively associated with the ABW, total intestinal length, serum levels of GSH-Px, SOD and immunoglobulins (p < 0.001) and negatively associated with the TC and TNF-α (p < 0.01), suggesting an association of the changes of gut microbiota and improvement of broiler health. Meanwhile, Eucommia ulmoides supplementation enriched the Kyoto Encyclopedia of Genes and Genomes pathway of exocrine secretion from the pancreas, circadian entrainment and inhibited lipopolysaccharide biosynthesis. In conclusion, Eucommia ulmoides water extract can be used as a feed additive to improve poultry industry production.

Detecting fa leptin receptor mutation in Zucker rats with tetra-primer amplification-refractory mutation system (ARMS)-PCR.

Due to the genetic mutation (fa) in the gene encoding for leptin receptor, homozygous Zucker rats (fa-/-) develop excessive adiposity and become an experimental animal model in obesity and metabolic-related diseases research. Based on tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), we developed a method to quickly genotype Zucker rats with a mutated fa allele from their wildtype littermates. The three genotypes are clearly discriminated on 2.0% agarose gel. Our method can be used as a reliable tool to set up and maintain the breeding colony in animal facilities as well as assign animals to control and treatment groups based on their genotypes for animal studies.

Vitamin A: too good to be bad?

Vitamin A is a micronutrient important for vision, cell growth, reproduction and immunity. Both deficiency and excess consuming of vitamin A cause severe health consequences. Although discovered as the first lipophilic vitamin already more than a century ago and the definition of precise biological roles of vitamin A in the setting of health and disease, there are still many unresolved issues related to that vitamin. Prototypically, the liver that plays a key role in the storage, metabolism and homeostasis of vitamin A critically responds to the vitamin A status. Acute and chronic excess vitamin A is associated with liver damage and fibrosis, while also hypovitaminosis A is associated with alterations in liver morphology and function. Hepatic stellate cells are the main storage site of vitamin A. These cells have multiple physiological roles from balancing retinol content of the body to mediating inflammatory responses in the liver. Strikingly, different animal disease models also respond to vitamin A statuses differently or even opposing. In this review, we discuss some of these controversial issues in understanding vitamin A biology. More studies of the interactions of vitamin A with animal genomes and epigenetic settings are anticipated in the future.

Optimally controlling nutrition and propulsion force in a long distance running race.

Introduction: Runners competing in races are looking to optimize their performance. In this paper, a runner's performance in a race, such as a marathon, is formulated as an optimal control problem where the controls are: the nutrition intake throughout the race and the propulsion force of the runner. As nutrition is an integral part of successfully running long distance races, it needs to be included in models of running strategies. Methods: We formulate a system of ordinary differential equations to represent the velocity, fat energy, glycogen energy, and nutrition for a runner competing in a long-distance race. The energy compartments represent the energy sources available in the runner's body. We allocate the energy source from which the runner draws, based on how fast the runner is moving. The food consumed during the race is a source term for the nutrition differential equation. With our model, we are investigating strategies to manage the nutrition and propulsion force in order to minimize the running time in a fixed distance race. This requires the solution of a nontrivial singular control problem. Results: As the goal of an optimal control model is to determine the optimal strategy, comparing our results against real data presents a challenge; however, in comparing our results to the world record for the marathon, our results differed by 0.4%, 31 seconds. Per each additional gel consumed, the runner is able to run 0.5 to 0.7 kilometers further in the same amount of time, resulting in a 7.75% increase in taking five 100 calorie gels vs no nutrition. Discussion: Our results confirm the belief that the most effective way to run a race is to run approximately the same pace the entire race without letting one's energies hit zero, by consuming in-race nutrition. While this model does not take all factors into account, we consider it a building block for future models, considering our novel energy representation, and in-race nutrition.

The nutritional functions of dietary sphingomyelin and its applications in food.

Sphingolipids are common structural components of cell membranes and are crucial for cell functions in physiological and pathophysiological conditions. Sphingomyelin and its metabolites, such as sphingoid bases, ceramide, ceramide-1-phosphate, and sphingosine-1-phosphate, play signaling roles in the regulation of human health. The diverse structures of sphingolipids elicit various functions in cellular membranes and signal transduction, which may affect cell growth, differentiation, apoptosis, and maintain biological activities. As nutrients, dietary sphingomyelin and its metabolites have wide applications in the food and pharmaceutical industry. In this review, we summarized the distribution, classifications, structures, digestion, absorption and metabolic pathways of sphingolipids, and discussed the nutritional functioning of sphingomyelin in chronic metabolic diseases. The possible implications of dietary sphingomyelin in the modern food preparations including dairy products and infant formula, skin improvement, delivery system and oil organogels are also evaluated. The production of endogenous sphingomyelin is linked to pathological changes in obesity, diabetes, and atherosclerosis. However, dietary supplementations of sphingomyelin and its metabolites have been shown to maintain cholesterol homeostasis and lipid metabolism, and to prevent or treat these diseases. This seemly paradoxical phenomenon shows that dietary sphingomyelin and its metabolites are candidates for food additives and functional food development for the prevention and treatment of chronic metabolic diseases in humans.

Urotensin II level is elevated in inflammatory bowel disease patients.

It was reported that the urotensin II (U-II) level in inflammatory bowel disease (IBD) patients are significantly higher than in controls. To provide future guidance for the management of cardiovascular risk factors in IBD patients, the sample size of the current study appears to be limited, and more clinical samples to compare U-II levels in IBD patients and controls are needed. This will clarify the possible roles of inflammation factors and related signaling pathways (like EPK1/2, NF-κB and Rho/ROCK) in the pathophysiology of IBD. Therefore, large multicenter studies should be done to confirm the findings and underlying mechanisms in the future.

Replenishment of vitamin A for 7 days partially restored hepatic gene expressions altered by its deficiency in rats.

We investigated the effects of vitamin A (VA) status on metabolism of Zucker rats with different genders and genotypes, and of short-term refeeding of a VA sufficient (VAS) diet on VA deficient (VAD) animals. First, male and female Zucker lean (ZL) and fatty (ZF) rats at weaning were fed a VAD or VAS diet for 8 weeks. Second, male VAD ZL rats were fed a VAS diet for 3 (VAD-VAS3d) or 7 (VAD-VAS7d) days. The body weight (BW), blood parameters, and hepatic expressions of genes for metabolism were determined. VA deficiency reduced BW gain in ZL and ZF rats of either gender. VAD ZL rats had lower plasma glucose, insulin, and leptin levels than VAS ZL rats. VAD-VAS3d and VAD-VAS7d rats had higher plasma glucose, insulin, and leptin levels than that in the VAD rats. The hepatic mRNA levels of Gck, Cyp26a1, Srebp-1c, Igf1, Rarb, Rxra, Rxrg, Pparg, and Ppard were lowered by VA deficiency. Refeeding of the VAS diet for 3 days restored the Gck and Cyp26a1 expressions, and for 7 days restored the Gck, Cyp26a1, Igf1, and Rxrb expressions significantly. The 7-day VA replenishment partially restored the hepatic gene expressions and metabolic changes in VAD ZL rats.

Inflammation Induced by Lipopolysaccharide and Palmitic Acid Increases Cholesterol Accumulation via Enhancing Myeloid Differentiation Factor 88 Expression in HepG2 Cells.

Recently, multiple studies have shown that chronic inflammation disturbs cholesterol homeostasis and promotes its accumulation in the liver. The underlying molecular mechanism remains to be revealed. The relationship between the toll-like receptor 4 (TLR4) inflammatory signaling pathway and cholesterol accumulation was investigated in HepG2 cells treated with lipopolysaccharide (LPS) or palmitic acid (PA) for different lengths of time. In addition, the effects of pretreatment with 20µmol/L ST2825 (MyD88 inhibitor) were also studied in LPS- or PA-treated HepG2 cells and myeloid differentiation factor 88 (MyD88)-overexpressing HEK293T cells. The intracellular total and free cholesterol levels were measured using a commercial kit and filipin staining, respectively. The expression levels of sterol regulatory element-binding protein-2 (SREBP-2) and components in the TLR4 signaling pathway were determined using Western blotting. The treatments with LPS for 12 h and with PA for 24 h significantly increased the contents of intracellular total and free cholesterol, as well as the expression levels of SREBP-2 and components in the TLR4 signaling pathway. The inhibition of MyD88 by ST2825 significantly decreased the cholesterol content and the expression levels of SREBP-2 and components of the TLR4/MyD88/NF-κB pathway in HepG2 cells, as well as MyD88-overexpressing HEK293T cells. These results indicated that LPS and PA treatments increase SREBP-2-mediated cholesterol accumulation via the activation of the TLR4/MyD88/NF-κB signaling pathway in HepG2 cells.

Can nutrition interventions tackle the global insulin affordability via improving diabetes management and reducing insulin demand?

Diabetes, a global health concern, requires insulin therapy. As insulin demand and prices rise dramatically, insulin affordability has increasingly become an issue facing patients with diabetes worldwide. To cut insulin costs, many patients ration their supply, which may have dire health consequences. This particularly affects lower-income populations, who are often forced to choose between purchasing their medications or paying for other necessities. Nutrition might be one solution for this. This commentary aims to provide comprehensive insight with historical context into intersectional components of diabetes in the global arena through analyses of insulin affordability, coupled with the critical role of nutrition intervention after searching the PubMed for relevant articles. More studies in personalized nutrition, supplementations, and dietary behaviors may develop evidence-based nutrition interventions to control diabetes. We argue that alongside price regulation, a greater focus to nutrition to address issues of food insecurity and food assistance programs may help to improve insulin affordability.

Reduction in the Dietary VA Status Prevents Type 2 Diabetes and Obesity in Zucker Diabetic Fatty Rats.

We hypothesized that the vitamin A (VA) status regulates type 2 diabetes (T2D) development in Zucker diabetic fatty (ZDF) rats. Zucker Lean and ZDF rats at weaning were fed a VA deficient with basal fat (VAD-BF, no VA and 22.1% fat energy), VA marginal with BF (VAM-BF, 0.35 mg retinyl palmitate (RP)/kg), VA sufficient with BF (VAS-BF, 4.0 mg RP/kg), VAD with high fat (VAD-HF, 60% fat energy), VAM-HF or VAS-HF diet for 8 weeks, including an oral glucose tolerance test (OGTT) at week 7.5. The hepatic mRNA and proteins levels were determined using real-time PCR and Western blot, respectively. The VAD-BF/HF and VAM-BF/HF diets prevented peripheral hyperglycemia and attenuated obesity in ZDF rats, which occurred in the presence of the VAS-BF/HF diets. This lowered VA status reduced venous blood hyperglycemia, hyperinsulinemia and hyperlipidemia, and improved OGTT and homeostasis model assessment for insulin resistance results in ZDF rats. The expression levels of key hepatic genes for glucose and fat metabolism were regulated by VA status and dietary fat contents. An interaction between VA and HF condition was also observed. We conclude that the reduction in the dietary VA status in both BF and HF conditions prevents T2D and obesity in ZDF rats.

The Extraction of ß-Carotene from Microalgae for Testing Their Health Benefits.

ß-carotene, a member of the carotenoid family, is a provitamin A, and can be converted into vitamin A (retinol), which plays essential roles in the regulation of physiological functions in animal bodies. Microalgae synthesize a variety of carotenoids including ß-carotene and are a rich source of natural ß-carotene. This has attracted the attention of researchers in academia and the biotech industry. Methods to enrich or purify ß-carotene from microalgae have been investigated, and experiments to understand the biological functions of microalgae products containing ß-carotene have been conducted. To better understand the use of microalgae to produce ß-carotene and other carotenoids, we have searched PubMed in August 2021 for the recent studies that are focused on microalgae carotenoid content, the extraction methods to produce ß-carotene from microalgae, and the bioactivities of ß-carotene from microalgae. Articles published in peer-reviewed scientific journals were identified, screened, and summarized here. So far, various types and amounts of carotenoids have been identified and extracted in different types of microalgae. Diverse methods have been developed overtime to extract ß-carotene efficiently and practically from microalgae for mass production. It appears that methods have been developed to simplify the steps and extract ß-carotene directly and efficiently. Multiple studies have shown that extracts or whole organism of microalgae containing ß-carotene have activities to promote lifespan in lab animals and reduce oxidative stress in culture cells, etc. Nevertheless, more studies are warranted to study the health benefits and functional mechanisms of ß-carotene in these microalgae extracts, which may benefit human and animal health in the future.

The Interactions of Insulin and Vitamin A Signaling Systems for the Regulation of Hepatic Glucose and Lipid Metabolism.

The pandemics of obesity and type 2 diabetes have become a concern of public health. Nutrition plays a key role in these concerns. Insulin as an anabolic hormonal was discovered exactly 100 years ago due to its activity in controlling blood glucose level. Vitamin A (VA), a lipophilic micronutrient, has been shown to regulate glucose and fat metabolism. VA's physiological roles are mainly mediated by its metabolite, retinoic acid (RA), which activates retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are two transcription factors. The VA status and activations of RARs and RXRs by RA and synthetic agonists have shown to affect the glucose and lipid metabolism in animal models. Both insulin and RA signaling systems regulate the expression levels of genes involved in the regulation of hepatic glucose and lipid metabolism. Interactions of insulin and RA signaling systems have been observed. This review is aimed at summarizing the history of diabetes, insulin and VA signaling systems; the effects of VA status and activation of RARs and RXRs on metabolism and RAR and RXR phosphorylation; and possible interactions of insulin and RA in the regulation of hepatic genes for glucose and lipid metabolism. In addition, some future research perspectives for understanding of nutrient and hormone interactions are provided.

The Potential Use of Vitamin C to Prevent Kidney Injury in Patients with COVID-19.

The newly found SARS-CoV-2 has led to the pandemic of COVID-19, which has caused respiratory distress syndrome and even death worldwide. This has become a global public health crisis. Unfortunately, elders and subjects with comorbidities have high mortality rates. One main feature of COVID-19 is the cytokine storm, which can cause damage in cells and tissues including the kidneys. Here, we reviewed the current literature on renal impairments in patients with COVID-19 and analyzed the possible etiology and mechanisms. In addition, we investigated the potential use of vitamin C for the prevention of renal injury in those patients. It appears that vitamin C could be helpful to improve the outcomes of patients with COVID-19. Lastly, we discussed the possible protective effects of vitamin C on renal functions in COVID-19 patients with existing kidney conditions.

Roles of vitamin A in the regulation of fatty acid synthesis.

Dietary macronutrients and micronutrients play important roles in human health. On the other hand, the excessive energy derived from food is stored in the form of triacylglycerol. A variety of dietary and hormonal factors affect this process through the regulation of the activities and expression levels of those key player enzymes involved in fatty acid biosynthesis such as acetyl-CoA carboxylase, fatty acid synthase, fatty acid elongases, and desaturases. As a micronutrient, vitamin A is essential for the health of humans. Recently, vitamin A has been shown to play a role in the regulation of glucose and lipid metabolism. This review summarizes recent research progresses about the roles of vitamin A in fatty acid synthesis. It focuses on the effects of vitamin A on the activities and expression levels of mRNA and proteins of key enzymes for fatty acid synthesis in vitro and in vivo. It appears that vitamin A status and its signaling pathway regulate the expression levels of enzymes involved in fatty acid synthesis. Future research directions are also discussed.

Vitamin A and Diabetes.

Recently, research data have shown that vitamin A (VA, retinol) as a micronutrient participates in the regulation of glucose and lipid metabolism. Since diabetes is a metabolic disease, it is imperative to reveal the relationship of VA and diabetes. This review was aimed to summarize the current understanding of VA and its metabolites in diabetes. Since April of 2020, the authors have searched the PubMed using key words and retrieved articles that focused on diabetes and VA or its metabolites. Based on the published data, it appears that the development of type 1 diabetes leads to reduction of blood VA level in human and animals, and increase of hepatic VA store in experimental animals. On the other hand, the mutual impacts of type 2 diabetes and VA intake and blood VA level on each other appear to be uncertain. Retinoic acid, the active metabolite of VA, has been studied extensively for the treatment of diabetic complications. The current data appear to indicate that the development of diabetes is associated with changes of VA metabolism. More carefully designed clinical and laboratory experiments are needed to reveal the impacts of diabetes on VA metabolism and the role of VA in the development and treatment of diabetes.

Current understanding of glucose transporter 4 expression and functional mechanisms.

Glucose is used aerobically and anaerobically to generate energy for cells. Glucose transporters (GLUTs) are transmembrane proteins that transport glucose across the cell membrane. Insulin promotes glucose utilization in part through promoting glucose entry into the skeletal and adipose tissues. This has been thought to be achieved through insulin-induced GLUT4 translocation from intracellular compartments to the cell membrane, which increases the overall rate of glucose flux into a cell. The insulin-induced GLUT4 translocation has been investigated extensively. Recently, significant progress has been made in our understanding of GLUT4 expression and translocation. Here, we summarized the methods and reagents used to determine the expression levels of Slc2a4 mRNA and GLUT4 protein, and GLUT4 translocation in the skeletal muscle, adipose tissues, heart and brain. Overall, a variety of methods such real-time polymerase chain reaction, immunohistochemistry, fluorescence microscopy, fusion proteins, stable cell line and transgenic animals have been used to answer particular questions related to GLUT4 system and insulin action. It seems that insulin-induced GLUT4 translocation can be observed in the heart and brain in addition to the skeletal muscle and adipocytes. Hormones other than insulin can induce GLUT4 translocation. Clearly, more studies of GLUT4 are warranted in the future to advance of our understanding of glucose homeostasis.