-
Blood Jun 2024X-linked sideroblastic anemia (XLSA) and X-linked protoporphyria (XLPP) are uncommon diseases caused by loss-of-function and gain-of-function mutations, respectively, in...
X-linked sideroblastic anemia (XLSA) and X-linked protoporphyria (XLPP) are uncommon diseases caused by loss-of-function and gain-of-function mutations, respectively, in the erythroid form of 5-aminolevulinic acid synthetase, ALAS2, which encodes the first enzyme in heme biosynthesis. A related sideroblastic anemia is due to mutations in SLC25A38, which supplies mitochondrial glycine for ALAS2 (SLC25A38-CSA). The lack of viable animal models has limited studies on the pathophysiology and development of therapies for these conditions. Here, using CRISPR-CAS9 gene editing technology, we have generated knock-in mouse models that recapitulate the main features of XLSA and XLPP, and, using conventional conditional gene targeting in embryonic stem cells, we also developed a faithful model of the SLC25A38-CSA. In addition to examining the phenotypes and natural history of each disease, we determine the effect of restriction or supplementation of dietary pyridoxine (vitamin B6), the essential cofactor of ALAS2, on the anemia and porphyria. In addition to the well-documented response of XLSA mutations to pyridoxine supplementation, we also demonstrate the relative insensitivity of the XLPP porphyria, severe sensitivity of the XLSA models, and an extreme hypersensitivity of the SLC25A38-CSA model to pyridoxine deficiency, a phenotype that is not shared with another mouse hereditary anemia model, Hbbth3/+ -thalassemia intermedia. Thus, in addition to generating animal models useful for examining the pathophysiology and treatment of these diseases, we have uncovered an unsuspected conditional synthetic lethality between the heme synthesis-related CSAs and pyridoxine deficiency. These findings have the potential to inform novel therapeutic paradigms for the treatment of these diseases.
PubMed: 38900972
DOI: 10.1182/blood.2023023078 -
Nutrients Jun 2024Beef is an important source of high-quality protein and several micronutrients, including iron, zinc, and B vitamins. We determined beef intake and its relationship with...
Beef Consumption Is Associated with Higher Intakes and Adequacy of Key Nutrients in Older Adults Age 60+ Years: National Health and Nutrition Examination Survey 2011-2018 Analysis.
Beef is an important source of high-quality protein and several micronutrients, including iron, zinc, and B vitamins. We determined beef intake and its relationship with intakes of nutrients and their adequacy using 24 h dietary recall data from 5868 older adults. Usual intakes from foods were determined using the National Cancer Institute method, and the percent of the population below the estimated average requirement or above adequate intake was estimated. A high percentage of older adults did not meet nutrient recommendations for vitamin D (96%), choline (96%), vitamin E (84%), potassium (70%), calcium (63%), magnesium (60%), vitamin C (46%), vitamin A (39%), zinc (21%), vitamin B (19%), and folate (15%). About 68% of older adults were beef consumers with a mean intake of 56 g/day. Beef consumers had higher ( < 0.05) intakes of energy, protein, calcium, iron, phosphorus, selenium, sodium, zinc, thiamin, riboflavin, niacin, vitamin B, and choline, and a higher ( < 0.05) proportion met nutrient recommendations for protein, calcium, copper, zinc, thiamin, folate, and vitamin B than non-consumers. Consumers of fresh, ground, and processed beef also had generally higher intakes and lower inadequacies of many nutrients depending on the beef type. In conclusion, older adults generally had poor nutrient adequacy from their diets, while beef consumers had higher nutrient intakes and adequacy for certain key nutrients, which are inherently generally available from beef or from foods consumed with beef.
Topics: Humans; Aged; Male; Female; Middle Aged; Nutrition Surveys; Red Meat; Diet; Nutrients; Nutritional Status; Micronutrients; United States; Aged, 80 and over; Recommended Dietary Allowances; Nutritive Value; Cattle; Animals; Nutritional Requirements
PubMed: 38892711
DOI: 10.3390/nu16111779 -
Nutrients Jun 2024Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or humid scenarios, may be at particular risk for dehydration with ensuing loss of electrolytes, leading to sluggishness and impaired physical performance.
METHODS
We evaluated an electrolyte and amino acid product containing L-alanine and L-glutamine, as well as select vitamins [B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), and vitamin C (ascorbic acid)]. Subjects ( = 40; four groups, = 10) were randomized to consume either a placebo packet or one, two, or three packets daily of the test product for 4 weeks with site visits at 0, 2, and 4 weeks. We tested safety and tolerability by analyzing hematological parameters (complete blood counts), metabolic parameters (hepatic, renal, acid-base balance), urinalysis end products, thyroid status [T3 (triiodothyronine), T4 (thyroxine), TSH (thyroid-stimulating hormone)], tolerability (via questionnaire), vital signs, and dietary intake.
RESULTS
Statistical analyses displayed ten significant main effects ( < 0.05) with white blood cells, lymphocytes, neutrophils, urinary pH, thyroxine, urination frequency, calcium, calories, fat, and cholesterol. Interactions for time and group ( < 0.05) were observed for MCV, eGFR, potassium, overall tolerability, bloating, and cramping-demonstrating mild GA disturbances. Little to no change of physiological relevance was noted for any outcome variable, regardless of dosing level.
CONCLUSIONS
Our results indicate the product was well-tolerated at all dosing levels and no significant adverse changes occurred in any of the test parameters compared to the placebo group, indicating relative safety of ingestion over a 4-week treatment period, at the volumes used, and outside the context of physical stress.
Topics: Humans; Female; Male; Adult; Amino Acids; Beverages; Young Adult; Dehydration; Double-Blind Method; Middle Aged; Electrolytes; Vitamins; Water-Electrolyte Balance
PubMed: 38892699
DOI: 10.3390/nu16111766 -
Nutrients May 2024Hashimoto's thyroiditis (HT) is the leading cause of hypothyroidism, affecting mainly the female population. Many patients with HT have metabolic disorders and...
Assessment of Vitamin Concentrations in Patients with Hashimoto's Thyroiditis and Their Relationships with Thyroid Function, Biochemical Status, and Anthropometric Parameters-A Preliminary Study.
Hashimoto's thyroiditis (HT) is the leading cause of hypothyroidism, affecting mainly the female population. Many patients with HT have metabolic disorders and nutritional deficiencies. The aim of this study was to evaluate vitamin D, A, E, B2, and B6 concentrations, thyroid function, metabolic profile, and anthropometric parameters of patients with Hashimoto's thyroiditis. In 81 female patients with HT (study group), vitamin A and B2 concentrations were significantly lower than in 34 healthy women (control group). No differences were noted in vitamin D, E, and B6 concentrations between groups. Moreover, HT patients had similar anthropometric parameters, lipid profiles, and glucose and insulin concentrations compared to controls. This study showed some relationships between vitamin concentrations and anthropometric or biochemical profiles in HT patients. Among others, in the HT group, the concentration of vitamin D was positively correlated with the level of HDL and negatively correlated with BMI, total fat mass, and insulin level, which influence cardiovascular risk. The results indicate that patients with HT should be routinely tested for vitamin concentrations to prevent nutritional deficiencies. Further studies are also needed on the role of vitamins in the development and progression of HT and the presence of metabolic complications in this population.
Topics: Humans; Female; Hashimoto Disease; Adult; Thyroid Gland; Middle Aged; Vitamins; Anthropometry; Thyroid Function Tests; Case-Control Studies; Nutritional Status; Vitamin D; Body Mass Index; Blood Glucose
PubMed: 38892627
DOI: 10.3390/nu16111694 -
Nutrients May 2024The acceleration of aging is a risk factor for numerous diseases, and diet has been identified as an especially effective anti-aging method. Currently, research on the...
The acceleration of aging is a risk factor for numerous diseases, and diet has been identified as an especially effective anti-aging method. Currently, research on the relationship between dietary nutrient intake and accelerated aging remains limited, with existing studies focusing on the intake of a small number of individual dietary nutrients. Comprehensive research on the single and mixed anti-aging effects of dietary nutrients has not been conducted. This study aimed to comprehensively explore the effects of numerous dietary nutrient intakes, both singly and in combination, on the acceleration of aging. Data for this study were extracted from the 2015-2018 National Health and Nutrition Examination Surveys (NHANES). The acceleration of aging was measured by phenotypic age acceleration. Linear regression (linear), restricted cubic spline (RCS) (nonlinear), and weighted quantile sum (WQS) (mixed effect) models were used to explore the association between dietary nutrient intake and accelerated aging. A total of 4692 participants aged ≥ 20 were included in this study. In fully adjusted models, intakes of 16 nutrients were negatively associated with accelerated aging (protein, vitamin E, vitamin A, beta-carotene, vitamin B1, vitamin B2, vitamin B6, vitamin K, phosphorus, magnesium, iron, zinc, copper, potassium, dietary fiber, and alcohol). Intakes of total sugars, vitamin C, vitamin K, caffeine, and alcohol showed significant nonlinear associations with accelerated aging. Additionally, mixed dietary nutrient intakes were negatively associated with accelerated aging. Single dietary nutrients as well as mixed nutrient intake may mitigate accelerated aging. Moderately increasing the intake of specific dietary nutrients and maintaining dietary balance may be key strategies to prevent accelerated aging.
Topics: Humans; Nutrition Surveys; Female; Male; Middle Aged; Adult; Diet; Nutrients; Aging; Aged; Young Adult; Eating; Linear Models
PubMed: 38892569
DOI: 10.3390/nu16111635 -
Nutrients May 2024Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized...
Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5'-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40-75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: -39.7% to -20.3%) and LDL-C by 7.5% (95% CI: -10.3% to -4.7%), compared to the placebo ( < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: -62.3% to -34.3%, < 0.01) compared to mixed allele carriers (18.6%, 95% CI: -25.6% to -11.6%, < 0.01), with a notable intergroup difference (29.7%, 95% CI: -50.7% to -8.7%, < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms.
Topics: Humans; Middle Aged; Homocysteine; Female; Male; Dietary Supplements; Methylenetetrahydrofolate Reductase (NADPH2); Double-Blind Method; 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Cholesterol, LDL; Aged; Vitamin B 12; Pyridoxal Phosphate; Adult; Ferredoxin-NADP Reductase; Tetrahydrofolates; Polymorphism, Genetic; Vitamin B Complex
PubMed: 38892484
DOI: 10.3390/nu16111550 -
Frontiers in Nutrition 2024This study investigated the efficacy of a mixed beet-based supplement (BEET) versus placebo (PL) in countering inflammation during recovery from 2.25 h of intensive...
OBJECTIVES
This study investigated the efficacy of a mixed beet-based supplement (BEET) versus placebo (PL) in countering inflammation during recovery from 2.25 h of intensive cycling in 20 male and female cyclists. A multi-omics approach was used that included untargeted proteomics and a targeted oxylipin panel.
METHODS
A randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and a 2-week washout period. Supplementation periods were followed by a 2.25 h cycling bout at close to 70%VO. The BEET supplement provided 212 mg of nitrates per day, 200 mg caffeine from green tea extract, 44 mg vitamin C from Camu Camu berry, B-vitamins from quinoa sprouts (40% Daily Value for thiamin, riboflavin, niacin, and vitamin B6), and 2.5 g of a mushroom blend containing Cordyceps sinensis and Inonotus obliquus. Six blood samples were collected before and after supplementation (overnight fasted state), immediately post-exercise, and at 1.5 h-, 3 h-, and 24 h-post-exercise.
RESULTS
The 2.25 h cycling bout increased plasma levels of 41 of 67 oxylipins detected. BEET supplementation significantly increased plasma nitrate (NO ) and nitrite (NO ) (sum, NO + NO ) concentrations (interaction effect, < 0.001) and two anti-inflammatory oxylipins [18-hydroxyeicosapentaenoic acid (18-HEPE) and 4-hydroxy-docosahexanoic acid (4-HDoHE)]. The untargeted proteomics analysis identified 616 proteins (458 across all times points), and 2-way ANOVA revealed a cluster of 45 proteins that were decreased and a cluster of 21 that were increased in the BEET versus PL trials. Functional enrichment supported significant BEET-related reductions in inflammation-related proteins including several proteins related to complement activation, the acute phase response, and immune cell adhesion, migration, and differentiation.
DISCUSSION
Intake of a BEET-based supplement during a 2-week period was linked to higher plasma levels of NO + NO , elevated post-exercise levels of two anti-inflammatory oxylipins, and a significant decrease in a cluster of proteins involved in complement activation and inflammation. These data support that 2-weeks intake of nitrate from a mixed beet-based supplement moderated protein biomarkers of exercise-induced inflammation in athletes.
PubMed: 38873567
DOI: 10.3389/fnut.2024.1408804 -
Food Science & Nutrition Jun 2024Water kefir grains are an important source of probiotics, mainly containing lactic acid bacteria and yeasts. The aim of this study is to investigate the changes in...
Water kefir grains are an important source of probiotics, mainly containing lactic acid bacteria and yeasts. The aim of this study is to investigate the changes in microbial and chemical properties of water kefir grains during 1-month storage at +4°C and -18°C. The initial content of lactobacilli, lactococci, and yeast in water kefir grains was 6.06, 6.33, and 5.93 log CFU/g, respectively. The number of lactobacilli, , and spp. in the water kefir grains were comparable, with slight changes at the end of refrigerated storage ( > .05). Lactococci and yeasts decreased significantly after both storage conditions compared to the initial content ( < .05). The dry matter and ash contents remained unchanged during storage ( > .05). Water kefir grains contained significant amounts of calcium, vitamin B, vitamin B, vitamin B, and vitamin B. Storage at both +4°C and -18°C did not affect the mineral and vitamin contents, except for Cu and Vitamin B. The results indicate that the water kefir grains remained viable after storage at both temperatures. If water kefir grains need to be stored, it is recommended to store them at +4°C in sugared water as it ensures better survivability of the microbiota of the grains.
PubMed: 38873456
DOI: 10.1002/fsn3.4074 -
Experimental and Therapeutic Medicine Aug 2024Excessive alcohol consumption is considered to be a major risk factor of alcohol-induced osteonecrosis of the femoral head (AONFH). The gut microbiota (GM) has been...
Excessive alcohol consumption is considered to be a major risk factor of alcohol-induced osteonecrosis of the femoral head (AONFH). The gut microbiota (GM) has been reported to aid in the regulation of human physiology and its composition can be altered by alcohol consumption. The aim of the present study was to improve the understanding of the GM and its metabolites in patients with AONFH. Metabolomic sequencing and 16S rDNA analysis of fecal samples were performed using liquid chromatography-mass spectrometry to characterize the GM of patients with AONFH and healthy normal controls (NCs). Metagenomic sequencing of fecal samples was performed to identify whether GM changes on the species level were associated with the expression of gut bacteria genes or their associated functions in patients with AONFH. The abundance of 58 genera was found to differ between the NC group and the AONFH group. Specifically, , , and were significantly more abundant in the AONFH group compared with those in the NC group. Metagenomic sequencing demonstrated that the majority of the bacterial species that exhibited significantly different abundance in patients with AONFH belonged to the genus . Fecal metabolomic analysis demonstrated that several metabolites were present at significantly different concentrations in the AONFH group compared with those in the NC group. These metabolites were products of vitamin B6 metabolism, retinol metabolism, pentose and glucuronate interconversions and glycerophospholipid metabolism. In addition, these changes in metabolite levels were observed to be associated with the altered abundance of specific bacterial species, such as , and . According to the results of the present study, a comprehensive landscape of the GM and metabolites in patients with AONFH was revealed, suggesting the existence of interplay between the gut microbiome and metabolome in AONFH pathogenesis.
PubMed: 38873043
DOI: 10.3892/etm.2024.12599 -
Schizophrenia Bulletin Jun 2024Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia...
BACKGROUND
Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear.
DESIGN
We performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on July 24, 2023. We included randomized clinical trials comparing 1 or more treatment strategies for antipsychotic-induced akathisia against each other or control conditions. We included adults with schizophrenia or other psychiatric disorders treated with antipsychotics. The primary outcome was akathisia severity at posttreatment. Secondary outcomes included akathisia response, all-cause dropout, psychotic symptoms, and long-term akathisia severity. We synthesized data in random effects frequentist network meta-analyses and assessed confidence in the evidence using CINeMA.
RESULTS
We identified 19 trials with 661 randomized participants (mean age 35.9 [standard deviation 12.0]; 36.7% [195 of 532] women). No trials examined dose reduction or switching of antipsychotics. Findings suggested 5-HT2A antagonists (k = 6, n = 108; standardized mean difference [SMD] -1.07 [95% confidence interval, -1.42; -0.71]) and beta-blockers (k = 8, n = 105; SMD -0.46 [-0.85; -0.07]) may improve akathisia severity, but confidence in the evidence was deemed low. We also found that benzodiazepines (k = 2, n = 13; SMD -1.62 [-2.64; -0.59]) and vitamin B6 (k = 3, n = 67; SMD -0.99 [-1.49; -0.50]) might also be beneficial, but confidence in the evidence was very low. Analyses of secondary outcomes did not provide additional insights.
CONCLUSIONS
Our findings suggest that 5-HT2A antagonists, beta-blockers, and with a lesser certainty, benzodiazepines, and vitamin B6 might improve akathisia. Given the low to very low confidence in the evidence of add-on agents and the absence of evidence of their long-term efficacy, careful consideration of side effects is warranted. These recommendations are extremely preliminary and further trials are needed.
PubMed: 38869177
DOI: 10.1093/schbul/sbae098