Search Results (128)

A total of 38% of Americans do not meet the Recommended Dietary Allowance (RDA) for calcium including those at risk for osteoporosis. To increase the percentage of patients at risk for osteoporosis who achieve goal calcium RDA intake, a collaborative specialty pharmacy-registered dietitian-nutritionist (RDN) quality improvement program was developed. Patients aged 18 to 90 years old receiving osteoporosis therapy (denosumab, teriparatide, zoledronic acid) or medications that increase bone loss (elagolix, oral prednisone) were provided with a structured assessment and educational intervention. Daily calcium intake included patient self-reported dietary intake plus supplement use. Written and verbal education on increasing dietary intake based on patient preferences was provided with 5 calcium-rich food-source store coupons. Recommendations for supplement selection (citrate vs. carbonate) and/or medication-related problem resolution were provided. Follow-up occurred at 3–6 months. Fifty patients enrolled [94% female, mean age 66.6 years (SD 15.3)] were taking denosumab (36), teriparatide (1), zoledronic acid (1), elagolix (7) and prednisone (5). The mean baseline daily dietary calcium intake was 500 mg (SD 247) with none achieving goal intake with diet alone. Average calcium supplement use in 22 (44%) patients was 686 mg daily (SD 284). At baseline, 17 (34%) met goal daily calcium intake compared to 30 (60%) at post intervention follow-up (p = 0.009). Over half of the store coupons were redeemed. A specialty pharmacy-RDN customized intervention program provides a model for aiding patients to modify calcium intake. Full article

Background/Objectives: Dendrobium nobile Lindl. (DNL), a traditional dietary supplement, exhibits therapeutic potential for type 2 diabetes mellitus (T2DM), yet its mechanisms remain unclear. Methods: T2DM was induced in db/db mice. DNL (10 g/kg/d) or metformin (65 mg/kg/d) was administered for 4 weeks. This study integrated pharmacodynamic evaluation and multi-omics to elucidate DNL’s anti-diabetic effects in db/db mice. Results: DNL intervention significantly ameliorated T2DM phenotypes, reducing hyperglycemia, insulin resistance, and renal dysfunction. Metabolomics analysis identified 39 differential metabolites (19 upregulated, 20 downregulated) linked to citrate cycle, oxidative phosphorylation, and glycerophospholipid metabolism, while proteomics revealed 113 differentially expressed proteins, with multi-omics integration highlighting DNL’s modulation of three proteins (Ckm, Ache, Selenbp1) and four metabolites (4-guanidinobutanoic acid, phosphorylcholine, homocysteine, succinic acid) across arginine/proline metabolism, glycerophospholipid metabolism, and sulfur metabolism. Pathway analysis demonstrated DNL’s restoration of dysregulated processes, including inflammation suppression via NF-κB and PI3K-Akt pathways, enhanced insulin sensitivity through glycerophospholipid balance, and mitigation of oxidative stress via sulfur metabolism. Key correlations between metabolites and proteins underscored DNL’s multi-target action. Conclusions: These findings systematically decode therapeutic mechanisms of Dendrobium nobile Lindl., emphasizing its role in rectifying metabolic disorders and inflammatory signaling, thereby providing a molecular basis for its clinical application in T2DM management. Full article

Secondary iron overload exacerbates osteoporosis by elevating reactive oxygen species (ROS), which suppress osteoblast function and enhance osteoclast activity, disrupting bone remodeling. Reducing iron overload and oxidative stress may improve bone health. Epigallocatechin-3-gallate (EGCG), the main bioactive compound in green tea extract (GTE), is recognized for its antioxidant and iron-chelating properties. This study examined the effect of GTE on bone formation and mineralization in iron-overloaded human osteoblast-like MG-63 cells. An iron-overloaded model was established using ferric ammonium citrate (FAC), followed by treatment with GTE, deferiprone (DFP), or their combination. GTE significantly reduced intracellular iron, ROS levels, and lipid peroxidation while upregulating the osteogenic marker BGLAP, the anti-resorptive marker OPG, and osteogenic mineralization, indicating restored bone health. These results suggest that EGCG-containing GTE mitigates iron-induced oxidative stress and promotes osteogenesis, highlighting its potential as a natural therapeutic supplement for managing iron-overload-associated osteoporosis. Full article

This study aimed to investigate the effects of adding 360 mg/kg niacinamide (NAM) to diets on nutrient metabolism, providing insights into how dietary NAM supplementation enhances nitrogen utilization and growth performance in pigs. Forty growing–finishing pigs were randomly assigned to one of four experimental diets as follows: basal diet + 30 mg/kg NAM (CON), basal diet + 360 mg/kg NAM (CON + NAM), low-protein diet + 30 mg/kg NAM (LP), and low-protein diet + 360 mg/kg NAM (LP + NAM). Results showed that supplementation of both the CON and LP diets with 360 mg/kg NAM resulted in decreased urea nitrogen concentrations and carbamyl phosphate synthetase-I activity (p < 0.05). The pyruvate dehydrogenase activity in the serum and liver, as well as the activity of pyruvate dehydrogenase, citrate synthase, and glutamate dehydrogenase 1 in the ileum mucosa, was increased by supplementing the LP diet with 360 mg/kg NAM (p < 0.05). The LP diet with 360 mg/kg NAM increased the villi length to crypt depth, mRNA expression of glucose transporters 1 and 2 and alanine-serine-cysteine transporter 1, and mRNA expression of mechanistic target of the rapamycin 1 in the ileum (p < 0.05). Additionally, 360 mg/kg NAM supplementation in the LP diet reduced ileal Lactobacillus abundance (LDA > 4) and increased ileal microbial nucleotide and purine metabolism (p < 0.05). Our findings suggest that addition of 360 mg/kg NAM to the LP diet reduced urea production in the liver, enhanced glucose and amino acid absorption and transport in the ileum, and improved glucose metabolism. Full article

Polyunsaturated fatty acids are vital for brain health, supporting cognitive development and helping to prevent neurodegenerative diseases. Since the body cannot produce them, they must be obtained through food. This study aimed to assess the effects of corn oil on the behavior and biochemical parameters of Drosophila melanogaster. The flies were fed a diet supplemented with different concentrations of corn oil from the larval stage until the fifth day of adulthood. A diet containing corn oil (37.8 mg/mL of linoleic acid) reduced mortality under starvation conditions and enhanced locomotor performance (p < 0.01). Biochemical analyses revealed increased levels of glutathione (p < 0.001), citrate synthase activity (p < 0.05), and mitochondrial phosphorylation (p < 0.05), indicating a potential boost in energy metabolism. Conversely, a decrease in acetylcholinesterase activity (p < 0.05) was observed, suggesting cholinergic modulation. These results demonstrate that corn oil supplementation supports neural health in this animal model, opening pathways for further research into non-pharmacological treatments for neurodegenerative diseases such as Alzheimer’s disease. Full article

Previous studies have shown that 5-aminolevulinic acid phosphate together with sodium ferrous citrate, which is marketed as a food supplement, appears to be an important metabolic regulator in depleted T cell metabolism. Therefore, it was hypothesized that its administration in subjects vaccinated against COVID-19 could enhance their immune system. Therefore, the aim of our proof-of-concept study was to determine the safety (by adverse events monitoring) and the tolerability (by subject questionnaires) and to investigate immune-boosting properties (by Immunoglobulins) in which 200 subjects were randomized in a ratio of 1:1 within 2 arms. In the intervention arm, the study product was administered together with the vaccines Covishield or Covaxin, and up to 21 days thereafter with a 150 mg daily dose, whereas in the control arm, the subjects were vaccinated only. No safety issues were detected, and the evaluation of the subject questionnaires showed no limitation of the well-being, which confirms the excellent tolerability of 5-aminolevulinic acid phosphate with sodium ferrous citrate. Moreover, the ‘Change in Immunoglobulin G levels’, although statistically insignificant, showed strong signals of its immune supportive potential. However, further studies are recommended to verify the results. Full article

Objective: Growth retardation in adolescents caused by nutritional deficiency requires effective intervention. A novel dietary supplement containing bamboo shoot extract, amino acids, and calcium citrate (Kidtal + Ca, KDTCa) was evaluated for its growth-promoting effects. Methods: After acclimatization, sixty-three 3-week-old male Sprague-Dawley (SD) rats were randomly divided into a normal control group and model groups. Growth retardation was induced in the modeling groups through calcium-deficient feeding, followed by administration of KDTCa, bamboo shoot extract and amino acids (Kidtal), or calcium citrate (CC). After 6 weeks of intragastric administration, the mechanical properties, microstructure, and growth plate development of bone were evaluated using three-point bending, micro-CT, and H&E staining, respectively. Bone calcium/phosphorus distribution and fecal calcium apparent absorption rate were measured by ICP-MS. Results: All inter-group differences were analyzed using one-way analysis of variance and checked using the Tuckey test. KDTCa treatment dose-dependently enhanced bone development in calcium-deficient rats. Compared to the model group, H-KDTCa significantly restored naso-anal length (p < 0.05) and body weight (p < 0.01). KDTCa supplementation significantly restored calcium and phosphorus levels in blood and bone. Three-point bending experiments showed that the stiffness and bending energy were increased by 142.58% and 384.7%. In bone microarchitecture, both bone mineral density (BMD) and microstructural parameters were significantly improved. These findings were consistent with the increased long bone length (p < 0.05) and decreased serum BALP/TRACP levels (p < 0.001). Dose-dependent IGF-1 elevation (p < 0.01) potentially mediated growth plate elongation by 35.34%. Notably, KDTCa increased calcium apparent absorption by 6.1% versus calcium-only supplementation at equal intake. Conclusions: KDTCa improves bone microstructure and strength, restores bone metabolism, and enhances growth plate height via promoting IGF-1 secretion to facilitate bone development. Further studies are needed to determine whether the components and calcium in Kidtal have a synergistic effect. Full article

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age. Treatment or management of this syndrome includes several pharmacological and non-pharmacological treatment approaches for different manifestations of the disease that vary with the patient’s age, symptoms, requirements, and geographical location. Objective: This systematic review aims to conduct a comprehensive and evidence-based analysis of the various available treatment options and identify knowledge gaps in PCOS management in India. Methods: A comprehensive search was conducted in PubMed, Scopus, and Embase databases from January 2010 till February 2024. We included randomized control trials (RCTs) using any pharmacological drugs (e.g., insulin sensitizers, anti-androgens, anti-obesity drugs, oral contraceptive pills, ovulation induction drugs, etc.) or non-pharmacological intervention (e.g., yoga, diet, herbal supplements, etc.) with Indian PCOS patients for improving common manifestations of PCOS and written in the English language. Studies were screened by two authors independently in a two-level process. Data extraction was also performed by two authors. Risk of bias was performed using the RoB 2 Tool. Subgroup analysis and meta-analysis were performed using the RevMan tool. Results: Thirty RCTs on pharmacological and eight on non-pharmacological interventions were included in the study. However, all the RCTs were so heterogeneous in terms of intervention used, subject recruited, and outcomes measured that meta-analysis was possible for only three subgroups (metformin vs. inositol, metformin vs. metformin+ inositol, and letrozole vs. clomiphene citrate), with only two or three studies per analysis. Most studies were single-centric and small-sized and had a high risk of bias, limiting their generalizability. Conclusions: This systematic review synthesized existing research and evaluated the effectiveness and safety of existing treatments. Limitations and gaps in the current research were identified, which may inform future research for better understanding and management of PCOS in the Indian context. Full article

In this study, solid-state fermentation for growth and bacteriocin production by Lactiplantibacillus plantarum LD1 was carried out using wheat bran, a lignocellulosic substrate. This is the first report showing bacteriocin production using L. plantarum LD1 in solid-state fermentation. Wheat bran supported higher production of bacteriocin (391.69 ± 12.58 AU/mL) than other substrates. Appropriate conditions were achieved using statistical designs. Significant factors identified by Plackett–Burman Design and their interactions were studied using response surface methodology. Enhanced production of bacteriocin (582.86 ± 0.87 AU/mL) and optimal growth (log₁₀ CFU/mL 8.56 ± 0.42) were attained in wheat bran medium supplemented with peptone (1.13%), yeast extract (1.13%), glucose (1.56%), and tri-ammonium citrate (0.50%). Growth in non-optimized medium (MRS) was almost similar (log₁₀ CFU/mL 8.15 ± 0.20), but the bacteriocin production level was lower (391.69 ± 0.58 AU/mL). Bacteriocin production was sustainable using varied quantities of wheat bran, showing the suitability of the optimized bioprocess for large-scale production. The cost for bacteriocin production in the optimized medium was found to be 444,583.60 AU/USD, which is about 4 times more economical than the cost of the commercial MRS medium, 121,497.18 AU/USD). Thus, an almost 1.5-fold improvement in bacteriocin production was achieved using wheat bran as the substrate. The cost of the production medium was reduced by approximately 25%, making the bioprocess economical. Full article

Background/Objectives: Cancer cells often display altered energy metabolism. In particular, expression levels and activity of the tricarboxylic acid cycle (TCA cycle) enzymes may change in cancer, and dysregulation of the TCA cycle is a frequent hallmark of cancer cell metabolism. MEMO1, a modulator of cancer metastasis, has been shown to bind iron and regulate iron homeostasis in the cells. MEMO1 knockout changed mitochondrial morphology and iron content in breast cancer cells. Our previous genome-wide analysis of MEMO1 genetic interactions across multiple cancer cell lines revealed that gene sets involved in mitochondrial respiration and the TCA cycle are enriched among the gain-of-function interaction partners of MEMO1. Based on these findings, we measured the TCA cycle metabolite levels in breast cancer cells with varying levels of MEMO1 expression. Methods: ShRNA knockdown assay was performed to test essentiality of key TCA cycle enzymes. TCA metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in MDA-MB-231 (high MEMO1), M67-2 (MEMO1 knockdown), and M67-9 (MEMO1 knockout) cells under iron-depleted, basal iron, and iron-supplemented conditions. Results:ACO2 and OGDH knockdowns inhibit cell proliferation, indicating an essential role of the TCA cycle in MDA-MB-231 metabolism. α-Ketoglutarate and citrate levels exhibited an inverse relationship with MEMO1 expression, increasing significantly in MEMO1 knockout cells regardless of iron availability. In contrast, fumarate, malate, and glutamate levels were elevated in MEMO1 knockout cells specifically under low iron conditions, suggesting an iron-dependent effect. Conclusions: Overall, our results indicate that MEMO1 plays a role in regulating the TCA in cancer cells in an iron-dependent manner. Full article

Background: The efficacy of intravenous iron preparations for chronic heart failure with iron deficiency has been reported, but the efficacy of oral iron preparations has not been demonstrated. In this study, we conducted a prospective clinical study using ferric citrate hydrate tablets in patients with chronic heart failure complicated by iron deficiency anemia. Methods and Results: A prospective study was conducted using ferric citrate hydrate in patients with chronic heart failure complicated by iron deficiency anemia. The registered patients were divided into two groups: those administered ferric citrate hydrate and those switched from iron sulfate sustained-release to ferric citrate hydrate. The primary endpoint was hemoglobin level. The secondary endpoints included hematocrit, serum iron, saturation, ferritin, and cardiac-, renal-, and hepatic-related biomarkers. A total of 141 patients were enrolled in this study, including 95 patients who were newly administered ferric citrate hydrate and 46 patients who were switched from iron sulfate sustained-release to ferric citrate hydrate. Conclusions: Ferric citrate hydrate significantly increased hemoglobin, serum iron, transferrin saturation (TSAT), and ferritin levels, and decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Ferric citrate hydrate could be continued without side effects such as gastrointestinal symptoms. Improvement in iron metabolism and anemia due to iron supplementation with ferric citrate hydrate led to improvement in heart failure biomarkers. Full article

Autism spectrum disorder (ASD) is associated with mitochondrial dysfunction, but studies demonstrating the efficacy of treatments are scarce. We sought to determine whether a mitochondrial-targeted dietary supplement designed for children with ASD improved mitochondrial function and ASD symptomatology using a double-blind placebo-controlled cross-over design. Sixteen children [mean age 9 years 4 months; 88% male] with non-syndromic ASD and mitochondrial enzyme abnormalities, as measured by MitoSwab (Religen, Plymouth Meeting, PA, USA), received weight-adjusted SpectrumNeeds^® (NeuroNeeds, Old Lyme, CT, USA) and QNeeds^® (NeuroNeeds, Old Lyme, CT, USA) and placebos matched on taste, texture and appearance during two separate 12-week blocks. Which product was received first was randomized. The treatment significantly normalized citrate synthase and complex IV activity as measured by the MitoSwab. Mitochondrial respiration of peripheral blood mononuclear cell respiration, as measured by the Seahorse XFe96 (Agilent, Santa Clara, CA, USA) with the mitochondrial oxidative stress test, became more resilient to oxidative stress after the treatment, particularly in children with poor neurodevelopment. The mitochondrial supplement demonstrated significant improvement in standardized parent-rated scales in neurodevelopment, social withdrawal, and hyperactivity with large effect sizes (Cohen’s d’ = 0.77–1.25), while changes measured by the clinical and psychometric instruments were not significantly different. Adverse effects were minimal. This small study on children with ASD and mitochondrial abnormalities demonstrates that a simple, well-tolerated mitochondrial-targeted dietary supplement can improve mitochondrial physiology and ASD symptoms. Further larger controlled studies need to verify and extend these findings. These findings are significant as children with ASD have few other effective treatments. Full article

This study explored the metabolic effects of branched-chain amino acids (BCAAs) on the hepatocytes of spotted seabass (Lateolabrax maculatus) under high-glucose (HG) or high-fat (HF) conditions. Hepatocytes were cultured under five different conditions: control, high glucose (HG), HG + BCAAs (Leu 0.8 mM, Ile 0.4 mM, Val 0.8 mM), high fat (HF), and HF + BCAAs (Leu 0.8 mM, Ile 0.8 mM, Val 0.8 mM). After 72 h of culture, cells and cell supernatants were collected to measure relevant indicators. The results revealed that BCAAs supplementation significantly reduced glycogen and lipid accumulation in hepatocytes exposed to HG or HF conditions (p < 0.05). Additionally, alanine aminotransferase and aspartate aminotransferase activities in the supernatant were significantly decreased, indicating that BCAAs supplementation alleviated hepatocyte damage induced by these conditions. Furthermore, BCAAs addition markedly enhanced antioxidant defense by increasing superoxide dismutase and catalase activities, improving total antioxidant capacity, and reducing malondialdehyde levels. Metabolic enzyme activity analysis revealed that BCAAs significantly increased the activities of citrate synthase (CS), alpha-ketoglutarate dehydrogenase complex (α-KGDHC), succinate dehydrogenase (SDH), phosphoenolpyruvate carboxykinase (PEPCK), and liver pyruvate kinase (LPS), while significantly decreasing fatty acid synthase (FAS) activity. Gene expression analysis further demonstrated that BCAAs supplementation downregulated the expression of lipogenic genes (fas and srebp-1c) and upregulated the expression of lipolytic genes (ppaα and atgl) and glucose metabolism-related genes (g6pd, hk, pfk, pk, fbp, and g6pase). Under HG or HF conditions, hepatocytes exhibited decreased adenosine triphosphate (ATP) content, increased reactive oxygen species (ROS) levels, and reduced mitochondrial membrane potential. These adverse effects were mitigated by BCAAs supplementation. In conclusion, BCAAs supplementation alleviated hepatocyte damage caused by HG or HF conditions, enhanced antioxidant defenses, and protected mitochondrial activity and function by promoting glucose and lipid metabolism. Full article

The combination of 5-aminolevulinic acid (5-ALA) phosphate and sodium ferrous citrate (SFC) has been approved as an ingredient in dietary supplements in several countries, owing to its broad applicability in healthcare. This study aimed to assess the safety of oral administration of 5-ALA and SFC in healthy adults at doses several times higher than those commercially available. This study included 22 healthy subjects (11 males and 11 females) aged 21–59. Doses of 250 mg 5-ALA phosphate and 143.4 mg SFC (15 mg Fe) per day were administered orally for 28 days. Blood tests, urinalysis, and medical interviews were performed to assess safety. No test compound-related adverse events or abnormal changes were observed, except for elevated serum Fe levels, which were mild-to-moderate and transient. In conclusion, the combined oral administration of 5-ALA phosphate and SFC in healthy adults was safe and well-tolerated at the dose and duration investigated in this study. Full article

Iron is a trace element that is indispensable for the growth and development of animals. Excessive iron supplementation may lead to iron overload and elevated reactive oxygen species (ROS) production in animals, causing cellular damage. Nevertheless, the precise mechanism by which iron overload causes cell injury remains to be fully elucidated. In this study, 16 male SD rats aged 6 to 7 weeks were randomly assigned to either a control group (CON) or an iron overload group (IO). Rats in the iron overload group received 150 mg/kg iron dextran injections every three days for a duration of four weeks. The results indicated that iron treatment with iron dextran significantly increased the scores of steatosis (p < 0.05) and inflammation (p < 0.05) in the NAS score. The integrated transcriptomic and proteomic analysis suggests that HO-1 and Lnc286.2 are potentially significant in iron overload-induced liver injury in rats. In vitro experiments utilizing ferric ammonium citrate (FAC) were conducted to establish an iron overload model in rat liver-derived BRL-3A cells. The result found that FAC treatment can significantly increase the BRL-3A cell’s Fe²⁺ content (p < 0.05), ROS (p < 0.01), lipid ROS (p < 0.01) levels, and the expression of the HO-1 gene and protein (p < 0.01), aligning with proteomic and transcriptomic findings. HO-1 inhibition can significantly decrease BRL-3A cell vitality (p < 0.01) and promote ROS (p < 0.05) and lipid ROS (p < 0.01), thus aggravating FAC-induced BRL-3A cell iron overload damage. Using the agonist of HO-1 agonist cobalt protoporphyrin (CoPP) to induce HO-1 overexpression can significantly alleviate the decrease in FAC-induced BRL-3A cell viability (p < 0.01), ROS (p < 0.01), and lipid ROS (p < 0.01). In addition, siLnc286.2 treatment can increase HO-1 expression, alleviate the decline of FAC-induced BRL-3A cell activity, and increase lipid ROS (p < 0.05) content. In conclusion, the findings of this study suggest that by suppressing the expression of Lnc286.2, we can enhance the expression of HO-1, which in turn alleviates lipid peroxidation in cells and increases their antioxidant capacity, thereby exerting a protective effect against liver cell injury induced by iron overload. Full article