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Annals of Internal Medicine Jul 2023An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking.
OBJECTIVE
To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP.
DESIGN
Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384).
SETTING
13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022.
PARTICIPANTS
352 women in early pregnancy with moderate to severe NVP.
INTERVENTION
Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days.
MEASUREMENTS
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications.
RESULTS
No significant interaction was detected between the interventions ( = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]).
LIMITATION
The placebo effects of the interventions and natural regression of the disease were not evaluated.
CONCLUSION
Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone.
PRIMARY FUNDING SOURCE
The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.
Topics: Pregnancy; Child; Female; Humans; Doxylamine; Pyridoxine; Antiemetics; Quality of Life; Vomiting; Nausea; Pregnancy Complications; Acupuncture Therapy
PubMed: 37335994
DOI: 10.7326/M22-2974 -
Nature Communications Oct 2023Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease...
Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease in B vitamin-related liver enzymes as a hallmark of systemic metabolic changes occurring in cancer cachexia. Metabolomics of multiple mouse models highlights cachexia-associated reductions of niacin, vitamin B6, and a glycine-related subset of one-carbon (C1) metabolites in the liver. Integration of proteomics and metabolomics reveals that liver enzymes related to niacin, vitamin B6, and glycine-related C1 enzymes dependent on B vitamins decrease linearly with their associated metabolites, likely reflecting stoichiometric cofactor-enzyme interactions. The decrease of B vitamin-related enzymes is also found to depend on protein abundance and cofactor subtype. These metabolic/proteomic changes and decreased protein malonylation, another cachexia feature identified by protein post-translational modification analysis, are reflected in blood samples from mouse models and gastric cancer patients with cachexia, underscoring the clinical relevance of our findings.
Topics: Mice; Animals; Humans; Vitamin B Complex; Niacin; Cachexia; Proteomics; Pyridoxine; Vitamin B 6; Stomach Neoplasms; Liver; Glycine
PubMed: 37803016
DOI: 10.1038/s41467-023-41952-w -
Archives of Gynecology and Obstetrics Oct 2023Nausea and vomiting during pregnancy (NVP) are common symptoms in pregnancy. Although no definitive treatment option for NVP, pyridoxine (Vitamin B6) supplementation has... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Nausea and vomiting during pregnancy (NVP) are common symptoms in pregnancy. Although no definitive treatment option for NVP, pyridoxine (Vitamin B6) supplementation has been used widely. The present study aims to systematically evaluate the current evidence regarding pyridoxine for the treatment of NVP.
METHODS
Data were obtained using a stepwise search process using keywords in the following online medical databases; PubMed, Web of Science, and Scopus for studies published before 1st May 2021. Studies reporting intervention with pyridoxine supplementation alone and/or with other active substances were included. A meta-analysis was performed on the PUQE score and Rhode's score for nausea and vomiting.
FINDINGS
Initial database searching indicated 548 potentially eligible articles, of which 18 studies satisfying the inclusion criteria were selected. Eight studies showed beneficial effects with pyridoxine alone as the supplementation, while six others found that the supplementation of pyridoxine in combination with another active substance had favourable effects. Supplementation of pyridoxine alone as well as combined treatment of pyridoxine with an active ingredient as the intervention significantly improved the symptoms of nausea according to Rhode's score [0.78 [95% CI: 0.26, 1.31; p = 0.003; I2 = 57%, p = 0.10)] and PUQE score [0.75 (95% CI: 0.28, 1.22; p = 0.002; I2 = 0%, p = 0.51)], respectively.
CONCLUSION
Supplementation of pyridoxine alone as well as with an active ingredient demonstrated beneficial effects for women suffering from NVP.
Topics: Pregnancy; Female; Humans; Pyridoxine; Vitamin B 6; Vomiting; Nausea; Pregnancy Complications; Dietary Supplements; Antiemetics
PubMed: 36719452
DOI: 10.1007/s00404-023-06925-w -
BJOG : An International Journal of... Jun 2024An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be...
An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].
Topics: Humans; Female; Pregnancy; Hyperemesis Gravidarum; Antiemetics; Ondansetron; Morning Sickness; Nausea; Pyridoxine; Metoclopramide; Severity of Illness Index; Pregnancy Complications
PubMed: 38311315
DOI: 10.1111/1471-0528.17739 -
Cancer Discovery Jan 2024Nutritional factors play crucial roles in immune responses. The tumor-caused nutritional deficiencies are known to affect antitumor immunity. Here, we demonstrate that...
UNLABELLED
Nutritional factors play crucial roles in immune responses. The tumor-caused nutritional deficiencies are known to affect antitumor immunity. Here, we demonstrate that pancreatic ductal adenocarcinoma (PDAC) cells can suppress NK-cell cytotoxicity by restricting the accessibility of vitamin B6 (VB6). PDAC cells actively consume VB6 to support one-carbon metabolism, and thus tumor cell growth, causing VB6 deprivation in the tumor microenvironment. In comparison, NK cells require VB6 for intracellular glycogen breakdown, which serves as a critical energy source for NK-cell activation. VB6 supplementation in combination with one-carbon metabolism blockage effectively diminishes tumor burden in vivo. Our results expand the understanding of the critical role of micronutrients in regulating cancer progression and antitumor immunity, and open new avenues for developing novel therapeutic strategies against PDAC.
SIGNIFICANCE
The nutrient competition among the different tumor microenvironment components drives tumor growth, immune tolerance, and therapeutic resistance. PDAC cells demand a high amount of VB6, thus competitively causing NK-cell dysfunction. Supplying VB6 with blocking VB6-dependent one-carbon metabolism amplifies the NK-cell antitumor immunity and inhibits tumor growth in PDAC models. This article is featured in Selected Articles from This Issue, p. 5.
Topics: Humans; Vitamin B 6; Tumor Microenvironment; Killer Cells, Natural; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Carbon
PubMed: 37931287
DOI: 10.1158/2159-8290.CD-23-0334 -
JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527 -
Nutrients Jul 2023Tryptophan is an essential nutrient required to generate vitamin B3 (niacin), which is mainly involved in energy metabolism and DNA production. Alterations in tryptophan... (Review)
Review
Tryptophan is an essential nutrient required to generate vitamin B3 (niacin), which is mainly involved in energy metabolism and DNA production. Alterations in tryptophan metabolism could have significant effects on aging and musculoskeletal health. The kynurenine pathway, essential in tryptophan catabolism, is modulated by inflammatory factors that are increased in older persons, a process known as inflammaging. Osteoporosis, sarcopenia, osteosarcopenia, and frailty have also been linked with chronically increased levels of inflammatory factors. Due to the disruption of the kynurenine pathway by chronic inflammation and/or changes in the gut microbiota, serum levels of toxic metabolites are increased and are associated with the pathophysiology of those conditions. In contrast, anabolic products of this pathway, such as picolinic acid, have demonstrated a positive effect on skeletal muscle and bone. In addition, physical activity can modulate this pathway by promoting the secretion of anabolic kynurenines. According to the evidence collected, kynurenines could have a promising role as biomarkers for osteoporosis sarcopenia, osteosarcopenia, and frailty in older persons. In addition, some of these metabolites could become important targets for developing new pharmacological treatments for these conditions.
Topics: Humans; Aged; Aged, 80 and over; Kynurenine; Tryptophan; Sarcopenia; Frailty; Osteoporosis
PubMed: 37513550
DOI: 10.3390/nu15143132 -
Cellular & Molecular Immunology Jul 2023Interleukin-33 (IL-33) is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis. The fine-tuned regulation of IL-33 in...
Interleukin-33 (IL-33) is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis. The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immune response in airway inflammation, but the mechanism is still unclear. Here, we found that healthy individuals had higher phosphate-pyridoxal (PLP, an active form of vitamin B6) concentrations in the serum than asthma patients. Lower serum PLP concentrations in asthma patients were strongly associated with worse lung function and inflammation. In a mouse model of lung inflammation, we revealed that PLP alleviated the type 2 immune response and that this inhibitory effect relied on the activity of IL-33. A mechanistic study showed that in vivo, pyridoxal (PL) needed to be converted into PLP, which inhibited the type 2 response by regulating IL-33 stability. In mice heterozygous for pyridoxal kinase (PDXK), the conversion of PL to PLP was limited, and IL-33 levels were increased in the lungs, aggravating type 2 inflammation. Furthermore, we found that the mouse double minute 2 homolog (MDM2) protein, an E3 ubiquitin-protein ligase, could ubiquitinate the N-terminus of IL-33 and sustain IL-33 stability in epithelial cells. PLP reduced MDM2-mediated IL-33 polyubiquitination and decreased the level of IL-33 through the proteasome pathway. In addition, inhalation of PLP alleviated asthma-related effects in mouse models. In summary, our data indicate that vitamin B6 regulates MDM2-mediated IL-33 stability to constrain the type 2 response, which might help develop a potential preventive and therapeutic agent for allergy-related diseases.
Topics: Mice; Animals; Vitamin B 6; Interleukin-33; Pyridoxal; Inflammation; Asthma; Disease Models, Animal; Homeostasis
PubMed: 37217797
DOI: 10.1038/s41423-023-01029-6 -
Journal of the Neurological Sciences Jul 2023The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available... (Review)
Review
The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available and affordable. PwPD are at higher risk of having abnormal serum levels of vitamin B6, which are associated with polyneuropathy and epilepsy that are potentially preventable and treatable. Potential contributors to abnormal B6 levels in PwPD include age, dietary habits, vitamin supplement misuse, gastrointestinal dysfunction and complex interactions with levodopa. The literature on the potential consequences of abnormal B6 levels in PwPD is limited by a small number of observational studies focused on polyneuropathy and epilepsy. Abnormal B6 levels have been reported in 60 of 145 PwPD (41.4% relative frequency). Low B6 levels were reported in 52 PwPD and high B6 levels were reported in 8 PwPD. There were 14 PwPD, polyneuropathy and low B6. There were 4 PwPD, polyneuropathy and high B6. There were 4 PwPD, epilepsy and low B6. Vitamin B6 level was low in 44.6% of PwPD receiving levodopa-carbidopa intestinal gel and in 30.1% of PwPD receiving oral levodopa-carbidopa. In almost all studies reporting low B6 in PwPD receiving oral levodopa-carbidopa, the dose of levodopa was ≥1000 mg/day. Rigorous epidemiological studies will clarify the prevalence, natural history and clinical relevance of abnormal serum levels of vitamin B6 in PwPD. These studies should account for diet, vitamin supplement use, gastrointestinal dysfunction, concurrent levels of vitamin B12, folate, homocysteine and methylmalonic acid, formulations and dosages of levodopa and other medications commonly used in PwPD.
Topics: Humans; Aged; Levodopa; Parkinson Disease; Carbidopa; Antiparkinson Agents; Vitamin B 6; Polyneuropathies; Vitamin B 12; Epilepsy; Vitamins
PubMed: 37210937
DOI: 10.1016/j.jns.2023.120690