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The Cochrane Database of Systematic... May 2021Reference standard indices of iron deficiency and iron overload are generally invasive, expensive, and can be unpleasant or occasionally risky. Ferritin is an iron... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Reference standard indices of iron deficiency and iron overload are generally invasive, expensive, and can be unpleasant or occasionally risky. Ferritin is an iron storage protein and its concentration in the plasma or serum reflects iron stores; low ferritin indicates iron deficiency, while elevated ferritin reflects risk of iron overload. However, ferritin is also an acute-phase protein and its levels are elevated in inflammation and infection. The use of ferritin as a diagnostic test of iron deficiency and overload is a common clinical practice.
OBJECTIVES
To determine the diagnostic accuracy of ferritin concentrations (serum or plasma) for detecting iron deficiency and risk of iron overload in primary and secondary iron-loading syndromes.
SEARCH METHODS
We searched the following databases (10 June 2020): DARE (Cochrane Library) Issue 2 of 4 2015, HTA (Cochrane Library) Issue 4 of 4 2016, CENTRAL (Cochrane Library) Issue 6 of 12 2020, MEDLINE (OVID) 1946 to 9 June 2020, Embase (OVID) 1947 to week 23 2020, CINAHL (Ebsco) 1982 to June 2020, Web of Science (ISI) SCI, SSCI, CPCI-exp & CPCI-SSH to June 2020, POPLINE 16/8/18, Open Grey (10/6/20), TRoPHI (10/6/20), Bibliomap (10/6/20), IBECS (10/6/20), SCIELO (10/6/20), Global Index Medicus (10/6/20) AIM, IMSEAR, WPRIM, IMEMR, LILACS (10/6/20), PAHO (10/6/20), WHOLIS 10/6/20, IndMED (16/8/18) and Native Health Research Database (10/6/20). We also searched two trials registers and contacted relevant organisations for unpublished studies.
SELECTION CRITERIA
We included all study designs seeking to evaluate serum or plasma ferritin concentrations measured by any current or previously available quantitative assay as an index of iron status in individuals of any age, sex, clinical and physiological status from any country.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods. We designed the data extraction form to record results for ferritin concentration as the index test, and bone marrow iron content for iron deficiency and liver iron content for iron overload as the reference standards. Two other authors further extracted and validated the number of true positive, true negative, false positive, false negative cases, and extracted or derived the sensitivity, specificity, positive and negative predictive values for each threshold presented for iron deficiency and iron overload in included studies. We assessed risk of bias and applicability using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. We used GRADE assessment to enable the quality of evidence and hence strength of evidence for our conclusions.
MAIN RESULTS
Our search was conducted initially in 2014 and updated in 2017, 2018 and 2020 (10 June). We identified 21,217 records and screened 14,244 records after duplicates were removed. We assessed 316 records in full text. We excluded 190 studies (193 records) with reasons and included 108 studies (111 records) in the qualitative and quantitative analysis. There were 11 studies (12 records) that we screened from the last search update and appeared eligible for a future analysis. We decided to enter these as awaiting classification. We stratified the analysis first by participant clinical status: apparently healthy and non-healthy populations. We then stratified by age and pregnancy status as: infants and children, adolescents, pregnant women, and adults. Iron deficiency We included 72 studies (75 records) involving 6059 participants. Apparently healthy populations Five studies screened for iron deficiency in people without apparent illness. In the general adult population, three studies reported sensitivities of 63% to 100% at the optimum cutoff for ferritin, with corresponding specificities of 92% to 98%, but the ferritin cutoffs varied between studies. One study in healthy children reported a sensitivity of 74% and a specificity of 77%. One study in pregnant women reported a sensitivity of 88% and a specificity of 100%. Overall confidence in these estimates was very low because of potential bias, indirectness, and sparse and heterogenous evidence. No studies screened for iron overload in apparently healthy people. People presenting for medical care There were 63 studies among adults presenting for medical care (5042 participants). For a sample of 1000 subjects with a 35% prevalence of iron deficiency (of the included studies in this category) and supposing a 85% specificity, there would be 315 iron-deficient subjects correctly classified as having iron deficiency and 35 iron-deficient subjects incorrectly classified as not having iron deficiency, leading to a 90% sensitivity. Thresholds proposed by the authors of the included studies ranged between 12 to 200 µg/L. The estimated diagnostic odds ratio was 50. Among non-healthy adults using a fixed threshold of 30 μg/L (nine studies, 512 participants, low-certainty evidence), the pooled estimate for sensitivity was 79% with a 95% confidence interval of (58%, 91%) and specificity of 98%, with a 95% confidence interval of (91%, 100%). The estimated diagnostic odds ratio was 140, a relatively highly informative test. Iron overload We included 36 studies (36 records) involving 1927 participants. All studies concerned non-healthy populations. There were no studies targeting either infants, children, or pregnant women. Among all populations (one threshold for males and females; 36 studies, 1927 participants, very low-certainty evidence): for a sample of 1000 subjects with a 42% prevalence of iron overload (of the included studies in this category) and supposing a 65% specificity, there would be 332 iron-overloaded subjects correctly classified as having iron overload and 85 iron-overloaded subjects incorrectly classified as not having iron overload, leading to a 80% sensitivity. The estimated diagnostic odds ratio was 8.
AUTHORS' CONCLUSIONS
At a threshold of 30 micrograms/L, there is low-certainty evidence that blood ferritin concentration is reasonably sensitive and a very specific test for iron deficiency in people presenting for medical care. There is very low certainty that high concentrations of ferritin provide a sensitive test for iron overload in people where this condition is suspected. There is insufficient evidence to know whether ferritin concentration performs similarly when screening asymptomatic people for iron deficiency or overload.
Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Bias; Biomarkers; Child; Child, Preschool; Female; Ferritins; Humans; Infant; Iron Overload; Male; Middle Aged; Pregnancy; Pregnant Women; Sensitivity and Specificity; Young Adult
PubMed: 34028001
DOI: 10.1002/14651858.CD011817.pub2 -
Sports (Basel, Switzerland) May 2023The aim of this systematic review is twofold: (i) to examine the effects of micronutrient intake on athletic performance and (ii) to determine the specific... (Review)
Review
The aim of this systematic review is twofold: (i) to examine the effects of micronutrient intake on athletic performance and (ii) to determine the specific micronutrients, such as vitamins, minerals, and antioxidants, that offer the most significant enhancements in terms of athletic performance, with the goal of providing guidance to athletes and coaches in optimizing their nutritional strategies. The study conducted a systematic search of electronic databases (i.e., PubMed, Web of Science, Scopus) using keywords pertaining to micronutrients, athletic performance, and exercise. The search involved particular criteria of studies published in English between 1950 and 2023. The findings suggest that vitamins and minerals are crucial for an athlete's health and physical performance, and no single micronutrient is more important than others. Micronutrients are necessary for optimal metabolic body's functions such as energy production, muscle growth, and recovery, which are all important for sport performance. Meeting the daily intake requirement of micronutrients is essential for athletes, and while a balanced diet that includes healthy lean protein sources, whole grains, fruits, and vegetables is generally sufficient, athletes who are unable to meet their micronutrient needs due to malabsorption or specific deficiencies may benefit from taking multivitamin supplements. However, athletes should only take micronutrient supplements with the consultation of a specialized physician or nutritionist and avoid taking them without confirming a deficiency.
PubMed: 37368559
DOI: 10.3390/sports11060109 -
Nutrients Mar 2018Observational studies have indicated an inverse association between vitamin D levels and the risk of diabetes, yet evidence from population interventions remains... (Meta-Analysis)
Meta-Analysis Review
Observational studies have indicated an inverse association between vitamin D levels and the risk of diabetes, yet evidence from population interventions remains inconsistent. PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were searched up to September 2017. Data from studies regarding serum 25(OH)D, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were pooled. Twenty studies ( = 2703) were included in the meta-analysis. Vitamin D supplementation resulted in a significant improvement in serum 25(OH)D levels (weighted mean difference (WMD) = 33.98; 95%CI: 24.60-43.37) and HOMA-IR (standardized mean difference (SMD) = -0.57; 95%CI: -1.09~-0.04), but not in other outcomes. However, preferred changes were observed in subgroups as follows: short-term (WMD = -8.44; 95%CI: -12.72~-4.15), high dose (WMD = -8.70; 95%CI: -12.96~-4.44), non-obese (SMD = -1.80; 95%CI: -2.66~-0.95), Middle Easterners (WMD = -10.43; 95%CI: -14.80~-6.06), baseline vitamin D deficient individuals (WMD = -5.77; 95%CI: -10.48~-1.05) and well-controlled HbA1c individuals (WMD = -4.09; 95%CI: -15.44~7.27). Vitamin D supplementation was shown to increase serum 25(OH)D and reduce insulin resistance effectively. This effect was especially prominent when vitamin D was given in large doses and for a short period of time, and to patients who were non-obese, Middle Eastern, vitamin D deficient, or with optimal glycemic control at baseline.
Topics: Adult; Aged; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Treatment Outcome; Vitamin D; Vitamin D Deficiency
PubMed: 29562681
DOI: 10.3390/nu10030375 -
Maturitas Aug 2019This systematic review and meta-analysis assesses the prevalence of protein-energy malnutrition risk across different health-care settings in European older adults,... (Meta-Analysis)
Meta-Analysis
Prevalence of protein-energy malnutrition risk in European older adults in community, residential and hospital settings, according to 22 malnutrition screening tools validated for use in adults ≥65 years: A systematic review and meta-analysis.
This systematic review and meta-analysis assesses the prevalence of protein-energy malnutrition risk across different health-care settings in European older adults, using 22 malnutrition screening tools recently validated for use in older adults. Systematic searches were performed in six electronic databases (2006 through 2017). Included were studies which reported malnutrition risk in adults aged ≥65y in Europe. Frequency of high and moderate malnutrition risk for each malnutrition screening tool was collated. Meta-analyses of malnutrition risk using a random-effects model were performed where data from at least 10 study samples were available. Of 21,465 studies, 196 studies were available for data extraction, representing 223 study samples from 24 European countries and 583,972 older adults. Pooled prevalence rates of high malnutrition risk across all countries and malnutrition screening tools were 28.0% (n = 127 study samples), 17.5% (n = 30), and 8.5% (n = 32), for the hospital, residential care and community settings respectively. Using meta-regression, prevalence rates were higher in adults aged >80y (p < 0.0001), in women (p = 0.03) and in patients with one or multiple comorbidities (p < 0.0001). Prevalence rates differed by country, from 15.2% in Spain to 37.7% in Switzerland, and by screening tool, from 14.9% using MNA-SF to 40.6% using NRS-2002. In conclusion, the prevalence of high malnutrition risk in European older adults varies widely between countries and across health-care settings. Malnutrition risk is associated with older age, gender and presence of disease. As prevalence rates differ depending on the screening tool used, the use of one preferred malnutrition screening tool per setting is strongly recommended.
Topics: Aged; Europe; Geriatric Assessment; Hospitals; Humans; Mass Screening; Nutrition Assessment; Prevalence; Protein-Energy Malnutrition
PubMed: 31239123
DOI: 10.1016/j.maturitas.2019.05.006 -
Frontiers in Immunology 2021Primary immune regulatory disorders (PIRD) are associated with autoimmunity, autoinflammation and/or dysregulation of lymphocyte homeostasis. Autoimmune... (Meta-Analysis)
Meta-Analysis
Primary immune regulatory disorders (PIRD) are associated with autoimmunity, autoinflammation and/or dysregulation of lymphocyte homeostasis. Autoimmune lymphoproliferative syndrome (ALPS) is a PIRD due to an apoptotic defect in Fas-FasL pathway and characterized by benign and chronic lymphoproliferation, autoimmunity and increased risk of lymphoma. Clinical manifestations and typical laboratory biomarkers of ALPS have also been found in patients with a gene defect out of the Fas-FasL pathway (ALPS-like disorders). Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), we identified more than 600 patients suffering from 24 distinct genetic defects described in the literature with an autoimmune lymphoproliferative phenotype (ALPS-like syndromes) corresponding to phenocopies of primary immunodeficiency (PID) (), susceptibility to EBV (), antibody deficiency ( gain of function (GOF) loss of function (LOF) GOF), regulatory T-cells defects ( GOF), combined immunodeficiencies (), defects in intrinsic and innate immunity and predisposition to infection ( GOF, ) and autoimmunity/autoinflammation (). CTLA4 and LRBA patients correspond around to 50% of total ALPS-like cases. However, only 100% of CTLA4, PRKCD, TET2 and NRAS/KRAS reported patients had an ALPS-like presentation, while the autoimmunity and lymphoproliferation combination resulted rare in other genetic defects. Recurrent infections, skin lesions, enteropathy and malignancy are the most common clinical manifestations. Some approaches available for the immunological study and identification of ALPS-like patients through flow cytometry and ALPS biomarkers are provided in this work. Protein expression assays for NKG2D, XIAP, SAP, CTLA4 and LRBA deficiencies and functional studies of AKT, STAT1 and STAT3 phosphorylation, are showed as useful tests. Patients suspected to suffer from one of these disorders require rapid and correct diagnosis allowing initiation of tailored specific therapeutic strategies and monitoring thereby improving the prognosis and their quality of life.
Topics: Autoimmune Lymphoproliferative Syndrome; Early Diagnosis; Humans; Primary Immunodeficiency Diseases
PubMed: 34447369
DOI: 10.3389/fimmu.2021.671755 -
The Cochrane Database of Systematic... Mar 2015Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most natural foods are excluded from diet and supplements are used to supply other nutrients. Recent publications report a decrease in blood phenylalanine concentration in some patients treated with sapropterin dihydrochloride. We examined the evidence for the use of sapropterin dihydrochloride to treat phenylketonuria. This is an update of a previously published Cochrane Review.
OBJECTIVES
To assess the safety and efficacy of sapropterin dihydrochloride in lowering blood phenylalanine concentration in people with phenylketonuria.
SEARCH METHODS
We identified relevant trials from the Group's Inborn Errors of Metabolism Trials Register. Date of last search: 11 August 2014.We also searched ClinicalTrials.gov and Current controlled trials. Last search: 4 September 2014We contacted the manufacturers of the drug (BioMarin Pharmaceutical Inc.) for information regarding any unpublished trials.
SELECTION CRITERIA
Randomized controlled trials comparing sapropterin with no supplementation or placebo in people with phenylketonuria due to phenylalanine hydroxylase deficiency.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials and extracted outcome data.
MAIN RESULTS
Two placebo-controlled trials were included. One trial administered 10 mg/kg/day sapropterin in 89 children and adults with phenylketonuria whose diets were not restricted and who had previously responded to saproterin.This trial measured change in blood phenylalanine concentration. The second trial screened 90 children (4 to 12 years) with phenylketonuria whose diet was restricted, for responsiveness to sapropterin. Forty-six responders entered the placebo-controlled part of the trial and received 20 mg/kg/day sapropterin. This trial measured change in both phenylalanine concentration and protein tolerance. Both trials reported adverse events. The trials showed an overall low risk of bias; but both are Biomarin-sponsored. One trial showed a significant lowering in blood phenylalanine concentration in the sapropterin group (10 mg/kg/day), mean difference -238.80 μmol/L (95% confidence interval -343.09 to -134.51); a second trial (20 mg/kg/day sapropterin) showed a non-significant difference, mean difference -51.90 μmol/L (95% confidence interval -197.27 to 93.47). The second trial also reported a significant increase in phenylalanine tolerance, mean difference18.00 mg/kg/day (95% confidence interval 12.28 to 23.72) in the 20 mg/kg/day sapropterin group.
AUTHORS' CONCLUSIONS
There is evidence of short-term benefit from using sapropterin in some people with sapropterin-responsive forms of phenylketonuria; blood phenylalanine concentration is lowered and protein tolerance increased. There are no serious adverse events associated with using sapropterin in the short term.There is no evidence on the long-term effects of sapropterin and no clear evidence of effectiveness in severe phenylketonuria.
Topics: Adult; Biopterins; Child; Child, Preschool; Humans; Phenylalanine; Phenylketonurias; Randomized Controlled Trials as Topic
PubMed: 25812600
DOI: 10.1002/14651858.CD008005.pub4 -
Journal of Clinical Laboratory Analysis Jul 2022The incidence of premature atherosclerotic cardiovascular disease in familial hypercholesterolemia (FH) is high. In recent years, novel therapeutic modalities have shown... (Review)
Review
BACKGROUND
The incidence of premature atherosclerotic cardiovascular disease in familial hypercholesterolemia (FH) is high. In recent years, novel therapeutic modalities have shown significant lipid-lowering ability. In this paper, we summarize the recent developments in novel therapies for FH via the treatment of different targets and discuss the characteristics of each targeted therapy. Based on the process of protein synthesis, we attempt to summarize the direct-effect targets including protein, RNA, and DNA.
METHODS
For this systematic review, relevant studies are assessed by searching in several databases including PubMed, Web of Science, Scopus, and Google Scholar. The publications of original researches are considered for screening.
RESULTS
Most drugs are protein-targeted such as molecule-based and monoclonal antibodies, including statins, ezetimibe, alirocumab, evolocumab, and evinacumab. Both antisense oligonucleotide (ASO) and small interfering RNA (siRNA) approaches, such as mipomersen, vupanorsen, inclisiran, and ARO-ANG3, are designed to reduce the number of mRNA transcripts and then degrade proteins. DNA-targeted therapies such as adeno-associated virus or CRISPR-Cas9 modification could be used to deliver or edit genes to address a genetic deficiency and improve the related phenotype.
CONCLUSION
While the therapies based on different targets including protein, RNA, and DNA are on different stages of development, the mechanisms of these novel therapies may provide new ideas for precision medicine.
Topics: Anticholesteremic Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Oligonucleotides, Antisense; RNA
PubMed: 35712827
DOI: 10.1002/jcla.24552 -
Orphanet Journal of Rare Diseases Mar 2015Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive disorder of the urea cycle. HHH has a panethnic distribution, with a... (Review)
Review
BACKGROUND
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive disorder of the urea cycle. HHH has a panethnic distribution, with a major prevalence in Canada, Italy and Japan. Acute clinical signs include intermittent episodes of vomiting, confusion or coma and hepatitis-like attacks. Alternatively, patients show a chronic course with aversion for protein rich foods, developmental delay/intellectual disability, myoclonic seizures, ataxia and pyramidal dysfunction. HHH syndrome is caused by impaired ornithine transport across the inner mitochondrial membrane due to mutations in SLC25A15 gene, which encodes for the mitochondrial ornithine carrier ORC1. The diagnosis relies on clinical signs and the peculiar metabolic triad of hyperammonemia, hyperornithinemia, and urinary excretion of homocitrulline. HHH syndrome enters in the differential diagnosis with other inherited or acquired conditions presenting with hyperammonemia.
METHODS
A systematic review of publications reporting patients with HHH syndrome was performed.
RESULTS
We retrospectively evaluated the clinical, biochemical and genetic profile of 111 HHH syndrome patients, 109 reported in 61 published articles, and two unpublished cases. Lethargy and coma are frequent at disease onset, whereas pyramidal dysfunction and cognitive/behavioural abnormalities represent the most common clinical features in late-onset cases or during the disease course. Two common mutations, F188del and R179* account respectively for about 30% and 15% of patients with the HHH syndrome. Interestingly, the majority of mutations are located in residues that have side chains protruding into the internal pore of ORC1, suggesting their possible interference with substrate translocation. Acute and chronic management consists in the control of hyperammonemia with protein-restricted diet supplemented with citrulline/arginine and ammonia scavengers. Prognosis of HHH syndrome is variable, ranging from a severe course with disabling manifestations to milder variants compatible with an almost normal life.
CONCLUSIONS
This paper provides detailed information on the clinical, metabolic and genetic profiles of all HHH syndrome patients published to date. The clinical phenotype is extremely variable and its severity does not correlate with the genotype or with recorded ammonium/ornithine plasma levels. Early intervention allows almost normal life span but the prognosis is variable, suggesting the need for a better understanding of the still unsolved pathophysiology of the disease.
Topics: Aging; Humans; Hyperammonemia; Mutation; Origin Recognition Complex; Ornithine; Protein Conformation; Urea Cycle Disorders, Inborn
PubMed: 25874378
DOI: 10.1186/s13023-015-0242-9 -
Clinical Endocrinology Mar 2023P450 side-chain cleavage deficiency (SCCD) patients present with primary adrenal insufficiency (PAI) with or without undervirilized external genitalia. The distinction...
OBJECTIVE
P450 side-chain cleavage deficiency (SCCD) patients present with primary adrenal insufficiency (PAI) with or without undervirilized external genitalia. The distinction between classic and nonclassic steroidogenic acute regulatory protein deficiency has been described, whereas in SCCD is unclear. The data on gonadal function and its correlation with SCCD genotype has not been studied. We describe our experience and perform a systematic review of genetically proven SCCD patients to determine the distinct phenotypic and genotypic characteristics of 46,XY SCCD patients with typical male external genitalia (SCCD-TMG) and atypical (SCCD-AG) external genitalia.
DESIGN, PATIENTS AND MEASUREMENTS
Retrospective review of three genetically proven SCCD patients from our centre and per-patient data analysis from a systematic review of 52 probands was performed. SCCD-TMG (n = 19) was defined as external genitalia of Sinnecker score 1 with 46,XY karyotype; the rest (Sinnecker 2-5) were classified as SCCD-AG (n = 15).
RESULTS
We report two new Indian cases of SCCD with three novel likely pathogenic variants and pubertal follow-up of a previously reported patient. In systematic review, age at diagnosis of PAI and elevated renin were not different between 46,XY SCCD-TMG (n = 19) and SCCD-AG (n = 15), whereas spontaneous puberty (9/9 vs. 0/3, p = .0045), normal prepubertal (5/5 vs. 6/6, p = .002), pubertal gonadotropins (2/9 vs. 0/3, p = 1) and normal pubertal testosterone (9/11 vs. 0/3, p = .027) were more common in SCCD-TMG. Testicular adrenal rest tumours were exclusive to SCCD-TMG (n = 4). SCCD-TMG was associated with four particular genotypes [monoallelic p.Glu314Lys with another deleterious variant on the second allele (p.Glu314Lys/X-CHS: X-compound heterozygous state), biallelic p.Arg451Trp, p.Phe215Ser/p.Arg232Ter and monoallelic p.Val79Ile]. 46,XX SCCD patients with p.Glu314Lys/X-CHS also had normal gonadotropins with spontaneous puberty.
CONCLUSION
SCCD-TMG is associated with four specific genotypes and distinct gonadal characteristics from SCCD-AG with overlapping features of PAI.
Topics: Humans; Male; Testosterone; Puberty; Testicular Neoplasms; Mutation
PubMed: 36357326
DOI: 10.1111/cen.14848 -
Reproductive Sciences (Thousand Oaks,... Apr 2023Uterine fibroids are the most common tumor of reproductive-age women worldwide and cause significant morbidity in affected women. Vitamin D has emerged as a potential... (Review)
Review
Uterine fibroids are the most common tumor of reproductive-age women worldwide and cause significant morbidity in affected women. Vitamin D has emerged as a potential therapy for uterine fibroids based on experimental and epidemiologic evidence. The objective of this systematic review was to evaluate the role of vitamin D in the pathophysiology of uterine fibroids and its efficacy for prevention and treatment of fibroids. A comprehensive search was conducted of Cochrane Library, Embase, PubMed, Scopus, and Web of Science from inception to March 2022. English-language publications that evaluated vitamin D and uterine fibroids in humans, whether experimental or clinical, were considered. The search yielded 960 publications, and 89 publications met inclusion criteria: 23 preclinical studies, 25 clinical studies, and 41 review articles. Preclinical studies indicated that the vitamin D receptor was decreased in fibroid cells. Vitamin D treatment of fibroid cells decreased proliferation, extracellular matrix protein expression, and Wnt/β-catenin signaling. Fourteen clinical studies (n = 3535 participants) assessed serum vitamin D level in women with ultrasound-proven fibroids, and all found an inverse correlation between serum vitamin D level and presence of fibroids. Five clinical studies (n = 472 patients) evaluated treatment of fibroids with vitamin D. Four of five studies showed vitamin D significantly inhibited fibroid growth. One pilot study (n = 109 patients) of vitamin D for secondary prevention of fibroids demonstrated smaller recurrent fibroids in the treated group. These studies provide evidence for vitamin D as a therapy for uterine fibroids and underscore the need for well-designed, randomized, placebo-controlled clinical trials.
Topics: Humans; Female; Vitamin D; Uterine Neoplasms; Pilot Projects; Leiomyoma
PubMed: 35960442
DOI: 10.1007/s43032-022-01011-z