Content uploaded by Edward Shipton
Author content
All content in this area was uploaded by Edward Shipton on May 23, 2016
Content may be subject to copyright.
A preview of the PDF is not available
Vitamin D Deficiency and Pain: Clinical Evidence of Low Levels of Vitamin D and Supplementation in Chronic Pain States
Abstract
A number of studies suggest a link between low levels of 25-hydroxy vitamin D and incidence of acute and chronic pain. Clinical studies of vitamin D supplementation in patients with known vitamin D deficiency have shown mixed results in improving pain scores.
In this article, vitamin D deficiency risk factors are observed and adequate levels of 25-hydroxy vitamin D defined. Clinical supplementation with vitamin D is explored, including the schedules used in published clinical trials. Evidence of the effectiveness of vitamin D supplementation for the treatment of chronic pain conditions from double-blind randomized controlled trials (RCTs) is examined.
The scientific evidence for vitamin D as a treatment option for chronic pain is limited due to lack of RCTs. It cannot be stated conclusively that vitamin D deficiency is directly linked to the etiology or maintenance of chronic pain states.
There remains a growing body of both clinical and laboratory evidence pointing to a potential relationship between low levels of 25-hydroxy vitamin D and a variety of chronic pain states. More focused research involving large RCTs is necessary.
... Previous epidemiological studies reported that vitamin D deficiency was associated with chronic musculoskeletal pain and depression, but underlying mechanisms were complex and unclear (10)(11)(12). Studies exploring the effect of vitamin D supplementation on non-specific chronic pain in the adult population and those with rheumatoid arthritis and osteoporosis have had inconsistent findings (12,13). ...
... Previous epidemiological studies reported that vitamin D deficiency was associated with chronic musculoskeletal pain and depression, but underlying mechanisms were complex and unclear (10)(11)(12). Studies exploring the effect of vitamin D supplementation on non-specific chronic pain in the adult population and those with rheumatoid arthritis and osteoporosis have had inconsistent findings (12,13). Besides, the efficacy of vitamin D supplementation on knee pain in patients with knee OA was also conflicting both for WOMAC pain score and VAS knee pain score (14,15). ...
... Previous studies have found that low levels of vitamin D are associated with chronic pain (12,28,29); but there is no previous work linking vitamin D deficiency to foot pain. In one ...
Objectives
This study aims to determine whether vitamin D supplementation or maintaining sufficient vitamin D level reduces foot pain over two years in patients with symptomatic knee OA.
Methods
A post hoc study was conducted from a randomized double‐blind placebo‐controlled trial named the VItamin D Effect on Osteoarthritis (VIDEO) study. Symptomatic knee OA patients with serum 25‐hydroxyvitamin D levels between 12.5 nmol/L to 60 nmol/L were included and randomly allocated to either monthly vitamin D3 or placebo treatment (1:1) for 2 years. Manchester Foot Pain and Disability Index (MFPDI) was used to evaluate foot pain and Disabling foot pain was defined as at least one of the 10 functional limitation items (items 1‐9,11) being documented as on ‘most/every day(s)’ in the last month. A repeated‐measure mixed effect model was used to analyze the change of MFPDI scores between groups adjusting for potential confounders.
Results
A total of 413 patients with a mean age of 63.2 years (49.7% males) were enrolled and 340 completed the study. The mean MFPDI score was 22.8±7.3, with 23.7% participants having disabling foot pain at baseline. There were significant differences in MFPDI scores change between groups over 2 years, with more improvements in vitamin D group than in placebo group (‐0.03 vs. 1.30, P=0.013) and more improvement in those maintaining sufficient vitamin D levels (n=226) than those who did not (n=114) (‐0.09 vs. 2.19, P=0.001).
Conclusion
Vitamin D supplementation and maintenance of sufficient vitamin D levels may improve foot pain in those with knee OA.
... Kronik ağrıdan muzdarip hastalarda uyku, anksiyete ve mizaç bozuklukları gibi komorbid durumlar sıklıkla rastlanmaktadır (39). Bu durum hastaların yaşam kalitesini bozmakta, iş gücü ve sosyal yaşamda kayıplara yol açabilmektedir (39)(40)(41). ...
... Kronik ağrıdan muzdarip hastalarda uyku, anksiyete ve mizaç bozuklukları gibi komorbid durumlar sıklıkla rastlanmaktadır (39). Bu durum hastaların yaşam kalitesini bozmakta, iş gücü ve sosyal yaşamda kayıplara yol açabilmektedir (39)(40)(41). Vitamin D süplementasyonun uyku, ağrı, yaşam kalitesi ve çeşitli indikatörlerde iyileşme kaydettiği bildirilmiştir (39)(40)(41)(42) ...
... Bu durum hastaların yaşam kalitesini bozmakta, iş gücü ve sosyal yaşamda kayıplara yol açabilmektedir (39)(40)(41). Vitamin D süplementasyonun uyku, ağrı, yaşam kalitesi ve çeşitli indikatörlerde iyileşme kaydettiği bildirilmiştir (39)(40)(41)(42) ...
Objective:This study aimed to determine the relationship between vitamin D levels and anxiety and depression in patients with chronic pain.Materials and Methods:A total of 160 patients, including 125 female and 35 male patients, who were >18 years old and capable of answering study questions were included in this study. Age, gender, height, weight, duration of disease, diagnosis and comorbid status of the patients were recorded. Body mass index (BMI) (kg/m2) was calculated for each patient. Pain was evaluated using the visual analogue scale (VAS), which ranges from 0 to 10. Hospital anxiety and depression scale (HADS) scores were recorded. The patients were divided into two groups (group 1 vitamin D: 0-19, group 2 vitamin D: 20-60 ng/mL) according to vitamin D levels. Also vitamin D levels were noted.Results:The mean age of the patients included in this study was 58.72±8.21 years. Vitamin D deficiency was found in 42.8% of the patients, of which 80.7% were female patients.In patients with chronic pain, there was no correlation between vitamin D levels and age (r=0.185, p=0.026); BMI (r=0.084, p=0.316); disease duration (r=0.067, p=0.420); VAS (r=0.038, p=0.648); HADS scores for anxiety (r=0.020, p=0.808) and HADS scores for depression (r=0.048, p=0.569). No relationship was noted between BMI and vitamin D levels (r =-0.117, p=0.165) in patients with chronic pain; however, a positive correlation was noted between BMI and VAS (r=0.305, p=0.000) and HADS scores for anxiety (r=0.185, p=0.001) and HADS scores for depression (r=0.0240, p=0.002).Conclusion:In the present study, we found no relationship between vitamin D levels and anxiety and depression in patients with chronic pain. However, we found a correlation between obesity and pain severity. Also we report that obesity is associated with anxiety and depression. Implementing lifestyle changes, such as weight loss and reduction of vitamin D deficiency, can improve anxiety and depression in patients with chronic pain.
... • Рекомендуется проведение исследования уровня 25-ОН витамина D в крови пациентам старше 60 лет с хронической болью с целью выявления недостаточности или дефицита витамина D [120,121,122,123]. ...
... Комментарии: целый ряд клинико-эпидемиологических исследований продемонстрировал увеличение риска ОА [122,124] при низком уровне витамина D 3 : риск ОА (ОР, 95% ДИ) -1,4 (1,9), риск ОА при высоком уровне ПТГ (ОР, 95% ДИ) -3,2 (1,1). Данное обстоятельство имеет понятное патофизиологическое объяснение. ...
The present document developed by the Russian Association of Gerontologists and Geriatricians represents the Clinical guidelines on chronic pain in older and senile patients. The Clinical guidelines were endorsed by Scientific Council of the Ministry of Health of the Russian Federation in December 2020.Clinical guidelines are focused on geriatricians providing medical care in outpatient and hospital settings, general practitioners, and physiotherapists.The document sets out the pain syndrom screening and diagnosis principles in older patients, management and treatment approaches in patients with chronic pain, as well as the prevention, rehabilitation, medical care organization issues and quality control criteria for its provision in this category of persons.
... • Рекомендуется проведение исследования уровня 25-ОН витамина D в крови пациентам старше 60 лет с хронической болью с целью выявления недостаточности или дефицита витамина D [120,121,122,123]. ...
... Комментарии: целый ряд клинико-эпидемиологических исследований продемонстрировал увеличение риска ОА [122,124] при низком уровне витамина D 3 : риск ОА (ОР, 95% ДИ) -1,4 (1,9), риск ОА при высоком уровне ПТГ (ОР, 95% ДИ) -3,2 (1,1). Данное обстоятельство имеет понятное патофизиологическое объяснение. ...
Background : Falls in elderly–a multifactorial syndrome. One of the modifiable factors is polypharmacy. STOPP/START criteria are used for correction of polypharmacy in geriatrics.
Aim : Assessment of the prevalence of polypharmacy, analysis and correction of pharmacotherapy using STOPP/START criteria in patients with falls.
Materials and methods : The study included 655 patients hospitalized in the geriatric department over 60 years of age, who were divided into two groups. Group 1 (n=332, 50.7%)–patients with 1 or more falls, group 2 (n=323,49.3%)–patients without falls. The analysis of the received therapy before hospitalization was performed. After that, based on the indications, contraindications and STOPP/START criteria, drug therapy was corrected in patients with falls.
Results : Patients of group 1 took 4.5±2.18 drugs, group 2–4.3±2.6. Polypharmacy was diagnosed in 150 (45.2%) patients with falls and in 122 (37.8%) patients without falls. Patients with falls were more likely to receive sleeping pills, NSAIDs. Univariate analysis showed that falls were associated with NSAIDs (OR 2.15, 95% CI 1.38–3.35, p=0.001) and sleeping pills (OR 2.03, 95% CI 1.02–4.02, p=0.047). An audit and correction of therapy was performed: in 108 (32.5%) patients the number of prescribed drugs was reduced. Patients with falls were prescribed statins, antidementia drugs, anticonvulsants and antidepressants as components of therapy for chronic pain syndrome, chondroitin sulfate and glucosamine sulfate for the treatment of osteoarthritis, calcium and antiresorbtive therapy, antianemic drugs, vitamin D. Antiplatelet agents, digoxin, sleeping pills and NSAIDs were less frequently prescribed. STOPP/START criteria and their frequency in patients with falls were analyzed. 141 cases of potentially non-recommended but prescribed medications were identified. STOPP criteria were for the administration of NSAIDs (n=53, 37.6%) and acetylsalicylic acid (n=62, 44%). There were 458 cases of potentially recommended but not prescribed medications. The most common START criteria were not for the administration of vitamin D and statins.
Conclusion . Half of elderly patients with falls have polypharmacy. These patients are more likely to take sleeping pills and NSAIDs. STOPP criteria most often concerned the appointment of NSAIDs and acetylsalicylic acid, and the START criteria revealed the absence of the appointment of vitamin D and statins.
... 6 However a number of other studies have indicated varying results on evaluating the effects of vitamin D in states of chronic pain. 18 Even though Pain is a highly varying phenomenon, in our study maximum effort was made to assess patients with no previous history of trauma or invasive dental treatment. The underlying vitamin D levels of patients seeking orthodontic treatment need to be assessed in a greater sample of various populations. ...
... Poor body vitamin D status may represent an important risk factor for development and/or maintenance of both acute and chronic pain in various nonspecific musculoskeletal pain [98]. More recent evidence suggests that deficiency of vitamin D is linked to a higher prevalence of musculoskeletal pain [99], chronic pain [100], failed back surgery syndrome (FBSS) [101], neuropathic pain [102], fibromyalgia [103], OA [104] and rheumatoid arthritis [105]. On the other hand, supplementation of vitamin D has been found to improve pain in ambulatory subjects with nonspecific musculoskeletal pain [106], fibromyalgia [107], knee OA [108,109] and in palliative care [110]. ...
Introduction:
The present paper focuses on the possible contribution of food compounds to alleviate symptomatic pains. Chronic pain can more easily be linked to anticipatory signals such as thirst and hunger than it is to sensory perceptions as its chronicity makes it fall under the behavioural category rather than it does senses. In fact, pain often negatively affects one's normal feeding behavioural patterns, both directly and indirectly, as it is associated with pain or because of its prostrating effects.
Nutritional compounds for pain:
Several nutraceuticals and Foods for Special Medical Purposes (FSMPs) are reported to have significant pain relief efficacy with multiple antioxidant and anti-inflammatory properties. Apart from the aforementioned properties, amino acids, fatty acids, trace elements and vitamins may have a role in the modulation of pain signals to and within the nervous system.
Conclusion:
In our opinion, this review could be of great interest to clinicians, as it offers a complementary perspective in the management of pain. Trials with well-defined patient and symptoms selection and a robust pharmacological design are pivotal points to let these promising compounds become better accepted by the medical community.
... Socioeconomic background also is a key risk factor with those that are less economically advantaged experiencing more chronic pain, and the severity is worse in people who are of low socioeconomic status (19). Other lifestyle risk factors include work stress (20), unemployment (21), smoking habits (22), alcohol use (23), lack of physical activity (24), and even lack of sunshine (25). ...
Reclassification of chronic pain as a disease may be helpful because patients with chronic pain require significant treatment and rehabilitation with a clear diagnosis. This can help address critical factors, including suffering, quality of life, participation, and with family and social life, which continue to become more important in evaluating the quality of the health care we give our patients today. During the past decade of the opioid epidemic, methadone was the primary treatment for opioid addiction until buprenorphine was approved. Buprenorphine’s high-affinity partial agonist properties make it a good alternative to methadone due to lower abuse potential and safer adverse effect profile while maintaining significant efficacy. Expanded out-patient prescribing options has permitted physician and physician extenders, such as Physician Assistants and Nurse Practitioners, to treat these patients that otherwise would have been required to utilize methadone. With unique pharmacological properties, buprenorphine is a safe and effective analgesic for chronic pain. The literature for buprenorphine shows great potential for its utilization in the treatment of chronic pain.
Introduction: The study was planned to investigate memory-enhancing, anti-inflammatory, and antiaging potential of cannabidiol (CBD) on vitamin D3 deficient diet (VDD)-induced rats. Materials and Methods: Cytochrome P-450 enzymes were analyzed by RT-PCR method and others biomarkers by enzyme-linked immunosorbent assay. Results: CYP2R1 and CYP27B1-mRNA were significantly increased by 39.29 and 38.37%, respectively, while; CYP24A1-mRNA was significantly reduced by 21.39% compared to VDD. Vitamin D3 receptor protein expression was significantly increased by 148.3%, 60.48%, and 142.03% in liver, kidney, and brain, respectively, compared to VDD group. Vitamin D3 metabolites and serotonin were significantly increased more than 60% and 100%, respectively, compared to VDD. Spatial memory (in terms of total distance, escape latency) and pain score were improved compared to VDD. Cytokines were significantly reduced than VDD. Besides, levels of superoxide dismutase (49.61%), glutathione peroxidase (178.87%), acetylcholine (25.40%), and klotho (145.57%) were significantly increased than VDD. Conclusions: Study findings supported that CBD interacts with CYP2R1, CYP27B1, CYP24A1, and vitamin D receptors, resulting in increased vitamin D3 metabolites, which improved memory, pain tolerance, reduced inflammation, and aging through modulating antioxidative enzymes, cytokines, and neurotransmitters in VDD-induced rats.
Objective: To demonstrate the prevalence of vitamin D deficiency in patients with chronic diseases like Diabetes and Hypertension presenting to medicine clinic Methods: It was an observational and Cross-Sectional study. The data was collected from patients visiting the Medicine clinic in Bahria International Hospital, Lahore from June 2017 to March 2018. A total of 115 patients were included in this study with a convenient sampling technique used to reach outpatients with a history of diabetes and hypertension. The data was analyzed the data through descriptive statistics and represented in the form of figures, tables frequencies, and percentages. Results: Retrospectively 115 patients were analyzed. Patients with level <30ng/ml were considered deficient. We found 112/115 patients with vitamin D deficiency i.e. with levels <30ng/ml. Females were more affected (n= 69) than males (n=46). Conclusion Present study concludes that vitamin D deficiency is still an under-diagnosed and underestimated problem as it is more common in individuals with chronic diseases like Diabetes and Hypertension.
Research has implicated immune system inflammation as an underlying etiology of multi-symptom illnesses, and vitamin D has been shown to have a significant role in immune system function. In this retrospective review performed on the medical charts of service members who presented with signs and symptoms of multi-symptom illnesses, we focused on serum 25(OH)D3 levels and looked for associations of vitamin D status (deficient, insufficient, and normal) with age (20–31 years versus 31–56 years) and deployment status (war zones versus other). Two groups (U.S. Marines and Navy Sailors) were sampled and both showed high incidences of below normal vitamin D levels. However, with the Marines, age-related differences in serum levels (p = 0.009) were found only among those who deployed to Iraq/Afghanistan in comparison to those in non-combat locations. The comparison within the Navy sample showed that mobilized sailors had lower 25(OH)D3 levels than the group that did not deploy (p = 0.04). In addition, 100% of the sailors who deployed had below normal levels versus only 33% in the cadre group. The data suggest that personnel returning from a war zone with signs of early multi-symptom illness should be checked for low vitamin D status.
Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800–1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations.
Recent evidence suggests that vitamin D intakes above current recommendations may be associated with better health outcomes. However, optimal serum concentrations of 25-hydroxyvitamin D [25(OH)D] have not been defined. This review summarizes evidence from studies that evaluated thresholds for serum 25(OH)D concentrations in relation to bone mineral density (BMD), lower-extremity function, dental health, and risk of falls, fractures, and colorectal cancer. For all endpoints, the most advantageous serum concentrations of 25(OH)D begin at 75 nmol/L (30 ng/mL), and the best are between 90 and 100 nmol/L (36-40 ng/mL). In most persons, these concentrations could not be reached with the currently recommended intakes of 200 and 600 IU vitamin D/d for younger and older adults, respectively. A comparison of vitamin D intakes with achieved serum concentrations of 25(OH)D for the purpose of estimating optimal intakes led us to suggest that, for bone health in younger adults and all studied outcomes in older adults, an increase in the currently recommended intake of vitamin D is warranted. An intake for all adults of > or =1000 IU (25 microg) [DOSAGE ERROR CORRECTED] vitamin D (cholecalciferol)/d is needed to bring vitamin D concentrations in no less than 50% of the population up to 75 nmol/L. The implications of higher doses for the entire adult population should be addressed in future studies.
To determine the prevalence of hypovitaminosis D in primary care outpatients with persistent, nonspecific musculoskeletal pain syndromes refractory to standard therapies.
In this cross-sectional study, 150 patients presented consecutively between February 2000 and June 2002 with persistent, nonspecific musculoskeletal pain to the Community University Health Care Center, a university-affiliated inner city primary care clinic in Minneapolis, Minn (45 degrees north). Immigrant (n = 83) and nonimmigrant (n = 67) persons of both sexes, aged 10 to 65 years, from 6 broad ethnic groups were screened for vitamin D status. Serum 25-hydroxyvitamin D levels were determined by radioimmunoassay.
Of the African American, East African, Hispanic, and American Indian patients, 100% had deficient levels of vitamin D (< or = 20 ng/mL). Of all patients, 93% (140/ 150) had deficient levels of vitamin D (mean, 12.08 ng/mL; 95% confidence interval, 11.18-12.99 ng/mL). Nonimmigrants had vitamin D levels as deficient as immigrants (P = .48). Levels of vitamin D in men were as deficient as in women (P = .42). Of all patients, 28% (42/150) had severely deficient vitamin D levels (< or = 8 ng/mL), including 55% of whom were younger than 30 years. Five patients, 4 of whom were aged 35 years or younger, had vitamin D serum levels below the level of detection. The severity of deficiency was disproportionate by age for young women (P < .001), by sex for East African patients (P < .001), and by race for African American patients (P = .006). Season was not a significant factor in determining vitamin D serum levels (P = .06).
All patients with persistent, nonspecific musculoskeletal pain are at high risk for the consequences of unrecognized and untreated severe hypovitaminosis D. This risk extends to those considered at low risk for vitamin D deficiency: nonelderly, nonhousebound, or nonimmigrant persons of either sex. Nonimmigrant women of childbearing age with such pain appear to be at greatest risk for misdiagnosis or delayed diagnosis. Because osteomalacia is a known cause of persistent, nonspecific musculoskeletal pain, screening all outpatients with such pain for hypovitaminosis D should be standard practice in clinical care.
INTRODUCTION AND AIMS: Interleukin-1β (IL-1β) is an important inflammatory mediator of immune complex-induced glomerulonephritis (GN). As IL-1β
is activated by Caspase 1 in an inflammasome-dependent intracellular process, we examined the functional role of the inflammasome
components Nlrp3 and its adapter molecule Asc in autologous murine nephrotoxic serum nephritis (NTN), a model of immune complex-mediated
GN.
METHODS: NTN was induced in wild-type, Nlrp3- and Asc-deficient C57BL/6 mice after preimmunisation with rabbit IgG. After 21 days
functional parameters (serum urea, total serum protein, serum cholesterol, albuminuria), renal histology and renal leukocyte
infiltrates were compared between the three groups. Moreover, cellular and humoral immune responses against rabbit IgG were
analysed.
RESULTS: In comparison to wild-type, Nlrp3 knockout mice revealed significantly lower serum urea levels and developed a less pronounced
nephrotic syndrome (less hypoproteinemia, hypercholesterolemia, and albuminuria). Consistently, renal leukocyte infiltrates
were significantly decreased in Nlrp3-deficient mice compared to wild-type. The reductions in renal leukocyte counts were
45% for CD45+ leukocytes, 50% for CD4+ T-cells, 40% for CD8+ T-cells, 39% for CD11c+ dendritic cells, and 50% for F4/80+ mononuclear
phagocytes. The reduced accumulation of renal leukocytes correlated with a significantly decreased expression of renal mRNA
for inflammatory chemokines and cytokines like Ccl2, Ccl5, Cxcl10, Ccr6, Tnf, Inf-γ, and IL-1β.
In contrast, NTN was not attenuated in Asc-deficient mice. Functional parameters and leukocyte infiltration were comparable
between Asc knockout mice and wild-type controls.
Analysis of systemic immune responses revealed a decreased cellular activation of Nlrp3-deficient splenocytes after re-stimulation
with rabbit-IgG (reduced surface expression of CD69 on CD4+ T-cells, less secretion of Inf-γ). However, humoral immunity was
exacerbated in Nlrp3-deficient mice, as indicated by increased autologous anti rabbit-IgG serum titers. Asc knockout mice
also demonstrated an attenuated cellular immune response, with humoral immune responses being comparable to those of wild-type
controls.
CONCLUSIONS: In summary, these results identify Nlrp3 as an important pro-inflammatory mediator of immune complex glomerulonephritis.
Surprisingly, we could demonstrate an inflammatory function of Nlrp3 independently of its adapter molecule Asc. Thus, therapeutic
blockade of Nlrp3 receptors, but not Asc may be a new strategy in the treatment of immune complex nephritis.