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Vitamin D Deficiency and Pain: Clinical Evidence of Low Levels of Vitamin D and Supplementation in Chronic Pain States

DOI:10.1007/s40122-015-0036-8
Authors:
Elspeth Shipton at University of Notre Dame Australia
Elspeth Shipton
Edward Shipton at University of Otago
Edward Shipton
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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.
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... Estudios in vitro revelan que la vitamina D inhibe la síntesis de Prostaglandina E2 (PGE2) (3). Tanto estudios observacionales como intervencionistas indican que la vitamina D puede tener un papel en la intensidad del dolor y en su tratamiento en diferentes contextos clínicos (4)(5)(6)(7)(8)(9)(10). ...
... Este hallazgo ha impulsado la realización de múltiples ensayos clínicos aleatorizados en distintas poblaciones de pacientes con dolor crónico. Sin embargo, a pesar de estos datos, tres metanálisis de ensayos clínicos aleatorizados (ECA) comparados con placebo no pudieron establecer una correlación entre la suplementación con vitamina D y la reducción del dolor (8,41,42). En contraste, una reciente revisión sistemática de ECA publicados (no incluidos en los tres metaanálisis anteriores) concluyó que la suplementación con vitamina D lleva a una disminución significativamente mayor en el puntaje de dolor en comparación con el placebo en pacientes con dolor crónico (43). En el año 2015, se publicó una revisión de Cochrane con el propósito de evaluar la eficacia y seguridad de la suplementación con vitamina D en pacientes aquejados de dolor crónico. ...
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... There is biological evidence that vitamin D deficiency negatively affects skeletal muscle function through oxidative stress and mitochondrial dysfunction [4]. Vitamin D also acts as a neuroactive steroid that modulates neuronal excitability in the pain pathway [1]. Hence, vitamin D deficiency may result in a central neuronal hypersensitivity state associated with chronic pain. ...
... Vitamin D is an essential nutrient mainly synthesized endogenously with sunlight exposure [1]. It has a significant role in the metabolism of bone and skeletal muscle. ...
Prevalence and risk factors of vitamin D deficiency among patients with chronic myofascial pain syndrome: a cross-sectional study
Article
Full-text available
  • Nov 2023
Background Myofascial pain syndrome (MPS) is a common muscle condition characterized by painful trigger points. Vitamin D deficiency has been recognized as a precipitating factor of MPS. The present study aimed to determine the prevalence and risk factors of vitamin D deficiency in patients with chronic MPS. Methods A cross-sectional study was conducted, using a structured face-to-face interview to collect demographic information, clinical characteristics, pain duration and location, as well as the bodily pain subscale of SF36 and EQ-5D-5 L. The Elecsys vitamin D total II assay was used to measure serum total 25-hydroxyvitamin D level. Results Of 120 participants, vitamin D insufficiency (20 to 29.9 ng/ml) and deficiency (< 20 ng/ml) were 47.5% (95% CI: 38.3–56.8%) and 34.2% (95% CI: 25.8–43.4%), respectively. The adjusted odds ratios for vitamin D deficiency of participants aged < 45 years and who reported having ≤ 15 min sunlight exposure per day were 3.5 (95% CI: 1.54 to 7.98) and 2.38 (95% CI: 1.05 to 5.26), respectively. The bodily pain score (r = − 0.02, P = 0.86) and EQ-5D-5 L utility (r = 0.04, P = 0.66) did not significantly correlate with vitamin D levels. Conclusion Approximately one third of patients with chronic MPS had vitamin D deficiency. Age < 45 years and sunlight exposure ≤ 15 min/day were identified as potential risk factors for vitamin D deficiency in MPS patients.
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... Similarly, some patients with FM may have health problems associated with low levels of vitamin D (Bjørklund et al. 2018). It is important to emphasize that deficiency of vitamin D is related to the development of myopathy and severe muscle weakness, depression, and anxiety (Shipton and Shipton 2015), similar to the complaints of patients with COVID-19 and FM. In this way, therapy with vitamin D could improve the FM patient's quality of life (Bjørklund et al. 2018), reduce the progression of COVID-19 and enhance the survival rate (Forcados et al. 2021). ...
Could the fibromyalgia syndrome be triggered or enhanced by COVID-19?
Article
Full-text available
Fibromyalgia (FM) is a complex disease with an uncertain aetiology and intricate pathophysiology. Although its genesis is not fully explained, potential environmental factors, such as viral infections might trigger FM or worsen patients' clinical outcomes. The SARS-CoV-2 virus may affect central and peripheral nervous systems, leading to musculoskeletal, neurological, and psychological disturbances. These symptoms might persist at least 12 months beyond the recovery, often referred to as post-COVID syndrome, which resembles FM syndrome. In this sense, we argued the potential consequences of COVID-19 exclusively on FM syndrome. First, we have described post-COVID syndrome and its painful symptoms. Afterwards, we argued whether FM syndrome could be triggered or enhanced by COVID-19 infection or by numerous and persistent stressors imposed daily by the pandemic setting (isolation, uncertainty, depression, mental stress, generalized anxiety, and fear of the virus). In addition, we have demonstrated similarities between pathophysiological mechanisms and cardinal symptoms of FM and COVID-19, speculating that SARS-CoV-2 might represent a critical mediator of FM or an exacerbator of its symptoms once both syndromes share similar mechanisms and complaints. Therefore, pharmacologic and non-pharmacological approaches commonly used to treat FM could serve as strategic therapies to attenuate painful and neurological manifestations of post-COVID syndrome. Although it is still theoretical, clinicians and researchers should be alert of patients who develop symptoms similar to FM or those who had their FM symptoms increased post-COVID to manage them better. Graphical Abstract
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... Moreover, both clinical and experimental studies have shown that vitamin D deficiency causes an increase in pain sensitivity as a result of hyperinnervation and hypersensitivity in nerve fibers [9,20]. It has also been reported that low vitamin D levels cause increased central neuronal sensitivity in chronic painful diseases such as fibromyalgia and migraine [9,21]. All these mechanisms show that vitamin D has an analgesic effect on various types of pain. ...
Serum vitamin D levels are associated with acute postoperative pain and opioid analgesic consumption after laparoscopic cholecystectomy: a strobe compliant prospective observational study
Article
Full-text available
  • Feb 2023
Background/aim: In this prospective observational study, we aimed to evaluate the relationship between serum levels of vitamin D and acute postoperative pain scores, as well as opioid analgesic consumption in patients undergoing laparoscopic cholecystectomy. Materials and methods: The study was performed in the Medical Faculty Hospital, from April 2020 to April 2021. Postoperative visual analog scale (VAS) pain scores, total tramadol consumption, number of requests on patient-controlled analgesia (PCA) were compared between the vitamin D deficient (≤20 ng/mL; n = 25) and vitamin D nondeficient (>20 ng/mL; n = 55) groups at five time points (T0: in the recovery room, T1: 1st hour in the ward, T2: 6th hour, T3: 12th hour, and T4: 24th hour). Results: Postoperative VAS pain scores were similar in the vitamin D deficient group at all time points (T0-4), but differed significantly only at the T-0 time point (p = 0.020). The mean cumulative tramadol consumption was significantly higher in the vitamin D deficiency group than in the nondeficiency group (p = 0.005). Vitamin D levels were lower in patients with VAS ≥ 4 at the postoperative T-0 time point (p = 0.009). In the multivariate linear regression analysis, 15.7% of cumulative tramadol consumption was due to vitamin D deficiency (β = –0.188). Conclusion: Our study shows that preoperative low vitamin D level was associated with an increase in acute postoperative pain scores and consumption of opioid analgesics in patients undergoing laparoscopic cholecystectomy. Our findings may be useful for postoperative pain management in patients with vitamin D deficiency.
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... A comprehensive review of eight RCTs concluded there were not sufficient data to suggest the use of vitamin D outside chronic pain states, and that further large-scale RCTs were required in this regard. 60 Muscogiuri et al. 11 reported that currently available evidence does not support the role of vitamin D in other chronic diseases except for bone health; however, they highlighted the need for vitamin D supplementation in vitamin D deficiency to reduce the risk of developing chronic disease. In recent narrative 17,22,23,61 and systematic reviews, 26,62,63 sufficient evidence was not found for the use of vitamin D supplementation in chronic pain conditions or CWP/FM and no causative relationship was suggested; further studies were suggested to prove possible benefits in some specific painful conditions. ...
Vitamin D Deficiency and Chronic Widespread Pain
Article
  • Aug 2017
Vitamin D acts as a steroid hormone possessing important functions in calcium and phosphorus balance and bone health. The presence of vitamin D receptors (VDRs) in many tissues in the human body shows that this vitamin might have effects other than its role in maintaining bone health. Hence, many studies in the last two decades have reported an association between vitamin D deficiency and many musculoskeletal and extra-skeletal diseases. Despite the presence of clear evidence suggesting a causative relationship between musculoskeletal pain and osteomalacia developing as a result of long-term and severe vitamin D deficiency, a putative relationship between vitamin D deficiency and chronic widespread pain (CWP) has recently been an exciting area of discussion. The hypothetical role of vitamin D in the pathophysiology of pain, the availability of VDRs in the muscle tissue and central nervous system, particularly in the hypothalamus, and the reports on the development of muscle hypersensitivity associated with vitamin D deficiency, have provided a basis for a putative relationship between CWP and vitamin D status. This review will discuss these two problems that commonly occur within the general population, and endeavour to reveal this relationship in light of currently available studies.
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... These results are supported by other research findings where mild vitamin d deficiency was associated with knee joint pain and mild vitamin D deficiency. 32 Furthermore, an Indian study investigated the association between vitamin D levels and arthritis and reported that serum vitamin D levels were significantly lower in patients with arthritis than in healthy controls. The study concludes that vitamin D deficiency is one of the causes contributing to the worsening and raising the susceptibility of Arthritis due to vitamin D's immunomodulatory activity. ...
Vitamin D Deficiency Association with Comorbid Diseases in Palestine: “A Cross-Sectional Observation Study”
Article
Full-text available
  • Nov 2022
Background: Vitamin D deficiency (VDD) is a global health concern. This study aimed to determine the prevalence of vitamin D deficiency and its associated comorbidities in Palestine, such as diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular and autoimmune diseases. Methods: A retrospective, descriptive study retrieved medical data from the Nat Health insurance processor database from 2014 to 2020. Patient information included age, sex, vitamin D laboratory order, symptoms, and comorbidities. This study included patients prescribed vitamin D at a dose of 50000IU for vitamin D deficiency confirmed by a serum vitamin D laboratory test. The collected data were analyzed using IBM SPSS. In addition, a chi-square test was conducted to assess the association between vitamin D deficiency, symptoms, and comorbidities. Results: Data of 3011 patients were collected; 639 patients were diagnosed with osteoporosis, and 39 patients prescribed vitamin D without a laboratory test were excluded. Approximately, 1837 (78%) participants had vitamin D deficiency. A total of 1330 women (81.3%) were significantly more likely to have vitamin D deficiency than males, 507 (72.7%; P < 0.001). Joint pain, back pain, and cervicalgia were significantly associated with vitamin D deficiency (P < 0.001). Asymptomatic participants (2.1%) were significantly less likely to have vitamin D deficiency than symptomatic participants (9.5%, p < 0.001). Hypothyroidism is significantly associated with vitamin D deficiency (p = 0.048). Conclusion: In this retrospective study, the prevalence of vitamin D was high and alarming. There was a significant association between VDD, patients who presented with back pain, arthritis, and cervicalgia symptoms, and patients diagnosed with hypothyroidism. Therefore, health initiative programs are warranted to increase awareness regarding screening, prevention, and treatment. Further studies are needed to confirm the relationship between vitamin D supplementation and the reduced risk of comorbid diseases.
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... According to previous studies, patients with lower vitamin D levels (<30 nmol/L) are more likely to benefit from vitamin supplements, thus indicating that these patients may suffer from more severe pain. 21,22 Therefore, the connection between vitamin D levels and postoperative pain may be more obvious in patients with severer pain and lower vitamin D levels. ...
Preoperative Vitamin D Level is Associated with Acute Pain After Video-Assisted Thoracoscopic Surgery: A Retrospective Cohort Study
Article
Full-text available
  • Oct 2022
Purpose: Low vitamin D levels have been associated with musculoskeletal pain, cancer pain, chronic postoperative pain, and post-traumatic pain. However, their association with postoperative pain after video-assisted thoracoscopic surgery has not been explored. The aim of this study was to examine the association between vitamin D levels and postoperative pain after video-assisted thoracoscopic surgery. Patients and methods: This study enrolled 194 adult patients who underwent elective non-cardiac thoracic surgery in Shanghai Pulmonary Hospital from February 2021 to June 2021. Following application of the exclusion criteria, 135 patients who underwent video-assisted thoracoscopic surgery were included in the final analysis. The primary outcome was the incidence of acute postoperative moderate-severe pain. Secondary outcomes included C-reactive protein (CRP), interleukin (IL)-1, IL-6, and tumor necrosis factor-α levels in the immediate postoperative (48 hours) period, as well as pain scores at 3 months after surgery. A multivariable logistic regression model was used to analyze the association between vitamin D levels and acute postoperative moderate-severe pain. Results: Among 135 patients, 54.1% were categorized as having a low vitamin D level (<30 nmol/L). On multivariable analysis, patients with a low 25-hydroxy-vitamin D (25[OH]D) level had a higher risk of postoperative moderate-severe pain (odds ratio, 2.44; 95% confidence interval, 1.181-5.041; P = 0.016) when compared to patients with a sufficient 25(OH)D level. Static and dynamic pain scores at 3 months after surgery, as well as serum levels of CRP, IL-1, IL-6, and tumor necrosis factor-α were not significantly different between patients with low and sufficient 25(OH)D levels. Conclusion: Patients with low vitamin D levels are at a higher risk of acute moderate-severe pain after video-assisted thoracoscopic surgery. Trial registration: http://www.chictr.org.cn, ChiCTR2100052380.
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Association between serum 25-hydroxyvitamin D and osteoarthritis: A national population-based analysis of NHANES 2001–2018
Article
Full-text available
  • Feb 2023
Background: Previous studies have not provided a consensus on the effect of serum 25-hydroxyvitamin D [25(OH)D] on osteoarthritis (OA). We aimed to evaluate the association using a large, nationally representative sample. Methods: The cross-sectional data were obtained from the 2001 to 2018 National Health and Nutrition Examination Survey (NHANES). Individuals aged ≥40 years who had information of serum 25(OH)D, self-report OA, and related covariates were included. Multivariable logistic regression analysis was employed to assess the association between serum 25(OH)D and osteoarthritis. Results: Among the 21,334 participants included (weighted mean age, 56.9 years; 48.5% men), the proportion of participants with high serum 25(OH)D concentrations (≥100 nmol/L) increased significantly from 4.2% in 2001-2006 to 18.8% in 2013-2018. Higher serum 25(OH)D levels were associated with more osteoarthritis prevalence in fully adjusted model (odd ratio [OR] 1.25 [95% CI: 1.10, 1.43] for the 50-75 nmol/L group; OR 1.62 [95% CI: 1.42, 1.85] for the 75-100 nmol/L group; OR 1.91 [95% CI: 1.59, 2.30] for the ≥100 nmol/L group; with <50 nmol/L group as the reference) (p < 0.001 for trend). The association was consistent across several sensitivity analyses, including propensity score methods and excluding participants who had received vitamin D supplement. In subgroup analysis, the OR for the association increased significantly with body mass index (BMI) (BMI < 25 kg/m2, 1.01 [95% CI: 1.04, 1.08]; BMI 25-30 kg/m2, 1.05 [95% CI: 1.01, 1.08]; BMI ≥ 30 kg/m2, 1.10 [95% CI: 1.06, 1.13]; p = 0.004 for interaction). Conclusion: There was a positive correlation between serum 25(OH)D and osteoarthritis with a possible modification by BMI. Our finding raises concerns about the potential adverse effects of high serum 25(OH)D on osteoarthritis, particularly among obese individuals. More well-designed studies are still needed to validate our findings in future.
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Association between urinary phthalate levels and chronic pain in US adults, 1999–2004: A nationally representative survey
Article
Full-text available
  • Feb 2023
Introduction Chronic pain is a public health concern throughout the world. Ascertaining and managing its risk factors helps develop well-directed treatment plans and prevention strategies. Phthalates (PAEs) exposure leads to various health problems. The present study aims to explore the potential correlation between urinary PAEs metabolites and chronic pain in adults. Methods The study population data were extracted from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2004 in the United States. Seven urinary PAEs metabolites were used to assess long-term PAEs exposure. The assessment of chronic pain was determined by a self-report questionnaire. Weighted analyses were conducted to consider the complex sampling design. Models were adjusted by demographic data and lifestyle factors. Urinary PAEs metabolites were assessed as both continuous and categorical variables. Tertile 1 was considered as the reference. Stratified analyses were performed by gender and pain site. All data analyses were conducted with STATA, version 15.1. P < 0.05 was considered with statistical significance. Results A total of 4,196 participants were considered in our final analysis. Chronic pain prevalence reached 52.19% ( n = 2,138) among the participants, with women accounting for a large proportion (57.75% vs. 42.25%). After multivariable logistic regression analysis, a higher prevalence of chronic pain was observed among participants in the third tertile of mono-(2-ethyl)-hexyl phthalate (MEHP) (OR = 1.23, 95% CI = 1.02–1.48, P = 0.034) and mono-benzyl phthalate (MBzP) (OR = 1.28, 95% CI = 1.04–1.58, P = 0.022) in our adjusted model. The logtransformed concentration of MBzP also showed a significant association with chronic pain prevalence (OR = 1.09, 95% CI = 1.01–1.18, P = 0.036) in the adjusted model. In further analysis, the positive correlations of urinary phthalate metabolites with chronic pain remained robust when stratified by gender and chronic pain site. Conclusions Our findings presented a positive correlation between urinary PAEs metabolites and chronic pain among adult participants, and more causal research should be conducted to ascertain the interactions between the two and to expound their underlying mechanisms.
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Vitamin D deficiency: a worldwide problem with health consequences
Article
  • Apr 2008
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.
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Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes (vol 84, pg 18, 2006)
Article
  • Sep 2007
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.
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Prevalence of Severe Hypovitaminosis D in Patients With Persistent, Nonspecific Musculoskeletal Pain
Article
  • Dec 2003
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.
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