Vitamin D deficiency is associated with anxiety and depression in fibromyalgia
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- Armstrong, D.J., Meenagh, G.K., Bickle, I. et al. Clin Rheumatol (2007) 26: 551. doi:10.1007/s10067-006-0348-5
Fibromyalgia is a complex problem in which symptoms of anxiety and depression feature prominently. Low levels of vitamin D have been frequently reported in fibromyalgia, but no relationship was demonstrated with anxiety and depression. Seventy-five Caucasian patients who fulfilled the ACR criteria for fibromyalgia had serum vitamin D levels measured and completed the Fibromyalgia Impact Questionnaire (FIQ) and Hospital Anxiety and Depression Score (HADS). Deficient levels of vitamin D was found in 13.3% of the patients, while 56.0% had insufficient levels and 30.7% had normal levels. Patients with vitamin D deficiency (<25 nmol/l) had higher HADS [median, IQR, 31.0 (23.8–36.8] than patients with insufficient levels [25–50 nmol/l; HADS 22.5 (17.0–26.0)] or than patients with normal levels [50 nmol/l or greater; HADS 23.5 (19.0–27.5); Kruskal–Wallis ANOVA on ranks p<0.05]. There was no relationship with global measures of disease impact or musculoskeletal symptoms. Vitamin D deficiency is common in fibromyalgia and occurs more frequently in patients with anxiety and depression. The nature and direction of the causal relationship remains unclear, but there are definite implications for long-term bone health.
Fibromyalgia (FMS) is a common condition characterized by widespread pain, multiple tender points, fatigue, poor sleep pattern and depression . It predominantly affects women. Various studies have addressed the issue of bone health in FMS, but findings have been inconsistent. Fibromyalgia patients in Scotland had slightly lower bone mineral density (BMD) at the mid-distal forearm compared with controls, but overall BMD was comparable with healthy individuals . In contrast, 24 Canadian FMS patients had significantly lower BMD at the lumbar spine than age-matched controls, but only at the femoral neck in older individuals . Danish patients had no difference in BMD in any area compared with controls, but those with more disabling FMS appeared to have lower BMD . It was suggested that up to 50% of Caucasian FMS patients might have low levels of vitamin D, although a link with “disease activity” was hard to demonstrate, and that vitamin D insufficiency is common in South Asians living in the UK who suffer from widespread pain . Vitamin D deficiency has also been linked to depression and conditions such as Seasonal Affective Disorder (SAD).
In this study, we measured vitamin D levels in Caucasian patients with primary fibromyalgia and compared these with scores of fibromyalgia impact and also with assessments of anxiety and depression.
Materials and methods
Seventy-five consecutive White Caucasian patients (5 men and 70 women, median age 50.0 years, range 21–75 years), who fulfilled the ACR criteria for fibromyalgia  and who attended a rheumatology outpatient clinic, had serum vitamin D levels measured and completed the Fibromyalgia Impact Questionnaire (FIQ)  and Hospital Anxiety and Depression Score (HADS)  as part of their routine assessment. As these patients had all been referred to a rheumatology clinic and, therefore, musculoskeletal symptoms were likely to be prominent, we also recorded separately the individual pain and stiffness components of the FIQ. Prescribed medication was recorded. All samples were collected between October and early April, which corresponds to the winter season in Belfast (latitude 54° 37′N).
Statistical analysis was performed using rank correlation and Wilcoxon tests as appropriate.
Vitamin D assay was performed using a radioimmunoassay kit to detect 25-hydroxylated vitamin D (Immunodiagnostic Sysytems, Boldon, UK).
Seventy-five patients completed the study. Most patients were taking simple analgesia on a PRN basis. Forty percent of the patients were taking amitriptyline at a dose of 10 mg or 20 mg at night, whereas a further 55% of them were taking prescribed antidepressant medication. There was no relationship between vitamin D levels, FIQ score, or HADS and whether the patient was taking antidepressant medication.
Serum vitamin D levels and bone metabolism markers in fibromyalgia patients
Vitamin D level (nmol/l)
Number of patients (%)
Calcium, mmol/l (median, IQR)
Phosphate, mmol/l (median, IQR)
Alk Phos, U/l (median, IQR)
50 or greater
FIQ scores in fibromyalgia patients
Number of patients (%)
Below average disability
70 or greater
The Hospital Anxiety and Depression Score is a validated tool designed for the assessment of mood disorders specifically in the hospital clinic setting. It is scored out of 42. Median score was 26.0 (IQR 18.0–29.0).
There was no statistically significant link between age and FIQ score, HADS, or with the pain or stiffness components of the FIQ score, although the highest FIQ and HADS scores tended to be in the younger patients (data not shown). There was no relationship between age and vitamin D levels.
Fibromyalgia impact questionnaire
An average FIQ of 74.8 indicates a high level of disability among this cohort of patients. There was no significant correlation between FIQ and age or vitamin D levels. Median (IQR) FIQ in vitamin D deficient patients was 78.2 (74.4–90.6) compared with 73.9 (64.4–85.5) in insufficient and 76.7 (68.7–83.9) in normal patients (Kruskal–Wallis analysis of variance on ranks, p=0.11). There was, however, a correlation between FIQ and HADS scores (r=0.55, p<0.01).
Hospital anxiety and depression score
There was a wide variation in HADS, with the highest scores seen in the youngest patients. Patients with vitamin D deficiency (<25 nmol/l) had higher HADS [median, IQR, 31.0 (23.8–36.8)] than patients with insufficient levels [25–50 nmol/l; HADS 22.5 (17.0–26.0)] or than patients with normal levels [50 nmol/l or greater; HADS 23.5 (19.0–27.5)]. A Kruskal–Wallis ANOVA on ranks was performed and confirmed significant differences between the deficient group and each of the other groups (p<0.05).
There was no relationship between vitamin D levels and the anxiety or depression subscales of the HADS (data not shown).
Pain and stiffness
As most of our patients had a strong musculoskeletal component to their disease, we analyzed separately the scores in the pain and stiffness categories of the FIQ. Although vitamin D deficient patients tended to score higher in both categories (9.0 vs 8.0 for pain, 9.5 vs 9.0 for stiffness), there was no statistical significance (p>0.1 for both).
This study has demonstrated high impact and depression scores in the subset of FMS patients referred to secondary care and, although the non-FMS control group was included for direct comparison, a significant proportion of these patients had insufficient or deficient levels of vitamin D. Furthermore, it has demonstrated a link between vitamin D deficiency and anxiety and depression in FMS, which is unrelated to the FIQ score, and has implications for other aspects of patient care, especially long-term bone health. Low levels of vitamin D have been associated with increased bone turnover and increased risk of hip fracture in postmenopausal women, and up to 97% of patients hospitalized with fracture, regardless of age, were found to have levels of vitamin D considered inadequate according to local standards .
Sixty-eight percent of this cohort is defined as “severely afflicted” by the FIQ, which is higher than some recent comparable studies in which the average FIQ score was between 60 and 65 [2, 10]. This might reflect referral bias, as all of our subjects had been recently referred from primary care with “active” FMS, whereas other studies have sought patients in the community with a varying degree of FMS-related disability.
The most important question raised by this study is the nature and direction of the causal relationship between vitamin D levels and anxiety and depression in FMS. There is evidence for both sides of the argument. In the first instance, it might be that FMS patients with high levels of anxiety and depression are less exposed to sunlight and take less vitamin D in the diet; therefore, it is the fibromyalgia which “causes” the low levels of the vitamin. Fibromyalgia patients are less mobile and have reduced functional ability as compared with controls , and it has been shown that increased stress and anxiety levels correlate well with the inability to maintain aerobic exercise in FMS , thus decreasing the chances of outdoor sunlight exposure. In addition, intake of vitamin D may be suboptimal in FMS. Depression is associated with poor quality diet and obesity, which further reduces mobility, and adherence to vegetarian or vegan-type diets, with little vitamin D, is a popular alternative therapy option in fibromyalgia.
It is also possible that vitamin D has a direct effect on the mood. The symptoms and signs of clinical vitamin D deficiency are not dissimilar in some respects to FMS, and vitamin D given in a placebo-controlled double-blind trial to SAD sufferers improved the effect . Vitamin D treatment of vitamin D-deficient FMS patients was also suggested to improve subjective global symptomatology in a small group of subjects . Vitamin D receptors are found in neurons, glial cells, and the pituitary gland in the brain , and although their exact function remains unclear, the distribution of 1,25-dihydroxy vitamin D3 receptor suggests that vitamin D may act in a similar fashion to other neurosteroids.
In conclusion, we have shown that the majority of FMS patients referred to a rheumatology clinic have insufficient levels of vitamin D. Although there is no strong correlation between overall fibromyalgia impact and vitamin D levels, there is a clear relationship between low vitamin D levels and high levels of anxiety and depression. Whether vitamin D deficiency contributes to low mood and other symptoms in FMS, or whether it is purely related to reduced sunlight exposure or poor diet, the findings have important implications for bone health and fracture risk in fibromyalgia sufferers.
The authors wish to acknowledge the assistance of Mrs. Norma Parker and Miss Clara Rose Armstrong in the collection and processing of the data.