Vitamin D Status in Rheumatoid Arthritis Patients
Vitamin D Status in Rheumatoid Arthritis Patients
Several studies have confirmed that vitamin D deficiency is common in RA. In our study, a majority of RA and OA patients were vitamin D deficient with no significant difference between examined groups. Recent surveys suggest that at least 80% of the Polish population shows vitamin D deficiency, so supposedly the latitude of our country is the primary determinant of the patients' low vitamin D status. Many studies have demonstrated a negative correlation between serum 25(OH)D concentration and RA activity. In a large cross-sectional study, Rossini et al have found significantly lower 25(OH)D values in patients with active disease, responding poorly to treatment, and with the worst functional state. Haga et al did not find any association between vitamin D concentration and DAS28, but a subpopulation with severe deficiency was characterized by a high percentage of patients with very high disease activity. In a placebo-controlled observational study with high-dose vitamin D supplementation, no benefit in disease activity or patient's global health was confirmed, but the number of participants was small. In a recent study conducted by Higgins et al, DAS28-erythrocyte sedimentation rate was calculated both with and without the patient's rating of their symptoms on the VAS scale. Only the correlation of vitamin D level with VAS was significant, suggesting that vitamin D deficiency simply increases pain perception. In our study, we did not find any correlation of vitamin D level with VAS pain and VAS fatigue, but we have found negative correlation between 25(OH)D and DAS28; however, it was significant only for the patients with active arthritis (DAS28 ≥2.6). Our results are comparable with a study in which 25(OH)D concentration was moderately and inversely associated with DAS28, and no significant associations between 25(OH)D and these variables in patients in remission were found. It has been suggested that 25(OH)D serum concentrations may decrease in the acute-phase response, thereby explaining the low levels in patients with high disease activity. Consequently, low vitamin D level may also be the result of disease activity. In another recent study, there was no correlation between seasonal serum 25(OH)D3 and disease activity in patients with RA; however, the majority of the patients were not vitamin D deficient. The evidence that disease activity correlates with lower 25(OH)D serum levels needs further studies.
There are numerous studies examining the relationship of vitamin D deficiency with different aspects of QoL, but most of them are population-based studies. In the study evaluating the effect of vitamin D supplementation in outpatient veterans, the improvement of sleep, pain, general health, VT, and SF was observed. In a British national community sample of people 65 years or older, 25(OH)D levels correlated negatively with the number of depressive symptoms. Similar findings were reported in studies from Italy and the United States. In Iowa Women's Health Study, the researchers have found overall association between lower vitamin D daily intake and poorer QoL scores, including MH, RE, SF, VT, and GH. However, adding PA to the multivariable model attenuated the overall association, and the significance remained only for MH and SF. In our study, in fact, the level of PA presented the essential difference between vitamin D–sufficient and –deficient patients. Inclusion of the level of PA as a variable has made most of the associations between vitamin D and QoL indices insignificant. Previous studies have indicated an association between physical components of QoL and PA, suggesting that those with lower levels of PA have also lower QoL. In addition, the association between PA and vitamin D was found in a number of studies. The Longitudinal Aging Study Amsterdam study has shown that PA was positively associated with 25(OH)D serum concentration in women. Vitamin D deficiency was associated with worse physical performance. The correlation between vitamin D deficiency and loss of muscle strength and muscle mass was found in a prospective study. The patients with serum 25(OH)D of less than 25.0 nmol/L (10 ng/dL) had significantly lower physical performance than did those with serum 25(OH)D of 25 nmol/L or greater. Vitamin D deficiency in elderly was associated with a worse coordination in women, a slower walking time in men, and with lower strength and aerobic capacity in both sexes. The changes in 25(OH)D level correlated positively with the growth of muscle mass and strength in older adults, even in absence of regular physical exercises. The most relevant changes in physical abilities were observed at 25(OH)D levels between 10 and 30 ng/dL, with the effect threshold of around 40 to 50 ng/dL, above which further improvement of neuromuscular performance was not observed. These studies indicate that PA may lie on the causal pathway between vitamin D status and QoL, so considering PA as an independent factor may be inappropriate.
Our study has several limitations. First, we decided to include in the study only the patients without vitamin D supplementation. Vitamin D supplementation with 1(OH)D (alfacalcidol) was quite popular in Poland, and many RA patients were not sure what kind of substance they had used as vitamin D, so we were unable to exactly evaluate vitamin D status in patients taking different vitamin D metabolites. Second, inclusion of consecutive RA inpatients resulted in presence of a substantial group of early RA patients, which are more likely to have higher disease activity and worse outcomes in most QoL scales. As a result, the most important analyses were performed in a group of 70 patients. The other weakness of our study is that the serum 25(OH)D was measured only once. Furthermore, we did not assess some factors that may alter the association between vitamin D status and MH, such as education, marital and economic status, smoking, and alcohol consumption. Despite this, and probably because of the high prevalence of vitamin deficiency in examined group, we managed to find significant associations between vitamin D status and mental and physical aspects of QoL, as well as with disease activity.
Discussion
Several studies have confirmed that vitamin D deficiency is common in RA. In our study, a majority of RA and OA patients were vitamin D deficient with no significant difference between examined groups. Recent surveys suggest that at least 80% of the Polish population shows vitamin D deficiency, so supposedly the latitude of our country is the primary determinant of the patients' low vitamin D status. Many studies have demonstrated a negative correlation between serum 25(OH)D concentration and RA activity. In a large cross-sectional study, Rossini et al have found significantly lower 25(OH)D values in patients with active disease, responding poorly to treatment, and with the worst functional state. Haga et al did not find any association between vitamin D concentration and DAS28, but a subpopulation with severe deficiency was characterized by a high percentage of patients with very high disease activity. In a placebo-controlled observational study with high-dose vitamin D supplementation, no benefit in disease activity or patient's global health was confirmed, but the number of participants was small. In a recent study conducted by Higgins et al, DAS28-erythrocyte sedimentation rate was calculated both with and without the patient's rating of their symptoms on the VAS scale. Only the correlation of vitamin D level with VAS was significant, suggesting that vitamin D deficiency simply increases pain perception. In our study, we did not find any correlation of vitamin D level with VAS pain and VAS fatigue, but we have found negative correlation between 25(OH)D and DAS28; however, it was significant only for the patients with active arthritis (DAS28 ≥2.6). Our results are comparable with a study in which 25(OH)D concentration was moderately and inversely associated with DAS28, and no significant associations between 25(OH)D and these variables in patients in remission were found. It has been suggested that 25(OH)D serum concentrations may decrease in the acute-phase response, thereby explaining the low levels in patients with high disease activity. Consequently, low vitamin D level may also be the result of disease activity. In another recent study, there was no correlation between seasonal serum 25(OH)D3 and disease activity in patients with RA; however, the majority of the patients were not vitamin D deficient. The evidence that disease activity correlates with lower 25(OH)D serum levels needs further studies.
There are numerous studies examining the relationship of vitamin D deficiency with different aspects of QoL, but most of them are population-based studies. In the study evaluating the effect of vitamin D supplementation in outpatient veterans, the improvement of sleep, pain, general health, VT, and SF was observed. In a British national community sample of people 65 years or older, 25(OH)D levels correlated negatively with the number of depressive symptoms. Similar findings were reported in studies from Italy and the United States. In Iowa Women's Health Study, the researchers have found overall association between lower vitamin D daily intake and poorer QoL scores, including MH, RE, SF, VT, and GH. However, adding PA to the multivariable model attenuated the overall association, and the significance remained only for MH and SF. In our study, in fact, the level of PA presented the essential difference between vitamin D–sufficient and –deficient patients. Inclusion of the level of PA as a variable has made most of the associations between vitamin D and QoL indices insignificant. Previous studies have indicated an association between physical components of QoL and PA, suggesting that those with lower levels of PA have also lower QoL. In addition, the association between PA and vitamin D was found in a number of studies. The Longitudinal Aging Study Amsterdam study has shown that PA was positively associated with 25(OH)D serum concentration in women. Vitamin D deficiency was associated with worse physical performance. The correlation between vitamin D deficiency and loss of muscle strength and muscle mass was found in a prospective study. The patients with serum 25(OH)D of less than 25.0 nmol/L (10 ng/dL) had significantly lower physical performance than did those with serum 25(OH)D of 25 nmol/L or greater. Vitamin D deficiency in elderly was associated with a worse coordination in women, a slower walking time in men, and with lower strength and aerobic capacity in both sexes. The changes in 25(OH)D level correlated positively with the growth of muscle mass and strength in older adults, even in absence of regular physical exercises. The most relevant changes in physical abilities were observed at 25(OH)D levels between 10 and 30 ng/dL, with the effect threshold of around 40 to 50 ng/dL, above which further improvement of neuromuscular performance was not observed. These studies indicate that PA may lie on the causal pathway between vitamin D status and QoL, so considering PA as an independent factor may be inappropriate.
Our study has several limitations. First, we decided to include in the study only the patients without vitamin D supplementation. Vitamin D supplementation with 1(OH)D (alfacalcidol) was quite popular in Poland, and many RA patients were not sure what kind of substance they had used as vitamin D, so we were unable to exactly evaluate vitamin D status in patients taking different vitamin D metabolites. Second, inclusion of consecutive RA inpatients resulted in presence of a substantial group of early RA patients, which are more likely to have higher disease activity and worse outcomes in most QoL scales. As a result, the most important analyses were performed in a group of 70 patients. The other weakness of our study is that the serum 25(OH)D was measured only once. Furthermore, we did not assess some factors that may alter the association between vitamin D status and MH, such as education, marital and economic status, smoking, and alcohol consumption. Despite this, and probably because of the high prevalence of vitamin deficiency in examined group, we managed to find significant associations between vitamin D status and mental and physical aspects of QoL, as well as with disease activity.
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