The Open Rheumatology Journal




ISSN: 1874-3129 ― Volume 13, 2019
RESEARCH ARTICLE

Comparison of Vitamin D Serum Values between Rheumatoid Arthritis and Lupus Populations: An Observational Study



Sahebari Maryam1, Elham Atabati1, 2, *, Ravanshad Yalda3
1 Rheumatic Diseases Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2 Cellular and Molecular Research Center, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
3 Clinical Research Development Unit, Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Background:

In recent years, the role of Vitamin D (VitD), as an immunomedulator in autoimmune diseases, has been evaluated in basic science and practice. There is a considerable volume of data on the effect of VitD position in lupus and rheumatoid arthritis exacerbation.

Objective:

This study aims to compare VitD serum values in lupus (SLE) and Rheumatoid Arthritis (RA) in the geographical region of northeastern Iran.

Methods:

Lupus and RA Patients were selected with various disease activity levels. All the patients received an equal amount of VitD supplementation and were selected by the same inclusion and exclusion criteria. VitD serum values were measured by a commercial ELISA kit. Data were analyzed in SPSS-15.

Results:

A total of 148 SLE and 156 RA patients were studied. VitD serum levels were 66.54±41.2 nmol/l in the SLE group and 83.74±46.45 nmol/l in the RA group. Statistical analysis showed that VitD serum levels were lower in lupus patients than RA ones (p=0.006).

Conclusion:

Since VitD deficiency is very common in Iran, physiologic doses of VitD supplementation in patients lead to higher serum levels of VitD. Lower VitD values in lupus patients compared with RA ones may stem from intestinal malabsorption, higher doses of corticosteroid therapy, renal involvement and proteinuria, different polymorphisms of VitD receptors, and more sun protection strategies in lupus patients.

Keywords: Vitamin D, 25(OH) D, VitD, Rheumatoid Arthritis, Lupus, SLE, RA.


Article Information


Identifiers and Pagination:

Year: 2018
Volume: 12
First Page: 65
Last Page: 69
Publisher Id: TORJ-12-65
DOI: 10.2174/1874312901812010065

Article History:

Received Date: 11/12/2017
Revision Received Date: 09/02/2018
Acceptance Date: 05/04/2018
Electronic publication date: 10/04/2018

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© 2018 Maryam et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Elham Atabati, Mashhad, Iran; Tel:4989173000474 / +985138012753; Email: elham1405@yahoo.com




1. INTRODUCTION

Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) are two important autoimmune diseases in which the immunomedulatory role of vitamin D (VitD) has been evaluated appropriately. However, there is still some debate about the immunomodulatory role, optimal dose, and type of VitD that should be prescribed.

VitD has been diagnosed in recent years more as a secosteroid than a mere vitamin. It contributes to the modulation of the immune response by inhibiting actions of innate and adaptive immune cells [1Toubi E, Shoenfeld Y. The role of vitamin D in regulating immune responses. Isr Med Assoc J 2010; 12(3): 174-5.[PMID: 20684184] ]. There is some evidence that B cells are inactivated by binding VitD to VitD receptors (VDRs) on their surface [2Sahebari M, Nabavi N, Salehi M. Correlation between serum 25(OH)D values and lupus disease activity: An original article and a systematic review with meta-analysis focusing on serum VitD confounders. Lupus 2014; 23(11): 1164-77.[http://dx.doi.org/10.1177/0961203314540966] [PMID: 24961748] -4Albert PJ, Proal AD, Marshall TG. Vitamin D: The alternative hypothesis. Autoimmun Rev 2009; 8(8): 639-44.[http://dx.doi.org/10.1016/j.autrev.2009.02.011] [PMID: 19393200] ]. Furthermore, VitD inhibits autoantibody production Suppression of dendritic cell-related pathways leads to the inhibition of T cell activation [5Jones BJ, Twomey PJ. Issues with vitamin D in routine clinical practice. Rheumatology (Oxford) 2008; 47(9): 1267-8.[http://dx.doi.org/10.1093/rheumatology/ken301] [PMID: 18658199] ]. Additional VitD immunomodulatory activities is conducted by 1,25(OH)D [6van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: Basic concepts. J Steroid Biochem Mol Biol 2005; 97(1-2): 93-101.[http://dx.doi.org/10.1016/j.jsbmb.2005.06.002] [PMID: 16046118] ]. VitD inhibits B cell proliferation prior to acquiring immunoglobulin secreting capabilities. It also blocks differentiation of monocytes into dendritic cells (DC), decreases the production of IL-12, INF-γ, IL-2, and enhances IL-10 production [6van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: Basic concepts. J Steroid Biochem Mol Biol 2005; 97(1-2): 93-101.[http://dx.doi.org/10.1016/j.jsbmb.2005.06.002] [PMID: 16046118] ]. Other roles of VitD include increased monocyte-macrophage differentiation and control over macrophage responses [4Albert PJ, Proal AD, Marshall TG. Vitamin D: The alternative hypothesis. Autoimmun Rev 2009; 8(8): 639-44.[http://dx.doi.org/10.1016/j.autrev.2009.02.011] [PMID: 19393200] -5Jones BJ, Twomey PJ. Issues with vitamin D in routine clinical practice. Rheumatology (Oxford) 2008; 47(9): 1267-8.[http://dx.doi.org/10.1093/rheumatology/ken301] [PMID: 18658199] , 7Szodoray P, Nakken B, Gaal J, et al. The complex role of vitamin D in autoimmune diseases. Scand J Immunol 2008; 68(3): 261-9.[http://dx.doi.org/10.1111/j.1365-3083.2008.02127.x] [PMID: 18510590] -8Ghoryani M, Sahebari M, Mahmoudi M, et al. Immunomodulatory vitamin D effects on regulatory T-cells and cytokines in an in vitro study on patients with systemic lupus erythematosus. Food Agric Immunol 2015; 27(3): 1-11.].

Several studies have supported the fact that VitD deficiency acts not only as a predisposing factor for RA and SLE development but also as an enhancer of disease severity and activity [2Sahebari M, Nabavi N, Salehi M. Correlation between serum 25(OH)D values and lupus disease activity: An original article and a systematic review with meta-analysis focusing on serum VitD confounders. Lupus 2014; 23(11): 1164-77.[http://dx.doi.org/10.1177/0961203314540966] [PMID: 24961748] -3Sahebari M, Mirfeizi Z, Rezaieyazdi Z, Rafatpanah H, Goshyeshi L. 25(OH) vitamin D serum values and rheumatoid arthritis disease activity (DA S28 ESR). Caspian J Intern Med 2014; 5(3): 148-55.[PMID: 25202442] , 9Goshayeshi L, Saber H, Sahebari M, et al. Association between metabolic syndrome, BMI, and serum vitamin D concentrations in rheumatoid arthritis. Clin Rheumatol 2012; 31(8): 1197-203.[http://dx.doi.org/10.1007/s10067-012-1995-3] [PMID: 22581277] ]. On the other hand, each disease course leads to VitD deficiency due to treatment strategies, malnutrition, sedentary life style, sun protection especially in SLE, and several other factors [2Sahebari M, Nabavi N, Salehi M. Correlation between serum 25(OH)D values and lupus disease activity: An original article and a systematic review with meta-analysis focusing on serum VitD confounders. Lupus 2014; 23(11): 1164-77.[http://dx.doi.org/10.1177/0961203314540966] [PMID: 24961748] -3Sahebari M, Mirfeizi Z, Rezaieyazdi Z, Rafatpanah H, Goshyeshi L. 25(OH) vitamin D serum values and rheumatoid arthritis disease activity (DA S28 ESR). Caspian J Intern Med 2014; 5(3): 148-55.[PMID: 25202442] , 9Goshayeshi L, Saber H, Sahebari M, et al. Association between metabolic syndrome, BMI, and serum vitamin D concentrations in rheumatoid arthritis. Clin Rheumatol 2012; 31(8): 1197-203.[http://dx.doi.org/10.1007/s10067-012-1995-3] [PMID: 22581277] -11Gopinath K, Danda D. Supplementation of 1,25 dihydroxy vitamin D3 in patients with treatment naive early rheumatoid arthritis: A randomised controlled trial. Int J Rheum Dis 2011; 14(4): 332-9.[http://dx.doi.org/10.1111/j.1756-185X.2011.01684.x] [PMID: 22004229] ]. This article compares 25(OH)D serum values in patients with SLE and RA in the same geographical area by an equal amount of VitD supplementation to demonstrate differences. The hypothesis is that VitD in SLE patients may be less than in RA patients. It is important to understand the difference between RA and SLE when there is an equal dose of VitD supplementation.

2. MATERIALS AND METHODS

This article is a retrospective analysis of two previous cross-sectional studies in which VitD serum values in RA patients, SLE patients, and healthy populations were studied. Both studies were conducted in Mashhad, Iran, located at 360.20° latitude and 59.35° east longitude over a solar year (2013). In the two previous articles, we had a total of 148 SLE and 156 RA patients (case and control, respectively) were studied.

Over six months, from April to September, it tends to be sunny and warm in the region, if not hot. In the following six months, i.e. from October to March, it tends to be usually cold and cloudy [12Moradzadeh K, Larijani B, Keshtkar A, et al. Normative values of vitamin D among Iranian population: A population based study. Int J Osteo Met Dis 2008; 1: 8-15.].

A total of 99 RA patients diagnosed with ACR criteria [3Sahebari M, Mirfeizi Z, Rezaieyazdi Z, Rafatpanah H, Goshyeshi L. 25(OH) vitamin D serum values and rheumatoid arthritis disease activity (DA S28 ESR). Caspian J Intern Med 2014; 5(3): 148-55.[PMID: 25202442] ] and 82 patients who fulfilled the American College of Rheumatology (ACR) criteria for lupus [2Sahebari M, Nabavi N, Salehi M. Correlation between serum 25(OH)D values and lupus disease activity: An original article and a systematic review with meta-analysis focusing on serum VitD confounders. Lupus 2014; 23(11): 1164-77.[http://dx.doi.org/10.1177/0961203314540966] [PMID: 24961748] ] were included for both studies in the Rheumatic Diseases Research Center affiliated with Mashhad University of Medical Sciences (2014). In both studies, the exclusion criteria included systemic co-morbidities such as chronic kidney or liver disease, malnourishment, and malabsorption (serum albumin less than 2.2 mg/dl, cholesterol below 100 mg/dl, and BMI<18.5 kg/m2). Smokers, pregnant women, postpartum and nursing mothers and individuals with BMI>30 kg/m2 were also excluded (since there is a hypothesis stating that lower VitD in overweight people may simply be representative of a larger volume of distribution of this vitamin because of fat solubility of 25(OH)D [13Aghdassi E, Morrison S, Landolt-Marticorena C, et al. The use of micronutrient supplements is not associated with better quality of life and disease activity in Canadian patients with systemic lupus erythematosus The Journal of Rheumatology. 2009:jrheum. 090761.]). Moreover, individuals with supra-physiologic doses (>800 U/day) or injectable proportion of VitD from six months prior to sampling or those under chronic anticonvulsive therapy were excluded.

Both groups of patients received 1000 to 1200 mg calcium and 800 U VitD in addition to 400 mg hydroxychloroquine. Other medications were analyzed in detail in each article [3Sahebari M, Mirfeizi Z, Rezaieyazdi Z, Rafatpanah H, Goshyeshi L. 25(OH) vitamin D serum values and rheumatoid arthritis disease activity (DA S28 ESR). Caspian J Intern Med 2014; 5(3): 148-55.[PMID: 25202442] , 9Goshayeshi L, Saber H, Sahebari M, et al. Association between metabolic syndrome, BMI, and serum vitamin D concentrations in rheumatoid arthritis. Clin Rheumatol 2012; 31(8): 1197-203.[http://dx.doi.org/10.1007/s10067-012-1995-3] [PMID: 22581277] ].

VitD measurement was conducted by ELISA kit (Immundiagnostik AG, Bensheim, Germany) from the sera of participants.

Kolmogorov-Smirnov test was utilized to measure normality of data distribution. ANOVA test was used to calculate differences between VitD serum values in each group. Post-hoc analysis was used for further analysis. Advanced analysis was accomplished by linear regression model. As it was a retrospective research on previous complete data, there was no missing data.

3. RESULTS

A total of 82 patients (12 males, 70 females) were enrolled in the SLE group and 99 patients (11 males, 89 females) in the RA group. The average age was (29.96±11.47 yrs) in SLE and (43.44±14.31 yrs) in RA groups with a significant difference (p<0.0001). Gender distribution in the two groups was compared using chi-square test, which showed similar distribution (p=0.4). The mean duration of disease in SLE patients was 3(0.5-5.7 IQR) yrs. In RA group, disease duration was 5.9±5.6 yrs, which was significantly higher than in the SLE patients (t=0.03, Man-Whitney test).

VitD serum levels in SLE and RA groups were 66.54±41.2 nmol/l and 83.74±46.45 nmol/l, respectively. Kolmogorov-Smirnov test showed that VitD levels were not normally distributed in SLE group. Statistical analysis showed that VitD serum values were lower in SLE patients than RA ones (p=0.006, Man-Whitney test).

In this study, the values of vitD were fitted with explanatory variables (i.e., age, disease duration, RA and SLE patients) and modeled by multiple linear regression technique. The final analysis is displayed in Table 1. It shows that only lupus as a variable affects VitD serum values negatively, and age and disease duration have no statistically significant impact on VitD serum levels.

Table 1
Regression analysis on the influence of age, RA vs. Lupus duration and disease type on Vit D serum level as an independent variable.


4. DISCUSSION

This study assessed serum values of VitD in SLE and RA patients in the northeast of Iran. We found lower plasma levels of VitD in SLE than RA under similar bio-geographical conditions, sex distribution, VitD and calcium supplementation, and the same inclusion and exclusion criteria. Regression analysis demonstrated that age did not affect VitD serum values in RA and SLE. Furthermore, regression analysis demonstrated that age and disease duration did not affect the difference in VitD serum values between RA and SLE. The mean±SD of VitD serum values in SLE patients was below optimal goal despite supplement therapy [12Moradzadeh K, Larijani B, Keshtkar A, et al. Normative values of vitamin D among Iranian population: A population based study. Int J Osteo Met Dis 2008; 1: 8-15.].

To describe the difference between RA and SLE patients, several facts are proposed. Given the important role of UVB damage in dermatological and systemic manifestations of lupus, sun protection is a rule in lupus which is considered as a risk factor for 25(OH)D deficiency [14Ruiz-Irastorza G, Egurbide MV, Olivares N, Martinez-Berriotxoa A, Aguirre C. Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology (Oxford) 2008; 47(6): 920-3.[http://dx.doi.org/10.1093/rheumatology/ken121] [PMID: 18411213] -15Cusack C, Danby C, Fallon JC, et al. Photoprotective behaviour and sunscreen use: Impact on vitamin D levels in cutaneous lupus erythematosus. Photodermatol Photoimmunol Photomed 2008; 24(5): 260-7.[http://dx.doi.org/10.1111/j.1600-0781.2008.00373.x] [PMID: 18811868] ].

Moreover, renal involvement in lupus may influence protein bindings for VitD and production of 1,25(OH)D. Increasing data has revealed that nephritis is a significant underlying risk factor for VitD deficiency in SLE [16Cutolo M. Vitamin D and autoimmune rheumatic diseases. Rheumatology (Oxford) 2009; 48(3): 210-2.[http://dx.doi.org/10.1093/rheumatology/ken394] [PMID: 18930963] ].

Besides, the medication prescribed for the treatment of SLE may aggregate VitD deficiency [7Szodoray P, Nakken B, Gaal J, et al. The complex role of vitamin D in autoimmune diseases. Scand J Immunol 2008; 68(3): 261-9.[http://dx.doi.org/10.1111/j.1365-3083.2008.02127.x] [PMID: 18510590] ]. Compared with RA, chronic higher doses of glucocorticoid therapy in SLE decline intestinal absorption and accelerate the catabolism of VitD through increasing 24α-hydroxylase activity [17Steinman L. A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med 2007; 13(2): 139-45.[http://dx.doi.org/10.1038/nm1551] [PMID: 17290272] -20Cutolo M, Otsa K. Review: vitamin D, immunity and lupus. lupus. 2008;17(1):6-10.]. Some research studies propose that the interaction between over-activation of the immune system related to T-regs in SLE can affect the activation of VitD [21Cippitelli M, Santoni A. Vitamin D3: a transcriptional modulator of the interferon-gamma gene. Eur J Immunol 1998; 28(10): 3017-30.[http://dx.doi.org/10.1002/(SICI)1521-4141(199810)28:10<3017::AID-IMMU3017>3.0.CO;2-6] [PMID: 9808170] -23Pelajo CF, Lopez-Benitez JM, Miller LC. Vitamin D and autoimmune rheumatologic disorders. Autoimmun Rev 2010; 9(7): 507-10.[http://dx.doi.org/10.1016/j.autrev.2010.02.011] [PMID: 20146942] ].

Anti-VitD antibodies related to antiDNA have been evaluated in patients with SLE that may reduce VitD functions [24Wright TB, Shults J, Leonard MB, Zemel BS, Burnham JM. Hypovitaminosis D is associated with greater body mass index and disease activity in pediatric systemic lupus erythematosus. J Pediatr 2009; 155(2): 260-5.[http://dx.doi.org/10.1016/j.jpeds.2009.02.033] [PMID: 19446841] , 25Costenbader KH, Feskanich D, Holmes M, Karlson EW, Benito-Garcia E. Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women. Ann Rheum Dis 2008; 67(4): 530-5.[http://dx.doi.org/10.1136/ard.2007.072736] [PMID: 17666449] ].

Finally, polymorphism of VDR genes could be a part of VitD imbalance in SLE and RA, as different polymorphisms have been reported in those diseases [14Ruiz-Irastorza G, Egurbide MV, Olivares N, Martinez-Berriotxoa A, Aguirre C. Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology (Oxford) 2008; 47(6): 920-3.[http://dx.doi.org/10.1093/rheumatology/ken121] [PMID: 18411213] , 26Aranow C. Vitamin D and the immune system. J Investig Med 2011; 59(6): 881-6.[http://dx.doi.org/10.2310/JIM.0b013e31821b8755] [PMID: 21527855] ].

CONCLUSION

This study demonstrated that 25(OH)D serum values in SLE patients are significantly lower than RA patients with the same geographic location, VitD supplementation, and other risk factors. Therefore, VitD deficiency should be considered in SLE patients more profoundly. Further studies can determine whether this is a consequence of SLE or a basic difference in the pathogenesis of two diseases.

DISCLOSER

We certify that there is no actual or potential conflict of interest in relation to this article.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

Not applicable.

HUMAN AND ANIMAL RIGHTS

No animals/humans were used for studies that are the basis of this research.

CONSENT FOR PUBLICATION

Not applicable.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

This article is a short communication on VitD in RA and SLE built on two previous researches supported by Mashhad University of Medical Sciences Research Council [grant number 87609 & 87835].

REFERENCES

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[5] Jones BJ, Twomey PJ. Issues with vitamin D in routine clinical practice. Rheumatology (Oxford) 2008; 47(9): 1267-8.[http://dx.doi.org/10.1093/rheumatology/ken301] [PMID: 18658199]
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[13] Aghdassi E, Morrison S, Landolt-Marticorena C, et al. The use of micronutrient supplements is not associated with better quality of life and disease activity in Canadian patients with systemic lupus erythematosus The Journal of Rheumatology. 2009:jrheum. 090761.
[14] Ruiz-Irastorza G, Egurbide MV, Olivares N, Martinez-Berriotxoa A, Aguirre C. Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology (Oxford) 2008; 47(6): 920-3.[http://dx.doi.org/10.1093/rheumatology/ken121] [PMID: 18411213]
[15] Cusack C, Danby C, Fallon JC, et al. Photoprotective behaviour and sunscreen use: Impact on vitamin D levels in cutaneous lupus erythematosus. Photodermatol Photoimmunol Photomed 2008; 24(5): 260-7.[http://dx.doi.org/10.1111/j.1600-0781.2008.00373.x] [PMID: 18811868]
[16] Cutolo M. Vitamin D and autoimmune rheumatic diseases. Rheumatology (Oxford) 2009; 48(3): 210-2.[http://dx.doi.org/10.1093/rheumatology/ken394] [PMID: 18930963]
[17] Steinman L. A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med 2007; 13(2): 139-45.[http://dx.doi.org/10.1038/nm1551] [PMID: 17290272]
[18] Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 2005; 26(5): 662-87.[http://dx.doi.org/10.1210/er.2004-0002] [PMID: 15798098]
[19] Akeno N, Matsunuma A, Maeda T, Kawane T, Horiuchi N. Regulation of vitamin D-1alpha-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney. J Endocrinol 2000; 164(3): 339-48.[http://dx.doi.org/10.1677/joe.0.1640339] [PMID: 10694374]
[20] Cutolo M, Otsa K. Review: vitamin D, immunity and lupus. lupus. 2008;17(1):6-10.
[21] Cippitelli M, Santoni A. Vitamin D3: a transcriptional modulator of the interferon-gamma gene. Eur J Immunol 1998; 28(10): 3017-30.[http://dx.doi.org/10.1002/(SICI)1521-4141(199810)28:10<3017::AID-IMMU3017>3.0.CO;2-6] [PMID: 9808170]
[22] Mao S, Huang S. Association between vitamin D receptor gene BsmI, FokI, ApaI and TaqI polymorphisms and the risk of systemic lupus erythematosus: a meta-analysis. Rheumatol Int 2014; 34(3): 381-8.[http://dx.doi.org/10.1007/s00296-013-2898-6] [PMID: 24212677]
[23] Pelajo CF, Lopez-Benitez JM, Miller LC. Vitamin D and autoimmune rheumatologic disorders. Autoimmun Rev 2010; 9(7): 507-10.[http://dx.doi.org/10.1016/j.autrev.2010.02.011] [PMID: 20146942]
[24] Wright TB, Shults J, Leonard MB, Zemel BS, Burnham JM. Hypovitaminosis D is associated with greater body mass index and disease activity in pediatric systemic lupus erythematosus. J Pediatr 2009; 155(2): 260-5.[http://dx.doi.org/10.1016/j.jpeds.2009.02.033] [PMID: 19446841]
[25] Costenbader KH, Feskanich D, Holmes M, Karlson EW, Benito-Garcia E. Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women. Ann Rheum Dis 2008; 67(4): 530-5.[http://dx.doi.org/10.1136/ard.2007.072736] [PMID: 17666449]
[26] Aranow C. Vitamin D and the immune system. J Investig Med 2011; 59(6): 881-6.[http://dx.doi.org/10.2310/JIM.0b013e31821b8755] [PMID: 21527855]

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Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


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