The use of complementary and alternative medicine (CAM) is common among patients with systemic lupus erythematosus (SLE), especially those with active disease who often have poorer quality of life and significant unmet needs. It is important for the rheumatologist to be aware of these therapies and to ask the patient with SLE about their active use or future interest in CAM. Future studies on the effectiveness of the aforementioned therapies will be crucial to find better ways for the rheumatologist to integrate their use into the care of the patient with SLE.
Systemic lupus erythematosus (SLE) is a chronic and relapsing autoimmune disorder involving immune dysregulation and chronic widespread inflammation. Manifestations can include malar, discoid, and photosensitive skin rashes, arthralgias and arthritis, constitutional symptoms, potentially widespread internal organ disease, including dysfunction of renal, pulmonary, cardiac, neurologic, and/or gastrointestinal systems, as well as autoantibody production most typically identified by the presence of an antinuclear antibody (ANA). Criteria have been established by the American College of Rheumatology (ACR) to combine both clinical and serologic traits to aide in diagnosis.
The disease manifestations of SLE vary widely from patient to patient and, thus, treatment options cover a wide spectrum. Strategies range from conservative measures, such as acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs) for joint pain, to topical steroid creams and careful use of sunblock for dermatologic manifestations, to more directed immunologic therapies that vary in their immunosuppressive potential. Complementary and alternative medicine (CAM) is also an increasingly common supplement to standardized treatment and the prevalence and details of its application in SLE are crucial for the rheumatologist to understand.
A need for alternative therapies in SLE?
Overall treatment of SLE requires a comprehensive, multidisciplinary approach to the patient’s individual and unique needs that typically extend beyond the treatment of the disease’s immunologic dysfunction. Complaints of pain, fatigue, constitutional symptoms, and psychiatric disturbances are often difficult for patients to articulate and for the physician to diagnose and treat. In addition, their existence may fall outside the domain of the expertise of the rheumatologist who often supplements the primary care provider as a general overseer of the patient’s global health.
Specific identifiable needs of the SLE patient are very diverse. Widespread pain can occur in joints and muscles in the absence of other disease activity and challenge conventional pain management strategies. Arthritis and arthralgia occur in between 53% and 88% of patients with SLE; additional complications of tendonitis, avascular necrosis, and myalgias also occur. Overall physical function in SLE has been shown to be worse than in healthy controls. Clinical investigations have shown a high prevalence of chronic pain syndromes, such as fibromyalgia, in some populations of patients with SLE.
Beyond pain, there are many other sources of distress for patients with SLE. Fatigue is strongly associated. A review of 34 articles by the Ad Hoc Committee on SLE identified fatigue as among the most prevalent and disabling complications of SLE. The committee found that fatigue was strongly linked with comorbidities, such as depression, anxiety, and poor quality of life. Depression and anxiety are also common sequelae of SLE. A 2009 study by Bachen and colleagues found that in 236 white women with SLE, 65% were diagnosed with at least 1 major mood disorder (depression, general anxiety, bipolar disorder); major depression occurred in 47%. Other findings included a 6-fold increased prevalence of bipolar disorder, an 11-fold increased risk of obsessive compulsive disorder (OCD) and a 2.5-fold increased risk of panic disorder. Equally concerning results showed that patients, especially those with anxiety, OCD, and dysthymia, frequently did not disclose symptoms to their physicians. Neuropsychiatric manifestations are common and often nondescript, adversely affecting quality of life.
Evidence can be found to support and to refute a relationship between quality of life and disease activity in lupus. Some investigators argue that quality of life in patients with SLE is not associated directly with disease activity. This has been attributed by some to study design issues. It can be difficult to match control groups to patient groups because of variability of population size, culture, and other factors. However, others have demonstrated that the overall effect of pain and mental health issues, in addition to physical dysfunction, organ disease, side effects of medications, and the emotional and psychological burden of having a chronic disease, can be considerable. An interesting study from the University of Chicago compared 90 patients with SLE to other patients groups with adult chronic diseases such as diabetes mellitus, congestive heart failure, myocardial infarction, and major depression. Patients with SLE had perceptions of vitality and physical functioning similar to patients with chronic heart failure but fared worse in categories including mental health and social functioning. A similar loss of quality of life is experienced by the pediatric patient with SLE, as children struggle to retain some sense of control of their lives. A patient’s self-esteem, vitality, self-perception of illness, and its effect on their daily life can be profoundly negative in SLE. Some studies have shown that the more active the disease, the worse this can be. Poorer mental functioning and quality of life has been shown to be directly related to higher disease activity and SLE Disease Activity Index (SLEDAI) scores in several studies. Lupus patients can develop a large degree of learned helplessness that can have a further effect on morbidity and quality of life. Patients see SLE as an unpredictable and potentially uncontrollable disease that can impede their pursuit of personal goals and an overall normal life. The presence of chronic pain, specifically fibromyalgia, is also associated with poorer quality of life. Most agree that SLE is associated with an overall reduced quality of life compared with healthy controls and on the importance of including quality of life as a measure in creating treatment strategies for patients with SLE.
Social factors may also play an important role in disease activity and quality of life in SLE. Higher levels of SLE activity have been linked to poor social support and resources available to the patients. Challenges in access to care, education levels, and social class have been linked to SLE activity in some studies but not in others.
All of these factors combine to create a set of patient needs that westernized allopathic medicine often does not meet. A study by Danoff-Burg and Friedberg analyzing surveys completed by 112 patients with SLE found that 100% of respondents had at least 1 unmet need in the setting on conventional SLE management with 91% having at least 1 unmet psychosocial need (78.6% feeling it was a significantly unmet need). A similar Australian study of 233 patients with SLE found 94% had an unmet need; the top 2 unmet needs were fatigue management (81%) and pain control (73%).
The demographics of CAM use
Understanding the who and the why behind the use of CAM in SLE is based on the fact that patients seek supportive treatments in addition to the traditional therapy overseen by the rheumatologist to fill their unmet needs. Patients with SLE and autoimmune disorders in general use CAM more often than the general population. The TRINATION study (a multicenter international study of patients with SLE in Canada, Great Brittan, and the United States) reported that patients with SLE who use CAM have a slightly reduced satisfaction and perception of conventional medicine; patient self-perception of illness is higher although patients are not necessarily sicker when measured by objective markers. In another study of patients with SLE, the overall disease activity of SLE was negatively associated with general satisfaction of the health care system.
Other studies have correlated CAM use in patients with SLE with poorer physical function, higher cumulative disease damage, and higher self-perception of disease activity. The TRINATION study did not conclude that objective measures of disease activity are associated with rates of CAM use. A patient’s cultural beliefs influences their expectations of conventional medicine and their use of CAM, but studies performed in communities where CAM use is more prevalent continue to demonstrate a correlation between disease activity and CAM use. A Singapore study of 192 patients with SLE found that 128 used some form of CAM with 57% of users citing continued disease activity and need for relief as opposed to 42% whose CAM use was driven by preference alone. An additional study showed CAM use in patients with SLE in Singapore was influenced by the presence of pain and arthritis, the degree of satisfaction with conventional care, self-perception of health, and overall cost.
The TRINATION study assessing CAM use in 707 patients from England, Canada, and the United States found 352 (49.8%) admitted use of at least 1 CAM therapy to the same extent in all 3 countries. A letter to the editor described 70 of 107 Mexican patients surveyed having used CAM ; another reported 52.6% of Mexican patients with SLE used 2 CAM remedies or more, and a third stated that 43.1% of 445 patients surveyed had tried a CAM therapy.
Studies have varied in the demographic characteristics they have identified as having been associated with CAM use. A study investigating the use of CAM among Hispanics found that in 179 patients with SLE, 63% used CAM. These users were more likely to be women (75%) and of lower income and education levels. On the other hand, the TRINATION study found no difference in CAM use between various income levels and instead suggested CAM users were more likely to be younger and on average have more years of education.
The demographics of CAM use
Understanding the who and the why behind the use of CAM in SLE is based on the fact that patients seek supportive treatments in addition to the traditional therapy overseen by the rheumatologist to fill their unmet needs. Patients with SLE and autoimmune disorders in general use CAM more often than the general population. The TRINATION study (a multicenter international study of patients with SLE in Canada, Great Brittan, and the United States) reported that patients with SLE who use CAM have a slightly reduced satisfaction and perception of conventional medicine; patient self-perception of illness is higher although patients are not necessarily sicker when measured by objective markers. In another study of patients with SLE, the overall disease activity of SLE was negatively associated with general satisfaction of the health care system.
Other studies have correlated CAM use in patients with SLE with poorer physical function, higher cumulative disease damage, and higher self-perception of disease activity. The TRINATION study did not conclude that objective measures of disease activity are associated with rates of CAM use. A patient’s cultural beliefs influences their expectations of conventional medicine and their use of CAM, but studies performed in communities where CAM use is more prevalent continue to demonstrate a correlation between disease activity and CAM use. A Singapore study of 192 patients with SLE found that 128 used some form of CAM with 57% of users citing continued disease activity and need for relief as opposed to 42% whose CAM use was driven by preference alone. An additional study showed CAM use in patients with SLE in Singapore was influenced by the presence of pain and arthritis, the degree of satisfaction with conventional care, self-perception of health, and overall cost.
The TRINATION study assessing CAM use in 707 patients from England, Canada, and the United States found 352 (49.8%) admitted use of at least 1 CAM therapy to the same extent in all 3 countries. A letter to the editor described 70 of 107 Mexican patients surveyed having used CAM ; another reported 52.6% of Mexican patients with SLE used 2 CAM remedies or more, and a third stated that 43.1% of 445 patients surveyed had tried a CAM therapy.
Studies have varied in the demographic characteristics they have identified as having been associated with CAM use. A study investigating the use of CAM among Hispanics found that in 179 patients with SLE, 63% used CAM. These users were more likely to be women (75%) and of lower income and education levels. On the other hand, the TRINATION study found no difference in CAM use between various income levels and instead suggested CAM users were more likely to be younger and on average have more years of education.
Specific practices of complementary medicine in SLE
The definition of CAM supported by the ACR is broadly defined and includes those treatments, products, and practices that fall outside the mainstream of traditional western allopathic medicine. They may range from being safe and effective to being unsafe and ineffective. In this review, attention is given to those therapies not commonly associated with traditional rheumatology office visits. A thorough review of the literature included topics such as acupuncture, massage therapy, mind-body relaxation and biofeedback techniques, exercise and stretching therapy, herbal and vitamin supplements, and psychosocial counseling among others. The paucity of controlled research trials in many of these areas is noticeable and data in many of these areas are lacking. A reporting and analysis of those interventions that have been identified as commonly used among patients with SLE and have been either the subject of individual studies or analyzed in review is included in this article.
Acupuncture
Acupuncture is an important component of CAM; it is used for several rheumatologic conditions including SLE. Its effectiveness in pain management has been best demonstrated in patients with chronic back pain where reduction in use of nonopioid analgesics was achieved in a randomized controlled cross-over trial of 10 years duration. Additional evidence supports using acupuncture for pain relief in knee osteoarthritis and for short-term benefit in the management of fibromyalgia pain, fatigue, and anxiety. Studies are consistent in demonstrating a strong safety profile and minimal side effects, although serious side effects have been reported. Others have suggested that reporting of adverse events has not been comprehensive enough, as shown by the Consolidated Standards of Reporting Trials (CONSORT).
Clinical trials demonstrating positive results of acupuncture in fibromyalgia and osteoarthritis are encouraging because of the potential they suggest for treating pain, fatigue, and psychological disturbances commonly seen in patients with SLE. Unfortunately, there is very limited literature exploring the use of acupuncture in SLE directly. Greco and colleagues’ randomized controlled trial used 3 comparison groups: usual medical care alone, with acupuncture, or with minimal needling. The study chose outcome measures that included pain, fatigue, disease activity, and serologic levels of inflammatory cytokines. The trial suggested superiority of acupuncture and minimal needling over usual medical care alone. However, it did not demonstrate that sham acupuncture was inferior to true acupuncture. The study acknowledged the lack of statistical significance but suggested the true benefits were not seen in part because of inadequate sample size and power. Although side effects in Greco and colleagues’ study were higher (23%, or 33 incidents, in 144 acupuncture sessions) than in previous studies, most adverse events were minor and ranged from pain during needle insertion and local bruising to dizziness and lightheadedness.
There were no serious adverse events in this trial, as has been the case in most published acupuncture studies. However, because acupuncture has not been shown to be efficacious specifically in SLE and is not widely covered by insurance plans, it is not often used. Further studies will be needed before rheumatologists can suggest acupuncture as a reasonable option for manifestations of lupus.
Meditation and Yoga
Mind-body techniques are commonly used CAM strategies that can provide the patient with a sense of some control of their disease. Included in this topic are the practices of meditation, yoga, and tai chi. Specific studies looking at the effect of meditation and tai chi on SLE activity are lacking, but there are studies detailing its use in other chronic medical illnesses. Reports on meditative prayer, Kundalini yoga, Sahaja yoga, Hatha yoga, mindfulness, and relaxation techniques are available.
Yoga has been shown to be effective in controlling symptoms in several chronic conditions. In a large review from Arias and colleagues, 82 studies were examined to analyze the efficacy and safety of meditative practices in treating medical illnesses. The review concluded that there is potential efficacy of meditative practices in treating nonpsychotic mood disturbances and anxiety disorders. Some evidence also suggests that relaxation techniques may be helpful for symptoms of menopausal and premenstrual syndrome. Yoga has been shown to have some positive effects with different strength of evidence in epilepsy, depression, OCD, opiate dependence, and sleep disturbance in patients with cancer. In a prospective randomized trial on epilepsy management, Panjwani and colleagues reported changes in some of the electrophysiologic responses studied in patients with epilepsy who included auditory evoked potentials and visual contrast sensitivity. In a second epilepsy study, the same author randomized a group of 32 subjects to yoga for 6 months or to a control group. Those who practiced yoga had a reduction in electrocardiograph changes consistent with seizures. Another study focused on yoga in patients with depression. Janakiramaiah and colleagues reported a randomized study that compared yoga breath work to therapies for depression such as medications and electroconvulsive therapy (ECT). Woolery and colleagues reported a short-term improvement in depression symptoms in mildly depressed young adults. One study on patients with OCD showed improvement in symptoms was more likely in patients practicing yoga than mindfulness meditation.
To date, studies have not shown consistent reproducible results nor have they used randomized, placebo-, or sham-controlled designs. Many have lacked objective outcome measures. Nonetheless, side effects such as depersonalization have been very rarely reported, Yoga has not been specifically evaluated in SLE. However, lupus shares unmet needs of disturbed psychosocial functioning and fatigue common with other chronic illnesses. Until studies involving patients with SLE have been performed, yoga cannot be recommended for treatment of the manifestations of SLE.
Counseling, Behavioral Therapy, and Stress Management
An extension of mind-body interventions can include cognitive and behavioral therapies and several studies have investigated the benefit of psychosocial support provided to patients with SLE. The previously mentioned study by Moses and colleagues found that 6 of the top 10 unmet needs of patients with SLE were psychological, spiritual, or social in nature. Another study found 78.6% of 112 patients with SLE surveyed had unmet anxiety and social support needs; 70.5% felt there was an unmet need in depression management. Poor disease coping, especially passive coping strategies, focusing on self-blame and wishful thinking, are present in SLE and associated with worse psychological and function status. Those patients lacking psychosocial support and self-efficacy have higher self-reported disease activity. Another study correlated lower socioeconomic status of patients with SLE with higher rates of depression and association with poorer mental and physical functioning.
The last few years have seen more focused studies investigating the benefits of various counseling methods, including creating social networks for coping, 1-on-1 education sessions, stress reduction, and behavioral and psychological therapies for anxiety and depression. Patients with SLE receiving generalized social support and counseling show improved self-reporting of physical function, body pain, social function, and vitality. Such counseling and education have a positive effect on overall disease management. Counseling may have a buffering effect on disease activity, resulting in improved pain and fatigue. An interesting study from Bae and colleagues analyzed which demographic characteristics of patients with SLE would improve most with better social support resources. They found the greatest effect was in patients already above the poverty line; this study concluded that social support and counseling are most beneficial in those who already have financial and social advantages.
Counseling is included in this review as an alternative therapy because it serves to supplement cognitive and behavioral therapy in improving coping strategies in patients with SLE. Counseling involves either individual or group sessions and focuses most often on coping strategies and stress reduction. Studies of group counseling on disease and drug education, exercise, coping strategies, and stress reduction have found overall improvement in quality of life. These same studies, however, note no association between improvement and disease activity. A study by Karlson and colleagues reported that counseling sessions aimed at improving education, social support, and problem solving for patients with SLE and their spouses had a sustained effect on self-efficacy, mental health, and overall fatigue 12 months after the initial intervention. In a study of 8 patients by Maisiak and colleagues, counseling was provided by telephone. Significant psychological benefit was found using the Arthritis Impact Measurement Scale in subjects receiving counseling by phone compared with those receiving standard care. Telephone-based counseling was used in another study of 58 patients with SLE and improvements in self-reported physical function and social support were seen. In 1 unique study in which the phone interviewers themselves had SLE, providing counseling to other patients with SLE had a positive effect on overall well-being. One may conclude from such studies that encouraging participation in local support groups may have an effect on a patient’s cognitive health even if the effect on the disease process itself is negligible.
Several studies have focused more specifically on treating depression and anxiety in SLE. Groups focusing on education and coping strategies for anxiety and stress and cognitive behavioral therapy both demonstrated improvements in overall psychological function and self-esteem. An individual case report examining 1-on-1 psychotherapy in SLE showed improvement in self-identity and function. Supportive-expressive group therapy was tested in a study from McGill University on 133 female patients with SLE with outcomes measuring quality of life, disease activity, and overall distress. The therapy was associated with some improvement in coping and overall distress, but a definitive benefit to the group could not be demonstrated. The technique was used in a second study that focused on the potential effect on life domains, defined as relationship, intimacy, and instrumental life, such as work. Fifty-eight patients with SLE were assigned to therapy and compared with 66 patients with SLE in usual care. Significant and sustained improvements were noted in illness intrusiveness into the life domains of relationships and partner intimacy.
Studies investigating the benefit of cognitive and behavioral therapies in SLE have been limited by small sample size and inadequate control groups. Results have been conflicting but these techniques have generally been shown to improve quality of life.
Exercise Therapy
Exercise is a useful tool in all patients to improve cardiovascular fitness, decrease metabolic abnormalities, reduce insulin resistance, reduce fatigue, and improve quality of life through pain reduction. Exercise is especially important for patients with SLE given their heightened susceptibility to cardiovascular events, as are modification of risk factors such as hyperlipidemia, hypertension, diabetes, sedentary lifestyle, and smoking. The mean age of the first myocardial infarction for patients with SLE is 49 years, significantly earlier than healthy controls. Risks of low bone density are higher in patients with SLE as are risks of fractures. Pain, fatigue, depression, and poor sleep in SLE can also result in poorer efforts toward physical activity.
Patients with SLE have demonstrated worse exercise capacity and strength than sedentary healthy controls. Tench and colleagues compared a group of patients with SLE to matched normal controls and found that they have less aerobic fitness and reduced muscle strength unrelated to disease activity.
Several studies support use of exercise in SLE. Low physical activity is associated with increased high-density lipoprotein and atherosclerosis in SLE. Increased strenuous exercise may reduce the risk of atherosclerosis in patients with SLE. Cardiovascular exercise programs have also been shown to be effective in improving quality of life. Bone loss can be attenuated in SLE with regular aerobic activity. Inflammatory cytokines, including interleukin-6 and C-reactive protein, decrease in obese patients after exercise, and these antiinflammatory effects of exercise that could be of interest in autoimmune disease. Exercise may also improve poor sleep and is helpful in managing pain syndromes like fibromyalgia, both often seen in SLE. Although there are no prospective randomized controlled trials, pilot studies suggest that exercise helps with fatigue in SLE.
Vitamins and Dietary Supplements
Dihydroepiandrosterone
Low levels of dihydroepiandrosterone (DHEA) are seen in conditions such as aging, cardiovascular disease, and SLE. Small studies have been done to determine the efficacy of DHEA supplementation in patients with SLE. In 1 open-label study, DHEA was used in 10 patients with SLE for 3 to 6 months. Outcome measures included the SLEDAI score and physician’s overall assessment. DHEA 200 mg daily was associated with improved SLEDAI scores and decreased glucocorticoid requirements. A subsequent double-blind randomized trial in 191 patients with SLE confirmed that DHEA supplementation could be associated with a modest stabilization of disease and reduction in steroid dose. The most frequently noted side effect was mild acneiform dermatitis; no serious adverse events were associated with DHEA.
Another study done in 2005 by Nordmak and colleagues analyzed the effect of DHEA in patients with SLE treated with glucocorticoids to evaluate efficacy on health-related quality of life. Patients were randomized to receive either DHEA or placebo for 6 months; subsequently, all patients were given DHEA. Health-related quality of life was assessed at baseline, 6, and 12 months using 4 validated questionnaires. The subjects’ partners completed a questionnaire assessing mood and behavior at 6 months. Results demonstrated DHEA treatment increased serum levels of sulfated DHEA to normal levels. The DHEA group improved in SF-36 role emotional score and the HSCL-56 total score. The placebo group improved after subsequent DHEA treatment in the SF-36 mental health domain. Both groups improved in McCoy’s Sex Scale during active treatment. There were no serious side effects reported.
A double-blinded, randomized, placebo-controlled clinical trial was conducted in 2009 to evaluate the effects of DHEA on fatigue and well-being in women with quiescent SLE by Hartkamp and colleagues. Sixty women with quiescent lupus were randomized to receive oral DHEA 200 mg or placebo. Outcome parameters of general fatigue, depressed mood, mental well-being, and physical functioning were assessed before, during, and after treatment. Both groups improved nearly equally in the categories of general fatigue and mental well-being. The strong response of the placebo group suggested that the belief in taking DHEA was a stronger predictor for improvement than any differential effect of DHEA itself.
Studies to date have suggested a limited effect of DHEA on SLE activity and they are limited in sample size. Larger double-blind, placebo-controlled, randomized trials will be necessary to decide whether DHEA has a significant role in the treatment of lupus.
Fish oil
Fish oil has found use as a dietary supplement in conditions such as hypertriglyceridemia and IgA nephropathy. Data on SLE are limited.
One prospective, double-blind, cross-over study assessed the effects of a diet low in fat and high in fish oil in 27 patients with active SLE treated for 34 weeks. Fourteen patients receiving marine oil improved in self-assessed daily function, whereas 13 patients receiving placebo (20 g olive oil) were rated as worse or no change. Another double-blind, double placebo-controlled trial was performed on 52 patients with SLE. Two out of the 4 groups in the trial received 1 g fish oil daily and disease activity was measured by the revised Systemic Lupus Activity Measure (SLAM-R). The treatment group demonstrated significant improvement in SLAM-R scores. No effect was seen on hematologic, biochemical, and immunologic indices measured at baseline and 6, 12, and 24 weeks.
Another study randomized patients to 2 double-blinded groups for 24 weeks: 1 received placebo, the other 3 g of fish oil daily. Disease activity was measured with the SLAM-R and British Isles Lupus Assessment Group (BILAG) index at baseline and the investigators found a statistically significant improvement 24 weeks in SLAM-R and BILAG. This was accounted for largely by improvement in constitutional, neuromotor, integument, and joint scores.
Vitamin D
Reports have suggested that patients with SLE have lower levels of vitamin D than healthy controls. It is unknown why this seems to be the case. One study demonstrated a slightly higher incidence (although not statistically significant) of autoantibodies against vitamin D in a small SLE patient population. A study of pediatric patients with SLE demonstrated lower vitamin D levels in general and an association with heightened disease activity in particular.
Lower vitamin D levels in SLE were also seen in a study of the interaction of SLE disease activity and bone metabolism. Comparisons were made between 2 groups of patients with SLE classified as high activity or minimal activity by SLEDAI scores. The group labeled as having high activity had statistically significantly lower vitamin D, osteocalcin, and bone-specific alkaline phosphatase levels. Although disease activity may contribute, sun avoidance, and the use of sunscreen may account for low vitamin D levels. Predictors for low vitamin D in patients with SLE reported elsewhere include the presence of renal disease and photosensitivity.
Although the importance of assessing vitamin D levels in SLE is crucial for maintenance of overall bone health, the effect of supplementing vitamin D on SLE activity is not known. Exploring the causes of deficiency and effects of replacement will require studies that include larger numbers of patients and tracking vitamin D levels before, during, and after disease flares.
Other vitamins
Vitamin C is a common dietary supplement. A popular use is reducing the severity of the common cold.
Several trials have investigated the use of vitamin C in SLE. In 1999, Minami and colleagues showed that dietary nutrients may modify the clinical course of the disease in female patients with SLE, and that vitamin C intake is inversely associated with the risk of active disease. In the study, disease activity was evaluated based on the Lupus Activity Criteria Count. Patients were followed for 4 years and the study included 279 female patients. The study concluded that vitamin C may reduce SLE activity. The trial is limited in its poor estimation of the dosage requirements because the nutrient goal was estimated only by a semi-quantitative food frequency questionnaire. In addition, there is no indication of taking a specific vitamin C dose, and the conclusion was based on revealing an inverse association of intake of vitamin C with the risk of active disease.
Tam and colleagues conducted a study in 2005 to evaluate the effects of long-term antioxidant vitamins on markers of oxidative stress and antioxidant defense and endothelial function in 39 patients with SLE. The patients were randomized into 2 groups, 1 receiving placebo and the other receiving vitamin C 500 mg and vitamin E 800 IU for 12 weeks. Markers were measured for oxidative stress and included malondialdehyde and allantoin. Antioxidants measured included erythrocyte superoxide dismutase, glutathione peroxidase, ascorbic acid, and vitamin E concentrations. Endothelial function was assessed by flow-mediated dilatation of the brachial artery and plasma concentration of von Willebrand factor and plasminogen activator inhibitor type 1. After treatment for 12 weeks, plasma ascorbic acid and α-tocopherol concentrations were significantly increased in the vitamin-treated group, and 1 oxidative stress marker, malondialdehyde, was significantly decreased. All other markers were unchanged. The study is limited in its effect because it was conducted for only 12 weeks and it did not look at clinical outcomes.
Weinmann and Hermann conducted a study in a SLE mouse model (MRL/lpr) to study the potential of the antioxidant vitamin E to modulate the progress of SLE. Mice were supplemented with vitamin E 0.4 mg daily 5 times per week from 8 weeks of age onwards and compared with mice on a vitamin E–deficient diet. Supplementation with vitamin E extended the mean survival time from 157 to 196 days, and reduced the massive spleen and lymph node enlargement, titers of anti–double-stranded DNA antibodies and proteinuria. How this translates into humans is unclear. A double-blind, randomized, placebo-controlled trial is needed, keeping in mind that a judgment about affecting clinical outcomes needs good definition of these outcomes and adequate trial length to allow appropriate assessment of the frequencies of different organ involvement.