Omega-3 Polyunsaturated Fatty Acid Intervention Against Established Autoimmunity in a Murine Model of Toxicant-Triggered Lupus.

Workplace exposure to respirable crystalline silica dust (cSiO2) has been etiologically linked to the development of lupus and other human autoimmune diseases. Lupus triggering can be recapitulated in female NZBWF1 mice by four weekly intranasal instillations with 1 mg cSiO2. This elicits inflammatory/autoimmune gene expression and ectopic lymphoid structure (ELS) development in the lung within 1 week, ultimately driving early onset of systemic autoimmunity and glomerulonephritis. Intriguingly, dietary supplementation with docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid (PUFA) found in fish oil, beginning 2 week prior to cSiO2 challenge, prevented inflammation and autoimmune flaring in this novel model. However, it is not yet known how ω-3 PUFA intervention influences established autoimmunity in this murine model of toxicant-triggered lupus. Here we tested the hypothesis that DHA intervention after cSiO2-initiated intrapulmonary autoimmunity will suppress lupus progression in the NZBWF1 mouse. Six-week old NZWBF1 female mice were fed purified isocaloric diet for 2 weeks and then intranasally instilled with 1 mg cSiO2 or saline vehicle weekly for 4 consecutive weeks. One week after the final instillation, which marks onset of ELS formation, mice were fed diets supplemented with 0, 4, or 10 g/kg DHA. One cohort of mice (n = 8/group) was terminated 13 weeks after the last cSiO2 instillation and assessed for autoimmune hallmarks. A second cohort of mice (n = 8/group) remained on experimental diets and was monitored for proteinuria and moribund criteria to ascertain progression of glomerulonephritis and survival, respectively. DHA consumption dose-dependently increased ω-3 PUFA content in the plasma, lung, and kidney at the expense of the ω-6 PUFA arachidonic acid. Dietary intervention with high but not low DHA after cSiO2 treatment suppressed or delayed: (i) recruitment of T cells and B cells to the lung, (ii) development of pulmonary ELS, (iii) elevation of a wide spectrum of plasma autoantibodies associated with lupus and other autoimmune diseases, (iv) initiation and progression of glomerulonephritis, and (v) onset of the moribund state. Taken together, these preclinical findings suggest that DHA supplementation at a human caloric equivalent of 5 g/d was an effective therapeutic regimen for slowing progression of established autoimmunity triggered by the environmental toxicant cSiO2.

Requisite Omega-3 HUFA Biomarker Thresholds for Preventing Murine Lupus Flaring.

Lupus is a systemic autoimmune disease typified by uncontrolled inflammation, disruption of immune tolerance, and intermittent flaring - events triggerable by environmental factors. Preclinical and clinical studies reveal that consumption of the marine ω-3 highly unsaturated fatty acids (HUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) might be used as a precision nutrition intervention to lessen lupus symptoms. The anti-inflammatory and pro-resolving effects of ω-3 HUFAs are inextricably linked to their presence in membrane phospholipids. The ω-3 HUFA score, calculated as [100 × (ω-3 HUFAs/(ω-3 HUFAs + ω-6 HUFAs))] in red blood cells (RBCs), and the Omega-3 Index (O3I), calculated as [100 × ((DHA+EPA)/total fatty acids)] in RBCs, are two biomarkers potentially amenable to relating tissue HUFA balance to clinical outcomes in individuals with lupus. Using data from three prior preclinical DHA supplementation studies, we tested the hypothesis that the ω-3 HUFA score and the O3I inversely correlate with indicators of autoimmune pathogenesis in the cSiO2-triggered lupus flaring model. The three studies employed both low and high fat rodent diets, as well as more complex diets emulating the U.S. dietary pattern. The ω-3 HUFA scores in RBCs were comparatively more robust than the O3I at predicting HUFA balances in the kidney, liver, spleen, and lung. Importantly, increases in both the ω-3 HUFA score (>40%) and the O3I (>10%) were strongly associated with suppression of cSiO2-triggered (1) expression of interferon-regulated genes, proinflammatory cytokine production, leukocyte infiltration, and ectopic lymphoid structure development in the lung, (2) pulmonary and systemic autoantibody production, and (3) glomerulonephritis. Collectively, these findings identify achievable ω-3 HUFA scores and O3I thresholds that could be targeted in future human intervention studies querying how ω-3 HUFA consumption influences lupus and other autoimmune diseases.

Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement, including the skin, joints, kidneys, lungs, central nervous system and the haematopoietic system, with a large number of complications. Despite years of study, the etiology of SLE remains unclear; thus, safe and specifically targeted therapies are lacking. In the last 20 years, researchers have explored the potential of nutritional factors on SLE and have suggested complementary treatment options through diet. This study systematically reviews and evaluates the clinical and preclinical scientific evidence of diet and dietary supplementation that either alleviate or exacerbate the symptoms of SLE. For this review, a systematic literature search was conducted using PubMed, Scopus and Google Scholar databases only for articles written in the English language. Based on the currently published literature, it was observed that a low-calorie and low-protein diet with high contents of fiber, polyunsaturated fatty acids, vitamins, minerals and polyphenols contain sufficient potential macronutrients and micronutrients to regulate the activity of the overall disease by modulating the inflammation and immune functions of SLE.

Influence of total western diet on docosahexaenoic acid suppression of silica-triggered lupus flaring in NZBWF1 mice.

Lupus is a debilitating multi-organ autoimmune disease clinically typified by periods of flare and remission. Exposing lupus-prone female NZBWF1 mice to crystalline silica (cSiO2), a known human autoimmune trigger, mimics flaring by inducing interferon-related gene (IRG) expression, inflammation, ectopic lymphoid structure (ELS) development, and autoantibody production in the lung that collectively accelerate glomerulonephritis. cSiO2-triggered flaring in this model can be prevented by supplementing mouse diet with the ω-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). A limitation of previous studies was the use of purified diet that, although optimized for rodent health, does not reflect the high American intake of saturated fatty acid (SFA), ω-6 PUFAs, and total fat. To address this, we employed here a modified Total Western Diet (mTWD) emulating the 50th percentile U.S. macronutrient distribution to discern how DHA supplementation and/or SFA and ω-6 reduction influences cSiO2-triggered lupus flaring in female NZBWF1 mice. Six-week-old mice were fed isocaloric experimental diets for 2 wks, intranasally instilled with cSiO2 or saline vehicle weekly for 4 wks, and tissues assessed for lupus endpoints 11 wks following cSiO2 instillation. In mice fed basal mTWD, cSiO2 induced robust IRG expression, proinflammatory cytokine and chemokine elevation, leukocyte infiltration, ELS neogenesis, and autoantibody production in the lung, as well as early kidney nephritis onset compared to vehicle-treated mice fed mTWD. Consumption of mTWD containing DHA at the caloric equivalent to a human dose of 5 g/day dramatically suppressed induction of all lupus-associated endpoints. While decreasing SFA and ω-6 in mTWD modestly inhibited some disease markers, DHA addition to this diet was required for maximal protection against lupus development. Taken together, DHA supplementation at a translationally relevant dose was highly effective in preventing cSiO2-triggered lupus flaring in NZBWF1 mice, even against the background of a typical Western diet.

Dietary intervention and health in patients with systemic lupus erythematosus: A systematic review of the evidence.

Objective: The aim of this study was to evaluate the scientific evidence of dietary intervention, either through diet or supplementation, and its effects on the health of patients with systemic lupus erythematosus. Methods: Literature searches were conducted using Scopus, PubMed, BioMed Central and Science Direct databases. The terms used for the search were diet, nutritional support, nutrition therapy and systemic lupus erythematosus. Results: Eleven studies with interventions related to supplementation of omega-3 fatty acids, vitamin D and turmeric, as well as changes in diet composition, such as low glycaemic index diet were identified. Conclusions: The studies evidenced that omega-3 supplementation reduced inflammation, disease activity, endothelial dysfunction and oxidative stress; vitamin D supplementation increased serum levels, reduced inflammatory and hemostatic markers; turmeric supplementation reduced proteinuria, hematuria and systolic blood pressure; and low glycaemic index diet caused weight loss and reduced fatigue.

Virgin olive oil and its phenol fraction modulate monocyte/macrophage functionality: a potential therapeutic strategy in the treatment of systemic lupus erythematosus.

Monocytes and macrophages are critical effectors and regulators of inflammation and innate immune response, which appear altered in different autoimmune diseases such as systemic lupus erythematosus (SLE). Recent studies suggested that virgin olive oil (VOO) and particularly its phenol compounds might possess preventive effects on different immune-inflammatory diseases, including SLE. Here, we evaluated the effects of VOO (and sunflower oil) on lipopolysaccharide (LPS)-activated peritoneal macrophages from a model of pristane-induced SLE in BALB/c mice, as well as those of the phenol fraction (PF) from VOO on the immune-inflammatory activity and plasticity in monocytes and monocyte-derived macrophages from healthy volunteers. The release of nitrite and inflammatory cytokines was lower in LPS-treated peritoneal macrophages from pristane-SLE mice fed the VOO diet when compared with the sunflower oil diet. PF from VOO similarly decreased the secretion of nitrite and inflammatory cytokines and expression of inducible nitric oxide, PPARγ and Toll-like receptor 4 in LPS-treated human monocytes. PF from VOO also prevented the deregulation of human monocyte subset distribution by LPS and blocked the genetic signature of M1 macrophages while favouring the phenotype of M2 macrophages upon canonical polarisation of naïve human macrophages. For the first time, our study provides several lines of in vivo and in vitro evidence that VOO and PF from VOO target and counteract inflammatory pathways in the monocyte-macrophage lineage of mice with pristane-induced SLE and of healthy subjects, which is a meaningful foundation for further development and application in preclinical and clinical use of PF from VOO in patients with SLE.

Insuficiencia y deficiencia de vitamina D en pacientes mexicanas con lupus eritematoso sistémico: prevalencia y relación con actividad de la enfermedad / Vitamin D insufficiency and deficiency in mexican patients with systemic lupus erythematosus: prevalence and relationship with disease activity

Objetivos. Determinar la prevalencia de insuficiencia y deficiencia de vitamina D en pacientes con lupus eritematoso sistémico (LES) y compararlas con actividad de la enfermedad. Pacientes y métodos. Estudio comparativo, observacional, transversal y prolectivo. Se incluyeron 137mujeres con LES según los criterios del Colegio Americano de Reumatología. Se excluyeron pacientes con enfermedad renal crónica, cáncer, hiperparatiroidismo, embarazo y lactancia. La actividad fue medida mediante el índice MEX-SLEDAI, considerando actividad ≥3. Se obtuvieron los siguientes datos: diabetes mellitus, uso de glucocorticoides, cloroquina e inmunosupresores, fotoprotección y suplementación con vitamina D. Los niveles de vitamina D se midieron con inmunoanálisis quimioluminiscente considerando insuficiencia a niveles séricos de 25-hidroxivitamina D < 30 ng/ml y deficiencia < 10 ng/ml. Resultados. Se evaluaron 137mujeres con LES (edad promedio 45,9±11,6años, duración de la enfermedad 7,7±3,4 años). La mediana de actividad mediante MEX-SLEDAI fue 2 (0-8),106pacientes en inactividad y 31 con actividad (77,4% versus 22,6%). La insuficiencia y deficiencia de vitamina D se encontró en 122 (89,0%) y 4 (2,9%) pacientes respectivamente. Al comparar los niveles de vitamina D entre pacientes con y sin actividad no existieron diferencias estadísticamente significativas (19,3±4,5 versus 19,7±6,8; p=0,75); tampoco se encontró una correlación con el puntaje MEX-SLEDAI (p=0,21) ni fotosensibilidad, fotoprotección, uso de prednisona, cloroquina ni suplementación con vitamina D. Conclusiones. Las mujeres con LES presentaron elevada prevalencia de insuficiencia de vitamina D. No se encontró asociación de niveles de vitamina D con actividad de la enfermedad (AU)

Objectives. To determine and compare the prevalence of vitamin D insufficiency and deficiency in patients with systemic lupus erythematosus (SLE) with and without disease activity. Patients and methods. We made a comparative, observational, cross-sectional, prospective study of 137 women with SLE according to American College of Rheumatology criteria. Patients with chronic kidney disease, cancer, hyperparathyroidism, pregnancy, and lactation were excluded. Disease activity was assessed using the MEX-SLEDAI score: a score of ≥3 was considered as disease activity. Data were collected on diabetes mellitus, the use of corticosteroids, chloroquine, and immunosuppressants, photoprotection and vitamin D supplementation. Vitamin D levels were measured by chemiluminescent immunoassay: insufficiency was defined as serum 25-hydroxyvitamin D <30ng/ml and deficiency as <10ng/ml. Results. 137 women with SLE (mean age 45.9±11.6 years, disease duration 7.7±3.4 years) were evaluated. Mean disease activity was 2 (0-8): 106 patients had no disease activity and 31 had active disease (77.4% versus 22.6%). Vitamin D insufficiency and deficiency was found in 122(89.0%) and 4 (2.9%) patients, respectively. There was no significant difference in vitamin D levels between patients with and without active disease (19.3±4.5 versus 19.7±6.8; P=.75). No correlation between the MEX-SLEDAI score (P=.21), photosensitivity, photoprotection, prednisone or chloroquine use and vitamin D supplementation was found. Conclusions. Women with SLE had a high prevalence of vitamin D insufficient. No association between vitamin D levels and disease activity was found (AU)

Nutrición y trastornos del sistema inmune / Nutrition and immune system disorders

Introducción: la energía y los nutrientes que obtenemos a través de la alimentación ejercen un papel importante en el desarrollo y preservación del sistema inmune, por lo que cualquier desequilibrio nutricional en el individuo afecta a su competencia e integridad. Objetivos: conocer el abordaje nutricional sobre diferentes trastornos del sistema inmune. Métodos: se ha realizado una revisión sobre los trastornos inmunológicos de mayor prevalencia en países desarrollados, las características nutricionales a los que se encuentran asociados y su abordaje nutricional. Resultados: el abordaje nutricional de los trastornos inmunológicos se ha centrado en los últimos años en los AGP-ω3 y la vitamina D. Mantener el peso corporal, evitar estados de desnutrición y catabolismo proteico, son estrategias clave del tratamiento nutricional. Este debe adecuarse a cada fase de la enfermedad, por lo que se trata de un proceso dinámico. Conclusiones: el abordaje nutricional de los trastornos inmunológicos, sobre todo en las enfermedades autoinmunes, no siempre es del todo claro, debido a los estados agudos y de remisión que presentan. La anorexia es uno de los síntomas más característicos, derivada del tratamiento farmacológico y el proceso inflamatorio. La dieta debe contener una elevada densidad en nutrientes que eviten el deterioro. El abordaje nutricional de los trastornos inmunológicos debe tener como objetivo mantener un estado óptimo de nutrición durante los periodos sintomáticos, prevenir su deterioro durante los episodios agudos y mejorarlo durante los periodos estables libres de sintomatología (AU)

Introduction: Energy and nutrients obtained through food play an important role in the development and preservation of the immune system therefore any nutritional imbalance affects its competence and integrity. Objectives: knowing the nutritional approach on different disorders of the immune system. Methods: A review has been carried out on the most prevalent immunological disorders in developed countries, the nutritional characteristics to which they are associated and their nutritional approach. Results: Nutritional treatment for immune disorders has focused in recent years on the role of PUFA-ω3 and vitamin D. Maintaining body weight, preventing malnutrition and protein catabolism are key strategies for nutritional treatment. This should be adapted to each disease stage because it is a dynamic process. Conclusions: Nutritional treatment for immunological disorders, especially in autoimmune diseases, is not always clear because they present acute and remission states. Anorexia is one of the most characteristic symptoms derived mainly from pharmacological treatment and inflammatory processes. Diet should be dense in nutrients that prevent deterioration. Nutritional treatment of immunological disorders should aim to maintain an optimal state of nutrition during symptomatic periods, prevent their deterioration during acute episodes and improve during stable periods free of symptoms (AU)

Dietary factors regulate cytokines in murine models of systemic lupus erythematosus.

Cytokines play the active roles in the pathogenesis of systemic lupus erythematosus (SLE) and contribute significantly to the immune imbalance in this disease. Conservative therapeutic approaches, such as dietary modifications have been shown to have some beneficial impact on the disease activity of the SLE. Over the past years, accumulating evidences have supported a major role for specific dietary factors, including calorie restriction, n-3/n-6 fatty acids, vitamin A, vitamin D, vitamin E, phytoestrogens or herbal medicine in the regulation of cytokines involved in SLE development. Although there are many reviews that discuss the issue of nutrition and immunity, there are relatively few articles that focus on the regulation of cytokines by dietary factors. This concise review will summarize those animal studies that investigated not only the outcome of autoantibody production and proteinuria, but also cytokines production. However, the field of dietary factors in the immunomodulation of SLE is still in its infancy. More clinical studies are needed to confirm the preliminary results and advance the knowledge in this field. Lifestyle modification and adjustments in diet are important and encouraged to be suggested as an adjuvant therapy for SLE.

The use of micronutrient supplements is not associated with better quality of life and disease activity in Canadian patients with systemic lupus erythematosus.

OBJECTIVE: Associations between the use of micronutrient supplements (MS) and disease activity, quality of life (QOL), and healthcare resource utilization were studied in a Canadian population of patients with systemic lupus erythematosus (SLE). METHODS: QOL was assessed by the Medical Outcomes Study 36-item Short Form. Healthcare resource utilization and disease activity/damage were determined. RESULTS: Of the 259 subjects studied, 53% were MS users and 34% used only calcium/vitamin D. MS users had a higher Systemic Lupus International Collaborating Clinics score and utilized more healthcare resources. Disease activity and QOL were similar between MS users and nonusers. CONCLUSION: MS are frequently used by patients with SLE and are not associated with concomitant benefit on QOL. MS users utilized more healthcare resources.

Soy isoflavones supplementation alleviates disease severity in autoimmune-prone MRL-lpr/lpr mice.

Soy isoflavones supplements, which are phyto-oestrogens widely used as alternatives to alleviate menopausal syndromes or prevent chronic diseases, may exert oestrogenic and anti-oestrogenic activities. This study aimed to investigate the effects of soy isoflavones supplement on oestrogen-related autoimmune disease, such as systemic lupus erythematosus, using autoimmune-prone female MRL-lpr/lpr mice. Eighty mice of 8 weeks were divided into five groups: 0 (Control), 2 (Isf 2), 10 (Isf 10) and 20 (Isf 20) mg/kg BW/day Phyto Soya isoflavones or 0.375 mg/kg BW/day tamoxifen (TAM) as the positive control, by tube-feeding. Some mice were killed at age 15 weeks for cellular cytokine secretion. The data suggested that the Isf 20 and TAM groups had higher weight gain and survival compared with the control group. At age 22 weeks, the Isf 20 group still had 75% survival comparable to mice treated with TAM. At age 14 weeks, the TAM group showed significantly lower serum anti-double-stranded (ds) DNA IgG and anti-cardiolipin IgG. The mice in the Isf 10 and Isf 20 groups also had lower anti-dsDNA IgG and anti-cardiolipin IgG. The interferon (IFN)-gamma secretion from mitogen-stimulated T cells in the Isf 20 and TAM groups were significantly lower than those of control mice. Furthermore, the oestrogenic activity of the methanol extracts of soy isoflavones for oestrogen receptor (ER)beta, but not ERalpha, significantly increased, suggesting that soy isoflavones have a selective modulation of ER activation. Thus, soy isoflavone supplementation did not aggravate murine lupus, but apparently ameliorated the disease.

Effects of vitamins C and E on oxidative stress markers and endothelial function in patients with systemic lupus erythematosus: a double blind, placebo controlled pilot study.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) experience excess morbidity and mortality due to coronary artery disease (CAD) that cannot be fully explained by the classical CAD risk factors. Among emerging CAD risk factors, oxidative stress is currently being emphasized. We evaluated the effects of longterm antioxidant vitamins on markers of oxidative stress and antioxidant defense and endothelial function in 39 patients with SLE. METHODS: Patients were randomized to receive either placebo or vitamins (500 mg vitamin C and 800 IU vitamin E daily) for 12 weeks. Markers of oxidative stress included malondialdehyde (MDA) and allantoin. Antioxidants measured included erythrocyte superoxide dismutase and glutathione peroxidase, plasma total antioxidant power (as FRAP value), and ascorbic acid and vitamin E concentrations. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery and plasma concentration of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1). Primary outcome of the study included the change in lipid peroxidation as revealed by MDA levels. Secondary outcomes included changes in allantoin and antioxidant levels and change in endothelial function. RESULTS: After treatment, plasma ascorbic acid and alpha-tocopherol concentrations were significantly (p < 0.05) increased only in the vitamin-treated group, associated with a significant decrease (p < 0.05) in plasma MDA. Other oxidative stress markers and antioxidant levels remained unchanged in both groups. FMD and vWF and PAI-1 levels remained unchanged in both groups. CONCLUSION: Combined administration of vitamins C and E was associated with decreased lipid peroxidation, but did not affect endothelial function in patients with SLE after 3 months of therapy.

[Characteristics of rehabilitation in patients with rheumatic diseases]. / Ossobennosti vosstanovitel'nogo lecheniia bol'nykh revmatologicheskogo profilia.

The paper deals with problems of rehabilitation of patients with rheumatoid arthritis, osteoarthrosis and systemic lupus erythematosus. These problems are rather topical in view of high prevalence of rheumatic diseases, their severe course and a high rate of invalidization at the most productive age. Relevant multifactorial therapeutic measures should be staged, aimed at lowering and stabilization of the disease activity. The role of updated medication, joint surgery, diet therapy, etc. is shown.

Dietary CLA decreased weight loss and extended survival following the onset of kidney failure in NZB/W F1 mice.

In an earlier study, we showed that feeding CLA immediately after weaning prolonged survival of NZB/W F1 mice after onset of proteinuria. In the present study, the feeding of CLA was delayed until mice had developed proteinuria. Thirty NZB/W F1 mice were fed a regular rodent chow after weaning. Urine samples were collected to detect proteinuria. Once a mouse was proteinuria positive, it was then randomly assigned to a 0.5% CLA supplement semipurified diet or a control diet (supplement 0.5% corn oil). The next proteinuria positive mouse was then assigned to the opposite diet to which the first mouse was assigned. Mice fed the control diet lost 25% more body weight (13.0 g) than mice fed the CLA diet (9.7 g). Moreover, CLA-fed mice survived an average 1.7-fold longer (148 d) than mice fed the control diet (89 d) after the onset of proteinuria. This follow-up study confirmed that dietary CLA had a beneficial effect in the autoimmune NZB/W F1 mouse. In summary, the cachectic symptom of systemic lupus erythematosus was decreased by dietary CLA and survival days were increased over control group.

Current concepts for the management of systemic lupus erythematosus in adults: a therapeutic challenge.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune rheumatic disease with many clinical presentations typically affecting women of childbearing age. The successful therapy of SLE depends upon treating both symptoms and the underlying inflammation. Both non-pharmacological as well as pharmacological therapies are invariably required. Non-pharmacological therapy includes avoiding over-exposure to sunlight with the use of adequate sunscreen protection, avoiding "live" vaccination if on immunosuppressive agents, adherence to a diet low in saturated fat and high in fish oil, stress avoidance, and smoking cessation. Pharmacological measures revolve around four main classes of drugs: non-steroidal anti-inflammatory drugs, antimalarials, corticosteroids, and cytotoxic agents. Cyclophosphamide and azathioprine are the two most commonly used cytotoxic agents and these in combination with corticosteroids need to be employed early if there is major organ involvement to prevent or minimise irreversible damage. The potential side effects of corticosteroids and cytotoxic agents need constant consideration. The rapid developments in biotechnology of recent years may soon lead to new and more specific therapies for patients with SLE.

Natural medicine and nutritional therapy as an alternative treatment in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder without a known cure. Conventional medicine typically approaches the disease with a treatment plan that includes the use of corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), antimalarial drugs, and chemotherapeutic agents. The results vary and safety is questionable. Conservative treatment methods, such as the use of vitamins, minerals, and fatty acids, have been shown to have an impact on the activity of the disease. Alternative medicine treatments, including the use of dehydroepiandrosterone (DHEA) and Chinese medicines, such as Tripterygium wilfordii Hook F (TwHF), have gained a growing interest recently and may prove to be viable treatment options in the future. The elimination of possible associated factors, such as food allergens and SLE-symptom eliciting foods like alfalfa seeds, have also been shown to affect disease activity. Conservative alternative medicine approaches have been shown to provide some benefit in SLE studies; however, the evidence is limited, and the overall effectiveness and long-term safety have not been established. More research must be conducted in this area to further establish firm treatment protocols which provide maximum therapeutic benefit and minimum treatment-related side effects.

Diet and lupus.

The effect of dietary modifications has been extensively studied in lupus animal models. Calorie, protein, and especially fat restriction, caused a significant reduction in immune-complex deposition in the kidney, reduced proteinuria and prolongation of the mice's life span. The addition of polyunsaturated fatty acids (PUFAs), such as fish oil or linseed oil, was also related to decreased mice morbidity and mortality in animal models of lupus and of antiphospholipid syndrome. PUFAs such as eicosapetaenoic acid (EPA) and docosahexaenoic acid (DHA) competitively inhibit arachidonic acid with a resultant decrease in inflammatory eicosanoids and cytokines. Human studies support the effect of a PUFAs-enriched diet, both scrologically and clinically. Large scale clinical studies are needed to confirm the primary results.

Lupus erythematosus and nutrition: a review of the literature.

The purpose of this review was to search the scientific literature for dietary compounds that alleviate or exacerbate symptoms of lupus erythematosus (LE) in both animal and human models. A detailed literature review was undertaken to find articles showing a relationship between LE and nutrition by using MEDLINE/INDEX MEDICUS (1950-March 2000) for English-language articles, followed by cross-referencing. Aggravating substances appear to include excess calories, excess protein, high fat (especially saturated and omega-6 polyunsaturated fatty acids), zinc, iron, and L-canavanine found in alfalfa tablets. Possible beneficial dietary compounds include vitamin E, vitamin A (beta-carotene), selenium, fish oils (omega-3 polyunsaturated fatty acids), evening primrose oil, flaxseed, a plant herb (Tripterygium wilfordii), dehydroepiandrosterone, and calcium plus vitamin D (if taking corticosteroids). Some people with systemic LE placed on food allergy elimination diets reported improvement in their LE symptoms; however, this may be related to a decrease of other substances in the diet. Also, although no direct evidence was reported on the beneficial effects of either bromelain or a vegetarian diet (possibly allowing fish), it is suggested that they might be beneficial. Limitations to this research are that the findings are based on relatively few studies, many of which were without control groups or extrapolated from animal models. No large-scale studies have been performed with LE patients to substantiate the benefit, if any, of these individual dietary interventions, and if they were conducted, the remission and exacerbation pattern of LE may interfere with elucidating their effectiveness. Also, dietary changes should not be attempted without a physician's approval/monitoring.

Polyunsaturated fatty acids and renal disease.

An upregulation of arachidonate metabolism often accompanies renal pathophysiologic states. The resulting eicosanoids contribute to, or modify, the underlying process. Recent investigations suggest that platelet-neutrophil interactions, as well as alterations in the expression of the inducible isoform of cyclooxygenase, play a critical role in mediating changes in arachidonate metabolism in renal inflammation. The importance of arachidonate to renal pathophysiology has been highlighted by prior investigations which have demonstrated a beneficial effect of dietary polyunsaturated fatty acid (PUFA) modulation in a variety of models of experimental renal disease. More recent work has established that this beneficial effect may depend upon alterations in both lipid mediator generation as well as changes in cell function. In light of the benefits of dietary PUFA modulation in models of experimental renal disease, there have been numerous recent clinical trials of dietary (n-3) PUFA supplementation in patients with a variety of renal disorders. These clinical trials suggest that such therapy may be an important addition to the clinical armamentarium, especially in the treatment of IgA nephropathy.