Lupus – Prevention and Treatment with a Plant-Based Diet

This article was published in Orthopedics and Rheumatology Open Access Journal.

Abstract

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune rheumatic disease in which disease flares are interspersed with episodes of remission. In contrast to organ-specific autoimmune diseases, SLE comprises a constellation of signs and symptoms that can affect multiple organ systems.

A plant-based diet may have a beneficial effect on SLE patients, due not only to the direct action of nutrients on the immune system and inflammation, but also to an indirect effect on insulin resistance, obesity and associated co-morbidities.

Accelerated atherosclerosis is a significant comorbidity and the leading cause of death for patients with SLE. Patients are also more likely to experience metabolic syndrome leading to type II diabetes, obesity, and chronic kidney disease. A plant-based diet is a safe and efficacious prophylaxis and treatment for all these comorbidities.

Three small interventional studies with a plant-based diet showed a beneficial effect on patients’ symptoms and therefore their quality of life.  A plant-based diet has the advantage of having no adverse reactions or contraindications and can be an effective adjunct to standard treatments.

To cite this article: Rose S, Strombom A. Lupus – prevention and treatment with a plant-based diet. Ortho & Rheum Open Access J. 2023:21(1);556060

 

Introduction

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune rheumatic disease in which disease flares are interspersed with episodes of remission. In contrast to organ-specific autoimmune diseases, SLE comprises a constellation of signs and symptoms that can affect multiple organ systems. (1) Common symptoms include fatigue, joint and muscle pains and skin lesions, as well as more severe manifestations affecting the kidneys, central nervous system, heart and lungs. Symptoms can be heterogeneous, intermittent and range in severity, (2) requiring the establishment of eleven criteria with four needed for the formal diagnosis of SLE. (3) (4)

SLE affects up to 322,000 adults in the United States. (5) It can begin at any age and affect both sexes, but more than 90% of new patients presenting with SLE are women in the childbearing years, most often at the end of the patient’s second decade and beginning of the third decade of life. (6) (7)

 

Pathophysiology and Epidemiology

Genetic predisposition, environmental triggers, and the hormonal milieu, interplay in SLE disease development and activity. (8) The action of these pathogenic factors results in the generation of autoantibodies, immune complexes, autoreactive or inflammatory T cells and inflammatory cytokines that may initiate and amplify inflammation and damage to various organs, contributing to the clinical manifestations of SLE.

It is characterized by a deposition of immune complexes, formed in large amounts as antinuclear antibodies bind to the abundant nuclear material in blood and tissues, along with disturbances in both innate and adaptive immunity manifest by disorders in cytokines, apoptotic cell clearance, B-cell immunity and T-cell signaling. (9) (10)

SLE Patients with active SLE exhibit high cytokine levels, including IFN-γ, TNF, IL-4, IL-6, IL-10, IL-12, IL-17 and IL-18 in serum and plasma; by contrast, IL-2 levels are lower in comparison with healthy controls. (11)

Comorbidities

Accelerated atherosclerosis is a significant co-morbidity and the leading cause of death for patients with SLE. (12)  Patients suffering with SLE have approximately double the risk of atherosclerotic cardiovascular disease (CVD), stroke, heart failure and atrial fibrillation compared with the general population. (13)  One study showed that more than half of the patients with SLE presented three or more risk factors for CVD (mostly obesity, hypertension and dyslipidemias). (14) In another study, patients with SLE were identified to have a twofold to threefold higher risk of stroke and MI. (15)

In patients with SLE, traditional risk factors for CVD (age, hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, and positive family history) are more prominent than non-traditional factors, and appear to have a major role in lupus-enhanced atherogenesis. (16) In particular hypertension and hypercholesterolemia have been shown to be independently associated with premature atherosclerosis in several SLE cohorts. (17) (18) (19)  The prevalence of dyslipidemia, with elevations in total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), and apolipoprotein B (ApoB), are about 30% at the diagnosis of SLE rising to 60% after 3 years. (20) CV events occur both early and late during the disease course, with younger patients being at much higher risk than their age-matched counterparts. (13)

However, cohort studies have revealed that traditional atherosclerotic risk factors do not fully account for the CVD susceptibility in patients with SLE.  It may also be due to pathophysiologic intermediates such as type I interferons and other inflammatory cytokines, oxidative stress, activated granulocytes and production of extracellular chromatin traps, antiphospholipid and other autoantibodies causing dysfunction of lipoproteins, altogether resulting in endothelial injury and pro-atherogenic dyslipidemia. (13)

In SLE, autoantibodies and cytokines are able to modulate and decrease lipoprotein lipase activity, a key enzyme in lipid metabolism, producing the ‘lupus pattern’ of dyslipoproteinemia, characterized by elevated levels of VLDL (very low density LDL) and triglycerides and low HDL-cholesterol levels, which are directly correlated with SLE disease activity index (SLEDAI) scores. (21) These mechanisms may be further aggravated by chronic intake of prednisone, even at doses <7.5 mg/day (13)

Studies have reported a high prevalence of overweight and obese patients with SLE (22) (23) In a representative sample of women with SLE, obesity (as defined by both FMI [fat mass index] and BMI) was independently associated with worse patient-reported outcomes  including disease activity, depressive symptoms, and symptoms of pain and fatigue. Obesity may represent a modifiable target for improving outcomes among obese women with SLE. (24)

With regards to diabetes mellitus risk, a study showed that patients with SLE are more likely to have metabolic syndrome. (25) Treatment with a daily glucocorticoid ≥10 mg prednisolone-equivalent dose was associated with increased risk of developing diabetes mellitus. (26) Interestingly, patients treated with hydroxychloroquine had their risk of type II diabetes attenuated. (26)

Renal involvement is present in about 50% of patients with lupus, with a predilection for certain ethnic groups such as African-Americans (70%). (27) Early detection and treatment are paramount since lupus nephritis is a major cause of morbidity and mortality in SLE and delayed diagnosis is a risk factor for end-stage renal disease. (28) (29)

Death in patients with SLE may be due to lupus activity (when vital organs or systems are involved), complications of treatment (particularly infections), or long-term sequelae (such as cardiovascular disease). (28)

Dietary Factors

A healthy diet may have a beneficial role in SLE patients, due not only to a direct action of nutrients on the immune system and inflammation, but also to an indirect effect on insulin resistance, obesity and associated co-morbidities. (30) (31)

Unhealthy dietary patterns may contribute to the development and course of SLE. (32) (33) Specific dietary factors, including vitamins, mineral elements, fatty acids and polyphenols, play a major role in the modulation of immune responses, so an inadequate diet could constitute an important risk factor in SLE epidemiology. (34) (35) (36) (37)

Insufficient study has been done in this area, but in one study, women in the highest (versus lowest) AHEI-2010 (alternative healthy eating index) tertile of nut and legume intake had a 41% decreased risk of SLE. (38)

Vitamin D deficiency may be a risk factor for SLE (39). Vitamin D deficiency is commonly reported in SLE patients, (40) and can contribute to the morbidity and mortality of these patients (41). SLE may lead to lower vitamin D levels and vitamin D deficiency may have a causative role in SLE etiology and/or aggravation (42).

One study found that 67% of the SLE patients were vitamin D deficient, with mean levels significantly lower among African Americans (15.9 ng/ml) compared to Caucasians (31.3 ng/ml). Critically low vitamin D levels (<10 ng/ml) were found in a number of SLE patients.  (43)

 

Dietary Intervention studies

Interventional studies of SLE can be difficult to perform, given that SLE causes immunologically mediated injury in multiple body systems and symptoms can be heterogeneous, intermittent and range in severity. (1) However, one small study and two case studies have given us some information.

In an interventional study, patients adhering to a WFPB (whole food plant-based) diet were more likely to experience benefits from dietary change, including a significant 26% decrease in SLE symptom severity, especially for SLE patients with initially severe symptoms. (2)

In a case study of a 24-year-old female patient treated with a WFPB diet, her estimated glomerular filtration rate increased from 14 to 27 ml/min in 6 weeks, and it was determined that she no longer needed dialysis or a kidney transplant. Her energy and joint pain levels also significantly improved. (44)

In another case study of a 41-year-old male patient treated with a WFPB diet, symptoms resolved and laboratory tests were normalized on the diet. However, this patient experienced challenges with adhering to the diet, and it was clear that whenever he deviated from it, symptoms reappeared and his estimated glomerular filtration worsened. (44)

Looking specifically at fatty acid intake in patients with stable disease, a diet rich in polyunsaturated fatty acids (PUFA) was found to have a positive impact on overall clinical status. (37) With a concentration of 70% omega-3 PUFA and rich in α-linolenic acid, daily intake of 30g of flaxseed oil was found to lower serum creatinine in SLE patients with renal dysfunction. (45) (46)

A study, monitoring the dietary impact of two isocaloric diets on pregnant patients with SLE and antiphospholipid syndrome, emphasized that the diet with higher level of PUFA reduced the risk of fetal loss and symptoms. (47)

Increasing polyunsaturated fatty acids and phytoestrogens showed a decrease in proteinuria and glomerulonephritis in animal models of SLE. (48)

 

Clinical Considerations

SLE is characterized by its clinical and pathogenic complexity, difficult diagnosis and the high number of complications that can affect the patients’ quality of life. The high morbidity and mortality associated with patients with SLE may be related to late diagnosis, problems in access to care, less effective treatments, and poor adherence to therapeutic regimens. (49)

SLE management remains complicated owing to the biological heterogeneity between patients and the lack of safe and specific targeted therapies. Thus the search for new therapeutic targets and strategies that can act more selectively on certain routes or biological processes, and improve the course of disease or reverse the outbreak phase, without generating collateral damage to unaffected tissues and organs, is the pillar underlying current research in SLE. (32)

Pharmacological treatment in SLE aims to prevent organ damage and achieve remission. The choice of treatment is dictated by the organ system/systems involved and the severity of involvement.  It ranges from minimal treatment (NSAIDs, antimalarials) to intensive treatment (cytotoxic drugs, corticosteroids). Newer agents for treatment of SLE are the B-lymphocyte inhibitor belimumab, the interferon antagonist anifrolumab, and the calcineurin inhibitor voclosporin.

The autoimmunity and inflammatory processes of SLE are related to the presence of dyslipidemia, obesity, systemic arterial hypertension, and metabolic syndrome. It is of prime importance to treat these comorbidities in order to decrease cardiovascular risk. (50) A diet with moderate protein and energy content, but rich in vitamins, minerals, antioxidants and mono/polyunsaturated fatty acids, can provide a beneficial protective effect against tissue damage and suppression of inflammatory activity, in addition to helping the treatment of comorbidities. (45)

For over 50 years, evidence from interventional studies has strongly indicated that a low-fat plant-based diet is both safe and efficacious in the treatment of coronary artery disease (CAD). (51) (52) (53) (54) (55) (56) (57)  In particular, epidemiological studies show a 40% risk reduction of ischemic heart disease (58) and a 50% risk reduction of coronary heart disease mortality (59) for those following a vegetarian diet.

Plant-based diets are effective in treating hypercholesterolemia. (60) (61) (62) In particular, a plant-based diet has been shown to be as effective as Lovastatin in treating hypercholesterolemia (61). Studies also show a large reduction in the frequency of angina pectoris episodes using a plant-based diet (52) (63) (64) and coronary artery stenosis can show modest but significant regression or can be halted. (57)

Studies have shown that the vast majority of patients can maintain a plant-based diet for at least 4 years, and experience its resulting benefits during that time. (52) (53) (54)  Mortality due to myocardial infarction can therefore be greatly reduced. (51)

Those following a plant-based diet have a 78% reduction risk of type II diabetes mellitus, as well as a 56% reduced risk of metabolic syndrome. (65) Interventional studies using a plant-based diet show a reduction of HbA1C by as much as 2.4 percentage pts, which is more than is usually achieved with the leading medication, Metformin. (66) (67)

While dietary regimens for patients with SLE are mainly aimed at reducing CVD risk, recent evidence suggests that healthier dietary habits could also improve inflammatory markers and immune function, with possible benefit on many disease symptoms. (45) (33)  In particular a plant-based diet reduces the risk of a number of other pathologies such as type 2 diabetes, (65) stroke, (68) osteoarthritis, (69) prostate and colon cancer, (70) (71) diverticular disease, (72) ulcerative colitis, (73) Crohn’s disease, (74) chronic kidney disease, (75) Grave’s disease, Hashimoto’s thyroiditis (76) and rheumatoid arthritis (77) just to name a few.

Significant weight loss can also be achieved with a plant-based diet. (52) Vegetarian diets generally are associated with lower BMI in observational and randomized controlled studies. A study of American vegans found that they had a mean BMI of 23.6. (78)  A European study found the average BMI of vegetarians and vegans to be 23.3 and 22.4 respectively for men and 22.8 and 21.8 for women. (79) A study of German vegans found an average BMI of 22.3. (80) In contrast, the average BMI for American men over age 20 for the year 2015-2016 is 29.1. The average BMI for American women over age 20 for the year 2015-2016 is 29.6. (81)

Plant-based diets are no longer very unusual as they have become more popular in the general population in recent years. Given all of the benefits, the plant-based diet deserves a place among the physician’s treatment options for SLE.

In a study looking at the motivation for patients with SLE making dietary changes, the main reasons given for patients making dietary changes were to become healthier overall (83%) or to improve lupus symptoms (77%). In contrast, common reasons reported for not changing eating habits were due to not having enough information (41%). (2)

In another study, patients reported that there was a lack of clinical counselling regarding diet, with only 24% stating their doctor had spoken to them about diet. Despite this, 100% of patients stated they would change their diet if they knew it would help their symptoms. (82)  This suggests that specific dietary advice is likely to be welcomed by patients, when carefully explained.

Since 90% of patients are female and of child-rearing age, it is important to note that well-planned plant-based diets have been confirmed as safe during pregnancy and lactation, as well as conferring additional health advantages, such as lower risk of excessive gestational weight gain and preeclampsia. (83)

When treating comorbidities, it’s important to titrate relevant medications as the effect of the plant-based diet become evident. Lab work should be done before starting treatment with a plant-based diet and then 6 to 8 weeks afterwards, since the therapeutic effects of a plant-based diet often take several weeks to become evident.

Vitamin D deficiency can affect disease activity and disease damage in SLE patients (84). In addition, patients with SLE may avoid the sun because of photosensitive rashes and potential for disease flare, (41) so adequate vitamin D supplementation is vital for them. Lab work for SLE patients should include testing for vitamin D deficiency. (85)

 

Discussion

Treatment goals for patients with SLE include long term patient survival, prevention of organ damage, and optimization of health-related quality of life. Achieving these goals can be challenging for patients and physicians alike.

A plant-based diet can help prevent and treat comorbidities commonly associated with SLE. It is a safe and efficacious prophylaxis and treatment for hypercholesterolemia, atherosclerosis, essential hypertension and coronary artery disease. It is also a safe and efficacious treatment for chronic kidney disease, type 2 diabetes and obesity. The plant-based diet can reduce symptoms and increase quality of life of SLE patients.

While medications are available to treat SLE, it’s important to note that the plant-based diet has no adverse reactions or contraindications and can therefore act as a useful adjunct to standard treatments, both for SLE and its comorbidities. It can also be a valuable monotherapy between flare ups. Its safety profile can be especially valuable for pregnant patients or patients wishing to become pregnant.

SLE patients often face large healthcare costs. A healthy plant-based diet costs no more than a standard diet.  Given its efficacy, it can also decrease the cost of treating comorbidities.

 

Conflict of Interest

The authors state no conflicts of interest.

 

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