Diet in Systemic Lupus Erythematosus: Comparison
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In recent years, an increasing interest in the influence of diet in rheumatic and musculoskeletal diseases (RMDs) led to the publication of several articles exploring the role of food/nutrients in both the risk of developing these conditions in normal subjects and the natural history of the disease in patients with established RMDs. Diet may be a possible facilitator of RMDs due to both the direct pro-inflammatory properties of some nutrients and the indirect action on insulin resistance, obesity and associated co-morbidities. A consistent body of research has been conducted in rheumatoid arthritis (RA), while studies in systemic lupus erythematosus (SLE) are scarce and have been conducted mainly on experimental models of the disease.

  • systemic lupus erythematosus
  • rheumatoid arthritis
  • cardiovascular risk
  • Mediterranean diet
  • polyunsaturated fatty acids

1. Introduction

The relationship between diet and chronic diseases has been extensively investigated with the so-called “Western-type” diet, characterized by high intake of refined grains, desserts and sweets, processed meat, red meat, condiments, and pizza, which are associated with cardiovascular (CV) disease and mortality risk in large prospective cohort studies [1]. Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are systemic autoimmune diseases, and patients suffering with these conditions have approximately double the risk of atherosclerotic CV disease, stroke, heart failure and atrial fibrillation compared with the general population [2,3]. Recently, specific recommendations for the management of CV risk in inflammatory arthritis have been issued, incorporating the concept that besides conventional CV risk factors, chronic inflammation accounts for this increased CV risk [4]. Since this also applies to SLE, a dual approach has been pursued in patients with RA and SLE. This dual approach is based on targeting conventional CV risk factor reduction and on the reduction of disease activity for the primary and secondary prevention of CV events and mortality in these patients [5,6].

The relationship between diet and chronic diseases has been extensively investigated with the so-called “Western-type” diet, characterized by high intake of refined grains, desserts and sweets, processed meat, red meat, condiments, and pizza, which are associated with cardiovascular (CV) disease and mortality risk in large prospective cohort studies [1]. Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are systemic autoimmune diseases, and patients suffering with these conditions have approximately double the risk of atherosclerotic CV disease, stroke, heart failure and atrial fibrillation compared with the general population [2][3]. Recently, specific recommendations for the management of CV risk in inflammatory arthritis have been issued, incorporating the concept that besides conventional CV risk factors, chronic inflammation accounts for this increased CV risk [4]. Since this also applies to SLE, a dual approach has been pursued in patients with RA and SLE. This dual approach is based on targeting conventional CV risk factor reduction and on the reduction of disease activity for the primary and secondary prevention of CV events and mortality in these patients [5][6].

Over the last decades, an increasing number of studies explored the possible impact of nutrients and different dietary patterns on the risk of developing rheumatic and musculoskeletal diseases (RMDs), particularly RA [7,8]. Diet may be a possible facilitator of RMDs due to both the direct pro-inflammatory properties of some nutrients and their indirect action on insulin resistance, obesity and associated co-morbidities [9,10]. Further, the balance of macronutrients and omega-6/omega-3 fatty acids in the daily diet has been described to modulate the expression of inflammatory genes [11].

Over the last decades, an increasing number of studies explored the possible impact of nutrients and different dietary patterns on the risk of developing rheumatic and musculoskeletal diseases (RMDs), particularly RA [7][8]. Diet may be a possible facilitator of RMDs due to both the direct pro-inflammatory properties of some nutrients and their indirect action on insulin resistance, obesity and associated co-morbidities [9][10]. Further, the balance of macronutrients and omega-6/omega-3 fatty acids in the daily diet has been described to modulate the expression of inflammatory genes [11].

However, single dietary components may confer only modest benefits. Since individual foods are part of complex dietary patterns, in recent years scores of overall dietary quality have received increasing attention in disease prevention. Dietary pattern scores provide a broader perspective on this matter and a relative measure of the healthfulness of an individual’s diet. Hence, they may provide insights not only on the role of individual nutrients but also their combination.

In addition, diet may also have an effect in worsening/improving RMDs in patients with established diseases, and differences may exist across various conditions [8,12].

In addition, diet may also have an effect in worsening/improving RMDs in patients with established diseases, and differences may exist across various conditions [8][12].

2. Diet and Risk of SLE Development

While there are several studies exploring the role of nutrients in the risk of developing RA [7], literature on SLE is scarce (

Table 1

). The Western type of diet was not associated with a higher risk of developing SLE, and the healthiest prudent pattern—reflecting a diet higher in vegetables, fruit, legumes, fish, tomatoes, poultry, and whole grains—was not associated with a lower risk of developing the disease [13].

Table 1.
 Comparison of data available about different dietary patterns and the risk of developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in normal subjects.
Dietary Pattern or Nutrient, Ref N RA N SLE
AHEI-2010 total score [14,15][14][15] 76,597 ↓ risk 204,055 no association
AHEI-2010 alcohol domain (moderate intake) [14,15][14][15] 76,597 ↓ risk 204,055 no association
AHEI-2010 red meat domain (lower intake) [14,15][14][15] 76,597 ↓ risk 204,055 no association
AHEI-2010 nut/legume intake (higher intake) [14,15][14][15] 76,597 no association 204,055 ↓ risk
aMed [15] 204,055 no association 204,055 no association
DASH [15] 204,055 no association 204,055 no association
EDIP [15,16][15][16] 173,560 ↑ risk 204,055 no association
AHEI, alternative healthy eating index; aMed, alternate mediterranean diet; DASH, dietary approach to stop hypertension; EDIP, empirical dietary inflammatory pattern.

As far as the scores of overall dietary quality are concerned, the Nurses’ Health Study (NHS) and NHS II provided important insights on this matter. These studies involved two large prospective cohorts that allowed the exploration of the risk of developing RMDs based on dietary habits, monitored over time with validated instruments [14][15].

2.1. Alternative Healthy Eating Index (AHEI-2010) and Its Domains

Although a healthier diet, as defined by a higher adherence to the 2010 alternative healthy eating index (AHEI-2010), was associated with a reduced risk of RA, particularly seropositive, occurring at 55 years of age or younger [14], no association between long-term adherence to the AHEI-2010 and SLE risk was observed [15]. The AHEI-2010 was developed by researchers at the Harvard School of Public Health as an alternative measure of diet quality to identify future risk of diet-related chronic disease [17]. It includes a variety of foods/nutrients and defines fruits, vegetables, whole grains, nuts, long-chain n-3 polyunsaturated fatty acids (LC-PUFAs), and moderate alcohol consumption as healthy items, while sugar-sweetened beverages, red/processed meat, trans fat and sodium intake are classified as unhealthy components. As far as AHEI-2010 subdomains are concerned, a higher score of alcohol (moderate intake) or red meat consumption (lower intake) was significantly associated with a reduced RA risk regardless of body mass index (BMI). Conversely, women in the highest AHEI-2010 tertile of nut/legume intake had a decreased risk of developing SLE compared to those in the lowest tertile, but no other association was observed [15].

The data on alcohol consumption and RA are in line with a recent meta-analysis of prospective studies demonstrating that low to moderate intake is inversely associated with the development of RA in a dose, time and gender-dependent manner [18].

As far as the scores of overall dietary quality are concerned, the Nurses’ Health Study (NHS) and NHS II provided important insights on this matter. These studies involved two large prospective cohorts that allowed the exploration of the risk of developing RMDs based on dietary habits, monitored over time with validated instruments [14,15].

On the contrary, the link between alcohol consumption and SLE risk remains controversial. A meta-analysis conducted in 2008 demonstrated that moderate alcohol intake had a protective effect on the development of SLE [19], and the subsequent studies were in line with the previous literature [20][21][22][23]. However, no genetic association in this regard has been identified [24]. Furthermore, no association for a higher risk in heavy alcohol consumers was reported by other studies [25][26].

2.1. Alternative Healthy Eating Index (AHEI-2010) and Its Domains

Although a healthier diet, as defined by a higher adherence to the 2010 alternative healthy eating index (AHEI-2010), was associated with a reduced risk of RA, particularly seropositive, occurring at 55 years of age or younger [14], no association between long-term adherence to the AHEI-2010 and SLE risk was observed [15]. The AHEI-2010 was developed by researchers at the Harvard School of Public Health as an alternative measure of diet quality to identify future risk of diet-related chronic disease [17]. It includes a variety of foods/nutrients and defines fruits, vegetables, whole grains, nuts, long-chain n-3 polyunsaturated fatty acids (LC-PUFAs), and moderate alcohol consumption as healthy items, while sugar-sweetened beverages, red/processed meat, trans fat and sodium intake are classified as unhealthy components. As far as AHEI-2010 subdomains are concerned, a higher score of alcohol (moderate intake) or red meat consumption (lower intake) was significantly associated with a reduced RA risk regardless of body mass index (BMI). Conversely, women in the highest AHEI-2010 tertile of nut/legume intake had a decreased risk of developing SLE compared to those in the lowest tertile, but no other association was observed [15].
The data on alcohol consumption and RA are in line with a recent meta-analysis of prospective studies demonstrating that low to moderate intake is inversely associated with the development of RA in a dose, time and gender-dependent manner [18].
On the contrary, the link between alcohol consumption and SLE risk remains controversial. A meta-analysis conducted in 2008 demonstrated that moderate alcohol intake had a protective effect on the development of SLE [19], and the subsequent studies were in line with the previous literature [20,21,22,23]. However, no genetic association in this regard has been identified [24]. Furthermore, no association for a higher risk in heavy alcohol consumers was reported by other studies [25,26].
Other dietary quality scores have also been explored in relation to the risk of RA or SLE onset in the NHS and NHS II cohorts.

Other dietary quality scores have also been explored in relation to the risk of RA or SLE onset in the NHS and NHS II cohorts.

2.2. Mediterranean Diet, the Dietary Approach to Stop Hypertension (DASH) and the Empirical Dietary Inflammatory Pattern (EDIP)

The Mediterranean diet is a dietary pattern based on whole or minimally processed foods and a high intake of vegetables, fruits, whole grains, fish and olive oil, with moderate consumption of red meat and wine. The adherence to the Mediterranean diet proved to be effective in preventing metabolic diseases such as diabetes and CV diseases [27,28,29]. The alternate Mediterranean diet (aMed) score is a modified version of an existing Mediterranean diet scale containing nine components including vegetables (not potatoes), fruits, nuts, whole grains, legumes, fish, the ratio of monounsaturated to saturated fat, red and processed meats and alcohol [30]. Greater adherence to a Mediterranean dietary pattern, as measured by the aMed score, did not affect the risk of developing RA or SLE [15] in healthy individuals.

The Mediterranean diet is a dietary pattern based on whole or minimally processed foods and a high intake of vegetables, fruits, whole grains, fish and olive oil, with moderate consumption of red meat and wine. The adherence to the Mediterranean diet proved to be effective in preventing metabolic diseases such as diabetes and CV diseases [27][28][29]. The alternate Mediterranean diet (aMed) score is a modified version of an existing Mediterranean diet scale containing nine components including vegetables (not potatoes), fruits, nuts, whole grains, legumes, fish, the ratio of monounsaturated to saturated fat, red and processed meats and alcohol [30]. Greater adherence to a Mediterranean dietary pattern, as measured by the aMed score, did not affect the risk of developing RA or SLE [15] in healthy individuals.

The Dietary Approach to Stop Hypertension (DASH) is a healthy dietary pattern focused on eight components: high intake of fruits, vegetables, nuts and legumes, low-fat dairy products and whole grains, and low intake of sodium, sweetened beverages and red and processed meats [31]. Although previously evaluated only in metabolic diseases, including gout, the recent evidence of a pivotal role of sodium in the induction of autoimmunity led investigators to also explore this pattern in RA and SLE; however no direct association with the risk of developing either disease was demonstrated [15].

The empirical dietary inflammatory pattern (EDIP) includes different foods based on their association with plasma levels of inflammatory biomarkers (including C-reactive protein and IL-6) [32]. The nine anti-inflammatory groups include beer, wine, tea, coffee, dark yellow vegetables, leafy green vegetables, snacks, fruit juice and pizza. The nine pro-inflammatory groups include processed meat, red meat, organ meat, non-dark meat fish, other vegetables, refined grains, high-energy beverages, low-energy beverages and tomatoes. In RA, increasing EDIP scores (namely, most inflammatory dietary intake) were associated with increased risk of seropositive RA among women aged 55 years or below [16]. Conversely, no association between EDIP scores and SLE risk was observed [15].

A detailed analysis of the NHS and NHS II cohorts with regard to the intake of antioxidants from foods and supplements was also conducted; however, it ruled out any protective effect of both the range of antioxidant intakes and of the overall antioxidant intake on the risk of developing RA or SLE [33]. Moreover, it was reported that omega-3 fatty acids could prevent the development of RA, improve muscle metabolism and reduce muscle atrophy in subjects at high metabolic risk [34].

The existing literature does not allow any definitive conclusions to be drawn either in favor or against a role of diet in the risk of developing SLE onset. However, with the only exception of alcohol consumption, studies on other nutrients as well as on dietary patterns are still too few. Therefore, any association (or lack thereof) deserves to be further explored, focusing also, for example, on the possible interaction between food and microbiome, given its role in SLE pathogenesis [35].

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