Food for Thought: On Eating & Inflammation in Rheumatic Disease

ACR CONVERGENCE 2020—At a food-focused ACR Convergence session, rheumatologists shared recent data on the effects of nutrients, herbal supplements and dietary patterns on inflammation, as well as tips for talking with patients about diet and other healthy lifestyle interventions.

Short-Term Fasting
Strict diets usually result in low compliance. “Calorie restriction has been known for a long time to have anti-inflammatory effects, but it is also very difficult to do,” said biogerontologist Valter Longo, PhD, director of the University of Southern California Longevity Institute in Los Angeles. His laboratory team developed a fasting mimicking diet (FMD) low in calories, protein and sugar, and high in unsaturated fats. The FMD includes high levels of prebiotic ingredients in meals, such as leafy greens, tomatoes, carrots and mushrooms, he said.

Valter Longo, PhD

In his group’s recent research, both mice and humans who ate short cycles of the FMD had reduced inflammation or improved symptoms. Mice fed the FMD for five-day cycles had reduced levels of IGF-1, IGFBP-1, glucose and ketone bodies. Middle-aged mice who ate four-day cycles of the FMD twice a month and a normal diet the rest of the month had dramatic increases in white blood cells and lymphoid/myeloid cells, and reduced dermatitis and visceral fat.¹

“Some of these effects appear to be due to a reprogramming of white blood cell counts,” he said. “After eight cycles of the FMD and refeeding, or going back to a normal diet, we saw what looks like a rejuvenation, or at least an increase in white blood cells in the mice back to their youthful levels.”

Symptoms Reversed
In trials a year later, Dr. Longo’s group injected mice with myelin oligodendrocyte glycoprotein to induce a multiple sclerosis (MS) like autoimmune encephalomyelitis. Mice were randomized to eat either three, three-day cycles of FMD alternated with normal feeding, a continuous protein-rich ketogenic diet or a continuous normal diet. All FMD group mice experienced reduced clinical disease severity, and 20% of these mice had reversal of all symptoms. Mice on the ketogenic diet experienced a short-lived, slight decrease in symptoms.²

“We know that early on in the FMD process, there is an increase in corticosteroid levels, sort of a natural, anti-inflammatory effect,” said Dr. Longo. On day 14 of the FMD/refeeding regimen, mice had lower levels of inflammatory lymphocyte infiltrates in their spinal cords, which is associated with reduced demyelination. The FMD mice also appeared to show reduced levels of autoimmune T-regulatory cells. “We see that FMDs can intervene in two ways: increased apoptosis of autoimmune cells, and reduced inflammation. At the same time, there was a reduction in oligodendrocyte precursor cells leading to regeneration,” Dr. Longo said.

Would an FMD/refeeding regimen work in humans? The researchers randomly assigned 60 patients with relapsing-remitting MS to follow either a normal or ketogenic diet for six months, or a modified human FMD for seven days followed by a Mediterranean diet for six months. Health-related quality of life scores in the FMD group were 50% higher than those on the ketogenic diet. Patients were highly compliant with all three diets.

In a recent trial, the researchers injected mice with dextran sodium sulfate (DSS) to trigger inflammatory bowel disease. They found the mice had increased levels of inflammatory CD4+ and CD8+ T cell infiltrates in the villi of their small intestine, as well as shortened colons. The mice were fed short cycles of the FMD followed by refeeding.³

Their intestinal T cell levels reverted to near normal and their colons were also restored to normal lengths, a possible sign that the diet can promote tissue regeneration, said Dr. Longo. Fecal tests also showed the mice had higher levels of protective gut bacteria after the diet trial (including Lactobacillaceae, Erysipelotrichaceae and Bifidobacteriaceae), possibly due to eating so many vegetables. “We think the prebiotic-rich ingredients give fuel to the bacteria, which grow and take over the gut, and they may contribute to the regeneration of stem cells and an anti-inflammatory effect.”

Diet, RA & SLE
Certain nutrients or dietary patterns may affect inflammation and rheumatic disease risk in certain populations, said Sara Tedeschi, MD, MPH, a rheumatologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, Boston.

“Patients with rheumatic diseases often ask their rheumatologists what they should eat and, specifically, whether they should eat more of or avoid certain foods to improve their disease,” she said. Recommended nutrients include omega-3 fatty acids found in fish, poultry or nuts. They may decrease production of inflammatory eicosanoids and cytokines, and downregulate NLRP3 in the inflammasome. Dietary fiber may have an anti-inflammatory effect. “When fiber is ingested in the diet, it’s cleaved to short-chain fatty acids by the intestinal microbiome, and it’s thought that short-chain fatty acids then exert anti-inflammatory effects on macrophages, dendritic cells and regulatory T cells.”⁴

Recent evidence suggests omega-3s in the diet may lower rheumatoid arthritis (RA) risk in people at higher genetic susceptibility. Higher omega-3 levels in erythrocyte membranes were associated with lower risk of developing anti-cyclic citrullinated peptide (CCP) and rheumatoid factor positivity, as well as incident seropositive RA.⁵ A meta-analysis of seven studies on fish consumption and risk of incident RA indicated a non-significant inverse relationship between each additional serving of fish eaten per week and risk of RA.⁶

Women who enjoy a small glass of wine after work may be at lower risk for rheumatic diseases too. “Moderate alcohol use, equating to half of a standard drink per day, was associated with about a 25% lower risk for RA compared to rarely or never drinking alcohol,” Dr. Tedeschi said.⁷ The same amount of drinking was also associated with a significantly decreased risk of systemic lupus erythematosus (SLE) in women.⁸

Women should cut back on sugar-sweetened soda. Data from the Nurses’ Health Study found that “women who drank one or more servings of sugar-sweetened soda per day had a 33% increased risk of RA and a 63% increased risk of seropositive RA compared to women who drank less than one serving per month,” said Dr. Tedeschi. Diet soda was not associated with RA risk.⁹

Mediterranean Diet = Positive Results
Dietary patterns, such as following a Mediterranean or standard Western diet, may affect RA risk too. In a study of women age 55 or younger, those with unhealthier dietary pattern scores, or having either high inflammatory index or low healthy eating scores, had a 33% increased risk of RA.¹⁰ Women who were current or past smokers also had a 9% decreased risk of RA for every one-point increase in their Mediterranean diet scores.¹¹ No dietary pattern scores were associated with SLE risk in women.¹²

Fish oil may improve symptoms and disease activity in patients diagnosed with RA. A double-blind, randomized controlled trial of 140 patients with recent-onset RA took either high- or low-dose fish oil supplements for 12 months. All patients received triple disease-modifying anti-rheumatic drug (DMARD) therapy. After a year, achieving remission was more likely and therapy failure was less likely in those who took high-dose supplements.¹³ Low-dose omega-3 supplements showed some improvements in disease activity scores in patients with SLE as well.¹⁴

In a review of 14 different diet trials focused on people with RA, pain scores improved with two interventions: a fasting period followed by a vegetarian diet for 13 months, and eating a Mediterranean diet for 12 weeks.¹⁵ In another trial of 51 patients with long-standing RA who ate either a Mediterranean-type diet or standard hospital food for 12 weeks, those on the Mediterranean diet had significantly greater reductions in Disease Activity Score 28 (DAS28) scores (–0.6 compared with –0.1).¹⁶ “Mean weight loss was also significant with the Mediterranean diet (a loss of 3 kg), but not with the control diet, and weight loss may have driven the observed decreases in disease activity,” Dr. Tedeschi said.

Think Beyond the Prescription Pad

Neha Shah, MD

Nearly one-third of patients with RA in a recent survey were dissatisfied with their treatment plan, and in another survey of adults with self-reported, doctor-diagnosed arthritis, almost 40% said they had sought out a complementary or alternative therapy for their symptoms.^17,18 “So our patients are seeking care outside of the rheumatologist’s office. We can move in the direction of more patient-centered care by using complementary medicine,” said rheumatologist Neha S. Shah, MD, assistant professor of medicine at Stanford University in California.

Rheumatologists may help patients build self-efficacy (i.e., the perception that they can do something to cope with their disease) by talking with them about lifestyle habits, such as nutrition, exercise, tobacco use, sleep or stress, and help them set goals to improve these habits.

“This lifestyle-medicine approach is one way we can empower our patients and allow them to put some control back into their lives,” said Dr. Shah. “To be an integrative rheumatologist, one need not do an 800-hour acupuncture course or get a master’s in nutrition or become a certified yoga instructor. What it really takes is asking the right questions” and carefully listening to patients’ answers, she said.

For patients who ask about herbal treatments, Dr. Shah discussed the potentially positive effects of two Ayurvedic herbs (turmeric and ginger) on rheumatic disease patients, who may easily incorporate these spices into their daily diet or take them as supplements. Turmeric, also called curcumin, improved knee osteoarthritis pain in a 2019 double-blind, randomized, placebo-controlled trial.¹⁹ Ginger supplementation improved some immunity and inflammation gene expression in patients with active RA in a 2019 trial.²⁰

Rheumatologists may feel they have little time to cover these topics during busy clinic hours, so Dr. Shah suggests virtual meetings with groups of patients interested in complementary medicine.

“This ideal of perfect health may not be attainable for our patients who are in advanced stages of autoimmune disease, but helping them get one step closer to their optimal state of well-being is certainly within our power,” she said.

Susan Bernstein is a freelance journalist based in Atlanta.

References

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