There’s growing interest and evidence to suggest that dietary changes can improve symptoms and inflammatory markers in people with rheumatoid arthritis (RA). Many arthritis clinics now routinely include a nutritionist as part of the healthcare team that treats people with the autoimmune disorder.

New findings on the benefits of the anti-inflammatory ITIS diet, described by the Arthritis Foundation as a “supercharged Mediterranean diet” and the “Mediterranean Diet 2.0,” showed improvements in joint pain and swelling, as well as one of the more difficult to treat symptoms of RA: fatigue.

Although the study was small, these results are promising, says Roxana Coras, MD, a postdoctoral scholar at the University of California at San Diego School of Medicine and the lead author of the research, which was presented in November 2021 at the American College of Rheumatology Convergence virtual conference.

“Fatigue in rheumatoid arthritis is such a debilitating symptom. It interferes with the daily activities of patients, and as of right now, we don’t have any effective treatment for it,” says Dr. Coras, adding that even when RA treatments improve pain and inflammation, fatigue can often linger.

Although studies that look at diet interventions in rheumatic diseases are hard to conduct and in short supply, this is a very important topic for people with RA, says John M. Davis III, MD, a rheumatologist at the Mayo Clinic in Rochester, Minnesota. Dr. Davis was not involved in the research.

“Patients with RA constantly ask us, ‘What else can I do to help control my disease, increase my energy, reduce my inflammation and pain, and help me be more functional?’ How diet may impact those issues is a part of that conversation. I think there’s a huge need for this kind of research,” he says.

The ITIS Diet Is Specifically Designed for People With RA

Eating a Mediterranean diet — which uses olive oil as the primary oil; emphasizes the intake of fruits, vegetables, legumes, whole grains, nuts, and seeds; and advises moderate amounts of fish and dairy products and limited amounts of red and processed meats and sugar — is associated with a reduction in pain and improvement in physical function in people with RA when used along with standard medications, according to a review published in December 2017 in Rheumatology International.

The ITIS study authors took many components from the Mediterranean diet but then tweaked it to specifically address symptoms of rheumatoid arthritis, says Coras.

“One reason that we chose to study the impact of the diet on people with active RA is that one of the study authors has a friend with rheumatoid arthritis. This friend would often tell her that when she ate specific foods, she noticed that her joints would start to swell,” says Coras.

The diet design process and the science behind it was detailed in a paper published in March 2020 in Contemporary Clinical Trials Communications. Food and ingredient choices were selected or omitted because of their impact on inflammation, the gut microbiome, overall health value, and digestion.

Although the ITIS diet has been used on a case-by-case basis by the nutritionist on the research team, this study, which began in 2018, is the first to formally look at the diet, she says.

ITIS Means 'Inflammation'

Why is the diet called ITIS? Coras explains that the suffix “-itis” comes from Latin [and Greek] and, in medicine, denotes inflammation of an organ or tissue. “Conditions with inflammation end in -itis, for example, arthritis, which is inflammation of the joints, or colitis, which is the inflammation of the colon. We decided to name our diet ITIS because it is anti-inflammatory,” she says.

The ITIS Diet Explained

Although ITIS is based on the Mediterranean diet, it has some key differences, stemming from the authors’ research on foods and ingredients associated with inflammation and pain reduction.

Key components of the ITIS diet include the following:

A homemade green drink containing green vegetables and fruit every morning
Fruits high in enzymes, such as pineapple and papaya
Oily fish, such as sardines, salmon, or tuna, at least twice a week
Avocado, nuts, sesame seeds, or sesame butter (tahini)
Daily chia seeds and flaxseed oil
Unsweetened yogurt and miso (fermented soybean paste)
Substitute daily green tea for coffee
Turmeric (used with black pepper for better absorption) and ginger

“We emphasize seeds in this diet: sesame seeds, flaxseeds, chia seeds. These not only contain polyunsaturated fatty acids, which have been thought to help with inflammation, but chia seeds also include tryptophan, which is an amino acid that helps in the production of serotonin, which helps with pain,” says Coras.

Probiotics, which are found in yogurt and miso, and prebiotics, found in grains, fruits, and vegetables, are both thought to improve the gut microbiome.

What’s the microbiome? The gastrointestinal tract (the gut) is full of bacteria and fungi, and the activity and composition of these microorganisms are collectively known as the gut microbiota or microbiome.

“We believe that these types of food are good for health in general but may also help produce metabolites that may help with pain and inflammation,” says Coras.

The ITIS Diet Is Stricter Than the Mediterranean Diet

ITIS excludes some things the Mediterranean diet allows. On the not-allowed list:

Wheat flour and gluten
Tomatoes, potatoes, and eggplant
Salt
Dairy, with the exception of yogurt
Alcohol

Creators of the ITIS diet believe that the way that foods are combined when you eat them matters as well. “We advise people on the diet not to combine meat, which has a large amount of protein, with legumes or grains, which have protein but also fiber. If you eat them together, they are actually more difficult to digest,” she says.

Instead, they recommend combining meat with salad and having legumes with salad or other vegetables. “Our theory is that if digestion is easier, it will actually help you better absorb all those healthy ingredients that are included in the diet,” says Coras.

Red meat, sugar, soda, and processed or fast foods are not recommended in the Mediterranean or ITIS diets.

Participants in the ITIS diet were also counseled to prepare their food at home. “Takeout foods and foods you buy at the supermarket can have a lot of additives,” Coras adds.

New Analysis Shows Improvement in Fatigue

The analysis only included patients with active disease, which means participants had pain and inflammation in their joints, says Coras.

“After the two-week diet intervention, there was an improvement in disease activity — pain and inflammation improved. Our main finding was the diet’s impact on fatigue,” she says. Fatigue was improved by 50 percent or more in 9 out of 20 participants.

Although this trial was small and open-label, these results are encouraging, says Davis. “There are a lot of unmet needs in treating rheumatoid arthritis, and one of those certainly is how to improve fatigue, which can be a pervasive and persistent problem in many patients,” he says.

Both Davis and Coras note that eating any kind of diet, no matter how healthy, should be used to complement standard treatment for RA, such as medication, not as a replacement.

The fatigue improvement didn’t correlate with inflammation activity — meaning that in patients where pain and inflammation improved, there was no improvement in fatigue, and vice versa, explains Coras. “This is actually not surprising,” she says.

The Funny Thing About Fatigue

Research on fatigue, as related to not only RA but also other rheumatic diseases, has shown that fatigue is not necessarily related to the level of inflammation and pain, says Coras. “When patients who have a high level of disease activity are treated with medication and their pain and inflammation improves, the fatigue often persists,” she says, adding that more research is needed to find out what causes fatigue.

Although the improvements in fatigue were associated with changes in the fecal microbiome and anti-inflammatory compounds, Coras is not ready to draw many conclusions from that finding. “We need more data to understand the impact of this diet on the microbiome,” she says.

Earlier Research Suggests That the ITIS Diet Improved Joint Tenderness and Swelling

An earlier analysis by the same group was presented in November 2019 at the American College of Rheumatology's annual meeting and found that just two weeks on the ITIS diet was associated with improvements in symptoms like joint tenderness and swelling in rheumatoid arthritis.

Although basically a pilot study, these initial findings are impressive, according to Davis. “It’s certainly compelling that perhaps we can achieve a meaningful benefit over a short time frame,” he says. “The authors even report an effect on the clinical disease activity, which is really the level of inflammation of the joints. I was actually impressed that they were able to observe such a large effect.”

Clinical Symptoms and Inflammatory Markers Were Affected by Diet Changes

The participants were the same individuals in the 2021 analysis and included a total of 22 women with an average age of 55. Two weeks before the study, investigators established each participant’s clinical and biological baseline. Symptoms and disease severity were measured with two standard methods of evaluating RA: the DAS28 and the Clinical Disease Activity Index.

How Rheumatoid Arthritis Disease Activity Was Measured

In the DAS28, DAS stands for "disease activity score," and the 28 is the number of joints examined in the assessment. The score is based on a wide range of measures, including joint swelling and tenderness, global scores of pain, blood markers of inflammation, questionnaires that assess function, and imaging such as ultrasound or MRI.

The Clinical Disease Activity Index (CDAI) is a composite score that uses the number of tender joints, the number of swollen joints, the patient’s assessment of disease activity on a 0 to 10 scale, and the doctor’s assessment of disease activity on a 0 to 10 scale.

The day before the study began, clinical parameters were taken a second time, and individuals were instructed on how to follow the diet and keep a daily diet log. After 14 days, subjects were evaluated on the basis of bloodwork, clinical measures, and diet adherence. A total of 17 women went through the complete trial.

Number of Swollen Joints and Other Arthritis Symptoms Compared Before and After Diet Changes

Investigators found significant improvements using both the DAS28 and the CDAI after the two-week period. The number of tender and swollen joints as observed by the doctor and felt by the patient both went down. There were also decreases in fatigue, stress, and stiffness.

Several pro- and anti-inflammatory linoleic acid–derived oxylipins significantly changed after the diet and correlated with the disease index score, according to researchers. “Oxylipins are by-products of fatty acids — it’s what the fatty acids are metabolized to,” says Heather L. Kramm, MD, a rheumatologist at UW Medicine in Seattle. Dr. Kramm was not involved in this research.

How Systemic Inflammation Was Measured

There are pro-inflammatory oxylipins as well as anti-inflammatory oxylipins, Kramm explains. “Oxylipins aren’t used clinically; it’s not something that I’ve ever checked in a patient,” she says. It’s not completely clear how much disease they cause or whether oxylipins are just an association with certain conditions, according to Kramm. “Though these are markers that are being measured in some RA studies, it’s early in the research, and their role is not completely understood,” she says. Oxylipins are thought to play a role in atherosclerosis and Alzheimer’s disease, adds Kramm.

You Are What You Eat, Especially When You Have RA

These findings are very interesting, as there are many unanswered questions about how diet impacts RA, says Kramm. “Clinically, these results validate what I’m seeing in patients. I wouldn’t have expected changes quite this early, but I have seen that dietary modifications can truly make a difference,” she says. “This sort of validates what we know: We are what we eat.”

“We have a nutritionist as part of our clinic, and it’s quite humbling how much she can help people without side effects,” says Kramm. “That being said, diet is one piece of the treatment. I would caution patients that these results aren’t predictive of joint damage.”

Kramm emphasizes that dietary changes are not a replacement for Food and Drug Administration–approved RA therapies that have been proven to prevent joint damage and erosion. "I would say that changes in diet are helpful as complementary medicine,” she says.

There Are Caveats to the Research

There are a few caveats to the study findings, according to Kramm. “The study is not randomized, and it wasn’t blinded, so it’s hard to know how much of a role placebo played,” she says.

“I do feel that clinically, particularly with gluten, dairy, and sugar elimination, dietary changes do help,” says Kramm. “I encourage my patients to see a nutritionist, not only for the anti-inflammatory diet guidance but also for this whole new concept of the microbiome, not only how it may contribute to autoimmune diseases, including RA, but also how it may play a role in treating them.”

Researchers Are Looking at the ITIS Diet in a Longer, Randomized Trial

Coras and her team are now studying ITIS in a randomized clinical trial that will include a control diet and a longer intervention, three months instead of just two weeks. “We are hoping that all the hypotheses found in this trial can be explored further, and we’ll be able to draw more significant conclusions,” says Coras.

The researchers also suspect that the ITIS diet may be helpful in several other inflammatory conditions, but there needs to be more research to confirm that, she notes.

A longer intervention may prove to be more challenging to conduct, but that’s what’s needed to strengthen these results, says Davis. “If these findings are confirmed through more research, it helps make the case for why eating an anti-inflammatory diet like ITIS is worth it. If it can actually improve your energy and make it easier to do the things you weren’t physically or mentally able to do before, we might get some buy-in from patients,” he says.