Rita Baron-Faust, MPH, CHES

Advancing Wellness on Many Fronts


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THE AUTOIMMUNE CONNECTION BLOG

Can What You Eat Help Fight Autoimmune Disease?

July 25, 2016

Tags: Anti-inflammatory foods, omega 3 fats, gluten, green tea, autoimmune diet, rheumatoid arthritis, lupus, Sjögren’s Syndrome

One of the most frequent questions I’m asked at autoimmune patient forums is about diet, anti-inflammatory foods, and autoimmunity.

There’s a lot of popular pseudo-science out there claiming that the right diet can “cure” autoimmune disease. Much of the “evidence” I’m asked about is anecdotal, largely based on reports of how patients were helped – or not – by eating -- or not eating -- certain foods (notably gluten). It’s difficult to argue with success stories and equally difficult to prove real cause and effect.

However, there’s plenty of solid scientific evidence to support the idea of an anti-inflammatory diet.

Much of what we know about the relationship between diet and inflammation comes from studies about the effects of the Mediterranean diet (and its components) in reducing inflammatory markers in cardiovascular disease (CVD)1 – a well-established risk in autoimmune diseases including rheumatoid arthritis (RA), lupus, and inflammatory bowel disease.

The Mediterranean diet encompasses many anti-inflammatory foods, notably omega-3 fatty acids found in olive and other oils, cold-water fatty fish (like salmon, mackerel, and sardines), nuts, and flax seeds. Olives and olive oil also contain compounds that act similarly to non-steroidal anti-inflammatory drugs (NSAIDs).2 Additionally, the diet includes lots of fresh fruits and vegetables rich in anti-inflammatory plant chemicals.

The diet has been shown to lower inflammatory markers in blood tied to both CVD and autoimmune diseases, including C-reactive protein (CRP), interleukins,and tumor-necrosis factor alpha (TNF-α).1 Studies also show that it helps reduce pain, joint swelling, and other symptoms of RA and other autoimmune diseases – and has beneficial effects on the immune system itself (such as moderating T-cell activity).3

It’s been suggested for years that our “Western” diet high in saturated fats and red meat may not only play a role in CVD but also in autoimmune diseases.4 Indeed, in one study, RA patients assigned to a Mediterranean diet showed a reduction in inflammatory activity and an increase in physical function compared to those assigned to a “Western” diet. 5

THE BIG FOUR INFLAMMATION FIGHTERS

•Fatty Fish & Omega 3's

Of all inflammation fighting foods in the Mediterranean diet, we know the most about fatty fish and fish oil, which contain the omega polyunsaturated fats (PUFAS) eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA).

As far back as 1991, researchers suggested that the omega-3 fats in fish may help reduce disease severity in lupus.6 More recently we’ve learned that omega 3’s may help protect against RA. A prospective study of more than 32,000 older Swedish women in 2013 found that eating one or more servings of fatty fish a week was associated with a 29% lower risk of developing RA and long-term intake of high-dose fish oil decreased the risk of RA by 52%).7

A recent British review reported that eating more fish high in omega-3s modestly reduced joint swelling, pain and morning stiffness in RA, leading to less use of NSAIDs.8 A randomized, controlled trial in people with early RA found that around 40% of those given high-dose fish oil to take with their conventional disease modifying anti-rheumatic drugs DMARDs)were in remission after a year.9

However, fairly high amounts of fish oil are needed to achieve an effect (about 3 grams of EPA and DHA in a concentrated fish oil supplement). Fish oil is also an anticoagulant and doesn’t agree with everyone.10 So consult your doctor before adding it to your diet.

Other types of omega-3 fats can be are found in olives, flax seeds, pumpkin seeds and walnuts.

•Olives & Olive Oil

Certain anti-inflammatory properties in olives and olive oil may be a big reason why the Mediterranean diet helps in autoimmune diseases.

Olives and virgin olive oil have been found to contain a polyphenol compound called oleocanthal, which blocks production of the pro-inflammatory enzymes and cyclooxygenase-2 (COX-1 and COX-2) much as NSAIDs do. In fact, research shows oleocanthal has properties similar to ibuprofen.11

The fruit of the olive tree, Olea europaea, also contains oleic acid, a monounsaturated fatty acid which also helps modulate the immune system.12

Olive oil, as well as nuts, sunflower and flax seeds, and avocados are also packed with vitamin E, which helps prevent cell damage in joints and may have anti-inflammatory properties as well.

•Fresh Fruits & Vegetables

The Mediterranean-style diet includes plenty of fresh fruits, vegetables, and beans rich in fiber plus inflammation-fighting plant chemicals (phytochemicals) and antioxidants such as vitamin A, beta carotene, vitamin E, zinc and selenium.

In particular, raspberries and cherries are packed with antioxidants called anthocyanins and vegetables containing flavonoids like onions and garlic are thought to regulate expression of key inflammatory enzymes.

•Green Tea

I meet many autoimmune patients who swear by green tea, which is a good source of antioxidant polyphenols.

Its active ingredient, epigallocatechin-3-gallate (EGCG), has been shown to improve symptoms and reduce the pathology in some animal models of autoimmune diseases.

The effects of EGCG help suppress production of autoreactive T cells and also pro-inflammatory cytokines (such as interleukin-1).13 A recent study showed that EGCG improved rheumatoid arthritis in mice, while another showed effects in lab rats. But there’s an unfortunate lack of research in humans for this healthy beverage.

GLUTEN: GUILTY AS CHARGED?

There are a number of experts who claim that any anti-inflammatory diet must exclude gluten.

There’s no question that gluten, a naturally-occurring protein in wheat, barley and rye, causes celiac disease in genetically susceptible individuals. Gluten triggers an autoimmune inflammatory reaction that damages the small finger-like projections in the small intestine (villi) which absorb many nutrients.

The only treatment for celiac disease is eliminating gluten. It can stop the symptoms of chronic diarrhea, stomach pain, bloating, and gas and help repair damage to the villi. Intestinal healing can take three to six months in children and several years in adults, according to the National Institutes of Health.14

Some people are allergic to wheat or have non-celiac gluten sensitivity and experience severe GI symptoms. While neither problem damages the small intestine, for these people going gluten-free also makes sense.

What’s not so clear is gluten’s effects elsewhere in the body (like the brain) and whether going gluten-free helps other autoimmune diseases, prevents or even “cures” them.

“There is no evidence that a gluten free diet helps autoimmune diseases such as Hashimoto's thyroiditis. Celiac disease is the one autoimmune disease that is appropriate for the gluten-free diet,” Peter H.R. Green, MD, director of the Celiac Disease Center at Columbia University told me in an email. “It is as though celiac disease has given the gluten-free a medical legitimacy that other diet trends lack.”

As a result of what he terms a “media epidemic,” “almost a third of all American and UK consumers are trying to avoid gluten,” many of them unnecessarily, he writes in a new book, “Gluten Exposed,” (2016, William Morrow, NY).15

VEGETARIAN AND VEGAN DIETS

Any elimination diet can have adverse effects, Dr. Green adds, cutting out crucial nutrients such as fiber and essential vitamins and minerals.

The Arthritis Foundation, the Sjögren’s Syndrome Foundation, and other organizations, report that studies since the 1990s have found vegetarian diets to be beneficial for some autoimmune patients. However, you need to get plenty of plant protein from legumes and beans, among other things.

A vegan diet -- which excludes meat, fish, dairy or other animal products -- may also be helpful, possibly because of the types of polyunsaturated fatty acids included in the diet, say British arthritis researchers.10

However, if you go vegan make sure you get vital nutrients you need, especially calcium, vitamin B12, vitamin D, zinc, and selenium.

References


1 Giugliano D, Ceriello A, and Esposito K, The Effects of Diet on Inflammation. Journal of the American College of Cardiology. 2006;48(4):677–85. doi:10.1016/j.jacc.2006.03.052.

2 Rahmani AH, Abutti AS, and Ali SM. Therapeutics role of olive fruits/oil in the prevention of diseases via modulation of anti-oxidant, anti-tumour and genetic activity. Int J Clin Exp Med. 2014. 7(4 ):799-808. PMCID: PMC4057827. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057827/ Accessed July 20, 2016.

3 Shepshelovich D and Shoenfeld Y.Prediction and prevention of autoimmune diseases: additional aspects of the mosaic of autoimmunity. Lupus. 2006. 15(3):183-190. doi: 10.1191/0961203306lu2274rr s

4 Manzel A, Muller DN, Hafler DA et al., Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014;14:404. DOI 10.1007/s11882-013-0404-6.

5 Sköldstam L, Hagfors L, Johansson G. An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis. Ann Rheum Dis. 2003;62:208–214.

6 Walton AJ, Snaith ML, Locniskar M, et al. Dietary fish oil and the severity of symptoms in patients with systemic lupus erythematosus. Ann Rheum Dis. 1991; 50:463–466.

7 Di Giuseppe D, Wallin A, Bottai M, et al., Long-term intake of dietary long-chain n-3 polyunsaturated fatty acids and risk of rheumatoid arthritis: a prospective cohort study of women. Ann Rheum Dis. 2014 Nov;73(11):1949-53. doi: 10.1136/annrheumdis-2013-203338.

8 Miles EA, Calder PC, Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis. Br J Nutr. 2012 Jun;107 Suppl 2:S171-84. doi: 10.1017/S0007114512001560.

9 Proudman SM, James MJ, Spargo LD, et al. Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use. Ann Rheum Dis. 2015. 74:89-95 doi:10.1136/annrheumdis-2013-204145.

10 Arthritis Research UK, Diet and Supplements. http://www.arthritisresearchuk.org/arthritis-information/complementary-and-alternative-medicines/complementary-therapies/diet-and-supplements.aspx#sthash.g3ajjiyB.dpuf Accessed July 19, 2016.

11 Lucas L, Russell A, Keast R. Molecular mechanisms of inflammation. Anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal. Curr Pharm Design. 2011;17(8):754–68. DOI: 10.2174/138161211795428911. http://www.ncbi.nlm.nih.gov/pubmed/21443487 Accessed July 19, 2016.

12 Sales-Campos H, Souza PR, Peghini BC, et al., An Overview of the Modulatory Effects of Oleic Acid in Health and Disease. Mini Reviews in Medicinal Chemistry. 2013;13(2):201-210. DOI: 10.2174/13895575113130220003.

13 Wu D, Wang J, Pae M, Meydani SN. Green tea EGCG, T cells, and T cell-mediated autoimmune diseases. Mol Aspects Med. 2012 Feb;33(1):107-18. doi: 10.1016/j.mam.2011.10.001. Epub 2011 Oct 14. http://www.ncbi.nlm.nih.gov/pubmed/22020144. Accessed July 19, 2016.

14 Treatment for Celiac disease. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/celiac-disease/Pages/treatment.aspx Accessed July 19, 2016.

15 Green PR, Jones R. “Gluten Exposed: The Science Behind the Hype and How to Navigate A Healthy, Symptom-Free Life,” (2016, William Morrow, NY).

16 The Arthritis Foundation: Eat Right for Your Type of Arthritis. http://www.arthritis.org/living-with-arthritis/arthritis-diet/anti-inflammatory/eat-to-beat-inflammation.php Accessed July 19, 2016

Introducing The Autoimmune Connection(s) blog: The ongoing, online supplement to the 2nd edition of “The Autoimmune Connection."

July 5, 2016

Tags: systemic lupus erythematosus, lupus, SLE, cervical cancer, human papilloma virus, cervical cancer screening, cervical cytology

Why “Autoimmune ConnectionS” plural?

Ongoing research is revealing new connections in autoimmunity, bolstering the more speculative links, and disproving others.

For example: a connection between lupus and an increased risk of cervical cancer has been suggested for years – it has now been confirmed. This is an important issue if you have SLE and possibly other autoimmune diseases.

The confirmation came at the recent European League Against Rheumatism (EULAR) annual meeting in London. A new study from Sweden found a doubled rate of cervical dysplasia or neoplasms – premalignant abnormal cell growth – among women with SLE in general and a greater risk among women treated with immunosuppressant drugs.

“We know that the therapies we use to treat lupus, particularly complicated lupus, are therapies that compromise normal immune function. They are also therapies we use in the organ transplant setting, where we know there are a number of malignancies that occur more often than expected, in particular premalignancies and frank malignancies of the female cervix,” explained study co-author Johan Askling, MD, PhD, a professor and senior physician at the Karolinska Institute in Stockholm at a EULAR press briefing.

“Is this driven by premalignant cell changes or frank malignancies or was the risk driven by the disease or the other things, such as the therapies we use? The aim of our study was to settle the controversy,” he commented.

Dr. Askling and colleagues examined medical data for 4,550 SLE patients in Sweden’s National Patient Register, separating them into two groups: 1,981 treated with immunosuppressants, such as azathioprine (Imuran), and 1,783 treated with anti-malarials, like hydrochloroquine. Then they compared the SLE patients to 28,113 age-matched women in the general population.

When the researchers looked at cervical cancer screening records between 2006 and 2012 from the Cervical Screening Registry and the Swedish Cancer Registry, they found the rate of cervical dysplasia or invasive cancer among women with SLE was 2.12 greater than for women in the general population.

Among lupus patients given antimalarials, the rate was 1.52 but it was 2.72 for patients on immunosuppressants (with or without antimalarials). The risk held up even when factoring in age and earlier cervical screening in the previous five years.

The study, published in abstract form in the June Annals of the Rheumatic Diseases, concludes that “SLE patients treated with immunosuppressants are at risk of cervical neoplasia and should be adequately monitored, regardless of whether the risk increase is due to disease severity or treatment.”1

The SLE-Cervical Cancer Connection

An elevated rate of cervical dysplasia among lupus patients has been reported for a number of years2,3 and associated with exposure to immunosuppressive drugs, including azathioprine.

“An altered clearance of cancer related viral agents in SLE (due to the disease and/or immunosuppression) may contribute to this risk and may also drive the risk for other cancers (such as vulvovaginal and hepatic carcinomas) in SLE,” the authors of a 2012 Canadian study note. 4 Immunosuppressive drugs may also be associated with increased susceptibility to human papilloma virus (HPV), which causes most cervical cancers and has been detected more frequently in women with SLE.4

The current Swedish analysis is significant because it’s large – almost 33,000 people – and analyzes results of cervical screening among women with and without SLE as well as SLE patients on anti-malarials or immunosuppressants, comparing then with women in the general population. So this analysis is able to quantify the risk.

However, we should stress that the Swedish data come from an abstract reported at a scientific meeting, are not final, and haven’t yet been peer-reviewed. Plus, population studies such as this can’t prove cause-and-effect -- just an “association” with increased risk.

Dr. Askling, who has been studying cardiovascular disease and cancer risk in rheumatoid arthritis and other autoimmune diseases, also notes that both RA and CVD are, in part, driven by inflammation. Studies of cancer in autoimmune diseases also show that higher disease activity may also increase risk.

Should SLE Patients be Alarmed?

Fortunately, screening tests using new liquid based cell analysis cytology) which can detect DNA from HPV are very sensitive. And, if cervical dysplasia or intraepithelial neoplasia (CIN) are found the condition can be treated with freezing or electrocauterization before it can progress to cancer.

Considering the potentially increased risk for women with SLE, is more frequent cervical screening needed? That’s something to ask your gynecologist.

Depending on a woman’s health history, 2016 guidelines from the American College of Obstetricians and Gynecologists (ACOG), the American Cancer Society (ACS), and other groups advise cervical cytology screening every three years for sexually active women ages 21–29 at average risk;5 the ACS recommends both cervical screening and HPV testing.6 Women ages 30–65 years are urged to have both tests every 5 years with high-risk HPV strains. Since cervical cancer is less common in older women, after age 65 screening can be stopped if consecutive Pap and HPV tests have been negative.6

Women with SLE are screened at about the same rate as women in the general population (around 89% ), Dr. Askling told interviewers at the EULAR meeting.7 “And we should keep encouraging women with lupus to be screened because it has “demonstrated true value. And here’s a group with an increased risk potentially more driven by the earlier stages of cervical cancer than by invasive cancer.”7

Also important: the Lupus Foundation notes that women with SLE also seem to be more vulnerable to the effects of certain cancer-linked viruses than the general population.8 A case in point: human papilloma virus. So younger lupus patients may also want to ask their doctors about the HPV vaccine.

New liquid-based cytology tests can detect DNA of HPV in cervical cells even before dysplasia or CIN occur. That’s another reason to be regularly screened. As we advised in “The Autoimmune Connection,” find a gynecologist familiar with ADs to help guide you in deciding how frequently to be screened.

Since immunosuppressant drugs like azathioprine appear to play a role in this increased risk, you may also want to discuss alternative treatments with your rheumatologist. Ultimately, the choice depends on the medication that best controls your SLE.


References

1 H. Wadström, E.V. Arkema, C. Sjöwall , J. Askling , et al., Rate of Cervical Neoplasia in Systemic Lupus Erythematosus: A Nationwide Cohort Study. EULAR Abstract: OP0189. Annals of the Rheumatic Diseases. June 2016. DOI: 10.1136/annrheumdis-2016-eular.2142.

2 Tessier-Cloutier B , Clarke AE , Ramsey-Goldman R, et al., Systemic lupus erythematosus and malignancies: a review article. Rheum Dis Clin North Am. 2014 Aug;40(3):497506, viii. doi: 10.1016/j.rdc.2014.04.005. Epub 2014 Jun 3.

3 Gayed M , Bernatsky S, Ramsey-Goldman R, Clarke A, Gordon C. Lupus and cancer. Lupus. 2009 May;18(6):47985. doi: 10.1177/0961203309102556.

4 Bernatsky S , Kale M, Ramsey-Goldman R, Gordon C, Clarke AE. Systemic lupus and malignancies. Curr Opin Rheumatol. 2012 Mar;24(2):17781. doi: 10.1097/BOR.0b013e32834ff258.

5 ACOG Practice Bulletin No. 157 Summary: Cervical Cancer Screening and Prevention. Obstetrics & Gynecology, January 2016; 127(1):185-187. doi: 10.1097/AOG.0000000000001256.

6 Sawaya GF, MD; Kulasingam S, Denberg TD, et. al., Cervical Cancer Screening in Average-Risk Women: Best Practice, Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015;162:851-859. doi:10.7326/M14-2426.

7 Johan Askling profile page, Karolinska Intitutet. http://ki.se/en/people/johask. Accessed July 1, 2016

8 The Lupus Foundation, Cancer and Lupus, 15 Questions. www.lupus.org/resources/15-questions-with-Sasha-Bernatsky-cancer-and lupus/ Accessed July 1, 2016.