Natural Foods Merchandiser

When good cells go bad

The immune system is the body's first line of defense against disease. But what happens when the immune system turns on the body and attacks its own tissues? In the simplest sense, this is the process behind autoimmune disease.

Autoimmune diseases affects 14 million to 22 million Americans, about 5 percent to 8 percent of the population.1 This makes autoimmune disease the third most common category of disease in the United States, after heart disease and cancer. More than 80 different autoimmune conditions are known, including the digestive disorders celiac disease, Crohn's disease and ulcerative colitis, as well as multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus (commonly called lupus) and type 1 diabetes.

Autoimmune problems tend to manifest in specific body parts or systems. Rheumatoid arthritis principally targets the joints, while psoriasis affects the skin. Crohn's disease primarily affects the digestive tract. While these conditions cause a wide range of symptoms and problems, they have a common element—there is no cure for the abnormal autoimmune response. Treatment generally is aimed at slowing the progression of the disease, controlling symptoms and improving quality of life.

There are many nutrients and dietary supplements that may offer benefits for autoimmune conditions. Here's a look at recent research on some nutrients that may help in the fight against these chronic conditions, with a focus on type 1 diabetes, celiac disease and rheumatoid arthritis.

The origins of autoimmune disease: a role for vitamin D?
Researchers have proposed many theories about what causes autoimmune disease. Infection, hormones, genetics, oxidative stress and environmental factors have all been studied as possible culprits.1 The autoimmune response itself appears to be governed by T-helper cells that malfunction and attack the body's tissues.2

Growing evidence points to vitamin D as a possible environmental factor in the development of some autoimmune diseases. Low levels of this vitamin have been associated with inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis and type 1 diabetes.2,3,4,5 Animal studies have shown that vitamin D deficiency can accelerate the development of multiple sclerosis and type 1 diabetes,2 and treatment with vitamin D prevented the development of multiple sclerosis and Crohn's disease in other animal studies.4

Some researchers have suggested that increased vitamin D intake, especially in childhood, might help prevent the development of certain autoimmune problems.2,3,4,6 There is also some evidence that those who already have autoimmune disease might experience a slowing of disease progression after increased vitamin D intake.2,4 According to these researchers, the U.S. vitamin D recommendations are much too low for protective effects against autoimmune diseases.2,6 The current U.S. Dietary Reference Intake is 200 IU a day for children and adults up to age 50, 400 IU a day for adults ages 51 to 70, and 600 IU for adults older than 70.7 Researchers call for additional studies to investigate the safety and effectiveness of doses as high as 800 IU to 1,000 IU a day.2,4,6 Vitamin D toxicity—associated with long-term use of supplements providing doses higher than 1,000 IU a day for children or 2,000 IU a day for adults—can cause nausea, vomiting, constipation, weakness and weight loss, and can also elevate blood calcium levels.7 Vitamin D toxicity is associated only with excess supplement consumption, not with dietary vitamin D or sun exposure.7 There remains controversy as to what constitutes a safe upper limit for vitamin D intake; more research in this area is needed before recommendations can be made


Vitamin D and type 1 diabetes
Type 1 diabetes mellitus is characterized by a loss of insulin-secreting beta cells in the pancreas. This leads to an inability to produce insulin, a hormone that regulates blood sugar levels. Type 1 diabetes is usually diagnosed in childhood or early adulthood, and is typically treated with insulin replacement. However, in the past 20 years, type 2 diabetes, which is not an autoimmune disease and was formerly known as adult-onset diabetes, has been diagnosed in children and teens more frequently, reports the Centers for Disease Control and Prevention.

A number of population studies have concluded that adequate consumption of vitamin D in early childhood may play an important role in preventing the development of this serious disease.5,6,8,9,10,11 However, some research suggests that doses as high as 2,000 IU a day may be necessary to prevent type 1 diabetes, and studies to assess the long-term safety of such high doses have not yet been conducted.5,6,8

Nicotinamide for type 1 diabetes
Preliminary studies suggested that nicotinamide (a form of vitamin B3, also known as niacinamide) might help preserve or improve the function of the insulin-secreting beta cells in the pancreas. A 1996 New Zealand trial generated excitement when it concluded that 1,000 mg a day of nicotinamide reduced the incidence of diabetes in high-risk children, but unfortunately the study had methodological shortcomings.12

Most recently, a large-scale, randomized, double-blind, placebo-controlled European nicotinamide trial had disappointing results based on a specific dosage. The European Nicotinamide Diabetes Intervention Trial, which began in 1994, involved 552 high-risk children who had first-degree relatives with type 1 diabetes.13 The study participants, who were recruited from Europe, Canada and the United States, were randomly assigned to receive 1.2 g per m2 each day of oral nicotinamide or placebo for five years. (A measurement of m2 means an amount based on total body size—meters squared of surface body area.) At the end of the study, there was no significant difference between the two groups in the number of children who developed diabetes. The researchers concluded nicotinamide was ineffective in preventing type 1 diabetes at the dose used in the study.14

One researcher suggests that future studies in this area should focus on a metabolite of nicotinamide called N(1)-methylnicotinamide, which has demonstrated some promise in animal studies.14

Enzymes for celiac disease
Celiac disease, also known as celiac sprue, primarily affects the digestive tract. The condition is caused by an abnormal immune response to dietary gluten, a protein that occurs naturally in wheat, rye, barley and triticale. Symptoms of this genetic gluten intolerance include intestinal cramping, gas, bloating, chronic diarrhea or constipation, and fatty stools—although digestive symptoms may be very subtle and easily missed. Celiac disease also disrupts the body's absorption of nutrients, sometimes leading to long-term dietary deficiencies and malnutrition. Celiac disease is quite common, affecting as many as one in 133 Americans.15

The main treatment is simply avoiding all gluten-containing foods. This can be very tricky, because it is difficult to detect hidden gluten in processed foods, beverages and medications. However, recent research suggests that a combination of digestive enzymes may have the ability to break down gluten and detoxify it for celiac sufferers, making the protein easier for them to tolerate in small amounts.16,17 A two-enzyme "cocktail" shows special promise.17,18 The combination consists of a digestive enzyme called prolyl endopeptase, which works to enhance the digestion of gluten in the small intestine, combined with a glutamine-specific prolyl endopeptase digestive enzyme derived from the fungus Aspergillus niger. The glutamine-specific enzyme, called EP-B2, remains stable even in the presence of stomach acids and thus has the ability to inactivate gluten in the stomach.18 Under experimental conditions, the enzyme combination inactivated gluten within 10 minutes.17 While this is exciting news for millions of people with celiac disease, clinical research is needed to confirm the results and determine optimal dosages.

Fish oil for rheumatoid arthritis
Rheumatoid arthritis is a disabling autoimmune condition marked by joint pain, inflammation and a crippling loss of variable functions in the body. The disease primarily attacks the musculoskeletal system, although it may also affect skin, lung, heart and blood vessel tissues. Osteoarthritis ("wear-and-tear arthritis") also causes pain and inflammation, but is not an autoimmune condition. Rheumatoid arthritis is commonly treated with nonsteroidal anti-inflammatory drugs, which reduce pain and inflammation but can cause many serious side effects.

A strong and growing body of evidence supports the use of fish oil—rich in omega-3 fatty acids, particularly eicosapentaenoic acid and docosahexaenoic acid—as a natural anti-inflammatory agent. Thus, fish oil is widely recommended to help with symptoms of RA.19,20 But does it really help?

According to clinical evidence from well-controlled studies, fish oil is modestly effective in reducing symptoms of RA, including morning stiffness and the number of painful joints.19,20,21,22,23,24 Fish oil may also allow a lowered dosage of the NSAIDs used to treat RA, a significant benefit in its own right.19,20 For pain-relieving and anti-inflammatory effects, people with RA should take at least 2.6 g per day of fish oil.22 One recent, small, placebo-controlled study showed that after three years of treatment, people taking fish oil not only were able to reduce their use of NSAIDs by 75 percent, they also had lowered risks of heart disease.25

Among the more than 900 clinical studies conducted to date with fish oil, there is also evidence that the supplement can help with other autoimmune conditions, including Crohn's disease, lupus, multiple sclerosis and psoriasis.

The bottom line: improving quality of life
There are no known natural treatments that simply "tone down" an overactive immune system in the way that some enhance or balance sluggish immune function. However, it is clear that some nutrients—certainly including vitamin D and fish oil—have important contributions to make in preventing or ameliorating the suffering caused by autoimmune diseases.

Evelyn Leigh is a freelance writer and natural-health advocate based in Boulder, Colo.

Why women are more susceptible
For reasons that are not entirely clear, women are far more likely than men to develop autoimmune disease. In the United States, almost 80 percent of all cases of autoimmune disease affect women,1 and autoimmune disease is one of the leading causes of death in young to middle-aged women.2 According to the Arthritis Foundation, 70 percent of rheumatoid arthritis sufferers are women.27 Other autoimmune diseases that affect more women than men include lupus, multiple sclerosis, myasthenia gravis and scleroderma.

Researchers have not yet determined exactly why women are more susceptible to autoimmune disease than men. One theory is that, in general, women have a stronger immune response and produce more antibodies than men.1 Other evidence links the development of autoimmune disease with viral or bacterial infection earlier in life. When these two factors are combined with the observation that female hormones have been shown to have pro-inflammatory effects on cultured immune cells, it is possible that some autoimmune diseases may result from a complex interaction between female hormones and women's naturally heightened immune response to infection.1


Healthy sources of vitamin D
The body uses the ultraviolet rays in sunshine to produce vitamin D, so one good way to increase vitamin D levels is to expose skin to the sun. Five to 15 minutes of sun exposure per day during spring, summer and fall is adequate.4 Sunscreen use, time of year, geographic latitude and cloud cover all affect the ability of the skin to make vitamin D. People with dark skin may be more prone to vitamin D deficiency, because melanin (skin pigment) impairs the skin's ability to produce vitamin D.7 A note of caution: Those with lupus should be careful to avoid sun exposure, because it can exacerbate the disease.26

Cod liver oil is by far the best food source of vitamin D, providing 1,360 IU per tablespoon.7 Other good food sources of vitamin D include salmon (360 IU per 3.5 oz serving), mackerel (345 IU per 3.5 oz serving), and canned sardines (250 IU per 1.75 oz serving). One cup of vitamin D-fortified nonfat milk provides 98 IU of vitamin D.7


1. Fairweather D, Rose NR. Women and autoimmune diseases. Emerg Infect Dis 2004; 10(11): 2005-11.
2. Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med. 2004; 229(11):1136-42.
3. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006 Mar;81(3):353-73.
4. Holick MF. The vitamin D epidemic and its health consequences. J Nutr 2005; 135(11):2739S-48S.
5. Ponsonby AL, et al. UVR, vitamin D and three autoimmune diseases—multiple sclerosis, type 1 diabetes, rheumatoid arthritis. Photochem Photobiol 2005; 81(6):1267-75.
6. Harris SS. Vitamin D in type 1 diabetes prevention. J Nutr 2005;135(2):323-5.
7. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press; 1997.
8. Mathieu C, Badenhoop K. Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab 2005; 16(6).
9. Stene LC, et al. Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type diabetes: a large, population-based, case-control study. Am J Clin Nutr 2003; 78(6)1128-34.
10. Hypponen E, et al. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001; 358(9292):1500-3.
11. No authors listed. Vitamin D supplement in early childhood and risk for type 1 (insulin-dependent) diabetes mellitus. The EURODIAB Substudy 2 Study Group. Diabetologia 1999; 42(10:51-4.
12. Elliot RP, et al. A population based strategy to prevent insulin-dependent diabetes using nicotinamide. J Pediatr Endocrinol Metab 1996; 9(5):501-9.
13. Gale EA, et al. European nicotinamide diabetes interventional trial (ENDIT): a randomized controlled trial of intervention before the onset of type 1 diabetes. Lancet 2004; 363(9413):925-31.
14. Gosteli J. Nicotinamide trials in diabetes intervention. Does a metabolite provide benefit? Med Hypotheses 2005;64(5):1062-3.
15. Celiac disease. Celiac Disease Foundation. Accessed Sept. 3, 2006.
16. Cerf-Bensussan N, et al. Oral proteases: a new approach to managing celiac disease. Gut 2006; Sept. 1 [E-pub ahead of print]
17. Siegel M, Bethune MT, Gass J, et al. Rational design of combination enzyme therapy for celiac sprue. Chem Biol 2006; 13(6):649-58.
18. Stepaniak D, at al. Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. Am J Physiol Gastrointest Liver Physiol 2006; May 11 [Epub ahead of print].
19. Cleland LG, et al. Fish oil: what the prescriber needs to know. Arth Res Ther 2006; 8(4):402.
20. Oh R. Practical applications of fish oil (Omega-3 fatty acids) in primary care. J Am Board Fam Pract 2005;18(1):28-36.
21. Fortin PR, et al. Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. J Clin Epidemiol 1995; 48(11):1379-90.
22. Shahidi F, Miraliakbari H. Omega-3 fatty acids in health and disease: part 2—health effects of omega-3 fatty acids in autoimmune diseases, mental health, and gene expression. J Med Food 2005;8(2):133-48.
23. Cleland LG, et al. The role of fish oils in the treatment of rheumatoid arthritis. Drugs 2003; 63(9):845-53.
24. Stamp LK, James MJ, Cleland LG. Diet and rheumatoid arthritis: a review of the literature. Semin Arthritis Rheum 2005 Oct;35(2):77-94.
25. Cleland LG, et al. Reduction of cardiovascular risk factors with long term fish oil treatment in early rheumatoid arthritis. J Rheumatol 2006; Aug. 1 [E-pub ahead of print].
26. Facts and Overview. Lupus Foundation of America. Accessed Sept. 7, 2006.
27. Rheumatoid arthritis. The Arthritis Foundation. Accessed Sept. 3, 2006.

Natural Foods Merchandiser volume XXVII/number 11/p. 36, 38-39

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