Diet and rheumatoid arthritis in women

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Diet and rheumatoid arthritis in women: a possible protective effect of fish

consumption.

Journal: Epidemiology 1996; 7(3):256-63.

Author(s): Shapiro J, Koepsell T, Voigt L, Dugowson C, Kestin M

Glossary:

Rheumatoid factors: Antigens often found in the blood of arthritis sufferers and

patients with other autoimmune diseases. They cause agglutination of certain

blood particles. If they are present in detectable quantities, the patient is

considered seropositive for rheumatoid factors.

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This study examined 1,569 women in the Seattle area using a form derived from

the dietary section of the U.S. Health Habits and History Questionnaire. Three

hundred and twenty-four of these subjects were rheumatoid arthritis sufferers;

and of these half tested positive for rheumatoid factors.

There were four fish items on the questionnaire: fried fish or fish sandwich;

tuna, tuna salad or tuna casserole; shellfish; and other fish, broiled or baked.

There were 94 other food items, plus supplementary questions such as whether the

subject ate the skin on her chicken, what fat was used in cooking, and whether

the subject used vitamin supplements.

The dietary habits of the subjects were analyzed to estimate the total caloric

intake, and the quantities of protein, vitamin, fibre, minerals and omega-3

fatty acids. Factors such as height, weight, tobacco or alcohol use and age were

also taken into account, but were not found to have any significant impact on

arthritis rates. It was found that a diet high in calories was associated with

increased risk, the top quartile in this respect showing a risk after adjustment

62% greater than the bottom quartile. On the other hand, if a large proportion

of caloric intake came from protein rather than other sources, there was a

marked protective effect, the top quartile in this respect facing a risk only

65% as great as the bottom quartile.

Fish eating habits were divided into less than one serving of baked or broiled

fish per week, one to two, and two or more. Those who ate two or more servings

per week were only 57% as likely to develop rheumatoid arthritis as those who

ate less than one. When estimated omega-3 fatty acid consumption was examined,

it appeared that the 10% who consumed most were only 77% as likely to contract

the disease as the 25% who consumed the least.

When the cases were restricted to those who were seropositive for rheumatoid

factors, the correlation became far stronger. Those who ate two or more servings

of baked or broiled fish a week were only 32% as likely to develop the

seropositive form of the illness as those who ate less than one. When only

seronegative cases were compared with the controls, the risk for those who ate

fish at least twice a week was 88% of that faced by those who ate fish less than

once a week.

The types of fish that are commonly baked or broiled in the Seattle area include

whitefish like cod and halibut, swordfish, and considerable quantities of

salmon. All of these are high in omega-3 fatty acids, which are left intact by

these cooking methods. Tuna, shellfish, or fried fish do not contain similar

concentrations of omega-3, and this explains why only those who gave high

answers to the baked or broiled fish question showed evidence of protection

against rheumatoid arthritis.

The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid

(DHA), are long-chain polyunsaturated molecules not unlike the omega-6

polyunsaturated fatty acid arachidonic acid commonly found in humans. All of

these acids can synthesize eicosanoids, which are important mediators of

inflammation. Both omega-3s compete with omega-6 arachidonic acid to synthesize

eicosanoids, but those produced by the fish fatty acid are generally less

inflammatory. Thus the eicosanoid leukotriene B5, derived from EPA, is only

about one-tenth as inflammatory as leukotriene B4, derived from arachidonic

acid. This is presumed to be the mechanism at work in fish prophylaxis of

rheumatoid arthritis.

The researchers did not confine themselves to fish, but also examined the

possible effects of various vitamins and minerals. They concluded that vitamins

A, C and E had no relevance for arthritis risk, contradicting a previous Finnish

study which suggested that low serum levels of certain A provitamins and E

vitamins were a serious risk factor. Among minerals, only calcium seemed to play

a significant role, with the top consumption quartile of subjects 68% as likely

as the bottom quartile to develop rheumatoid arthritis after supplements had

been taken into account.

Questions for Shapiro:

1. Are you confident that your results will hold true for men?

I'm not even confident that they will hold true for women. These should be seen

very much as preliminary results, and more research is needed before we can say

for sure that the effect is real. However, based on our hypothesis of what might

be the mechanism behind this, there should be no difference in the effect just

because of gender.

2. Why might the seropositive form of the disease be more effectively prevented

by omega-3 consumption than seronegative rheumatoid arthritis?

One likely reason is that seropositive patients have a more severe, progressed

form of the disease, and any prophylactic measure is more likely to prevent the

disease reaching its more advanced stages. Another possibility is simply that

some of those classed as seronegative were not actually arthritic at all.

There's a method of classification according to symptoms, but if someone doesn't

test positive for rheumatoid factors, you can't be absolutely sure they've got

the disease. Obviously the presence of false cases in the seronegative group

would water down the results.

3. What might be the mechanism of calcium's apparent beneficial effect?

I have no theory as to how calcium might affect the development of rheumatoid

arthritis. We avoided such a suggestion in the paper because the figure fell

short of statistical significance.

4. Is it possible that fish might be useful in treatment as well as prevention?

The reason we undertook this study was that previous research had looked at the

possibilities of treating patients with fish oil, and these did suggest some

beneficial effect. We can't be sure, but it does seem possible.

Diet and rheumatoid arthritis in women: a possible protective effect of fish

consumption.

A. Shapiro, D. Koepsell, Lynda F. Voigt, Carin E. Dugowson, Mark

Kestin, J. Lee .

Some researchers have hypothesized that omega-3 fatty acids, found primarily in

fish oils, may protect against the development of rheumatoid arthritis. We

conducted a population-based case-control study in women, comparing 324 incident

rheumatoid arthritis cases with 1,245 controls. We used a food frequency

questionnaire to ascertain diet during a one-year period five years before a

reference date (first physician visit for joint symptoms). Consumption of

broiled or baked fish, but not of other types of fish, was associated with a

decreased risk of rheumatoid arthritis. The adjusted odds ratios (OR) for 1-<2

servings and 2 servings of broiled or baked fish per week, compared with <1

serving, were 0.78 (95% confidence interval (CI) = 0.53-1.14) and 0.57 (95% CI =

0.35-0.93). Other analyses showed associations with protein as a percentage of

calories (adjusted OR for the top quartile as compared with the bottom quartile

= 0.65; 95% CI = 0.46-0.94) and total calories (adjusted OR for the top quartile

= 1.62; 95% CI = 1.15-2.28). The associations with broiled or baked fish,

protein, and calories became stronger when we restricted our analysis to cases

positive for rheumatoid factor. The results support the hypothesis that omega-3

fatty acids may help prevent rheumatoid arthritis.

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