The time intervals between the 1st and 2nd, and between the 2nd and 3rd studies were approximately ten years. One of the authors was local clinical research coordinator for all three projects. The studies were conducted in three different regions of Sweden. However, the patient populations were very much alike, as all patients were recruited from similar clinical settings at the central out patient rheumatology clinic of each region.
In all three studies the patients had been aggressively treated pharmacologically according to the internationally recommended guidelines that were prevailing at the time of each study. As a consequence of the more efficient disease modifying drugs of the 1990ths, the arthritis activity was better controlled in the 3rd study than in the two earlier studies. With all three studies the participating patients had showed active interest for the kind of diet that was under investigation. At the time of the first two studies, vegetarian diets were advocated by laymen, while in the 1990ths much attention was focused on Mediterranean diets. Although different, these three diets shared some common characteristics which we believe were of importance with respect to control of inflammation. Compared to ordinary western diets they contained less of saturated fats from meat and dairy products. They had more of fresh fruits and of green vegetables. The MD was also rich in fats from sea foods, which was not a feature of the two vegetarian variants.
Another consequence of the time difference between the three studies was that the RA measures were not completely identical. They had successively been changed in line with the international recommendations of good scientific standards. Thus, comparable absolute baseline estimations of pain-score, acute phase response, physical function or tender joint count were not available due to their different definitions during the three intervention studies. Nevertheless, as explained in "methods", for the present analysis the outcome results of these variables were well defined, as they were dichotomously characterised as improvement, or no improvement.
The cross over design of the 2nd study, with 7 patients assessed first as controls and later as diet patients, weakens the statistical power of the pooled statistical analysis only marginally.
In the three studies of ours each intervention i.e. with lacto-vegetarian, vegan or modified Cretan Mediterranean diet had rendered the patients a weight fall of on the average 2.4 kg over a trial length of 3–4 months. In the pooled analysis of change in body weight versus change in clinical outcome measurements the results were fairly clear. Apart from a univariate correlation between improvement in acute phase response and reduction in body weight, no statistically significant correlation was seen with the multiple logistic regression analysis between weight loss and the concomitantly obtained change in RA disease measurements. Thus the body weight loss seemed to have had no statistical significant anti inflammatory effect. However, although the number of patients was increased from pooling three different studies, the total amount of data was still relatively small. Therefore a possible anti inflammatory effect of weight reduction should not be completely discarded. Furthermore, the potential effect that weight reduction may have, should ideally be studied by itself, i.e. the test and control diets should differ only with respect to their contents of energy.
As for comparison of diet intervention versus control diet, the multiple logistic regression analysis, showed highly significant statistical correlations between diet intervention and improvement in RA outcome variables. These data indicate that dietary factors may have a potential role in treatment of RA. With regards to vegan diets, our observation is supported by the results of at least two independent, randomised and controlled studies [6, 9].
Of course, the beneficial factors that the tested diets share need to be identified. A noteworthy candidate is their relatively low content of saturated fats . Another is their high content of fresh fruits and vegetables.
Patients with active RA tend to have an abnormally increased peripheral insulin resistance . Deliberate weight reduction in a group of patients with gout  was accompanied by reduction of insulin resistance and less numbers of inflammatory events. Whether this strategy for gout would work for patients with RA, and improve their arthritis, is an important clinical question. Some recent observational data indicate that overweight and obesity might be a risk factor for RA . From experimental studies in mice  it is known that long-term pure energy under-nutrition has anti-inflammatory effects. In humans, deliberately undertaken short term fasting is well known to induce immune suppression and improvement in RA disease activity . There are no controlled long-term studies of reduced energy intake without mal-nutrition on patients with RA. However, Iwasahige et al.  recently conducted a regiment for 54 days of caloric restriction combined with fasting in ten patients with RA. The patients lost in weight, and interestingly, the composite disease activity score of Lansbury was significantly reduced.
We know of two other small studies on deliberately undertaken weight reduction in patients with RA. In an uncontrolled pilot study  with 19 overweight patients with RA, Danish researchers had instructed the patients to lower their energy intake by 30% to achieve weight reduction. After a period of 12 weeks, the mean weight loss was 4.5 kg. No change was obtained in joint pain, morning stiffness, number of tender joints, or in sedimentation rate. Neither did Gordon et al. from their uncontrolled pilot study report any short-term favourable effects from assisting obese RA patients to reduce their body weight .
In conclusion, it seems as weight reduction strategies have little if any influence on RA inflammation. Perhaps this is not surprising with regards to what is already known from research on the metabolic syndrome and on atherosclerotic vascular disease, where isolated overweight is rank as a less important factor of risk .
Before conclusion of this discussion we need to remember that there is a controversy in letting patients with RA test an experimental regiment, which would involve prolonged reduction of their energy intake. During the course of RA most RA patients including those with overweight will develop a muscle wasting condition known as rheumatoid cachexia . Although not directly fatal, this form of cachexia is believed to contribute to co-morbidity and reduced life expectancy. It is caused by the rheumatoid inflammation by itself and is refractory to nutritional therapy.