Introduction

In the past years, a natural product, as a dietary food for special medical purposes (i. e. medical food) for cancer patients, has been approved by the health authorities of two EU countries (Hungary, Czech Republic). This medical food – called FWGE ® – is a water soluble granulate which contains a standardized fermented wheat germ extract (FWGE) manufactured under good manufacturing practice (GMP) conditions in Hungary (1). FWGE ® is the first original product with approved oncological indication, developed by Hungarians and, brought on the market after a pause of more than 30 years. This medical food has been demonstrated to have supportive effects in the treatment of colorectal (2), oral cavity (1), head- and neck (3), breast (1) and lung (1) cancers, in skin melanoma (4) and, inhibited the development of febrile neutropenia in high-dose chemotherapy treated children (5). One of us (G.B.) observed that rheumatoid arthritis (RA) patients, who had concurrent cancer and were taking FWGE ® on a continuous basis, showed surprisingly significant improvements in their RA symptoms. Therefore, a feasibility pilot clinical study with FWGE ® in RA was carried out to test whether such patients could indeed benefit from taking this medical food.

Patients and methods 

To be eligible for this study, patients had to have a severe RA according to the ACR (American College of Rheumatology) classification, and had to have either a stable disease with an insufficient outcome, or a progressive disease at least for three months prior to study entry. 

 For statistical analyses the Wilcoxon test, where P < 0.05 indicated a statistical significance, was used. Patients gave written informed consent, and the Regional Committee of the National Council of Health approved the protocol. The Declaration of Helsinki principles had been followed, and the patients were free to withdraw their consent at any time during the study.

Results

In Budapest, at the National Institute of Rheumatology and Physiotherapy, 15 refractory RA patients (ambulatory female patients; average age 54, range 44-68 years), whose disease was in Steinbrocker anatomical and functional categories of II and III, were enrolled in this open-label, non-randomized, pilot study. The average duration of their disease was 8.2 (range 3-25) years. All but one patient were seropositive. At the time of entry, 8 patients received DMARD (methotrexate/4, cyclosporine/3, chloroquine) plus corticosteroid (methylprednisolone/5, prednisolone/2, triamcinolone), while 2 patients received DMARD (methotrexate, sulfasalazine), and 3 patients received corticosteroid (methylprednisolone, prednisolone, dexamethasone) therapies alone. By the end of the first 6 months of the study, the steroid dosage could be decreased in 5, and remained unchanged in 6 patients (significant change) (Fig. 1). By the end of the 12th months, it remained unchanged in 6, was decreased in 4, and was increased in 1 patient (not significant change). In 6 patients, the DMARD therapy remained unchanged during the whole study and, it was reduced in 3, increased in 1 patient (not significant change). 

Compared to baseline data, the Ritchie index, the HAQ as well as the morning stiffness, all shown significant improvements by the end of the first 6th month of the trial and, these improvements have remained steady since then (Figs. 2-5). There were no consistent changes in the laboratory parameters. Though by the 6th month of the study a significant decrease in the sedimentation rate (from 46 to 28, P = 0.033) and a non-significant one in CRP (from 11 to 9, P = 0.187), indicators of systemic inflammation, could be detected, the values approached the baseline by the end of the study. During the 12 months treatment period no side effects of FWGE ® were observed. Few patients complained of an unpleasant taste of the product, but no patients withdrew their consent due to this reason.

Discussion

This is the first report on a wheat derived nutraceutical showing an adjunctive therapeutic effect in RA. Although the mechanisms that contribute to the pathogenesis of RA are, at least partially, unknown, synovial macrophages and fibroblasts are now considered as targets for therapeutic intervention in RA, because insufficient apoptosis of these cells might contribute to the increased numbers of chronic inflammatory cells in RA joints and thus, to the persistence of the disease (9). Therefore, the resolution of chronic inflammation seems to require the apoptosis of effector cells, such as macrophages and synovial fibroblasts,downstream proteases, including the cleavage of the poly(ADP-ribose) polymerase (PARP) enzyme, which is considered to be a hallmark of activation of caspase-3 like proteases during apoptosis, thus leading to genomic instabilities and disintegration in the target cells.