IntegraRE Project: Pioneering Study Examines Food Supplement Use in Rheumatological Care Across Italy

What is the IntegraRE Project All About?

The IntegraRE project is setting out to address a significant knowledge gap in rheumatology: the use of food supplements and their role in patient care. This nationwide Italian study aims to comprehensively evaluate both rheumatologists' clinical practices and patients' consumption patterns of food supplements, an increasingly popular yet understudied aspect of rheumatological care. With over 200 identified rheumatological conditions affecting millions globally, including prevalent disorders like osteoarthritis (7.6%), gout (3.3%), spondylarthritis (0.5%-2%), rheumatoid arthritis (0.2%) and systemic lupus erythematosus (0.003%-0.5%), the management of these chronic, potentially disabling conditions presents ongoing challenges for healthcare providers. While conventional treatments like non-steroidal anti-inflammatory drugs, corticosteroids, conventional synthetic, targeted synthetic, and biologic disease-modifying antirheumatic drugs remain essential, their potential adverse effects and limitations have prompted both clinicians and patients to explore complementary approaches, with food supplements emerging as a prominent alternative strategy. The European Union defines food supplements as 'food products intended to supplement the normal diet and which constitute a concentrated source of nutrients, such as vitamins and minerals, or other substances with a nutritional or physiological effect, including but not limited to amino acids, essential fatty acids, fibres and plant extracts, either mono-components or multi-components, in pre-dosed forms'. Their market has expanded considerably due to the common perception that they offer "natural" health benefits without side effects. However, this perception overlooks documented cases of supplement-related adverse events, including vitamin toxicities and herb-drug interactions. Recent studies have highlighted cases of intoxication due to overuse of supplements containing vitamins D, E, and A, as well as interactions between vitamin K and oral anticoagulants. The situation becomes even more complex with botanical ingredients, with reported cases of hepatotoxicity attributed to Curcuma longa and well-known potential risks of pharmacological interactions between supplements containing Saint John's Wort (Hypericum perforatum) and conventional drugs.

The situation is further complicated by the fact that supplements do not require prescriptions and can be freely purchased through various channels (pharmacies, parapharmacies, large-scale distribution, and the Internet), often without medical supervision. Additionally, physicians themselves frequently lack adequate training and clear guidelines to provide effective advice on supplement use, placing them in a challenging position when patients seek guidance. The role of diet in inflammatory processes has recently gained attention, with studies showing that nutrition can directly influence inflammatory processes and potentially play a role in various rheumatological conditions, such as rheumatoid arthritis and osteoarthritis. Diet is also involved in the onset of comorbidities associated with rheumatological conditions, such as cardiovascular disease, obesity, and diabetes, which greatly contribute to reducing patients' life expectancy.

How Does the Dual-Phase Survey Provide Valuable Insights?

The IntegraRE project employs a dual-phase cross-sectional survey approach to address these issues. The first phase, lasting six months, targets rheumatologists across Italy through a Knowledge, Attitudes, and Practices (KAP) questionnaire distributed via the Italian Rheumatologists College (CReI). With a target sample of 287 physicians from a population of 1,134 rheumatologists stratified by region (North 40%, Centre 22%, South 24%, and Islands 14%), this phase aims to estimate the proportion of specialists who recommend supplements, characterize what is recommended, and assess their knowledge and attitudes toward these products. Between phases, a dedicated training day for rheumatology physicians will be organized by the Italian National Institute of Health (ISS) with the support of CReI to standardize knowledge and improve awareness about appropriate supplement use. During this training, key regulatory, nutritional, and safety aspects of food supplements will be addressed, with particular attention to potential benefits and risks. The preliminary data collected in Phase 1 and the objectives of Phase 2 will also be presented, along with instructions on administering the questionnaire to patients.

The second phase, extending over 18 months, will engage at least 2,000 patients nationwide who consult with participating rheumatologists. Through anonymously completed paper questionnaires administered in waiting rooms, this phase will estimate the prevalence of supplement use among patients, identify specific products and reasons for use, determine sources of advice, and assess perceived benefits and safety concerns. The questionnaires have been specifically designed for this study, with the physician survey undergoing test-retest reliability assessment after 20 days. Data analysis will include descriptive statistics, correlation analyses, and logistic regression to identify predictors of supplement recommendation and consumption. The study's design ensures regional representation through careful stratification, with minimum thresholds established for smaller regions to maintain national representativeness.

Could These Findings Transform Clinical Practice and Patient Communication?

The Phase 1 questionnaire includes five sections: one focused on collecting sociodemographic data (age, gender, lifestyle information, type and location of their clinic or facility, years of work experience, and average number of patients seen per year), one on knowledge about supplements (20 questions on a Likert scale), another on attitudes (17 questions on a Likert scale), and a fourth on clinical practice (19 questions primarily on a Likert scale, with some open-ended items). The last section is aimed at generating an alphanumeric code for matching questionnaires during reliability testing. Knowledge of supplements is defined as achieving at least 52% correct answers. The Phase 2 questionnaire collects information regarding demographic factors (age, gender, educational qualification, income, health conditions, lifestyle), anamnestic factors (chronic rheumatological and non-rheumatological diseases and medications), and knowledge, use, and perception of food supplements. It specifically assesses food supplement use over the past month, including specific products taken, duration of use, dosage, reasons for use, who recommended the products, and whether referring physicians are aware of their intake. It also evaluates potential seasonality in consumption and patients' perceptions of benefits or adverse effects. This comprehensive approach will provide valuable insights into current practices and perceptions, potentially informing future guidelines and educational initiatives for both healthcare providers and patients.

The study's innovative approach of examining both the provider and consumer perspectives simultaneously represents a significant strength, as it will allow for a more complete understanding of supplement use in rheumatology. By including rheumatologists across different practice settings and regions, the survey will capture diverse perspectives and practices, enhancing the generalizability of findings. Additionally, the development of validated questionnaires through this project will provide valuable tools for future research in this field, potentially adaptable to other medical specialties with minor modifications. The training component between phases not only serves to standardize knowledge among participating physicians but also represents an intervention that could directly improve clinical practice. Furthermore, the detailed collection of information on specific supplement products and consumption patterns will enable the assessment of compliance with established maximum limits and evaluation of scientific evidence supporting their use. Despite these strengths, several limitations warrant consideration. The voluntary nature of participation may lead to selection bias, with those more interested in supplements being more likely to respond. To mitigate this, the researchers have implemented multiple recruitment strategies and regular reminders. Recall bias is another concern, particularly for patients reporting supplement use. This is being addressed by limiting the reporting period to the past month and ensuring anonymity to reduce social desirability bias. Additionally, the cross-sectional design precludes causal inference, and the self-reported nature of data without objective verification represents another limitation.

The potential impact of the IntegraRE project extends beyond academic interest, with significant implications for clinical practice, patient care, and public health. By identifying patterns in supplement recommendation and use, the study could help establish evidence-based guidelines for incorporating supplements into rheumatological care when appropriate. This is particularly important given the chronic nature of rheumatological conditions and patients' ongoing search for complementary approaches to manage symptoms and improve quality of life. The project may also highlight critical knowledge gaps among physicians, informing targeted educational interventions to enhance their confidence in discussing supplements with patients. For patients, the findings could lead to more transparent communication about supplement use, potentially reducing the risk of adverse events and drug interactions. From a public health perspective, understanding consumption patterns could inform regulatory approaches and safety monitoring systems for supplements commonly used in rheumatology. The dissemination strategy, which includes both scientific publications and public-facing materials through the ISS website (www.iss.it/integrare), ensures that findings will reach both healthcare professionals and the general public, maximizing the study's impact. As the first nationwide investigation of its kind in Italy, the IntegraRE project represents a pioneering effort to bridge a significant knowledge gap in rheumatological care. Could this comprehensive approach to understanding supplement use in rheumatology serve as a model for similar investigations in other medical specialties where supplement use is prevalent? How might the findings influence the integration of nutritional strategies into standard care protocols for chronic inflammatory conditions?

The IntegraRE project also addresses an often-overlooked aspect of patient care: the disconnect between what physicians recommend and what patients actually do. By examining both perspectives, the study may reveal important discrepancies in communication and understanding about supplements. For instance, patients may be using supplements without disclosing this to their rheumatologists, potentially due to fear of disapproval or dismissal. Alternatively, they might misinterpret physicians' recommendations, leading to improper dosing or use of inappropriate products. These insights could lead to improved communication strategies and shared decision-making tools specifically focused on supplement use. Furthermore, the study's attention to regional variations across Italy may uncover geographic disparities in both recommendation and consumption patterns, potentially reflecting differences in access to information, cultural attitudes toward supplements, or socioeconomic factors. Such findings would be valuable for developing targeted interventions that account for regional contexts. Beyond its immediate objectives, the IntegraRE project lays groundwork for future research directions, including longitudinal studies examining the long-term effects of supplement use in rheumatological conditions, investigations into cost-effectiveness of various supplementation strategies, and development of decision support tools to guide personalized supplement recommendations. As healthcare systems increasingly emphasize patient-centered approaches and integrated care models, understanding the role of supplements in rheumatology becomes essential for comprehensive disease management. Could standardized assessment of supplement use become a routine part of rheumatological care, similar to medication reconciliation? How might digital health tools be leveraged to support evidence-based supplement use and monitoring in rheumatology patients? The IntegraRE project takes an important first step toward addressing these forward-looking questions, potentially transforming how supplements are viewed and utilized within mainstream rheumatological practice.

Summary

The IntegraRE project represents a groundbreaking nationwide Italian study designed to comprehensively evaluate the use of food supplements in rheumatological care from both physician and patient perspectives. Addressing a significant knowledge gap in a field where over 200 rheumatological conditions affect millions globally, the project employs a dual-phase cross-sectional survey approach. Phase 1 targets 287 rheumatologists across Italy through a Knowledge, Attitudes, and Practices questionnaire to assess their recommendation patterns, knowledge levels, and attitudes toward supplements. Between phases, a dedicated training day organized by the Italian National Institute of Health will standardize knowledge among participating physicians. Phase 2 extends over 18 months, engaging at least 2,000 patients to determine prevalence of supplement use, identify specific products consumed, assess reasons for use, and evaluate perceived benefits and safety concerns. The study addresses the complex landscape where supplements are increasingly popular yet potentially risky, with documented cases of vitamin toxicities, herb-drug interactions, and hepatotoxicity. By examining both provider and consumer perspectives simultaneously, the project aims to bridge the disconnect between medical recommendations and actual patient practices, potentially revealing critical communication gaps and regional disparities. The findings are expected to inform evidence-based guidelines for incorporating supplements into rheumatological care, enhance physician education, improve patient communication, and influence regulatory approaches. As the first nationwide investigation of its kind in Italy, IntegraRE could serve as a model for similar research in other medical specialties and contribute to the development of integrated care models that appropriately incorporate nutritional strategies into standard protocols for chronic inflammatory conditions.