Toward a holistic model of personalized and integrative medicine: The distinctive role of Persian medicine

Abstract

Modern personalized medicine is transforming healthcare by customizing treatments based on individual genetic, environmental, and lifestyle profiles. However, its application remains complex and often technologically intensive. Traditional systems, particularly Persian Medicine (PM), offer distinctive frameworks that align with and can enrich contemporary personalized care. Unlike other traditional systems, PM is grounded in a unique philosophical concept of health governed by Nature (Tabi'at)—an intrinsic healing force—and operationalized through the concept of temperament (Mizaj). In this article, we systematically review both classical sources and contemporary clinical research to explore how PM offers structured diagnostic methods, preventive principles, and therapeutic modalities. We present a descriptive comparative overview of PM, Ayurveda, and Traditional Chinese Medicine (TCM) and provide practical models of integration into modern healthcare. We propose that PM provides a philosophically coherent and empirically grounded model that complements genomic medicine while fostering truly patient-centered, integrative care. However, the evidence base remains nascent, and further high-quality research is needed to validate its integrative potential.

1. Introduction

Personalized medicine represents a transformative approach in modern healthcare, emphasizing individualized strategies in diagnosis, prevention, and treatment based on genomic, environmental, and lifestyle data [[1], [2], [3], [4]]. However, despite remarkable technological advances, current personalized medicine faces gaps in accessibility, cultural inclusivity, and holistic prevention [5].

Traditional systems such as Ayurveda, Traditional Chinese Medicine (TCM), and Persian Medicine (PM) have long employed personalized frameworks. Recent reviews suggest that PM can contribute to bridging the divide between modern precision tools and holistic patient care [[6], [7], [8]]. These systems, often rooted in holistic philosophy, provide insights that complement the reductionist orientation of biomedicine [9]. Personalized integrative medicine represents a holistic approach that effectively connects the principles of complementary and alternative medicine (CAM) with the rigor of evidence-based medicine (EBM). This fusion aims to create a tailored treatment plan that respects individual patient preferences, cultural backgrounds, and unique health needs while simultaneously relying on scientifically validated practices and interventions. By emphasizing patient-centered care, personalized integrative medicine encourages a collaborative relationship between practitioners and patients, allowing for a more comprehensive understanding of health that includes both traditional healing methods and modern medical advancements. This synthesis not only expands therapeutic options but also enhances the overall effectiveness and safety of patient care [10].

On the other hand, variable response to modern medicine and side effects of its medications and interventions have led to a growing interest in traditional, complementary medicine (T&CM) all over the world [4]. The WHO emphasizes T&CM integration into modern medicine [11].

Persian medicine (PM), as a historical system of health rooted in Persian intellectual tradition, exemplifies a holistic and personalized medical approach. PM emphasizes the maintenance of health and the restoration of balance in disease through individual-specific evaluation and interventions. Its distinctive philosophical framework is built upon the concept of Tabi'at (Nature)—the body's intrinsic healing force—which is operationalized through a sophisticated system of temperament, or Mizaj. This system embodies its holistic personalized approach in etiology, semiology, prevention, and treatment. It stands out not only for its historical depth but also for its philosophical and clinical distinctiveness. While the concept of individualized care, such as lifestyle assessment, pulse analysis, and urine examination, is common to many traditional systems, PM's uniqueness lies in its integrated theory of health and disease and its Mizaj-based classification system. [12,13]. These concepts provide a nuanced structure for understanding patient individuality that extends beyond symptomatology or constitution to encompass the dynamic interaction between mind, body, and environment.

Moreover, the stepwise therapeutic model in PM, from lifestyle correction to natural pharmacotherapy and manual interventions, is deeply rooted in the principle of minimal intervention and personalized adjustment. This stratified yet flexible approach exemplifies a holistic, patient-centered model that remains underutilized in modern personalized medicine.

This paper aims to articulate the holistic personalized framework of PM and its relevance to contemporary personalized and integrative medicine, proposing that PM is not merely a complementary tradition but a valuable partner in shaping the future of integrative, personalized healthcare. Yet, a clear synthesis of PM's unique contributions compared with other systems remains underexplored. This article addresses this knowledge gap while also critically appraising the current state of evidence and challenges to integration.

2. Methodology

2.1. Eligibility criteria

We included peer-reviewed studies, clinical trials, reviews, and relevant classical Persian texts that addressed concepts of Mizaj (temperament), Tab i'at (nature), preventive strategies, diagnostic tools, or treatment modalities in PM. Articles were considered if they were published in English or Persian (with translation). Non-peer-reviewed opinion pieces and non-medical historical texts were excluded.

2.2. Information sources

Databases searched included PubMed, Scopus, SID (Scientific Information Database), and Google Scholar. In addition, major classical sources such as Avicenna's Canon of Medicine, Jorjani's Zakhireh Kharazmshahi, and Rhazes' Al-Hawi were reviewed.

2.3. Search strategy

Search terms used were: “Persian Medicine,” “Mizaj,” “Tabi'at,” “integrative medicine,” and “personalized healthcare.” The search was conducted without time restrictions and was updated through March 2025.

2.4. Study selection process

Titles and abstracts were screened for relevance, followed by full-text review of potentially eligible sources. Studies were included if they provided empirical data, theoretical frameworks, or historical descriptions relevant to PM's role in personalized or integrative medicine. The study selection process is summarized in a PRISMA-style flow diagram (Fig. 1).

Fig. 1.

PRISMA flow diagram of study selection.

2.5. Risk of bias assessment

Given the heterogeneity of included studies, a formal quality appraisal was applied using appropriate tools. For randomized controlled trials (RCTs), the Cochrane Risk of Bias 2 (RoB 2) tool was used. For observational studies, the Newcastle-Ottawa Scale (NOS) was applied. The overall quality of evidence for key findings was considered low to moderate, constrained by common limitations such as small sample sizes, lack of blinding, inconsistent implementation of interventions, and lack of standardized outcome measures in several PM trials. The potential for publication bias is acknowledged.

2.6. Holistic foundations of Persian medicine

PM contextualizes disease within temperament, environment, and lifestyle. Unlike a purely reductionist model, PM emphasizes the operational principle of Tab i'at—analogous to self-regulation in systems biology. For accessibility, Tab i'at can be compared to “homeostasis” in modern physiology, while Mizaj resembles a dynamic phenotype shaped by genetic and environmental interaction. This systemic view allows PM to align with the core objectives of personalized healthcare while offering predictive and preventive strategies based on centuries-old insights. PM conceptualizes health not as the absence of disease, but as a dynamic state of balance influenced by an individual's temperament, lifestyle, emotions, and environment. Unlike modern personalized medicine, which often relies on genetic markers and molecular diagnostics, PM grounds its personalization in the qualitative assessment of bodily functions and harmony, guided by Tab i'at. To further clarify the distinctive features of PM, we provide a comparative overview with Ayurveda and TCM (Table 1).

Table 1.

Comparative overview of Persian medicine, Ayurveda, and TCM.

Feature	Persian Medicine (PM)	Ayurveda	Traditional Chinese Medicine (TCM)
Core Principle	Balance guided by Tab i'at (Nature), an intrinsic healing force	Balance of three bioenergies, the Tridosha (Vata, Pitta, Kapha)	Balance of opposing forces, Yin and Yang, and flow of Qi (vital energy)
Constitutional Typology	Nine primary categories of Mizaj (Temperament) based on hot/cold/wet/dry qualities	Three primary Doshic types (Prakriti: Vata, Pitta, Kapha)	Multiple body constitution patterns (e.g., Qi-deficient, Damp-heat)
Primary Diagnostic Methods	Pulse, urine examination (Qarȗreh), detailed Mizaj-based physical & psychological evaluation	Pulse, tongue examination, and assessment of Dosha imbalance	Pulse, tongue examination, and assessment via meridian theory
Core Preventive Strategies	Adherence to the six essential lifestyle principles (Setteh-ye-zarȗriyah)	Daily and seasonal routines (Dinacharya, Ritucharya)	Dietary and lifestyle alignment with seasons and individual constitution
Common Therapeutic Modalities	Lifestyle modification, herbal pharmacotherapy, manual therapies (dalk, ghamz, hijamat)	Purification procedures (Panchakarma), herbal remedies, and diet	Acupuncture, herbal medicine, movement therapies (e.g., Qi Gong)
State of Modern Integration	Growing research interest; integration pilots in Iran and niche settings internationally	Widely integrated into the national healthcare system in India	Increasingly researched and integrated into TCM hospitals and clinics worldwide

2.7. Etiology in Persian medicine: A personalized perspective

PM evaluates disease etiology through both intrinsic and extrinsic factors. These include genetic predispositions, lifestyle habits, emotional states, and environmental exposures [10]. This multidimensional understanding parallels the determinants of health in modern personalized medicine and supports a more nuanced approach to disease risk assessment.

2.8. Semiology: diagnostic tools in PM

PM utilizes a variety of diagnostic tools tailored to individual characteristics:

• •Mizaj (Temperament): Central to PM diagnosis, mizaj defines the qualitative nature of an individual, influenced by organ-specific temperaments. Health is seen as the equilibrium of these temperaments, while dystemperament leads to disease [13,14]. Diagnosis involves a detailed review of the body's systems, akin to a functional health assessment. There are ten clinical criteria, including physical, physiological, and psychological features, which are used in PM practice to determine a person's mizaj known as Ajnas-e-Ashare (Ten Features): obesity and thinness, skin color, hair condition, physique, temperature of skin touch, quality of functions, characteristics of waste matters, sleep and wakefulness, impressibility from hotness, coldness, dryness, and wetness, and psychic functions [15]. Efforts are underway to prepare standard scales and assessment tools [[16], [17], [18]]. In addition to general temperament assessment, there are specific signs and symptoms related to each organ to evaluate its temperament [[19], [20], [21], [22]]. A key challenge for research is establishing the inter-rater reliability of these assessments.
• •Pulsology: PM interprets the pulse to assess not only cardiac function but also the organs and integrated whole body condition, offering insight into systemic imbalances [23]. It analyses pulse beyond rate and rhythm, assessing qualitative features. The unique evaluation of pulse in PM includes ten items: dimensions (length, width, and depth), strength, speed, frequency (rate), vessel consistency, intravascular volume, temperature, regularity (rhythm), harmony, and appropriateness [15].
• •Urine Examination: A sophisticated method to assess internal organ states and assist in differential diagnoses, often comparable in detail to modern urinalysis. The distinct urine analysis in PM, known as qȃrȗreh, includes seven features: color, sediment, density, transparency, foam, odor, and volume. These items that should be checked in a specific condition, and evaluated oner time, provide insights into organ health and humor imbalances [24]. These techniques were historically rigorous and can be analogized to functional biomarkers in modern diagnostics.

2.9. Preventive strategies in PM

Prevention is a cornerstone of PM. The system is built upon six foundational lifestyle principles (Setteh-ye-zarȗriyeh), which include: air and environment; nutrition and diet; physical activity and rest; sleep and wakefulness; psychological states; and excretion and retention. These six principles have been increasingly discussed in modern public health as parallel to the “six pillars of lifestyle medicine,” creating a bridge between PM concepts and contemporary prevention models [13,25]. In addition, PM recognizes nine primary temperaments (Mizaj categories): warm-wet, warm-dry, cold-wet, cold-dry, along with balanced and mixed forms. These classifications provide the framework for tailoring preventive advice, such as adjusting diet, sleep patterns, or seasonal routines according to the individual's temperament. PM also proposes recommendations for vulnerable populations such as children, the elderly, and pregnant women [13,26,27]. These lifestyle principles offer a holistic approach to noncommunicable diseases [28].

Clinical Evidence Example: A randomized controlled trial, detailed in the Results section, evaluated the efficacy of Persian Medicine–based lifestyle modification on functional bloating and found a significant reduction in symptom severity [29]. These findings, while promising, are from a single, small trial and suggest that PM lifestyle education warrants further investigation as a practical preventive and therapeutic strategy for gastrointestinal disorders.

2.10. Treatment modalities in Persian medicine

Persian medicine (PM) offers a structured, hierarchical approach to treatment that prioritizes harmony with the patient's intrinsic temperament and the body's natural healing intelligence (Tabi'at). This stepwise methodology is not only preventive and therapeutic but also philosophically grounded, aiming to restore balance rather than suppress symptoms. The distinctive hallmark of PM lies in its integrative framework, wherein each intervention is selected according to a nuanced, individualized assessment encompassing the patient's temperament, environmental conditions, occupational exposures, emotional tendencies, and habitual behaviors [30]:

• 1.Lifestyle Modifications: Lifestyle regulation represents the foundational and often most potent therapeutic strategy in PM. In contrast to many modern systems that introduce lifestyle changes as adjuncts, PM regards lifestyle as the cornerstone of treatment. The six essential factors (Setteh-ye-zarȗriyeh), detailed in the Preventive Strategies section, are meticulously modulated to align with the patient's temperament and pathophysiological state. Unlike generalized wellness advice, PM's lifestyle prescriptions are precise, temperament-specific, and dynamically adjusted over time. Emerging clinical studies have begun to validate the effectiveness of PM-based lifestyle interventions in managing chronic conditions such as metabolic disorders, gastrointestinal diseases, and mood disturbances [25].
• 2.Pharmacotherapy: PM's pharmacological approach is deeply rooted in the doctrine of Mizaj and the qualitative properties of natural substances. Medicinal prescriptions are crafted based on the temperament of the patient and the corrective properties of individual herbs or compounds. These remedies are predominantly plant-based, but may also include mineral and animal-derived substances. One of the distinguishing factors of PM pharmacotherapy is its emphasis on “corrective pairing” (Mosleh)—the art of combining substances to balance and neutralize undesirable effects and adding specific features such as “drug targeting”—and the notion of gradual, long-term modulation rather than immediate symptom relief. Dosages, routes of administration, and timing are all personalized, reflecting a sophisticated pharmaco-therapeutic system developed centuries before the advent of modern pharmacogenomics [31].
• 3.
  Manual Therapies: Manual therapies in PM are therapeutic procedures intended to restore humoral balance, remove blockages, and facilitate the flow of vital energies (Rȗh) and essential substances (Akhlȃt). These include:

  • •
    Massage (Dalk): Used to stimulate circulation, balance temperament, and alleviate musculoskeletal or neurological discomforts [32].
  • •
    Acupressure (Ghamz): A lesser-known yet integral manual therapy in PM, Ghamz involves applying targeted pressure with fingers to specific points on the body to stimulate internal organs, relieve pain, and harmonize energy flow [33]. While it shares similarities with techniques in other traditional systems (e.g., Chinese acupressure), Ghamz in PM is rooted in the theory of organ-humor relationships and temperament-specific responses. It is particularly effective in treating various disorders such as chronic fatigue, digestive disorders, musculoskeletal pains [34,35], and stress-related imbalances.
  • •
    Cupping Therapy (Hijamat): Wet and dry cupping are employed for detoxification, humoral balance, and enhancement of organ function [36].
  • •
    Leech Therapy (Alaq): Applied in cases of localized congestion, inflammatory conditions, and venous disorders [37].
  • •
    Phlebotomy (Fasd): A controlled form of bloodletting used to evacuate excess or corrupted humors from the body [38].

Emerging clinical studies have begun to explore the efficacy of these manual therapies as adjuncts to conventional care [33,34].

These interventions are not reflexively applied but are chosen based on a comprehensive diagnostic evaluation, including pulse and urine analysis, physical examination, and temperament assessment. Their goal is not merely to treat symptoms but to reorganize the internal terrain of the body toward homeostasis.

Together, these treatment modalities reflect PM's integrative ethos, where prevention and personalization are not ancillary but are essential, guiding principles of practice. Unlike reductionist models that isolate pathology from the person, PM's therapeutic logic is holistic, situational, and deeply patient-centered. It provides a paradigmatic example of how a traditional system can inform and enhance contemporary models of personalized and integrative medicine, not through historical reverence alone but through its sophisticated, individualized logic of care.

3. Results

3.1. Study selection

Our search identified approximately 120 publications. After screening titles and abstracts, 67 were retained for full-text review. Of these, 39 studies were included in this narrative synthesis: 12 randomized controlled trials (RCTs), 10 observational studies, 7 reviews, and 10 classical or conceptual sources. The flow of study selection is detailed in Fig. 1.

3.2. Study characteristics

The included RCTs addressed conditions such as gastrointestinal disorders (functional bloating, dyspepsia), obstetric outcomes, metabolic diseases, musculoskeletal pain, and neurological conditions. Most trials had sample sizes between 40 and 120 participants and intervention durations ranging from 4 to 12 weeks.

Quality assessment using the RoB 2 tool indicated a high risk of bias in several studies, primarily due to issues with randomization processes, lack of blinding of participants and personnel, and potential selection bias in reporting results.

3.3. Empirical evidence

• •A randomized controlled trial demonstrated that PM-based lifestyle modification reduced symptoms of functional bloating by 51.8 % compared with controls [29]. However, the lack of blinding and a sham intervention group limits the strength of this conclusion.
• •Another RCT found that prenatal recommendations in PM improved obstetric outcomes, including reduced dystocia [27].
• •Clinical studies on manual therapies such as Dalk and Ghamz reported improved outcomes for musculoskeletal pain and mobility [33,34]. These studies suggest potential as adjunct therapies but require larger-scale replication.
• •Observational and survey-based studies confirm the applicability of PM lifestyle principles in primary health care [25].

3.4. Risk of bias

As noted, the current evidence base for PM interventions has significant limitations. The predominance of small-scale studies, heterogeneity in interventions and outcome measures, and high risk of bias in several RCTs mean that the overall strength of evidence is low to moderate. The potential for publication bias is a concern, as many PM studies are published in regional journals not indexed in international databases.

3.5. Application of Persian medicine in contemporary healthcare

Several models demonstrate how PM principles can be practically integrated into modern health systems:

• •Clinical Practice: PM dietary counseling has been successfully combined with standard diabetic care, offering personalized meal plans aligned with patients' temperaments.
• •Public Health: WHO's emphasis on integrating traditional and complementary medicine creates an opportunity to incorporate PM's six lifestyle principles into chronic disease prevention frameworks.
• •Education: The Canadian College of Integrative Medicine has piloted modules introducing PM concepts to integrative medicine practitioners, showing the feasibility of cross-cultural training.
• •Rehabilitation: Manual therapies such as Dalk and Ghamz are being explored as adjuncts to physiotherapy for musculoskeletal disorders.

These examples illustrate that PM can move beyond theoretical discussions and provide practical, integrative strategies that enhance patient-centered care. Their success, however, depends on rigorous evaluation within robust clinical frameworks.

3.6. The unique contribution of Persian medicine to integrative personalized healthcare

Integrative medicine aims to combine conventional biomedical approaches with evidence-informed traditional systems to create more holistic, patient-centered models of care. In this context, PM offers not merely complementary techniques, but a coherent medical philosophy and structured methodology that align remarkably with modern personalized medicine. While individualized lifestyle interventions, pulse and urine analysis, and temperament-based diagnosis are shared features among several traditional medical systems, such as Ayurveda and Traditional Chinese Medicine (TCM), PM distinguishes itself in several critical and underexplored ways that make it a unique contributor to integrative healthcare:

• 1.A Distinct Philosophical Framework Rooted in Nature (Tabi'at): At the core of PM lies the concept of Tab i'at, which functions as the operational principle guiding all clinical decisions. This notion offers a conceptual bridge between ancient wisdom and modern systems biology, where the body is viewed as a self-organizing, adaptive system. Although foundational work has been done to create and validate tools for Mizaj assessment [[16], [17], [18]], a primary research priority remains establishing their high inter-rater reliability and broader clinical predictive validity However, the full clinical validation of this framework and its application across different diseases remains a key focus for future research, a challenge compounded by the fact that CAM's clinical diagnosis of pre-pathologic stages of diseases can be a challenge for conventional physicians [39].
• 2.Advanced Temperament Theory (Mizaj): Although the concept of constitutional types appears across many traditions, PM's mizaj typology is among the most nuanced. It classifies individuals into nine main temperamental categories based on a synthesis of physical, physiological, and psychological markers. This classification goes beyond personality traits or dosha types—it governs the diagnosis, prevention, drug selection, dosing, and even prognosis. Importantly, PM recognizes dynamic shifts in temperament due to age, environment, season, and emotional state, allowing for more context-sensitive personalization.
• 3.Systematized Diagnostic Tools: The diagnostic use of pulse and urine analysis in PM is highly systematic. Pulse diagnosis (Nabz-shenasi) assesses not just rate and rhythm but qualitative attributes such as intensity, width, length, etc., all interpreted within a temperament framework. Urine examination (Qarooreh) similarly evaluates color, density, odor, and other patterns to assess internal humoral imbalances. Unlike conventional diagnostics, these methods are qualitative yet replicable within the PM framework, offering a personalized yet structured form of clinical reasoning. Their correlation with modern biochemical and imaging biomarkers is a fertile area for future research.
• 4.Embedded Preventive Logic: Modern personalized medicine, often driven by high-cost omics technologies, tends to emphasize prediction and pharmacogenomics. In contrast, PM emphasizes low-cost, culturally embedded preventive strategies that can be widely applied. These include early intervention based on subtle temperament shifts, environment-specific lifestyle adaptations, and food-based therapy customized by temperament and season, offering scalable tools for public health within an integrative model.
• 5.Complementarity with Systems Medicine: The PM model aligns with systems biology in viewing the human being as an integrated network of dynamic processes rather than a sum of isolated parts. However, PM adds a layer of experiential insight into how these processes manifest subjectively and contextually in each patient. This allows for a biopsychosocial-energetic integration that is often missing in modern personalized frameworks.

In summary, Persian Medicine provides a philosophically robust, diagnostically rich, and practically applicable model of personalization that complements and expands current integrative healthcare strategies. Its unique temperament theory, emphasis on Tab i'at, and context-specific lifestyle interventions offer actionable insights for modern personalized medicine while preserving cultural relevance and therapeutic coherence. The translation of this theoretical potential into validated clinical practice remains the central challenge.

3.7. Challenges and future research directions

The integration of PM faces several significant challenges that must be addressed by future research:

• 1.Standardization and Validation: A paramount challenge is the development and validation of reliable, objective tools for diagnosing Mizaj and assessing the outcomes of PM interventions.
• 2.Safety and Interactions: The safety profile of PM therapies, particularly pharmacotherapy, and their potential interactions with conventional drugs require systematic pharmacovigilance studies.
• 3.Mechanistic Studies: Research is needed to explore the biological mechanisms underlying PM concepts like Tab i'at and dystemperament using systems biology and other modern scientific approaches.
• 4.Pragmatic Trials: Large, well-designed pragmatic trials are necessary to evaluate the effectiveness and cost-effectiveness of PM interventions in real-world clinical settings compared to usual care.

3.8. Limitations

This narrative review has several limitations. First, the included empirical studies are relatively few, often with small sample sizes and short follow-up periods, limiting the generalizability of findings. Second, heterogeneity in PM interventions and the lack of standardized outcome measures make comparison across studies difficult. Third, the risk of publication bias cannot be excluded, as many PM studies are not indexed in international databases. Finally, while we included major Persian classical texts and modern publications, the absence of a fully systematic search and the use of a narrative synthesis approach limit reproducibility and increase the potential for selection bias.

4. Conclusion

Persian medicine represents an early and sophisticated model of personalized healthcare. Its integration into the broader landscape of modern medicine not only honors cultural heritage but also offers valuable strategies for enhancing preventive and individualized care. The current evidence, while promising, is preliminary. Future research should focus on addressing the identified challenges through robust clinical trials, systems biology approaches, and evidence-based validation to further bridge these complementary paradigms.

The integrative potential of PM lies in its shared aims with modern personalized medicine—predictive, preventive, and individualized care—while offering a philosophically distinct and empirically rich framework. By reconciling traditional diagnostic and therapeutic systems with contemporary clinical research, a more comprehensive and effective healthcare model can emerge. This will require a collaborative effort that respects traditional knowledge while adhering to the rigorous standards of modern scientific inquiry.

PM's emphasis on lifestyle, environmental awareness, and internal balance offers a critical supplement to technology-driven medicine. Its personalized lens reinforces the need for culturally competent and holistic care, especially in regions where PM remains a living tradition. Realizing its full potential will depend on a concerted and critical research agenda.

Author contributions

YV: Conceptualization, Primary draft.

BD: Conceptualization, Writing, Editing.

MN: Editing and revising the final draft.

Declaration of generative AI in scientific writing

ChatGPT and Grammarly have been used to improve the writing of the paper. Authors have revised and approved the final version of the paper, confirming their authorship responsibility.

Funding sources

None.

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.