Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as a public health issue across the globe. Its complex etiopathology and association with diverse comorbidities poses significant challenges to conventional pharmacological drugs derived from the “lock-and-key” paradigm of pharmacology. To overcome the challenges of complexity and non-linear dynamics underlying the disease biology of MASLD, this article proposes a transdisciplinary framework combining holistic disease management principles of traditional medicines with molecular precision of modern biomedicine. Ayurveda - an exceptionally designed and widely practiced Indian Systems of Medicine (ISM) - is explored as a representative model for this framework. This article outlines a unified, biologically plausible transdisciplinary approach incorporating dual-diagnostic workflows, integrative decision interface, and stage-adaptive management algorithm for prevention, early intervention, and advanced disease care. The framework emphasizes integrative and personalized strategies integrating nutrition, lifestyle modification and drug interventions, harnessing the molecular precision of biomedicine alongside the systemic effects of phytochemical diversity. The transdisciplinary model seeks to shift the focus from ‘disease treatment’ to ‘health restoration’ and long-term wellness. The article highlights the scopes and challenges of this framework to offer more comprehensive, sustainable, and patient-centred solutions for MASLD.
1 Introduction
The rising global prevalence of non-communicable diseases (NCDs), and associated mortality and reduced quality and expectancy of life, poses one of the most pressing public health challenges of the 21st century (Hunter and Reddy, 2013; World Health Organization, 2014; World Health Organization, 2025). Modifiable and non-modifiable risk factors such as unhealthy diet, physical inactivity, globalization-induced lifestyle changes, aging, stress, metabolic abnormalities, tobacco and alcohol use, as well as genetic and environmental factors are fuelling the prevalence of NCDs (Cuevas Garciá-Dorado et al., 2019; Brauer et al., 2024; Formichi et al., 2025). Metabolic dysfunction-associated steatotic liver disease (MASLD), driven primarily by dysregulated glucose and lipid metabolism, is one such emerging global health issue (Feng et al., 2024; Scoditti et al., 2024). The multifactorial aetiology and systemic pathophysiology of MASLD often constrain the effectiveness of conventional molecular medicines, making an integrative medicine approach, effectively merging holistic and reductionist views of biology, relevant and imperative. This perspective article underscores the urgency of creating a transdisciplinary knowledge framework, bridging epistemologically and ontologically different medical systems, for an omniscient view of the MASLD disease biology; and examines its potential benefits, opportunities, and challenges in advancing MASLD management within the evolving landscape of NCDs.
1.1 MASLD - the “silent epidemic”: disease trajectory and global trends
MASLD is a spectrum of liver disorders ranging from simple steatosis to progressive metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and MASH-associated hepatocellular carcinoma (HCC) (Tacke et al., 2024). As a cause and consequence of systemic metabolic imbalance, MASLD is characterized by excessive triglyceride accumulation within hepatocytes, accompanied by at least one cardiometabolic risk factor such as hypertension, overweight, increased plasma triglycerides, reduced plasma HDL-cholesterol and type 2 diabetes (T2D) (Rinella et al., 2023). The condition was first described in 1980 as non-alcoholic steatohepatitis (NASH) to distinguish from alcohol-induced hepatic steatosis. It was renamed as non-alcoholic fatty liver disease (NAFLD) in 1986, and later redefined as metabolic dysfunction-associated fatty liver disease (MAFLD) to capture a broader clinical spectrum linked to obesity or T2D or both (Ludwig et al., 1980; Schaffner and Thaler, 1986; Eslam et al., 2020). In 2023, a multi-society Delphi consensus among three major liver associations in Europe, North America, and Latin America adopted the term MASLD, aligning the nomenclature with its complex pathophysiology and metabolic determinants (Rinella et al., 2023).
A recent meta-analysis on MASLD reports a global prevalence of 32.4%, projected to reach 55.4% by 2040, posing substantial clinical and economic burdens (Nguyen et al., 2022; Riazi et al., 2022). While the prevalence is highest in Latin America (44.4%) and lowest in Western Europe (25.1%), a rapid increase in obesity and T2D in regions like Middle East and North Africa (MENA), and Asia drives these global statistics (Younossi et al., 2023, 2024a; 2024b). In India, the prevalence is much higher than the global average (68.2%) and corroborates with India’s status as “global capital of diabetes” (Mohan et al., 2025). The growing global prevalence of MASLD, the observed regional disparities, and its bidirectional association with overweight, obesity and T2D draws urgent attention to MASLD as a public health issue comparable to other epidemics and emphasize the need of tailored region-specific and personalized management strategies (Quek et al., 2023; Zargar et al., 2025). Noticeably India is the first country to include MASLD into the National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) which aims at tackling the NCDs (Prasad et al., 2023).
1.2 The multisystem pathophysiology of MASLD is centred around impaired glucose and lipid metabolism
The disease trajectory and global trends of MASLD reveal two key aspects; its complex multisystem consequences and strong association with impaired glucose and lipid metabolism (Sandireddy et al., 2024; Targher et al., 2024; Steinberg et al., 2025). In normal physiology, dietary glucose is transported to the liver for glycogen storage or energy production, while insulin released from pancreatic β-cells suppresses hepatic gluconeogenesis and stimulates glucose uptake into muscle and adipose tissue. Both the liver and adipose together regulate the synthesis, storage, and breakdown of lipids. Excess glucose reaching these tissues will undergo de novo lipogenesis (DNL) and stored as triglycerides. During the fed-fasting cycle, the body efficiently switches between glucose and fat as the primary energy source through insulin-regulated coordination of lipolysis and gluconeogenesis between adipose, liver and muscle. Disruptions of this ‘metabolic flexibility’ due to behavioural, physiological and psychological factors is a key driver of NCDs like MASLD (Sanders and Griffin, 2015; Adeva-Andany et al., 2016; Luo and Liu, 2016; Cho et al., 2023).
In MASLD, diets rich in carbohydrates over-activate transcription factors like carbohydrate-responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), increasing hepatic DNL and triglyceride synthesis, leading to lipid overload, peripheral insulin resistance (IR), hyperinsulinemia and hyperglycaemia (Gastaldelli and Cusi, 2019). IR in liver further increases gluconeogenesis and DNL, while muscle and adipose tissue become resistant to insulin-mediated glucose uptake. Also, the increase in lipolysis in the adipose tissue releases excess free fatty acids (FFAs) into circulation, overburdening hepatic β-oxidation and causing accumulation of triglycerides, diacylglycerol and ceramides ultimately leading to hepatic steatosis (Trauner et al., 2010; Gastaldelli and Cusi, 2019; Kahn et al., 2019; Merz and Thurmond, 2020; Ahmed et al., 2021). All these biochemical changes progressively disrupt glucose and lipid homeostasis, which is a hallmark of the body’s metabolic dysfunction and MASLD pathogenesis (Bril et al., 2014). Chronic low-grade inflammation, recognised as a consequence of obesity induced IR, and lipotoxicity triggered release of nuclear factor-κB (NF-κB) and pro-inflammatory markers such as tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) are also known to contribute to the pathogenesis of MASLD, liver injury and fibrosis (Rohm et al., 2022; Dong et al., 2024) (Figure 1).
FIGURE 1
Among the extrahepatic consequences of MASLD, cardiovascular diseases (CVDs) are the leading cause of mortality due to pro-atherogenic lipid profile resulting from endothelial dysfunction, dyslipidaemia, increased VLDL secretion, and reduced LDL clearance (Villanova et al., 2005; Lawler et al., 2021; Younossi et al., 2023). Malignancies like pancreatic, colorectal, stomach, lung, breast, ovarian and prostate cancers represent the second most common death (Mantovani et al., 2022b; Azimi et al., 2025; Issa et al., 2025; Kogiso et al., 2025). MASLD also predicts the onset and progression of chronic kidney disease (CKD); shows a bidirectional relationship with muscle protein metabolism causing sarcopenia; and intrinsically connected with endocrine disorders like polycystic ovary syndrome (PCOS) and hypothyroidism (Bhanji et al., 2017; Mantovani et al., 2022a; Hong et al., 2023; Hutchison et al., 2023; Bilson et al., 2024; Li et al., 2024; Xu et al., 2024). These diverse diseases reflect the multidirectional systemic crosstalk in MASLD involving a shared metabolic milieu of obesity, hypertension, insulin resistance and mitochondrial dysfunction and proinflammatory cytokines, primarily driven by impaired glucose and lipid metabolism (Sandireddy et al., 2024).
2 Diagnosis and treatment of MASLD: challenges and the imperative for a paradigm shift
The complex pathophysiology, asymptomatic early stages, lack of consensus on standard diagnostic protocols, absence of universally accepted pharmacological interventions, and strong association with multiple comorbidities make early diagnosis and effective management of MASLD a great challenge (Ma et al., 2025; Adinolfi et al., 2026). Although non-invasive and invasive diagnostic options like biomarkers, imaging techniques and liver biopsy exist, their limited accessibility, affordability and patient compliance restrict widespread use (Garg et al., 2025; Nowak et al., 2025). MASLD diagnosis is often incidental during routine health check-ups as most of the early-stage symptoms like mild fatigue, bloating and abdominal discomfort are non-specific and often overlooked. Sometimes even the advanced stages like fibrosis, cirrhosis and cancer remain with non-specific symptoms or asymptomatic making MASLD underdiagnosed until serious outcomes (cirrhosis or HCC) occur (Sharma and Arora, 2020; Mishra et al., 2022).
Management approaches for MASLD can be broadly categorized into preventive, therapeutic and surgical interventions. Although lifestyle and dietary modifications remain as the cornerstone of MASLD prevention, poor patient adherence often limits long-term benefits (Arora et al., 2021; Wang et al., 2023). For instance, while the Mediterranean diet is beneficial for MASLD management, its global adoption is limited due to cultural, geographic, seasonal, and socioeconomic differences (Tsofliou et al., 2022; Cueto-Galán et al., 2025). Similarly, aerobic exercise and resistance training for weight loss is limited by resources, supervision, and difficulty in sustaining significant weight loss (Willis et al., 2012; Mahmood et al., 2023).
The major challenge in therapeutics is the absence of FDA-approved drugs for MASLD or cirrhosis (Mallet et al., 2024; Drygalski and Drygalski, 2025). Resmetirom (a thyroid hormone receptor beta (THR-β) agonist), the first FDA-approved drug for MASH and Saroglitazor (a dual PPARα/γ agonist), approved in India for T2D and MASH treatment are promising drug options, but needs more data on sustained histological benefits and long-term safety (Chhabra et al., 2022; Chaudhuri et al., 2023; Harrison et al., 2024; Mir et al., 2024).
Other pharmacological targets like incretin hormone agonists (Semaglutide and Trizeptide), SGLT2 inhibitors, FGF-21 analogue, PPAR agonists, antioxidants, and anti-inflammatory agents are actively investigated for MASLD management, but none have demonstrated clinically significant improvement in liver outcomes across diverse patient populations (Musso et al., 2017; Francque et al., 2021; Loomba et al., 2023, 2024; Sanyal et al., 2025). Surgical approaches including Roux-en-Y gastric bypass and liver transplantation, forms the third strategy. Though bariatric surgery and endoscopic bariatric therapies are beneficial to some extent, patients with end stage cirrhosis are generally left with liver transplantation as the only solution and it is expensive and associated with higher rates of complications, malnutrition, sarcopenia, morbidity and mortality. They often require multi-speciality care including hepatologists, endocrinologists, cardiologists, and dietitians (Fakhry et al., 2019; Lassailly et al., 2020; Aminian et al., 2021). The perpetually growing prevalence and strong association with co-morbid conditions makes a one-size-fits-all approach irrelevant for MASLD diagnosis and management.
Are current clinical frameworks for MASLD overlooking something essential? Probably ‘YES’. Philosophically the epistemology and ontology of modern biomedicine is grounded in molecular reductionism emphasizing a lock-and-key model of disease mechanisms and drug discovery. While this approach has been highly effective in treating infectious diseases, its limitations in managing complex lifestyle disorders like MASLD are increasingly evident. Its non-linear dynamics, multisystem pathophysiology and the role of systemic metabolic dysfunction in the pathogenesis demands integration of molecular and systemic perspectives for early diagnosis, prevention, and therapy. Resonating with the global interest in complementary and alternative medicine (CAM), the MASLD management landscape calls for an integrative framework that incorporates holistic principles of disease biology from complementary systems (World health organization, 2023). Indian Systems of Medicine (ISMs) like Ayurveda and Traditional Chinese Medicine (TCM) are driving transformative progress in this direction. Of the two, Ayurveda stands out as the oldest codified medical system deeply rooted in the Indian philosophical axioms of logic, epistemology and metaphysics.
3 The liver and MASLD in Ayurveda - distinctive understanding of its biology and pathophysiology
Ayurveda, a holistic system of medicine originating from the Indian subcontinent, offers a distinct epistemology and ontology for understanding the biological mechanisms underlying human health and disease. This unique worldview, however, presents challenges when attempting to integrate it with contemporary scientific discourse. The following section provides a brief overview of how Ayurveda understands the liver, its biological functions and the disease biology. A glossary is provided separately for readers to understand the unique Sanskrit terminologies used in Ayurveda.
In Ayurveda, the liver is referred to by the term Yakrit, a Sanskrit word meaning “to govern” (Apte, 1890). The description of Yakrit highlights its principal and crucial role in modulating “Agni” - the metabolic fire responsible for digestion, metabolism, and nutrient transformation (Sastry, 1997e). In Ayurveda parlance, after digestion, the food (Ahara) is transformed into an absorbable form referred to as “Ahara Rasa” which then transforms into “Rasa Dhatu,” the basic element of nourishment that circulates throughout the body (Sastry, 1997b; Murthy, 2001a). Upon reaching Yakrit (liver), Rasa Dhatu transforms into “Rakta Dhatu” (whole blood), producing “Pitta” (∼ bile juice) as a byproduct that get secreted into the gastro-intestinal tract (GIT) to support digestion, metabolism and nutrient transformation (Acharya, 1992a; Sastry, 1997f; Sastry, 1997d; Sastry, 1997a; Murthy, 2001b; Murthy, 2001c).
Although Ayurvedic narrative of liver biology does not map directly to the contemporary biological understanding of hepatology and the disease construct of MASLD, as a science that studies biological changes, Ayurveda offers a structured explanation of disease pathophysiology through a unique “six-stage disease progression model” referred to as Shad-Kriyakala (Chaple et al., 2016; Chauhan et al., 2017; Bishnoi et al., 2024). This framework centres around a few core concepts of Ayurveda, central to the biology of health and disease: Ama, Agni, Kapha and Pitta. Ama represents the accumulated ‘metabolic waste’ in the body arising from improper and incomplete nutrient metabolism. Agni refers to the digestive and metabolic functions responsible for preventing Ama accumulation (Sastry, 1997c; Naaz et al., 2025). Kapha and Pitta constitute two of the three fundamental biological forces (Dosha) that govern the physiological and biochemical homeostasis. Drawing from this model in Ayurveda, this article proposes an Ayurveda-Biology hypothesis of MASLD progression, with plausible correlation of Ayurvedic concepts of disease progression with molecular events (Figure 1). However, this correlation requires more detailed research for deeper scientific validation. Ayurveda posits that the MASLD progression begins when inappropriate diet and lifestyle - particularly those increasing Kapha and Pitta - impair Agni functions and lead to Ama accumulation (Sanchaya stage). Excess consumption of sweet, sour, savour, oily and heavy to digest foods are typically known to impair Dosha (Kaptha and Pitta) and Agni functions at GIT. The vitiated Dosha and accumulated Ama disrupts the dynamic equilibrium of physiological and biochemical functions in different parts of the body (Prakopa stage) (Asija and Singh, 2016; Saini and Lata, 2025). Eventually the absorbable form of food (Ahara Rasa) and nourishment (Rasa Dhatu) get vitiated, but circulate in the body and reach Yakrit, the liver (Prasara stage) (Acharya, 1992b; Murthy, 2001d). A simple analogy can illustrate this phenomenon: If the body is viewed as a house, each organ is a room with a defined function. When the accumulated waste in one room remains undisposed, it decomposes and eventually affects the entire house. At the liver, the pathophysiology is localized (Sthana Samshraya stage) causing liver steatosis, which in turn manifests with various clinical symptoms (Vyakti stage) and ends-up with complications (Bheda stage).
The key insight from this perspective is the foundational role of the gut in systemic health. An earlier work from Thottapillil and colleagues highlighted gut as a convergence point for an integrative Ayurveda-Biology framework of diabetes management; which holds true for MASLD as well (Thottapillil et al., 2021). Dietary quality and quantity, eating behaviour, seasonal and circadian rhythms, physical activity, and mental stress are key determinants of gut functions that influence nutrient transformation and metabolic balance. From an Ayurvedic perspective, impaired digestive–metabolic capacity (Agni-mandya) and accumulation of Ama create an internal milieu that can be conceptually aligned to inflammation and gut-microbiome dysbiosis resulting in compromised intestinal barrier function and ‘leaky-gut’ effect (Mishra et al., 2025; Shruti et al., 2025). This permits microbes, their products and other toxins to reach the liver, eventually triggering inflammation and oxidative stress culminating in MASLD and cirrhosis (Ray, 2015; Portincasa et al., 2021). Therefore, the emphasis Ayurveda gives for proper regulation of gut functions (Agni) to reduce Ama provides avenues for early-stage management of MASLD through diet, lifestyle modifications and therapeutic interventions (Feng et al., 2017; Fujisaka et al., 2024; Sharma, 2024).
The distinctive conceptualization of liver biology in Ayurveda and other traditional medical systems of South and South-East Asia provides a unique logic for systems-based therapeutics to restore the body’s metabolic homeostasis. These traditions extensively use medicinal plants by leveraging their phytochemical diversity, to create a rational blend of pharmacological properties that modulate interconnected metabolic pathways; thereby promoting adaptive and dynamic metabolic homeostasis. In Ayurveda, this pharmaceutical logic is systematically articulated through the concepts of Rasapanchaka of Dravyaguṇa (Joshi et al., 2007; Rath et al., 2014; Thakur et al., 2022). While this approach contrasts with reductionist pharmacology, it is increasingly supported by systems biology and network pharmacology; and is essential for managing diseases like MASLD that are arising from systemic dysregulation involving inter-organ communication (Chandran et al., 2017; Thottappillil et al., 2024). Supplementary Table 1 provides a curated list of medicinal plants illustrating how Ayurveda-informed phenotypic determinants translate into the selection of pharmacologically coherent, multi-target interventions relevant to MASLD.
4 Transdisciplinary framework for MASLD management: what is the way forward?
The interconnected tapestry of etio-pathophysiology of MASLD, governed by biological, lifestyle, environmental and sociocultural factors, demands an approach that transcends any single therapeutic framework. The very foundation of trans-disciplinarity is rooted in the principles of complexity science and chaos theory - disciplines that reveal an interconnected yet non-linear nature of reality. Human health and disease exemplify non-linear dynamic systems that require the integration of multiple, and often epistemologically distinct, knowledge systems (Jayasinghe, 2012; Biswas et al., 2018). The limitations of traditional lock-and-key framework in addressing the interconnectedness of complex etiopathological determinants highlight the need for systems approach and precision medicine models (Priego-Parra et al., 2025). Within this context, Ayurveda, as a whole-system medical tradition grounded in principles aligned with P4 medicine, offers a space for developing novel integrative strategies for MASLD management. Creating a transdisciplinary framework that bridges Ayurveda and conventional biomedicine opens new avenues for early detection, prevention, and personalized interventions to restore and maintain the dynamic metabolic homeostasis (Figure 2). The primary goal of this framework should be to prevent disease onset and progression of MASLD while improving the individual and population level quality of life through personalized, culturally-sensitive, and evidence-based strategies.
FIGURE 2
4.1 Dual-diagnostic workflow: integrating phenotyping and molecular pathology
Effective MASLD management requires early detection and personalization. However, no single diagnostic system adequately captures both metabolic vulnerability and structural pathology of the liver. To overcome this, a transdisciplinary dual-diagnostic framework, integrating Ayurveda-based phenotyping with established biomarkers would guide an integrative decision-making interface across the disease continuum (Figure 2). In this model, the readouts like molecular markers, fibrosis indices and imaging results provide objective quantification of hepatic pathophysiology and disease staging. Whereas Ayurveda-based diagnosis like roga–rogi pareeksha (disease and patient assessment) and other physiological assessments (prakriti, vikriti, agni, ama, and srotodushti) provides a systems-level abstraction of metabolic dysregulations arising from lifestyle and psychosomatic imbalance; which may precede overt biochemical or radiological readouts. These Ayurveda-based phenotyping can be leveraged to individualize lifestyle, dietary, circadian, and mind–body interventions for early stage management of MASLD.
4.2 Operationalizing transdisciplinary disease management algorithm
Diagnostic discordance between epistemologically distinct medical systems is anticipated and must be systematically addressed at the translational decision-making layer. Figure 2 proposes a four-level transdisciplinary management algorithm based on an integrative decision making framework. For example, individuals who have normal biomedical readouts but disturbed metabolic homeostasis on Ayurveda assessment are prioritized for preventive, low-risk lifestyle and dietary interventions (Level - 1), following integrative nutrition strategies combining principles of modern and Ayurveda dietetics. Ayurveda dietetics incorporates circadian and circannual rhythms, along with regional, cultural, and ecological determinants of food intake (Banerjee et al., 2015). When integrated with principles of food chemistry, nutrient bioavailability, and metabolic biochemistry it enables a novel framework that supports individualized dietary prescriptions tailored to ethnicity, nativity, and socioeconomic context. Beyond nutrition, the regulation of metabolic homeostasis in MASLD is increasingly recognized as a systems-level phenomenon governed by the psycho–neuro–endocrine–immunological (PNEI) network and the body–mind axis. Ayurvedic lifestyle practices such as Yoga, meditation, and structured physical activity are positioned as biologically relevant modulators of PNEI dynamics, with the potential to mitigate disease progression and enhance long-term metabolic resilience (González-Díaz et al., 2017).
As the disease progresses, the absence of liver-specific pharmacotherapies remains a major clinical challenge. In a transdisciplinary framework, the Ayurvedic assessment of the metabolic status of the disease through systematic evaluation of vitiated Doshas, affected Dhatus and Agni function can inform about the status of metabolic resilience, detoxification capacity, and tolerance to therapeutic load, which are particularly critical in the context of compromised hepatic drug metabolism (Kaur et al., 2024; Jayasuriya et al., 2025). In parallel, biomedical indicators including liver enzyme trends, quantitative steatosis, and glycaemic control provide objective measures of disease severity and physiological constraint. Together these insights are operationalized at the translational decision-making layer to modify therapeutic strategies that include evidence-based, well-tolerated Shodhana and Shamana modalities with minimal herb–drug interaction potential (Supplementary Table 1). At the advanced stages of MASLD with progressive inflammation, fibrosis, aggravated Dosha (Pitta) and Dhatukshaya, the treatment protocol shifts to guideline-based pharmacotherapy like Resmeritrom and careful non-interacting Shamana and Shodhana interventions; along with personalized nutrition and lifestyle support.
In the terminal-stage of disease, including decompensated cirrhosis and reduced quality of life, bariatric surgery and liver transplantation remain the cornerstone of management. However, integrative peri-operative care guided by biomedical surgical risk stratification and Ayurvedic functional assessment can support recovery through targeted nutritional optimization, functional conditioning, and stress modulation. These interventions are explicitly positioned as supportive and rehabilitative, not disease-modifying, and are aligned with standard-of-care clinical pathways (Figure 2).
Both biomedical and Ayurvedic systems converge on diet and lifestyle modification as foundational strategies for metabolic health. The transdisciplinary framework proposes the integration of Ayurveda’s seasonal and regional dietary guidance, informed by prakriti based body–mind phenotyping and agni assessment, as upstream strategies for personalized caloric moderation and whole-food dietary patterns. When systematically integrated into the public health nutrition policies, these principles can be combined with scalable interventions such as structured physical activity and mind–body practices such as yoga, enabling the operationalization of individualized metabolic health concepts into population-level preventive and promotive health strategies.
4.3 Challenges in operationalizing a transdisciplinary framework
Operationalizing a transdisciplinary framework necessitates the collaboration of teams proficient in both biomedical and traditional systems of medicine with a shared decision making algorithm supported by rigorous phytochemical standardization, GMP compliance for herbal products, robust pharmacovigilance frameworks to monitor potential drug–herb interactions, and the development of research infrastructure for personalization-focused Ayurveda clinical trials, multi-omics profiling, and computational biology. These measures are essential to transform integrative medicine from a co-practice model to a transdisciplinary paradigm for MASLD management ensuring safety, reproducibility, and clinical credibility.
4.3.1 Quality control of drugs and pharmacovigilance
A central prerequisite for the successful clinical translation of any integrative or transdisciplinary framework involving herbal interventions is rigorous material characterization and standardization. The reproducibility crisis in herbal and traditional medicine research arises primarily from inadequate quality control and batch-to-batch variability of study materials; and therefore adherence to pharmacognostic and phytochemical standards is mandatory (Tandon, 2018; Tandon and Sharma, 2019). Comprehensive phytochemical profiling using state-of-the-art chromatographic fingerprinting methods and marker based standardizations following international standards like Consensus on Phytochemical Markers (ConPhyMP), to ensure botanical identity, chemical consistency, and traceability are advisable (Heinrich et al., 2022). While these are considered as a minimum requirement, the real need of the hour is to develop novel multi-marker or chemometrics approaches to capture the complexity of polyherbal preparations. Additionally, the Good Manufacturing Practice (GMP) compliance and robust pharmacovigilance mechanism to monitor potential herb–drug interactions are indispensable to ensure patient safety (Wal et al., 2011; Shaw et al., 2012). Perhaps pharmacovigilance is the most important aspect wherein hepatic drug-metabolizing capacity is drastically impaired in MASLD causing herb–drug interactions (HDIs) as a major clinical risk, potentially leading to herb-induced liver injury (HILI) (Volak et al., 2008; Al-Jenoobi et al., 2014; Ma et al., 2023; Somabattini et al., 2024). The proposed framework explicitly rejects the lay-man notion that “natural products are safe” and strongly argues for embedding phytochemical standardization and quality control as non-negotiable methodological requirements; enabling the framework to move beyond ‘philosophical hypothesis’ to a ‘pharmacologically and clinically accountable model’.
4.3.2 Regulatory harmonization and ethical considerations
The clinical implementation of a transdisciplinary framework integrating Ayurvedic and biomedical interventions requires careful navigation of substantial regulatory and ethical complexities (Dubale et al., 2025). Across jurisdictions, traditional medicines and conventional pharmaceuticals are governed under distinct legal frameworks, creating asymmetries in approval pathways, quality oversight, and liability attribution (Chaudhary and Singh, 2011; Thamizhoviya, 2025; Tillu, 2025). For example, in India, Ayurvedic formulations are regulated under the Ministry of AYUSH, whereas biomedical drugs fall under the purview of the Central Drugs Standard Control Organization (CDSCO). In contrast, in many Western countries, Ayurvedic products are frequently marketed as dietary supplements with variable regulatory oversight. Such divergence raises critical questions regarding clinical responsibility and liability, particularly in the event of adverse outcomes arising from combined use. Here again, the article argues against any unsupervised or ad-hoc integration but emphasizes the need of regulatory harmonization through formally endorsed Integrative Treatment Guidelines. These guidelines should be ideally co-developed by regulatory authorities, professional medical councils, and traditional medicine bodies by clearly defining permissible combinations, safety requirements, documentation standards, and accountability structures for integrative care in MASLD. Furthermore, from an ethics point-of-view, the patients must be clearly informed about the rationale for integrative decision-making, the nature of the interventions, the existing level of evidence, and potential risks including herb–drug interactions; which will make the transdisciplinary framework a more disciplined, accountable, and patient-centred strategy that can evolve as a health policy (Gatt et al., 2024).
5 Conclusion
The global trend of traditional medicine-based disease management, particularly noncommunicable diseases, highlighted in the WHO’s Traditional Medicine Global Summit report (2023) (World Health Organization, 2023) underscores the need of harnessing the holistic understanding of the disease pathophysiology of the TMs with the mainstream treatment protocols. The proposed framework for MASLD management, integrating systemic insights of Ayurveda with molecular precision of biomedicine, offers promising early and preventive interventions, culturally aligned and personalized care, and multi-targeted therapeutics. However, the heterogeneity of herbal products, regulatory divergence across jurisdictions, limited mechanistic understanding of multi-targeted therapeutics, and the need for clinician cross-training remain as challenges. Overcoming them through coordinated education, research, and policy initiatives can open up novel integrative, globally adaptive and patient-centred management strategies for MASLD.
6 Future directions
For advancing the proposed transdisciplinary Ayurveda–Biology framework from a conceptual note to clinical implementation, the following priority areas warrant focused attention.
Standardization and Material Reproducibility: Rigorous phytochemical characterization and batch-to-batch standardization of Ayurvedic interventions using validated analytical platforms to ensure reproducibility, safety, and translational credibility.
Systems-Level Mechanistic Investigations: Development of innovative in vitro, in vivo and in silico model systems, employing transcriptomics, metabolomics, lipidomics, and network pharmacology, to capture the multi-component-multi-target mode of action of traditional formulations.
Robust Translational Decision Algorithms: Development of a carefully curated and scientifically validated translational framework to enable unified clinical decision-making rather than parallel practice.
Adaptive and Pragmatic Clinical Trial Designs: Establishing real-world evidence studies and personalization-focused clinical trials along with higher dimensional statistical analysis for overcoming the limitations of conventional randomized controlled trials.
Safety, Regulatory Guidelines and Capacity Building: Development of curated HDI databases, pharmacovigilance platforms, and unified regulatory guidelines for integrative treatments, endorsed by regulatory bodies. Providing structured training programs that equip clinicians and researchers with cross-disciplinary literacy for successful and sustainable implementation of a transdisciplinary framework.
7 Glossary of key Ayurveda terminologies used in the article
Agni: The simple translation of Agni is ‘fire’. However, in Ayurveda, Agni is a phenomenon that can be understood as a fundamental ‘energy form’ and governing principle of the biotransformation of substances in the body. At a gross level of physiology, Agni encompasses all the functions regulating digestion and absorption of nutrients from ingested food. At cellular and tissue level, Agni denotes the collective molecular pathways involved in biotransformation of nutrients to produce tissues (dhatus), and energy. Agni is also responsible for catabolic activities. There are 13 types of Agni described in Ayurveda.
Agni-mandya: Refers to inappropriate functioning of Agni which eventually affects the digestion, absorption and assimilation of nutrients in the body.
Ahara: Food, drinks and other dietary substances consumed by the living organisms.
Ahara Rasa: The primary nutritive essence, generated after the digestion of food and drinks, that can be absorbed and ideally assimilated into the body. It supports seven tissue systems (dhatus- further explained) of the body.
Ama: It is used to denote the products and process of incomplete or inappropriate biotransformation of the nutrients at gastrointestinal tract and tissue levels. It also includes impaired products such as immunogenic precursors or aberrant metabolic intermediates of cellular biochemical transformation that eventually alter the normal biological functions. Ama formation is happening when the Agni functions are not proper. Ama is eliminated and further, its formation is prevented by modulating Agni through various methods including the medicinal herbs and formulations.
Dhatu (seven types): From Ayurveda epistemology, Dhatu denotes the fundamental building blocks of the body (roughly equivalent to the tissues in modern biology). There are seven Dhatus sequentially named as Rasa (∼ nutrient rich chyme), Rakta (∼blood), Mamsa (∼muscle), Meda (∼ adipose tissue), Asthi (∼ skeletal tissue), Majja (∼ bone marrow) and Sukra (∼ reproductive tissue). Rasa Dhatu is the first derivation from ingested food and each of the subsequent Dhatu derives from the previous one in the sequence. However, each dhatu can be directly derived from Ahara rasa.
Dhatu Agni: Seven Agni are involved in the biotransformation of each Dhatu from its respective precursors. For e.g., The Rasa Dhatu Agni is responsible for conversion of Ahara rasa into Rasa Dhatu.
Dravyaguna: The Ayurvedic discipline that studies medicinal substances and explains their therapeutic actions based on their properties, actions, and interactions with the body.
Prakriti: Describes an individual’s inherent pattern of physical, physiological, and psychological traits, considered as a stable baseline that helps explain why people differ in metabolism, resilience, and health risks. Prakriti is defined as the independent or combined dominance of either Vata, Pitta or Kapha Dosha.
Rasapanchaka: The Ayurvedic framework describing drug action through five determinants referred as rasa (taste), guna (qualities), virya (potency), vipaka (post-digestive effect), and prabhava (specific action).
Srotodushti: Refers to the dysfunctions or disturbances in the body’s internal transport and communication pathways, known as srotas, which are responsible for the movement of nutrients, wastes, fluids, and signals throughout the body.
Vikriti: Denotes the “current state of imbalance” in a person’s body and mind, which reflects how lifestyle, diet, stress, environment, illness, or aging have temporarily disturbed the physiological homeostasis. Vikriti guides personalized corrective measures such as dietary changes, lifestyle adjustments, or treatments to restore health.
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The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
Author contributions
SK: Conceptualization, Visualization, Writing – original draft, Writing – review and editing. SS: Writing – original draft, Writing – review and editing. AB: Writing – original draft, Writing – review and editing. SuK: Conceptualization, Supervision, Visualization, Writing – review and editing. CV: Conceptualization, Supervision, Visualization, Writing – original draft, Writing – review and editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. The authors gratefully acknowledge the Indian Council of Medical Research (ICMR) for awarding the ICMR-SRF fellowship to Sania Kouser (File No. 3/1/2(13)/OBS/2022-NCD-II). The authors acknowledge Rural India Support Trust (RIST) for partial salary support of the senior investigators.
Acknowledgments
The authors also thank the University of Trans-Disciplinary Health Sciences and technology (TDU), Bangalore, for providing the necessary infrastructure and facilities.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2026.1767844/full#supplementary-material
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Summary
Keywords
Ayurveda, MASLD, precision medicine, transdisciplinary, treatment
Citation
Kouser S, Sharma SV, Bhanu A, Kukkupuni SK and Vishnuprasad CN (2026) A transdisciplinary framework for managing metabolic dysfunction associated steatotic liver disease. Front. Pharmacol. 17:1767844. doi: 10.3389/fphar.2026.1767844
Received
15 December 2025
Revised
24 January 2026
Accepted
26 January 2026
Published
24 February 2026
Volume
17 - 2026
Edited by
Safaet Alam, Bangladesh Council of Scientific and Industrial Research (BCSIR), Bangladesh
Reviewed by
Adnan Akif, University of Nevada Reno, United States
Fahmida Tasnim Richi, University of Asia Pacific, Bangladesh
Updates
Copyright
© 2026 Kouser, Sharma, Bhanu, Kukkupuni and Vishnuprasad.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Subrahmanya Kumar Kukkupuni, s.kumar@tdu.edu.in; Chethala N. Vishnuprasad, drcnvp@tdu.edu.in
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