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Review

Effectiveness of Lifestyle-Based Approaches for Adults with Multiple Chemical Sensitivity: A Systematic Review

by
Isidro Miguel Martín Pérez
1,*,
David Alejandro Parra Castillo
2,
Carlos Pastor Ruiz de la Fuente
2 and
Sebastián Eustaquio Martín Pérez
1,2,3,*
1
Escuela de Doctorado y Estudios de Posgrado, Universidad de La Laguna, 38203 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain
2
Faculty of Health Sciences, Universidad Europea de Canarias, 38300 Santa Cruz de Tenerife, Santa Cruz de Tenerife, Spain
3
Faculty of Medicine, Health and Sports, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Madrid, Spain
*
Authors to whom correspondence should be addressed.
Therapeutics 2025, 2(3), 13; https://doi.org/10.3390/therapeutics2030013
Submission received: 7 April 2025 / Revised: 29 June 2025 / Accepted: 14 July 2025 / Published: 22 July 2025
(This article belongs to the Topic New Trends in Physiotherapy Care: Improvements in Functionality, Pain Management, and Quality of Life)
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Abstract

Background: Multiple Chemical Sensitivity (MCS) is a complex, disabling condition marked by non-specific symptoms in response to low-level chemical exposures. It often leads to substantial impairments in quality of life, psychological health, and daily functioning. Although non-pharmacological approaches—such as lifestyle and psychological interventions—are widely used, their clinical effectiveness remains unclear. Objective: We aim to evaluate the effectiveness of lifestyle-based approaches in improving clinical and psychosocial outcomes in adults with Multiple Chemical Sensitivity. Methods: A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420251013537). Literature searches were carried out in MEDLINE (PubMed), CINAHL, Google Scholar, and ResearchGate between March and April 2025. Eligible studies included adults (≥18 years) with a confirmed diagnosis of MCS and reported outcomes such as perceived stress, anxiety, depressive symptoms, or quality of life. Methodological quality and risk of bias were independently assessed using the PEDro scale, NIH Quality Assessment Tool, CEBMa checklist, and Cochrane RoB 2.0. Results: Twelve studies (N = 378) met the inclusion criteria. Cognitive and behavioral therapies demonstrated the most consistent evidence of efficacy, with reductions in symptom severity, maladaptive cognitive patterns, and functional limitations. Mindfulness-based stress reduction showed favorable outcomes, while other mindfulness-based interventions yielded mixed results. Exposure-based therapies contributed to increased chemical tolerance and reduced avoidance behavior. Electromagnetic and biomedical approaches demonstrated preliminary but limited effectiveness. Aromatherapy was well tolerated and perceived as relaxing, though its clinical impact was modest. Conclusions: Cognitive and behavioral therapies appear to be most effective among lifestyle-based interventions for MCS/IEI. However, study heterogeneity limits the generalizability of findings, underscoring the need for more rigorous research.

1. Introduction

Multiple Chemical Sensitivity or Idiopathic Environmental Intolerance (MCS/IEI)—also referred to in the literature as chemical intolerance—is an acquired, chronic condition characterized by the recurrence of non-specific, multisystem symptoms triggered by exposure to environmental chemicals at concentrations not typically considered harmful to the general population [1,2]. Originally described by Cullen in 1987 [3], MCS/IEI has an estimated prevalence ranging from 0.1% to 5%, with a higher incidence among individuals with a history of allergic conditions [4,5]. Notably, between 30% and 50% of patients with MCS/IEI also meet diagnostic criteria for chronic fatigue syndrome or fibromyalgia [6], suggesting overlapping symptomatology and potentially shared pathophysiological pathways [7,8].
The clinical presentation of MCS/IEI is heterogeneous, often involving multiple body systems—respiratory, ocular, gastrointestinal, musculoskeletal, reproductive, and neurological systems [9]. Among the most disabling manifestations are neurological symptoms, including headaches [10], cognitive impairment [11,12], sleep disturbances [3,13], and irritability, which contribute substantially to functional limitations, reduced quality of life, and social withdrawal [14,15]. One of the most commonly reported symptoms is cacosmia, a heightened and often distorted sensitivity to odors (e.g., hyperosmia, dysosmia) that is typically triggered by low-level chemical exposures [16]. These symptoms may appear during or shortly after exposure and persist for several days, even in the absence of the trigger. Although olfactory stimuli are the most frequent inducers [17], some individuals also report worsening symptoms after exposure to auditory inputs [18], specific dietary components [19], or pharmacological agents [1,10].
Traditionally interpreted through cognitive and psychogenic avoidance reactions, MCS/IEI has more recently been explored from biological and immunological perspectives. Emerging evidence points to the involvement of mast cell activation, oxidative stress, chronic low-grade inflammation, and central nervous system (CNS) sensitization as key mechanisms in its pathophysiology [10,20]. In fact, a plausible theoretical model, such as Toxicant-Induced Loss of Tolerance (TILT), has also been proposed to explain how repeated low-level chemical exposures may disrupt adaptive responses, leading to multisystem hypersensitivity [21].
Despite increasing clinical recognition, effective treatments for MCS/IEI remain elusive. In this sense, common approaches such as chemical avoidance [22], nutritional supplementation [23], and alternative therapies are often inconsistent in their outcomes and sometimes lack a solid evidence base. Among the few interventions with more consistent support are Cognitive Behavioral Therapy (CBT), supportive psychotherapy, and olfactory desensitization, all of which may improve symptom management and coping strategies in individuals living with chemical intolerance [24,25].
In parallel, there is growing interest in non-pharmacological, lifestyle-based approaches that are accessible, person-centered, and tailored to individual needs. These include diet modifications [23,26], regular physical activity [27], mindfulness-based stress reduction [28], yoga, and environmental adaptations such as air quality control measures [29,30]. According to preliminary studies, these interventions may offer significant benefits by targeting modifiable factors and enhancing functional capacity, quality of life, and overall well-being [31,32].
Nevertheless, the existing body of evidence remains fragmented, with marked heterogeneity in design, outcomes, and methodological quality [16]. To date, no systematic review has comprehensively evaluated the effectiveness, safety, and applicability of lifestyle-based interventions in individuals with MCS/IEI or chemical intolerance. This highlights a critical gap in the literature and the urgent need for evidence-based guidance. Therefore, the objective of the present systematic review is to examine the efficacy of lifestyle interventions in adults diagnosed with MCS/IEI, with a focus on their impact on symptom severity, functional outcomes, quality of life, and biopsychosocial well-being.

2. Materials and Methods

2.1. Data Sources and Search Strategy

A systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [33]. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420251013537 (https://www.crd.york.ac.uk/PROSPERO/view/CRD420251013537, accessed on 6 April 2025), thereby ensuring methodological rigor, transparency, and compliance with established international standards.
The literature search was performed between 17 March 2025 and 6 April 2025 to identify all relevant studies that evaluated the effectiveness of interventions aimed at alleviating physical and psychological symptoms in individuals diagnosed with MCS. The following electronic databases were systematically searched: MEDLINE (PubMed), PEDro, Scopus, CINAHL Complete, and Web of Science. For MEDLINE (PubMed), the search strategy employed the following terms: “multiple chemical sensitivity” [MeSH] OR “environmental sensitivity” [Tiab] OR “chemical intolerance” [Tiab] OR “environmental illness” [Tiab]. Equivalent queries, adjusted to the specific syntax of each platform, were applied to the remaining databases to ensure comprehensive coverage of the topic.
The initial screening of titles and abstracts was conducted independently by two reviewers (D.A.P.C. and C.P.R.d.l.F.). Full-text articles were subsequently assessed by a blinded third reviewer (S.E.M.P.). Any disagreements were resolved through consultation with a fourth reviewer (I.M.M.P.), who facilitated consensus. The complete search strategy, including keyword combinations and Boolean operators used across all databases, is presented in Table S1.

2.2. Study Selection

The selection of studies was conducted according to predefined eligibility criteria to ensure methodological rigor and relevance. On the one hand, eligible studies met the following conditions: (1) employed randomized or non-randomized controlled designs, case–control, case series, case reports, or ongoing trials; (2) published up to 31 March 2025; (3) written in English or Spanish; and (4) available in full-text format. The target population included (5) adults (≥18 years) with a confirmed diagnosis of MCS/IEI.
Additionally, (6) studies had to assess lifestyle-based interventions—such as dietary profile changes, environmental modifications, physical activity, or mind–body practices—aimed at improving MCS/IEI management. Lastly, (7) at least one outcome related to stress perception, illness perception, anxiety, depression, work capacity, or quality of life had to be reported.
On the other hand, the exclusion criteria comprised the following: (1) studies involving participants under 18 years; (2) absence of confirmed MCS/IEI diagnosis; (3) exclusive focus on pharmacological treatments or non-lifestyle-related diagnostics; (4) unavailability of full-text; (5) languages other than English or Spanish; (6) publication types such as reviews, editorials, commentaries, letters, or abstracts lacking original data; and (7) studies focused on exposure without therapeutic intent or where MCS/IEI was not the primary condition examined.

2.3. Data Extraction

Data extraction was performed independently by two authors (D.A.P.C. and C.P.R.d.l.F.) using a standardized PICO-based template to extract relevant information. The extracted data included study characteristics (authors, year, and country of publication), study design, study objectives, sample characteristics (sample size, demographic data, disease classification, and intervention details), and outcome measures. Additionally, details regarding the intervention and control groups, statistical results, and conclusions were recorded. A pilot test was conducted to ensure the reliability of the data extraction process, following the Cochrane Handbook for Systematic Reviews of Interventions (v.5.1.0). In cases of disagreement, a third author (S.E.M.P.) resolved the discrepancies.

2.4. Methodological Quality Assessment

The methodological quality of the included studies was appraised using standardized, design-specific tools to ensure consistency and rigor. For randomized controlled trials (RCTs), the Physiotherapy Evidence Database (PEDro) scale [34] was employed to assess internal validity and the interpretability of statistical findings. Based on total scores, studies were rated as excellent (9–10), good (6–8), fair (4–5), or poor (<4).
Moreover, case series were evaluated using the NIH Quality Assessment Tool for Case Series Studies [35], which assesses domains such as study objectives, selection criteria, data collection methods, outcome measurement, statistical analysis, and ethical considerations. For case reports, the CEBMa Case Study Evaluation Tool [36] was applied, focusing on the clarity of the clinical question, methodological soundness, data analysis, practical implications, and adherence to ethical standards.

2.5. Risk of Bias Assessment

The risk of bias in randomized clinical trials was assessed using the Cochrane Risk of Bias Tool 2.0 (RoB 2.0) [37], which evaluates five key domains: randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selective reporting. Based on these criteria, studies were categorized as having a low risk of bias, some concerns, or a high risk of bias, depending on the potential impact of methodological flaws on study outcomes. All assessments were conducted independently by two reviewers, with any disagreements resolved through discussion. In cases of persistent discrepancies, a third investigator (S.E.M.P.) provided the final judgment.

3. Results

3.1. Study Selection

A total of 137 records were initially retrieved through systematic searches conducted across five major international databases: MEDLINE (PubMed) (n = 32), PEDro (n = 32), Scopus (n = 28), CINAHL (n = 20), and Web of Science (n = 25). After removing 16 duplicate entries, 121 references remained and were screened for relevance based on titles and abstracts. Of these, 63 records were excluded for not meeting the basic eligibility criteria at the preliminary stage.
The remaining 58 full-text articles were then assessed for eligibility according to the predefined inclusion and exclusion criteria. A total of 45 studies were excluded during this phase for the following reasons: absence of a confirmed MCS/IEI diagnosis (n = 12), non-eligible study design (n = 18), and language not matching the inclusion criteria (n = 15).
Ultimately, 12 studies fulfilled all eligibility criteria and were included in the qualitative synthesis. This study’s selection process is detailed in Figure 1, which presents the PRISMA 2020 flow diagram, summarizing each stage of this review. The figure illustrates the number of records identified, screened, assessed for eligibility, and the reasons for exclusion at each phase.

3.2. Characteristics of the Included Studies

A total of 12 studies were included [38,39,40,41,42,43,44,45,46,47,48,49], encompassing a range of research designs such as RCTs [40,41,42], pilot studies [44,45], case reports [38,43,46,47], a case series [48], a single-case experimental design [39], and an ongoing observational case–control study [49], with a combined sample size of 378 participants [38,39,40,41,42,43,44,45,46,47,48,49]. Most studies focused on individuals diagnosed with MCS/IEI [38,39,40,41,42,43,44,45,46,47,48], with the exception of one observational case–control study conducted on healthy individuals who were age- and gender-matched to IEI patients as part of a matched-control comparison [49].
Psychological and biopsychosocial interventions were predominant, particularly those based on CBT [38,39,40,48,49,50]. These interventions typically incorporated components such as cognitive restructuring, relaxation techniques, psychoeducation, and graded exposure. In this sense, Mindfulness-based interventions (MBIs) were also prominent, including Mindfulness-Based Cognitive Therapy (MBCT) [41,42] and Mindfulness-based Stress Reduction (MBSR) [45]. Furthermore, the duration of these interventions varied widely, ranging from brief programs to structured 8-week interventions, with some lasting up to 11 months in some cases [46].
Additional therapeutic approaches included Pulsed Electromagnetic Field (PEMF) therapy [40], Electroconvulsive Therapy (ECT) [43], and aromatherapy massage [44]. While all were reported as feasible and well-tolerated, clinical outcomes varied across studies. Several interventions also integrated biomedical education and lifestyle modifications within a broader biopsychosocial framework [46].
Follow-up periods extended up to six months in some studies [38,49], allowing for a limited assessment of long-term effects. Geographically, the studies were conducted in Denmark [40,41,42,43], Sweden [39], the United States [38,48], Canada [45,46,47], Japan [44], and France [49], reflecting a diverse and international evidence base. A summary of study characteristics and key findings is presented in Table 1.

3.3. Methodological Quality Assessment

The overall methodological quality of the studies included in this review varied from low to excellent, with an average score of 6.2 out of 10 (SD = 2.39), as assessed using a modified 10-item version of the PEDro scale. Among the five studies evaluated, one study was rated as having excellent methodological quality [40], two were classified as good quality [41,42], one was classified as acceptable [43], and one was classified as having low methodological quality [44].
A recurring methodological limitation across these studies was the lack of blinding procedures. Only one study reported the blinding of participants, therapists, and outcome assessors [40]. In contrast, the remaining studies did not include the blinding of participants [41,42,43,44], therapists [41,42,43,44], or assessors [41,42,43], which may increase the risk of performance and detection bias. This limitation is common in psychological and behavioral intervention trials, where full blinding is often infeasible due to the nature of the interventions. Table 2 presents a detailed overview of the methodological quality assessment based on the 10-item PEDro criteria.

3.3.1. Case Series

The methodological quality of the included case series, assessed using the NIH Case Series Quality Assessment Tool [34], was rated as moderate overall. One study met 7 out of 9 applicable criteria and was therefore rated as having good methodological quality [39]. The second study fulfilled 5 out of 9 criteria, corresponding to an acceptable quality rating [48]. Both studies exhibited certain limitations. Notably, the study rated as acceptable [48] did not report whether participants were recruited consecutively and lacked clearly defined inclusion and exclusion criteria. Furthermore, both studies lacked the blinding of outcome assessors and did not conduct or report statistical analyses to support their findings. Additional information can be found in Table 3.

3.3.2. Case Reports

The methodological quality of the included case reports was assessed using the CEBMa Case Study Evaluation Tool [35], which includes ten criteria focused on transparency, replicability, and clinical relevance. The studies scored between 6 and 9 out of 10, with a mean score of 7.3, indicating moderate to good methodological quality across the four included reports [38,44,46,47].
All case reports provided a clear description of the clinical problem, the intervention implemented, and the observed outcomes [38,44,46,47]. However, consistent limitations were identified in items 5 to 7, particularly regarding the clarity and replicability of the intervention [44,46,47], the completeness of outcome reporting [44,46], and the inclusion of adverse events [44,46,47].
In several cases, the interventions were not described in sufficient detail to ensure replicability [44,46,47], and follow-up periods were either short or not clearly specified [44,46]. Furthermore, none of the reports referenced similar previously published cases, which limits their external validity and generalizability. More details are provided in Table 4.

3.4. Risk of Bias Analysis

The risk of bias across the five included randomized controlled trials was assessed using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool [36], which evaluates five domains: bias arising from the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. As shown in Figure 2, the overall risk of bias was judged to be high in the majority of studies, with only one study rated as having low risk across all domains [40].
A high risk of bias was most frequently observed in the domains of the selection of the reported result and deviations from intended interventions, affecting over half of the trials [42,43,44]. Common issues included the lack of blinding of participants and personnel and selective outcome reporting, particularly in pilot or exploratory studies [42,43,44].
In the domain related to the randomization process, three studies [43,44] were rated as high risk due to inadequate concealment of allocation or insufficient reporting. While most studies showed low concerns regarding missing outcome data and outcome measurement, some concerns remained due to the reliance on self-reported outcomes and the absence of pre-registered protocols.
Given these findings and considering the exploratory nature of several included trials, the internal validity of results should be interpreted with caution. A detailed summary of the individual risk of bias judgments is presented in Figure 2.

3.5. Synthesis of Main Results

3.5.1. Cognitive Behavioral Therapy in Reducing MCS/IEI Symptoms

CBT emerged as the most frequently implemented intervention across the reviewed studies [38,39,40,46,47,48]. Overall, CBT showed consistent efficacy in alleviating symptom severity associated with MCS/IEI. Participants reported significant improvements in somatic complaints, hypersensitivity reactions, and overall symptom burden. Furthermore, several studies documented reductions in catastrophic thinking and symptom-related anxiety, underscoring cognitive restructuring as a key therapeutic mechanism [38,39,48].
Regarding functional outcomes, individuals receiving CBT exhibited increased engagement in daily activities, successful return to work, and decreased avoidance of environmental triggers [46,47]. Notably, in studies with extended intervention durations, these therapeutic gains were sustained at follow-up assessments [38,47]. Graded exposure, a core component in several CBT protocols, played a critical role in facilitating desensitization to chemical stimuli and promoting behavioral re-engagement.

3.5.2. Mindfulness-Based Therapy in Reducing MCS/IEI Symptoms

MBIs were evaluated in three studies employing distinct delivery modalities, including MBCT [41,43] and MBSR [44]. Among the interventions assessed, MBSR yielded the most favorable outcomes, with statistically significant reductions in psychological distress and improvements across several mental health domains, both immediately post-intervention and at follow-up [44].
In contrast, MBCT did not produce statistically significant changes in symptom severity or measures of life impact [41,43]. Nevertheless, participants reported perceived improvements in illness perception and coping abilities, indicating potential cognitive-emotional benefits despite the absence of statistically robust effects.

3.5.3. Exposure-Based Therapies in Reducing MCS/IEI Symptoms

Exposure-based techniques, implemented either as standalone interventions or integrated within broader CBT frameworks, were described in four studies [38,46,47,48]. These interventions were designed to gradually enhance tolerance to chemical stimuli perceived as noxious or threatening. Reported outcomes included a reduction in avoidance behaviors, increased tolerance to common environmental triggers (e.g., perfumes, synthetic materials), and functional improvements in daily living activities [46,47].
The effectiveness of these exposure protocols appeared to be influenced by several factors, including the use of a structured and progressive approach, consistent therapist guidance, and the integration of cognitive strategies targeting maladaptive beliefs and anxiety-related responses.

3.5.4. Electromagnetic and Biomedical Therapies

One randomized clinical trial investigated the efficacy of transcranial PEMF in individuals diagnosed with MCS/IEI [40]. The intervention led to a statistically significant reduction in symptom severity; however, no significant effects were observed in terms of life impact or functional outcomes. Post hoc analyses indicated a decrease in hyperalgesia among participants classified as responders to PEMF.
Additionally, ECT was described in a single case report involving a patient with severe MCS/IEI and no comorbid depressive disorder [44]. The case showed marked improvements in symptom severity and the restoration of social functioning, with therapeutic benefits maintained during a biweekly ECT maintenance phase.

3.5.5. Complementary Interventions in Reducing MCS/IEI Symptoms

A pilot crossover study assessed the effects of aromatherapy using essential oils in individuals with MCS/IEI [42]. The intervention was associated with short-term improvements in mood, as measured by the POMS. However, no significant changes were observed in MCS/IEI symptomatology or anxiety levels. The treatment was well tolerated and subjectively perceived as relaxing by participants, suggesting its potential utility as a supportive, adjunctive intervention rather than a primary therapeutic approach.

4. Discussion

This systematic review critically synthesizes the current evidence on the effectiveness of lifestyle-based interventions for adults with MCS/IEI. The results show promising therapeutic outcomes for CBT interventions [38,39,40,46,47,48], mindfulness-based programs [41,43,44], and exposure-focused therapies [38,46,47,48], despite notable heterogeneity in methodological designs and sample characteristics.
These findings align with emerging integrative models—both neurophysiological and biopsychosocial—that consider MCS/IEI as a functional somatic disorder underpinned by the altered CNS processing of sensory stimuli, emotional dysregulation, and heightened salience attribution [40,41,46]. At the same time, the growing biomedical literature highlights the involvement of peripheral mechanisms that may contribute to symptoms’ arousal and chronicity, including mast cell activation, neurogenic inflammation, and oxidative stress.
In fact, an increase in mast cell proliferation and degranulation has been associated with increased histamine release, vascular permeability, and neuroimmune sensitization [20,21]. Likewise, in MCS/IEI adults, neurogenic inflammation—mediated by substances such as substance P and calcitonin gene-related peptides (CGRPs)—has been implicated in the amplification of nociceptive and irritant responses to low-dose chemical exposures [10,13]. See details of the pathophysiology of MCS/IEI in Figure 3.
Among all interventions reviewed, CBT remains the most extensively studied and consistently effective modality in mediating fear-related mechanisms. Across multiple trials, CBT significantly reduced somatic symptoms, maladaptive cognitive patterns, and avoidance behaviors while improving psychosocial functioning and daily life participation [38,39,40,46,47,48]. These positive effects support the hypothesis that CBT exerts top–down neuromodulatory control over central circuits, particularly the limbic and paralimbic regions involved in threat detection, interoceptive awareness, and emotional regulation [50,51,52,53,54].
Against this background, CBT may be understood not only as a psychotherapeutic strategy but also as a targeted neuromodulatory intervention. By enhancing prefrontal control and restructuring maladaptive beliefs [55,56], facilitating graduated exposure to feared stimuli [57], and encouraging behavioral activation [58], it has been effective for supporting the reestablishment of cognitive–emotional equilibrium in those suffering from MCS/IEI. These mechanisms may reduce central sensitization, disrupt hypervigilant perceptual loops, and restore more adaptive predictive processing—key elements in the predictive coding models of functional somatic syndromes [59,60,61]. In these frameworks, maladaptive priors override ambiguous sensory inputs, generating persistent symptoms even in the absence of pathophysiological findings [49,55].
Moreover, MBIs, including MBSR and MBCT, also showed benefits—particularly in reducing psychological distress [41,42,45] and improving illness perception and perceived control [62]. These effects may be partially explained by the capacity of mindfulness practices to enhance parasympathetic tone, modulate the HPA axis, and increase functional connectivity in prefrontal and ACC regions [63,64]. However, MBIs showed more modest or inconsistent effects on core MCS/IEI symptoms, suggesting their optimal use may be as adjunctive tools for emotional resilience and stress management rather than standalone interventions for symptom resolution [3,28].
Furthermore, exposure-based therapies, whether applied independently or within CBT protocols, were associated with notable reductions in environmental avoidance and improved chemical tolerance [38,39,45,46,47,48]. These positive results are consistent with established mechanisms of fear extinction and limbic desensitization, wherein repeated, non-threatening exposure to conditioned stimuli leads to the downregulation of threat-related neural responses [16,65]. As a result, these therapies may facilitate the normalization of cognitive threat appraisal and mitigate the intensity of central sensitization circuits [66,67,68,69,70].
In addition to psychological interventions, emerging evidence also supports the potential of neuromodulatory and biomedical therapies. Interventions such as transcranial PEMF therapy [40,71] and ECT [44] have shown preliminary efficacy in reducing symptom severity, particularly in refractory cases. Specifically, PEMF has been hypothesized to alter cortical excitability, attenuate neuroinflammatory responses, and modulate autonomic tone, while ECT may exert widespread effects on neurotransmitter systems and large-scale neural networks [72,73].
Environmental management remains a cornerstone in the treatment of MCS/IEI. Personalized adaptations—such as improving indoor air quality and reducing exposure to contextual environmental factors (e.g., exposure to volatile organic compound [VOCs], atmospheric pollen transport, desert dust intrusions, similar aero-contaminants, etc.)—provide essential foundational support to cope with disruptions and maladaptive multisystem hypersensitivity [29,30,74,75].
Likewise, complementary interventions, including aromatherapy, may yield modest benefits in enhancing mood and emotional well-being [42]. However, when applied in isolation, these measures may inadvertently reinforce hypervigilance toward environmental stimuli, limiting their long-term effectiveness. This highlights the need for integrative, multimodal approaches that also address the cognitive, emotional, and behavioral dimensions of the condition.

4.1. Clinical Implications and Future Research Directions

The present findings highlight the importance of adopting a biopsychosocial framework in the clinical management of MCS/IEI. Symptom persistence is often shaped by central sensitization, maladaptive beliefs, and behavioral avoidance rather than by toxic exposure alone. Maintaining a purely environmental or somatic interpretation may inadvertently reinforce disability and hinder functional recovery.
Furthermore, psychological interventions should be considered core components of treatment. CBT has demonstrated efficacy in reducing catastrophic thinking, emotional reactivity, and avoidance behaviors. Likewise, mindfulness-based approaches can enhance interoceptive awareness, emotional regulation, and stress tolerance, offering a plausible tool in clinical settings. A summary of recommended lifestyle and therapeutic interventions for MCS is presented in Figure 4.
In addition to psychological support, gradual exposure and functional reactivation plans are essential to restore autonomy and reduce chronic avoidance patterns. Environmental control strategies—such as VOCs monitoring and indoor air quality improvements—may provide supportive benefits, but they should be applied judiciously to prevent reinforcing hypervigilance or dependency.
Furthermore, in more complex or refractory cases, clinicians should consider potential biological contributors, including mast cell activation, oxidative stress, and autonomic dysfunction. These mechanisms may justify multidisciplinary interventions combining psychotherapy, Heart Rate Variability (HRV) biofeedback, sleep hygiene, and anti-inflammatory dietary strategies.
Lastly, future research should move toward high-quality randomized controlled trials with standardized outcome measures and long-term follow-up. The identification of biomarkers and neurophysiological correlates remains a critical step to enable personalized, mechanism-based approaches in the care of individuals with MCS/IEI.

4.2. Limitations

This review has several limitations that must be considered. The limited number of high-quality randomized controlled trials weakens the strength of the evidence, as many studies were pilot trials or non-randomized, often lacking control groups. This increases the risk of bias and may overestimate treatment effects.
Inadequate blinding, especially in psychological interventions, raises concerns due to expectancy effects on subjective outcomes. Additionally, high heterogeneity in interventions, outcome measures, and follow-up periods limits comparability and precludes meta-analysis. Finally, the scarcity of studies evaluating neuromodulatory therapies in MCS/IEI restricts conclusions about their efficacy.

5. Conclusions

CBT appears to be the most effective intervention for MCS/IEI, with consistent benefits observed in symptom reduction and functional improvement. Mindfulness- and exposure-based therapies may offer additional support, particularly for emotional regulation and desensitization. Despite these promising findings, the limited quality and heterogeneity of existing studies call for more rigorous, standardized research to guide clinical practice.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/therapeutics2030013/s1, Table S1: Search strategy.

Author Contributions

Conceptualization, S.E.M.P. and I.M.M.P.; methodology, S.E.M.P. and I.M.M.P.; software, S.E.M.P. and I.M.M.P.; validation, S.E.M.P. and I.M.M.P.; formal analysis, S.E.M.P. and I.M.M.P.; investigation, S.E.M.P., D.A.P.C., C.P.R.d.l.F. and I.M.M.P.; resources, S.E.M.P. and I.M.M.P.; data curation, S.E.M.P. and I.M.M.P.; writing—original draft preparation, D.A.P.C. and C.P.R.d.l.F.; writing—review and editing, S.E.M.P. and I.M.M.P.; visualization, S.E.M.P. and I.M.M.P.; supervision, S.E.M.P. and I.M.M.P.; project administration, S.E.M.P. and I.M.M.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data supporting the reported results can be found in the manuscript.

Conflicts of Interest

The authors declare no conflicts of interest. The funders had no role in the design of this study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Figure 1. PRISMA 2020 flow diagram.
Figure 1. PRISMA 2020 flow diagram.
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Figure 2. Risk of bias assessment for the included studies. The bar chart illustrates the overall distribution of risk of bias across all included studies, categorized by each domain of the Cochrane Risk of Bias 2.0 tool. Colors indicate the proportion of studies rated as low risk (green), some concerns (yellow), or high risk (red) within each domain and for the overall bias judgment. Note. References shown in the figure include: Tran et al. (2016) [40], Haugue et al. (2015) [41], Araki et al. (2012) [42], Skovbjerg et al. (2012) [43], and Sampalli et al. (2009) [45].
Figure 2. Risk of bias assessment for the included studies. The bar chart illustrates the overall distribution of risk of bias across all included studies, categorized by each domain of the Cochrane Risk of Bias 2.0 tool. Colors indicate the proportion of studies rated as low risk (green), some concerns (yellow), or high risk (red) within each domain and for the overall bias judgment. Note. References shown in the figure include: Tran et al. (2016) [40], Haugue et al. (2015) [41], Araki et al. (2012) [42], Skovbjerg et al. (2012) [43], and Sampalli et al. (2009) [45].
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Figure 3. Pathophysiological model of MCS/IEI integrating central and peripheral mechanisms.
Figure 3. Pathophysiological model of MCS/IEI integrating central and peripheral mechanisms.
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Figure 4. Summary of lifestyle interventions for MCS/IEI, highlighting therapeutic categories, mechanisms of action, and clinical effects. Cognitive-behavioral and exposure-based therapies show the strongest evidence, while complementary and biomedical strategies offer limited but supportive benefits.
Figure 4. Summary of lifestyle interventions for MCS/IEI, highlighting therapeutic categories, mechanisms of action, and clinical effects. Cognitive-behavioral and exposure-based therapies show the strongest evidence, while complementary and biomedical strategies offer limited but supportive benefits.
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Table 1. Characteristics of included studies.
Table 1. Characteristics of included studies.
Author, Year and CountryStudy DesignParticipantsInterventionComparisonResultsConclusion
Woolfolk et al.,
2018 [38]
United States		Case–
report		N = 1 woman, age 58, with MCS confirmed by clinical history 8-session individual CBET: includes relaxation, cognitive restructuring, and exposure techniques.None↓ Somatic symptoms (PHQ)
↓ Function maintained at 6-month follow-up		CBET may improve symptoms and function; trials needed.
Amin & Forslund (2018) [39]
Sweden		SCED replicated AB designN = 5 women, ages 32–61 meeting Cullen’s criteria (1987) CBT based on Van den Bergh model: 6–8 sessions over 9 weeks; integrates psychoeducation, exposure, and acceptance strategies.No control group↓ Chemical sensitivity (3/5)
↓ Symptom
distress
↓Catastrophizing		CBT may reduce symptoms; explore individual differences.
Tran et al.
(2016) [40]
Denmark		RCT, double-blind, placebo-controlledN = 39 adults with MCS (20 PEMF, 19 placebo), classified using Cullen’s criteria (1987) PEMFs: applied twice daily for 30 min over 6 weeks.Sham PEMF device↓ Symptom severity (QEESI-SSS)
↔ Life impact (QEESI-LIS)
↓ Depression (SCL-92)
↓ Hyperalgesia 		PEMF may reduce symptoms; long-term effects unclear.
Hauge et al.
(2015) [41]
Denmark		RCT, 1-year follow-upN = 69 adults with MCS (MBCT n = 37, TAU n = 32) confirmed by SCAN psychiatric interview and QEESI scoresMBCT: 8-week program plus 3 booster sessions; focused on awareness and acceptance.TAU↔ Life impact (QEESI).
↓ Illness perception
↑ personal control.		MBCT safe but ineffective on symptoms; further research needed.
Araki et al.
(2012) [42]
Japan		Non-blinded crossover pilot trialN = 16 patients with Idiopathic IEI confirmed by symptom diaries and structured interviewsAromatherapy massage: Four 1 h sessions every 2 weeks using Melissa, Rosemary, and Juniper essential oils.Aromatherapy only after 2-month follow-up↔ IEI symptoms/anxiety (SAI)
↑ Mood (POMS, p < 0.05)		Aromatherapy improved mood; not core symptoms.
Skovbjerg et al. (2012) [43]
Denmark		Randomized pilot clinical trialN = 37 adults with MCS (17 MBCT, 20 TAU) confirmed by SCAN psychiatric interview and QEESI scoresGroup MBCT: 8-week intervention with 2.5 h weekly sessions and structured home practice; led by trained therapists.TAU↔ Depression/anxiety (SCL-92)
↑ Coping and sleep (verbal report)		MBCT feasible; no significant effects; larger trials needed.
Elberling et al. (2010) [44]
Denmark		Case–reportN = 1 man, 45 y/o, with disabling MCS, no depression classified using Cullen’s criteria (1987) ECT: 8 sessions (3 bilateral, 5 unilateral) plus biweekly maintenance ECT.None↓ Symptoms (95→30/100)
↑ Social function
↑ Mild relapse managed
Ø Side effects		ECT may help severe MCS; controlled trials needed.
Sampalli et al. (2009) [45]
Canada		Controlled non-randomized trialN = 50 (intervention) + 26 (WL control), all women with MCS, CFS, or FM confirmed by structured interviewsMBSR: 10-week group program (2.5 h/week) plus daily home practice; based on Kabat-Zinn’s method.WL control group↓ Psychological distress (SCL-90R, GSI)
↑ 5/9 scales post
↑ 8/9 at 3-month follow-up		MBSR improved mental health; promising adjunct therapy.
Busse et al.
(2008) [46]
Canada		Case– report (with narrative review)N = 1 woman, 35 y/o, MCS + functional syndromes meeting Cullen’s criteria (1987)Biopsychosocial rehabilitation program: 11 months of CBT, graded exposure, physical activation, and social reintegration.None↑ Function and symptom control
↓ Avoidance
↑ Attribution shift		CBT + exposure may aid recovery in MCS.
Stenn et al.
(1998) [47]
Canada		Case– reportN = 1 woman, 43 y/o, with MCS and panic symptoms confirmed by clinical history CBT + SSRI (paroxetine): 10-week psychological desensitization (imaginal and in vivo) plus 20 mg/day paroxetine.No intervention↓ Allergy-like attacks
↑ Tolerance to triggers (6-months)		CBT + SSRI reduced symptoms; supports panic model.
Guglielmi et al. (1994) [48]
United States		Case series (N = 3) + theoretical modelN = 3 adults (2 female, 1 male) with disabling MCS included by behavioral assessment and symptom history5-day intensive CBT protocol: includes biofeedback-assisted relaxation, chemical exposure, and cognitive restructuring.None↑ Tolerance
↓ Avoidance; ⅓ maintained at 6 months; others relapsed		Behavioral therapy reduced symptoms; supports phobia model.
Ongoing studies
Lemogne et al., (2025–2028)
NCT05973214 [49]
France		Case–
control		N = 64 (healthy controls age- and gender-matched to IEI patients from BELIEFS study) confirmed by structured psychiatric interview and cognitive/behavioral testingCognitive and behavioral bias assessment: Single-session study using tasks (e.g., Belief Updating, Affective Picture Paradigm).Compared to IEI patients (BELIEFS study)Results pendingWill assess cognitive/nocebo biases in IEI vs. controls.
Abbreviations: CBET (Cognitive Behavioral Exposure Therapy), CBT (Cognitive Behavioral Therapy), CFS (Chronic Fatigue Syndrome), ECT (Electroconvulsive Therapy), FM (Fibromyalgia), GSI (Global Severity Index), IEI (Idiopathic Environmental Intolerance), IG (Intervention Group), MBCT (Mindfulness-Based Cognitive Therapy), MBSR (Mindfulness-Based Stress Reduction), MCS (Multiple Chemical Sensitivity), PEMF (Pulsed Electromagnetic Field), PHQ (Patient Health Questionnaire), POMS (Profile of Mood States), QEESI (Quick Environmental Exposure and Sensitivity Inventory), QEESI-LIS (Life Impact Scale of the Quick Environmental Exposure and Sensitivity Inventory), QEESI-SSS (Symptom Severity Scale of the Quick Environmental Exposure and Sensitivity Inventory), RCT (Randomized Clinical Trial), SAI (State Anxiety Inventory), SCAN (Schedules for Clinical Assessment in Neuropsychiatry), SCED (Single-case Experimental Design), SCL-90R (Symptom Checklist-90-Revised), SCL-92 (Symptoms Checklist 92), SSRI (Selective Serotonin Reuptake Inhibitors), TAU (Treatment As Usual) and WL (Waitlist). Note. Arrows indicate direction of change: ↓ = decrease/improvement; ↑ = increase; ↔ = no change; Ø = absence or none (e.g., no side effects reported).
Table 2. Methodological quality analysis (PEDro Scale).
Table 2. Methodological quality analysis (PEDro Scale).
Year, AuthorScoreQuality1234567891011
Tran et al. (2016) [40]10ExcellentYesYesYesYesYesYesYesYesYesYesYes
Haugue et al. (2015) [41]7GoodYesYesYesYesNoNoNoYesYesYesYes
Araki et al. (2012) [42]6GoodYesYesYesNoNoNoNoYesYesYesYes
Skovbjerg et al. (2012) [43]5AcceptableYesYesYesYesNoNoNoNoNoNoYes
Sampalli et al. (2009) [44]3LowYesNoNoYesNoNoNoNoNoYesYes
Methodological quality assessment of the included studies was assessed using the PEDro Scale [33], which comprises 11 items: (1) eligibility criteria (not scored), (2) random allocation, (3) concealed allocation, (4) baseline comparability, (5) blinding of participants, (6) blinding of therapists, (7) blinding of outcome assessors, (8) adequate follow-up (>85%), (9) intention-to-treat analysis, (10) between-group statistical comparisons, and (11) reporting of point estimates and variability. Note. In the assessment table, each item is rated as “Yes” if the criterion is fulfilled or “No” if it is not. The total PEDro score, ranging from 0 to 10 (excluding item 1), reflects overall methodological rigor, with higher scores indicating better quality.
Table 3. Methodological quality analysis (NIH Case Series Quality Assessment Tool).
Table 3. Methodological quality analysis (NIH Case Series Quality Assessment Tool).
Year, AuthorScoreQuality12345678910
Amin & Forslund (2018) [39]7/9Good+++?++++?NA
Guglielmi
et al. (1994) [48]		5/9Acceptable−??+++−++NA
Methodological quality assessment of the included studies was conducted using the NIH Case Series Quality Assessment Tool [34], which consists of 10 items: (1) clear objective; (2) defined population; (3) consecutive inclusion; (4) intervention described; (5) valid/reliable measures; (6) adequate follow-up; (7) complete outcomes; (8) statistical analysis; (9) outcomes described; (10) prospective design. Note. “+” = criterion clearly met; “−” = criterion not met; “?” = unclear or not enough information to assess. The total score (out of 9) reflects the number of criteria clearly met. Quality is categorized as Good (7–9), Acceptable (4–6), or Poor (0–3).
Table 4. Methodological quality analysis (Case Report Evaluation Tool, CEBMa).
Table 4. Methodological quality analysis (Case Report Evaluation Tool, CEBMa).
Year, AuthorScoreQuality12345678910
Woolfolk
et al. (2018) [38]		9/9Good++++++?+++
Elberling
et al. (2010) [44]		6/9Acceptable+++??−−+++
Busse
et al. (2008) [46]		7/9Good++++−−−+++
Stenn
et al. (1998) [47]		7/9Good++++??−+++
Methodological quality assessment of the included studies was conducted using the NIH Case Series Quality Assessment Tool [35], which consists of 10 items: (1) clear description of the case; (2) clear timeline; (3) diagnostic tests/results clearly described; (4) intervention (s) clearly described; (5) post-intervention outcomes clearly described; (6) adverse events reported; (7) takeaway lessons provided; (8) patient’s perspective included; (9) ethical approval stated; (10) conclusions grounded in evidence. Note. “+” = criterion clearly met; “−” = criterion not met; “?” = unclear or not enough information to assess. The total score (out of 9) reflects the number of criteria clearly met. Quality is categorized as Good (7–9), Acceptable (4–6), or Poor (0–3).
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Martín Pérez, I.M.; Parra Castillo, D.A.; Ruiz de la Fuente, C.P.; Martín Pérez, S.E. Effectiveness of Lifestyle-Based Approaches for Adults with Multiple Chemical Sensitivity: A Systematic Review. Therapeutics 2025, 2, 13. https://doi.org/10.3390/therapeutics2030013

AMA Style

Martín Pérez IM, Parra Castillo DA, Ruiz de la Fuente CP, Martín Pérez SE. Effectiveness of Lifestyle-Based Approaches for Adults with Multiple Chemical Sensitivity: A Systematic Review. Therapeutics. 2025; 2(3):13. https://doi.org/10.3390/therapeutics2030013

Chicago/Turabian Style

Martín Pérez, Isidro Miguel, David Alejandro Parra Castillo, Carlos Pastor Ruiz de la Fuente, and Sebastián Eustaquio Martín Pérez. 2025. "Effectiveness of Lifestyle-Based Approaches for Adults with Multiple Chemical Sensitivity: A Systematic Review" Therapeutics 2, no. 3: 13. https://doi.org/10.3390/therapeutics2030013

APA Style

Martín Pérez, I. M., Parra Castillo, D. A., Ruiz de la Fuente, C. P., & Martín Pérez, S. E. (2025). Effectiveness of Lifestyle-Based Approaches for Adults with Multiple Chemical Sensitivity: A Systematic Review. Therapeutics, 2(3), 13. https://doi.org/10.3390/therapeutics2030013

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