Critique of The Gupta Program

The Gupta Program , also known as Amygdala and Insula Retraining (AIR), is a neuroplasticity-based mind-body program incorporating brain retraining, mindfulness, breathwork, meditation, somatic practices and lifestyle approaches.

The program has attracted debate, particularly within the ME/CFS community. Criticisms have focused on the evidence supporting its proposed neurological mechanism, the size and independence of the clinical evidence base, historical advertising claims, its use across multiple chronic conditions, and concerns that brain retraining approaches may be interpreted as suggesting that physical illnesses are primarily psychological.

Some of these criticisms originated when relatively little clinical research into AIR was available. Since then, the evidence base has expanded and now includes several randomized controlled studies and other peer-reviewed research. These studies have reported statistically significant improvements across outcomes including fatigue, energy, pain, sleep, physical functioning, cognitive functioning, anxiety, depression and quality of life, with moderate, large and, in some studies, very large effect sizes.

The evidence base remains developing, and further large-scale independent research would help establish the size, durability and generalisability of these effects. There is also currently stronger evidence for clinical improvements associated with AIR-based interventions than for the specific neurological mechanism proposed to explain them.

Scientific evidence

Development of the evidence base

The evidence base for the Gupta Program and Amygdala and Insula Retraining has expanded considerably since the program's earliest studies.

Published research now includes several randomized controlled studies investigating AIR or interventions incorporating AIR, alongside observational research and clinical audit data.

Randomized studies have reported statistically significant improvements in outcomes including fatigue, energy, physical health, pain, fibromyalgia impact, sleep, cognitive functioning, anxiety, depression and quality of life.

Some studies have reported moderate-to-large, large or extremely large effect sizes for particular outcomes.

This means that earlier descriptions of the Gupta Program as having "no empirical evidence" are no longer accurate.

The quality and strength of the evidence varies between studies. Several trials have relatively small samples, many outcomes are self-reported, some interventions combine AIR with other therapeutic components, and independent replication remains limited.

A more accurate description is therefore that AIR has an emerging clinical evidence base, with several randomized studies reporting promising results, while further larger and independently replicated trials would increase confidence in these findings.

Randomized controlled research

2025 Fibromyalgia randomized controlled trial

A 2025 randomized controlled study compared Amygdala and Insula Retraining, physical activity and pregabalin among women diagnosed with fibromyalgia.

Participants were randomly allocated to AIR, a physical activity intervention, or a control group receiving pregabalin. Outcomes included cognitive functioning, sleep disturbance, pain catastrophizing, depressive symptoms and overall fibromyalgia impact.

Both AIR and physical activity significantly improved all measured outcomes compared with baseline and the pregabalin control group.

AIR also produced significantly superior outcomes for pain catastrophizing, depressive symptoms and overall fibromyalgia impact, with large to extremely large effect sizes reported.

The findings provide randomized controlled evidence suggesting that AIR may offer clinical benefit for people with fibromyalgia.

The study involved a relatively small sample of Iranian women, so further trials in larger and more diverse populations would help establish the generalisability of the results.

Study:

Norouzi, Ebrahim; Pournazari, Mehran; Joybari, Toraj Ahmadi; Sufivand, Parviz; Asar, Shirin; Bratty, Alexandra J.; Khazaie, Habibolah (April 15, 2025). "Two non-pharmacological interventions, amygdala and insula retraining (AIR) and physical activity, are both significantly more effective than standard medication in improving symptoms of fibromyalgia".

2024 randomized study incorporating AIR

A 2024 randomized controlled study investigated an intervention combining physical activity with selected components of Amygdala and Insula Retraining (PAAIR) among older men.

Participants receiving PAAIR demonstrated greater improvements in sleep quality, working memory and emotion regulation, as well as reductions in depressive symptoms, compared with the control group. Large to extremely large effect sizes were reported for several outcomes.

The study provides additional randomized evidence relating to techniques incorporated within AIR.

However, it did not evaluate the complete Gupta Program. Because AIR components were combined with a physical activity intervention, their individual contribution cannot be isolated.

Study:

Ghaleni, Monireh Asadi; Masrour, Forouzan Fattahi; Saryar, Narjes; Bratty, Alexandra J.; Norouzi, Ebrahim; Fernandes, Matheus Santos de Sousa; Badicu, Georgian (2024). "Effects of an intervention combining physical activity and components of Amygdala and Insula Retraining (AIR) on sleep and working memory among older male adults".

2023 Long COVID randomized controlled trial

A 2023 randomized controlled trial evaluated AIR among people with Long COVID.

Participants were randomized to AIR or a structurally equivalent health and wellness intervention.

The AIR group experienced statistically significant reductions in fatigue and increases in energy compared with the active control group.

The reported effect size for fatigue reduction in the AIR group was more than four times that observed in the control group, while the effect size for increased energy was approximately twice that of the control.

The findings provide direct randomized controlled evidence suggesting that AIR may improve fatigue and energy in people with Long COVID.

The trial was relatively small and relied primarily on self-reported outcomes. Further larger studies would help establish the reliability and generalisability of the effect and examine longer-term outcomes.

The study did not investigate neuroimaging or biomarkers capable of confirming the neurological mechanism proposed by the Gupta Program. Its findings therefore relate to clinical outcomes rather than establishing the cause of Long COVID or AIR's mechanism of action.

Study:

Toussaint, Loren L.; Bratty, Alexandra J. (July 2023). "Amygdala and Insula Retraining (AIR) Significantly Reduces Fatigue and Increases Energy in People with Long COVID".

2020 Fibromyalgia pilot randomized controlled trial

A 2020 pilot randomized controlled trial investigated mindfulness plus Amygdala and Insula Retraining (MAIR) among women with fibromyalgia.

Forty-one participants were randomized to MAIR or a structurally equivalent relaxation therapy control, with both interventions provided alongside treatment as usual.

MAIR produced significantly greater reductions in functional impairment, anxiety and depression and greater improvements in mindfulness and self-compassion at post-treatment and follow-up. Moderate-to-large effect sizes were reported.

At follow-up, significant improvements were also observed in pain catastrophizing, psychological inflexibility, clinical severity and health-related quality of life, with large effect sizes.

For a reduction of at least 50% on the Fibromyalgia Impact Questionnaire, the study reported a number needed to treat of three.

The study also investigated biological measures and found a significant difference in brain-derived neurotrophic factor (BDNF) compared with the active control, although significant effects were not found across the inflammatory markers investigated.

These findings provide randomized controlled evidence supporting potential clinical benefit from the combined MAIR intervention.

Because the intervention combined mindfulness with AIR, the individual contribution of AIR cannot be determined from this study alone. The authors also described the research as a pilot trial, and larger studies would help confirm the results.

Study:

Juan P Sanabria-Mazo; Montero-Marin, Jesus; Feliu-Soler, Albert; Gasión, Virginia; Navarro-Gil, Mayte; Morillo-Sarto 8,, Héctor; Colomer-Carbonell, Ariadna; Borràs, Xavier; Tops, Mattie; Luciano, Juan V; García-Campayo, Javier (September 2020). "Mindfulness-Based Program Plus Amygdala and Insula Retraining (MAIR) for the Treatment of Women with Fibromyalgia: A Pilot Randomized Controlled Trial"

2012 Fibromyalgia and chronic fatigue randomized controlled trial

A 2012 single-blind randomized controlled trial investigated amygdala retraining alongside standard care in people with fibromyalgia, chronic fatigue syndrome, or both.

Participants were randomized to receive amygdala retraining alongside standard care or standard care alone.

The study reported statistically significant improvements in physical health, energy, pain, symptom distress and fatigue among participants receiving amygdala retraining compared with standard care.

Outcomes were assessed using validated self-report questionnaires including the SF-36, Multidimensional Fatigue Inventory and Fibromyalgia Impact Questionnaire.

The trial therefore provided early randomized controlled evidence suggesting potential clinical benefits from amygdala retraining in people with chronic fatigue and fibromyalgia.

The study experienced substantial attrition. Of 44 randomized participants completing baseline assessments, 21 completed the study, including seven in the amygdala retraining group. The small final sample means the findings require confirmation in larger trials.

Study:

Toussaint, Loren L.; Whipple, Mary O.; Abboud, Lana L.; Vincent, Ann; Wahner-Roedler, Dietlind L. (March 2012). "A Mind-Body Technique for Symptoms Related to Fibromyalgia and Chronic Fatigue"

Observational research

2023 multi-condition study

A 2023 exploratory study investigated self-reported changes in overall health and functioning among people using AIR across 16 chronic conditions.

The primary analysis focused on people who had actively used AIR for at least three months.

Statistically significant improvements in health and functioning were reported for 14 of the 16 conditions examined.

Eleven of these findings had large effect sizes and three had medium effect sizes.

Among the conditions reaching statistical significance were ME/CFS, fibromyalgia and Long COVID. The study reported post-AIR mean health scores that were 70% higher for ME/CFS, 62% higher for fibromyalgia and 84% higher for Long COVID compared with retrospective pre-AIR ratings.

The results provide observational evidence consistent with potential benefits across a range of chronic conditions.

The study did not include a control group and relied on participants retrospectively rating their health before and after using AIR. Recruitment through the Gupta Program database also creates potential for selection, recall and response bias.

The findings therefore cannot establish efficacy for each individual condition, but they provide supportive observational evidence alongside the randomized research.

Study:

Bratty, Alexandra J (December 2023). "Neuroplasticity Intervention, Amygdala and Insula Retraining (AIR), Significantly Improves Overall Health and Functioning Across Various Chronic Conditions".

Further randomized research

Further randomized research into AIR has also been developed.

A separate randomized controlled trial involving approximately 100 people with Long COVID was designed to evaluate AIR combined with mindfulness against a structurally equivalent relaxation intervention.

Planned outcomes include quality of life, fatigue, pain, anxiety, memory and sleep quality.

Researchers involved are affiliated with institutions including the Aragon Institute for Health Research, University of Zaragoza and University of Oxford.

A peer-reviewed protocol for the trial was published in 2023. As a protocol, it demonstrates further controlled investigation of the intervention but should not be treated as evidence of efficacy until results are published.

Protocol:

Gasión, Virginia; Barceló-Soler, Alberto; Beltrán-Ruiz, María; Hijar-Aguinaga, Rinchen; Camarero-Grados, Loreto; López-del-Hoyo, Yolanda; García-Campayo, Javier; Montero-Marin, Jesus (November 9, 2023). "Effectiveness of an amygdala and insula retraining program combined with mindfulness training to improve the quality of life in patients with long COVID: a randomized controlled trial protocol".

2018 Advertising Standards Authority ruling

In 2018, the UK Advertising Standards Authority (ASA) investigated advertising claims that the Gupta Program could treat fibromyalgia, ME/CFS and electrical sensitivities.

At the time, the evidence submitted included an early randomized controlled study, a clinical audit and an unpublished manuscript.

The ASA concluded that the evidence presented was insufficient to substantiate the specific treatment claims being made and upheld all three complaints.

It instructed Harley Street Solutions Ltd not to state or imply that the Gupta Program could treat the conditions unless adequate substantiation was held.

The ruling remains relevant to the advertising assessed in 2018.

However, it predates the 2020 fibromyalgia pilot RCT, the 2023 Long COVID RCT, the 2023 multi-condition study, the 2024 randomized PAAIR study and the 2025 fibromyalgia RCT.

It should therefore be understood as an assessment of the evidence supporting particular advertising claims at that time, rather than as a systematic assessment of the current evidence base.

"Harley Street Solutions Ltd - ASA | CAP". www.asa.org.uk. Retrieved August 26, 2026

Long COVID

Early concerns

The Gupta Program began offering material relating to COVID-19 during the early stages of the pandemic.

In March 2020, it released a package called the "10 Day Coronavirus Challenge". Promotional material reportedly stated that some of the tools included had been scientifically shown to reduce the chances of contracting a viral infection by more than 80%.

A complaint was made to the ASA, which reportedly referred the matter to its compliance team in light of its earlier ruling.

The subsequent promotion of the Gupta Program to people with Long COVID was also criticised because condition-specific clinical research into AIR and Long COVID had not yet been published.

These criticisms reflected the evidence available at the time.

Subsequent evidence

The evidence base has since changed.

The 2023 randomized controlled Long COVID trial found significantly greater reductions in fatigue and increases in energy among participants receiving AIR compared with an active health-and-wellness control.

A separate randomized controlled trial of AIR combined with mindfulness in Long COVID has also been developed, with its peer-reviewed protocol published in 2023.

It is therefore no longer accurate to state that there is no empirical research evaluating AIR in Long COVID.

The available research does not establish that Long COVID is caused by an overactive amygdala or insula. The clinical effectiveness of an intervention and the biological cause of a disease are separate questions.

Proposed neurological mechanism

The Gupta Program is based on a hypothesis that persistent patterns of threat processing involving neural systems including the amygdala and insula may contribute to the maintenance of symptoms in some chronic conditions.

According to the model, an initial trigger such as infection, injury or prolonged physiological or psychological stress may sensitise neural pathways involved in detecting threat.

The brain may subsequently continue responding to internal sensations or other stimuli as danger signals after the original trigger has passed. The model proposes that persistent activation may influence autonomic, endocrine and immune responses and contribute to a self-reinforcing cycle of symptoms and threat signalling.

Evidence for the mechanism

A key area of uncertainty is whether the specific neurological mechanism proposed by the Gupta Program has been demonstrated directly.

Clinical trials have reported improvements following AIR, but these findings do not by themselves establish that improvements occurred because of changes in amygdala or insula activity.

No published neuroimaging study has yet directly demonstrated the specific neural changes proposed by the program following participation in AIR.

At the same time, neuroplasticity is an established property of the nervous system, and research in related fields demonstrates that behavioral and psychological interventions can influence activity and connectivity within neural systems involved in emotion, threat processing and interoception.

The evidence therefore supports distinguishing between two separate questions: whether AIR can improve clinical outcomes and whether the Gupta Program's proposed neurological explanation for those improvements is correct.

The first has now been investigated in several randomized studies with promising findings. The second requires further direct investigation.

Use across multiple chronic conditions

The Gupta Program is used by people with a range of chronic conditions, including ME/CFS, fibromyalgia, Long COVID and other illnesses.

Critics have questioned whether a single intervention can benefit conditions with different and potentially complex biological mechanisms.

The Gupta model does not necessarily propose that these illnesses have identical pathology. Instead, it proposes that maladaptive threat processing and nervous-system responses may act as a perpetuating factor across different conditions.

The 2023 observational study reported statistically significant improvements in health and functioning across 14 of 16 conditions studied, with medium or large effect sizes.

These findings provide preliminary support for the possibility of cross-condition benefits, although condition-specific randomized controlled trials are needed to determine whether the effects are reproducible across different patient populations.

ME/CFS and post-exertional malaise

The use of brain retraining interventions in ME/CFS has attracted particular debate because post-exertional malaise (PEM) is a characteristic feature of the condition.

PEM can involve delayed worsening of symptoms following physical, cognitive or emotional exertion. Concerns have therefore been raised about interventions that encourage people with ME/CFS to increase activity beyond their individual capacity.

The Gupta Program includes pacing guidance and encourages participants to remain within their energy boundaries rather than deliberately pushing through symptoms. It also provides guidance for periods of increased symptoms or "dips".

Some individuals have reported experiencing symptom exacerbations while undertaking brain retraining programs. These reports are relevant to patient experience but cannot establish how frequently deterioration occurs or whether AIR itself caused it.

Future trials would benefit from systematic reporting of adverse events, deterioration and withdrawals alongside measures of improvement, particularly among participants with ME/CFS.

NICE guidance and NLP

The NICE guideline for ME/CFS advises against therapies based on fixed incremental increases in physical activity and against therapies derived from osteopathy, life coaching or neurolinguistic programming, giving the Lightning Process as an example.

The Gupta Program has sometimes been grouped with NLP-based interventions, leading critics to suggest that this NICE recommendation applies to it.

However, NICE does not specifically name or evaluate the Gupta Program in this recommendation.

The Gupta Program incorporates cognitive and behavioral elements alongside mindfulness, meditation, breathwork, somatic practices, pacing and lifestyle approaches.

It is therefore important to distinguish a recommendation relating to specified categories of therapy from a direct NICE assessment of the Gupta Program.

Relationship to psychological and behavioral models of ME/CFS

Brain retraining has attracted controversy partly because of the history of psychological and behavioral approaches to ME/CFS.

Debates surrounding cognitive behavioral therapy, graded exercise therapy, the PACE trial and the biopsychosocial model have contributed to concerns that interventions such as AIR may imply that ME/CFS is primarily psychological.

The Gupta Program uses cognitive and behavioral techniques but describes its model primarily in terms of neuroplasticity, learned threat responses and nervous-system regulation. It does not use the same intervention protocol as graded exercise therapy.

The wider history of psychological treatment in ME/CFS helps explain why brain retraining is controversial, but does not itself establish whether AIR is effective or ineffective.

That question is better assessed through AIR's own clinical evidence, safety data and proposed mechanisms.

Psychological versus physical illness

Some critics have argued that brain retraining risks reinforcing the idea that conditions such as ME/CFS, fibromyalgia and Long COVID are psychological rather than biological.

However, demonstrating that a behavioral, psychological or neuroplasticity-based intervention influences symptoms would not establish that an illness is psychological in origin.

Interventions acting through the nervous system can influence symptoms and physiological processes in conditions with biological pathology.

Likewise, evidence of immune, autonomic, neurological or metabolic abnormalities would not by itself demonstrate that interventions involving the central nervous system cannot influence symptoms.

The relevant questions are therefore whether AIR produces clinically meaningful benefits, for whom, with what risks, and through which mechanisms.

Patient responsibility and self-blame

Some critics have raised concerns that participants who do not improve with brain retraining may interpret this as a failure to practise sufficiently or to adopt the correct mindset.

This is a relevant consideration for any intervention in which active participation and regular practice are important.

However, failure to improve does not demonstrate a lack of effort, motivation or belief. Treatment responses vary between individuals for many reasons, and current evidence does not establish that AIR works for everyone who undertakes it.

Gender and medical bias

ME/CFS, fibromyalgia and several other chronic conditions addressed by the Gupta Program disproportionately affect women.

The historical tendency to attribute poorly understood symptoms in women to psychological causes has therefore contributed to concerns about mind-body approaches to these conditions.

This history provides relevant context for patient concerns.

However, it does not establish that the Gupta Program itself is a continuation of historical "hysteria" models. The program is more appropriately assessed according to its specific claims, evidence, safety and proposed mechanisms.

Qualifications and regulation

Ashok Gupta, who developed the Gupta Program, is not a medical doctor or clinical psychologist.

This has led some critics to question whether a person without regulated clinical qualifications should develop an intervention for people with complex chronic illnesses.

Developing a behavioral, educational or self-management intervention does not necessarily require the developer to be a physician. However, medical treatment claims require appropriate supporting evidence and may be subject to healthcare and advertising regulation.

The Gupta Program should not be considered a substitute for appropriate medical assessment, diagnosis or necessary medical treatment.

Research independence and conflicts of interest

Some AIR publications report professional or financial relationships involving researchers and the Gupta Program.

For example, Alexandra J. Bratty has disclosed that her research consultancy provides consulting services to the Gupta Program. Such relationships are relevant when evaluating the evidence.

Potential conflicts of interest do not automatically invalidate research findings, but independent replication is particularly valuable for proprietary or commercially available interventions.

AIR research has also involved researchers from academic and clinical institutions outside the Gupta Program.

Further large-scale trials conducted by independent research groups would strengthen confidence in the evidence and help establish whether existing findings can be consistently reproduced.

Patient experiences and safety

Both positive and negative experiences of the Gupta Program have been reported.

Some participants report substantial improvements or recovery, while others report little benefit or worsening of symptoms.

Individual testimonials can provide information about people's experiences but cannot establish treatment efficacy or the frequency of adverse effects.

Randomized trials provide stronger evidence of average clinical effects. Future research would nevertheless benefit from consistent reporting of adverse events, symptom deterioration, withdrawals and long-term outcomes alongside measures of improvement.

Debate around scientific framing

Critics have questioned the Gupta Program's use of neuroscience concepts such as neuroplasticity, amygdala activation and insula activity because its specific neurological mechanism has not yet been demonstrated directly.

This criticism highlights an important distinction between established evidence concerning neuroplasticity in general and evidence for the specific mechanism proposed by AIR.

However, the clinical effects of AIR are empirically testable and have now been investigated in several peer-reviewed randomized studies.

The most useful scientific approach is therefore to evaluate the quality, findings, limitations and reproducibility of this research rather than categorically accepting or rejecting the intervention based on its theoretical model alone.

Current evidence provides promising clinical findings for AIR or AIR-containing interventions across several populations, while the proposed neurological mechanism remains less established.

Current state of the evidence

The evidence surrounding the Gupta Program has changed substantially since many of the original criticisms were first raised.

Early research consisted mainly of a small randomized controlled trial and an uncontrolled clinical audit. In 2018, the ASA concluded that the evidence presented at the time was insufficient to substantiate the specific treatment claims then being advertised.

Since then, the research base has expanded.

It now includes:

• a 2020 pilot randomized controlled trial of mindfulness plus AIR in fibromyalgia;
• a 2023 randomized controlled trial of AIR in Long COVID;
• a 2023 observational study across 16 chronic conditions;
• a 2024 randomized controlled study combining physical activity with AIR components;
• a 2025 randomized controlled trial comparing AIR and physical activity with pregabalin in fibromyalgia; and
• a published protocol for further randomized investigation of AIR plus mindfulness in Long COVID.

Across the completed randomized studies, statistically significant improvements have been reported in outcomes including fatigue, energy, physical health, pain, fibromyalgia impact, sleep, cognitive functioning, anxiety, depression and quality of life.

Some studies have reported moderate, large or extremely large effect sizes.

The evidence base is still developing. Larger samples, longer follow-up, systematic adverse-event reporting, objective outcomes where appropriate, and further replication by independent research teams would help clarify the size and durability of the effects and identify which patient groups are most likely to benefit.

Overall, the current literature provides promising evidence that AIR-based interventions may improve a range of clinical outcomes, while further research is needed to establish the strength and generalisability of these findings and to determine whether the specific neurological mechanism proposed by the Gupta Program explains the observed effects.

See also

• Gupta Program
• Amygdala and Insula Retraining
• Brain retraining
• ME/CFS
• Fibromyalgia
• Long COVID
• Post-exertional malaise
• Neuroplasticity
• Cognitive behavioral therapy
• Biopsychosocial model
• PACE trial
• Gupta Program research overview https://guptaprogram.com/research/