ME/CFS and the thalamus as a precision gate: what reversible thalamocortical connectivity reveals about central gain in post-infectious fatigue

Abstract:

Kim and colleagues report a finding that is easy to understate: thalamic hyperconnectivity with sensorimotor and visuo-occipital cortices, present in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) at baseline, shifts back toward the pattern seen in healthy controls after hyperbaric oxygen therapy and does so most in the patients who improve clinically. To my knowledge, this is the first treatment-coupled, apparently reversible thalamocortical signature in ME/CFS.

Viewed through predictive processing (the framework in which the brain continually predicts its own sensory and bodily inputs), the thalamus is theorised to be a gain-control gate that helps set the precision or weight assigned to ascending bodily signals. I argue that the baseline hyperconnectivity reflects deficient filtering of expected input, and that its post-treatment reduction may index restored filtering. The same failure of attenuation offers a parsimonious account of several symptoms that often co-occur in patients, including sensory hypersensitivity, pain, orthostatic intolerance, and cognitive “brain fog”, as one mechanism expressed across exteroceptive, nociceptive, autonomic, and cognitive domains.

Because hyperbaric oxygen therapy is a vascular intervention and resting-state connectivity is an indirect measure this gain interpretation remains a hypothesis and I outline how it can be tested across exertion and post-exertional malaise rather than at baseline alone.

Source: Strube A. ME/CFS and the thalamus as a precision gate: what reversible thalamocortical connectivity reveals about central gain in post-infectious fatigue. J Transl Med. 2026 Jul 29;24(1):1345. doi: 10.1186/s12967-026-08718-6. PMID: 42934697. https://link.springer.com/article/10.1186/s12967-026-08718-6 (Full text)

Natural Strategies for Stopping a Common Energy Drain in ME/CFS and Fibromyalgia

By Jacob Teitelbaum, MD

www.ProHealth.com • October 12, 2011

Dr. Teitelbaum, a well-known fatigue and pain specialist who contracted CFS as a medical student, has researched ME/CFS/FM patients’ nutritional and therapeutic needs for more than 20 years. This article is reproduced with kind permission* from his educational web site at https://www.vitality101.com/

Reprinted with the kind permission of ProHealth: 10/12/11

______________________________________

Treating Low Blood Volume & Decreased Heart Function in CFS & FM

In this important article we will discuss a critical but usually overlooked part of treating Chronic Fatigue Syndrome and fibromyalgia effectively. It can be relatively easy to treat, but is not very glamorous, and is therefore often forgotten.

We will focus on research by Dr. Barry Hurwitz and a team of University of Miami researchers, including Dr. Nancy Klimas, who is wonderful and one of my favorite people in the CFS community… Their [2009] study shows that patients with CFS have:

1. A lower blood volume (basically are dehydrated).

2. Fewer red blood cells to carry oxygen and nutrients (basically anemia, despite normal blood tests).

The study also discusses that although the heart may be smaller in CFS and beats less efficiently, this is likely caused by the dehydration and low blood volume, as opposed to primarily being a heart problem. (More on the details later.)

The good news is that all of these issues can be effectively treated and optimized naturally – which can leave you feeling much better!

THE BOTTOM LINE FIRST

There are several key things that you can do to treat the low blood volume and low blood cell levels that will leave you feeling better:

1. Treat the Dehydration.

Despite your increased thirst and drinking a lot (“like a fish”), most of you are still dehydrated because you’re urinating even more. This occurs for several reasons, including underactive adrenal function and a decrease in antidiuretic hormone (“anti-peeing hormone”), both of which are routinely present in CFS because of the hypothalamic dysfunction (“blowing a fuse”) that we often discuss….

Quick Fixes:

a. Drink more water! Instead of counting glasses of water (an annoying way to spend the rest of your life), check your mouth and lips to see if they are dry. If they are, drink!

b. Eat more salt. Unless you have high blood pressure or heart failure, you need more salt than most people. In fact, many studies have shown that the more salt people eat the longer they live [see sidebar at end of article, “High Salt Intake is Associated with BETTER Health”], and for most people the need to avoid salt has been a problematic medical myth (see six dangerous “Medical Myths“). Use an iodized salt or better yet sea salts… Enjoy salty foods as well.

c. Improve adrenal function. This is discussed at more length in “The Adrenal Gland, and Symptoms of Adrenal Insufficiency,” but a simple way to do this is with an excellent product called Adrenal Stress End.

d. Saline IVs. Clinical experience has also shown that salt water (saline) IVs can be very helpful. The effects are transient though, unless other nutrients are added  – e.g., the Myers’ Cocktails [which are IV vitamin and mineral therapies first conceived in the 1970s by the late John Myers, MD, at Johns Hopkins] administered at holistic physicians’ offices [such as] the Fibromyalgia and Fatigue Centers.

2. Increase Your Body’s Production of Red Blood Cells.

Although treating the infections and hormonal problems we discuss overall in the SHINE Protocol will do this (addressing possible problems with Sleep, Hormones, Infection, Nutrition, and Exercise), below are key things that will help.

a. Treat for low iron – even if your blood tests are normal but modestly low. The best blood test is called a “ferritin” level. Your doctor will say it is normal if it is over 12, but research has shown(2) that in people with chronic fatigue, iron supplementation increased energy dramatically in people with a ferritin under 50 (see Iron Helps Fatigue – Even with Normal Iron Levels and No Anemia) who were not anemic. If the ferritin blood test is under 50, or the iron percent saturation blood test is under 25%, take 1-2 tablets of iron (29 mg with vitamin C) each afternoon or evening on an empty stomach for 4-6 months.

b. Treat for low testosterone and low thyroid levels – despite the normal blood tests. Both of these, especially the testosterone (use only the safe and natural bioidentical forms), increase red blood cell production.

3. Improve Your Heart Function

Though the study discussed in this article notes that the low blood volume and anemia are key, other studies and clinical experience show that nutrients that improve heart function also improve energy in CFS patients. These include:

a. Ribose (Corvalen) 5 gm (1 scoop) 3x day for 3 weeks, then twice a day.

b. Acetyl L-carnitine 500 mg 2x day. [See for example “Long-chain acylcarnitine deficiency in patients with Chronic Fatigue Syndrome,” Journal of Internal Medicine, Jul 2011].

c. The Energy Revitalization System vitamin powder (contains 50 nutrients including B vitamins and magnesium).

d. Coenzyme Q10 at 200 mg daily.

Give the above treatments 6-12 weeks to see the effect. But by one month, most of you will be feeling a lot better with these treatments. In addition, if you have not already done so, do the free Symptom Analysis Program to tailor an overall treatment protocol to your case. Although you do not need to have your blood tests results, if they are available the program will also analyze the more important tests.

WHAT THE UNIVERSITY OF MIAMI STUDY SHOWS

The study(1) looked at 146 people with chronic fatigue syndrome, 30 of whom were very severely affected. It compared them to healthy controls and then factored in how active or sedentary the people were.

People with CFS showed 25% lower heart contractility, so they pumped much less blood.

They then did specialized testing which showed what the person’s total blood volume was and also whether they had enough red blood cells, both of which have been shown to be low in the majority of those with severe CFS.

As all of the above problems have been shown to be common in CFS, the study explored whether there was predominantly a heart problem or whether all of these findings could be explained by dehydration and having too few red blood cells. I would note that, normally, having too few red blood cells would be called being anemic.

Unfortunately, the standard blood tests for anemia compare the amount of blood cells relative to the blood volume. As both are low, the blood count tests come back as normal despite CFS patients in reality being functionally very anemic.

As the study authors note, “The elevated prevalence of low red blood cell volume suggests that the CFS subjects may have an anemia type that goes undetected by standard hematologic evaluations.”

In other words, people with CFS are likely to be anemic despite normal testing (being 6% to 13% lower than optimal, depending on the severity of their CFS).

The role of decreased heart function in CFS has been a major focus of work by Dr. Paul Cheney, MD, PhD, a chronic fatigue syndrome expert who is intimately familiar with the effects of heart problems, as he needed a heart transplant himself. He theorizes (and I am markedly oversimplifying his theory) that heart function decreases as an adaptation to not being able to properly handle the oxygen needed to make energy in CFS.

Chronic disease in general can trigger dehydration and low red blood cell volume, so there are many possible reasons for these occurring in CFS. Deconditioning can also then decrease heart function.

This study was associated with another study looking at whether injections of a prescription blood cell stimulating hormone called
“erythropoietin” would be helpful in CFS, which would naturally lead to some focus towards interpreting the results as being associated with a deficiency of blood cells as opposed to a heart problem. The benefits of erythropoietin treatment were modest relative to the cost and hassle, though, and I think the researchers’ bias is fairly modest.

The authors conclude, “Given these findings, it may be prudent in the clinical setting to perform a direct examination of blood volume status in CFS patients and consider treatment for those with abnormal levels. A blood volume deficit may:

• Impact adversely oxygen delivery and nutrient supply,

• Impair hemodynamic regulation (e.g., blood pressure and heart function),

• And contribute to the exacerbation of fatigue and other CFS symptomatology.”

As their earlier study showed minimal benefit from only increasing the amount of red blood cells using erythropoietin, it again shows the need to use an overall treatment approach to treat all the problems present in CFS.

These include raising red blood cell mass and treating the dehydration, but also treating the underlying infections, adrenal under activity, and other problems that are at the root of these problems.

As we know that most people with CFS will have the dehydration and “anemia despite normal blood testing,” I do not think it is worth the cost of doing these expensive nuclear scans, but instead recommend the simple treatments discussed in the summary above, which we know are helpful in CFS. (Again, these are part of the SHINE Protocol.)

* * * *

SIDEBAR: High Salt Intake is Associated with BETTER Health
Re: “Sodium Intake & Mortality Follow-Up in the Third National Health and Nutrition Examination Survey – NHANES III.”

This study is a fascinating one. It is based on the NHANES data base, which is one of the most respected (if not the most respected) nutritional data bases in the country. What the study showed is the opposite of what we have been led to believe medically.

It showed that the lower the salt intake, the HIGHER the risk of death. Put differently, our advice to people to avoid salt is more likely to be harmful than helpful!

On the other hand, though there was no significant evidence that salt was harmful, the evidence for a low salt diet being harmful was modest, so if people want to avoid salt it probably won’t hurt them too much.

The possibility of a low salt diet being harmful was also likely affected by more people in the low salt diet group having high blood pressure, so it may have been the underlying high blood pressure which caused their higher death risk (i.e., people with high blood pressure were told by their doctors to be on low salt diets, and this could be a “confounding variable” that makes people misinterpret the data. The low salt didn’t kill them, but rather it was their earlier high blood pressure).

Bottom line – Enjoy yourself! Eat the amount of salt that your body wants and don’t worry about it (if you don’t have high blood pressure or heart failure).

The Abstract:
“Sodium Intake and Mortality Follow-Up in the Third National Health and Nutrition Examination Survey – NHANES III.” (The full text article is here – https://pmc.ncbi.nlm.nih.gov/articles/PMC2518033/)

Background: Sodium restriction is commonly recommended as a measure to lower blood pressure and thus reduce cardiovascular disease (CVD) and all cause mortality. However, some studies have observed higher mortality associated with lower sodium intake.

Objective: To test the hypothesis that lower sodium is associated with subsequent higher cardiovascular disease (CVD) and all cause mortality in the Third National Health and Nutrition Examination Survey (NHANES III).

Design: Observational cohort study of mortality subsequent to a baseline survey.

Participants: Representative sample (n=8,699) of non-institutionalized US adults age 30 and older, without history of CVD events, recruited between 1988-1994.

Measurements and Main Results: Dietary sodium and calorie intakes estimated from a single baseline 24-h dietary recall. Vital status and cause of death were obtained from the National Death Index through the year 2000.

Hazard ratio (HR) for CVD mortality of lowest to highest quartile of sodium, adjusted for calories and other CVD risk factors, in a Cox model, was 1.80 (95% CI 1.05, 3.08, p=0.03). [Note: an HR of 1.0 would represent no difference; so a ratio of 1.80 would indicate that individuals in the lowest sodium intake quartile were 80% more likely on average to die of a cardiovascular event than those in the highest sodium intake group.]

Non-significant trends of an inverse association of continuous sodium (per 1,000 mg) intake with CVD and all-cause mortality were observed with a 99% CI of 0.73, 1.06 (p=0.07) and 0.86, 1.04 (p=0.11), respectively, while trends for a direct association were not observed.

Conclusion: Observed associations of lower sodium with higher mortality [all causes] were modest and mostly not statistically significant. However, these findings also suggest that for the general US adult population, higher sodium is unlikely to be independently associated with higher CVD or all-cause mortality.

___

1. Low Blood Volume and Red Blood Cell Mass Study, Abstract: “Chronic fatigue syndrome: Illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function,” Barry E. Hurwitz, Nancy G. Klimas, et al. Behavioral Medicine Research Center, University of Miami, Florida. Clinical Science (Lond), Oct 19, 2009.

2. Reference for Iron Study: “Iron supplementation for unexplained fatigue in non-anaemic women: Double blind randomised placebo controlled trial,” F Verdon, et al. BMJ, May 2003.

* Copyright © 2011 by The Annapolis Chronic Fatigue and Fibromyalgia Research Center for Effective CFS/FMS Therapies. All rights reserved.

Disclaimer: These statements have not been evaluated by the FDA. This information and the supplements discussed are not intended to diagnose, prevent, treat or cure any illness, condition or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

Cerebrospinal fluid opening pressure in relation to symptomatology and craniocervical anatomy in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease that affects millions worldwide. Its cause remains unknown, although many physiological mechanisms are impaired. Structural abnormalities in the craniocervical region seem to be more prevalent in patients with ME/CFS, with a possible impact on intracranial pressure (ICP) and lumbar puncture (LP) measurements. This study aimed to quantify the occurrence of elevated cerebrospinal fluid (CSF) opening pressure and a possible association with clinical symptoms and radiological variables in craniocervical segments in a cohort of patients with ME/CFS.

Methods: This study included 34 patients previously diagnosed with ME/CFS as part of a larger case-control study, for whom LP was performed only in the case group. Key measurements included age, sex, opening pressure from LP, symptomatic relief post-LP, and radiological variables with potential influence on CSF dynamics. Individuals were stratified into two groups according to opening pressure (OP) measurements using 20 cmH2O as the cutoff value, with subsequent statistical comparisons.

Results: Overall, the majority of participants reported moderate disease severity (65%) and concomitant self-reported low quality of life. The median CSF opening pressure was 18 (IQR 8) cmH2O, ranging from 11 to 29.5. Opening pressure stratification showed that 21 of the 34 cases (62%) had an OP measurement of <20 cmH2O (low-OP group) and 13 cases (38%) had an OP measurement of ≥20 cmH2O (high-OP group). The two OP groups did not differ significantly in baseline characteristics, including disease severity and quality of life. However, for certain radiological measurements, the high-OP group presented with measures reflecting a wider spinal canal, including a significantly larger foramen magnum diameter (33.9 mm), which was higher than the measures in the low-OP group (31.7 mm). Estimates of symptom relief 1-4 days post-LP were significantly higher among patients in the high-OP group (80%) than among those in the low-OP group (19%).

Conclusion: This study suggests that a proportion of patients with ME/CFS have elevated CSF opening pressures and may experience symptom relief following CSF subtraction. Our data indicate that some anatomical structures in the craniocervical area may be related to CSF pressure, although interpretation is challenging and merits further investigation.

Source: Jolley C, Bragée B, Soinne L, Huhmar H, Billing H, Bertilson B, Sjogren P. Cerebrospinal fluid opening pressure in relation to symptomatology and craniocervical anatomy in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Front Med (Lausanne). 2026 Aug 4;13:1869714. doi: 10.3389/fmed.2026.1869714. PMID: 42614190; PMCID: PMC13481257. https://pmc.ncbi.nlm.nih.gov/articles/PMC13481257/ (Full text)

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study

Abstract:

Background: Hyperbaric oxygen therapy (HBOT) has been proposed as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but evidence remains limited. This study evaluated its clinical effectiveness and feasibility, as well as associated functional brain changes.

Methods: Thirty patients with ME/CFS (mean age 42.3 ± 11.7 years; 7 males, 23 females) received 40 HBOT sessions. Clinical outcomes were assessed at baseline, during treatment, and four weeks post-treatment. The primary outcome was change in the physical functioning subscale of the Short Form-36 Health Survey (SF-36 PF). Secondary outcomes included severity of core symptoms assessed via questionnaires, exercise capacity, handgrip strength, cognitive performance, orthostatic intolerance, and brain magnetic resonance imaging (MRI; volumetry and functional connectivity [FC]). Thirty age- and sex-matched healthy controls (mean age 42.3 ± 11.3 years; 7 males, 23 females) were included for MRI comparison.

Results: SF-36 PF significantly improved during HBOT compared with baseline (g = 0.71, p = 0.006). SF-36 pain (p = 0.002, g = 0.79) and Chalder Fatigue Scale also showed clinically meaningful reductions (p < 0.001, g = -0.87). Exercise capacity (g = 0.66), muscle strength (g = 0.40), and information processing speed (g = 0.52) improved significantly after treatment (all p < 0.05). Treatment adherence was high and tolerability was favorable, with no major adverse events reported. Functional MRI analyses revealed increased thalamic FC in ME/CFS patients compared to healthy controls in bilateral sensorimotor (p < 0.001, t = 5.65, FDR-corrected) and visuo-occipital regions (p < 0.001, t = 5.40, FDR-corrected) at baseline. Following HBOT, thalamic hyperconnectivity shifted toward patterns observed in healthy controls. Responders, defined as a ≥ 10 points increase in SF-36 PF, showed greater reductions in thalamic hyperconnectivity than non-responders (p < 0.001, t = -4.34 to -5.18, FDR-corrected).

Conclusions: HBOT was well tolerated and associated with significant improvements in physical functioning, fatigue, pain, and cognitive performance in ME/CFS. The post-treatment shift in thalamocortical connectivity toward healthy control patterns and its association with clinical response support the hypothesis that functional thalamic dysregulation contributes to ME/CFS pathophysiology and may be modulated by HBOT. This provides a network-level rationale for controlled trials to confirm therapeutic efficacy.

Trial registration: ClinicalTrials.gov NCT06118138. Registered 01 November 2023 – Retrospectively registered, https://clinicaltrials.gov/study/NCT06118138?cond=ME%2FCFSamp;term=HBOTamp;rank=1.

Source: Kim L, Cammà G, Peters CK, Mantwill M, Müller O, Leprêtre N, Heindrich C, Rust R, Krill M, Hartung TJ, Reeß LG, Krohn S, Heymann CV, Wittke K, Finke C, Scheibenbogen C. Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study. J Transl Med. 2026 Jun 5. doi: 10.1186/s12967-026-08324-6. Epub ahead of print. PMID: 42249466. https://link.springer.com/article/10.1186/s12967-026-08324-6 (Full study available as PDF file)

Low-Dose Naltrexone: What is the Evidence? A Narrative Review

Abstract:

Naltrexone is prescribed off-label at low doses, typically 0.5-6.0 mg, for a variety of therapeutic indications. This review evaluates the clinical evidence for low-dose naltrexone (LDN). A literature search was conducted in February 2026 across PubMed, Embase and CINAHL for studies published from 1989 to 2026.

Title and abstract searches for “low dose naltrexone” identified peer-reviewed English-language studies using doses of ≤ 12.5 mg in humans. A total of 105 studies were reviewed, including 15 randomised controlled trials (RCTs) in chronic pain, autoimmune and neuroimmune disorders, gastrointestinal disease, dermatological conditions, post-infectious syndromes, mental health and oncology.

Across these fields, early positive findings from uncontrolled studies were rarely replicated in placebo-controlled trials. Most available evidence consists of case reports and small feasibility studies that are prone to publication bias and rely heavily on subjective outcomes. LDN is generally safe, inexpensive and well tolerated, with most studies using a daily dose of 4.5 mg.

Although these features contribute to its appeal, current evidence does not support routine clinical use. LDN may have a pragmatic role in treatment-resistant cases where standard therapies have failed, provided its experimental status and uncertain efficacy are clearly explained. Larger, well-designed RCTs with objective endpoints, along with N-of-1 approaches to identify potential responders, are needed to clarify its true clinical value.

Source: Gouda AHK, Aitcheson NEC, Steadman KJ. Low-Dose Naltrexone: What is the Evidence? A Narrative Review. Adv Ther. 2026 Apr 30. doi: 10.1007/s12325-026-03612-5. Epub ahead of print. PMID: 42060160. https://link.springer.com/article/10.1007/s12325-026-03612-5 (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Successful Therapeutic Plasma Exchange Treatment After SARS-CoV-2 Infection-A Case Report

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex neuroimmunological disorder characterized by disabling symptoms that are often difficult to manage. More recently, in the context of SARS-CoV-2 infection, potential pathophysiological overlaps and disease modulation have been hypothesized. Our successful case highlights the need to investigate novel therapeutic approaches, including plasma exchange.

Source: Ciobanu G, Arn N. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Successful Therapeutic Plasma Exchange Treatment After SARS-CoV-2 Infection-A Case Report. Clin Case Rep. 2026 May 17;14:e72725. doi: 10.1002/ccr3.72725. PMID: 42158223; PMCID: PMC13180788. https://pmc.ncbi.nlm.nih.gov/articles/PMC13180788/ (Full text)

Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation

Abstract:

Purpose: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem neurologic disease characterized by profound fatigue and decreased functional capacity, postexertional malaise, and unrefreshing sleep, along with cognitive impairment and/or orthostatic intolerance. Its prevalence has risen exponentially with the COVID-19 pandemic. Pharmacologic therapies have been used successfully by ME/CFS specialists but may be underused by the general medical field.

Methods: To assess this potential practice gap, we retrospectively analyzed the records of 571 patients with an ME/CFS diagnosis referred to our ME/CFS specialty clinic in Minnesota during 2018-2022. We ascertained medications that had already been tried at the time of consultation and also ascertained supplement use.

Results: With the exception of medications primarily used for pain and anxiety, use of pharmacotherapy for ME/CFS symptom management as proposed by specialists was limited. Overall, 68.3% of patients had had at least 1 medication potentially prescribed for ME/CFS; the most common were serotonin-norepinephrine reuptake inhibitors, gabapentin, and tricyclic antidepressants. A slightly larger share of patients, 72.2%, reported having taken at least 1 dietary supplement; the most common were vitamin D, vitamin B12 and B complex, and fish oil.

Conclusion: Our findings suggest that potentially helpful medications for ME/CFS are being underprescribed in the general medical field and that patients may resort to supplements to manage symptoms. Better education of clinicians about available treatment options and treatment guides may improve management of this debilitating disease.

Source: Grach SL, Seltzer J, Mueller MR, Aakre CA, Natividad LT, Lawson DK, Ganesh R, Hurt RT. Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation. Ann Fam Med. 2026 Apr 29:250266. doi: 10.1370/afm.250266. Epub ahead of print. PMID: 42055743. https://www.annfammed.org/content/early/2026/04/24/afm.250266-0 (Full text available as PDF file)

Testing a Personalised Dysautonomia Management Protocol in Patients with Orthostatic Intolerance and a Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Long COVID

Abstract:

Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC) are complex multisystem conditions with significant functional disability. Many patients experience symptoms of orthostatic intolerance, which can be captured in some cases as Orthostatic Hypotension (OH) or Postural orthostatic Tachycardia Syndrome (PoTS) on objective testing. Conservative treatments are recommended for first-line symptom management, but there is a lack of efficacy evidence. This study aims to assess the feasibility of an 8-week clinically supervised, personalised Dysautonomia Management Protocol (DMP) in a cohort of ME/CFS and LC patients with subjective and objective evidence of orthostatic intolerance (dysautonomia).

Methods: ME/CFS and LC patients with objective dysautonomia on the 10 min active Lean Test (LT) were recruited to an 8-week DMP, with interventions introduced cumulatively every two weeks. Interventions included increasing daily fluid intake to 3 litres and salt intake to 10 g, pacing to avoid crashes and calf activation. Baseline and weekly data collection included the LT, Composite Autonomic Symptom Score questionnaire (COMPASS-31) and Yorkshire Rehabilitation Scale (YRS).

Results: Sixteen participants completed the 8-week program, five discontinued during the program, and one was withdrawn following a severe crash. The COMPASS-31 improved by 7.7 points from week 1 to week 8 (p = 0.045), with a medium Cohen’s d effect size of 0.55. For the same period, there was a non-significant (p = 0.16) improvement in the YRS symptom severity score by 2 points. Comparing the final two weeks of the program with the first two weeks, mean heart rate during the LT decreased by 4.8 beats per minute (p = 0.032), with a medium Cohen’s d effect size of 0.44. Adherence to the interventions was highly variable, with none of the patients able to fully employ all four recommendations.

Conclusions: The results suggest that targeted conservative interventions could influence autonomic function and symptom reduction. However, the magnitude of change was limited, and statistical significance might not necessarily relate to a clinically significant improvement in symptoms.

Source: Barr J, Marsden L, Dassanayake T, Almutairi N, McKeever V, Gaber T, Tarrant R, Godfrey B, Witton S, Sivan M. Testing a Personalised Dysautonomia Management Protocol in Patients with Orthostatic Intolerance and a Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Long COVID. J Clin Med. 2026 Mar 25;15(7):2510. doi: 10.3390/jcm15072510. PMID: 41976810. https://www.mdpi.com/2077-0383/15/7/2510 (Full text)

Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness characterized by profound fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction, yet it currently lacks FDA-approved treatments. Molecular hydrogen (H2), administered primarily as hydrogen-rich water (HRW), has emerged as a potential therapeutic candidate due to its selective antioxidant effects, anti-inflammatory activity, and support of mitochondrial and cellular homeostasis. These mechanisms align with several biological abnormalities implicated in ME/CFS, including oxidative stress, chronic inflammation, and impaired energy metabolism. This narrative mini-review summarizes mechanistic evidence relevant to ME/CFS and evaluates three developmental clinical studies of HRW in this population.

Although early trials are small and methodologically limited, moderate-dose HRW consumed over extended durations has demonstrated feasibility and preliminary benefits in reducing fatigue and improving physical function, with generally mild side effects. Overlapping findings in Long COVID further suggest potential applicability across related post-viral fatigue conditions. Key limitations include small sample sizes, reliance on self-report outcomes, and the absence of objective biomarkers.

Future research should prioritize larger, rigorously controlled trials incorporating remote biometric and biochemical assessments to clarify mechanisms of action and identify responsive subgroups. Overall, molecular hydrogen represents a promising, low-burden adjunctive therapy warranting further investigation in ME/CFS.

Source:Friedberg F and LeBaron TW (2026) Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale. Front. Med. 13:1760210. doi: 10.3389/fmed.2026.1760210 https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1760210/full (Full text)

A Continuous Oral Regimen of High-Dose Cromolyn Sodium Is Effective for Some Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients With Mast Cell Activation Syndrome

Abstract:

Our clinical experience in the last four years using oral cromolyn in patients with mast cell activation syndrome (MCAS) suggests that a continuous oral regimen of high-dose cromolyn may enhance compliance with the medication. The five patients described in this retrospective case series were given instructions to take oral cromolyn using a continuous dosing regimen, placing the entire day’s dose in an opaque bottle that is then filled with water, and sipping the solution throughout the day. If a conventional maximum dose of eight vials daily (800 mg) was tolerated but ineffective after a week, the patients were instructed to increase to 1600-2400 mg daily until reaching an optimal effect.

We report that a cromolyn dose of 1600-2400 mg daily, administered using the continuous oral dosing regimen during the day, was effective in controlling signs and symptoms of mast cell activation. All five patients benefitted from a dose of cromolyn that is higher than usual and customary recommendations, but within the safety guidelines of the original Food and Drug Administration (FDA) application. The continuous oral regimen has some theoretical advantages over four discrete doses per day, though further study is needed.

Source: Christoforou ME, van Campen LC, Visser FC, Lee CK, Lemmon SL, Rowe PC, Azola AM. A Continuous Oral Regimen of High-Dose Cromolyn Sodium Is Effective for Some Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients With Mast Cell Activation Syndrome. Cureus. 2026 Jan 22;18(1):e102064. doi: 10.7759/cureus.102064. PMID: 41728426; PMCID: PMC12924640. https://pmc.ncbi.nlm.nih.gov/articles/PMC12924640/ (Full text)