A reader asked me to assemble information from studies on Low Dosage Naltrexone. For conditions like Fibromyalgia, we have 49 studies with good or no effects.  I speculate that the effectiveness is dependent upon the microbiome prior to starting.

A lot of the published literature are case-reports (i.e. on individuals). My general impression from larger studies is that it is a 50-50 toss of the coin if improvement will happen. There is an absence of literature on its impact on different bacteria in the microbiome.

• Efficacy and Safety of Low Dose Naltrexone for Chronic Pain [2024]
  • “Seven (23%) reported side effects. LDN was associated with a statistically significant reduction in PEG in adult chronic pain patients, however the clinical significance is unclear as over 75% of patients discontinued LDN due to lack of benefit.”
• Low-Dose Naltrexone Improves post-COVID-19 condition Symptoms [2024]
  • “The relative hazard of improvement for those taking low-dose naltrexone was 5.04 (95% CI, 1.22-20.77; P = 0.02) compared with physical therapy alone. Both fatigue and pain were improved in patients taking low-dose naltrexone”
• Low-dose naltrexone use for the management of post-acute sequelae of COVID-19 [2023]
  • “The use of LDN was associated with a fewer number of symptoms, improved clinical symptoms (fatigue, post-exertional malaise, unrefreshing sleep, and abnormal sleep pattern), and a better functional status.”
• A systematic literature review on the clinical efficacy of low dose naltrexone and its effect on putative pathophysiological mechanisms among patients diagnosed with fibromyalgia [2023]
  • “One study reported baseline erythrocyte sedimentation rate (ESR) predicted LDN response (≥30% reduction in fibromyalgia symptoms) and a second study showed plasma concentrations of inflammatory biomarkers were lower after LDN treatment.”
• Complex Presentations, Identification and Treatment of Mast Cell Activation Syndrome and Associated Conditions: A Case Report [2023]
  • “The patient was ultimately deemed to have other associated conditions including a mast cell-mediated disorder as well as joint hypermobility due to her response to antihistamine and mast cell stabilizing agents. Final outcomes include immense improvement upon mast cell stabilization with ketotifen, and remission of SIBO with low-dose naltrexone (LDN).”
• Low-dose naltrexone as a treatment for chronic fatigue syndrome [2020] – Three(3) Case Reports
  • “it was clear she was stable and well, and could walk, and more recently, cycle, without problems. Prior to starting LDN, her intellectual and cognitive functioning was very limited. “
  • “She no longer requires acupuncture for symptomatic pain relief. However, her functional level did not improve with LDN. also continues with other symptoms of myalgic encephalomyelitis including postexertional neuroimmune exhaustion, periodic muscle weakness, orthostatic intolerance, symptomatic sinus tachycardia, urticarial rashes and susceptibility to bacterial infections”
  • “His functional level improved from being mild–moderately limited on a daily basis (60%–70% on a functional activity scale) to mild limitations (80%–90% on a functional activity scale). “
• Repurposing low-dose naltrexone for the prevention and treatment of immunothrombosis in COVID-19 [2022] “we hypothesize that the immune-modulating and known pharmacologic properties of LDN could be leveraged as a novel therapeutic strategy in COVID-19.”
• Low-dose Naltrexone Therapy for Psoriasis [2020]
  • Three adverse events included insomnia, diarrhea, and self-limited headache. Marked improvement was seen by 53% of the 15 patients. Low-dose naltrexone regulates lymphocyte responses, reduces cytokine production, and likely reduces mast cell activity.
• Low Dose Naltrexone in Dermatology [2019]
• Pharmacology Update: Low-Dose Naltrexone as a Possible Nonopioid Modality for Some Chronic, Nonmalignant Pain Syndromes [2019]
  • “When used in doses of 1 to 5 mg it acts as a glial modulator with a neuroprotective effect via inhibition of microglial activation. It binds to Toll-like receptor 4 and acts as an antagonist, therefore inhibiting the downstream cellular signaling pathways that ultimately lead to pro-inflammatory cytokines, therefore reducing inflammatory response. Low-dose naltrexone (LDN) may also have utility in improving mood disorders and the potential to enhance the quality of life”
• The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn’s Disease, and Other Chronic Pain Disorders [2018]
  • “Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn’s disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited.”
• Low dose naltrexone for induction of remission in Crohn’s disease [2018]
  • “The results of the study in adult patients suggest that low dose naltrexone may provide a benefit in terms of clinical response (i.e. an improvement in disease symptoms) and endoscopic response (i.e. a reduction in inflammation of the gut as shown by examining the gut with a scope)”
• Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment [2018]
• The Effect of Low-Dose Naltrexone on Medication in Inflammatory Bowel Disease: A Quasi Experimental Before-and-After Prescription Database Study [2018]

A reader that does microbiome analysis of her ME/CFS daughter’s microbiome using Microbiome Prescription expert system sent me this note with some literature. The daughter has Celiac Disease and ME/CFS.

Your wonderful system recommended beta-glucans [also written β-Glucan] for my daughter,  and when I looked further, I found this. I’m trying her on them for a month-, after testing her for reactions for three days- the first week has been hopeful. Will keep you posted if you wish.

Reader

β-Glucan is a nonstarch polysaccharide having documented health benefits and industrial applications. It can be extracted from various sources, including cereals, bacteria, molds, and fungi. The chemical nature of extracted β-glucan from these sources differs slightly. This variation in chemistry defines its industrial uses and health benefits.

Biopolymers for Food Design, 2018

Literature

There is not much literature available for ME/CFS.

• “The findings showed that the beta-glucan supplementation significantly improved cognitive fatigue (assessed with FIS-40 scores) after the 36-week treatment compared to the baseline (p = 0.0338). Taken together, this study presents the novel finding that yeast-derived beta-glucan may alleviate cognitive fatigue symptoms in ME/CFS.” [2023]
• β-Glucan Improves Conditions of Chronic Fatigue in Mice by Stimulation of Immunity [2020] Reduces TNF-α (which is connected to mast cell issues)
• Effects of β-(1,3–1,6)-d-glucan on irritable bowel syndrome-related colonic hypersensitivity [2012]
  “β-Glucan did not affect the pain response in general but specifically affects the visceral pain response.”
• Serum concentrations of 2′,5′-oligoadenylate synthetase, neopterin, and beta-glucan in patients with chronic fatigue syndrome and in patients with major depression. [1994]
• “ the dosage of supplementation ranged from 2.5 to 1000 mg daily [of beta-glucan] for up to 6.5 months … The primary physiological outcome of the majority of the interventions was immunomodulation, which resulted in (a) strengthened immune defense that reduces the incidence and symptoms of cold, flu and other respiratory infections and (b) improvement of allergic symptoms.” [2021]
• β-glucan attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice [2020]

Some literature for Autism

• Improvement of sleep and melatonin in children with autism spectrum disorder after β-1,3/1,6-glucan consumption: An open-label prospective pilot clinical study [2022]
• Study: Beta glucan improves behaviour in autistic children [2022]
• Benefits of Gut Microbiota Reconstitution by Beta 1,3-1,6 Glucans in Subjects with Autism Spectrum Disorder and Other Neurodegenerative Diseases [2023]
• Improvement of behavioural pattern and alpha-synuclein levels in autism spectrum disorder after consumption of a beta–glucan food supplement in a randomised, parallel-group pilot clinical study. [2022]

Many Sources of Beta Glucan

Often the expert system on Microbiome Prescription comes up with Barley as a strong recommendation for ME/CFS people. Barley is an excellent source. Personally, I have oats or barley porridge a couple of times every week. The impact of the β-Glucan in the Barley may be the mechanism — we just do not have as many studies as we do for Barley.

• “The primary sources of food β-glucan for humans are cereals (especially oats and barley), fungi, algae, and yeast ” [2023] A table from this article is below

• “β-glucans bind to specific receptors on immune cells and initiate immune responses…. In vitro study found that the fermentation of barley and oat β-glucan by human fecal samples show variations in SCFAs production and the bacterial populations of Clostridium histolyticum and the ratio of Bacteroides–Prevotella species. Absorption of these SCFAs by the gut epithelial cells helps in regulating cell differentiation, proliferation, apoptosis, and gene expression (210). Butyrate increases the protein expression of tight junctions such as ZO-1 and claudin-1, resulting in enhanced intestinal barrier function.”
  “β-glucan is an essential food ingredient in controlling metabolic dysregulations linked to metabolic syndrome. β-glucans have a very minimal probability of having any unfavorable side effects and are reasonably inexpensive.” [2023]

Bottom Line

Real simple: Barley or Oats porridge for breakfast each day! Since there are some chemical differences between the β-glucans in these two grains– rotate between these (and different brands) at least monthly.

Using the generic suggestions for me/cfs we see both barley and B-glucan are positive (but oats are slightly negative). The more detailed citizen science suggestions are still be worked on, but I expect similar.

Reviewing Clinical Trials, my impression is 1 gram/day of β-glucans which translates to 20 grams of Barley or 40 grams of Oats per day.

“30g uncooked oats or barley will make a fairly small bowl of porridge whilst 70-80g will provide a particularly large serving for one person. Traditional porridge recipes tend to use oatmeal with approximately 200ml of water per 50g oats, and a pinch of salt.”

University of Aberdeen

Some people will advocate just eat mushroom. While correct that it contains beta-glucans, we need to be careful not to slip into homeopathic dosages!

Among those, mushrooms feature a particularly high level, so it’s no exaggeration when we say “for beta glucans, look to mushrooms!” The amounts of beta glucans found per 100 g of raw mushroom include 2.3 g (maitake), 2.0 g (bunapi), 1.9 g (eryngii), 1.8 g (bunashimeji) and 1.5 g (shimofuri hiratake) (Hokuto data).

https://www.hokto-kinoko.co.jp/lang/en/kouka/jiten/jiten06/

When we go to typical US mushrooms (i.e. Button), we drop to .75 g/100 grams [FDA]. So we are talking about 5-6 oz of mushrooms per day. That 3/4 of the typical mushroom package per day per person.

Celiac and Gluten Sensitive Issue

Most beta glucan supplements are produced from Saccharomyces cerevisiae (thus gluten free). For example the item below is about US$17.00 and gives 100 days at 1 gram per day.

I should note that there are different forms of beta glucan, for example above it is the 1,3/1,6 forms. Another product has 1,3/1,4 and is derived from Oats (you will have to write the company to see if it is gluten free or low gluten).

The cost per gram is much lower as bulk powders than with pre-filled “premium” capsules – the same volume of beta glucan can be as high as $250 (12x more) with some products.