A reader continues going thru traditional folk medicine looking for items off the beaten path that may be of interest and sending candidates to me.

The latest request for me to research is a gem. Mast cell inhibitor, anti-allergy, reduces gut inflammation, likely help with SIBO, etc

Perilla frutescens var. crispa, or shiso containing 58-65% alpha-linolenic acid [2006] [2008], It is sometimes referred to as purple mint

• Health effects of omega-3,6,9 fatty acids: Perilla frutescens is a good example of plant oils. [2011]
  • Dietary Perilla seed oil supplement increases plasma omega-3 polyunsaturated fatty acids and ameliorates immunoglobulin A nephropathy in high immunoglobulin A strain of ddY mice. [2011]
• ” Rosmarinic acid (RA) is a natural polyphenol present in several Lamiaceae herbs like Perilla frutescens, and RA is becoming an integral component of animal nutrition as it counters the effect of reactive oxygen species induced in the body as a consequence of different kinds of stressors. Studies have further ascertained the capability of RA to work as an anti-microbial, immunomodulatory, anti-diabetic, anti-allergic, anti-inflammatory, hepato- and renal-protectant agent, as well as to have beneficial effects during skin afflictions.  ” [2017]
• Rosmarinic Acid Potentiates Pentobarbital-Induced Sleep Behaviors and Non-Rapid Eye Movement (NREM) Sleep through the Activation of GABA_A-ergic Systems. [2017] – better sleep
• Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by Perilla frutescens.[2000]
• “It was found that more than 100 compounds have been reported for P. frutescens and most of them are contributed to its medical benefits such as anti-allergic, anti-inflammatory, anti-oxidant, anticancer, anti-microbial, anti-depressive and anti-cough effects.” [2017]
• Intestinal Anti-Inflammatory Activity of Perillaldehyde. [2018]
  • Anti-inflammatory effects of Perilla frutescens in activated human neutrophils through two independent pathways: Src family kinases and Calcium.[2015]
• Rosmarinic acid suppresses colonic inflammation in dextran sulphate sodium (DSS)-induced mice via dual inhibition of NF-κB and STAT3 activation. [2017]
  • Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines. [2016]
  • Perilla extract improves gastrointestinal discomfort in a randomized placebo controlled double blind human pilot study. [2015]
• A flavanone derivative from the Asian medicinal herb (Perilla frutescens) potently suppresses IgE-mediated immediate hypersensitivity reactions. [2017]
  • Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. [2002]
• ” These results suggest that habitual drinking of shiso tea is effective in preventing the onset of diabetes. ” [2010]
• Neuroprotective Effect of Perilla Extracts on PC12 Cells. [2016]
  • Alpha-Linolenic Acid from Perilla frutescens var. japonica Oil Protects Aβ-Induced Cognitive Impairment through Regulation of APP Processing and Aβ Degradation. [2017]
  • The Neuro-Protective Effect of the Methanolic Extract of Perilla frutescens var. japonicaand Rosmarinic Acid against H₂O₂-Induced Oxidative Stress in C6 Glial Cells. [2016]
  • Perilla frutescens Extract Ameliorates Acetylcholinesterase and Trimethyltin Chloride-Induced Neurotoxicity. [2016]
  • Antidepressant-like effect of essential oil of Perilla frutescens in a chronic, unpredictable, mild stress-induced depression model mice. [2014]
  • Antidepressant-like effects of Perilla frutescens seed oil during a forced swimming test. [2014]
  • Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test.[2003]
  • Improved spatial learning and memory by perilla diet is correlated with immunoreactivities to neurofilament and α-synuclein in hilus of dentate gyrus. [2012]
• Anti-Amyloidogenic Effects of Asarone Derivatives From Perilla frutescens Leaves against Beta-Amyloid Aggregation and Nitric Oxide Production. [2019] ”  these results suggest that asarone derivatives derived from P. frutescens are neuroprotective and have the prophylactic and therapeutic potential in Alzheimer’s Disease“.
• Drying the leaves of Perilla frutescens increases their content of anticancer nutraceuticals. [2019] ” Quantitative analysis of the concentrations of perillaldehyde, rosmarinic acid, apigenin, luteolin, 4-hydroxyphenyllactic acid, and 4-coumaric acid, some of which are known as nutraceuticals, revealed that the effect of drying significantly increased apigenin (28-fold) and luteolin (86-fold), but decreased rosmarinic acid in all leaf stages.”
• Antiobesity Effects of Purple Perilla (Perilla frutescens var. acuta) on Adipocyte Differentiation and Mice Fed a High-fat Diet. [2018]
• Anti-hyperglycemic effects and signaling mechanism of Perilla frutescens sprout extract. [2018]
• Bacterial Quorum Sensing Inhibition Activity of the Traditional Chinese Herbs, Ficus carica L. and Perilla frutescens. [2014]
• Rosmarinic acid down-regulates endothelial protein C receptor shedding in vitro and in vivo. [2013]
• Oxalate content in common Japanese foods. [1984] – It is high
• Antioxidant activities of polyphenols extracted from Perilla frutescens varieties. [2008]
  • Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. [2004]

Microbiome Impact

• Medicinal herbs as a potential strategy to decrease methane production by rumen microbiota: a systematic evaluation with a focus on Perilla frutescens seed extract.[2016]
  • ” The decreased CH₄ production induced by the P. frutescens seed extract was accompanied by an increased abundance of Ruminobacter, Selenomonas, Succinivibrio, Shuttleworthis, Pseudobutyrivbrio, Anaerovibrio, and Roseomonas and a decreased abundance of Methanobrevibacter millerae.  “
• Perilla oil regulates intestinal microbiota and alleviates insulin resistance through the PI3K/AKT signaling pathway in type-2 diabetic KKAy mice. [2020]
  • “Additionally, PerO treatment distinctly decreased the abundance of Aerococcus (& Streptococcus ) and facilitated the richness of Alloprevotella (& Akkermansia ) in the intestine, as well as accelerated the restoration of the gut microflora diversity. ”
• Optimization of antibacterial activity of Perilla frutescens var. acuta leaf against Pseudomonas aeruginosa using the evolutionary operation-factorial design technique. [2010]
• Antimicrobial activity of perilla seed polyphenols against oral pathogenic bacteria. [2002] Porphyromonas gingivalis

Bottom Line

For additional information, see https://content.selfdecode.com/perilla-oil/

Needless to say, it will be added to the database at http://microbiomeprescription.azurewebsites.net/ and increased the number of direct citations.

Over this weekend, we finally reached the threshold for citizen science to look at Autism (20+ symptom annotated uploads). This coming weekend I am attending a conference on Autism in Vancouver, British Columbia, Canada where Jason Hawrelak from Tasmania will be speaking (schedule below).

In preparation for this I decided to do a technical study comparing published studies on Autism and the results of citizen science. Is there agreement? What are the factors that come up with different results?

Source Data

Data comes from two sources (both are subject to change with time):

• Publish Studies – listed here with citations
• Citizen Science from Microbiome Prescription – showing the distributions

We had agreement on several items, namely:

• Sutterellaceae (family) being High
• Sutterella (genus) being High
• Blautia being Low
• Bifidobacterium being High (in some Published studies)
• Lactobacillus being High (in some Published studies)

We had disagreement on only one item:

• Veillonella was high on citizen science and low on published studies

Age is a significant factor for both Bifidobacterium and Lactobacillus. Studies on autism under 6, 6-12 and older will have significantly different amounts. This may account for disagreement between published studies.

Critique of Published Studies

Reproducibility of studies is important. There are 17 Pub Med studies on the autism microbiome. If you look at Publish Studies, the same bacteria is only reported 7 times at most. Many bacteria are only reported once. Whether a bacteria is evaluated depends on the equipment being used, for example – Bilophila is reported as significant in 2 studies but Thryve 16s results do not report it.

The usual criteria is to detect statistical significance of averages between the target group and the control group. This requires some major, likely false, assumptions:

• Representative samples in each group
• Normal distribution of the bacteria in each group

A single outlier in a group can cause statistical significance to appear while a more sensitive (but require more effort) test like Pearson’s chi-squared test would find nothing to publish about. It is important to note that Pearson’s usually results in sample sizes of at least 20; many published studies do not have that number.

If I exclude non-matches with at least 2 studies with consistent results (a single study in 17 studies is likely unreliable), then we have the following not detected yet with Citizen Science (which have barely enough studies to do any analysis).

On the flip side, Citizen Science reports on some bacteria not reported in published studies over 10 with high significance.

Bottom Line

Large representative samples and in depth skilled statistical analysis is needed to reliably identify the bacteria associated with a symptom, medical condition or characteristic.

From Publish Studies and Citizen Science, we have apparent agreement on 5 taxa, disagreement on 1, and silence in terms of repeatability on some 20 additional ones. I hope/ believe that as the number of samples in Citizen Science data set grows we will find more agreement with some of the published studies.

Below is a spreadsheet for interested parties.

For people not aware of the Microbiome Prescription site, this gives an overview.

Hello, a few months ago I saw a comment at the ME-Research Forum in which a sick commented that a doctor in Spain is prescribing hidroaltesona to the sick as palliative treatment for the ME.
I have tried to investigate about it since I have been taking 10 mg of hidroaltesona daily for a year having improved my intestinal problems (swelling and diarrhea, about 6 times a day in the last 15 years) passing to a Normal frequency.
My doctor put me the treatment for hipocortisolismo but the intestinal improvement was immediate.
Do you know studies or testimonies of people who have maintained this long-term treatment? 

From a reader

Hidroaltesona [C₂₁H₂₉Na₂O₈P] is related to Cortisol [
C₂₁H₃₁O₈P] (chemically different) containing two sodium atoms. Searching PubMed did not find any studies — I have never seen this happen before! I checked Hydrocortisone [C₂₁H₃₀O₅] and found studies but the absence of sodium and phosphate atoms left me with a feeling that it was only vaguely similar.

From Manufacturer Site

All indications of oral corticotherapy, except in states that involve life-threatening and require intravenous route. The most important ones are:

• Replacement therapy in primary or secondary adrenocortical insufficiency.
• Congenital adrenal hyperplasia.

Other indications are:

• Rheumatic and collagen diseases: treatment of exacerbations and / or maintenance therapy of rheumatoid arthritis, juvenile arthritis, ankylosing spondylitis and psoriatic arthritis when conservative treatments have been shown ineffective; Polymyalgia rheumatica; acute rheumatic fever; systemic lupus erythematosus; severe dermatomyositis; noia periarteritis; cranial arteritis and Wegener’s granulomatosis; scleroderma and dermatomyositis.
  
• Dermatological diseases: allergic eczema, bullous pemphigoid pemphigus, generalized exfoliative dermatitis, severe erythema multiforme, erythema nodosum and severe psoriasis.
• Serious allergic diseases: allergic rhinitis, contact dermatitis and bronchial asthma refractory to conventional therapy.
• Lung diseases: sarcoidosis with pulmonary disease, extrinsic allergic alveolitis (organic dust pneumoconiosis), desquamative interstitial pneumonia (idiopathic pulmonary fibrosis).
• Eye pathology: keratitis, choroiditis, chorioretinitis, iritis and iridocyclitis.
• Hematological diseases: idiopathic thrombocytopenia, hemolytic anemias and palliative treatment of leukemia and lymphomas.
• Gastrointestinal and hepatic pathology: ulcerative colitis, Crohn’s disease and hepatitis.

More Information

I found some experience from MDs with it at https://www.doctoralia.es/medicamentos/hidroaltesona/preguntas

That may be the best source to get solid information.

• “long-term corticosteroid treatments, and depending on the dose, can induce changes and side effects in practically the entire economy of the organism, affecting almost any “
• “What is the relationship between hydroaltesona and prednisone? Both active ingredients are corticosteroids, with different potency and are used in many processes and diseases. “
• ” In principle, in adrenal insufficiency, the doses range between 25 and 40 mg per day. ” – so this patient is on a low dosage.

PubMed on Hydrocortisone and ME/CFS

• ” Cortisol levels, before or after dex, did not differ between CFS and Healthy Controls (HCs). Cortisol levels were more variable in CFS than HCs. ” [2018]
• ” we found an inverse relationship between cortisol reactivity and symptom severity. There was no relationship between cortisol reactivity and illness duration. ” [2016]

• Low-dose Hydrocortisone in Chronic Fatigue Syndrome: A Randomised Crossover Trial [1999] ” Interpretation: In some patients with chronic fatigue syndrome, low-dose hydrocortisone reduces fatigue levels in the short term. Treatment for a longer time and follow-up studies are needed to find out whether this effect could be clinically useful. “
• ” The anti-inflammatory effect of cortisone at an adequate dose has, to my knowledge, not been investigated so far. I am left with the impression that the potential effect of cortisone on myalgic encephalopathy / chronic fatigue syndrome has been rejected on the basis of three studies that have investigated only low-dose hydrocortisone therapy of an hypocortisolism presumed and which are believed to have too little potency to conclude. with something. ” [2016]

Bottom Line

This drug is prescribed for ulcerative colitis, Crohn’s disease and is known to impact the entire body. We know that it inhibits many bacteria (list here).

Checking predictions on this page, it is predictive to help ME/CFS without IBS, but worsen ME/CFS with IBS and basic CFS. On the flip side, it is predictive to help IBS. The predictions are based on a naive estimate of it’s impact on the many reported shifts with these conditions.

I have often been asked that question. The general answer is “it depends”. This post gives you a science based answer.

Enter the probiotic Mixture

Once you are logged in, a new item appears on the menus as shown below

On the next screen enter a name (including the provider), for example

Now go back and get your suggestions.. What you just entered will be shown,

Bottom Line

A simple process. If you have your thryve (or other providers) custom probiotic mixtures handy, run them thru add add the results as a comment on this page.

A reader asked me to compile a list of of published studies and articles on the use of antibiotics with ME/CFS. Note that with gut dysbiosis as the model, the choice of antibiotics may depend on the details of the dysbiosis (this a 16s or shotgun GI report is suggested. Xenogene.es offers excellent reports).

At the Whittemore Peterson Institute (WPI) is a non-profit medical research institute dedicated to the support of those with a spectrum of neuro-immune diseases (NIDs) including: myalgic encephalomyelitis, (ME), fibromyalgia, and similar complex chronic diseases of the immune system and the brain. Dr. De Meirleir earned his medical degree from the Vrije Universiteit Brussel in 1977, and completed an internal medicine residency in the Department of Internal Medicine, University Hospital of Vrije Universiteit Brussel. His current research focuses on a subgroup of ME patients who show evidence of chronic bacterial infection and gut dysbiosis. These patients are responding to specific antibiotic/ probiotic therapy.

http://nvcbr.org/portfolio-items/kennydemeirleir/

• Azithromycin in Chronic Fatigue Syndrome (CFS), an Analysis of Clinical Data (2006) ” Results: Of the 99 patients investigated, 58 reported a decrease in the symptoms by the use of azithromycin.”
• Open-label Pilot for Treatment Targeting Gut Dysbiosis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Neuropsychological Symptoms and Sex Comparisons (2018) ” Large treatment ( alternate weeks of Erythromycin (400 mg of erythromycin as ethyl succinate salt) twice daily ) effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency).  “
• Chronic Fatigue Syndrome After Q Fever (2007) ” After 4-12 months they developed post-Q-fever fatigue syndrome and were treated with intracellular active antibiotics (fluoroquinolones and tetracycline) for 3-12 months. Efficacy of the treatment was observed in two patients, but in one patient the results were not encouraging. “
• Sleep Quality and the Treatment of Intestinal Microbiota Imbalance in Chronic Fatigue Syndrome: A Pilot Study (2015) ” Participants were administered erythromycin 400 mg b.d. for 6 days… Short term antibiotic treatment appears to be insufficient to effect sustainable changes in the gut ecosystem in most CFS participants. Some improvement in objective sleep parameters and mood were found in participants with reduced levels of gram-positive gut microbiota after antibiotic treatment, which is encouraging. Further study of possible links between gut microorganisms and sleep and mood disturbances is warranted. “
• On the Question of Infectious Aetiologies for Multiple Sclerosis, Schizophrenia and the Chronic Fatigue Syndrome and Their Treatment With Antibiotics (2009)… ” in the beginning of 2007 two female patients suffering from severe and long standing chronic fatigue syndrome were added. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement. “
• Mycoplasma Blood Infection in Chronic Fatigue and Fibromyalgia Syndromes (2003) ” Most patients with CFS/FMS who have mycoplasma infection appear to recover and reach their pre-illness state after long-term antibiotic therapy with doxycycline, and the infection can not be detected after recovery.  “
• ” Dr. Nicolson suggests long-term antibiotic treatment with drugs such as doxycycline, cyprofloxacin, azithromycin, or clarithromycin. By long-term he means a continuous 6-month course of antibiotics followed by multiple 6-week cycles. The extended antibiotic treatment is needed because of “the intracellular locations of mycoplasmas… the slow-growing nature of these infections, their inherent insensitivity to most antibiotics and the persistence of the infections in metabolically inactive forms.” [Src]
  • High prevalence of Mycoplasma infections among European chronic fatigue syndrome patients. Examination of four Mycoplasma species in blood of chronic fatigue syndrome patients (2002)
• Role of Rickettsiae and Chlamydiae in the Psychopathology of Chronic Fatigue Syndrome (CFS) Patients (2000) Results: Group one: 79.5% good and very good results; 4.1% fairly good; 16.4% failed. Group two: 82.3% good and very good results; 2.5% fairly good; 15.2% failed. … All of the Dr. Bottero’s therapeutic results are confirmed since 1991 by Dr. Cecile Jadin of Randburg (South Africa) for more than 3000 CFS and other psychopathological states (300): Sydney 98 CFS Conference, Australia.

A treatment plan (Cecile Jadin’s is similar)

Treatment with antibiotics is difficult because drugs have to penetrate the host cell wall as well as the intracellular organisms. Treatment needs to be prolonged and pulsed, because of continual replication of the intracellular forms. Until adequate diagnostic facilities are readily available treatment needs to be in two stages: the first stage, which is diagnostic, involves the use of two long-term bacteriostatic antibiotics for 6 weeks, and the second, meant to be curative, involves the introduction of a third bactericidal antibiotic.

One possible choice of antibiotics for the first stage is a combination of Doxycycline and Azithromycin. Initially, the Doxycyline needs to be given alone in low dosage for two weeks, because of the risk of a Herxheimer reaction resulting from the release of toxins by damaged bacteria. Such reactions are usually mild and short-lived. If stable after two weeks, Azithromycin in low dosage is added for 4 weeks. Roxithromycin can be used in place of Azithromycin. . Improvement of symptoms, or the occurrence of a Herxheimer reaction, confirms the diagnosis.

Chronic fatigue syndrome or myalgic encephalomyelitis (2007) in British Medical Journal

From Published Books

Bottom Line

There is a high success rate reported with antibiotics. Recent research suggests that the failures may be selection of inappropriate antibiotics for the person’s specific gut dysbiosis. IMHO, a 16s or shotgun (Xenogene) microbiome report should be done and carefully analyzed prior to selecting the various antibiotics needed.

The microbiomePrescription site supports evaluation of antibiotics against a microbiome, as well as other prescription drugs.

Unfortunately, there has been only one comprehensive study done, so relative ranking may not apply for many samples (i.e. do a show all and scan for the ones that are most acceptable)

With hand-picking against ME/CFS profiles, results can get quite good. All of the antibiotics involved with prior successful treatment were listed.