Book Review: Toxic by Dr. Neil Nathan Is a Must-Read!

This superb book by Dr. Neil Nathan is a must-read for anyone suffering from mold toxicity, Lyme disease, multiple chemical sensitivities, chronic environmental illness, fibromyalgia, or myalgic encephalomyelitis/chronic fatigue syndrome. These difficult-to-treat diseases, which are often ignored or dismissed by mainstream medical practitioners, present a challenge to any physician, but it is a challenge that Dr. Nathan meets with in-depth knowledge, compassion, and common sense. In addition to the above diseases, Dr. Nathan also discusses the important role of mast cell activation, porphyria, and carbon monoxide, the three “elephants in the room.” His discussion of mast cell activation syndromes, which he finds in half of his patients suffering from unusual sensitivities, is particularly enlightening. He not only presents symptoms and signs to look for, but how MCAS is diagnosed and treated.

Dr. Nathan  brings his decades of experience to bear by explaining how toxins can interact to produce a multiplicity of disease states simultaneously. His clear and concise explanation for how environmental diseases become chronic is the best I have ever read. In some individuals, toxins are not eliminated through normal channels. Instead, the toxins, once they are attached to bile, are recycled, sent back to the liver when the bile is reabsorbed in the large intestine. This would account for why people with exposure to mold, for example, do not recover after a single course of treatment.

People with any of the illnesses covered in this book will be delighted to find detailed descriptions of how Dr. Nathan and other experts in this field treat these diseases. Not only does Dr. Nathan offer a treatment blueprint for each disease, he provides many additional resources, as well as direct commentary by expert physicians. His bottom line is that it is not enough to kill infections, or rely on strict avoidance. Toxins must be safely removed. The underlying theme, namely chronic inflammation, is addressed in this context. Dr. Nathan’s chapters on” rebooting” as a model for treatment and healing are a goldmine for people seeking an effective long-term treatment strategy.

One of the most valuable takeaways from this book is Dr. Nathan’s sensible approach. Dr. Nathan takes “First, do not harm” seriously. Patients with environmental illnesses can be exquisitely sensitive, which means treatments must be started at miniscule doses, and proceed slowly. If a patient feels worse, stop. Why insist that a patient “push through” if it only leads to increased symptoms? This is so sensible, and so obvious, I am left wondering why more physicians don’t adopt a more gradual approach to treating environmental diseases.

Dr. Nathan’s conversational writing style makes this book a pleasure to read, despite the complexity of the topic. He increases the accessibility to lay readers by including helpful diagrams and graphics that convey information visually, as well as side notes that neatly summarize points. This is a book to keep by your bedside. You will want to refer to it often.

Available on Amazon and Barnes&Noble.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Comprehensive Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology that is recognized by the World Health Organization (WHO) and the United States Center for Disease Control and Prevention (US CDC) as a disorder of the brain. The disease predominantly affects adults, with a peak age of onset of between 20 and 45 years with a female to male ratio of 3:1. Although the clinical features of the disease have been well established within diagnostic criteria, the diagnosis of ME/CFS is still of exclusion, meaning that other medical conditions must be ruled out.

The pathophysiological mechanisms are unclear but the neuro-immuno-endocrinological pattern of CFS patients gleaned from various studies indicates that these three pillars may be the key point to understand the complexity of the disease. At the moment, there are no specific pharmacological therapies to treat the disease, but several studies’ aims and therapeutic approaches have been described in order to benefit patients’ prognosis, symptomatology relief, and the recovery of pre-existing function.

This review presents a pathophysiological approach to understanding the essential concepts of ME/CFS, with an emphasis on the population, clinical, and genetic concepts associated with ME/CFS.

Source: Cortes Rivera M, Mastronardi C, Silva-Aldana CT, Arcos-Burgos M, Lidbury BA. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Comprehensive Review. Diagnostics (Basel). 2019 Aug 7;9(3). pii: E91. doi: 10.3390/diagnostics9030091. https://www.ncbi.nlm.nih.gov/pubmed/31394725

Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test

Abstract:

The mitochondrial energy score (MES) protocol, developed by the Myhill group, is marketed as a diagnostic test for chronic fatigue syndrome/Myalgic Encephalomyelitis (CFS/ME). This study assessed the reliability and reproducibility of the test, currently provided by private clinics, to assess its potential to be developed as an NHS accredited laboratory test.

We replicated the MES protocol using neutrophils and peripheral blood mononuclear cells (PBMCs) from CFS/ME patients (10) and healthy controls (13). The protocol was then repeated in PBMCs and neutrophils from healthy controls to investigate the effect of delayed sample processing time used by the Myhill group.

Experiments using the established protocol showed no differences between CFS/ME patients and healthy controls in any of the components of the MES (p ≥ 0.059). Delaying blood sample processing by 24 hours (well within the 72 hour time frame quoted by the Myhill group) significantly altered many of the parameters used to calculate the MES in both neutrophils and PBMCs. The MES test does not have the reliability and reproducibility required of a diagnostic test and therefore should not currently be offered as a diagnostic test for CFS/ME. The differences observed by the Myhill group may be down to differences in sample processing time between cohorts.

Source: Tomas C, Lodge TA, Potter M, Elson JL, Newton JL, Morten KJ. Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test. Sci Rep. 2019 Aug 7;9(1):11464. doi: 10.1038/s41598-019-47966-z. https://www.ncbi.nlm.nih.gov/pubmed/31391529

Suggested pathology of systemic exertion intolerance disease: Impairment of the E3 subunit or crossover of swinging arms of the E2 subunit of the pyruvate dehydrogenase complex decreases regeneration of cofactor dihydrolipoic acid of the E2 subunit

Abstract:

Systemic Exertion Intolerance Disease (SEID) or myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) has an unknown aetiology, with no known treatment and a prevalence of approximately 22 million individuals (2%) in Western countries. Although strongly suspected, the role of lactate in pathology is unknown, nor has the nature of the two most central symptoms of the condition – post exertional malaise and fatigue. The proposed mechanism of action of pyruvate dehydrogenase complex (PDC) plays a central role in maintaining energy production with cofactors alpha-lipoic acid (LA) and its counterpart dihydrolipoic acid (DHLA), its regeneration suggested as the new rate limiting factor.

Decreased DHLA regeneration due to impairment of the E3 subunit or crossover of the swinging arms of the E2 subunit of PDC have been suggested as a cause of ME/CFS/SEID resulting in instantaneous fluctuations in lactate levels and instantaneous offset of the DHLA/LA ratio and defining the condition as an LA deficiency with chronic instantaneous hyperlactataemia with explicit stratification of symptoms. While instantaneous hyperlactataemia has been suggested to account for the PEM, the fatigue was explained by the downregulated throughput of pyruvate and consequently lower production of ATP with the residual enzymatic efficacy of the E3 subunit or crossover of the E2 as a proposed explanation of the fatigue severity. Functional diagnostics and visualization of instantaneous elevations of lactate and DHLA has been suggested.

Novel treatment strategies have been implicated to compensate for chronic PDC impairment and hyperlactataemia. This hypothesis potentially influences the current understanding and treatment methods for any type of hyperlactataemia, fatigue, ME/CFS/SEID, and conditions associated with PDC impairment.

Copyright © 2019. Published by Elsevier Ltd.

Source: Bohne VJB, Bohne Ø.Suggested pathology of systemic exertion intolerance disease: Impairment of the E3 subunit or crossover of swinging arms of the E2 subunit of the pyruvate dehydrogenase complex decreases regeneration of cofactor dihydrolipoic acid of the E2 subunit. Med Hypotheses. 2019 Sep;130:109260. doi: 10.1016/j.mehy.2019.109260. Epub 2019 Jun 14. https://www.ncbi.nlm.nih.gov/pubmed/31383326

Relationship satisfaction, communication self-efficacy, and chronic fatigue syndrome-related fatigue

Abstract:

RATIONALE: Relationship dissatisfaction has been linked with worse health outcomes in many patient populations, though the mechanism(s) underlying this effect are unclear. Among patients with chronic fatigue syndrome (CFS) and their partners, there is evidence for a bi-directional association between poorer relationship satisfaction and the severity of CFS-related fatigue.

OBJECTIVE: Here, we hypothesized that relationship dissatisfaction negatively impacts fatigue severity through greater depression and less patient satisfaction about communication about symptoms to partners.

METHOD: Baseline data were drawn from diagnosed CFS patients (N = 150) participating in a trial testing the efficacy of a stress management intervention. Data derived from fatigue severity (Fatigue Symptom Index, FSI), depression (Center for Epidemiologic Survey-Depression, CES-D), relationship quality (Dyadic Adjustment Scale, DAS) and communication satisfaction (Patient Symptom Disclosure Satisfaction, PSDS) questionnaires were used for bootstrapped indirect effect analyses using parallel mediation structural equation modeling in Mplus (v8). Age and BMI were entered as covariates.

RESULTS: Greater relationship satisfaction predicted greater communication satisfaction (p < 0.01) and lower CES-D scores (p < 0.01), which in turn were each significantly related to greater fatigue severity (p < 0.05). Tests of the indirect paths indicated that relationship satisfaction had a significant effect on fatigue severity through both constructs, but primarily via depression. There was no direct association between relationship satisfaction and fatigue severity after the intermediate variables (depression, communication satisfaction) were included in the model.

CONCLUSION: Results highlight the importance of considering depression and communication-related factors when examining the effects of relationship satisfaction on CFS symptoms such as fatigue. Further mechanism-based, longitudinal research might identify relationship-related mediating variables that can be targeted therapeutically.

Copyright © 2019. Published by Elsevier Ltd.

Source: Milrad SF, Hall DL, Jutagir DR, Lattie EG, Czaja SJ, Perdomo DM, Ironson G, Doss BD, Mendez A, Fletcher MA, Klimas N, Antoni MH. Relationship satisfaction, communication self-efficacy, and chronic fatigue syndrome-related fatigue. Soc Sci Med. 2019 Jul 16;237:112392. doi: 10.1016/j.socscimed.2019.112392. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31377502

Factors associated with work status in chronic fatigue syndrome

Abstract:

BACKGROUND: Work status in people with chronic fatigue syndrome (CFS) has not been extensively researched.

AIMS: To explore occupational outcomes in patients with CFS by socio-demographic, well-being and disease characteristics.

METHODS: We assessed cross-sectional data from patients attending a UK specialist CFS treatment service between 1 January 2007 and 31 December 2014. The main outcome was self-reported current employment status: currently in employment, temporarily interrupted employment or permanently interrupted employment. Other variables included sex, age, ethnicity, education, marital status, CFS duration, fatigue severity, anxiety, depression, activity limitations and functional impairment. We used multinominal logistic regression models to identify factors associated with current work status.

RESULTS: Two hundred and seventy-nine (55%) patients were currently working, with 83 (16%) reporting temporarily interrupted employment and 146 (29%) stopping work altogether. Factors strongly associated with permanently interrupted employment were older age (adjusted odds ratio (AOR) 5.24; 95% CI 2.67-10.28), poorer functioning (AOR 6.41; 95% CI 3.65-11.24) and depressive symptoms (AOR 2.89; 95% CI 1.82-4.58) compared to patients currently working. Higher educated patients (AOR 0.60; 95% CI 0.37-0.97) and being in a relationship (AOR 0.34; 95% CI 0.21-0.54) were associated with being currently employed. Anxiety symptoms were common; 230 patients (45%) met caseness criteria.

CONCLUSIONS: Many patients with CFS were not working. This was exacerbated by high levels of depressive symptoms. Health professionals should assess co-morbid mental health conditions and consider treatment options when patients with CFS present themselves. The early involvement of occupational health practitioners is recommended to maximize the chances of maintaining employment.

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Source: Stevelink SAM, Fear NT, Hotopf M, Chalder T. Factors associated with work status in chronic fatigue syndrome. Occup Med (Lond). 2019 Aug 3. pii: kqz108. doi: 10.1093/occmed/kqz108. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31375832

Symptom frequency and development of a generic functional disorder symptom scale suitable for use in studies of patients with irritable bowel syndrome, fibromyalgia syndrome or chronic fatigue syndrome

Abstract:

OBJECTIVES: To describe the extent to which irritable bowel syndrome (IBS), fibromyalgia syndrome (FMS), and chronic fatigue syndrome (CFS) exhibit symptom overlap, and to validate a patient-derived, generic symptom questionnaire.

METHODS: A patient-derived 61-item symptom-frequency questionnaire was completed by participants recruited through IBS, FMS and CFS self-help websites. Principal axis factor analysis with oblimin rotation was performed separately for those reporting an IBS, FMS or CFS diagnosis.

RESULTS: Questionnaires were completed by 1751 participants of whom 851 reported more than one of the three diagnoses. Stomach pain on at least a weekly basis was reported by 79% of IBS, 52% of FMS, and 43% of CFS single diagnosis participants. Pain increasing the day after activity was reported by 32% of IBS, 94% of FMS, and 85% of CFS single diagnosis participants. Waking still tired at least once weekly was reported by 75% of IBS, 97% of FMS, and 95% of CFS single diagnosis participants. Exploratory factor analysis produced consistent results across all three diagnostic groups, the 61 items loading on 12 correlated factors with a single higher order factor on which all items loaded. Frequency analysis led to the rejection of one item (cold sores on or near lips), and freeform reporting by participants of additional symptoms identified an additional five, namely, restless legs, hair loss/brittle hair/thinning, dizziness/balance problems, blurred vision and urination problems.

CONCLUSIONS: IBS, FMS and CFS are polysymptomatic spectrum disorders with a wide range of overlapping symptoms, many of which are unrelated to diagnostic criteria. Frequency analysis and factor analysis confirm the validity of using the same questionnaire across different diagnostic categories. The 65-item general symptom questionnaire (GSQ-65) is a valid generic symptom scale suitable for assessing the many different symptoms of people with IBS, FMS and CFS.

Source: Hyland ME, Bacon AM, Lanario JW, Davies AF. Symptom frequency and development of a generic functional disorder symptom scale suitable for use in studies of patients with irritable bowel syndrome, fibromyalgia syndrome or chronic fatigue syndrome. Chronic Dis Transl Med. 2019 Jun 24;5(2):129-138. doi: 10.1016/j.cdtm.2019.05.003. eCollection 2019 Jun. https://www.sciencedirect.com/science/article/pii/S2095882X18300987?via%3Dihub (Full article)

A perspective on causation of the chronic fatigue syndrome by considering its nosology

Abstract:

The causes of chronic fatigue syndrome (CFS) remain unknown, with many failures to replicate new findings. This may be because the condition is hard to diagnose, difficult to classify, or because of its heterogeneous nature. Authors have problems in differentiating CFS from myalgic encephalomyelitis (ME), which leads many to label it as a hybrid CFS/ME or ME/CFS. Attempts to validate the many published criterion-based definitions have ended in failure. The International Classification of Diseases provide several different descriptions to choose from, although the latest 11th edition has narrowed this down. This paper describes conventional attempts to define and classify the illness, suggesting that this may be what leads to a failure to replicate putative causes. The approach to CFS/ME may require a shift in the assumption that the illness is homogeneous. An alternative approach is provided by studies suggesting that the condition is heterogeneous. ‘

CONCLUSION: The way forward may be to be over-inclusive regarding the diagnosis as a first step, while subdividing the condition into likely subgroups as a means of finding valid and reliable associations with potential causes. Studies of aetiology must involve prospective designs since cross-sectional studies cannot inform either aetiology or pathophysiology.

© 2019 John Wiley & Sons, Ltd.

Source: White PD. A perspective on causation of the chronic fatigue syndrome by considering its nosology. J Eval Clin Pract. 2019 Aug 1. doi: 10.1111/jep.13240. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31373106

General theory of inflammation: patient self-administration of hydrocortisone safely achieves superior control of hydrocortisone-responding disorders by matching dosage with symptom intensity

Abstract:

Objective: To determine if patient self-administration of hydrocortisone will safely achieve superior symptom control for all hydrocortisone-responding disorders as it does for Addison’s disease and rheumatoid arthritis.

Methods: Two thousand four hundred and twenty-eight participants with hydrocortisone-responding disorders were brought to a minimum symptom state using daily administered hydrocortisone tablets in a 24-week, open study. Thereafter, participants used 5-day, low-dose hydrocortisone regimens to quench subsequent disorder exacerbations (flares) to maintain the minimum symptom state. Stressors such as emotional traumas, infections, allergies, and injuries were minimized to reduce disorder intensity, hydrocortisone consumption, and participant discomfort.

Results: Two thousand fifteen participants, 601 with fibromyalgia, 579 with osteoarthritis, 246 with rheumatoid arthritis, 226 with undifferentiated arthritis, 75 with back pain, 51 with Parkinson’s disease, 44 with polymyalgia rheumatica, 25 with neuropathy, 25 with chronic fatigue syndrome, 25 with dementia, 21 with migraine headache, 19 with multiple sclerosis, and 78 with other disorders completed the 24-week study to achieve a composite average symptom improvement of 76% with equal response rates. The participants averaged ingesting 12 mg of hydrocortisone per day. No significant adverse reactions were observed.

Conclusions: Patient self-administration of hydrocortisone safely achieves superior symptom control for 38 hydrocortisone-responding disorders at equal rates and symptom improvements to confirm and amplify an earlier double-blind study finding on rheumatoid arthritis. These results are consistent with the body having an inflammation control system and chronic inflammation being a disorder unto itself with differing symptoms sets dependent on its location.

Clinical Trials Government Identifier: NCT03558971.

Source: Irwin JB, Baldwin AL, Stenberg VI. General theory of inflammation: patient self-administration of hydrocortisone safely achieves superior control of hydrocortisone-responding disorders by matching dosage with symptom intensity. J Inflamm Res. 2019 Jun 13;12:161-166. doi: 10.2147/JIR.S195165. eCollection 2019. https://www.dovepress.com/general-theory-of-inflammation-patient-self-administration-of-hydrocor-peer-reviewed-article-JIR (Full article)

The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating noncommunicable disease brandishing an enormous worldwide disease burden with some evidence of inherited genetic risk. Absence of measurable changes in patients’ standard blood work has necessitated ad hoc symptom-driven therapies and a dearth of mechanistic hypotheses regarding its etiology and possible cure. A new hypothesis, the indolamine-2,3-dioxygenase (IDO) metabolic trap, was developed and formulated as a mathematical model.

The historical occurrence of ME/CFS outbreaks is a singular feature of the disease and implies that any predisposing genetic mutation must be common. A database search for common damaging mutations in human enzymes produces 208 hits, including IDO2 with four such mutations. Non-functional IDO2, combined with well-established substrate inhibition of IDO1 and kinetic asymmetry of the large neutral amino acid transporter, LAT1, yielded a mathematical model of tryptophan metabolism that displays both physiological and pathological steady-states. Escape from the pathological one requires an exogenous perturbation.

This model also identifies a critical point in cytosolic tryptophan abundance beyond which descent into the pathological steady-state is inevitable. If, however, means can be discovered to return cytosolic tryptophan below the critical point, return to the normal physiological steady-state is assured. Testing this hypothesis for any cell type requires only labelled tryptophan, a means to measure cytosolic tryptophan and kynurenine, and the standard tools of tracer kinetics.

Source: Alex A. Kashi, Ronald W. Davis and Robert D. Phair. The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS. Diagnostics 2019, 9(3), 82; https://doi.org/10.3390/diagnostics9030082 https://www.mdpi.com/2075-4418/9/3/82/htm (Full article)