Dr Kharrazian chronic fatigue and pain syndromes course

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Don't be !!! It made me smile on a day when there hasn't been much for me to smile about ....

My bad ...... It was an easy mistake, since you were responding to my quote in your post .....

Nothing I wrote was "emotional". It was all a pretty straight-up statement of facts ....
I think it's important to underline that I really like you and your posts so maybe I felt a bit offended and that emotional part was mine instead of yours. :)
 

Shanti1

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COURSE SUMMARY -
Dr Kharrazian chronic fatigue and pain syndromes course


There wasn’t anything in this course that isn’t discussed somewhere on the PR forum. The course was not specifically focused on ME/CFS and was a 2 day course with a huge amount of information. I put some of the info I thought PR members would be interested in below. If anyone wants more detail on something they see below, just ask.
This course addressed various fatigue syndromes including ME/CFS. More time was spent on non-ME fatigue than on ME/CFS. The diagnostic criteria presented for ME/CFS were the Canadian Consensus Criteria and Dr. K did acknowledge the severity and complexity of the condition, stating that the goal as a practitioner was to help the patient have more good days than bad days. He contrasted this with non-ME fatigue where patients typically recover once the underlying cause of the fatigue has been addressed. I appreciated his review of this paper Review of this this paper Evidence on Major ME/CFS Symptoms and Manifestations, which contains graphs on the various symptoms of ME/CFS patients compared to healthy controls. Here is an example of one of the graphs:
1632775358409.png
Dr. Kharrazian identified some of the triggers for ME/CFS discussed on this forum (Viruses and other pathogens, mold, toxins, traumatic brain injury), but he is not an expert in ME/CFS and I was dismayed that he really only advocated testing for EBV stating that you can look indefinitely for the pathogen and not find it. However, in the case studies he presented, he did test for EBV, CMV, HHV6 and Lyme and co-infections.
His treatment suggestions for non-ME fatigue involved identifying underlying mechanisms (thyroid, anemia, glycemic dysregulation, food sensitivities, SIBO, hormonal issues, adrenal concerns, sleep disorders etc). Of course, all of this needs to be addressed in the ME/CFS patient, but the difference is, the ME/CFS is still severely fatigued even after these have been addressed.
His treatment for ME/CFS mostly had to do with addressing the factors that disrupt mitochondrial function and improving mitochondrial function. My opinion was that the approach he outlined makes sense to try, but doesn’t seem to be impactful for many people. Many potential ME/CFS causes were not included and therapies discussed on this forum such as the use of antivirals, high dose thiamine, Oxymatrine, LDN, HBOT, IV saline, blood volume support, useful conventional meds, and many others, were not discussed.
I made two additional posts below:
Post 1- ME/CFS and Pain Syndrome treatment – this would be the most relevant info
Post 2- Everything else – Mitochondrial dysfunction and causes, Differential diagnosis of fatigue, Important testing, mechanisms behind chronic pain
 

Shanti1

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POST 1 -ME/CFS and Pain Syndrome Treatment
  • DIET: Because of multiple food sensitivities, association with autoimmunity, neuroinflammation, and anaerobic glycolysis with lactate production (Warburg effect) he suggests the use of an Autoimmune Paleo Diet. Consider an autoimmune paleo diet (low carb diet that also eliminates lectins, dairy and nightshades, grains, soy). Basically you can eat some vegetables, healthy fats, meats, eggs (if tolerated), limited fruits. The diet has the following objectives:
    • Remove the most common food allergies
    • Stabilize blood glucose and insulin
    • Promotes ketosis- ketones tend to be anti-inflammatory to the brain/CNS
    • Ketogenic diet may help because ketones and fatty acids bypass glycolysis and the pyruvate dehydrogenase enzyme, therefore greatly reducing lactate production. Disordered immunity and ROS will down regulate the pyruvate dehydrogenase enzyme.
    • (My comment: I have seen comments on PR where people feel worse on a ketogenic diet. This would make sense if the mitochondria is shut down at more than just the pyruvate dehydrogenase enzyme because they you wouldn’t get energy from glycolysis or oxphos)
1632775676550.png
Paper: Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Caloric restriction, fasting, and ketogenic diets
  • Lifestyle: Pacing, deep rest, removal of toxins and mold exposure etc
  • Nutrient support: Basically, making sure you have the co-factors for mitochondrial function, that you have strong antioxidant support to combat ROS from dysfunctional mitochondria, supporting mitochondrial division, supporting energy production using mitochondrial substrates/electron doners, turning on aerobic respiration (oxidative phosphorylation). See chart below:
1632775723512.png

  • D-Ribose-Simple sugar source for mitochondrial energy. Does not raise glucose or insulin, can lower blood glucose
  • Beta-Hydroxy Butyrate- used as immediate fuel in fatty acid oxidation pathways
  • Medium Chain Triglycerides- Immediately converted to ketones and utilized for energy
  • Butyrate- a short chain fatty acid immediately used for energy
  • Acetyl L-Carnitine- Transports Fat into the Mitochondria to be used for energy
  • CoQ10-Transfers electrons from complex I and II to complex III
  • Nicotinamide riboside- encourages production of NAD to support ATP levels
  • Creatine monohydrate- A high energy substrate that absorbs hydrogen ions in muscles leading to increased ATP levels.
  • Water- Necessary precursor H2O for energy metabolism
DCA- Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial. Supports a shift in metabolism from glycolysis to oxidative phosphorylation.
Pain and inflammation:
Top suggestions:

  • 1-5g of quercetin (mast cell stabilization and decrease leukotriene levels)
  • High dose fish oil 5-10g (decrease inflammatory prostaglandins)
  • Turmeric extract 500-3,000mg (Nf-KB)
  • Resveratrol 500-2,000mg (Nf-KB)
  • Liposomal glutathione, NAC 500mg-2000mg (powerful antioxidants)
  • Diet-No sugar, partially hydrogenated fat, processed food. Increase fatty fish and plant omega 3, olive oil, avocado oil, and antioxidant foods. Consider Autoimmune Paleo diet. Study
  • Ice applications as needed/ cold immersion / cold showers
Identification of Chemically Mediated Pain Triggers
Inflammation-
Tests- CRP, ESR, Cytokines
Prostaglandins + Leukotrienes (Fat based inflammatory mediators-act locally)
  • Test- Fatty Acid Profile- Omega 3, 6, 9 Arachadonic Acid Balance
  • Want to increase Omega 3 and GLA- This will favor the anti-inflammatory prostaglandin pathway
  • Person may have unhealthy skin, hair and nails
  • Therapy= high dose Fish Oils 5-10g, GLA, EPO
Histamine
  • Test serum histamine, total IgE, Food IgE and Environmental (pollen mold) IgE, tryptase
  • histamine and IgE will amplify pain syndromes. Screen for IgE and histamine reactions like seasonal and food allergies, high eosinophils, hives, flushing, dermatographia, migrains, itchy skin/eyes, acute GI reactions to food, nasal congestion, eczema, rashes
  • Therapy= 1-5 g of Quercetin, Baicalein, Luteolin, Stinging Nettle, Mangosteine, butterbur Vit C, low histamine diet, address IgE allergies, H1 and H2 histamine blockers
Inflammatory Cytokines (protein-based mediators- can act locally and systemically)-
  • Test for with cytokine panel / T+B cell profiling
  • Systemic pain, brain fog
  • Turmeric, resveratrol, systemic enzymes (Sarapeptase, nattokinase)
Free Radicals – worse with oxidative stress (chemicals and exercise), may appear older than their age
  • Urinary or serum oxidative stress functional medicine tests
  • Therapy- Consume high antioxidant foods, Antioxidant supplementation = liposomal Glutathione, NAC, SOD, resveratrol, curcumin, ALA, Green tea, rutin
  • Hydrogen tablets in water for immediate antioxidant need before and after activity
Hypoxia-
  • Test Oxygen Saturation, Sleep study, CBC
  • Poor circulation, muscle pain/burning, respiratory illness
  • Therapy=Activate circulation and endothelial NO, Vinpocetine, Hawthorn extract, ginkgo, beet root, feverfew, butcher’s broom. Address underlying issue (sleep apnea, lung disease) May need oxygen or HBOT
Insulin Surges
  • Test is Glucose Tolerance Test or fasting insulin and glucose.
  • Fatigue, sugar cravings after meals. High sugar meals increase pain, sleepy after meal.
  • Therapy= Diet, Berberine, cinnamon (with acetaldehyde removed), resveratrol, turmeric, lipoic acid, chromium, nopal, fiber, magnesium.
Glycosylated End Products- Promoted by high blood glucose. Mediate inflammation through RAGE receptor and immune activation.
  • Test HbA1C and Fructosamine
  • Worse after eating foods highest in AGEs, high blood sugar
  • Therapy=Glycation blockers (benzothiazine, Carnosine), Antioxidants (resveratrol, glutathione, turmeric, NAC, ALA, Centella asiatica, pycnogonid), control blood sugar
Adipokines from obesity- Fat makes inflammatory mediators including IL-6 (which increases CRP). People who are overweight often have elevated CRP.
  • Intermittent fasting, restore insulin sensitivity, weight management strategies
Catecholamines- Adrenalin and nor-adrenalin aka epinephrine and nor-epinephrine- our acute stress response hormones/neurotransmitters
  • Urinary catecholamine test
  • Anxiety, sympathetic overdrive
  • Theanine, gaba supporting nutrients, Lavender soft gels, skullcap, passionflower, kava
Substance P from Neurologic Inflammation
  • Substances made by damaged nerves that mediates pain
  • Therapy=dampen sympathetic response
Low Cortisol Patterns-
  • Salivary or serum cortisol
  • Results in inability to dampen inflammatory response
  • Symptoms-tendency toward hypoglycemia, stress intolerance, difficulty waking in AM, craving stimulants
  • Therapy= adrenal support, stabilize blood sugar (small meals with proteins and fats), consume enough salt, licorice root, B-Vit (esp B6), Mg, Vit C, branch chain amino acids, adaptogens (rhodiola, ashwagandha), adrenal glandular, improve sleep
Microbiome metabolites- LPS and other metabolites resulting in endotoxemia and systemic inflammation
  • Test- intestinal permeability panel (cyrex labs)
  • LPS
  • Symptoms- bloating, multiple food sensitivities, brain fog, signs of maldigestion
  • Therapy- Short Chain Fatty Acids, L-glutamine, vit D, Probiotics, Nacetyl glucosamein, Zinc carnosine, DGL, slippery elm etc, diet, enzymes, support HCL – He has an entire separate course on this
Sleep
  • Weighed blankets, esp with anxiety
  • Melatonin (esp for ME/CFS), white noise machine, CBD, Valerian, Kava, Passion flower, Magnesium citrate and taurine, glycine, Magnolia extract
  • Address nocturnal hypoglycemia, sleep apnea, cortisol concerns, nocturia, TBI
 

Shanti1

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POST 2
Introduction to Chemical and Physiological Bioenergetics

  • The intro was a very detailed overview of normal mitochondrial function and acquired (environmentally induced as opposed to genetic) mitochondrial dysfunction (he stated that genetic mitochondrial disease does not significantly respond functional medicine)
  • Examples of inducers of mitochondrial pathology are to viral and other infections, microbiome derived toxins (H2S, NO, and others), hyperinsulinemia, medications, chemical toxins, biotoxins etc.
  • Cellular pathways of how each of the above change mitochondrial function were detailed and include:
    • Damaged electron transport (ETC) complexes-àmitochondrial uncoupling -à↑ ROS
    • Damaged mitochondrial DNA
    • Direct inhibition of Citric Acid Cycle and ETC enzymes/proteins
    • Decreased fission and mitophagy ((process by which mitochondrial segregate damaged mDNA in to one portion of the mitochondria and fission that portion for autophagy).
    • Increased glycolysis, decreased oxidative phosphorylation
    • Smaller mitochondria with fewer inner mitochondrial folds (cristae)
    • Less mitochondrial biogenesis and fusion
  • Went through the multiple ways mitochondrial dysfunction can impact the body:
    • Generalized low hormones (no energy to produce them), fatigue, microglial activation
    • Damaged mitochondria induce ungated activation of the cellular inflammasome which can lead to cellular and tissue damage and immune impairment (think nervous system damage and IBD).
1632775873316.png

Evaluation of a Patient Suffering from Fatigue
Broke fatigue into: Intermittent Fatigue, Chronic Fatigue, and ME/CFS (which he accurately described as complex, severe, difficult to treat). This section focused on a diagnostic workup, lab studies and physical exam.
  • Ruling out major disease (cancer, hep C, lung disease. CHF, etc)
  • Ruling out typical fatigue causes and identifying comorbidities (anemia, thyroid, dysbiosis, sleep disorders, metabolic syndrome, SIBO, dysbiosis, hypoglycemia, dietary sensitivities, autoimmune, toxin exposure, nutritional deficiencies etc)
1632775970327.png

  • He stated that organic acid profiles are not stable in ME/CFS patients and are not worth doing
Treatment Applications of non-ME fatigue syndromes
  • Outlined treatment for all of most common causes of non-ME fatigue – not going to go into details as it is too much info and not of primary relevance
Treatment Applications of non-ME fatigue syndromes
  • Outlined treatment for all of most common causes of non-ME fatigue – not going to go into details as it is too much info and not of primary relevance

The Connection between Fatigue, Depression, and Pain Syndromes
  • Mitochondrial dysfunction causes:
  • Ungated inflammasome activation resulting in inflammation and tissue damage
  • Nerve destruction from mitochondrial induced inflammation and microglial activation
  • Inflammation and damage to microcirculation impede oxygen deliveryà ↑lactic acid àpain
  • Decreased mitochondrial function in neurons-à Low ATP production àInability to support the Na+/K+ to create a health resting membrane potentialà lowered nerve activation thresholdà lowered pain tolerance and pain syndromes
Dr. K spent significant time reviewing pain pathways and brain regions of pain perception, including distinguishing between pain perception and the Amygdala, which experiences the emotional suffering of pain and activates arousal and sympathetic response. The amygdala pathways are hyperactive in people with PTSD.
The areas of the brain that inhibit/dampen pain (Prefrontal Cortex, Periaqueductal grey, nucleus auccubins) do not work effectively in the unhealthy/ATP starved brain
Central and peripheral sensitization creates repetitive nerve pathways (continued stimulation will strengthen a firing pathway, such tat it can continue to fire even after the removal of the stimulus.
When pain become chronic, it is no longer about removing a stimulus, you have to untangle a complex web
Paper on pain pathways in RA: Pain Mechanism in Rheumatoid Arthritis: From Cytokines to Central Sensitization
Paper: Central Hypersensitivity in Chronic Musculoskeletal Pain
Paper: The Acute to Chronic Pain Transition
Paper: Assessment and manifestation of central sensitization across different chronic pain conditions
 

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OMIGOD @Shanti1!!! .... this was so far beyond kind and thoughty of you that I'm digging around for words to express my appreciation for the enormous effort and amount of time that you put in, not just in sharing some of the ore important info in a course a lot of us could probably not afford right now, but wouldnt have the acuity to absorb and process, and I can't find any that are up to the task.

You are totally BOMB!!!! Thank you from the pit of my waxy little shriveled heart !!!!

I've bookmarked this so I can refer to it repeatedly down the line.

THANK YOU, again and again :woot::woot::woot: :thumbsup::thumbsup: :hug::hug::hug::hug::hug::hug: :love: !!!
 

Shanti1

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OMIGOD @Shanti1!!! .... this was so far beyond kind and thoughty of you that I'm digging around for words to express my appreciation for the enormous effort and amount of time that you put in
It is my pleasure Yippee :). I only hope you find something useful in that wall of text that would make any pwME glaze over, lol. It is only through the suggestions and knowledge of people on this forum that I've improved enough to write all of those notes! so I'm happy to contribute how I can :star:
 

wastwater

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I take eye drops for glaucoma called latanoprost it’s a prostaglandin analogue and works well for the eye
I wondered if there is a similar thing for the brain as glaucoma is increasingly seen as a brain eye condition
 
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@Shanti1 wow, this is amazing! Thank you so much for taking the time to write all of this out!

It is very detailed and organised, and far exceeded what I was hoping you'd share from the course!

I'll reread it tomorrow as I'm about to go to sleep now. It does seem to be like what you said, mostly things that have been covered here in the past. However, it's good to see that there are increasingly more clinicians taking this seriously and somewhat converging on a testing and treatment strategy.

It's also definitely helpful to go over the list and make sure we've all had these investigations done. I'm missing a few that I do want to get into in the next few months.

Thanks again for your hard work!
 

Learner1

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@Shanti1 Thank you so much for attending and taking such great notes.

My doctors and I have used much of his approach as you describe, which has steadily increased my function over time.

I did not see it in your summary, but want to point out that throwing all of this at someone may have mixed results, because much of this is most useful when done in phases, providing missing nutrients to optimize pathways, supporting immune system and endocrine system, going after infections, removing toxins, and then repairing mitochondria. I also didn't see spinal issues addressed, and for some people, this may be the key.

Also, I didn't see folate and B12 as mito nutrients, and they are critical for some. Folate is usually B9 in what I've read - did he use B4 for folate?

Thanks again!
 

Shanti1

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@Learner1 Dr. K didn't discuss spinal issues, just TBI. He did go over B12/folate as part of a general fatigue work-up, not specific to ME/CFS. He didn't go into methylation defects or B4. I agree that most people would want to add things in one at a time and see how they react. For me personally, I have tried everything on his mitochondrial support list except DCA and am too sensitive to all of it except vitamins/minerals, CoQ10, and turmeric (can't do isolated curcumin). But it seems others do benefit from such nutrients.
 

Learner1

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I agree that most people would want to add things in one at a time and see how they react.
In some cases, this can be helpful. However many things work in pathways with other cofactors, and just adding one thing without ensuring the cofactors are sufficient may cause that one thing not to do anything or for a reaction to happen without having the benefits of the co-factors. It is best to understand the pathways when is trying to support and ensure one is actually supporting those pathways.
For me personally, I have tried everything on his mitochondrial support list except DCA and am too sensitive to all of it except vitamins/minerals, CoQ10, and turmeric (can't do isolated curcumin).
Interesting that turmeric, which is high oxalate helps you, when curcumin which doesn't have oxalates, but is anti-inflammatory, a Cox-2 inhibitor and an antioxidant does not.

So, supporting your mitochondria with mitochondrial nutrients causes negative reactions? Have you looked into what's going into your mitochondria? Do you have some sort of heavy metal toxicity or other sort of toxicity?
But it seems others do benefit from such nutrients.
We certainly do.
 

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Shanti1

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In some cases, this can be helpful. However many things work in pathways with other cofactors, and just adding one thing without ensuring the cofactors are sufficient may cause that one thing not to do anything or for a reaction to happen without having the benefits of the co-factors. It is best to understand the pathways when is trying to support and ensure one is actually supporting those pathways.
Yes, we are all individual in this regard. For those of us who are very sensitive, one thing at a time is often the needed approach. I agree that a good understanding of glycolysis, kreb, ETC and many other pathways in the body is important in trying to figure out what may be going on and why we individually react the way we do.
Heavy metals are a good thought, but it hasn't shown up on the comprehensive testing I've had, similarly, organic pollutants and glyphosate testing do not show that the issue is there. Anyhow, despite being so super reactive to most supplements, I have found some select things that really help and have more to try in the wings.