CFS Is Likely Hypometabolism Triggered By Environmental Stress

[energyandstruct]

T1AM HYPOTHESIS OF ME/CFS

 

[energyandstruct]

That's what happened to me. It has been like a pendulum swinging in the opposite direction that is just recently starting to stabilize. I never imagined how much time it would take. @aguilaroja described it once in a thread a long time ago that I'd love to find again because it helped me understand what I have been experiencing as just part of the healing process.

would you say to watch out for these things as one applies the approach to raising metabolism to heal from cfs? thyroid has occasionally raised blood pressure but I think it was somewhat temporary and I don't want to get thrown into metabolic syndrome. a couple times I had to chug juice cause of how feverish and weak I felt from thyroid and I wonder if this was like temporarily induced diabetes

 

[Blossom]

would you say to watch out for these things as one applies the approach to raising metabolism to heal from cfs? thyroid has occasionally raised blood pressure but I think it was somewhat temporary and I don't want to get thrown into metabolic syndrome. a couple times I had to chug juice cause of how feverish and weak I felt from thyroid and I wonder if this was like temporarily induced diabetes

Some of my experience above was probably related to extreme family and work stress. I also think I persisted too long in eating some foods that didn't agree with me just because I didn't want to be orthorexic.
Go as slow as you need to-this is not a race.
I don't think we can completely control what happens as our body heals though. It's not always going to be a bed of roses but you should see steady improvement regardless of the odd bad day here and there. I believe patience and perseverance are necessary but if you notice a trend over weeks or months of feeling worse I'd recommend taking a break from supplements and meds altogether and regrouping.
Trust but also question your inner guidance at all times and be brutally honest with yourself.
No matter your struggle always try to find some enjoyment in each day. Simple things can go along way to restoring our strength. Gentle movement, time in nature, a bit of sunshine or connecting with a loved one are all examples of free things we can do to help feel refreshed. Most of all don't put your life completely on hold and forget to live.
That's just my hindsight is 20/20 two cents. :)

 

[Blossom]

believe patience and perseverance are necessary but if you notice a trend over weeks or months of feeling worse I'd recommend taking a break from supplements and meds altogether and regrouping.

I must clarify this statement. I'm not recommending people stop any medication prescribed by their physician/medical team without consulting with them first. I'm only referring to substances being used to boost metabolism that aren't part of medical treatment. I've found it beneficial to stop everything several times over the years as my health has improved to see what I actually need to continue and what is no longer necessary.

 

[DesertRat]

Dear Mr DesertRat
You appear to be a high temperature version of Rattus Experimentus that is to be found extensively on this forum. Greetings to you and welcome.
I am interested in your 3 years of doing thyroid...excellent temps and pulse and the 'absolutely no difference whatsoever in exercise tolerance; indeed it has gotten worse" because I have found similar in some afflicted by CFS and am ever am focused on what might be 'missing'.
This really is a punt, but I wonder if exercise triggers hypoglycaemia more readily for some reason in these people and from there symptoms seem to recur as a protective mechanism against endotoxin ingress and mitochondrial poisoning thereupon. Is cellular memory involved and how do you program the body not to panic and shut down?
Once again I don't have a very clear question here, I have just seen an improvement in some CFS people with metabolic strategies but if they go anywhere near 'overdoing' things, they're suddenly shot. Many of them have long periods without food and much physical/mental strain in their past history which would suggest considerable endotoxin damage and that there has been a strong use of cortisol to cope - as I always say, I have not met a CFS who was a 'slacker', usually quite the opposite. And their frustration with themselves at suddenly falling in a hole again is very real and tragic to observe.
If you have any thoughts, and indeed data on what your temps and pulse do on exercise, I would be pleased to hear them, thank you.
Sincerely
SheilaOceaniaRattus

Dear Sheila, my temps have been about 98 on waking (up to 0.5 degree lower if I sleep poorly and not enough) and over 99 during the day. But if I overexercise, I soon begin to feel cold. I don' have data but I am sure my temperature internally drops as my inability to keep warm becomes rather intense. It rarely happens these days, but usually, before this sense of going down, I feel hungry and I always drink OJ and eat something salty.
I got the CFS diagnosis in 1987, sudden onset, but in 2011, a very good doctor identified potential causes as CIRS-mold (see definition at www.survivingmold.com) and Lyme, which arose from a tick bite in 1993. Thus the Lyme was not causative, but the mold certainly could have been, and my most successful healing strategy has been "extreme mold avoidance." This would certainly be in line with Haidut's statement above about the role of environmental toxins in ME-CFS; I do not like fragrances, dryer sheets, pesticides, and herbicides in the air I breathe either, but they rarely have as debilitating an effect as mold does. The last 10 months I was living in a rental which had mold, trying to reduce it with air purification and lots of time in the fresh air outdoors, but my exercise tolerance declined from being able to walk around town normally and hike for 45 minutes last November when we arrived, to barely being able to walk a few blocks in September when we left.
I have tested the hypoglycemia theory by carrying a thermos of OJ with niacinamide and salt that I sip while walking, or sweet coffee milk also with niacinamide, and it never makes a difference. But what DOES help, I have found, is intermittent resting. So if I am on some kind of tour and we stop every 5 minutes of so to look at something, or if on my own in town and I stop at a cafe for a coffee, I can go on for much longer. The VO2 repeat studies show that something is happening with the oxidative metabolism and so by keeping myself from entering too deeply into anaerobic metabolism -- which is the killer for me! -- I increase stamina and tolerance.

 

[DesertRat]

I know I missed a few replies earlier, sorry... I have to get back to work. Regarding SEROTONIN ANTAGONISTS and ME-CFS, I read this and decided to finally try the cryptoheptadine I had from IdeaLabs. One drop the first night, two drops last night: bad bad results. Although I nearly doubled my food intake, I had cold hands much of the day (for the first time in a very loooong time) after the first dose. After the second, I had a pounding heart. I woke after a few hours (at 3 am), had to eat again, and had the pounding heart until nearly 5 am.
This reaction is almost identical to my reaction to certain kinds of mold! So clearly there is something going on in either in the cholingeric or serotinergic pathways -- since a serotonin antagonist aggravates it in the same way as the toxins. But then, I have had a similarly opposite response to Benadryal, with agitation, insomnia, and tachycardia too, so it could be related to the histamine response.
Ritchie Shoemaker has studied the inflammatory cascade from biotoxins (here is a link to the pathways: https://www.survivingmold.com/diagnosis/the-biotoxin-pathway
Everyone I know with ME/CFS who has been tested for CIRS has been positive for CIRS-Lyme, CIRS-mold, or CIRS-multisusceptible (includes algae toxins and dinoflagellates). More more doctors should test for this.

 

[Sheila]

Dear Mr DesertRat,

Thank you for coming back to me after all this time, your responses were most interesting. I am going to trial the 'intermittent resting' with the person I have been thinking of who has such a continuously high pulse (120 resting) despite showing slow but cumulative improvement. Certainly there is also a heap of environmental toxins (pesticides) in her environment but pretty sure in her case, no mould.

The Last Psychiatrist had an interesting post which mentioned Benadryl. The Last Psychiatrist: Treating Insomnia With Less He has an interesting style of writing and alas posts no more as he was 'outed' - his day job is as a clinical psychiatrist. But anyway, here is the extract on Benadryl that you might find interesting from that blog:

"I tried antihistamines like Benadryl, and they don't work. In fact, they make me feel wired.

Ah, many people have this reaction. You'd be surprised to learn that this is due to, and a screen for, very low levels of testosterone.

What?!

Psyche.

The real reason is that it isn't actually an antihistamine. That's misleading.

What do you mean, misleading?

You know how I hate the FDA, and most everyone else in the world, because they use words to distort the truth, and get girls to sleep with them that would never sleep with me?

What?!

Pay attention.

Here is the affinity chart for Benadryl:

(from CNS Spectrums)


The drug has the most affinity for H1 receptors, sure, but look what else it does. M1 blockade (dry mouth, constipation, confusion.) It also has significant NE and serotonin reuptake blockade. Basically, the FDA decided to pick only one of these four properties and slap it on the box, in the same way as labeling a TV dinner as "Rice."

You'll also observe that it looks like it works the same way as Effexor or a tricyclic. You'd be right. Think about that.

So every time I take Benadryl, it's an antidepressant?

Depends on the dose.

If you eat all of this TV DINNER, you'll be getting several foods. But if you only take one single fork of the rice, then the only thing you ate was rice, even though the box says, "TV DINNER."

If you only take a low dose of Benadryl, then you are only getting H1 blockade. If you take a medium dose, then you are eating only the rice (H1 blockade) and the cogentin (M1 blockade.) A high dose gets you all of the TV DINNER and receptors blocked (and also a heart attack-- hey, the analogy holds!)

If you imagine that the drug prefers H1>M1>NET>a1>5HTT, then you see that the mistake most people make with Benadryl is that they increase the dose when if doesn't work. What you really want to do is decrease the dose, to get away from all the other things that could be stimulating (serotonin, NE, anticholinergic.)

-------------------------------------------------------------------------------------------------------------------
I hope that is useful to you. And, thinking about it, if you have any insights on elevated resting pulse I would be most interested. The standard suggestions here just don't cut it for this person, but permanent low level attack by pesticides might be enough to prevent the stress response from really turning off. This person lives in an area of intensive agricultural production.
I wish you continuing progress, all the best
Sheila

 

[DesertRat]

Hi Sheila, Long delays due to only getting notifications in the Sunday review unless I remember to click through a few links before I reply to get notifications.
What you write about Benadryl is super interesting especially since it obviously works opposite to the Peat goal of lowering Serotonin. I took the lowest possible dose, e.g. the smallest sized capsules available when I tried; I might have even tried those disgusting tasting liquids for babies to try less -- I don't recall. At least the Kirkland Sleep Aid which is doxylamine succinate usually doesn't give me palps and can be a bit sleep inducing. The information on all the other effects of Benadryl is a warning to research everything thoroughly though (which I rarely do these days as I want to get on with my life after devoting too many years to improving health) but as you know it can be challenging for those of us without a background in pharmacology.

Re your friend's high pulse, this is not uncommon in CFS when the system is constantly in a hyper alert state. One of common responses is an imbalance in the stress hormones, and that is always done in the basic screening. Can you friend look into the biotoxin illness issue? If you go to www.survivingmold.com, you'll find a list of practitioners that have trained in his approach, but there are also many more who know it and integrate it with other therapeutic approaches. The crucial thing is to figure out the source of the principal environmental toxicity, which is sometimes determined by testing and sometimes better by trial and error. Dr. Walter Crinnion does workshops and teaches practitioners about environmental toxicity and what to do about it, so this could be another useful place to seek information and guidance. The Environmental Health Century in Dallas (EHCD) is another great resource and has helped many, although I'm not sure they are taking new patients now that Dr. Rea, the founder of this field, passed away this year.

 

[Sheila]

Dear Desert Rat
I am just delighted you responded, thank you, I suspect your idea of 'intermittent resting' will be very useful. I have found that in other people - 10 - 40 mins of daytime sleep can work wonders than no supplements or fuel levels can match. In others it causes all manner of problems. But some people need that 'switch off'. I will certainly look further into biotoxins and strongly suspect they are playing a part in keeping her system feeling like it is under attack. She is about to move and out of a spray zone might be a very good idea. My friends with CFS are largely ag. people so familiarity with ag chemicals breeds contempt and we sort of forget the ubiquitous nature of pesticides in that environment (even if, ironically, most of those patients are super clean with their food, drinking water etc. One could say, too little too late sadly and much of this is multi-generational now also).
The person I am thinking of had 'your' response to Cypro, ditto Benadryl, and could take a boat load of Doxylamine succinate to no effect whatsoever. A 'feature' of CFS seems to me to be 'no response' when one thinks they should.
Which brings me to one more question if I may. Her response to Vitamin B2 at 100mg is quite marked. No bright yellow urine at all, the usual 'processed and excess excreted' marker for most in under 3hrs. Takes several days of B2 before she shows that response, do you have any idea if it is slower processing, no processing, or used up super quickly? That would suggest B2 might be useful particularly as it has some anti-biotic like qualities.
I will research further into the survivingmold site, thank you, have been through the diagram you linked to, seems perfectly reasonable to me. I fully suspect some latent pathogens in the mix, H2S from poor digestive function etc. CFS as you make clear is multi-factorial.
Thank you again for your responses,
Sincerely,
Sheila

 

[DesertRat]

I can't say about the B2, but I do recall Haidut had a thread about B2 use in ME-CFS based on some recent research at Stanford on the flavinoid pathways. From the lack of yellow urine, my guess would be depletion and a greater need. Perhaps some toxin is causing her to use up B2 because B2 is necessary to eliminate it. I really don't know. I am just the opposite; anything but a very small amount of B2 will trigger me, so I mix my own B's from powders to use a lower dose. It is important in the Kreb's or citric acid cycle, where all of us show some kind of backlog in the urinary metabolites per functional medicine testing.

Interesting that your friend had a similar Cypro and Benadryl response. I've also tried and had bad responses from methylene blue -- made my muscles very weak and my heart unable to tolerate a slight uphill walk -- even at a very low dose of 1 drop diluted so as to take less than one drop. Similarly, I could not deal with Lapochin which is supposed to be helpful for energy production.

Re the intermittent resting, in the past I was able to do quite a bit of yoga, I suppose because there were few repetitive movements given the muscles a rest, and there was a lot of slow breathing. I could often get through a full day workshop, even 2-3 day workshops, as long as I went back to my room and napped at lunch while others were socializing. Yet if I went on a bikeride or a walk, I was limited to about 15 minutes except for a few short periods when I was in remission, and could go up to an hour, but never could cross that limit.

 

[DesertRat]

Re: @Debored and other posts on ME-CFS poor tolerance for carbs, I found in my experience that the only fuel pathway working decently was burning aminos so I had to eat a lot of protein and always had high ammonia, which ends up negating the improved energy from burning aminos. But I found that over time, adding simple carbs like OJ and white sugar at first made me very relaxed and tired and actually too tired to even walk a block: in other words, they made the CFS feel like it was worse. Yet somehow intuitively I knew my body was trying to figure out a way to deal with it and I persisted wtih thyroid supplementation, and in about 9 months, my normal energy came back with about 10 extra pounds of body weight and with much better sleep than before. Now if I don't eat carbs at times, say, at a restaurant, I will feel a strong craving for them. There is definitely going to be a transition period and more fatigue in shifting to carbohydrate metabolism, but I don't know if persistence will pay off for everyone as it did for me.

 

[energyandstruct]

Dear Mr DesertRat,

Thank you for coming back to me after all this time, your responses were most interesting. I am going to trial the 'intermittent resting' with the person I have been thinking of who has such a continuously high pulse (120 resting) despite showing slow but cumulative improvement. Certainly there is also a heap of environmental toxins (pesticides) in her environment but pretty sure in her case, no mould.

The Last Psychiatrist had an interesting post which mentioned Benadryl. The Last Psychiatrist: Treating Insomnia With Less He has an interesting style of writing and alas posts no more as he was 'outed' - his day job is as a clinical psychiatrist. But anyway, here is the extract on Benadryl that you might find interesting from that blog:

"I tried antihistamines like Benadryl, and they don't work. In fact, they make me feel wired.

Ah, many people have this reaction. You'd be surprised to learn that this is due to, and a screen for, very low levels of testosterone.

What?!

Psyche.

The real reason is that it isn't actually an antihistamine. That's misleading.

What do you mean, misleading?

You know how I hate the FDA, and most everyone else in the world, because they use words to distort the truth, and get girls to sleep with them that would never sleep with me?

What?!

Pay attention.

Here is the affinity chart for Benadryl:

(from CNS Spectrums)


The drug has the most affinity for H1 receptors, sure, but look what else it does. M1 blockade (dry mouth, constipation, confusion.) It also has significant NE and serotonin reuptake blockade. Basically, the FDA decided to pick only one of these four properties and slap it on the box, in the same way as labeling a TV dinner as "Rice."

You'll also observe that it looks like it works the same way as Effexor or a tricyclic. You'd be right. Think about that.

So every time I take Benadryl, it's an antidepressant?

Depends on the dose.

If you eat all of this TV DINNER, you'll be getting several foods. But if you only take one single fork of the rice, then the only thing you ate was rice, even though the box says, "TV DINNER."

If you only take a low dose of Benadryl, then you are only getting H1 blockade. If you take a medium dose, then you are eating only the rice (H1 blockade) and the cogentin (M1 blockade.) A high dose gets you all of the TV DINNER and receptors blocked (and also a heart attack-- hey, the analogy holds!)

If you imagine that the drug prefers H1>M1>NET>a1>5HTT, then you see that the mistake most people make with Benadryl is that they increase the dose when if doesn't work. What you really want to do is decrease the dose, to get away from all the other things that could be stimulating (serotonin, NE, anticholinergic.)

-------------------------------------------------------------------------------------------------------------------
I hope that is useful to you. And, thinking about it, if you have any insights on elevated resting pulse I would be most interested. The standard suggestions here just don't cut it for this person, but permanent low level attack by pesticides might be enough to prevent the stress response from really turning off. This person lives in an area of intensive agricultural production.
I wish you continuing progress, all the best
Sheila

interesting, im surprised how insightful he is with regard to neurotransmitters, etc, ive only read a few of his pieces on culture and narcissism and always thought he was kind of a hack

 

[somuch4food]

and other posts on ME-CFS poor tolerance for carbs, I found in my experience that the only fuel pathway working decently was burning aminos so I had to eat a lot of protein and always had high ammonia, which ends up negating the improved energy from burning aminos. But I found that over time, adding simple carbs like OJ and white sugar at first made me very relaxed and tired and actually too tired to even walk a block: in other words, they made the CFS feel like it was worse.

I think that's the key. CFS feels like you have no energy, yet you are awake (probably stress hormones). Feeling really tired could be seen as a good sign that you're stress hormones that keep you awake are under control and that your body feels safe enough to relax and recover.

Lately, I have increased fat intake and it seems to make me feel more relaxed. I have started to see drowsiness as a good sign that I have my hormones in check.

 

[DesertRat]

Lately, I have increased fat intake and it seems to make me feel more relaxed. I have started to see drowsiness as a good sign that I have my hormones in check.

That's a good sign but be careful with fats -- you probably are avoiding PUFA if you're on this forum -- because fat metabolism can increase oxidative stress (ROS). Usually something is going on with the liver in CFS, as nearly everyone tested as exceedingly high phase 1 clearance and something incommensurate with phase 2 or 3 pathways, and phase 1 often raises the toxicity temporarily of whatever the liver is trying to clear so it can create more of a backlog. I guess what I'm saying is make sure you are supporting good liver clearance as you increase fat. For me, fruit and fruit juice really helps a lot, coffee of course, and I also do coffee enemas if I feel the need (like headache comes on)

 

[somuch4food]

That's a good sign but be careful with fats -- you probably are avoiding PUFA if you're on this forum -- because fat metabolism can increase oxidative stress (ROS). Usually something is going on with the liver in CFS, as nearly everyone tested as exceedingly high phase 1 clearance and something incommensurate with phase 2 or 3 pathways,

Yeah, my increased fat is mainly from cheese, butter and dark chocolate (30-50% of calories). I know it might not be a long term solution, but it has helped with digestion and focus.

I've been reading a lot about stuff related to the liver. My symptoms all seems to point to it as a main culprit. Saturated fat is supposed to protect the liver against fat oxidation. I've seen also that Choline is critical to its function in managing fat storage. I disliked eggs when I was young, now my son is allergic. I've been deficient all my life I think. So, I want to start eating liver regularly to get more choline to support the liver.

What's this about phases?

 

[DesertRat]

What's this about phases?

They're just a way that Functional Medicine testing categorizes steps in the activities of the liver. I think it's somewhat artificial in that there are not three distinct phases, but some things take place before others, and the categorization is helpful in determining where deficits or excesses might be.

 

[somuch4food]

They're just a way that Functional Medicine testing categorizes steps in the activities of the liver. I think it's somewhat artificial in that there are not three distinct phases, but some things take place before others, and the categorization is helpful in determining where deficits or excesses might be.

Can you explain each phase, or point me to an article?

 

[DesertRat]

Here's a few links.
Liver Detoxification Pathways - Ask The Scientists generalist view
Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application research on using food to affect detox pathways
Your Body’s Detoxification Pathways On the testing protocol developed to get an idea of how to figure out where the patient's problems lie

 

[Amazoniac]

Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach

"CFS has its highest impact in females, rather than in males [14,15]." "Estrogens and estrogen receptors, particularly the ER-beta, are impaired and lowly expressed in subjects with CFS, a circumstance that can be particularly exacerbated in female individuals [19,20]."

"The fatigue symptoms may aggravate with mental or physical activity, but they do not improve after resting periods. It has been demonstrated that CFS might be the result of a mix of factors, such as viral infections (human herpesvirus-6, mouse leukemia viruses, and Epstein-Barr virus (EBV), intracellular bacteria, environmental factors, and immune system disabilities, hormonal imbalances in the pituitary glands, adrenal glands, or hypothalamus [7,24,25]."

"Chronic activation of signaling pathways associated with innate antiviral defense is likely to be central in the pathogenesis of CFS, since many of the antiviral effector molecules (as well-known defense weapons), which are upregulated, are not specific enough to attack only viral nucleic acids or protein, without harming host cell macromolecules and functions (by inhibition of synthesis or enhanced degradation of the host cell macromolecule), as well."

"[..]simultaneous detection of increased levels of pro-inflammatory cytokines, such as TNF-alpha and IL- 1, in patients [58,59] is indicative of an infectious or inflammatory etiology. Increased neopterin levels in blood plasma also indicate an ongoing inflammation [58,59]."

"Past reports from Stejskal et al. investigated the role of dental amalgam removal in 111 patients with symptoms resembling CFS and metal hypersensitivity [63]. MELISA, the optimized lymphocyte transformation test, was used to test for the presence of metal allergy. When comparing 116 healthy subjects, a CSF-like syndrome has been reported, using metal-specific lymphocytes in the blood of a significant number of patients [63,64]. Nickel was reported as one of the most frequent sensitizers, followed by inorganic Hg, Ag, phenyl mercury, cadmium (Cd), and palladium (Pd) [64]."

"Although metal-induced inflammation is involved in the pathogenesis of CFS, important observations are suggesting that chronic viral infections may be an important part of the etiopathogenesis at least in a large subgroup of patients [46,65–67]. Presumably, the many factors that may contribute to suppression of the parts of the immune system that are important for fighting viruses will enhance the risk of chronic or long-lasting infection, resulting in the development of CFS. Potentially important contributory mechanisms in CFS, may be the reduced leukocyte growth rates and the reduced expression of high-affinity and/or intermediate-affinity receptors for interleukin-2 (IL-2) on leukocytes, resulting from poor functional Se status [66,68,69], due to the combined effect of suboptimal Se intake and a high total content of Se-antagonistic toxic metals [70,71]. Enhanced expression of the immunosuppressive cytokine TGF-ß may result from toxic metal exposure, because of the induction by the lipid peroxidation product 4-hydroxynonenal [72], an induction which is also triggered by poor Se status [73,74]."

"Sub-optimal Se intake or poor functional Se status, due to too much Se-antagonistic toxic metals, is expected to lead to an enhanced synthesis of prostaglandin E2 (PGE2) [75]. Oxidative activation of signaling pathways causing enhanced expression of cyclooxygenase-2 (COX-2) in individuals with poor Se status and a high ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) in the diet, will also cause an increased prostaglandin synthesis [75,76]. For example, the prostaglandin PGE2 is an important suppressor of leukocyte types that are important for fighting viral infections. At the same time, PGE2 is one of the important signal substances, skewing the phenotype of macrophages from being antiviral and antitumor soldiers to become immunosuppressive M2 macrophages [77]. This is an important snowball effect of deficient Se status and high intake of omega-6 PUFAs since PGE2 increases the expression of non-protective enzymes in leukocytes [78–80]."

"It is a plausible working hypothesis that CFS may be a disease perpetuating itself because of a number of interlocking vicious circles, leading to immunosuppression, due to the deleterious effect of infection per se or other chronic inflammatory conditions [81–83]. Gut microbiota is expected to exert a leading role in this sense [84]. The resulting inflammatory reactions may be self-perpetuating, which causes enhancement of oxidative and nitrative stress [2,59], as well as enhanced degradation of several nutrients. In turn, this can lead to persistence of various infections at a moderate level of activity, which is not acutely life-threatening but can lead to very remarkable impairment of the patient’s quality of life."

"In the gastrointestinal tract, it is conceivable that inhibition of a nucleolar protein might cause inhibition of the growth of enterocyte and colonocyte progenitor cells, as well as various forms of disturbance of immunological functions, which may play a role not only in chronic infections but also in allergic and autoimmune disorders [85]. Moreover, it is also conceivable that inhibition of nucleolar function might cause reduced production of various secreted proteins that are needed for the normal function of the gastrointestinal tract, and perhaps enhanced leakiness of the mucosal epithelium. Also, it has been revealed that chronic infections are the most common feature of illness in CFS patients [85]."

"Many CFS patients show nitrosative and oxidative stress, and a chronically activated innate immune system [2,91]. Recent studies have demonstrated that the generation of free radicals could be involved in CFS etiology [1,3,91]. Fatigue symptoms could be related to the loss in the effectiveness of the electron transport chain and declined mitochondrial function. Oxidative mitochondrial damage, particularly from Reactive Oxygen Species (ROS), induces damage to mitochondrial membrane lipids, which results in rapid loss of mitochondrial function, although it causes the peroxidation of proteins and DNA as well as the cellular mitochondrial lipids [92]. In other words, because of the formation of excess free radicals, oxidative stress could be involved in the CFS pathology, as well as being associated with symptomatic presentation [93]. Chronically activated immune-inflammatory responses and nitrosative and oxidative stress in CFS patients, induce brain disorders such as brain hypoperfusion/hypometabolism, neuroinflammation, DNA damage, mitochondrial dysfunctions, secondary autoimmune responses directed against disrupted proteins and lipid membrane components, and dysfunctional intracellular signaling pathways [2,3,93]."

"Morris and his colleagues reported that hypofunction of the hypothalamic-pituitary-adrenal axis in CFS patients is known as a consequence of nitrosative and oxidative pathways, and stimulated immune-inflammatory responses [1]. The explanations of this mechanism could be attributed to the elevated levels of tumor necrosis factor-, increased levels of nitric oxide, regulatory T cell responses with increased levels of transforming growth factor-ß and interleukin-10, and viral/bacterial-mediated pathways [1]. Oxidative stress and energy metabolism have been elucidated as a dysfunction in the metabolic pathways of CFS patients [94]. Moreover, the response of CFS patients to accumulative exercise is related with accentuated oxidative stress, as well as with noticeable changes in the muscle membrane dysfunction that induce post-exercise malaise and muscle pain reported by CFS patients [95,96]. Finally, IgM-associated immune responses, directed against disrupted lipid membrane components and proteins, could be induced by nitrosative or oxidative stress in CFS patients [97]."

"Numerous reviews reported that some nutritional deficiencies could be involved as etiologic agents for CFS. These include deficiencies of vitamin C, vitamin B complex, sodium, magnesium, zinc, folic acid, Lcarnitine, L-tryptophan, essential fatty acids, and coenzyme Q10 [107]. For example, a dose-response association and long-lasting effects of B12/folic acid provide a proper positive reaction in the examined CFS patients [108]. The low content of serum vitamin E during the remission and exacerbation phase of CFS patients revealed that high oxidative stress could be contributing to the CFS pathogenesis, and may be directly related to the severity of the symptoms of CFS patients, indicating that antioxidant supplementation could alleviate muscle symptoms in this syndrome [109]."

"A study examining alternative treatments, found some hints towards a positive effect on CFS, making use of magnesium, L-carnitine, and S-adenosylmethionine as supplements in CFS patients [113]. However, it should be highlighted that most trials are of poor quality, using different methods (including a dosage of nutrients), lacking documentation of dietary intake, showing only a short follow-up, examining only a small number of patients, using a heterogeneous population, and lacking sound clinical endpoints."

"A more recent evaluation could not demonstrate an effect on CFS outcome, but most trials did have an effect on symptoms, typically fatigue, using nicotinamide adenine dinucleotide hydride (NADH), probiotics, chocolate [?], and coenzyme Q10 [114]."

"Eventually, a meta-analysis was recently performed, not able to confirm that vitamin and mineral deficiencies altogether play a major role in CFS, but with some doubt remaining on vitamin E deficiency [115]."

"Finally, another systematic review suggested a positive effect of nutritional supplements again, such as D-ribose, albeit only on symptoms, with special regard to supplementation of omega-3 fatty acids, whose blood levels could also be linked to relief of symptoms [116]. Again, all the previously mentioned shortcomings continue to exist, and no final conclusion can be drawn at this point."

"Despite the huge amount of hypotheses, the most frequent suggestion is that an infectious etiology should be regarded as being plausible for the etiology of CFS. However, possible further causes related to the gut/brain axis and the microbiota-related immune disorders, including autoimmunity, are possible suggestions."

"Current studies on minerals and vitamins in CFS patients need large populationbased and age-matched prospective research, as well as well-observed interventional studies in CFS patients, to achieve more awareness in the efficacy of minerals and vitamins in the CFS pathophysiology. According to this analysis, vitamin A and vitamin E are promising vitamins that need further examination."​

they’ve done experiments in rabbits, taking a piece of foreign cartilage (like, from a cow) and it will produce very few antibodies in the rabitt. But if you twist it a little bit, structurally damage it, then it produces a terrific immune reaction. And any organ that gets strained or overworked tends to leak some of its proteins, and the immune system’s function, largely, is to clean up any mess. In fact, there’s an alternative interpretation of what the immune system is doing: rather than looking for foreign invading pathogens, this theory says it’s primarily cleaning up messes caused by anything which is pathogenic.

 

[energyandstruct]

Paul Cheney Seminar (2013)

The Energy Conundrum

That brings me to a model that I’ve developed based on some of those earlier slides I showed you.

Don’t concentrate on the red part. Just concentrate on the white part.

You have the mitochondria, and of course the red cells carry oxygen in the bloodstream. And then the oxygen is translated into the mitochondria to help you make ATP, which is the primary energy source in this impressive oxidative phosphorylation system that we call mitochondria.

There’s an interesting feedback loop right in here, where from the oxygen you generate energy, and then you couple that energy into systems, which is a magnesium-dependent process.

And by the way, it’s one of the big deals in chronic fatigue syndrome. Magnesium is wonderful for these patients. It’s probably the simplest, safest, best thing I’ve ever used to treat energy problems in this disease.

But tablets don’t work. Tablets are ineffective. Either you have to put it on your skin in a cream, or you have to squirt it on your tongue, or you have to inject it. And you don’t need very much for this.

You’ll notice that the magnesium couples ATP to ADP. That is sort of like taking your foot off the clutch. You’re making the same amount of energy, but when you take your foot of the clutch, the car actually moves.

The same is true here. You’re not making more energy with magnesium. You’re actually coupling it.

It’s coupled into ADP and then from there into AMP. This actually is a feedback loop for oxygen transfer. This means that if you’re not coupling ATP to ADP, there will be no oxygen transfer into the system. It’s a feedback locked-loop system.

If you look at a textbook of physiology, you’ll notice that oxygen transfer into the cell is primarily determined by ADP levels. If they’re low, there will be no oxygen transfer. That’s an important idea.

Of course, when you make ADP, you also make superoxide. And that’s a conundrum. An energy conundrum.

You cannot make energy without making oxidative stress in the form of superoxide.

The body knows this, of course, and it’s developed a fantastic redox cooling system composed of several different enzymes – SOD, GPx and catalase.

These are the kinetic speeds of these enzymes. These are the fastest enzymes systems in the human body. They’re incredibly speedy. And they have to be that way, because if they fail to take superoxide down to water, which is their job, then you cannot make energy. Because if you do, you’re just going to fry the mitochondrial membrane.

Because if this superoxide is not taken first to hydrogen peroxide and then to water by two different pathways, then the superoxide will turn into free radicals.

It will react with nitric oxide to form peroxynitrate. This is the OH/ONOO hypothesis of Marty Pall, which some of you may have heard or read about.

Or it reacts with hydrogen peroxide to form hydroxyradicals.

This impressive production of these free radicals will actually destroy the membranes – the mitochondrial membranes – and bring energy production to a halt.

The reason you do this is to save yourself. Because if you continue to generate energy and you cannot cool the system, then you have to bring down energy to save your life. And we think this is exactly what is going on.

In other words, the energy downregulation is not the problem.

The energy downregulation is the solution to prevent a deeper problem.

And the problem is that something’s wrong with this redox cooling system.

Studies on some of these elements – SOD and GPx and catalase and the NADPH which reduces glutathione made in the liver – there’s something wrong with this system. And you can see it and prove it and measure it in every single patient.

It’s there if you just look for it.

If you have a defect in redox cooling, then there will be increased oxidative stress, and if you’re lucky, that will feedback loop inhibit mitochondria from producing energy. And then you will equilibrate at a lower energy state to save your life.

That doesn’t mean that the low-energy state is pleasant. It doesn’t mean that there aren’t complications from that. But your life is preserved.

And that brings me to one of the interesting phenomena in this disease. I’ve watched these patients for 25 years, and they simply as a group don’t die that much. They go on and on and on.

They fade away, sure. But they’re not dropping dead like flies. As a matter of fact, I’m an internal medicine doctor, and if you ask internists my age “How many of your patients are left after thirty years?” the answer is only about half are left. Why? Because you only see an internist if you have a significant illness.

But not anywhere near that number have died in my hands. So there’s something preserving these patients. And what’s preserved is that they are equilibrating to a low energy state to prevent some sort of disease progression.