Chronic Fatigue Syndrome (ME/CFS) May Be Caused By Increased Serotonin Sensitivity

[energyandstruct]

as far as more selective serotonin antagonists, I wonder if there's any anecdotal evidence of improvements from them. I know ray discusses LSD as being a serotonin antagonist (although I thought that the research is unclear on whether it's pro or anti-serotonergic), and I have had a tryptamine psychedelic one time since having CFS. It did not dramatically alleviate my fatigue, but maybe the dose needs to be repeated. I also had odansetron and don't think I noticed anything.

 

[haidut]

That sounds oversimplified but I’ll admit I’m no expert. I’ve read quite a bit of the literature on chronic fatigue syndrome though, and by far the most compelling was naviauxs study on chronic fatigue syndrome using metabolomics. He talks about the cell danger response as something that has to do with purinergic signalling. It involves possibly every body system and makes sense as a unifying theory that links immune system response to metabolism. I saw your thread on that study so I know you're aware of it. I'm also aware that Ray disagrees with naviaux and thinks CFS is simpler--that it's simply hypothyroidism and/or reductive stress.

Does the serotonin theory fit with the purinergic signalling theory? Imo naviaux's theory is very convincing, and he had decent results with his suramin trial in autistic children. Empirical evidence is always the best test of a theory, and I think that Naviaux's metabolomics study on CFS was convincing for that reason--for the sheer volume of information he was collecting.
"Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism...

Our data show that despite the heterogeneity of factors leading to CFS, the cellular metabolic response in patients was homogeneous, statistically robust, and chemically similar to the evolutionarily conserved persistence response to environmental stress known as dauer."

Google for "central fatigue hypothesis".
Central nervous system fatigue - Wikipedia

 

[energyandstruct]

Google for "central fatigue hypothesis".
Central nervous system fatigue - Wikipedia

I just read that, and looked at some of the primary sources. It seems like some of the studies demonstrate that CFS patients have a higher perception of fatigue even before exhaustion but I've also seen studies that show actual lower physical performance on CPET tests, and lower VO2 max, so it seems like it's not all in the brain. and naviaux's study indicates not just cytokine differences, but differences in metabolism at the cellular level. Is that all caused by central serotonin sensitivity? Or is it more likely that some of it is caused by peripheral serotonin

 

[haidut]

I just read that, and looked at some of the primary sources. It seems like some of the studies demonstrate that CFS patients have a higher perception of fatigue even before exhaustion but I've also seen studies that show actual lower physical performance on CPET tests, and lower VO2 max, so it seems like it's not all in the brain. and naviaux's study indicates not just cytokine differences, but differences in metabolism at the cellular level. Is that all caused by central serotonin sensitivity? Or is it more likely that some of it is caused by peripheral serotonin

Serotonin will cause both CNS and peripheral fatigue. Try doing pushups before and then 1h after taking 2mg cyproheptadine. Aside from the sleepiness which cypro causes (which btw dissipates after a week of usage) the muscle usually can perform twice as good compared to before serotonin antagonist. The rationale for current clinical trials with TPH inhibitors for obesity and diabetes (high lactic acid and fatigue in both conditions) was exactly the observation that serotonin seems to drive both the pathology and the fatigue in these conditions. Since there trials are now almost complete and seem successful, I would venture a guess that serotonin is the primary driver but there may be multiple peripheral mechanisms that serotonin uses to manifests its effects - i.e. lactic acid, histamine, cytokines, elevated FFA, etc. Aspirin also helps for CFS and it is known to lower plasma serotonin, FFA and inflammatory mediators like the PGs.
Multiple Sclerosis Research: Aspirin as good as amantadine for fatigue? Or not?

Btw, that study above used amantadine as comparison. That's not a coincidence. As I mentioned earlier, all adamantane derivatives lower serotonin and increase dopamine. So, once again serotonin's role in fatigue is exposed.

 

[energyandstruct]

I know of 4 that were not able to do much except lie in bed all day (not even watch TV). All of those people are now employed and have active social lives. Two of them (one female and one male) started families (not with each other).

I had missed this, haidut. This is very near and dear to me as I've been getting worse under the treatment of my cfs doctor (antivirals). What serotonin antagonists did these pepople that recovered use? I've used cypro quite a few times without it helping. would odansetron be good?

 

[haidut]

I had missed this, haidut. This is very near and dear to me as I've been getting worse under the treatment of my cfs doctor (antivirals). What serotonin antagonists did these pepople that recovered use? I've used cypro quite a few times without it helping. would odansetron be good?

I think it was cypro, in higher doses like 8mg daily in divided doses, and one took thyroid. The girl said it took about a week of cypro at high doses and then suddenly the depression and fatigue were gone. I am guessing it was either the re-sensitization of glucocorticoid receptors or the antiviral effect. One of the guys had high herpes viral counts and those dropped to undetectable with cypro. Not sure if that counts or is related to CFS.

 

[energyandstruct]

I think it was cypro, in higher doses like 8mg daily in divided doses, and one took thyroid. The girl said it took about a week of cypro at high doses and then suddenly the depression and fatigue were gone. I am guessing it was either the re-sensitization of glucocorticoid receptors or the antiviral effect. One of the guys had high herpes viral counts and those dropped to undetectable with cypro. Not sure if that counts or is related to CFS.

interesting. Based on testing I know I have high IgE/mast cell problems. But cypro just makes me sleepy. maybe i need to try it for longer?

 

[Amazoniac]

- Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study

"Chronic fatigue syndrome (CFS), also referred to as myalgic encephalomyelitis, is a complex heterogeneous disease, most commonly characterized by disabling fatigue, cognitive impairment, disrupted sleep and concomitant skeletal and muscular pain, lasting for more than 6 months and not improving with rest (1, 2) [for a broader definition, see Ref. (3)]. Impaired physical and social functioning, vitality, emotional well-being and role limitations due to emotional problems (4) contribute to an impaired quality of life (5). Although most patients have mild or moderate symptoms, some suffer from severe CFS and are housebound or even unable to move from their beds (4)." "About 75% or more are female. The mean age of onset is 29–35 years and the mean illness [indeed] duration ranges from 3 to 9 years (6), which implies that the symptoms are reversible."

"Computational analysis using endocrine and gene expression data suggest that CFS is associated with immune-mediated loss of thyroid function, exacerbated by a blunted HPA axis response (10). Autonomic dysfunction, including orthostatic intolerance and syncope, microglial activation and structural changes, indicate involvement of the brain (11). There is accumulating evidence that the cardiovascular system is compromised, with reports of autonomic dysfunction, attenuated heart rate and blood pressure (12) and increased death rate from heart failure (13). The latter finding was related to a blunted cortisol response (14). Taken together, dysfunctional central housekeeping involving interactions between both the HPA and hypothalamus–pituitary–thyroid (HPT) axes and the sympathetic/adrenal medulla, rather than single-hormone-axis disturbances, might play a key role in the development of CFS symptoms (10, 11, 14)."

"A state of low-grade inflammation (22), as derived from elevated (hs)CRP (23), interleukin (IL)-6 (24), IL-1 and tumor necrosis factor (TNF)-α (22), and/or nuclear factor kappa B (NFκB) (25) has, however, not consistently been found (26–28), possibly because of differences in experimental approaches and patient conditions (28). Increased translocation of lipopolysaccharides (LPS) from Gram-negative enterobacteria with subsequent gut-derived inflammation was also found (29). Giloteaux et al. demonstrated intestinal dysbiosis resulting from a more proinflammatory gut microbiome that may trigger the immune system (30). Recently, the relationship between the thyroid with gut microbiome and inflammation became apparent from the associations of both hypothyroidism and levothyroxine use with small intestinal bacterial overgrowth (31)."

[31] Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: Results of a retrospective cohort study​

"Several symptoms resemble those of hypothyroidism. They are, however, not accompanied by the marked thyrotropin (TSH) increases of full-blown hypothyroidism (32). Fuite et al. (10) suggested immune-mediated loss of thyroid function in CFS patients. Low-grade inflammation and subclinical hypothyroidism are not mutually exclusive. Inflammation virtually affects all hormonal axes (33), including the HPT axis (34). Profound changes in this axis occur in the “non-thyroidal illness syndrome (NTIS),” also referred to as “euthyroid sick syndrome,” which has notably been investigated in critically ill patients (35). As part of the acute phase response, this condition may reflect an adaptation to counteract excessive catabolism during severe illness (34). The most important clinical chemical features of mild to moderate NTIS are normal/low-normal TSH, low total triiodothyronine (TT3) and free T3 (FT3) levels, normal/high-normal total thyroxine (TT4), decreased peripheral conversion of T4 to T3, and increased reverse T3 (rT3) levels (36). Chronic inflammation in rodents increases the expression of deiodinase 3 (D3), which inactivates both T3 and T4 with concomitant production of 3,3′-diiodothyronine (T2) and rT3, respectively (34). A recent study (37) also reported elevated concentrations of 3,5-T2 in humans affected by cardiac NTIS."

"Chronic fatigue syndrome has been described as an “allostatic overload condition” (38), where the physiological mechanisms employed to deal with stress (also named “allostatic states”) contribute to the perpetuation of the disorder. CFS patients are 1.9 times more likely to have a high allostatic load index than healthy controls (39) and this allostatic load also correlates positively with CFS symptoms (40). Thyroid allostasis-adaptive responses, presenting as NTIS, have been found in many conditions, ranging from critical illness, uremia and starvation to tumors (41). Taken together, it is possible that, despite TSH and T4 levels within reference ranges, CFS symptoms may be attributable in part to allostatic responses, i.e., lower thyroid hormone activity, secondary to chronic (low-grade) inflammation caused by, e.g., a compromised gut microbiome and gut wall integrity."

"In the present case–control study, we focused on signs of low-grade inflammation and subclinical hypothyroidism. We measured parameters of thyroid function, low-grade inflammation and gut wall integrity (42), together with secondary markers of inflammation, also named metabolic inflammation (43, 44), including insulin resistance-mediated de novo lipogenesis (DNL), HDL-cholesterol (HDL-C), and the status of nutrients influencing thyroid function (iodine and selenium) and inflammation [fish oil fatty acids (FA) and vitamin D]."

"The most remarkable observation in this case–control study was that, as a group, the present CFS patients exhibited lower FT3, TT4, TT3, %TT3, SPINA-GD, SPINA-GT, T3/T4 ratios, lower protein binding of thyroid hormones, and 24-h urinary iodine excretion, together with higher %rT3. Sixteen (16%) CFS patients exhibited the “low T3 syndrome” as compared to seven (7%) controls (Table (Table1).1). These observations were basically unaltered upon applying more stringent cutoff values for hCRP, BMI and WBC in our “sensitivity analyses” (Table S2 in Supplementary Material). CFS patients also showed some signs of (metabolic) low-grade inflammation, notably higher TC/HDL-C and ferritin, and lower HDL-C, tryptophan and kynurenine."

Peacuilaritise in people with chronic fatigue​

"Therefore, we conclude that, in the present study, we found subtle evidence of low-grade (metabolic) inflammation in CFS patients. Plasma 25(OH)D below the optimal cutoff value of 80 nmol/L was found in 59% of the CFS patients and 83% of controls."

"The “low T3 syndrome” encountered in a subgroup of CFS patients bears clinical chemical similarity with NTIS features. Both syndromes are biochemically characterized by low TT3 and FT3 together with normal/high-normal FT4 and normal TSH, at least in the mild and moderate forms of NTIS (36). The clinical disparity relates to the underlying severity of the diseases that are usually linked to NTIS, as opposed to the chronicity and less life-threatening nature of CFS (66). NTIS is a typical feature of critically ill patients in intensive care units, although similar changes in the HPT-axis have been observed during calorie restriction and in patients with non-critical chronic diseases, such as heart failure, chronic obstructive pulmonary disease, and diabetes mellitus (67), also referred to as mild, or atypical forms of NTIS (36, 67). All of these conditions, especially calorie restriction, might find a common denominator in an adaptive response aiming at saving energy and body protein in order to outstay any potential acute stress stimulus (68–70). Through coordinated changes in thyroid hormone metabolism, transport and receptors, NTIS might mechanistically reflect a cytokine-orchestrated allostatic condition that is remote from the well-known homeostatic negative feedback regulation of the HPT axis (71)."

"[..]induced hypothyroidism in humans for two weeks causes profound changes in FA metabolism (76). Another recent case–control study using metabolic profiling showed an altered serum amino acid profile in CFS patients, suggesting impaired mitochondrial pyruvate oxidation (74), a condition likely to reflect energy deficiency and excessive lactate production, with utilization of amino acids from endogenous protein as alternative TCA cycle substrate. The “low T3 syndrome” in a subgroup of CFS patients found in this study might be cause and consequence of the above noted epigenetic changes (72) and a driving force of the metabolic differences noted by others (73, 74) and by us. Through both genomic and non-genomic actions, T3 has profound impacts on mitochondria and metabolism (77), including several pathways regulating the expression of target genes contributing to mitochondrial biogenesis (78)."

"The association between low T3 and low hsCRP suggests that both CFS patients and controls with low FT3 are less responsive to inflammatory stimuli, which is in line with observations by others. In apparently healthy individuals, Hodkinson et al. (79) found, amongst others, that TT3 concentrations are positively related to monocyte phagocytic activity and expression of -6 (IL-6) by activated monocytes, while TT4 is positively related to CRP. Their data suggest that higher thyroid hormone concentrations within the normal range enhance innate and adaptive immunity by greater responsiveness to immune stimuli. Accordingly, Rozing et al. (80) showed that, although higher circulating levels of inflammatory markers were associated with lower levels of free serum FT3; higher serum FT3, but not higher TSH and FT4, are related to a higher production capacity of proinflammatory cytokines (IL-1β, IL-6, TNF-α) in whole blood of 85-year-old women and men, following ex vivo stimulation with LPS. They suggest a mutual association between T3 and proinflammatory cytokines, whereas T3 stimulates production of proinflammatory cytokines that subsequently diminish the conversion of T4 to T3. Finally, evidence of a diminished specific immune response has been found in patients with CFS. Investigating pokeweed mitogen-stimulated isolated peripheral blood mononuclear cells, Loebel et al. (81) found a deficient EBV-specific immune response in patients with CFS, possibly causing impaired EBV control."

"The encountered “low T3 syndrome” in our study resembles the thyroid hormone profile of a subgroup of hypothyroid patients receiving T4 monotherapy. Substitution with T4 is the currently recommended treatment of hypothyroid patients, like those with Hashimoto thyroiditis. Nevertheless, it is becoming increasingly clear that a subgroup of these patients experiences residual hypothyroid symptoms, including psychological and metabolic traces. These symptoms occur despite reaching a chemical euthyroid state, i.e., normal TSH (82, 83). In thyroidectomized rats, no single dose of T4 was able to simultaneously restore TSH, T4, and T3 in plasma and organs to normal levels (84). In so-called “euthyroid, yet symptomatic” patients, the basal metabolic rate and serum cholesterol, among others, are not fully restored and they are also likely to have both low TT3 and FT3. These findings of low T3 may be explained by a disrupted TSH-T3 shunt (41). The question whether they would benefit more from a T4 and T3 combination therapy or sustained-release T3 (85) is debated and subject of further research (82, 83). Hormone replacement therapy, notably T3, has also been suggested for severe NTIS (71, 86, 87)."

"Some features of CFS resemble those of a persistent response to environmental stress known as dauer (hypometabolic state). The cell danger response (CDR) is an evolutionarily conserved metabolic response, activated when a cell encounters a chemical, physical, or microbial threat that could injure or kill the cell (91). When the CDR is abnormally maintained, whole body metabolism and the gut microbiome become disturbed, the functionality of systems and organs becomes impaired and behavior is changed, resulting in chronic disease (91). Accordingly, the intestinal microbiota and virome have recently been implicated in CFS (92), while gene expression data show prominent roles for genes involved in immunity and defense (93). Psychological trauma, particularly during childhood, can also activate the CDR and produce chronic inflammation (91, 94). It has recently been shown that CFS patients are endowed with different psychological vulnerability factors, notably perfectionism and high moral standards (95). These may render them more susceptible to the psychological stress of current society, with possible effects on the immune system and thyroid axis (56, 62, 79, 80). Finally, the aforementioned case–control study by Naviaux et al. (73) showed that CFS patients present cellular metabolic responses similar to the evolutionarily conserved persistent response to environmental stress. Thus, the features of hypometabolism that characterize CFS may be a consequence of a persisting CDR, either or not inflammatory driven."

"Induction of D3 in muscle may occur in chronic inflammation (34), but D3 may also become induced by other factors, such as estradiol, progesterone, and growth hormone (96). Such mechanisms may be at the basis of CFS symptoms and may explain the lower urinary iodine excretion in CFS patients as compared with controls, although the latter also exhibited a relatively high prevalence of low iodine excretion (Table (Table1).1). Intracellular D3-catalyzed liberation of iodide from T4 and T3 may serve various antioxidant and defense functions that may potentially contribute to high intracellular “thyroid hormone consumption,” manifesting as the “low T3 syndrome” with negative iodine balance in the long term (67, 83, 97)."​

- Overlapping Conditions Among Patients With Chronic Fatigue Syndrome, Fibromyalgia, and Temporomandibular Disorder

"The rates of IBS among patients with CFS, FM, and TMD (92% [!], 77%, and 64%, respectively) were well above the frequency both in our control group (18%) and in the general population (9%-21%) as estimated using the Manning criteria.[21] The only study examining the overlap of IBS and chronic fatigue used identical standard diagnostic criteria and similarly reported a high prevalence of IBS among patients with chronic fatigue over a 1-year retrospective evaluation period (73%).[22] It should be noted that the prevalence of IBS in community surveys is typically assessed using a 3-month time frame, whereas this study ascertained lifetime prevalence. However, when we examined whether subjects currently met criteria for IBS (ie, >2 Manning symptoms endorsed on the day of questionnaire completion), we also found significantly higher rates of IBS among patients (17%-40%) compared with control subjects (5%). Thus, while IBS is certainly common in the general population, our patient groups were disproportionately affected with IBS. These results suggest that a common pathogenic mechanism related to bowel dysfunction may underlie CFS, FM, and TMD disorders. In this regard, some investigators have speculated that the serotonin abnormalities observed in patients with FM may be the result of defective absorption of the precursor amino acid tryptophan from the gut.[23]"​

- Supraphysiological Cyclic Dosing of Sustained Release T3 in Order to Reset Low Basal Body Temperature

 

[somuch4food]

Psychological trauma, particularly during childhood, can also activate the CDR and produce chronic inflammation (91, 94). It has recently been shown that CFS patients are endowed with different psychological vulnerability factors, notably perfectionism and high moral standards (95). These may render them more susceptible to the psychological stress of current society, with possible effects on the immune system and thyroid axis

I totally relate to this. My perfectionism and my obsession with wanting to do things "right" are at the heart of my health issues. My mental state is causing digestive issues and my digestive issues are causing mental problems. No wonder it is so difficult to achieve good health.

As a child, I was shy, always worried about being good, not hurting others. I still struggle with that. I am increasingly thinking that mental state plays as much a role as food in my health.

I am still not really good at reading studies. Does this mean that I should focus on lowering serotonin and tryptophan?

 

[Amazoniac]

I totally relate to this. My perfectionism and my obsession with wanting to do things "right" are at the heart of my health issues. My mental state is causing digestive issues and my digestive issues are causing mental problems. No wonder it is so difficult to achieve good health.

As a child, I was shy, always worried about being good, not hurting others. I still struggle with that. I am increasingly thinking that mental state plays as much a role as food in my health.

I am still not really good at reading studies. Does this mean that I should focus on lowering serotonin and tryptophan?

@Jennifer shared something similar.
What's behind the exaggerated fear of failure or disapproval?

Various nutrients that are essential for life can worsen gut infections if they tend to escape digestion. Niacin is digested quite fast, but tryptophan can travel further down the intestines and cause issues.
Tryptophan: ‘essential’ for the pathogenesis of irritable bowel syndrome?

Restriction provides relief, but it isn't enough to correct the problem on its own.

the problem isn't the serotonin, it's the excess gut flora

- Stress Just As Bad As High-PUFA Diet For Your Health
- CFS Is Likely Hypometabolism Triggered By Environmental Stress

 

[somuch4food]

@Jennifer shared something similar.
What's behind the exaggerated fear of failure or disapproval?

In my case, I think it stems from being unable to identify with others when I was younger. I always felt different. I was the girl with short hair that likes boys' stuff and has no interest in anything girly. I remember crying when I received earrings on one of my birthday.

I think I seek approval to compensate my inability to feel included.

I can relate to some autistic symptoms. Social cues have always been an enigma to me. So, I think that my current state is a result of a digestive issue that is amplified by my mental stress. It is difficult to entangle both while dealing with life.

Thanks to your question I think I understand myself a bit better. Crazy what childhood can reveal.

 

[Wagner83]

Behavioural effects of long term inhibition of 5-hydroxytryptamine receptors using metergoline. - PubMed - NCBI

https://www.sciencedirect.com/science/article/pii/0014299982905702?via=ihub

 

[Amazoniac]

In my case, I think it stems from being unable to identify with others when I was younger. I always felt different. I was the girl with short hair that likes boys' stuff and has no interest in anything girly. I remember crying when I received earrings on one of my birthday.

I think I seek approval to compensate my inability to feel included.

I can relate to some autistic symptoms. Social cues have always been an enigma to me. So, I think that my current state is a result of a digestive issue that is amplified by my mental stress. It is difficult to entangle both while dealing with life.

Thanks to your question I think I understand myself a bit better. Crazy what childhood can reveal.

While you can't change what has passed, it can be useful to know how it affects your behavior now. If you were too sensitive in relation to the people around you, you were more susceptible to suffer, therefore it isn't surprising if you've absorbed the punch. Finding your tribe or surrounding yourself with other sensitive people can help you to relate, but if you're only able to find one, you'll tend to please the person in fear of loss and you can feed that vicious cycle again.


It's useful to know what is safe or not in the diet, but trying to eat your way out of negative mindsets tends to lead people to unhealthy food habits. In my opinion it's better to assist the craved diet with supplements. Of course if someone is used to eating poor foods, that needs to be addressed, but if the person is already eating a more natural diet, it isn't good to try to trick cravings. However, it is possible to crave foods that perpetuate a state that you've become accustomed with, and this can be harder to identify.

Regarding digestive issues, these should help:
- Sun exposure
- Vitamin A or all the nutrients required for it to work
- Magnesium
- Red light on abdomen (Raj mentioned in one of his recent interviews that people can hit their belly with fingers to detect hollow sounds which can indicate stagnated pockets with too much bacterial action, it might be helpful to concentrate the light there)
- Vitamin C
- Adequate protein with enough glycine
- Physical activity
- Agreeable fibers
- Respecting but not fearing stress

Logging your food intake for a week on Cron-o-meter and getting a nutritional report for the averages can give you an idea if there isn't anything clearly missing. It might be worth adjusting the requirements for the B-vitamins that are directly involved in energy production 5x higher than the default if you're dealing with stress. With electrolytes you can probably double.

It's also worth paying attention to how proteins are being digested, especially casein and gluten, they can be quite problematic for a lot of people, impair healing and make gut issues worse.

 

[Blossom]

While you can't change what has passed, it can be useful to know how it affects your behavior now. If you were too sensitive in relation to the people around you, you were more susceptible to suffer, therefore it isn't surprising if you've absorbed the punch. Finding your tribe or surrounding yourself with other sensitive people can help you to relate, but if you're only able to find one, you'll tend to please the person in fear of loss and you can feed that vicious cycle again.


It's useful to know what is safe or not in the diet, but trying to eat your way out of negative mindsets tends to lead people to unhealthy food habits. In my opinion it's better to assist the craved diet with supplements. Of course if someone is used to eating poor foods, that needs to be addressed, but if the person is already eating a more natural diet, it isn't good to try to trick cravings. However, it is possible to crave foods that perpetuate a state that you've become accustomed with, and this can be harder to identify.

Regarding digestive issues, these should help:
- Sun exposure
- Vitamin A or all the nutrients required for it to work
- Magnesium
- Red light on abdomen (Raj mentioned in one of his recent interviews that people can hit their belly with fingers to detect hollow sounds which can indicate stagnated pockets with too much bacterial action, it might be helpful to concentrate the light there)
- Vitamin C
- Adequate protein with enough glycine
- Physical activity
- Agreeable fibers
- Respecting but not fearing stress

Logging your food intake for a week on Cron-o-meter and getting a nutritional report for the averages can give you an idea if there isn't anything clearly missing. It might be worth adjusting the requirements for the B-vitamins that are directly involved in energy production 5x higher than the default if you're dealing with stress. With electrolytes you can probably double.

It's also worth paying attention to how proteins are being digested, especially casein and gluten, they can be quite problematic for a lot of people, impair healing and make gut issues worse.

Great post!

 

[energyandstruct]

I know of 4 that were not able to do much except lie in bed all day (not even watch TV). All of those people are now employed and have active social lives. Two of them (one female and one male) started families (not with each other).

I really wonder about the high dose cypro for many days thing you mentioned. I have never tried pushing it that high. It is heartening to hear these stories. Have you seen the recent discussion of ongoing research of high intracellular tryptophan/kynurenine ratio due to broken IDO2 enzyme?

 

[Jennifer]

In my case, I think it stems from being unable to identify with others when I was younger. I always felt different. I was the girl with short hair that likes boys' stuff and has no interest in anything girly. I remember crying when I received earrings on one of my birthday.

I think I seek approval to compensate my inability to feel included.

I can relate to some autistic symptoms. Social cues have always been an enigma to me. So, I think that my current state is a result of a digestive issue that is amplified by my mental stress. It is difficult to entangle both while dealing with life.

Thanks to your question I think I understand myself a bit better. Crazy what childhood can reveal.

As Amazioniac mentioned, I can relate.

My shyness and perfectionistic tendencies were mainly the result of being teased relentlessly from the time I started kindergarten until high school. I was told if I ignored it that they would stop so I kept quiet, trying my best to be invisible in hopes that the boys would leave me alone and inadvertently became "shy" and adopted their views of me as my own, becoming very critical of myself. I was also molested at a young age and felt I needed to be perfect to make up for "my sin" so that I could be in heaven with my family when I died.

Once I learned my worth, really got it, not just told myself I'm worthy but got the magnitude of it and that it's innate, everything changed. I no longer have to dilute myself and wear myself ragged trying to please others in an attempt at winning their love and approval because I already have enough love and respect for myself. And I no longer require finding my tribe in order to feel like I belong. I actually put myself in places where I'm not the same as others around me. For example — here.

I've always been overly concerned with not hurting others to the point that I let others abuse me. It hadn't occurred to me that while I was trying my best to not hurt others, I was hurting myself in the process. Why is it okay to hurt ourselves, you know? Anyway, I wish you all the best in overcoming your health issues. :)

 

[somuch4food]

My shyness and perfectionistic tendencies were mainly the result of being teased relentlessly from the time I started kindergarten until high school. I was told if I ignored it that they would stop so I kept quiet, trying my best to be invisible in hopes that the boys

Totally, I was teased for looking like a boy all the time and also told to ignore it. I think going to a girl-only school (middle and high school) saved me from being overly focused on appearance, but I was still way too self-conscious about the fact that I didn't want to be girly.

I've always been overly concerned with not hurting others to the point that I let others abuse me. It hadn't occurred to me that while I was trying my best to not hurt others, I was hurting myself in the process.

That made me a good candidate for burnout at work at the beginning of my career

I am starting to think in a more assertive way. I still struggle with taking action, but I am changing slowly. For me, having a child seems to have made me feel worthy. I care less about others' opinions since giving birth and also finding Peat :)

 

[Cirion]

"The “low T3 syndrome” encountered in a subgroup of CFS patients bears clinical chemical similarity with NTIS features. Both syndromes are biochemically characterized by low TT3 and FT3 together with normal/high-normal FT4 and normal TSH, at least in the mild and moderate forms of NTIS (36). The clinical disparity relates to the underlying severity of the diseases that are usually linked to NTIS, as opposed to the chronicity and less life-threatening nature of CFS (66). NTIS is a typical feature of critically ill patients in intensive care units, although similar changes in the HPT-axis have been observed during calorie restriction and in patients with non-critical chronic diseases, such as heart failure, chronic obstructive pulmonary disease, and diabetes mellitus (67), also referred to as mild, or atypical forms of NTIS (36, 67). All of these conditions, especially calorie restriction, might find a common denominator in an adaptive response aiming at saving energy and body protein in order to outstay any potential acute stress stimulus (68–70). Through coordinated changes in thyroid hormone metabolism, transport and receptors, NTIS might mechanistically reflect a cytokine-orchestrated allostatic condition that is remote from the well-known homeostatic negative feedback regulation of the HPT axis (71)."

Sometimes its best not to overthink things. I think a lot of people, the problem is simply not enough calories due to a life of chronic dieting and whatnot. Othertimes, many people under-eat and not necessarily realize it. The body's ideal amount of calories is typically higher than the 2000 RDA value quoted especially for males, and I believe even some females around here eat upwards of 3000 calories. My optimal is easily 4000-5000 calories depending on the day.

 

[Regina]

As Amazioniac mentioned, I can relate.

My shyness and perfectionistic tendencies were mainly the result of being teased relentlessly from the time I started kindergarten until high school. I was told if I ignored it that they would stop so I kept quiet, trying my best to be invisible in hopes that the boys would leave me alone and inadvertently became "shy" and adopted their views of me as my own, becoming very critical of myself. I was also molested at a young age and felt I needed to be perfect to make up for "my sin" so that I could be in heaven with my family when I died.

Once I learned my worth, really got it, not just told myself I'm worthy but got the magnitude of it and that it's innate, everything changed. I no longer have to dilute myself and wear myself ragged trying to please others in an attempt at winning their love and approval because I already have enough love and respect for myself. And I no longer require finding my tribe in order to feel like I belong. I actually put myself in places where I'm not the same as others around me. For example — here.

I've always been overly concerned with not hurting others to the point that I let others abuse me. It hadn't occurred to me that while I was trying my best to not hurt others, I was hurting myself in the process. Why is it okay to hurt ourselves, you know? Anyway, I wish you all the best in overcoming your health issues. :)

Great explanation Jennifer. I love this "I no longer have to dilute myself and wear myself ragged" and "I no longer require finding my tribe...".

 

[zewe]

interesting. Based on testing I know I have high IgE/mast cell problems. But cypro just makes me sleepy. maybe i need to try it for longer?

Chronic Fatigue, Histamine & Mast Cells

Chalk up another one to a dysfunctional immune system – Chronic Fatigue Syndrome (CFS). Researchers recently proved (for the first time), that the condition is not psychosomatic (yeah, thanks for calling us hypochondriacs all these years). This wasn’t news to some: according to NHS funded researcher Dr. Theoharides, CFS is one of many mast cell linked conditions that he has known to be linked for years. It wasn’t so long ago that narcolepsy was pegged to an imbalance of brain histamine levels.

Scientists in Australia have found that immune cell receptor abnormalities are behind CFS debilitating symptoms. So basically a receptor defect, which is really a problem because there are many cells and so many receptors to mess with, can’t transfer calcium from the cell to the outside. The discovery of abnormal calcium cells coincides with where CFS pain usually happens, in the brain, spine, pancreas and stomach.

To date there’s still no cure for CFS. Doctors and researchers have been telling folks it’s all in their head and that all they need is more exercise (yes, I’m referring to the PACE trial debacle). The researchers say they believe that it affects from 1%-2% of the population (presumably Australia they mean?).

According to Dr. Theoharides, director of Immuno pharmacology and Drug Discovery at Tufts, CFS is a complex disease involving the nervous, hormonal and immune systems with symptoms that include fatigue, sleep disturbances, malaise, muscle aches, migraines, gastrointestinal complaints, and cognitive problems. Viruses and inflammatory cytokines (like those in mast cells which contain histamine) play a role. He says that the stress hormone CRH (corticotropin-releasing hormone) activates brain mast cells (which contain histamine and other inflammatory mediators), and that this causes blood-brain-barrier disruption. His research shows that there’s a relationship between the mitochondria, calcium and mast cell activation.

As someone who has literally fallen asleep on a plate of food, I can attest to the narcolepsy-histamine link. It all depended on how long it would take me to eat. If I had a short meal, I might make it to the sofa before falling into my food coma, but a long one meant face-in-food for dessert. The weird thing was I wasn’t actually asleep.

My eyes were forced closed, all movement would have to cease, and I’d be aware of the world around me, but incapable of interacting with it. The experience was more like something out of a nightmare where you’re paralysed but still able to be hurt. It’s apparently called syncope.

I’d lie there in a weak panic, feeling my heart beat slowly ebb away, as I begged my thoughts to magically reconnect with my voice to tell people, hey, I’m actually awake! Don’t be fooled, I’m not asleep. But no matter how hard I tried to convey this to people, they were all convinced I was dreaming it all up.

Symptoms like these were only manageable by eliminating scores of healthy food. Once I was stable however it took me a long time to work out how to add nutrition back – here’s how I did it.

Whether it was a histamine-narcolepsy link, or a mast cell-CFS one, I ended up spending about a year mostly in or on bed, and desperately trying to make people understand that my inability to climb a flight of stairs at times isn’t a lack of cardio fitness (mine could always be better but it’s still good) but rather a result of my mast cells having a temporary bout of madness.

Interestingly, Harvard neuroscientist Dr. Michael Van ElZakker has a hypothesis he’s working to prove, that an infection of the vagus nerve, which connects the brain to the stomach, can cause a prolonged “sickness response”. This human response to illness involves extreme fatigue, probably to force us to rest up and isolate us from other humans to not spread the virus. He believes that in some cases the vagus nerve, which is responsible for signaling the need for this response, remains on high alert, which keeps the body stuck in this more.
SOURCE:
https://healinghistamine.com/chronic-fatigue-histamine-mast-cells/