RED-S Syndrome, does it share ME/CFS metabolic Aetiology?

WantedAlive

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It has been documented that overtraining athletes can get ME/CFS. This has always perplexed me, perhaps this might be mistaken for RED-S Syndrome, but looking deeper might there be some common aetiology in both syndromes?

RED-S (Relative Energy Deficiency in Sport) is attributed to energy intake deficiency relative to energy expenditure required for health. It was formerly known as ‘Female Athlete Triad’ to describe the three interrelated components: disordered eating, menstrual dysfunction, low bone mass. It was then changed to RED-S to include males who also acquire the disorder (minus the menstrual dysfunction). Recently, the IOC has expanded the physiological impairments to include metabolic, immunity, cardiovascular, gastrointestinal, and haematological consequences.
Source: BMJ content/52/11/687

Clinical symptoms of RED-S may include disordered eating, fatigue, hair loss, cold hands and feet, dry skin, noticeable weight loss, increased healing time from injuries (e.g., lingering bruises), increased incidence of bone fracture and cessation of menses. Affected athletes may also struggle with low self-esteem and depression.
Upon physical examination, a physician may also note the following symptoms: elevated carotene in the blood, anaemia, orthostatic hypotension, electrolyte irregularities, hypoestrogenism, vaginal atrophy, and bradycardia.
Source: Wikipedia

RED-S results from low-energy diets (intentional or unintentional) and/or excessive exercise. Energy deficiency reduces hypothalamic pulsatile release of gonadotropin-releasing hormone, this impairing anterior pituitary release of gonadotropins. In women, reduced FSH and LH pulsatility produces hypoestrogenism, causing functional hypothalamic amenorrhea (absence of period) and decreased bone mass. In men, it reduces testosterone and negatively affects bone health.

Moreover, LEA (low energy availability) alters other hormonal pathways, causing physiological consequences, such as alteration of the thyroid hormone signaling pathways, leptin levels, carbohydrate metabolism, the growth hormone/insulin-like growth factor-1 axis, and sympathetic/parasympathetic tone. This review explains and clarifies the effects of RED-S in both sexes.
Source: pubmed/32557402

Obviously, LEA (low energy availability) is the common aetiological factor between RED-S and ME/CFS, but I’m quite surprised at how similar many of the symptoms are.

Treatment for RED-S includes reducing exercise and eating more. This, I find very interesting as a diagnosed severe PwME, as I have trouble eating enough. I have to eat very measured meals to avoid long-lasting dyspeptic symptoms through the night which completely ruin my ability to sleep. For me, it’s less about the food type, it’s the meal size that I have an intolerance to. When I do over-eat and trigger dyspeptic symptoms, I’ll have a god-awful night’s sleep, but strangely wake up with more energy the next day. This I attribute to increased energy intake from a more prolonged digestion of a slightly larger meal.

Now, here’s a story of a young student diagnosed with RED-S who was encouraged to eat more calories and bone building medicines. He didn’t improve much, and he later developed ulcerative colitis. He finally found remedy in the ketogenic diet - the very diet that athletes are warned to avoid for fear of developing RED-S!

Again, there is a similarity here with ME/CFS which is sometimes referred to as the ‘starvation disease’, yet many patients seem to do better on the ketogenic diet (a starvation diet) as have I.

My curiosity with RED-S is that it appears to be an energy supply-demand imbalance and that once the body’s energy reservoir is depleted beyond a certain level it is difficult to recover from. With ME/CFS being a hypermetabolic state simulating an overtraining athlete with insufficient nutrition, there could be a similar pathology at play. It’s as if the body is locked into breaking itself down for energy at a rate faster than nutrition can substitute both current and reserve energy demand. I suspect this may be a different phenomenon from refeeding syndrome. Slowing the metabolic rate along with adequate nutritional intake might be the only way to escape this.

I am assuming unlike ME/CFS that most RED-S patients recover eventually. It would be interesting to learn more about those recoveries in case there’s something that may aid ME/CFS. Have any PR members experienced RED-S or know anyone who has and can describe the experience? For example, I have not observed any description of PEM in RED-S, or even much discussion of levels of fatigue, I can only imagine it's pretty mild compared to ME/CFS.
 

WantedAlive

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I also have constant hypercarotenemia...
You do? I wasn't expecting that. But now that I look into it I see it's quite common in anorexia, so perhaps it's quite common in ME/CFS as well.
Increased serum lipids also cause hypercarotenemia because there are increased circulating lipoproteins that contain bound carotenoids. Finally, in certain disease states, the metabolism and conversion of carotenoids to retinol is slowed, which can lead to decreased clearance and increased plasma levels.
Source: Wikipedia

So, now I'm wondering about amenorrhea, hypoestrogenism and decreased bone mass in ME/CFS, anyone have that too?
 

vision blue

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Interesting stuff. Is this the Same warburg effect, glycolosis, fermentation, lactate And pyruvate again in different Wrapping paper ?

Another thing this made me think of is how Ive found msny with CFS describe themselves as super active before the illness- the kind of person who is high energy and goes from one activity to snother. Ive always wondered if this is just people trying to make a point that CFS really is a disease by emphasizing the contrast between before and after- or whether cfs folk On average were actually atypically more active and energetic than average before it hit.
 

xebex

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Interesting, I came down with ME when I was training as an athlete but I didn’t have an eating disorder or low bone mass but potentially did have silent celiac which could cause the same issues especially if training very hard- I dont believe I was Over training as was I training less than friends in the same Club and they were fine. My sister is officially diagnosed celiac and my test came up negative but gluten free diet does help with some symptoms, didn’t make a difference to my PEM though and over the years even though strictly gluten free I still got worse.
 
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I had RED-S and ignored all the signs, eventually ended up with ME. I never had low bone mass or menstrual irregularities (although my dietician said for the amount I was eating he was surprised I didn't) and from my understanding all three conditions in the original female athlete triad don't need to be present in order to be diagnosed with RED-S for a female.

When I had RED-S I was undereating and overtraining. I was tired most days, but I could still get in the gym and lift heavy weights or do a 30 min HIIT workout. No problems with sleep, slept a solid 8 hours a night and woke up feeling refreshed. No PEM, but I'd been training for years by that point and could recover from exercise fairly quickly. The main things I noted with RED-S were the daily sleepiness, and I was very very slow to grow any muscle. Lots of trouble losing any weight too.

ME has been different. PEM, muscle weakness/shakiness that I'd never experienced before. Out of control nervous system and insomnia. Also some fibro pain (recently diagnosed by my specialist).

Feel free to ask me any questions if you want to know more.
 

WantedAlive

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ME has been different. PEM, muscle weakness/shakiness that I'd never experienced before. Out of control nervous system and insomnia. Also some fibro pain (recently diagnosed by my specialist).
@Senta Very interesting, thanks for sharing. A component of the ME/CFS pathology is metabolic, which appears to manifest in a starvation state concurrent with a hypermetabolic state, and this imbalance appears to mirror RED-S (except in this case the hypermetabolism is exercise-induced). Did you experience hair loss, cold feet and hands, OH and some of the symptoms listed above that are also seen in ME/CFS? I'm fascinated by this, particularly cold hands/feet as it may hint to what's causing it in ME/CFS.

So did you have RED-S before ME/CFS? If so, did you recover from RED-S, how did you do this? As I eluded to in the thread, getting into an anorexic state is like a going past an energy crisis threshold the body sometimes struggles to recover from, and how you recover from RED-S may help some with ME/CFS diets.
 
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Did you experience hair loss, cold feet and hands, OH and some of the symptoms listed above that are also seen in ME/CFS?
No I didn't experience any of those symptoms. The hair loss and cold feet/hands especially sound to me like severe anorexia symptoms, I never got to a life threatening state with my undereating/overexercising.

So did you have RED-S before ME/CFS? If so, did you recover from RED-S, how did you do this?
I had RED-S before ME, it's what led me to developing ME as I ignored it for many years. I had my first severe ME crash in 2019(not realising it was ME at the time), and waited 6 months before finally seeing someone about it. I saw a dietician as I knew I wasn't eating enough and I had never heard of ME before anyway. He diagnosed with me RED-S initially and I made significant changes to my diet that improved my condition so much that I felt 90% recovered. My condition slowly worsened over the course of 2020 as I was still exercising heavily, that plus other stressors caused my second major ME crash in October last year.

I do think diet is extremely important for ME, I have no idea if I've recovered from RED-S because having ME means I'm tired a lot anyway but I do know I would be feeling a whole lot worse if I wasn't eating a balanced diet and still restricting calories.
 

pattismith

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I think iron deficiency (with or without anemia) highly correlates with this syndrome

Iron-deficient states are particularly frequent in highly trained athletes, and even more in women [16].
The mechanism of these deficiencies is complex: hemolysis resulting from mechanical damage on red
cells, higher iron loss in urine, faeces, or sweat, decrease in iron digestive absorption, some disturbances
in erythropoiesis, or inadequate intake.
In the case of “sports anemia” the effects of this deficiency on
performance are well known: there is a reduction in exercise performance and a decrease in working
capacity, with a higher accumulation of lactate into blood and a lower VO2max

. Relationships between iron deficiency in trained subjects, and either erythrocyte metabolism, oxygen consumption, or blood lactate have been extensively studied. However, whether iron deficiency is associated with hemorhe-ological changes is poorly known. Experimental studies in iron-deficient rats have evidenced a lower erythrocyte flexibility that seemed to be related at least in part to a lower hemoglobin content of erythro-cytes.

Therefore, we investigated relationships between iron status (as reflected by plasma ferritin) and blood
rheology in sportsmen. Our results show that sportsmen with low plasma ferritin exhibit a higher blood
viscosity, a higher plasma viscosity, and a higher red cell aggregabilitity when compared to sportsmen
with normal plasma ferritin
.

saida_iron.pdf (free.fr)

(PDF) Hemorheological disturbances in the overtraining syndrome (researchgate.net)


It has been documented that overtraining athletes can get ME/CFS. This has always perplexed me, perhaps this might be mistaken for RED-S Syndrome, but looking deeper might there be some common aetiology in both syndromes?

RED-S (Relative Energy Deficiency in Sport) is attributed to energy intake deficiency relative to energy expenditure required for health. It was formerly known as ‘Female Athlete Triad’ to describe the three interrelated components: disordered eating, menstrual dysfunction, low bone mass. It was then changed to RED-S to include males who also acquire the disorder (minus the menstrual dysfunction). Recently, the IOC has expanded the physiological impairments to include metabolic, immunity, cardiovascular, gastrointestinal, and haematological consequences.

Obviously, LEA (low energy availability) is the common aetiological factor between RED-S and ME/CFS, but I’m quite surprised at how similar many of the symptoms are.

Treatment for RED-S includes reducing exercise and eating more. This, I find very interesting as a diagnosed severe PwME, as I have trouble eating enough. I have to eat very measured meals to avoid long-lasting dyspeptic symptoms through the night which completely ruin my ability to sleep. For me, it’s less about the food type, it’s the meal size that I have an intolerance to. When I do over-eat and trigger dyspeptic symptoms, I’ll have a god-awful night’s sleep, but strangely wake up with more energy the next day. This I attribute to increased energy intake from a more prolonged digestion of a slightly larger meal.

Now, here’s a story of a young student diagnosed with RED-S who was encouraged to eat more calories and bone building medicines. He didn’t improve much, and he later developed ulcerative colitis. He finally found remedy in the ketogenic diet - the very diet that athletes are warned to avoid for fear of developing RED-S!
.