Overtraining Syndrome, Ketone Ester Supplementation as possible ME Rx?

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One of favorite non-guilty pleasures: reading OutsideOnline articles as a vicarious substitute for the active life I used to live over 2 decades ago. This month, they had a riveting podcast on OverTraining Syndrome (OTS), https://tinyurl.com/y6b6fwjx and IMO there are multiple parallels with M.E. that I just had to share. Recognizing that there are other posts on OTS,I think this is "new", info on OTS, with apologies if not.

IMO some of the key reasons we should keep our sights on OverTraining Syndrome:
- There is a LOT of money going into performance enhancement and metrics for elite and super-elite athletes. Think ketone esters that can put you into ketosis in 30 minutes; micro skin sensors for lactate that could avert a crash... so many exciting developments coming down the pipe.
- There is LOT of money (think DARPA) going into performance enhancement for the military. See the later post, and YouTube video link on Ketone Ester supplementation. IMO if Ketone Ester supplementation is good enough for Navy Seals etc, it's good enough for M.E. patients.
- The physiological parallels between M.E. and OTS might indicate that OTS research could help (subsets of?) M.E. patients
- IMO our community should piggy-back as much as possible on this parallel stream of research funding. (think Dr Klimas's GWI/ME/CFS work)

To keep the post lengths more manageable, I'm going to post this in a series of posts. Importantly, these are my very approximate transcripts of segments of the podcast.
1) Overtraining Syndrome (OTS) intro
2) The Fitness Buoy - IMO a fascinating correlate of Pacing
3) Functional vs Non-Functional over-reach
4) Hunger cues, calorie deprivation, Ketone-Ester supplementation, and OTS
5) Correlates with M.E. findings in high-performance athletics. Dauer, metabolic trap?
6) GDF-15; Growth-Differentiation Factor-15. A possible biomarker to catch OTS (or M.E.?) before it becomes full-blown?
7) Hot off the press - "Ketone ester supplementation blunts overreaching symptoms during endurance training overload." Is this a possible Rx for M.E. subgroups?
 
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1) OVERTRAINING SYNDROME.

  • 4:50 “OverTraining Syndrome (OTS) is a kind of a boogeyman for endurance athletes, a ghost of a sickness that leaves you a shadow of your former self, with few answers and fewer options.”
“Anyone who is seriously devoted to their sport, who takes a “more is more” approach to training, and constantly pushes to the edge, might come to find themselves completely, inexplicably fatigued. What do you do when your whole life has been about competing at an elite level, and suddenly you don’t have the energy to pull yourself out of bed?”
 
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2) THE FITNESS BUOY

10:49 Fascinating discussion on THE FITNESS BUOY (IMO so very relevant to pacing for ME/CFS).

“Imagine your fitness is a small foam buoy floating in the water. That water line? That’s your base level of fitness. To improve, you have to put stress on your body, whether it’s lifting weights, running or cycling. You can imagine any hard activity, any fatigue as a force pulling that buoy under water. Then, you rest. Let go of the buoy and it shoots back up to the original water line.

What’s more, if you get adequate rest, your fitness buoy pops ABOVE the water, at least for a while. That’s called compensation. Meaning your body adapts to handle a higher level of stress. And if you apply a new load just before your buoy begins to descend again, the buoy will rise even HIGHER after the next rest cycle. Do that over and over, and your fitness builds.

But here’s the catch. If you don’t allow your body enough rest and you apply more stress on your body, it’s like grabbing that buoy before it’s reached the surface, and pulling it down deeper than before. Now you need even more rest, just to return to your base fitness, let alone reach compensation. Repeat that enough times, pull that buoy deeper and deeper, and you’ll hit the bottom of the ocean.

So training is like a Goldilocks problem. Train just hard enough and rest just long enough, and you’ll get better, more fit. Train too hard or rest too little, and the fatigue pulls you farther and farther underwater, leading to underperformance, illness and injury.
 
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3) FUNCTIONAL VS NON-FUNCTIONAL OVER-REACH

14:35 See “Functional overreach” vs “Non-functional over-reach”.

Functional overreach – an athlete INTENTIONALLY over-cooks it for a training block… Hit this balance correctly, and your fitness buoy launches out of the water in what’s called, “Super-compensation”. But push a bit too hard, or fail to take enough rest and you’ve entered non-functional over-reach… Right as they’re trying to reach peak fitness, athletes over-train intentionally to stimulate super-compensation – athletes should only attempt this kind of functional over-reach a few times a year.

23:40: “Even though elite-level athletes are training under extreme loads, it’s rarely the professional that is bouncing from doctor to doctor, trying to figure out what’s wrong with them. Dr Robert Umrine, a sports physician in Missoula Montana who specializes in treating over-trained athletes, gives the example of one of the Olympians he works with.

“A high-level Olympic athlete, he always entertained me, because I’d ask what he was up to, and he’d say, “Oh, I’m going to take a nap”, and I was like, “Oh geez, it’s 4 in the afternoon”, and he’d say, “Yeah, I usually nep between 3 to 5 o’clock, and then I get up and socialize for an hour. And then I go back to bed and get like 13 hours of sleep and then wake up.”

“He probably trained 35 to 40 hours a week through cross-training, strength training etc… but then at the end of the day, he also slept 14,15 hours a day. And he never really had problems with the over-training type of concept because he had adequate time to rest. He had really nothing else in his life except his sport.

“With this in mind, it’s easy to see why Over-Training Syndrome began disproportionately plaguing the ultra-running community which – especially 10 years ago – had little professional infrastructure and was largely made up of amateur athletes trying to juggle everyday life with training for 100-mile races.”

25:40 “What Dr Umrine illustrates here is that it’s rarely the training itself that tips an athlete over the line from Non-Functional Overreach into full-blown OTS (Over-Training Syndrome). Rather, it’s the accumulation of stresses OUTSIDE of training that does it. An athlete performing at the very edge of their ability (or IMO an ME/CFS patient) needs EVERYTHING ELSE to be perfect. Getting enough sleep. Eating enough food. And staying removed from the everyday pressures of life.

Put another way, when you’re walking a tightrope, every gust of wind risks knocking you down.

And Karin – she was facing a storm. First, there was the boyfriend LOL….”
 
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4) HUNGER CUES, CALORIE DEPRIVATION, SYNTHETIC "KETONE ESTER SUPPLEMENTATION", AND OTS

28:02 Fascinating discussion! Is this an easy ketogenic Rx in ME/CFS?

“It should be no surprise to learn that chronic calorie deprivation is linked with OTS”

Description of a study in Belgium researchers at U Leuuven: They gave athletes a synthetic ketone (fuel only used in starvation) ketone-rich drink or placebo, and those who took the drink sustained 15% higher training load. “Rather than becoming overreached and losing steam, these athletes actually improved”.

“The Ketone Group – their caloric intake kept increasing (with training)… somehow taking ketone kept the body from suppressing their appetite - despite the intense training - and kept their hunger levels in line with their true caloric needs.”

Maybe, we can do something about, “when you’re so fried or cooked, that you just can’t manage to, or don’t choose or don’t want to eat as much as you actually need”
 
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5) CORRELATES WITH M.E. FINDINGS IN HIGH-PERFORMANCE ATHLETICS AND OTS: DAUER, METABOLIC TRAP?

35:27: FASCINATING discussion of what sounds a LOT like Dauer and the Metabolic Trap. “Dr Amrine likens this to what happens to the body in famine”. “The theory is that your body goes into safety mode…”

IMO the OMI and/or other biomedical ME/CFS conferences should invite some of these OTS specialists to our conferences/symposia.
 
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6) GDF-15; GROWTH-DIFFERENTIATION FACTOR-15. A POSSIBLE BIOMARKER TO CATCH OTS (OR M.E.?) BEFORE IT FULLY MANIFESTS?

37:43 “There is currently no cure for OTS other than absolute rest, with no guarantee that your body will ever return to its former performance levels. One of the major difficulties for athletes and doctors remains how to catch overtraining before it becomes OverTraining Syndrome. (NB: MIGHT THIS BE AN INDICATOR TO PROVE THE HARMS OF G.E.T.?)

“Elite athletes have to constantly push themselves right up to the edge of the cliff, extracting every ounce of fitness from their body without overdoing it. But there is simply no objective measure to point at, that says you’re at the risk of falling off (the cliff). Except… maybe that’s no longer true."

GDF-15; Growth-differentiation Factor 15; a marker to prove harms of GET?

38:14 One of the things they measured was appetite hormones. The recent ketone study might have accidentally found a signal that might tell athletes they’re on the verge of overtraining. Growth-differentiation factor-15. A stress-induced hormone that causes you to decrease food intake because you’re stressed out. Its levels were higher in the non-ketone group. Its levels started to climb in the placebo group BEFORE there were signs of overtraining. One of the things the researchers speculate: maybe this is the smoking gun that indicates overtraining is on the way. Could be correlation, coincidence, statistical randomness… all options on the table now. Intriguing pattern that maybe GDF15 is part of the key to this mystery… if athletes (or ME patients??) can take a blood test that shows their GDF15 levels are raised, that could be the kind of specific, objective test that convinces them they should back off before it’s too late.
We all know, your legs are dead, your performance is declining… it’s hard to back off if the medical tests are fine… now this marker might suggest you’re on the verge of overtraining. Maybe that will give the athletes what they need.


(AND MAYBE GDF-15 COULD HELP DE-BUNK G.E.T?)
 
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7) THE KETONE STUDY – HOT OFF THE PRESS!:

https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP277831 J Physiol. 2019 Jun;597(12):3009-3027. doi: 10.1113/JP277831. Epub 2019 May 22.

Ketone ester supplementation blunts overreaching symptoms during endurance training overload.

Subjects from both experimental groups received a 500 ml high‐dose protein–carbohydrate drink (Table 2) 30 min after each exercise session. In addition, immediately following each session and 30 min before sleep, KE subjects received 25 g of ketone ester [96% (R)‐3‐hydroxybutyl (R)‐3‐hydroxybutyrate] to elevate post‐exercise circulating plasma ketone concentrations, as previously shown by our lab (Vandoorne et al. 2017). The ketone ester supplements were purchased from TdeltaS Ltd (Thame, UK) (NOTE: DEVELOPED AT OXFORD UNIVERSITY).

Ketone ester supplements (EXPENSIVE!) available from: https://hvmn.com/ketone-ester
  • The ΔG® ketone ester was invented by Oxford and NIH scientists as part of DARPA “Metabolic Dominance” Program.
  • Protected by a family of US and Global Patents exclusive to HVMN.
  • Elevates blood ketone levels to 3-5 mM in 30 minutes without a salt, acid, or fat load.
Accelerate muscle protein and glycogen resynthesis by 2.5x1.
Reduce lactic acid production by 50%1.
Activate natural anti-inflammatory and longevity pathways4.

FOOTNOTE ON THE COST OF THIS TREATMENT: Each bottle is 25g. If I interpret this correctly, the study used 1 25g bottle after each exercise session, and 1 25g bottle before sleep. The manufacturer, HVMN recommends 25g before training. If you took one bottle, that’s over $30. If you did the research protocol from the study, that’s about $70/day. But interestingly, athletes are noticing impact from a single dose, so it may be worth trying.

The manufacturer is clearly getting up the curve on economies of scale. So if more people use this, the cost may well come down.

For now, IMO our well-capitalized M.E. patients (I know, an oxymoron in this community) might be able to be the early-adopters to report back on N of 1 trials. Then again, if enough of us do a $99 trial of 3 bottles, and response is sufficiently swift, it might provide clarity and direction for our researchers on short-term treatment options for the future. Could this help get patients out of a metabolic trap????
 
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The YouTube link from HVMN on ketone ester supplementation:

Ketosis in 45 minutes? Presentation by CEO of HVMN.

Disclosure: I am NOT affiliated with HVMN!
 
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Afternote: A bit of trivia. When I received IVIg treatments that put me into temporary but complete (2 wks-3mos) remission, my appetite and "growling stomach" would return. A hallmark of my over 2 decades of M.E. has been the loss of normal hunger pangs.

Not quite proof-of-principle that appetite hormones such as GDF-15 are relevant in the pathophysiology of M.E., but nevertheless IMO vastly intriguing.
 

junkcrap50

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I know nothing about Overtraining Syndrome (OTS), but I wonder if it is a version of CFS or mild CFS? Because CFS can be brought on by physical stress and physical injuries, not necessarily an infection. It would be interesting to do a metabolomics comparison of CFS and OTS. If they matched up or shared things in common, then I bet we could get a LOT more funding for CFS since it's linked to highly elite athletes who have come down with OTS.

EDIT:
Oops. Posted without thoroughly reading your first post.
- The physiological parallels between M.E. and OTS might indicate that OTS research could help (subsets of?) M.E. patients
- IMO our community should piggy-back as much as possible on this parallel stream of research funding. (think Dr Klimas's GWI/ME/CFS work)
Great minds think alike.
 
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sb4

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@Joy&K0$ I will add my experiences with ketones here. First ketone salts are hard on my stomach. So are MCT oils. I have, however, found that MCT oil improves my tolerance to carbs significantly. I have also found a way to increase the amount without GI upset. Perviously over 1tbsp would cause me trouble. Now I emulsify it in scrambled eggs and can get away with 4tbsps. I did try mct emulsions and powders but they also caused stomach issues, probably because they use fibre and emulsions that have shown to be inflammatory in the gut. I believe egg yolk / phosphatidylcholine to be safer.

I suspect the MCT works to reduce carb symptoms by increasing the amount of Acetyl CoA in the liver and other tissues. If the tissue then has a lot of pyruvate from the recent ingested carbs, it is unlikely to convert the pyruvate to more A CoA through PDH. Instead it will go through to oxaloacetate via PC. Thus averting inhibited PDH. No idea if this is right or if it is acting some other way but thought you might be interested.
 
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Thank you sb4 and junkcrap 50. Crashing badly, so this'll be brief.... What stands out for me are 2 things:
1) The potential biomarker (the appetite hormone GDF-15) that manifests as athletes descend into irreversible OTS; might this be a biomarker for ME/CFS progression that could help so many of us who feel that if we hadn't pushed it so far, we might have been able to avert ME/CFS?
2) The challenge of doing a ketogenic diet, and the promise of near-instant ketosis with this particular type of ketone esters. Oh yeah, and the fact that the ketone ester approach is said to reduce lactate production by 50%. 50%!!! I've tried keto a few times, and while it helped, the benefits were marginal, and it was soooo easy to tip out of ketosis. My understanding is that this literally military-grade formulation of ketone esters is vastly superior to any ketone salts, MCT oil, etc available on the market. And that one can achieve ketosis in 45 minutes. I am thinking of trying this stuff to see if it's possible to interrupt a bad crash - or whether one might avert a crash on super-important days. As I've personally had my ME/CFS switch flipped by IVIg into full (temporary) remission a few times, (see Kerr's articles on IVIg in ME/CFS), I very much believe this is a reversible phenomenon. Might ketone esters be a part of getting out of that metabolic trap?
 

sb4

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@Joy&K0$ I would be very interested in your results with ketone esters. I was going to experiment with them however they are f*****g expensive, if you are doing just a one of then the cost is okay.

One of the things that put me off esters is they seem to have the same GI issues as salts and mct. The gut just wants to get rid for whatever reason. I speculate that it could be because no natural food has this high level and it may be a sign to the body that the food has gone bad or something.
 

junkcrap50

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1) The potential biomarker (the appetite hormone GDF-15) that manifests as athletes descend into irreversible OTS; might this be a biomarker for ME/CFS progression that could help so many of us who feel that if we hadn't pushed it so far, we might have been able to avert ME/CFS?
GDF-15 is an available test from Mayo Clinic labs. So, might be interesting to see what kind of levels we have.

2) The challenge of doing a ketogenic diet, and the promise of near-instant ketosis with this particular type of ketone esters. Oh yeah, and the fact that the ketone ester approach is said to reduce lactate production by 50%. 50%!!! I've tried keto a few times, and while it helped, the benefits were marginal, and it was soooo easy to tip out of ketosis. My understanding is that this literally military-grade formulation of ketone esters is vastly superior to any ketone salts, MCT oil, etc available on the market. And that one can achieve ketosis in 45 minutes.
Unfortunately, this product will NOT immediately put you into "ketosis." Ketosis is using ketones as fuel, whether they're endogenous or exogenous ketones (like HVMN). Ketogensis is the metabolism of fat into endogenous ketones.

Yes, this product, ketone ester, will likely provide immediate and available exogenous ketones thus, providing you ketosis. Meaning, this ketone ester will provide you energy even while you're eating carbs and still have glycogen stores. This likely will provide an noticeable bump in energy for CFS patients, since ketones bypass PDH & glycogenesis. And it would give immediate brain fuel. So, good for use during finals/board exams/etc. However, a couple hours after ingesting this ketone ester, you will immediately fall out of ketosis, since you run out of exogenous ketones. You body never switches from glycogensis to ketogenesis when taking this product.

The marketing of this product is deceptive and tries to trick you. In order to use your body fat or edible fats as fuel, you still need to fast or eat zero carbs. You body first has to run out of all carbohydrate stores and glycogen. This product just provides an additional and alternative fuel source of energy while your body is still using glycogensis. Kind of like a "Fat/Ketone Rush" instead of sugar rush.

But this product is very expensive and is only a temporary fix. It'll help CFS patients, since it provides energy to enter the TCA. But as soon as you run out of this product, you'll be back where started. Unless, you go through several days of fasting or zero carbs.

Still interesting and may be helpful however!

I very much believe this is a reversible phenomenon. Might ketone esters be a part of getting out of that metabolic trap?
Perhaps, it might provide an immediate source of energy that the body may need to get out of the trap. (since we're in an ATP defecit). But unlikely to do it alone. It may be able to be used as an immediate escape out of PEM too.
 

BeADocToGoTo1

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2) The challenge of doing a ketogenic diet, and the promise of near-instant ketosis with this particular type of ketone esters... I've tried keto a few times, and while it helped, the benefits were marginal, and it was soooo easy to tip out of ketosis...
I like the idea of cross-over from the athlete community, it is where I first learnt about nutritional ketosis many years ago. However, when you are not feeling well you do have to be very careful with these types of products. I actually became quite ill from an exogenous ketone product, and am not the only one. Look closely at all the other ingredients that are included as well.

Nutritional Ketosis

The best way to get more ketones in your body is to take control of your nutrition and get them endogenously (produced by your own body)!

If you have already taken control of your nutrition (one of the very few things we have complete control over) you might already be in nutrional ketosis. There is no shortcut from having a poor, high carb diet and then just adding ketones exogenously. There is no need to go to extremes, as 0.5-3 mmol/L ketone level in the blood is healthy, very achievable and sustainable.

Nutritional ketosis is how most of our ancestors lived, even as early as a few generations ago.

Ketone Production

Your liver will either produce cholesterol as a vehicle to store excess energy (hence the high triglyceride levels of people eating excess carbs) or utilize internal energy stores (adipose fat) by producing ketones. Insulin and glucagon hormones from the pancreas will stop ketone production as the body realizes it needs to first burn off or store the available glucose in the blood. It is also why intermittent fasting, or eating all your calories during a limited (e.g. 10-12 hours) window during the day will help get you into nutritional ketosis.

Fat Burner vs Sugar Burner

Becoming an efficient 'fat burner' instead of an addicted 'sugar burner' is something I can highly recommend to anyone that is healthy and trying to avoid getting ill or for longevity, and for those of us that are struggling. The, initially stealth but accelerated over time, damage excess glucose and insulin spikes do to the body is not to be underestimated. Just by adding exogenous ketones, this will not go away.

One important factor is that many people tend go to the extreme, which is not sustainable. Ease into it. Keep within a 0.5-3 mmol/L ketone blood level, and determine what that equivalent level of carbs is for your own body. But, 50-100 grams of carbs (not including non-starchy veggies) and limiting the daily calorie window, which is far from extreme, can get you there. Once you are at your ideal body composition, you might even be able to go up a bit depending on your physical activity level. Anything over 150 grams per day, unless you are some type of athlete, and you get back into unhealthy territory again.

Description of a study in Belgium researchers at U Leuuven: They gave athletes a synthetic ketone (fuel only used in starvation)
It is comments like these that are annoying and misrepresenting of ketogenic diets. I have read this 'starvation' mode comment in many places along with the 'ketoacidosis danger' comment that is used often as well. It scares people unnecessarily from a perfectly healthy lifestyle. I would like to have the Belgium researchers look at Mark Sisson (who has been in nutritional ketosis for many, many years) in this link and tell me if he looks like he is starving...:)

https://www.marksdailyapple.com/keto/
 
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A little more on the various forms of ketone supplementation from an intriguing article on Tour de France cyclists, many of whom, it seems are supplementing with liquid ketone esters. https://cyclingmagazine.ca/sections...are-the-tour-de-frances-top-teams-using-them/ . I continue to be riveted by potential research crossovers between overtraining syndrome in elite athletes - and what they do to prevent it - and the possibility of preventing or mitigating PEM and other sequelae in M.E.

"Powdered ketone bodies (ketone salts) are either BHB (beta-hydroxybutyrate) linked to an amino acid or to a mineral salt (sodium, potassium or calcium). This allows the ketone body to exist in powder form and easily dissolve in water. The same way that one consumes protein powder or electrolytes.

Liquid ketone body supplements (ketone esters) contain only ketone bodies. They are attached by an ester linkage to a precursor of a ketone body such as butanediol or glycerol. Studies on fluid supplements are much more conclusive than studies with powdered supplements. These supplements are, however, much more expensive."


Interesting and educational comments, thanks above. Clearly, I'm not a ketosis expert - just posting what I find to be fascinating stuff that may or may not be helpful in our quest to both alleviate symptoms and tame/cure this awful disease.