Breaking the Stress Cycle

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Hey Dave,
I know you favor cyproheptadine a lot but after thinking about your recent unpleasant experience, I wanted to send some information your way. I’ve been learning as much as I can about serotonin and signalling in the body, and it is some pretty deep stuff.

Serotonin modulation is able to detect CO2 in your blood, energy in your liver, pH of stomach, all kinds of stuff. It is also able to coordinate energy production through the brain and liver. Pushing hard on certain aspects of the serotonin system can have profound effects on whole body metabolism. It can also change the bodies reaction to stress like lowered electrolytes and impaired cell respiration. Cyproheptadine I think can push pretty hard in that regard.
Taking it can definitely lead to increased feelings of well being and confidence, essentially the body thinks it’s under less stress than it was before the drug and will turn up production of androgens and will tell the liver to make more T3. The basal metabolic rate will increase. There can still be issues in the body though, that can override this condition. If for example the liver does not have the capacity to generate and use glycogen effectively, for whatever reason, the demands of increased metabolic rate can cause a lot of stress. The body will interpret this stress and act accordingly, which is usually increase of cortisol and adrenaline.
With enough pushing, the bodies long term homeostasis kicks in, and “receptors” in the cell change density to adapt to the new conditions. For instance, increased adrenaline and similar will change the density of adrenergic receptors, possibly causing inappropriate feelings of panic, fast heart rate, etc. The body tries to correct conditions in the blood, and will increase vascular tone and change the response of things like aldosterone, angiotensin, renin, etc.
If you add enough of these factors up, you set up conditions for periods of pretty intense stress in the body. This will be manifest as panic attacks, anxiety, sleep problems, all sorts of distress. The defect in metabolism will lead to more sensitive mast cells, and the histamine, serotonin, and other compounds that they release will cause further problems in cell respiration.
I’m not sure what your dosing was on cyproheptadine or for how long you took it, but it feels like it was a pretty good dose for a few months. That could have some pretty heavy impact (positive and negative) on your bodies ability to regulate. Cypro has pretty decent affinity for the various 5-HT “receptors” that control vascular tone and cellular tone. It has huge affinity for histamine H3 “receptors” which are pretty intimately involved with cell calcium balance. which is the bodies cardinal way of controlling the cells water structuring and energy production.
I wanted to pass that on to you to see if it makes any sense. Obviously when things aren’t going right there are so many things that could be the culprit, but I was thinking that cypro might have been a piece of that pie. Hope you feel good!

Ray Peat Forum Member Diokine, April 5, 2016

I appreciate your post. I’ve taken cyproheptadine in combination with B-vitamins, caffeine, methylene blue, and mineral supplements. At one point, I took over 32 milligrams daily, stopped abruptly, and experienced no noticeable rebound effects.
I’d never use pharmaceuticals indefinitely, and if I take cyproheptadine, it will be sporadically and with a lower dosage.

The problems that you mentioned do exist, as the body strives to remain homeostatic and will upregulate certain receptors. However, the drug will still have a net effect.
My over-prioritization of work and excessive coffee consumption increased my anxiety levels. It’s important to monitor your own response to coffee and adjust accordingly. Prior to developing any caffeine tolerance, just 200 milligrams caused insomnia and suppressed my appetite. This may have further depleted any glycogen in my liver. Abruptly raising the metabolic rate can clearly be disruptive.

Dave Foster, April 5, 2016

Excellent man, sounds like you’ve got things well sorted 🙂
It might be worth it to check out the adverse cardiovascular effects of antihistamines, as well as the mechanisms behind anticholinergic drug toxicity.

RAY PEAT FORUM MEMBER DIOKINE, APRIL 5 and 9, 2016

Thanks for the note.

Cardiovascular safety of antihistamines
Effects of potassium channel blockade and QT interval prolongation are not a class effect, but result from the action of only a few antihistamine drugs – arrhythmias with dramatic effects were observed only in the case of the withdrawn therapeutics – terfenadine and astemizole. Such phenomena are potentially manifested only in the cases of high overdose far beyond the suggested therapeutic levels.

I’m aware of problems such as tachycardia with anti-histamines, as well as elevated blood pressure with dyphenhydramine in particular.
Dr. Ray Peat goes into detail regarding mast cell activation in disease.
Do you know any preventative measures for coronary artery disease and strokes?

DAVE FOSTER, APRIL 9, 2016


Hey Dave,
I’m not speaking in the context of a select group of drugs, or a select group of adverse events related to a class of drugs. Antihistamines and anticholinergics can have a pretty wide impact. Drugs like Benadryl or even cypro for that matter will present with severe cardiac disturbances in the case of overdose, for instance. That is true of a lot of drugs, frankly speaking though. I think it’s safe to say that adverse cardiac events (aside from specific modalities) can be a class effect of antihistamines, given the proper context and dosage. I’m speaking more of the broader implications to the sympathetic nervous system via calcium regulation etc.
You’re absolutely right about the long list of benefits of cypro, but the dosages used are typically on the order of 4mg/day. Dr. Peat has himself said that dosages under a milligram per day may be appropriate to start. I’m really not trying to come off as patronizing or condescending, so I apologize if you get that vibe. Like you said before, context is really key here.
Regarding CAD or strokes; I spent a lot of time researching the mechanisms behind coronary vasospasm, ie. endothelial disruption and the issues it brings. Like nearly every other form of dis-ease, I think it comes down to the bioenergetics. In the absence of proper metabolism and inadequate levels of CO2, endothelial cells will be in more of a “stressed” state, with higher levels of intracellular calcium and increased water retention. This brings with it a whole slew of bioenergetic problems, including reduced ability to react to proper stimulus from the nervous system (adrenaline, etc.) Nitric oxide is the primary emergency vasodilator, but of course we know the problems it can stimulate. Taurine is exceptional in its ability to regulate this calcium flux. When the cells become stressed, and in the absence of CO2, the cells are unable to excrete accumulated water and essentially become “stuck” in this state. Energy production drops further and a vicious cycle sets in. Disruptions in FFA metabolism or PUFA will greatly increase this tendency. Decreased energy production leads to increased lipid oxidation potential, free radicals and other reactive species, and the immune system tries to do it’s best to clean this up. This is of course an extremely simplified view, many other things come into play.
I spent several years of my life with a lot of periods of severe anxiety including passing out, calling paramedics, etc. Not fun.

RAY PEAT FORUM MEMBER DIOKINE, APRIL 10, 2016

What personally helped you? When I periodically raised my CO2 levels with a Frolov breathing device, I entered into a state similar to what you’re talking about.
During cyproheptadine withdrawal, some experience effects associated with excess serotonin such as loss of appetite and diminished sleep quality.

DAVE FOSTER, APRIL 10, 2016

Regarding anxiety, I can remember one particular incident where I had made a smoothie with a bunch of berries, banana, cacao, an avacado, ice, some other stuff. I think I had put some cysteine in it as well, I had recently had my mercury fillings out and I was trying to chelate mercury with the sulfur in cysteine or something. Within minutes of drinking this stuff, I felt like I was going to die. My pulse shot to 160, I got sweaty, started panicking. Another time I called the paramedics after eating some food and popping some digestive enzymes. I got my blood pressure taken at the doctors office for an appointment one time and my blood pressure was 180/140. They did ECG, wanted to call an ambulance. It came down so they didnt make me go to the ER. This was after I had eaten some Olive Garden for lunch at work earlier, and I remarked that I thought it felt high.
Scary experiences. I know now that most of these episodes were caused by a runaway action precipitated by histamine and inadequate metabolism. That makes a huge difference, knowing that you have some idea of what’s going on. It might not help when your head is between your knees and you feel like your heart is going to stop beating, but it will help mitigate the long term effects of the stress caused by these events. It’s the whole learned helpessness paradigm; if you think you have some effective means of escape (whether it be by the knowledge of what to do next, or the realization that these are all lessons in the game of life,) your physiology will reflect that. That personally made a big difference for me, the more the pieces fit into the puzzle, the less I stressed out about things like headaches, light sensitivity, etc. The point being, if I feel like I have an understanding of the biology behind these mechanisms, it means I feel like I have some degree of control.
The effects of unmitigated stress in the body are devastating. A lot of things play into it, but when you start getting into a situation where the body is not able accurately reflect it’s current energy stores, or it’s not able to manipulate the cellular environment through different nervous tones, big problems become apparent. The shift from an environment characterized by high CO2 levels, efficient respiration, high mineral/H2O flux, and sensitivity of cells to androgens, to one characterized by respiration hampered by histamine and nitric oxide, under the influence of estrogen, cannot be understated. The sicker your cells are, the less you can handle. Pretty soon you get to a point where cells will not respond to thyroid, metabolism falls even further, and the body is primed for all sorts of dis-ease including degenerative nerve issues like MS or ALS, cancer, dementia, etc.
I would say recovery can be fairly swift (most major issues can probably be cleared in around a month, depending on conditions) once cellular respiration starts to produce enough energy to allow the cells to spend much of their time in a cooperative living state, with highly structured water and efficient metabolism. This absolutely requires lowering the influence of histamine and serotonin and consequently estrogen. Some steps you can take to do this are;
– Limiting low blood sugar. Keeping the cells in an environment where if they need fuel on short notice, they’re able to get it. This includes large blood sugar drops at night.
– Keeping salt intake high. Through many mechanisms, this can help keep the metabolic machinery moving even in the presence of assault.
– Encourage the turnover of histamine and serotonin. The best thing I’ve found is bright sunshine. It encourages the activity of MAO and DAO (enzymes that process histamine and serotonin.) Get as much of as it you can.
– Neuromodulatory amino acids like glycine. Be careful on the dosing with things like this (including taurine.) Sometimes less is more, and more is way too much. High doses of things like this are indicated for only very short term.
– Bag breathing/exercises and increasing CO2. This was huge for me, partly because it gave me a lot of opportunity to listen to my body and realize what happens to the nervous tone depending on how I’m breathing. If you allow yourself to get slightly starved for air, and be OK with it, it changes the tone of the sympathetic and parasympathetic nervous systems. You will maybe notice a little sweat breaking out on your forehead as you do this. This is good, it means that the CO2 is doing it’s job and cells are expelling water. On that note, if you notice you’re not very liable to sweat, and you’re urinating a lot, this is a good indication that the cells are not responding very well and metabolism may be low.
– Liver health. The liver is the organ responsible for maintaining blood sugar and other nutrient levels. Learn to listen to it. It can sense glucose, amino acids, salt, and many other things through the hepatoportal system. Concentrate on the feelings in the solar plexus area. You should learn to distinguish between when you need glucose, salt, protein, etc.
Some other things off the top of my head are coconut oil, saturated fats are pro metabolic and can be chemically and electrically “insulating” to the different metabolic processes. 4-6tbsp a day is a good amount. Sauna therapy, encourage lots of water/mineral flux in the cell. Sugar, salt, and sunshine are going to be extremely helpful. I see you’re starting some red light therapy, this is excellent. Aspirin can help to oppose the effects of estrogen and histamine, and can consequently lower the influence of serotonin. Use it cautiously, though. Make sure thyroid status is adequate. If your TSH is under 1.5, you probably don’t need any supplementation. Over 1.5, a VERY small amount of T4 (<50mcg/day) may be appropriate. I would probably hold off on thyroid supplements until you start to feel damn decent, otherwise it will make things harder. I like to look at pictures of smiling faces in the morning, this is pro-metabolic. If you’re tired, sleep.
I’ve attached the names to some interviews with Dr. Peat (from KMUD, these series of shows are GOLD by the way,) most of the info I’m presenting here I think would be considered “Classic Peat” as far as the metabolic details are concerned.
Herb Doctors: Autonomic Nervous System (2013)
Herb Doctors: Blood Pressure Regulation Heart Failure and Muscle Atrophy (2012)
Herb Doctors: Digestion and Emotion (NEW 2015)
These are just some select programs, really the entire series is full of so much good information I recommend fully that everyone check them out.

RAY PEAT FORUM MEMBER DIOKINE, APRIL 11, 2016

Thank you so much for all the helpful information. I’ve been consuming around two grams of PUFA daily and using a 10,000 LUX seasonal affective disorder light with positive results. Do you mind if I post your template for non-invasive modalities to restore metabolism?

DAVE FOSTER, APRIL 11, 2016

Hey Dave,
I think that I was probably a lot like you when I was younger. I’m a little older now (close to 30,) and I approach things a little differently. It is definitely valuable to be willing to experiment on yourself. Like William Blake says, “the true method of knowledge is experience.” The only other advice I’d offer in that regard, is that it’s not so much what you do, it’s what you know.
I prefer to control tone with things like breathing exercises, salt, and taurine, but I think GABA agonists can definitely be theraputic when dealing with cholinergic type symptoms (sympathetic response.) I use aspirin occasionally, and I think it can be a great drug in certain cases. I usually don’t use it if my liver is feeling goofy, or if I’m noticing mouth sores. I’ve read reports of people experiencing long term nausea after using it for extended periods of time, and I think it can really mess with the chemistry of the liver if there are other issues. Besides that, it’s great for lowering the influence of serotonin and estrogen. Niacinamide is great too but it can push my blood sugar around a bit.
I’m definitely doing better now, thanks for the comment. Incorporating Dr. Peat’s ideas, and making the decision to take control of my metabolism, has literally been life changing. It’s cleared up longstanding gut issues, skin issues, given me a manlier beard :D, and most importantly of all it has given me the tools to deal with stress. Plain and simple, I don’t get stressed out much anymore. Of course there are moments things get to me, but I understand where they are coming from and realize that I’m going to have no problem working through them. It’s also cleared up things like life long elevated liver enzymes and bilirubin, which was said to be Gilbert’s disease (which is actually a bioenergetic deficit in the UGT1a1 enzyme in the liver, and can be corrected/supported.)
I don’t mind if you post it if you think it will be helpful. It’s all “classic Peat,” like I said. The only caveat I add is that, like we’ve said before, context is key! I don’t necessarily believe in pushing thyroid hormone right away, so some people may disagree with that. It all comes down to knowing your biology and reading your body.
PS. I see you’re doing OJ concentrate. How does that treat you? I sometimes get heartburn/histamine reactions from OJ concentrate. Sadly for me, nothing cuts it but fresh squeezed oranges. I’m very particular about them too, once I find a good source I’ll go through a little under a case (40lbs) a week.

RAY PEAT FORUM MEMBER DIOKINE, APRIL 12, 2016

Nothing like a manlier beard! I’m having to trim mine a bit more often as well. Funny that you have elevated bilirubin, as I had Gilbert’s syndrome in high school during periods of ketogenic fasting.
Coconut oil has helped my gut issues. With around three tablespoons daily, I now tolerate almost any food, although starch still gives me fatigue.

You stress the importance of healthy liver function, and what would you recommend for that?

DAVE FOSTER, APRIL 12, 2016

Manlier beard, more hair in general it seems like. I do notice that with increased androgen activity comes increased chances for skin irritation, and I’m prone to that already so I’ve really got to be on top of stuff or my skin lets me know. I also did a ketogenic diet in high school, I lost about 75lbs but I think that it really precipitated a lot of health problems later on (no kidding?!)
Fresh squeezed oranges can definitely be expensive, I’m usually pretty stoked when I can find them around 50c / lb. They make such a difference for me that I find a way to justify the cost almost any way I can. I find similar things with coconut oil, especially if I’m in the middle of some cloudy days or something. When I was really pushing hard to correct metabolism I was probably doing close to 10tbsp of it per day and tolerating it really well. I’ve really noticed that whole body metabolism plays into things like food sensitivities. In other words, a reaction to something might be brought about because of specific or general metabolic deficits, and correcting that condition should limit reactions to food and other stressors.
I haven’t used the BreathSlim device, but it looks excellent. I think you’re right on with the respiratory resistance, the body seems to more or less set the tone based on conditions when it thinks its exhaling. I’ve thought of writing on different breathing exercises, I’ve found pretty different effects from the different ways. Also check out polyvagal theory, I want to do a post tying polyvagal theory and breathing exercises together and how they can make a profound difference on metabolism.
Liver health was a big one for me. Like I said, I’ve always had elevated enzymes and what would probably be considered a “sluggish” liver. I tried to pay as much attention to the sensations that I experience in the liver and solar plexus area after certain supplements, environmental conditions, or after eating something. You will learn to know when you need some protein, or when you need some salt, or if your blood sugar is dropping. I can tell very quickly if my blood sugar is dropping, first in my cognition and several minutes later in my liver. I can also tell how my cortisol response is overnight by how my hunger feels in the morning. Focus on the feelings you get when things are going well, like when you’re laughing or thinking of people that bring warm feelings. Those warm feelings are direct action on the liver via the vagal nerve and serotonin system. They can completely change the functionality of the liver in almost an instant. Considering your liver produces the most T3 in the body, and controls so many aspects of metabolism (consequently CO2) production, it can really pay off to make sure that it stays happy. I use red light directly on my liver, you can absolutely feel the physiological effect from this. I probably use 2-3 sessions of 10 minutes each, 630nm red LED (though a little further out, >800nm would probably be better) 25LED array. I’ve also started supplementing phosphadityl choline, around 10g mixed with cacao, 1g glycine, a little half and half, cinnamon, salt and maple syrup. I feel this has been helping a bit. I also drink coffee…. a lot of coffee. It’s one of the things I feel I tolerate really well and my body definitely tells me that it wants it. The sauna feels like it helps a lot as well.
Pleasure talking with you!

RAY PEAT FORUM MEMBER DIOKINE, APRIL 13, 2016

Thanks for the info. I’ll definitely read into polyvagal theory. I doubt that the red light from heat lamps will affect the liver, but the more powerful types might. Pleasure talking to you as well!

DAVE FOSTER, APRIL 13, 2016

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