Serotonin: The Misery Hormone

Similar to cholesterol causing heart disease and saturated fat clogging your arteries, serotonin's role in depression and anxiety, as portrayed by the mainstream, seems to be completely bogus. 

Serotonin's ability to increase ACTH, which increases cortisol, suggests that it precedes many functional models that attempt to "correct" stress related disorders (hair loss, leaky gut, insomnia, elevated cortisol, food intolerances, low testosterone, high estrogen, etc.).

Serotonin = Stress

One of Dr. Peat's central ideas is that estrogen, adrenaline, and serotonin are all part of the "emergency" stress response.

Corroborating Dr. Peat's theories are the works of Hans Selye and Constance R. Martin. In Endocrine Physiology (1985) Martin describe serotonin's role in stress:

"The amine [serotonin] plays important roles in the regulation of pituitary hormone secretion. It is implicated in promoting prolactin release in response to suckling stimulus, and it affects the secretions of growth hormone, ACTH, TSH, and the gonadotropins." (Martin) 

"Serotonin acts centrally to affect renin release, and it promotes ACTH secretion." (Martin)

While commonly thought of as a neurotransmitter found exclusively in the brain, serotonin is mostly found in the intestine:

"Approximately 98% of total serotonin is found outside of the central nervous system. The blood platelets and gastrointestinal tract account for around 95% and serotonin is a component of both central and peripheral mast cells." (Martin)

Serotonin can be increased several different ways:

• Because the largest concentrations of serotonin are found in the intestine, foods that digest poorly or are irritants (gluten, carrageenan) can cause increased levels of serotonin (Peat).
• Serotonin is bound in blood platelets. Platelets "spill" their serotonin when there is too little carbon dioxide in the blood (Martin, Peat).
• Elevated free fatty acids ("burning fat for fuel") generates less CO2 than the oxidation of sugar and can increase the influence of serotonin (Peat).

How The Hell Did This Idea Become So Backwards?

Besides being a visionary, Peat is a bona fide nutritional historian. In this interview, Peat recalls the details behind the promotion of serotonin from the "hormone of misery" to the "hormone of happiness."

"The misrepresentations about LSD, as a powerful antiserotonin agent, allowed a set of cultural stereotypes about serotonin to be established. Misconceptions about serotonin and melatonin and tryptophan, which are metabolically interrelated, have persisted, and it seems that the drug industry has exploited these mistakes to promote the “new generation” of psychoactive drugs as activators of serotonin responses. If LSD makes people go berserk, as the government claimed, then a product to amplify the effects of serotonin should make people sane."

Experiment

• If you completely zoned out, watch this video about serotonin's role in hair loss/health.
• Increase calcium consumption, which should increase CO2.
• Consume salt to taste, which will also increase CO2.
• Obtain adequate carbohydrate and protein, which will increase metabolic rate.
• Experiment with caffeine (also include adequate sugar). Caffeine can increase metabolic rate and B1 can increase CO2.
• Consume a raw carrot daily. The carrot acts as a natural antibiotic decreasing serotonin and the absorption of estrogen and endotoxin.
• Consider getting labs done for CO2, lactic acid, whole blood serotonin, ultra-sensitive estradiol, and a complete thyroid panel (TSH, FT3, FT4). 

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Comments

[Dylan]

You may recall in a radio interview with Ray Peat that a man asked why after eating a "big bowl of sweet cereal" he fell asleep and Ray Peat responded by saying that is what happens when you repair your thyroid. Given your first explanation of how serotonin can be increased, do you think it's possible that the nap inducing meal could be a result of gut irritants causing an increase in serotonin?

[Dr.Andro]

Who tells you whether serotonin is the chicken or the egg? I mean its production could well be increased in states of inflammation as a means to counter the latter... saying that it must be inflammatory, because it is elevated in states of inflammation is simply idiotic. That would mean that cortisol is inflammatory (which it obviously IS NOT) ... the same question arises for estrogen

here is some food for thought

Estrogen anti-inflammatory activity in brain: a therapeutic opportunity for menopause and neurodegenerative diseases
Elisabetta Vegeto, Valeria Benedusi, and Adriana Maggi*
Centre of Excellence on Neurodegenerative Disease, University of Milan via Balzaretti, 9 20133-Milan, Italy
*Corresponding Author Email: adriana.maggi@unimi.it
Small right arrow pointing to: The publisher's final edited version of this article is available at Front Neuroendocrinol
Small right arrow pointing to: See other articles in PMC that cite the published article.
Abstract
Recent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer’s and Parkinson’s Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia.
Keywords: Estrogen, microglia, neuroinflammation, Multiple Sclerosis, Alzheimer’s disease, Parkinson’s disease

if you listened to Lita Lee on the podcast where Peat usually appears, you will have noticed that she always talked about balance, and when asked "What balances serotonin" she was unable to come up with "Dopamin" < I mean BALANCE? Hello? This "black and white" thinking that is going on in the health-bloggosphere is really driving me nuts!

[Danny Roddy]

@ Dylan, which interview is that?

@Dr. Andro,

My research is based off Dr. Peats work. His central thesis is that estrogen and serotonin (and endotoxin) promote a wide array of stress hormones. Reviewing lab work of others with MPB, my own years of labs, and studying the work of Peat, have lead me to these ideas. It wasn't until I was able to decrease my serotonin levels that my prolactin and high estradiol levels fell.

How can I be for sure that it was serotonin? I can't be. Chicken or the egg? I'm not sure, but Peat is suggesting that serotonin one of the starting points in stress and I believe he's onto something that's often ignored in the mainstream.

How many patients of yours do you measure their whole blood serotonin?

[Dylan]

Interview on KMUD from 9/17/10 titled "Sugar I" at 44:00.

http://www.tempfiles.net/download/201109/210546/Kmud_SugarI_kmud_100917_190000fritalk.html

Ray Peat and the host approach the question trying to attribute sleepiness to the benefits of sugar on the thyroid and adrenaline but I wonder if it is possible that the sleepiness is related to serotonin as a result of gut irritation.

I've always been interested in why food can sometimes cause sleepiness and it sounds like serotonin could play a role in it.

[Björn]

Serotonin can't cross the blood/brain barrier. How do you propose that manipulating peripheral serotonin will have an effect on prolactin and acth secretion?

[Danny Roddy]

@Bjorn,

During stress there is an increase in free fatty acids. Peat has proposed that free fatty acids increase tryptophan's entry into the brain.

[Björn]

Yes, but you are also talking of not eating gluten because it causes serotonin release in the gut. I fail to see the logic behind that. Care to explain?

You also recommend "adequate sugar", but since an insulin response to a meal without protein results in higher tryptophane in the blood and as a result more serotonin in the brain it seems counter-intuitive. I'd be interested in your thoughts on the matter.

[Danny Roddy]

@Bjorn,

From my understanding, serotonin doesn't have to cross the blood brain barrier to be harmful.

"Serotonin's contribution to high blood pressure is well established. It activates the adrenal cortex both directly and through activation of the pituitary." Ray Peat

Simply having too much in the blood can cause inflammation, the promotion of other anti-hair hormones and fibrosis.

Allergens, like gluten, cause the gut to give off serotonin.

I recommend adequate protein and sugar. Specifically gelatin.

[Ryan]

Couple of questions. Doesn't the fructose in sugar get converted to free fatty acids by the liver? This would raise the levels in the blood and be the opposite of what is wanted, correct? Would a bowl of rice be more beneficial because it is straight glucose? Also, I thought activating the adrenal cortex would have an anti-inflammatory effect and not an inflammatory one?

[Danny Roddy]

@Ryan,

I'm not a biochemist and I don't pretend to know everything about the oxidation of glucose/fructose, but Peat has mentioned that while the liver has the highest ability to handle fructose, it is not the ONLY organ that can metabolize it.

The idea that fructose is tolerated better than glucose in diabetics goes back to the 1800s.

From my research fructose increases the utilization of glucose and is very efficient in refilling liver glycogen.

More info on fructose:

http://www.dannyroddy.com/main/2011/10/27/reader-mail-beneficial-effects-of-fructose-overweight-doctor.html
http://www.dannyroddy.com/main/2011/11/14/lets-drop-acid-smoke-fructose.html

Increased cortisol would have a temporary anti-inflammatory effect, while it destroys your tissue in the long run. Hardly worth the benefit.

[john]

Isn't insulin, so even a mixed meal, a main driver in increased tryptophan/serotonin?

Regarding CO2, high carb will not necessarily help in general, because glucose respiration inefficiency increases production of lactate. Ketone (and maybe fatty acid too) conversion to CO2 is more efficient, at least in the brain according to http://www.ncbi.nlm.nih.gov/pubmed/1114894, but I have also seen the same in other studies with lactate and high carb (or anything that increases glucose oxidation).

I've seen that vitamin A has some anti-serotonin effects (as well as pro-dopamine), and vitamin D may have pro-dopamine effects.

Serotonin receptor antagonists reverse UV-induced skin damage/cancer and increase slow wave [deep] sleep, but in some studies they hinder mental processes.

On sugar "repairing thyroid," why is this?...because stress hormones are temporarily lowered? I thought that post-meal tiredness was a hyper-insulin-serotonin release, creating a hibernation-like state...I would like to see a study looking at the sleep quality there. Also, I think that without continual sugar consumption, there is strong rebound of stress, so that is something to consider.

[Danny Roddy]

@John,

Thyroid, CO2, and estrogen seem to be the most important variables. Insulin resistance, a condition that is similar to hypothyroidism, which could decrease CO2 and increase serotonin due to reliance on free fatty acids.

Sugar and the thyroid, Peat has explained that thyroid hormone production can be affected locally by the amount of glycogen in the liver. Low glycogen = less thyroxine can be converted to T3.

[Louise]

Danny-- great stuff!!

One question-- how do you feel about HCL supplements to increase stomach acid/support digestion? I've never heard Peat talk much about digestion, but then again he does propose a diet for similar to that of young children (very easy to digest) ;) Also- does the digestive ease of raw food a reason you prefer it?

Keep it coming!
Louise

[Danny Roddy]

Thanks Louise,

I think HCl can be beneficial, but there is probably a specific reason digestion isn't up to par (thyroid).

For digestion Peat usually mentions the carrot along with upping thyroid function.

I'm not much of a raw foodist anymore. I do raw eggs and that's about it. I don't think it's necessary.