Serotonin has always been thought (or is still being though) of as the happy hormone and that by increasing it, it has an anti-depressant effect, right?
What if I told you that’s not true at all. SSRI drugs are the most commonly prescribed drug for depression, anxiety and other mental disorders and more than 90% of the people on anti-depressant medication are on SSRI. Doctors prescribe it at the drop of a hat and most don’t even know the severe side effects that come with it or educate their patient on them.
Now you might think, we’ll so many people do get benefits from SSRI, so why is that?
There are a few reasons, namely:
Although all SSRI drugs inhibit the uptake of serotonin and increase total serotonin levels, some of them actually inhibit certain serotonin receptors, increase allopregnanlone in the brain (alloprenanolone is a GABA agonist which is now approved for depression), increase dopamine as well, inhibit histamine and desensitize other serotonin receptors.
For example, prozac, one of the most common anti-depressant, increases allopregnanolone and inhibits the serotonin receptors, 5-HT2C and 5-HT3.
More recent SSRI drugs under development antagonize even more serotonin receptors. This is because medicine is finally catching up and realizing the serotonin doesn’t “cure” depression. Plus, people on SSRI drugs might tell you they feel better, but most of them experience anhedonia (lack of enjoyment in life), which is a key function of serotonin.
Dopamine is actually of the happy hormone which causes you to enjoy life more, feel motivated, want to do and achieve things and so on. You can read more on boosting dopamine here…
Serotonin is most often elevated alongside an overly active hypothalamic-pituitary-adrenal axis (HPA axis) due to stress, so lowering stress will also have a great impact on lowering serotonin However, chronic stress and trauma can cause chronically elevated serotonin and hypersensitivity even when the stress has passed.
Let me give a little background on serotonin. Serotonin is created from the amino acid tryptophan by the enzyme tryptophan hydroxylase (TPH). There are two such enzymes, with type II being in the brain and type I in the gut.
Gut serotonin accounts for between 95-99% of the total serotonin in the body and brain serotonin 1-5%, however, in abnormal conditions, up to 60% of the serotonin can be synthesized from tryptophan in the brain. Also, when the gut is irritated, gut serotonin production is dramatically increased. More on that later.
Serotonin binds to quite a few receptors, ranging from 5-HT1 to 5-HT7, and each receptor has sub-receptors, for example, 5-HT1 has 4 sub-receptors, 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D.
The serotonin receptor 5-HT1A acts as an auto-receptor, which means that when serotonin binds to the receptor, the body reduces serotonin production. So 5-HT1A is like a sensor for total serotonin in the body and helps to regulate serotonin levels. However, the receptor can get desensitized which leads to chronically elevated serotonin. Not good.
All the serotonin sub-receptors, 14 in total discovered so far, has different actions, which we’ll get more into later. I promise to make this as simple as possible.
Furthermore, once serotonin is released from neurons into the extracellular space, it can bind to it’s receptors, and from there it’s rounded up and taken back to the neurons by the serotonin transport, 5-HTT or SERT. Low SERT means that more serotonin is in the extracellular space and that can bind to serotonin receptors and potentiate the effect of serotonin. In order words, low SERT is not good.
Serotonin is mainly broken down by the enzyme monoamine oxidase-A (MAO-A) and aldehyde dehydrogenase (ADH) to the major serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA). Slow MAO-A activity will lead to high serotonin levels. Most SSRI drugs inhibit the MAO-A enzyme to increase serotonin levels.
Serotonin created in the gut is largely cleared/detoxified through glucuronidation, which requires proper liver function (R).
Now that you got a good background on serotonin synthesis, action and breakdown, lets discuss some of it’s side effects when elevated.
Psychological effect of serotonin
If you want to learn how serotonin could affect your mood/personality, please read my “High Serotonin Personality” article.
Physical effect of elevated serotonin
- bronchoconstriction, asthma and hives (together with histamine), migraines
- chronic fatigue syndrome
- edema and joint swelling are produced by the release of serotonin from platelets or other cells.
- decreased metabolism and can cause fat gain.
- flushing and sweating
- Sensitivity to light, sound, visual disturbances, easily frightened, feeling jumpy (coupled with adrenaline) and experience head twitching (R)
- Serotonin increase core temperate in response to exercise, which then also contributes to reduced exercise endurance (R). Inhibiting serotonin synthesis improves exercise performance.
Hormonal effects of serotonin
- Increases aldosterone (aldosterone increases blood pressure and causes water retention)
- Increases prolactin release (mainly through 5-HT2A) (R),
- Activates the adrenal axis, by increasing CRH, glucocorticoids & ACTH (mainly through 5-HT2C) as well as glucocorticoid receptors via the 5-HT7 receptor (R)
- Increases estrogen receptors (through 5-HT4) (R)
- inhibits testosterone synthesis
- inhibits dopamine release in frontal cortex (through 5-HT1B and 5-HT2C)
Alright, enough with all those alarming, very undesirable side effects. On to how to keep serotonin low.
First I want to discuss with you the most important things you can do on a day to day basis to keep serotonin low and then I’m going to show you which supplements are shown to lower serotonin.
Here follow 60 ways to lower serotonin
#1 Never give up
Giving up is one of the most common signs of high serotonin. When animal were given something to bite on in a seemingly helpless situation, they didn’t develop learned helplessness.
Similarly, if you fight back and conitue to look for an answer, serotonin is kept at bay.
But obviously, be smart with this, being too rigid is also a sign of high serotonin.
#2 Take care of your gut health
As most of the serotonin is made in the gut, it’s paramount to keep the gut in a good condition. Excess gut bacteria, or an excess of pathogenic gut bacteria, promotes the creation of all kinds of toxins in the gut, such as endotoxins (lipopolysaccharides), TMAO, toxic bile acids, harmful protein breakdown metabolites, D-lactate, etc.
Excess gut bacteria or an imbalance in gut bacteria is usually caused by hypothyroid, inadequate stomach acid, hard to digest food, low nutrient dense foods, little to no fruits and vegetables in the diet, stress, etc.
The excess gut bacteria and their toxic creations promote inflammation, gut permeability and bacterial translocation into the small intestine (which leads to SIBO and other gut disorders) (R, R, R, R).
Antibiotic treatment significantly reduces gut microbes and gut serotonin and lowers TPH1, which leads to less serotonin production in the gut (R).
Natural alternatives to antibiotics include:
- Propolis – (Amazon, iHerb)
- Berberine – (Amazon, iHerb)
- 1 tbsp activated charcoal + 1 tbsp coconut oil + 1 tbsp apple cider vinegar
- Essential oils, such as oregano oil, thyme oil, grapeseed oil and cinnamon oil
- Bitter melon – (Amazon, iHerb)
- Monolaurin – (Amazon, iHerb)
#3 Take note of what you eat & your digestion
Even if we’re actively trying to lower excess gut bacteria, we also have to pay close attention to the foods we eat and the effect they have on us.
In a compromised state, any food could cause a problem, whereas in a healthy state, we could tolerate most food. Foods that might cause issues in a compromised state are any pre-biotic or pre-biotic rich food, such as pectins and fructooligosaccharides (FOS), resistant starch, onions, artichoke, garlic, etc.
Signs and symptoms of gut irritation and undigested food include:
- Mini-pukes of the food you ate hours ago
- Tiredness after a meal
- Stomach turbulence
- Stomach cramps
- Eye floaters
- Diarrhea or constipation
- Nasal congestion
- Flu like symptoms
My rule of thumb would be to eliminate fibrous foods (or any food you might suspect is giving you problems) for a week and then to re-introduce them one by one and to see which one affects you negatively.
#4 Keep your liver healthy
Having a damaged liver, due to PUFA consumption, alcoholism, heavy metal toxicity, excess iron, steroid abuse, chronic gut issues, etc, can lead to an increase in serotonin, due to the inability to detoxify serotonin.
Fixing liver function is highly important for optimal health.
A good protocol/stack is to use:
- 600mg+ caffeine daily (can be split up in 200mg doses) – (Amazon, iHerb)
- 15-45mg vitamin K2 (MK-4) – (Amazon, iHerb)
- 5g taurine – (Amazon, iHerb)
- 5g+ glycine – (Amazon, iHerb)
- 400mg+ magnesium – (Amazon, iHerb)
- 1.5g+ niacinamide – (Amazon, iHerb)
The above mentioned supplements will help restore proper liver function, reduce liver enzymes and speed up the detoxification of serotonin and other toxin.
#5 Avoid polyunsaturated fats
Eating a diet high in omega-6 polyunsaturated fatty acids (PUFAs), will exert the most potent effect on increasing serotonin. Most omega 6 rich food is the typical junk food fried in vegetable oils (R). Most baked goodies, fatty pork and chicken, mayonnaise, salad dressing, etc., are also high in PUFAs.
Omega 3, DHA, is also highly serotonergic as it increases serotonin, TPH, serotonin receptor 5-HT2A and decreases serotonin turnover (R).
Omega 3, EPA, increases serotonin release from presynaptic neurons by reducing prostaglandin E2 (PGE2) (R). Omega 3 (cod liver oil) also increases dopamine in rats. (R) However, despite the boost in dopamine, I would stay away from PUFAs. The omega 3 requirement is actually really small, and eating about 4-6oz of Salmon per week should provide enough omega 3.
#6 Lower inflammation
Inflamm-aging is actually a term used in the scientific community used to describe that chronic low grade inflammation is detrimental to health and is one of the best metrics for longevity. Inflammation, such as elevated TNFα, IL-1β, CRP, IL-6, increases brain serotonin as well as serotonin receptors, 5-HT2A, which is implicated in depression, bipolar and anxiety (R, R). Inflammation just gets worse as we age, so stop it while you’re ahead, by eliminating PUFAs from your diet, eat clean, avoiding excess iron/heavy metal foods, etc… I elaborated more on inflamm-aging in this article.
#7 Eat salt & potassium
Salt and potassium, similarly to lithium, forms complexes with serotonin and melatonin, with potassium being more potent than sodium (R). The serotonin transport, SERT, is sodium dependent, so eating too little salt can lead to elevated serotonin in the brain. I recommend to salt food to taste.
#8 Optimize thyroid function
Proper thyroid function, alongside good liver function, is necessary to detoxify serotonin. Serotonin is significantly increased during hypothyroidism and poor nutrition.
Here are a few tips of optimize thyroid hormone production:
- Avoid goitrogenic foods (they inhibit the uptake of iodine by the thyroid), such as cruciferous vegetables such as bok choy, broccoli, brussels sprouts, cabbage, canola, cauliflower, Chinese cabbage, coy sum, collard greens, horseradish, kai-lan, kale, kohlrabi, mizuna, mustard greens, radishes, rapeseed, rapini, rutabagas, and turnips.
- Avoid halogens, such as fluoride (found in drinking water, toothpaste and other chemical production), chlorine (found in swimming polls) and bromide (found in baked goodies)
- Avoid excess stress. Cortisol lowers thyroid hormone production as well as conversion of T4 to T3. Cortisol also makes the body resistant to thyroid hormones.
- Don’t overtrain. Overreaching with proper deloading is still perfectly fine.
- Eat enough calories. A caloric deficit lowers thyroid hormones
- Eat enough protein.
- Eat lots of nutritious foods. A deficiency in vitamins and minerals can lower thyroid hormone production.
If you want an immediate solution for a slow thyroid, take a thyroid supplement in the meanwhile while you’re working on optimizing the rest. Here are a few options:
- TyroMax – a very high quality glandular product
- TyroMix – 3mcg T3 & 6mcg T4 per drop, 360 drops. Take 2 drops per meal to gauge the effect.
Or sometimes you just need selenium, which is very important for converting T4 into T3.
#9 Lower estrogen
Estrogen is one of the most potent inducers of serotonin as it increases serotonin synthesis, by upregulating TPH2, increases serotonin receptor 5-HT2A and prevents its clearance and breakdown by inhibiting SERT and MAO-A (R). Your can read more here on lowering estrogen:
- lower the aromatase or alternatively, get my list of the top 6 aromatase inhibitors here.
- de-activate estrogen receptors
- increase estrogen detoxification
#10 Avoid stress and lower cortisol
Cortisol and stress increases serotonin synthesis and desensitizes the autoreceptor, 5-HT1A, which leads to high baseline serotonin (R, R). Serotonin in turn can also increase cortisol levels, via activation of the 5-HT2C and 5-HT4 receptor (R). This can lead to a feed-forward loop where they boost each other.
Cortisol also increases serotonin uptake, increasing intracellular serotonin (preventing its clearance, similar to estrogen) (R) and is inversely correlated with 5-HIAA, the excretion metabolite (R). You can read more on lowering cortisol here…
Furthermore, cortisol inhibits thyroid function, prevent T4 to T3 conversion and also inhibits the liver from detoxifying toxins, such as estrogen, serotonin, heavy metals, etc…
#11 Eat enough protein
Protein is rich in amino acids, a few are tryptophan (serotonin precursor), phenylalanine and tyrosine (dopamine precursor) and other large neutral amino acids (LNAAs) such as the BCAAs that all compete with each other for entry into the brain.
Hence, eating of a natural protein source, usually containing roughly 0.5–1% tryptophan on average, results in a relatively small increase in tryptophan in the brain, but a larger increase in other LNAAs. This results in a decrease in the circulating tryptophan/LNAA ratio and thus reduced Trp influx to the brain and thus reduced serotonin synthesis. This could be one major reason why people that go on a carnivore diet experience such great mental benefits for a while.
A word on insulin is needed here. Insulin pulls all amino acids from the blood into the cell except for tryptophan and thus increases brain tryptophan. However this effect can be offset by adding a small amount of protein (2.5-4% of the total calories).
Insulin can also increase TPH, which can lead to high serotonin levels. (R, R) However, insulin resistance and hyperinsulinemia (diabetes) are not associated with a decrease or increase in serotonin, but rather a decrease in dopamine, due to an increase in MAO-B (the enzyme that breaks down dopamine) and oxidative stress (R).
A neat trick is to take 5g of BCAA powder with every big protein meal to provide even more competition, or you can take 5g of BCAA with 2.5g phenylalanine and/or 0.5g+ tyrosine on an empty stomach to boost dopamine production. Never take BCAA on it’s own as this will deplete both tryptophan and tyrosine in the brain and lead to reduced cognitive function and temporary depression.
#12 Lower free fatty acids
Some people think that insulin spikes brain tryptophan, but it’s actually free fatty acids (FFAs) than is responsible for increasing brain tryptophan.
Elevated free fatty acids are due to insulin resistance and elevated estrogen, cortisol and catecholamines, such as noradrenaline and adrenaline.
FFAs displace tryptophan from the binding proteins, thus increasing free trytophan, which causes more tryptophan to enter the brain and increase serotonin.
Two of the best supplements to lower excess FFAs are:
Both can be used together for a synergistic effect.
Remember, have you morning glucose and fasting FFAs tested before just going bonkers with lipolysis inhibitors.
#13 Enjoy some alcohol every now and then
Acute alcohol consumption has been shown to decrease the tryptophan/LNAA ratio by about 10% at about 30 minutes and 20%–25% at about 1.5 to 2 hours following ingestion (R). So enjoying a drink can help lower serotonin for a while.
Yet alcoholism increases serotonin in the long term. It’s better to enjoy a beer or a bit of whiskey/wine every now and then.
#14 Increase leptin sensitivity
Leptin is secreted by our fat tissue and it promotes satiety, speeds up the metabolism, heat production, steroidogenesis, etc.
Leptin decreases the expression of the TPH 2 enzyme in the brain and can help to lower serotonin (R).
Leptin is increased by an caloric surplus, glucose, insulin, however it can also be increased by estrogen, inflammation (TNF-α) and cortisol. People with obesity and diabetes have elevated leptin and leptin resistance, which is highly undesirable.
High protein intake (30% of total calories) and a high carbohydrate diet might increases leptin sensitivity (R, R). Lowering estrogen, inflammation and cortisol will also help to improve leptin sensitivity.
#15 Boost DHT
#16 Cold exposure
Cold inhibits TPH, and also serotonin release in the brain, leading to a drop in serotonin levels in the brain (R, R, R). People report an anti-depressant effect from ice baths, or doing contrast baths.
Cold water exposure also speeds up the metabolism, but only if you are not hypothyroid. Doing cold water treatment while being hypothyroid will only harm the metabolism to a greater degree and increase serotonin more.
#17 Increase GABA-B receptors
GABA-B receptor agonism induces a decrease of serotonin release (R). GABA-A agonist didn’t have this effect. GABA in general will help to keep serotonin at bay.
Homotaurine has been found to increase GABA-B receptors over time.
Ammonia is created from protein, more precisely, amino acids.
During hypothyroid and a low energy state, amino acids can very easily be converted to ammonia. Excess ammonia production, together with oleic acid, increases the synthesis is oleamide. Oleamide is linearly correlated with plasma ammonia and oleic acid. Oleamide binds to 5-HT1, 5-HT2 and 5-HT7.
Ammonia is mainly detoxified through the urea cycle, where it’s converted to urea. The urea cycle uses carbon dioxide (CO2), manganese (A), arginine (A), citrulline and ornithine (A). You can read more here on boosting CO2.
Maple syrup, pineapples, cocoa powder and kale are great sources of manganese.
Take two grams of each in the morning.
#19 Avoid exhaustion/overtraining/glycogen depletion
When exhausted and/or being glycogen depleted, serotonin becomes elevated to decrease energy expenditure, movement, motivation, energy production, etc., while promoting hunger, fat gain, anhedonia, depression, etc (R).
Being low carb for too long will lead to very elevated serotonin levels which would inhibit the metabolism, thyroid function, steroidogenesis, etc., and the whole organism just crashes. So, if you do want to go low carb, don’t…it’s not the answer.
#20 Stop punishing yourself
Punishment is one of the most effective means of stimulating serotonin release (R). This can be from outside sources, like other people, but this is also due to self-punishment. If you constantly feel you’re not good enough, or you don’t like how you look, you’re punishing yourself. Being constantly is such a state of mind will sky-rocket serotonin, which will lead to very bad self-confidence, depression, even suicidal thoughts, etc.
Learn to accept yourself, I know this is hard, but then actively plan on improving yourself, your situation, or whatever is causing you to punish yourself.
#21 Do exciting & creative things
Being stuck in a rut and doing the same things over and over in life without much enjoyment keeps dopamine at a low and can result in high serotonin.
Getting out and seeing new things, or seeing things differently, being creative and exploring will dramatically increase dopamine and brain energetics and lower serotonin.
#22 Avoid serotonergic substances
- Curcumin (agonist to 5-HT receptors, specifically 5-HT1A/1B and 5-HT2C subtypes) (R)
- St John’s Wort (R)
- Carvacrol (phenol isolated from aromatic herbs including oregano and thyme) (R)
- Proanthocyanidin (increases 5-HT concentrations in the hypothalamus, hippocampus, and frontal cortex) (R)
- Resveratrol (inhibits MAO and is also estrogenic) (R)
- Saffron (R)
- Rhodiola Rosea (inhibits MAO-A, but the effect is very mild. Still a good anti-stress supplement to use) (R)
- Nelumbinis semen (R)
- Acetyl-L-carnitine (R)
- High dose ashwagandha
- Berberine (inhibits MAO-A, but also increases SERT and dopamine, so the effect might not be highly serotonergic) (R)
Supplements that decrease serotonin
Theanine decreases serotonin levels globally in the brain, with region-specific increases in the striatum, hippocampus and hypothalamus (R, R). Theanine is also great for lowering cortisol, reducing anxiety, improving brain function and sleep.
#3 Aspirin/willow bark
Aspirin or willow bark contains salicylic acid (acetylsalicylic acid in the case of aspirin), which, when consumed with a meal, blocks tryptophan absorption from the gut. It also decreased serotonin receptors (5-HT2 and 5-HT3) (R, R) and increased serotonin turnover in the brain (R). Start with a baby aspirin (81mg) and work up from there. Too much aspirin, around 1g and higher, increases the risk of bleeding and needs to be taken with vitamin K2. Take every 300mg aspirin with 1mg K2.
- Aspirin – (Amazon)
Firstly gelatin is very low in tryptophan, and secondly, gelatin is high in glycine which aids the liver in serotonin detoxification. Glycine increases extracellular serotonin, which is due to NMDA activation, as glutamate stimulate serotonin synthesis (R). However, glycine decreases serotonin release in brain cells and decreases its synthesis in rostral raphe cells (R). Glycine also antagonizes the 5-HT2 receptor and activates Ca+ independent activation of PKC which also antagonize serotonin (R). More on glycine here…
#5 Vitamin E
Alpha-tocopherol (one of the forms of vitamin E; vitamin E consist of 8 different forms) reduces depression, as it’s shown that a vitamin E deficiency reduces the dopamine:serotonin ratio (R) and increases dopamine turnover (and not serotonin) and serotonin receptors, meaning low vitamin E will lead to an excess of serotonin compared to dopamine (R, R). More on vitamin E here…
Only a small amount of vitamin E is needed per day, around 100IU, but higher amounts, around 400-800IU, can be used if you have inflammation, have been eating a high PUFA diet for many years and have elevated estrogen and prolactin.
Magnesium concentration has an effect on serotonin and NMDA receptors (R). A magnesium deficiency is associated with stimulation of excitatory neurotransmitters such as serotonin and acetylcholine, due to overactive NMDA receptor activation (R).
Progesterone, being antagonistic to estrogen, inhibits the firing of serotonergic nerves and increases serotonin turnover (breakdown) (R). Progesterone is also a serotonin receptor antagonist (R). Testosterone and allopregnanolone are also 5-HT3 receptor antagonists (R).
Progesterone is generally considered a female hormone, but males also has a fair amount, and if it’s low can suffer from excess estrogen and pre-mature aging, such as hair loss and skin degeneration (wrinkling).
#8 Methylene blue
Methylene blue is an agonist to the 5-HT1A receptor, which will lower serorotonin levels. However, too high a dose, usually more than 15mg, will start to be more serotonergic as it also inhibits MAO-A. You’ll have to experiment with different doses to find your sweet spot. Usually 1mg provides all the benefits you need so that would be a good starting dose.
Zinc lowers serotonin by
- increases serotonin uptake possibly by promoting SERT (R)
- being an agonist to the 5-HT1a receptor (R)
You can read more on zinc here…
Red meat, organ meat such as liver and kidney and oysters are great sources of zinc. If you’re diet is low in zinc, consider a supplement.
However, yohimbine might promote anxiety as it’s an agonist to the 5-HT1A receptor at doses above 1 mg/kg (R). Using Magnolia with it will greatly aid in reducing the anxiety promoting properties.
L-lysine, acts like a serotonin receptor 4 (5-HT4) antagonist and prevents serotonin (5-HT)-induced anxiety, diarrhea, ileum contractions, and tachycardia and in stress-induced fecal excretion (R). Lysine is an excellent supplement to use against social anxiety. Start at 500mg in the morning. You can read on lysine here…
Feverfew extracts are potent inhibitors of serotonin release from platelets and neurons and it also blocks serotonin receptors, 5-HT2A and 2B (R).
#13 Gingko Biloba
Gingko Biloba extract (14 mg/kg) is able to restore stress-induced elevation in whole brain levels of catecholamines, serotonin and cortisol to near normal levels (R). It also antagonizes 5-HT2A receptors.
Ginger-mediated antiemetic (anti-vomit and nausea) effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT3) receptor activity. The ginger extract has similar effects to anti-emetic drug ondansetron (R). You can chop up raw ginger root into thin slices and make a nice tea with it, use it in smoothies, mix it with a dish or just use the essential oil.
#16 Silk tree
Silk tree inhibits 5-HT2C and helps to lower cortisol and stress and promote better sleep (R).
#17 Ziziphus (jujube)
Ziziphus has anti-depressant actions by antagonizes the 5-HT1B receptors, which lowers the excitatory glutamate and increase the release of GABA (R, R). Ziziphus is usually found together with magnolia, in the supplement Relora.
Magnolia extract has a modest antagonistic action with 5-HT6 (which promotes better sleep and enhances memory) (R), increases dopamine and acetylcholine release in the brain. Magnolol (a phenolic compound isolated from the stem bark of Magnolia officinalis) inhibits serotonin release and the total decrease in serotonin is not via the 5-HT autoreceptors at the 5-HT terminals, suggesting additional serotonin lower properties (R).
Phenylalanine is not only a precursor to dopamine, but also inhibits the synthesis of serotonin, by inhibiting TPH (R). Combine phenylalaine with BCAA for a more potent serotonin lowering effect.
Taurine supplementation inhibits the release and synthesis of newly formed serotonin from tryptophan only in rostral raphe cells (R). Taurine also inhibits serotonin through mediation of 5HT1A receptors and cAMP (R). You can read more on taurine here…
#21 Vitamin B1
A deficiency in thiamine increases serotonin synthesis and decreases its uptake, resulting in a stronger action of serotonin (R).
Increased intake of thiamine increases serotonin disposal and inhibits dopamine reuptake, thus resulting in a stronger action of dopamine. Vitamin B1 can also be used as a nootropic at doses of 300mg+. More on vitamin B1 here…
Long-term lithium treatment causes the down-regulation of postsynaptic 5-HT1 and 5-HT2 receptors (decreases their sensitivity) (R), however, it increases serotonin (R). Interestingly, lithium binds to serotonin and forms a complex which makes serotonin unavailable, and might explain some of the antidepressant effects of lithium (R).
Reserpine (extracted from the root of Rauwolfia vomitoria) induces a statistically significant (except for medial geniculate body) decrease in the rate of 5-HT synthesis (via TPH inhibition) in a large number of discrete brain structures and increases the urinary excretion of serotonin (R, R).
#25 Tonic water
The major antimalarial drug, quinine, reduces the uptake of tryptophan (R), is an antagonist to the 5-HT receptors and competitively inhibits TPH2 in the presence of tryptophan. Tonic water is a great source of quinine.
Caffeine increases serotonin receptors, which could indicate an antagonist effect to serotonin receptors, which is similar to the increase in adenosine receptors due to adenosine antagonism (R). The human equivalent dose from the study is 7mg/kg, which would be 560mg for a 80kg man, which would be around 5 coffees a day or 2-3 double esspressos.
Forced treadmill exercise increased TPH expression and caffeine administration suppressed the exercise-induced elevation in TPH expression (R), however not at rest. The human equivalent dose is just 60mg.
Niacinamide (and not any other form) is able to inhibit serotonin. 93mg/kg is needed to complete inhibit it and 57mg/kg is used for moderate inhibition (R). 3g daily is routinely used in studies against arthritis, other autoimmune diseases and cancer. You can read more on niacinamide here…
I you do decide to use 5g+ of niacinamide of per day, only do it short term for no more than 60 days in a row.
#28 Vitamin B2
Riboflavin has an anti-endotoxin (as it’s powerful antibacterial and antagonizes toll-like receptor 4 (TLR4)) effect and protects from colonic inflammation and prevents the increase in gut serotonin. Riboflavin is a cofactor of the enzyme MAO-A, which increases the degradation of serotonin. MAO-A predominantly breaks down serotonin, which is great for lowering serotonin and increasing the dopamine:serotonin ratio. More on vitamin B2 here…
#29 Vitamin D
Vitamin D promotes the gene expression of tyrosine hydroxylase, an essential enzyme involved in the synthesis of dopamine, but is also upregulates serotonin synthesis by activating the TPH2 in the brain (R).
Apart from it pro-serotonin effect in the brain, vitamin D inhibits serotonin synthesis in the gut, by inhibiting TPH1 (R). The decrease in gut serotonin is very good, especially for conditions such as IBS. If you do feel weird from taking vitamin D, you might already have too much serotonin and might benefit from using it with something that blocks TPH2. More on vitamin D here…
#30 Vitamin A
Vitamin A supplementation in rats increases MAO activity (R). The study did not specify between A or B, but it could be both. This will lead to a decrease in serotonin and also dopamine. Vitamin A is highly unsaturated, but vitamin E given with vitamin A would prevent its oxidation. 100IU vitamin E per every 10 000IU vitamin A would be sufficient to prevent auto-oxidation. I’d advise to always take vitamin A with vitamin D, E and K2, as they all work in synergy together. More on vitamin A here…
Adamantane is a naturally occurring substance that is anti-serotoninergic (R) and dopaminergic. It also acts directly on the water structure of a cell and increases its stability and integrity making it structurally protective. Cells with strong structure are more resistant to oxidative stress and toxins, and are better able to prevent entry to more water-soluble steroids such as aldosterone and estrogen, and allows more entry of fat-soluble steroids such as testosterone and DHT.
Most people report a great benefit to gut health (which indicate a reduction in gut serotonin) when using adamantane orally even in small doses such as 3 drop of the supplement mentioned below.
- Diamant – 33mg adamantane per serving, 30 servings.
Beta-alanine supplementation in mice decreased serotonin in the hypothalamus and increased carnosine, which increased BDNF (R). The human equivalent dose is around 2.5-3g. Carnosine also prevents the age-related increase in serotonin receptor binding (R).
α- and γ-mangostin (found in mangosteen) have anti-histaminergic properties and can selectively block serotonin type 2A receptors, a pathway that is a feature of some atypical antipsychotics, however, mangosteen might have general serotonin reuptake inhibitory properties, which will lead to elevated serotonin (R, R). Mangosteen (γ-mangostin) is also a potent aromatase inhibitor.
#34 Bacopa monneiri
Bacopa is a very well known nootropic herb, as it improves learning and memory and is anti-anxiety, but it is a bit of a mixed bag. It increases TPH, but also SERT. It also inhibits COMT, increases dopamine and antagonizes 5-HT2A and 5-HT6 (R). A decrease in COMT can increase dopamine, serotonin, noradrenaline, etc, which can further increase your serotonin if it’s already high. If you get high serotonin symptoms or are sensitive to serotonin, this might not be a good supplement to use.
Arginine is most known as an amino acid that increases the pump, by increasing nitric oxide. Arginine in itself is very effective at blocking the rise in hypothalamic serotonin induced by IL-1β in rats, and the increase in NO by arginine very effectively inactivates TPH as well as increase the enzyme that increases dopamine synthesis, tyrosine hydroxylase (R, R, R).
A good dose to start at would be 1g. You can even work up from there all the way to 10g in one dose or split it up 5g pre-workout and 5g before bed.
#36 White peony root
Paeonia radix root extract is able to potently lower TPH and serotonin in the exercising rat, however due to its phytoestrogen content, it might not be best to use in large amounts (R).
Valerian root and it’s active constituent, valerenic acid, are partial agonists to the 5-HT5A receptor, which will reduce serotonin as it’s an autoreceptor, and might improve sleep by reducing sympathetic nervous system activity (R). Valerian is also fantastic at boosting GABA.
#38 Brewers yeast
Brewers yeast, but not nutritional yeast, is a great source of natural chromium, which decreases the sensitivity of the 5-HT2A receptor (R). Thus chromium has an anti-depressant and anti-psychotics effects. Also, chromium extract from brewers yeast has a much longer half-life than other supplemental chromium forms.
One downside of brewers yeast is that it’s very high in phosphate and low in calcium, so take calcium along side brewers yeast.
#39 Some drugs
Lastly I’d like to mention a few anti-serotonin drugs that can be useful if no natural supplement seem to work. A few relatively safe anti-serotonin drugs include cyproheptadine, lisuride, metergoline and mirtazapine.
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