Serotonin is always thought of being the happy hormone and that by increasing it has an anti-depressant effect. As a matter of a fact, the majority of anti-depressants is selective serotonin reuptake inhibitors, and more than 90% of the people on anti-depressant medication is on SSRI.
Before SSRI became so popular, there were studies done showing the negative effects of serotonin, yet pharmaceutical companies and others with agendas did lots of fraudulent studies to show the “benefits” of serotonergic drugs. Dopamine is actually the happy hormone and promotes creativity, focus, relaxation, motivation, etc… More on boosting dopamine here…
Here are a few of serotonin’s side effects:
- psychosis and homicidal/suicidal behavior
- learned helplessness (acetylcholine also involved), rigid behavior and thinking, anti-novelty, obedient (zombie behavior)
- behavioral inhibition and harm avoidance
- procrastination, no motivation or focus, brain fog, etc
- lack of perspective or awareness
- reduced creative thought or desire to “play”
- social isolation and anxiety
- lack of appetite
- fatigue, chills, agitation, aggression
- shock/freeze (serotonin protects the organism when it perceives that the stressor is too big to overcome and causes shutdown)
- inhibits sensory responsiveness (not exclusive to high serotonin) (1)
- bronchoconstriction, asthma and hives (together with histamine), migraines
- chronic fatigue syndrome
- immunosuppression, nerve cell damage (neurological degeneration)
- edema, joint swelling are produced by the release of serotonin from platelets or other cells.
- gastrointestinal damage from alcohol, decrease stomach acid (2)
- decrease metabolism. 1) activates glycolysis, forming lactic acid 2) forms nitric oxide which inhibits mitochondria 3) inhibit thyroid function 4) inhibiting mitochondrial respiratory enzymes 5) reduction of oxygen delivery to tissues by vasoconstriction
- flushing, sweating (sometimes dark-colored), diarrhea (serotonin stimulates small intestine smooth muscle, but inhibits the large), nausea, reduced urination, muscle and joint pains, and, in late stages, very often disease (especially inflammation and fibrosis)
- Sensitivity to light, sound, visual disturbances, easily frightened, jumpy (coupled with adrenaline) and head twitching (5-HT1A agonists reduce head twitching, due to negative feedback signaling for serotonin production) (3)
- In a cool environment, the serotonin caused their temperature to fall, by decreasing their heat production, and increasing their loss of heat (by causing vasodilation in the skin, “flushing”). In a hot environment, serotonin can cause the animal’s temperature to rise. So you can have both chills and flushing caused by high serotonin.
Hormonal & neurotransmitters
- Increases aldosterone (aldosterone increase estrogen and high blood pressure)
- Increases prolactin release (mainly through 5-HT2A) (4),
- Elevates glucocorticoids & ACTH (mainly through 5-HT2C)
- Is correlated with estrogen receptors (through 5-HT4) (103)
- inhibits testosterone synthesis
- inhibits dopamine release in frontal cortex (through 5-HT1B)
In normal conditions about 1-5% of serotonin is made from the amino acid tryptophan in the brain, centrally within the neurons of the raphe in the brainstem, via the enzyme tryptophan hydroxylase type 2 (TPH2). However, in abnormal conditions, up to 60% of the serotonin can be synthesized from tryptophan. First, brain tryptophan is converted to 5-hydroxytryptophan by the tryptophan hydroxylase (TPH) enzyme (Oxygen, tetrahydrobiopterin and iron-dependent). Second, 5-hydroxytryptophan is converted to serotonin by the aromatic amino acid decarboxylase enzyme.
Serotonin can also be made in the gut (peripherally within the gut neurons and enterochromaffin cells), due to the absorption of endotoxins and activation of toll-like receptor 4 (TLR4), via the enzyme tryptophan hydroxylase type 1 (TPH1). Anything that irritates the gut, or is absorbed that is harmful, will increase serotonin. The enterochromaffin cells in the gastrointestinal epithelium account for ~90% of all serotonin synthesis.
Extracellular serotonin is bound to a transporter, which inhibits the effect serotonin can have on tissue, by reducing serotonin availability at synapses. Less serotonin transport = higher serotonin availability.
Degradation of serotonin is via monoamine oxidase type A (MAO-A) and aldehyde dehydrogenase (ADH) to the major serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA). Levels of serotonin are also influenced by the tryptophan-degrading enzyme, indoleamine 2,3-dioxygenase (IDO) and tetrahydrobiopterin, the cofactor of tryptophan hydroxylase. In the periphery, glucuronidation also plays an important role in serotonin detoxification. (5)
Here follow 57 ways to lower serotonin
Creatine is very effective at restoring brain bioenergetics at the cellular level. Creatine supplementation reduces plasma free-tryptophan and the free-tryptophan:tyrosine ratio (6), thus increasing dopamine:serotonin ratio.
- Creatine – 16oz
2) Lower inflammation
Inflammation (TNF, IL-1β) increases brain serotonin as well as serotonin receptors, 5-HT2A. (9, 109) 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…
3) Lower estrogen
Estrogen inhibits MOA-A, increases TPH2 gene expression, 5-HT2A receptor binding and interferes with extracellular serotonin clearance. (10) Estrogen and serotonin goes hand in hand. More on blocking the aromatase here…
Bad bacteria in the gut causes inflammation, gut permeability and bacteria translocation. (11, 12, 13, 14) Antibiotic treatment significant reduces gut microbes, serotonin and TPH1. (15) Gut bacteria interacts with TLRs and Treg cells in the gut and increases serotonin. Anti-biotics prevent this. (16, 17) Propolis is a natural anti-biotic. Coconut oil and apple cider vinegar also process potent anti-bacterial actions.
- Propolis – 500mg per cap, 240 caps (take 1 cap with every meal)
Theanine decreases serotonin levels globally in the brain, with region-specific increases in the striatum, hippocampus and hypothalamus. (18, 19) Theanine is also great for lowering cortisol, reducing anxiety, improving brain function and sleep.
- Theanine – 200mg per cap, 120 caps
6) Aspirin (salicylic acid)
When consuming aspirin with a meal, blocks tryptophan absorption from the gut. It also decreased serotonin receptors (5-HT2 and 5-HT3) (20, 21) and increased serotonin turnover in the brain. (22) 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.
GABAB receptor agonism induces a decrease of serotonin release in rostral raphe cells, and increases extracellular serotonin. (23) GABA-A agonist didn’t have this effect. Serotonin transporters can now bind to the extracellular serotonin and transport it for excretion.
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 and glutamate antagonism, as glutamate stimulate serotonin synthesis. (24) Glycine decreases serotonin release in brain cells and decreases its synthesis in rostral raphe cells. (25) Glycine also antagonizes the 5-HT2 receptor and activates Ca+ independent activation of PKC which also antagonize serotonin. (26) More on glycine here…
- Gelatin – 16oz
- Glycine – 1g per serving, 100 servings
9) Vitamin E
Alpha-tocopherol reduces depression, as it’s shown that a vitamin E deficiency reduces the dopamine:serotonin ratio (27) and increases dopamine turnover (and not serotonin) and serotonin receptors. (28, 29) More on vitamin E here…
- Unique E – 400IU per serving, 120 servings. (Mixed tocopherol, high alpha and gamma tocopherol)
- Tocovit – 400IU per serving, 30 servings. (Natural wheatgerm extract)
10) Avoid PUFAs
Eating a diet high in omega-6 polyunsaturated fatty acid, will exert the most influence on serotonin receptor and transporter binding. (30)
Omega 3, DHA, increases serotonin in frontal cortex and hippocampus (31), TPH, receptor 5-HT2A and decreases serotonin turnover.
Omega 3, EPA, increases serotonin release from presynaptic neurons by reducing prostaglandin E2 (PGE2). (32) Omega 3 (cod liver oil) also increases dopamine in rats. (33) I would stay away from PUFAs, including fish oils, as they increase cortisol, is catabolic, inhibit thyroid function, damage the liver, inhibit 5-alpha reductase (DHT synthesis), etc…
Magnesium concentration has an effect on serotonin receptors, nitric oxide synthesis and release and NMDA receptors. (34) Magnesium deficiency is associated with stimulation of excitatory neurotransmitters such as serotonin and acetylcholine. (35) And magnesium also enhances the effect of 5-HT1A receptor agonists, such as zinc, methylene blue, etc… (36) More on magnesium here…
- Magnesium glycinate – 200mg per serving, 180 servings
Progesterone, being antagonistic to estrogen, inhibits the firing of serotonergic nerves, increase serotonin turnover (breakdown) (37) and is also a serotonin receptor antagonist (38). Testosterone and allopregnanolone are also 5-HT3 receptor antagonists. (93)
- Progestene – 20mg per serving, 30 servings. (Excellent topical absorption) Start with 5mg daily, and increase the dose from there if you feel the need.
Zinc increases serotonin uptake, weakening its action, further amplifying dopamine’s effect. (39) Zinc is an agonist to the 5-HT1a receptor. (40) Activation of the 5-HT1a receptor actually has a negative feedback mechanism on serotonin release and increases dopamine release and lowers adrenaline. (w) More on zinc here…
- Zinc glycinate – 22mg per serving, 250 servings
14) Methylene blue
MB is also an agonist to the 5-HT1A receptor. However, too high a dose, usually more than 15mg, will start to be more serotonergic.
- Oxidal – 400mcg methylene blue per drop, 240 drops. Start with 3 drops daily. (This product is designed to increase oxidative phosphorylation and uncoupling)
Cortisol increases serotonin (5-HT1A) responsiveness and amplifies its synthesis. (41, 42) Serotonin can also increase cortisol, via activation of 5-HT4 and is positively coupled to adenylate cyclase. (43) This can lead to a feed-forward loop. Cortisol also increases serotonin uptake, increasing intracellular serotonin (preventing its clearance, similar to estrogen) (44) and is inversely correlated with 5-HIAA, the excretion metabolite. (45) More on lowering cortisol here…
Leptin decreases the expression of the TPH 2 enzyme (46) but hyperleptin increases it (due to being leptin resistant). Intermittent fasting, low carb diet and fat loss could aid in increasing leptin sensitivity.
Insulin pulls all amino acids into the cell except for tryptophan and increases albumin-bound tryptophan which is then taken up in the brain, due to less competition. Just 2.5-4% protein is needed to offset this effect, to provide enough amino acids for competition. Insulin also increases TPH. (47, 48) Insulin resistance (diabetes) are not associated with a decrease in serotonin, but rather dopamine, due to an increase in MAO-B (the enzyme that breaks down dopamine) and oxidative stress. (49)
18) Reduce tryptophan intake
Reducing tryptophan availability is also a great way of reducing serotonin. Although you won’t be able to avoid tryptophan completely, you can make choices of foods low in tryptophan compared to competing amino acids. A researcher, Fernstrom, made a ratio to calculate how much an effect a food would have on serotonin synthesis.
Fernstrom Ratio = (Tryptophan) ÷ (Tyr + Phe + Val + Ile + Leu)
However, not only those last named five amino acids compete with tryptophan uptake in the brain but also other amino acids. I think the following formula would be even better to calculate the effect certain foods will have on serotonin synthesis.
Ratio = (tryptophan) / (Try + Phe + Val + Ile + Leu + threonine + methionine + histidine)
Here I worked out a few foods with the above-mentioned formula. The lower the ratio the more competition tryptophan has with other amino acids. I calculated each food at 20g of protein.
- Whole egg: Ratio: 0.025
- Egg white: Ratio: 0.023
- Whey: Ratio: 0.058
- Casein: Ratio: 0.037 (Casein also delays tryptophan absorption (50)
- Turkey breast: Ratio: 0.042
- Beef rump: Ratio: 0.029
Another neat trick would be 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. Never take just BCAA as this will deplete both tryptophan and tyrosine in the brain and lead to depression.
Acute alcohol consumption has also been shown to decrease the tryptophan/Central amino acid ratio by about 10% at about 30 minutes and 20%–25% at about 1.5 to 2 hours following ingestion (51) Yet alcoholism increases serotonin. Better to enjoy a beer or a bit of whiskey/wine every now and then.
Yohimbine possesses 5-HT1A properties, and demonstrated that in doses above 1 mg/kg to significantly activate these receptors. (52) Yohimbine also inhibits 5-HT1B, 5-HT1D and 5-HT2 receptors and increases dopamine, blocks postsynaptic dopamine receptors and its action is on the D2 receptor. (53, 113, 114, 116)
- Yohimbine – 3mg yohimbine HCL per serving, 60 servings
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. (54) More on lysine here…
- Lysine – 500mg per cap, 250 caps. Start with 500mg with every meal. Lysine is best balanced with arginine. (Take lysine during the day, and equal amounts arginine before bed)
22) Agnus castus (chaste tree)
- Agnus castus – 400mg per cap, 100 caps
Feverfew extracts are not only potent inhibitors of serotonin release from platelets but also of polymorphonuclear leukocyte granules, providing a possible connection between the claimed benefit of feverfew in migraines and arthritis. (60) Feverfew extract potently and directly blocks 5-HT2B and 5-HT2A receptors and neuronally released 5-HT. Feverfew powder is more potent than any of its extract or parthenolide alone in its anti-serotonergic activity. (61)
- Feverfew – 325mg per cap, 100 caps (175mg feverfew extract, 0.5-0.7% parthenolide and 150mg feverfew powder)
24) Ginkgo biloba
Gingko Biloba extract (14 mg/kg p.o.) is able to restore stress-induced elevation in whole brain levels of catecholamines (NE, DA), 5-HT and plasma corticosterone to near normal levels. (62) It also antagonizes 5-HT2A receptors.
- Gingko Biloba – 120mg per cap, 60 caps
25) Ginger root
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 antiemetic drug ondansetron by blocking 5-HT-evoked responses. (63) You can chop up raw ginger root into thin slices and make a nice tea with it. You can add honey and lemon juice to it for added flavor.
- Ginger root – 550mg per serving, 100 caps
26) Ziziphus (jujube)
Magnolia extract has a modest antagonistic action with 5-HT6 (which promotes better sleep and enhances memory) (66), 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. (67)
- Magnolia – 400mg per serving, 60 servings
Phenylalanine is not only a precursor to dopamine, but also inhibits TPH (68).
- Phenylalanine – 500mg per cap, 120 caps. Start with 1.5mg daily, preferably in the morning.
Taurine supplementation inhibits the release and synthesis of newly formed serotonin from tryptophan only in rostral raphe cells. (69) Taurine also inhibits serotonin through mediation of 5HT1A receptors and cAMP. (70) More on taurine here…
- Taurine – 500mg per serving, 100 serving.
30) Thiamine (vitamin B1)
A deficiency in thiamine also increases serotonin synthesis and decreases its uptake, resulting in a stronger action of serotonin, which antagonizes dopamine further. (71)
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…
- Thiamine – 100mg per serving, 100 servings
Long-term lithium treatment causes the down-regulation of postsynaptic 5-HT1 and 5-HT2 receptors (73), however, it increases serotonin. (74) Most substances that increase a neurotransmitter, will decrease it’s receptors and vise versa, as that’s how the body re-balances itself. Lithium binds to serotonin and forms a complex which makes serotonin unavailable, and might explain the antidepressant effect of lithium. (94)
- Lithium orotate – 5mg per serving, 60 servings
Reserpine causes the release of serotonin (and noradrenaline) from the brain and increases its urinary excretion. (75) Reserpine induced 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. (76)
34) Cold exposure
Cold inhibits TPH, and also serotonin release in the brain, leading to a drop in serotonin levels in the brain. (77, 78, 79) Too cold for too long can lead to a stress reaction and rather an increase in serotonin.
Manganese supplementation decrease brain serotonin, aromatic L-amino-acid decarboxylase (DDC) activity (80) and increases 5HT1A sensitivity to agonists. (81) A decrease in DDC is not good as it also inhibits the synthesis of dopamine. (w) More on manganese here…
- Manganese glycinate – 8mg per serving, 100 tablets
Fermentable fibers (including pectins and fructooligosaccharides) support the formation of bacterial toxins, intestinal irritation, interaction with TLRs and an increase in the amount of serotonin circulating in the blood. Short chain fatty acids (SCFAs) that are produced from the fermentation of fiber in the gut, have recently been shown to regulate the synthesis of gut-derived 5-HT from EC cells. (82)
Luckily, some fibrous foods, such as carrots and bamboo shoots, contain antibacterial chemicals, which helps to reduce endotoxins and serotonin. Activated charcoal can absorb many toxins, including bacterial endotoxin, so it is likely to reduce serotonin synthesis in the intestines.
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.
Some fruits, such as bananas, pineapples and tomatoes are high in serotonin. Serotonin from foods or that is produced in the gut can not cross the blood-brain barrier, but can still do all it’s damage systematically.
The major antimalarial drug, quinine, reduces the uptake of tryptophan (83), is an antagonist to the 5-HT receptors and competitively inhibits TPH2 in the presence of the substrate tryptophan. Tonic water is a source of quinine.
Caffeine increases serotonin receptors, which indicate an antagonist effect to serotonin receptors, which is similar to the increase in adenosine receptors due to adenosine antagonism. (84) The human equivalent dose from the study is 7mg/kg, which would be 560mg for a 80kg man.
Forced treadmill exercise increased TPH expression and caffeine administration suppressed the exercise-induced elevation in TPH expression (85), however not at rest. The human equivalent dose is just 60mg.
This rat study shows that caffeine increases serotonin in the short term, but it then returns to baseline after 5 days and then just higher dopaminergic tone remains. (86)
- Caffeine – 200mg per cap, 100 caps
39) Niacinamide (vitamin B3)
Niacinamide (and not any other form) was able to inhibit serotonin. 93mg/kg is needed to complete inhibit it and 57mg/kg is used for moderate inhibition. (87) 3g daily is routinely advised against arthritis, other autoimmune diseases and cancer. I advise to start with 1.5g twice daily. More on niacinamide here…
- Niacinamide – 500mg per serving, 100 caps
40) Riboflavin (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. Riboflavin is a cofactor of the enzyme MAO-A, which increases catecholamine degradation such as serotonin and noradrenaline, thus keeping catecholamine levels in balance. MAO-A predominantly breaks down serotonin, which is great for lowering serotonin and increasing the dopamine:serotonin ratio. More on vitamin B2 here…
- Energin – 15mg R5P per serving, 30 servings. Also contains 50mg thiamine HCL, 100mg niacinamide, 6mg PLP, 1mg biotin. 90% absorption topically.
- Vitamin B2 – 100mg riboflavin HCL per cap, 100 caps
41) Liver function
Having a damaged liver, due to PUFA consumption, alcoholism, heavy metal toxicity, etc, can increase serotonin, due to the inability to detoxify serotonin. Fixing liver function is highly important for optimal health. A good protocol is to use 600mg+ caffeine daily with 45mg vitamin K2 (MK-4), 5g taurine, 1g+ glycine, 400mg+ magnesium and 3g+ niacinamide. A ketogenic diet is also very good for making the lean.
Proper thyroid function is also necessary to detoxify serotonin. Serotonin is significantly increased during hypothyroidism and poor nutrition. Cortisol inhibits thyroid function, prevent T4 to T3 conversion and also inhibits the liver from detoxifying toxins, such as estrogen, serotonin, heavy metals, etc…
43) Vitamin D
Vitamin D promotes the gene expression of tyrosine hydroxylase, an essential enzyme involved in the synthesis of norepinephrine and dopamine and also upregulates serotonin synthesis by activating the transcription of TPH2. (88) Calcitriol is the active form of vitamin D that increases TPH2 and inhibits TPH1. (89) The decrease in serotonin gut synthesis is very good, especially for conditions such as IBS, but I would not recommend taking vitamin D alone, but rather with something that inhibits TPH2. More on vitamin D here…
- Carcirol – 1000IU per drop, 240 drops. Excellent topical absorption.
- Vitamin D – 1000IU per cap, 180 caps
44) Vitamin A
Vitamin A supplementation in rats increases MAO activity. (90) 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 give with vitamin A would prevent it oxidation. 100IU vitamin E with 100 000IU vitamin A would be sufficient to prevent 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…
- Retinil – 2400IU retinyl per drop, 340 servings per container. Comes in both palmitate/acetate. Excellent topical absorption.
- Vitamin A – 2000IU retinyl palmitate per serving, 100 caps
- EstroBan – 5000IU per serving, 30 servings. Also contains 1000IU vitamin D, 100IU vitamin E, 1.5mg K2 (MK-4). Excellent topical absorption.
Adamantane is a naturally occurring substance that is anti-serotonin (91) and also a potent dopamine agonist. 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.
- Daimant – 33mg adamantane per serving, 30 servings. You can start with 5 drops daily, and increase from there if needed.
46) Salt & Potassium
Salt and potassium, similarly to lithium, also forms complexes with serotonin and melatonin. Highest to lowest affinity and stability for serotonin goes as follow: Li+ > K+ > Al3+ > Na+ > Ca2-. Highest affinity to lowest affinity and stability for melatonin goes as follow: K+ > Li+ > Na+ > Al3+ > Ca2+. This can explain the role of aluminium in Alzheimer disease. (94)
Beta-alanine supplementation in mice decreased serotonin in the hypothalamus and increased carnosine, which increased BDNF. (96) The human equivalent dose is around 2.5-3g. Carnosine also prevents the age-related increase in 5-HT receptor binding. (97)
- Beta-alanine – 500g container, pure powder
γ-mangostin (a component of mangosteen) enhances the expression of 5-HT(2A/2C), muscarinic, histamine and bradykinin receptor mRNA, which suggests that this compound has antagonistic effects. (99) Mangosteen (γ-mangostin) is also a potent aromatase inhibitor.
- Mangosteen extract – 187.5mg Mangosteen Fruit Rind Extract per serving, 60 servings
49) 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. (100) A decrease in COMT can increase dopamine, serotonin, noradrenaline, etc, which can further increase your serotonin if it’s already high. But due to its serotonin receptor antagonism, the effect might be more dopaminergic than serotonergic. If you get high serotonin symptoms from it, discontinue use.
- Bacopa monneiri – 100g container. Take 1/4 tsp once daily.
After receiving high dose (1g x3 daily) hypoxanthine (immediate metabolite of inosine) and allopurinol (100mg x3 daily), urinary serotonin excretion showed decreases to as much as 60% below initial values. The cause is probably a reduced synthesis or release of 5-HT. (102) When mice were given orally hypoxanthine 500 mg/kg, MAO-A and -B activities were all inhibited significantly 16 hours after administration, but the inhibitory action on MAO-A was weaker. (101) The human equivalent dose is 71.5mg/kg, which will be 5720mg for a 80kg individual. The dose is a bit high, but I think smaller doses would also have the same effect. Inosine is also known to lower adrenaline quite effectively.
- Inosine – 500mg per cap, 60 caps
51) High protein diet / liver damage / ammonia
When a high protein diet is eaten, more ammonia is produced as a byproduct. When the ammonia isn’t properly converted to urea and detoxified, more ammonia crosses the blood-brain barrier. This increase in ammonia, 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.
Panax ginseng is very widely used as an energy booster, and similar to ginger, antagonizes 5-HT3, which is very effective against nausea. (104) Ginseng also inhibits the uptake of neurotransmitters, in the following order of GABA = noradrenaline > dopamine > glutamate > serotonin, and this effect is concentration-dependent. (105)
Ginseng, however, does increase serotonin is some brain regions (corpus stratum and cerebellum), but decreases it in others (hypothalamus and midbrain) in mice. (106) If you experience increased serotonin symptoms (which might be unlikely) from this herb, discontinue use.
- Panax ginseng (10% ginsenosides RG1 & RB1) – 100mg per cap (10mg ginsenosides), 60 caps
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 (109, 110, 111)
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.
- Arginine powder – 1lb
54) White peony root (bai shoa yao / Paeonia radix)
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. (112)
55) Valerian root
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. (115)
- Valerian root – 500mg per cap, 250 caps
A few save anti-serotonin drugs include cyproheptadine, memantine (derivative of adamantane) and metergoline.
57) Substances to avoid
- Curcumin (agonist to 5-HT receptors, specifically 5-HT1A/1B and 5-HT2C subtypes) (92)
- St John’s Wort (95)
- Carvacrol (phenol isolated from aromatic herbs including oregano and thyme) (92)
- Proanthocyanidin (increases 5-HT concentrations in the hypothalamus, hippocampus, and frontal cortex) (92)
- Resveratrol (inhibits MAO and is also estrogenic) (92)
- Saffron (92)
- Rhodiola Rosea (inhibits MAO-A, but the effect is very mild. Still a good anti-stress supplement to use) (92)
- Nelumbinis semen (92)
- Acetyl-L-carnitine (94)
- High dose ashwagandha
- Berberine (inhibits MAO-A, but also increases SERT and dopamine, so the effect might be more dopaminergic than serotonergic) (98)