How does stable mood, good energy, mental clarity and good deep sleep sound to you?
And those are not the only benefits you’ll get from lower serotonin, but also less inflammation, between circulation, stronger bones, higher testosterone and dopamine, better sex drive and sexual health and so much more.
Serotonin is a stress hormone that is increased when the body is under stress. Any stress can increase serotonin. Exercise to exhaustion, glycogen depletion, worry, fear, sleep deprivation, etc., can all increase serotonin.
In our modern-day lives, stress is almost inevitable and so is elevated serotonin. But we can lower it to make sure we become stress-resilient.
Just because I’m going to give you a stack to lower serotonin, doesn’t mean you have to use it for the rest of your life to keep serotonin in check, but rather to replete deficiencies. After that, you can rely only on diet for your nutrients if you want.
Main components of the anti-serotonin stack
Two of the most important ingredients of this stack is vitamin B1 and magnesium. And the reason why is because they are essential for energy production and are rapidly depleted by stress.
#1 Vitamin B1
Low vitamin B1 levels in the body reduce ATP production from glucose, creates a state of low oxygen (hypoxia; due to low CO2 production) and increases brain serotonin synthesis and impair 5-HIAA (the breakdown metabolite of serotonin) efflux from the brain (R).
A common feature of stress is that it sensitizes the serotonin receptors 5-HT2, which exacerbates stress. A vitamin B1 deficiency also sensitizes the 5-HT2 receptors (R). Overactive 5-HT2 receptor expression can contribute to symptoms such as depression, anxiety, fear, PTSD like symptoms, hyperactive stress responses, overeating, poor sleep, etc.
Hypoxia itself, caused by low B1 levels, stimulates serotonin secretion (R). Serotonin itself also causes vasoconstriction, which can worsen the hypoxia.
Magnesium is a crucial piece if this stack, for 3 main reasons.
#1 It’s needed for the converting vitamin B1 into its active form.
#2 It’s essential for energy production. Magnesium is extremely necessary for proper ATP synthesis, because ATP is stored in the body as a combination of magnesium and ATP, which is known as MgATP. ATP requires magnesium in order to be stable. Without magnesium, ATP would easily break down into other components, ADP and inorganic phosphate. Low magnesium levels lead to a low ATP to ADP and AMP ratio and can also lead to elevated adenosine (adenosine is created from AMP). Excess adenosine can contribute to chronic fatigue. Furthermore, a low energy state leads to elevated serotonin.
#3 It helps to keep stress hormones in check and stress desensitizes the 5-HT1A receptor and upregulates the 5-HT2 receptors. Magnesium can help to prevent this as it’s very effective at restoring CRH, ACTH, cortisol, norepinephrine, histamine and glutamate (NMDA receptor activation increases serotonin release (R)) back to normal.
Lastly, magnesium inhibits platelet activity, which means, less free serotonin and histamine.
Vitamin D supplementation dramatically increases magnesium requirements, so if you take vitamin D, all the more reason to take magnesium as well.
I really like aspirin, or simply salicylate (I use sodium salicylate) as it helps with stress management, uncoupling (low core and brain temperature heighten anxiety and stress), magnesium retention (R), thyroid optimization and metabolic booster (R), dopamine synthesis (R) and last, but not least, for lowering serotonin.
It’s been shown that aspirin can decrease 5-HT2 receptors in certain areas of the brain (R, R), lower TPH1 (tryptophan hydroxylase 1; the enzyme that synthesizes serotonin) (R) and increase serotonin turnover.
Acetaminophen on the other hand (another NSAID) reduces serotonin turnover and can lead to excess serotonin (R).
Two additional ways aspirin can lower excess serotonin are by lowering estrogen and blocking excess lipolysis.
Aspirin inhibits the aromatase (R) as excess estrogen desensitizes 5-HT1A, lowers SERT (the enzyme that clears serotonin from the synapsis) and increases 5-HT2 and serotonin synthesis (TPH).
Lastly, aspirin inhibits excess lipolysis. Elevated free fatty acids induced by excess lipolysis increase free tryptophan which is then used for serotonin synthesis. Free tryptophan is the rate-limited factor in serotonin synthesis, and not actually the speed up TPH.
Not much to say here except that theanine can help to lower overall serotonin in the brain.
“Following the administration of theanine, the brain tryptophan content significantly increased or tended to increase, but the contents of serotonin and 5-hydroxyindole acetic acid (5HIAA) decreased.” (R)
#5 Vitamin K2
This study shows that 2-methyl-1,4-naphthoquinone (menadione – vitamin K3, the pro-drug to vitamin K2 MK-4) stimulates serotonin uptake in platelets in a manner similar to other serotonin reuptake enhancers such as tianeptine and in opposition to SSRI drugs like Prozac.
It does so through redox cycling.
…the redox cycling of 1,4-naphthoquinones caused an increase in (Na(+)-K+)ATPase activity that resulted in the stimulation of the rate of platelet 5-HT transport.Reference
As the action of vitamin K3 is through redox cycling, then other redox agents, such as beta-lapachone, emodin, methylene blue, thymoquinone, PQQ, CoQ10, etc.
Also, vitamin K3 has been shown to inhibits MAO-B 60 times stronger than MAO-A, leading to higher dopamine levels and high dopamine to serotonin ratio.
…we show that MAO-B was inhibited competitively by 1,4-NQ (K(i)=1.4 μM) whereas MAO-A was inhibited by non-competitive mechanism (K(i)=7.7 μM). Contrasting with TMN and 1,4-NQ, menadione exhibited a 60-fold selectivity for MAO-B (K(i)=0.4 μM) in comparison with MAO-A (K(i)=26 μM), which makes it as selective as rasagiline.Reference
Zinc. A lot of people don’t eat enough meat or drink enough milk to meet their daily zinc requirements. If they exercise, their zinc requirements are even higher. Zinc has been shown to increase SERT (the serotonin transporter) and 5-HT1A sensitivity, thus speeding up serotonin uptake and lowering serotonin synthesis.
Manganese supplementation lowers serotonin and increases total vitamin B1 in the body.
“Addition of manganese to the diets promotes an increase of the total thiamine content in the blood and the liver, heart and brain tissues. This trace element appreciably changes the correlation between different thiamine fractions. The free vitamin B1 level in the blood and tissues decreases, while the level of its bound form (pyrophosphatic) increases. All the administered manganese doses induced a statistically significant reduction of pyruvic acid concentration in the blood” (R).
Creatine. Exhaustion and glycogen depletion increase serotonin, so taking creatine post-workout is a great way of lowering post-workout serotonin by restoring energetics. Creatine has been shown to lower plasma free-tryptophan (Trp) and free-Trp:tyrosine ratio (R). Remember, free tryptophan is the rate-limited factor in serotonin synthesis, so creatine can increase the dopamine to serotonin ratio. This is most likely why it’s also so effective against depression. This is one reason why I have creatine in my Dopamine Dream Team stack.
Lastly, taurine and glycine lowers serotonin synthesis and release (R).
Anti-serotonin stack summary
- Thorne: Basic Nutrients 2/day (for vitamins and minerals, such as zinc and manganese)
- Allithiamine (for those that don’t respond to normal thiamine HCL supplementation)
- 1/2 tsp magnesium carbonate + 1/2 tsp sodium salicylate
- 5mg vitamin K2 (MK-4) – take with a fatty meal
- 3g Creatine
- 500mg-1g Glycine (small doses can increase alertness, whereas larger dose can be sedative)
- 500mg-1g Taurine
For those that don’t want to take a bunch of supplements, here are foods that are high in these nutrients. Just keep in mind that it can be very difficult to replenish vitamin B1 and magnesium levels with food alone if there is a severe deficiency and if the stressors are not removed.
- Vitamin B1 – milk, pork, macadamia nuts
- Magnesium – cocoa powder, spinach, oat
- Zinc – oysters, organ meat, red muscle meat
- Manganese – clams, maple syrup, kale, pineapple, and oat are great sources of manganese
- Creatine – red meat
- Glycine – bone broth from joints or gelatin supplement
- Taurine – scallops, mussels, clams
- Bonus: Kiwi – kiwi consumption has been shown to lower TPH1 and 2 (R)
If you want check out my vid on the anti-serotonin stack on YouTube, check it out here.
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