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24 Supplements That May Naturally Increase Serotonin

Written by Ana Aleksic, MSc (Pharmacy) | Reviewed by Biljana Novkovic, PhD | Last updated:
Jonathan Ritter
Matt Carland
Puya Yazdi

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Serotonin is important for both mental and physical well-being. Serotonin can affect everything from mood and behavior, to gut and heart health, to blood vessel function. Low levels of serotonin have been associated with mood disorders, migraines, and gut issues. Read on to discover supplements that may boost serotonin levels naturally!

What is Serotonin?

Serotonin is an important signaling molecule throughout the brain and body. It is commonly known as the “happiness neurotransmitter” or the “happiness hormone,” due to its prominent role in regulating mood.

Serotonin plays an important role in the brain, where its main job is to transmit messages between nerve cells. According to some scientific theories, serotonin is involved in all aspects of human behavior [1, 2].

24 Strategies For Increasing Serotonin Levels

When To See A Doctor

If your goal is to increase serotonin to improve your mood-related issues — including those of depression or anxiety — it’s vitally important to talk to your doctor, especially your mood is significantly impacting your daily life.

Major mood changes, such as excessive sadness, persistent low mood, euphoria, or anxiety, are all reasons to see a doctor.

Your doctor should diagnose and treat the condition causing your symptoms.

Remember that the existing evidence does not suggest that low brain serotonin directly causes mood disorders. Neither is serotonin necessarily the “only” or “main” causative factor. Complex disorders like depression involve multiple possible factors — including brain chemistry, environment, health status, and genetics — that can each vary significantly from one person to another.

Additionally, changes in brain chemistry are not something that people can change on their own with the approaches listed below. Instead, the factors listed here are meant to reduce daily stress and support overall mental health and well-being. In other words, the information in this post should never be used to replace conventional medical treatment—they are “complementary strategies” only.

Therefore, you may try the additional strategies listed below if you and your doctor determine that they could be appropriate. Read through the approaches listed here and discuss them with your doctor before trying them out. None of these strategies should ever be done in place of what your doctor recommends or prescribes.

If your mood is significantly impacting your daily life, it’s important to see a doctor or psychologist as soon as possible. They are best equipped to help you treat any underlying conditions and choose the best strategies to improve, which may or may not include any of the strategies below.

Main Supplements

Make sure to speak with your doctor before taking any supplements. Also be sure to let them know about any other prescriptions or over-the-counter medications you may be taking, including vitamins and herbal supplements, in order to minimize the risk of experiencing adverse interactions.

This is particularly important if you are already taking medications (such as antidepressants) or supplements that may increase serotonin levels. Adverse drug interactions or incorrect dosing can cause serotonin syndrome, a serious condition that results from having too much serotonin in the body.

If you and your doctor agree that supplementing is a good idea, make sure to only purchase and use products made by a trusted and reliable manufacturer. 

Remember that dietary supplements have not been officially approved by the FDA for medical use. Supplements generally lack solid clinical research. Legal regulations can set manufacturing standards for them, but don’t guarantee that they’re safe or effective. 

With all these important points in mind, here are some supplements that research suggests may help increase serotonin and support mood balance.

1) L-Tryptophan and 5-HTP

In the body, serotonin is made from 5-HTP, and 5-HTP is made from L-tryptophan. Therefore, increasing the levels of either of these “building blocks” (metabolic precursors) can, in theory, lead to increased overall levels of serotonin.

Limited research suggests that taking L-tryptophan may raise plasma serotonin, and may improve certain cognitive, motor, or gut issues in those who are deficient [3, 4].

A protein called alpha-Lactalbumin, a compound commonly found in milk, contains more tryptophan than many other proteins [5]. According to one study of 18 individuals, 12 grams of alpha-Lactalbumin was reported to increase the amount of tryptophan in blood plasma by up to 16% after 90 minutes [6].

In another study, 12.32 grams of tryptophan was reported to increase blood tryptophan levels by 43% after 1.5 hours, and improved memory in 23 subjects vulnerable to high stress [7].

In a pilot study of 13 female patients experiencing premenstrual syndrome (PMS), 6 grams of L-tryptophan taken daily for 14 days was reported to improve mood, irritability, difficulty sleeping, and cravings for carbohydrates [8].

Tryptophan can be purchased in the form of L-tryptophan supplements. 5-HTP (5-hydroxytryptophan) supplements are also available. However, it is important to note that “5-HTP” is not the same as “5-HT”, which is the chemical name for serotonin. 5-HTP freely crosses the blood-brain barrier (serotonin itself does not) to be converted into serotonin [9].

L-tryptophan and 5-HTP are the “building blocks” the body uses to make serotonin, and some research suggests that supplementing with these compounds may increase serotonin and improve mood. Of the two, 5-HTP can freely cross the blood-brain barrier.

2) Probiotics

In the digestive tract, probiotics restore the gut microbiome and influence the gut-brain axis. One of the ways in which gut bacteria are important is because they produce much of the tryptophan from which serotonin is made. Neurological disorders, such as Parkinson’s disease, have been linked to less diverse or fewer gut bacteria in some studies [10, 11].

According to one study, an 8-week probiotic regimen (2.0 x 109 CFU/g of Lactobacillus helveticus and 2.0 x 109 CFU/g of Bifidobacterium longum) was reported to increase tryptophan levels in 110 individuals with depression. Increased tryptophan can, theoretically, increase serotonin production [12, 13].

Similarly, an animal study has reported that a probiotic (Bifidobacteria infantis) given to rats for 14 days raised levels of blood tryptophan [14].

3) Vitamin D

Vitamin D helps the body make, release, and use serotonin, including in the brain. However, the benefits of supplementation are uncertain [15, 16].

Vitamin D activates an enzyme that converts tryptophan into serotonin. If vitamin D levels are low, our brains make less serotonin. Thus, increasing vitamin D intake may increase serotonin levels, thereby potentially supporting mental health [15, 16].

According to data from a cohort study of over 9,000 subjects, taking vitamin D supplements during the first year of life was associated with a 77% reduced risk of schizophrenia. In other words, preventing low vitamin D levels early in life may reduce the chance of having schizophrenia later in life, although large-scale studies will still be needed to verify this theory [17].

In theory, vitamin D is required for serotonin production and release in the brain. While some preliminary evidence points to some potential benefits of supplementing with vitamin D, the short- and long-term effects of supplementation are not yet fully understood.

4) Omega-3 Fatty Acids

While vitamin D helps neurons make serotonin, the omega-3 polyunsaturated fatty acids EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid), and ALA (alpha-linolenic acid) may help neurons release serotonin, as well as increase its overall activity (such as by increasing the sensitivity of serotonin receptors) [16].

Fish such as salmon and trout are especially rich high in omega-3 fatty acids. Omega 3 supplements are also sold in the form of fish oil capsules, although the benefits of supplementing are less clear than the effects associated with normal dietary intake of these compounds [16].

According to some researchers, inadequate omega-3 fatty acid intake may increase susceptibility to psychiatric illnesses, including depression. However, a clear link hasn’t yet been established, so this link remains speculative until more research is available [18].

In one study of 49 patients who engaged in self-harming behaviors, 1.2 grams of EPA and 0.9 grams of DHA capsules taken daily for 12 weeks were reported to reduce suicidal thinking by up to 45%, and overall depression symptoms by 30%. Nonetheless, this study was limited by its relatively small sample size and short duration, so more research will be needed to confirm these early findings [19].

An observational study of over 250,000 Japanese participants reported that people who ate fish daily tended to have lower rates of suicidal thoughts compared to people who did not eat fish daily. Similarly, in another observational study of 1,767 Finnish subjects, consuming fish less than twice a week was associated with a relatively increased risk of depression and suicidal thinking compared to those who consumed more fish [20, 21].

In one animal study in rats, low levels of omega-3 fatty acids — specifically alpha-linolenic acid (ALA) — were associated with lower serotonin activity. Relatedly, DHA deficiencies have been associated with reduced brain serotonin levels in piglets [22, 23].

In another animal study, groups of pregnant rats were fed with diets that were either deficient or rich in alpha-linolenic acid. The levels of serotonin in the prefrontal cortex of rats with an ALA-deficient diet were found to be up to 65% lower compared to the rats with an ALA-rich diet, thus further suggesting a potential link between omega-3 fatty acids and overall serotonin levels [24].

The omega-3 fatty acids EPA, DHA, and ALA help neurons release serotonin. Diets deficient in these fatty acids have been linked to poor mental health, while supplementing has improved mental health in some studies.

5) St. John’s Wort

St. John’s Wort is a popular supplement derived from the medicinal plant Hypericum perforatum. Although it has many uses, it is most commonly used as a supplement for mood or mild depression. However, according to the National Center for Complementary and Alternative Medicine (NCCIH), the results of studies on the effectiveness of St. John’s wort for depression are mixed [25].

Importantly, clear evidence shows that St. John’s Wort can interact in dangerous, potentially life-threatening ways with many common medicines [25]. Therefore, never take St. John’s Wort supplements without consulting a doctor first!

According to one large-scale review of data from 35 different studies (including data from over 6,900 patients with depression), standalone therapy with St. John’s Wort improved only mild-to-moderate symptoms of depression. However, the authors also noted the relatively low quality of many of the studies included included in this review, as well as considerable inconsistency in its reported effectiveness across different studies, which limit the conclusions that can be made on the basis of this data [26].

A number of animal studies have investigated the effects of St. John’s wort on serotonin levels and activity in animals. A number of preliminary findings suggest that some of the components of this plant may act by inhibiting the reuptake of serotonin from neural synapses, as well as potentially increasing the number of serotonin receptors in certain regions of the brain [27, 28, 29, 30, 31, 32]. However, much more research — especially in large samples of human patients — will be needed to find out if these mechanisms are relevant to human users as well.

St. John’s wort is among the best-known and best-studied supplements for increasing serotonin. It is effective enough that it can be extremely dangerous to combine with other supplements or drugs that increase serotonin.

6) S-Adenosyl Methionine (SAM-e)

SAM-e is a naturally-occurring compound that plays a critical role in many important biological processes, such as methylation and energy metabolism. It is also involved in the chemical process that the body uses to produce (synthesize) serotonin [33, 34].

Some limited preliminary data suggests that SAM-e may reduce symptoms in some people with major depressive disorder (MDD) who are not responding to conventional therapy, though large-scale trials are still lacking [35].

According to one study involving 73 MDD individuals unresponsive to therapy with conventional antidepressants (such as SSRIs), adding on a twice-daily treatment with 800 mg of SAM-e to their existing antidepressant medication was reported to significantly improve their symptoms of depression (compared to patients who received an inactive placebo treatment) [34].

In another study of 144 individuals with MDD, 1,600–3,200 mg of SAM-e daily for 12 weeks was reported to significantly improve mood [36].

Finally, a review of data from 132 studies (115 clinical and 17 preclinical) reported “promising but limited evidence” that SAM-e might be useful for depression. Additionally, the study’s authors suggest that SAM-e may also have some potential to treat certain symptoms of substance abuse and psychosis disorders, based on the preliminary data currently available at the time of this review. However, more clinical research still needs to be conducted to verify and extend these early findings [35].

7) B Vitamins

The body requires vitamin B6 to produce (synthesize) serotonin from its precursors, such as 5-HTP (specifically, vitamin B acts as enzyme cofactor) [37].

Additionally, vitamin B12 and folate (vitamin B9) are each necessary for the folate cycle, which helps convert tryptophan into serotonin (by producing and recycling essential cofactors) [38].

According to some preliminary research, a lack of B vitamins may be associated with the onset of mental health disorders, such as depression. Conversely, higher dietary intake of these vitamins may have some protective effect on the long-term risk of developing these conditions. However, this finding was based only on (retrospective) associations, and has not yet established a causal link between vitamin B and mental health [37].

In a cohort study of 549 community-dwelling seniors, those with vitamin B12 and B9 deficiencies (chronically low blood levels) were reported to be relatively more likely to show signs of “irreversible” problems with cognition (such as deficits in memory and attention) [39].

In an animal study in Rhesus monkeys, a single dose of vitamin B6 was reported to increase serotonin production in the brain [40]. Similarly, treatment of healthy adult rats with a vitamin B mixture was reported to raise the levels of serotonin in the brain [41].

While these early animal results are promising, more research will still be needed to verify whether vitamin B has similar effects on serotonin levels in humans as well.

Several different B vitamins (including B6, B9, and B12) are believed to be essential for serotonin production and release. Deficiencies have been linked with poor cognitive outcomes in some preliminary studies, although whether supplementing with these vitamins has direct mental health benefits in healthy human users has not yet been fully established.

8) Zinc

Based on some early research, some scientists believe that zinc may target and activate serotonin receptors [42].

According to one meta-analysis of data from 17 observational studies, blood zinc levels were reported to be lower in depressed individuals compared to non-depressed individuals, which may imply a serotonin-related mechanism [43].

In another study of 37 patients with major depressive disorder, 12 weeks of daily supplementation with 25 mg of zinc was reported to reduce depressive symptoms [44].

In addition to supplementing with it directly, dietary zinc can also be obtained through several common foods such as red meat, oysters, crab, and whole grains [45].

9) Magnesium

Researchers hypothesize that magnesium supplements might increase serotonin levels by increasing its availability (reducing reuptake) in the brain.

For example, according to one preliminary study, 8 weeks of daily supplementation with 500 mg of magnesium (magnesium chloride) was reported to significantly improve depression symptoms in 60 patients diagnosed with mild-to-moderate depression. This magnesium treatment was also reported to have a significant — though somewhat smaller — effect on anxiety symptoms as well [46].

Magnesium is naturally found in several common dietary sources including nuts, seeds, legumes, green leafy vegetables, and whole grains [45].

10) Inositol

Some early evidence from cell and animal studies suggests that the “vitamin-like” compound inositol may increase the sensitivity of serotonin receptors [47, 48].

Due to its interactions with the brain’s serotonin system, some researchers have proposed that inositol may act similar to common serotonin-targeting antidepressant drugs (such as selective serotonin reuptake inhibitors, or SSRIs) [49].

According to one study of 30 women experiencing symptoms of PMS-related mood disorders, treatment with myo-inositol over the course of six menstrual cycles (~6 months) was reported to reduce mood symptoms and improve overall mood [49].

Additionally, according to a few animal studies, inositol treatment has been reported to reduce depression-related behaviors in rats [50, 51].

While some of these early findings are promising, much more research will still be needed to confirm these effects in human populations.

11) Rhodiola

Rhodiola rosea is a flowering plant that may help improve anxiety and depression, though the evidence is insufficient.

According to one clinical trial in 89 patients with mild-to-moderate depression, 42 days of supplementation with Rhodiola rosea extracts (340 mg/day and 680 mg/day) was reported to improve overall depression symptoms, including insomnia and emotional instability [52].

In an animal study on rats with stress-induced depression and signs of serotonin deficiency, 3 weeks of supplementation with Rhodiola extract (1.5, 3, or 6g/kg) was reported to restore normal levels of serotonin. The authors also reported that the rats showed signs of increased neurogenesis in the hippocampus, which may also be a contributing factor in these effects [53].

Nonetheless, more research in humans will be needed to properly confirm these promising early findings.

Other Supplements (Weak Evidence)

No valid clinical evidence supports the use of the supplements listed below for serotonin- and mood-related problems. We provided a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, these studies should not be interpreted as supportive of any significant mood-related effect.

12) Vitamin C

According to one animal study, 6 weeks of supplementation with vitamin C was reported to increase brain serotonin levels in rats with drug-induced dementia [54].

13) Vitamin E

8 weeks of supplementation with vitamin E has been reported to increase serotonin levels in rats suffering from spinal cord injuries [55].

14) Curcumin / Turmeric

Curcumin is the active component of the common spice turmeric.

According to one animal study in stressed rats, curcumin was reported to extend the length of time that serotonin remained active in the brain (possibly by blocking the reuptake of serotonin). It also reportedly improved some measures of cognition, as well as reduced serum levels of corticosterone (an animal version of the human “stress hormone” cortisol) in rats [56].

In mice, a single dose of curcumin (10–80 mg/kg) was reported to increase serotonin levels [57].

15) Velvet Bean

According to some preliminary research, supplements derived from the plant Mucuna pruriens — also known as “velvet bean” — have been reported to potentially improve some symptoms of Parkinson’s disease.

Although it is believed that these effects are probably due primarily to the fact that mucuna is a rich source of L-dopa (an important metabolic precursor of dopamine), some studies have also reported that long-term use of the powder form of Mucuna pruriens increased serotonin levels in the brains of rats, thereby suggesting an additional potential mechanism of action [58].

However, the exact effects of mucuna on serotonin levels in humans have not been confirmed, and more research will be needed.

16) L-Theanine

L-theanine is an amino acid naturally found in tea leaves (e.g. green, black, or oolong tea) as well as in Bay Bolete mushrooms. However, out of all of these dietary sources, green tea is believed to contain the highest concentration of L-theanine [59, 60, 61].

Theanine has been reported to have generally “relaxing” effects on the mind, which may suggest a serotonin-related mechanism of action [61, 59, 62].

For example, according to a cohort study of over 42,000 Japanese individuals, those who consumed at least 5 cups of green tea a day reported experiencing significantly less day-to-day psychological distress — a symptom that is often associated with reduced serotonin levels [63].

Although serotonin-related mechanisms of theanine have not been directly confirmed by any human studies, one early animal study has reported that L-theanine may act by increasing serotonin levels in the brain. However, other studies have suggested that theanine may also act on other neurotransmitter systems — such as GABA and dopamine [62]. Therefore, more studies will be needed to confirm the precise mechanisms involved in theanine’s potential psychological effects.

17) Saffron

According to some preliminary research in both humans and animals, saffron (Crocus sativus) has been reported to have some potential anti-anxiety and anti-depressant effects, which may indicate a serotonin-related mechanism of action [64, 65, 66, 67, 68].

For example, one meta-analysis of data from five trials (including a total of 177 participants) reported that 6-8 weeks of daily supplementation with 30 mg of saffron capsules appeared to improve symptoms of depression in adults with major depressive disorder [68].

Although saffron contains many different bioactive components, researchers believe that the compounds safranal and crocin may be the specific ones responsible for interacting with the serotonin system [64, 65, 69].

However, not all studies have suggested a serotonin-based mechanism for saffron. For example, at least one study has reported that a saffron extract increased levels of the neurotransmitters dopamine and glutamate, but appeared to have no direct effect on brain serotonin levels [70]. Therefore, more research will still be needed to pin down saffron’s precise effects on the brain.

18) Magnolia Tree

The bark and seed cones of the Magnolia tree (Magnolia officinalis) have a long history of use in traditional medicine throughout several Asian cultures — and some preliminary research suggests that magnolia may have noteworthy anti-stress, anti-anxiety, anti-depressant, anti-oxidant, and anti-inflammatory effects [71].

Of the many bioactive components of magnolia, honokiol and magnolol are currently believed to be some of the main compounds responsible for this plant’s potential psychological effects (especially its reported “antidepressant-like” effects) [72].

According to one early animal study, supplementation with honokiol and magnolol was reported to counteract reduced serotonin levels in the brains of rats subjected to chronic stress — particularly in key brain regions including the prefrontal cortex, hippocampus, striatum, hypothalamus and nucleus accumbens [72].

In another animal study, mice who were treated with a combination of magnolia and ginger extracts were reported to show increased levels of serotonin and norepinephrine in the prefrontal cortex, hippocampus and striatum. While many different bioactive compounds were included in the treatment, the authors of the study concluded that it was likely the main active components of magnolia (honokiol and magnolol) which were primarily responsible for these effects [73].

However, more research in humans will still be required in order to confirm whether these effects translate beyond animal models.

19) Essential Oils

People often use essential oils as a complementary approach to anxiety, stress, low mood, and other common mental and physical health issues [74, 75, 76, 77, 78, 79, 78].

Although the exact mechanisms behind aromatherapy remain unclear, scientists posit that the act of smelling (inhaling) essential oils may activate the brain’s olfactory system, which may in turn help trigger the brain to increase the production or activity of various neurotransmitters (such as serotonin and dopamine) [80].

According to one study of aromatherapy in 60 elderly patients with depression, a 5 ml mixture of essential oils (containing lavender, sweet orange, bergamot, and almond oil) reportedly increased serotonin levels after application two times a week for 8 weeks [81].

While human studies on aromatherapy are limited, early evidence from animal and cell studies offers some additional support for the potential effectiveness of aromatherapy.

For example, essential oil from the plant ylang-ylang has been reported to increase serotonin levels in the brains of mice (specifically, in the hippocampus, a key brain area involved in learning and memory) [82].

Similarly, bitter orange is an essential oil that has been reported to reduce anxiety and improve mood in mice after 14 days of use — possibly by increasing serotonin activity throughout the brain [83].

Two animal studies have reported that aromatherapy with essential oils derived from bergamot may have significant anti-anxiety effects in rats [76, 84].

Finally, one cell study has suggested that one of the mechanisms behind the biological effects of lavender oil may be the inhibition of the serotonin transporter (SERT) — the protein that is responsible for clearing serotonin out of neural synapses after it is used — which would lead to increased amounts of active serotonin throughout the brain [85].

However, the exact mechanisms behind the potential effects of aromatherapy, as well as its overall effectiveness in actually treating psychiatric conditions or specific medical symptoms, remains unclear — and much more research will still be needed in order to understand the purported effects of aromatherapy and how they might work.

Some researchers believe that inhaling the vapors of essential oils may help increase serotonin and dopamine levels. However, the available evidence so far is mostly only suggestive — and more research will be needed to confirm the effects and mechanisms of aromatherapy in healthy human users.

20) Valerian Root

According to some early pre-clinical animal research in mice and rats, certain components of the root of the valerian plant (such as valerenic acid) may increase levels of serotonin and norepinephrine — specifically, by decreasing the rate at which these active neurotransmitters are broken down, or “metabolized,” into inactive forms [86, 87].

However, the effects of valerian might depend on context. For example, according to a study in rats with irritable bowel syndrome (IBS), valerian extracts were reported to decrease serotonin levels. This effect reportedly improved the symptoms of IBS, a condition which has been associated with elevated levels of serotonin in the gastrointestinal tract [88].

Nonetheless, these contrasting findings suggest that the effects of valerian on serotonin levels in different parts of the body may be complex and difficult to predict — and more research will be needed.

21) Apigenin

Apigenin is a nutrient found in many vegetables and fruits (especially citrus fruits). Some early research has suggested that it may have a variety of potential benefits on mood, cognition, and stress, as well as possibly protecting against oxidative stress and inflammation [89, 90].

While apigenin’s effects and mechanisms are not fully understood yet, some evidence from animal studies suggests that at least some of its potential effects may be due to its influence on serotonin levels.

For example, according to one preliminary animal study, treatment of mice with experimentally-induced seizures with apigenin for 20 days was reported to increase serotonin levels in the hippocampus, as well as increased BDNF and CREB. The apigenin treatment was also associated with reduced cognitive deficits and anxious behaviors [91].

In another animal study, apigenin was reported to prevent reduced levels of serotonin in rats subjected to chronic stress — possibly by reducing the rate at which serotonin is broken down (metabolized) throughout the brain [92].

22) Berberine

Berberine is a salt derived from the roots, rhizomes, stems, and barks of various plants in the Berberis family. The berberis family of plants includes barberry, tree turmeric, Oregon-grape, and many others [93].

Although its precise mechanisms are still being researched, some early findings suggest that some of the active compounds from berberis plants, such as berberine chloride, may increase serotonin levels by inhibiting MAO-A, one of the main enzymes that normally helps “break down” and “deactivate” serotonin [93].

According to one animal study, a single dose of berberine was reported to increase serotonin levels by up to 47% in the brains of depressed mice. Additionally, longer-term treatment (over 15 days) was associated with longer-lasting increases in serotonin levels (by 19%-53%, depending on the size of the dose) [93].

Finally, one other animal study has reported that berberine treatment alleviated depression-related behaviors in mice, and that these effects may be due to increased levels of serotonin and norepinephrine in the hippocampus and prefrontal cortex [94].

23) Acetyl-L-Carnitine

Acetyl-L-carnitine (ALCAR) is a modified form of carnitine, a common dietary supplement sold in health food stores. ALCAR has been marketed as helping protect the brain and improving mood, although sufficient human data are lacking to support its official medical use [95].

According to one preliminary animal study, 25 days of supplementation with ALCAR was reported to increase levels of serotonin and norepinephrine in the cortex and hippocampus of healthy mice. ALCAR treatment was also linked to increased brain levels of glucose, suggesting an additional effect on energy metabolism. Finally, the ALCAR treatment was also associated with “antidepressant-like” effects on the mices’ behavior, which the authors propose was likely due to some of these same mechanisms [95].

24) Lithium Orotate

Certain forms of lithium have long been used as mood stabilizers in the treatment of psychiatric disorders, such as bipolar disorder. Although the mechanisms involved in its effects are complex, some researchers believe that at least some of its main mood-stabilizing effects may be due to its ability to stimulate certain specific receptors throughout the brain’s serotonin system (such as 5-HT1A serotonin receptors) [96].

While these pharmaceutical forms of lithium (lithium citrate and lithium carbonate) are only used in a medical context, there are other forms of lithium — such as lithium orotate — that are sometimes used (albeit at much lower doses) as nutritional supplements by people looking to balance their mood.

In theory, lithium orotate may have similar effects as medical forms of lithium on the serotonin system: however, this idea is mostly only hypothetical, based on some of the apparent chemical and molecular similarities between these compounds. Nonetheless, hard evidence for the supposed psychological benefits of lithium orotate supplementation are lacking, and caution would be advised against supplementing with it until much more data is available regarding its effects and safety in healthy human users.

Drug Interactions

Like any bioactive substance in the body and brain, serotonin levels need to be carefully balanced in order to ensure optimal health.

Unfortunately, this fact sometimes gets lost in the way that many people discuss certain topics, such as serotonin and dopamine. It’s often possible to get the impression that having “more” of these is always “better” — which is definitely not the case!

While most people probably associate “low” serotonin levels with negative effects (such as depression and other mood disorders), it is very important to note that there are also risks associated with having serotonin levels that are too high!

For example, elevated levels of serotonin can cause serotonin syndrome — a serious medical condition that can be potentially fatal [97, 98, 99].

This also means that compounds that increase serotonin levels can be highly dangerous in excess. The more of these substances a person takes, the more their effects can potentially “add together” to cause serotonin syndrome.

Additionally, people who are already taking serotonin-targeting medications — such as selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and triptans — are at especially increased risk of serotonin syndrome and other negative side-effects, since these drugs already significantly raise serotonin levels. For this reason, people on serotonergic medications are especially advised against taking potent serotonin-targeting supplements, such as St. John’s Wort, SAM-e, or lithium [97, 98, 99].

Overall, it’s a bad idea to take multiple serotonin-boosting supplements at a time, or taking high doses of one right away without carefully testing it out at lower doses first. Always have a discussion with your doctor before personally experimenting with any new supplements, and make sure that he- or she- is fully up-to-date about any other medications you are taking, or any other pre-existing medical conditions you have, so that they can help you minimize the risks of negative side-effects and other adverse interactions.

To learn more about serotonin syndrome, check out this post.

Limitations and Caveats

Many of the existing studies on these supplements and their potential effects on serotonin levels or activity have major limitations, such as small sample sizes or short durations.

Additionally, many of these supplements and compounds have only been tested in animals. Further research in humans will be necessary to determine their effectiveness and safety, especially in healthy human users.

In addition to the concentration of serotonin, both the number of serotonin receptors and their sensitivity may also play an integral role in determining serotonin activity.

Though serotonin is mostly made, stored, and released in the gut, serotonin acts as an important neurotransmitter in the brain. Some of these natural remedies and supplements need further testing to determine if they are able to cross the blood-brain barrier. Long-term application of these remedies should also be further studied.

Further Reading

Takeaway

Serotonin is an important signaling molecule throughout the brain and body. It is commonly known as the “happiness neurotransmitter” or the “happiness hormone” due to its prominent role in regulating mood.

Some supplements have been found to increase serotonin in clinical studies. Among these, 5-HTP, vitamin D, omega-3 fatty acids, St. John’s wort, and certain probiotics have some of the strongest evidence. Many other supplements may also increase serotonin, but the evidence supporting their use is significantly weaker.

Too much serotonin in the body can result in serotonin syndrome, a potentially life-threatening condition. Combining any drugs or supplements that can increase serotonin may increase a person’s risk of serotonin syndrome. People who are currently taking serotonin-based medications, such as SSRI and MAOI antidepressants, are at especially high risk of serotonin syndrome, and are generally advised against taking serotonin-based supplements. As always, talk to your doctor before using any new substances or supplements to minimize your risk of experiencing negative side-effects or adverse drug interactions.

About the Author

Ana Aleksic

Ana Aleksic

MSc (Pharmacy)
Ana received her MS in Pharmacy from the University of Belgrade.
Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.

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