Supplements That May Have Mood-Related Effects
There are a number of supplements and dietary compounds that may have potentially-beneficial effects on mood.
However, keep in mind that the science behind these is still mostly preliminary, and none of these supplements have been officially approved for treating mood issues or any other psychological conditions.
In other words, there is still insufficient evidence for the efficacy of these supplements in treating mood disorders: therefore, none of these compounds should be used to replace any ongoing medical treatments that your doctor has recommended.
It’s also always a good idea to consult with your doctor before trying out any new supplements or other dietary changes, as there’s always the possibility that these compounds could have adverse interactions with other ongoing medications, pre-existing medical conditions, etc. Therefore, we don’t recommend “experimenting” with supplements on your own without at least discussing them with your doctor first!
With all that in mind, here’s what some of the latest science says about several supplements that might have potential mood-related effects.
Inositol has been concluded to be “likely effective” for depression, according to a meta-analysis of DB-RCTs .
Some evidence suggests that myo-inositol may act by decreasing serotonin transporter activity, thus increasing available serotonin .
St John’s Wort (Hypericum perforatum) is one of the most-studied herbs with supposed “antidepressant-like” effects, and is even widely prescribed for depression in Europe. The recommended dose is 900-1800 mg/day.
St John’s Wort has also been reported to potentially prevent or delay depression relapses in 426 patients (DB-RCT) .
St. John’s wort is believed to act in part by increasing serotonin receptors and dopamine signaling [9, 10]. It also may inhibit serotonin reuptake and glutamate release [11, 12]. However, these mechanisms are still only based on relatively early studies, and more research will be needed to figure out the exact biological mechanisms underneath this herb’s effects in the body and brain.
Adding omega-3s to the antidepressant Citalopram (an SSRI) was reported to improve depressive symptoms in 42 patients (RCT) .
Some researchers have proposed that omega-3s may reduce depression by lowering inflammation in the brain, although a lot more research will be needed to confirm this for sure .
In one study (DB-RCT) of 73 patients who did not respond to SSRIs, 800 mg of SAM-e taken twice a day for 6 weeks was reported to lead to improvements in depressive symptoms as well as reduced remission rates .
Some researchers have proposed that SAM-e may have therapeutic effects similar to those of common antidepressants, such as SSRIs . SAM-e may also have some other advantages over common depression medications, such as a relatively fast onset and increased safety (lower rates of adverse side-effects) in higher doses [23, 22].
Although its precise mechanisms are not yet fully known, some evidence suggests that SAM-e’s effects may stem from improved methylation of neurotransmitters (catecholamines), increased serotonin and norepinephrine levels, and increased dopamine activity . However, more research will still be needed to explore its potential mechanisms further, and how these might related to some of this substance’s purported effects on mood.
For example, curcumin taken at 1 g/day for 6 weeks reportedly reduced depression along with inflammatory cytokines and cortisol, and increased BDNF in 108 adults (DB-RCT) .
Similarly, another study in mice reported that curcumin increased serotonin and dopamine, and blocked MAO-A and MAO-B. It has also been suggested that curcumin may also promote the development of new brain cells in stressed rats [30, 31, 32].
However, it should be kept in mind that a lot of this evidence comes from animal studies, and so much more research in humans will be needed to confirm any of these effects and mechanisms for certain.
DHEA is believed to influence the release, breakdown, reuptake, and receptor binding activity of serotonin, dopamine, glutamate, and GABA, which may account for some of its purported effects .
Recently, scientists have proposed that the gut microbiota may have a surprisingly significant influence over brain function.
For example, it has been reported that people who have inflammatory gut diseases often also have depression .
According to some early human studies, probiotics may help reduce depressive symptoms in both healthy and depressed individuals, although a lot more clinical trials in humans will be needed to fully confirm this [39, 40].
Because serotonin is produced in the gut, changes to the gut’s microbiome may theoretically influence serotonin levels and activity in the brain . Using that logic, some have proposed that probiotics that enhance the diversity of the microbiome may promote a more favorable environment for serotonin synthesis.
Some early evidence suggests that probiotics may also reduce systemic inflammation, which is another factor that is often reported to be elevated in people in depression .
Between 1.5-3 grams/day for 30 to 60 days was reported to reduce depressive symptoms in elderly patients (DB-RCTs) .
Similarly, one DB-RCT of 204 patients with chronic depressive symptoms reported that acetyl-L-carnitine (1 gram/day for 12 weeks) improved depressive symptoms similarly to amisulpride, an antidepressant medication .
According to some researchers, acetyl-L-carnitine may act by increasing cell growth in the hippocampus, raising BDNF levels, stimulating glutamate release, and increasing serotonin levels and receptor activity .
15 mg/day of methylfolate for 6 months reportedly improved clinical and social depressive symptoms in a study (DB-RCT) of 123 depression and schizophrenia patients .
Folate may also improve responses to antidepressant drugs, at least according to one early study .
Folate is known for its role in the production of the neurotransmitters serotonin and dopamine. Some early evidence also suggests that folic acid may stimulate serotonin receptors in the brain, although more research will be needed to confirm the effects of folate in the brain [54, 55, 56].
One meta-analysis reported that 600-800 IU/day of vitamin D improved depressive symptoms .
According to one RCT study, 3,500 IU/day of vitamin D for 1 month was reported to improve symptoms of seasonal affective disorder (SAD), a seasonal form of depression .
Vitamin D supplementation also reportedly reduces suicide risk linked to vitamin D deficiencies .
One study also suggests that vitamin D may help protect against dopamine and serotonin depletion in the brain (specifically, in the striatum and nucleus accumbens) .
According to a few animal studies, valerian may have helped prevent stressed rats from developing depressive-like behaviors, while also increasing serotonin levels and overall cell growth in the hippocampus (a brain region believed to be involved in regulating mood, among other important functions) [73, 74]. However, more clinical studies in humans will be needed to verify this.
According to one DB-RCT study, 3 mg melatonin at bedtime for 6 months lowered depressive symptoms in 79 women .
Some early evidence suggests that melatonin may improve the circadian rhythm of a number of different important neurotransmitters that are believed to be disturbed in depression .
According to one animal study in rats, some of melatonin’s effects may be due to its influence on norepinephrine levels (specifically, by binding to norepinephrine transporters, and blocking the enzyme MAO-A) . However, whether this mechanism applies to humans (and not just rats) is not yet known for sure.
Although it’s not yet known what effects this herb has on human biology, in animals rhodiola rosea has been reported to lower cortisol, reduce stress-induced protein damage, decrease nitric oxide levels, and inhibit the MAO-A enzyme. It has also been reported to increase serotonin levels in the hippocampus, and may even play some role in repairing damaged hippocampal cells [86, 87, 88]. However, these mechanisms may not apply to humans, and more research will be needed to find out for sure.
However, no studies in humans have shown similar effects, so the results of these early animal studies should be taken with a major grain of salt until follow-up clinical trials in humans can confirm this.
Some researchers have proposed that magnolia bark’s effects may stem from activating GABA-A receptors, as well as potentially by blocking the activity of dopamine and serotonin transporters (thereby increasing the levels of these neurotransmitters) [93, 91, 94].
A few isolated medical case studies have reported rapid improvements in depression, anxiety, and sleep within one week of magnesium supplementation . However, these are only reports from single individual patients, and do not provide the same evidence that large-scale clinical trials in humans would — so more research will be needed.
According to a few studies, magnesium may improve depressive symptoms in people with postpartum depression, premenstrual syndrome, type 2 diabetes, and chronic fatigue syndrome [97, 98, 99, 100]. However, whether these effects would hold up in people without these specific medical conditions has yet to be confirmed.
Some researchers have speculated that magnesium may work by blocking the NMDA receptor, which could reduce the effect of the neurotransmitter glutamate .
According to one study in 20 patients with major depression, L-theanine intake (250 mg/day for 8 weeks) was reported to improve depressive symptoms, anxiety, sleep disturbances, and cognitive function .
In one animal study in mice exposed to chronic social stress, L-theanine reportedly reduced depression-associated behavior .
Some research has suggested that, due to its structural similarity to glutamate, theanine may act by binding to glutamate receptors and increasing overall glutamate activity (which is often reported to be disrupted in depression) .
Zinc deficiency has been associated with increased depression prevalence and severity. Furthermore, non-responders to antidepressant drugs have reportedly lower zinc levels than patients who respond successfully to conventional treatment .
One meta-analysis of multiple RCT studies concluded that zinc may be an effective standalone or supplementary treatment for depression .
Zinc (30 mg for 12 weeks) has been reported to increase BDNF levels according to one study (DB-RCT) of 50 people. These Increased levels of BDNF were correlated with lower depressive symptom severity, suggesting a potential relationship [105, 106, 107].
Chronic zinc treatment has been reported to increase serotonin receptors in rats, although this finding has yet to be directly confirmed by human studies .
One study has reported that Creatine supplementation (3-5 g/day for 4 and 8 weeks) may lower depression symptoms in people with methamphetamine dependence or treatment-resistant depression [109, 110, 111].
Creatine taken at 5 g/day with an SSRI improved symptoms more than SSRI alone in a study (DB-RCT) of 52 women with major depression .
However, all of the above evidence has come from people with specific medical conditions, and it is not yet possible to say with any certainty whether mood-related effects from creatine would also been seen in healthy human users.
On a mechanistic level, supplementing with creatine theoretically reduces the body’s need to synthesize creatine, which may increase the total available amount of S-adenosyl-L-methionine (SAMe) throughout the body and brain .
Application of lavender cream nightly for 8 weeks reportedly reduced depression, anxiety, and stress in another study (RCT) of 141 pregnant women .
According to an RCT of 45 depression patients, when combined with a traditional antidepressant medication, lavender was reported to reduce depression more than just the antidepressant alone .
Some evidence from studies in mice suggests that lavender oil may act by increasing dopamine receptors, as well as by binding to NMDA receptors to decrease their activity [122, 123]. However, it’s not certain whether this mechanism is relevant to human users, and more research will still be needed.
Some early evidence suggests that ginseng may act by increasing hippocampal dopamine, serotonin, and BDNF levels, and lowering the levels of nitric oxide and pro-inflammatory cytokines [127, 128, 129, 130].
According to one DB-RCT study in 54 healthy seniors, Bacopa extract (300 mg/day for 12 weeks) was reported to improve depression and anxiety symptoms, as well as increase working memory and attention .
Bacopa may help preserve dopamine levels that are otherwise depleted in chronic stress and drug-induced neurotoxicity, although research on bacopa’s potential mechanisms is still in an early stage [134, 135].
In one study (DB-RCT) of 196 patients with IBS, intake of 400 mg/day of berberine for 8 weeks reduced depression, anxiety, and IBS symptoms, while also improving the patients’ quality-of-life ratings .
However, because this study only looked at patients with a specific preexisting medical condition, more follow-up research will be needed to know if berberine might have similar effects in otherwise healthy human users as well.
An animal study also reported that berberine may be useful for alleviating depression and anxiety symptoms that follow morphine addiction .
Some studies have reported that decreased pregnenolone levels are often associated with cases of depression .
Depression has been associated with abnormalities in brain microtubule function. By increasing the formation and stability of tubules, pregnenolone’s effect on mood may come from an increase in the growth of brain cells (axons and dendrites) [148, 149].
5-HTP is one of the “ingredients” (metabolic precursors) the brain naturally uses to produce serotonin. Some early evidence suggests that the “antidepressant-like” effects of 5-HTP may be comparable to those of prescribed antidepressants — at least, according to one study .
According to another similar study, the combination of 5-HTP with a typical antidepressant medication (SSRI) raised serotonin levels by as much as 500% in 52 healthy men .
However, raising serotonin levels this much is not without its own risks, in part due to the possibility of serotonin syndrome. For this reason, some clinicians have recommended only using slow-release forms of 5-HTP when taken with SSRIs [152, 151, 153]. Nonetheless, because of this potential risk, combining 5-HTP with an ongoing antidepressant medication should only be done under medical supervision — so make sure to discuss this with your doctor first before casually experimenting with it!
According to one animal study, holy basil also reportedly showed antidepressant effects similar to commonly-prescribed antidepressants, and led to improved anxiety, memory, and cognitive function .
However, this is a very small sample size, and more research will be needed to see if these effects pertain to healthy human users as well.
However, a trial of 65 patients did not support tyrosine as an antidepressant . One possibility is that tyrosine might only help people with naturally low levels of dopamine and norepinephrine, although more research will be needed to figure out exactly who tyrosine might help, and when.
Borage (Echium amoenum) is an herb native to Iran, sometimes referred to as “ox-tongue.”
According to one study, 375 mg of Borage per day was reported to reduce depressive symptoms after 4 weeks in a study (DB-RCT) of 35 individuals. However, it was not effective after 6 weeks, suggesting that its effects may only be temporary .
This is only one study of the effects of Borage in humans, and much more research will be needed to confirm this early result.
Some early evidence suggests that olive oil may act by increasing the release and turnover of dopamine .
Other preliminary evidence suggests that the oleic acid in olive oil produces oleamide, which may act by increasing neurotransmitter binding to serotonin receptors .
According to one study, riboflavin intake was reported to prevent postpartum depression in 865 women .
A supplement containing 10 mg of each B1, B2, and B6 vitamins was reported to alleviate depression symptoms in a study (DB-RCT) of elderly depression patients .
However, riboflavin’s effects may depend on gender: for example, according to a study of 6,500 adolescents, increased riboflavin intake was associated with decreased depressive symptoms in girls, but not in boys .
Low B6 levels have been associated with increased depressive symptoms in one study of 140 healthy participants .
Women consuming more foods containing B6 were reported to have a lower risk of depression in one study of 170 women .
Watch the founder and CEO of SelfDecode Joe Cohen and Katie Wells discuss how to improve mood & mental health: