Bipolar disorder
Supplements studied for bipolar disorder.
Overview
Eleven supplements are indexed for bipolar disorder across 19 studies, mostly with low ratings.
Flaxseed Oil (WA 32; very low effect size, low evidence, medium trust) did not improve mania or depression in children and teens over 16 weeks. Melatonin (WA 40; very low effect size, high evidence, medium trust) may aid sleep in early research but larger trials show no overall symptom benefit; it may worsen depression in some people. Inositol (WA 48; low effect size, medium evidence, medium trust) combined with omega-3s may reduce mood symptoms in children more than either alone.
Folate (WA 52; low effect size, high evidence, medium trust) effects vary by co-medication—no added benefit with lithium, but possible mania reduction with valproate in one study. See the heatmap and evidence reviews below for all eleven supplements.
Effect graph
Relevant supplements
Relevant supplements sorted by DEX Score.
| Vitamin B9 (Folate) | ★★★★★ | Low |
| Inositol | ★★★★★ | Low |
| N-Acetyl Cysteine (NAC) | ★★★★★ | Low |
| Eleuthero | ★★★★★ | Low |
| Branched Chain Amino Acids (BCAAs) | ★★★★★ | Low |
| Ashwagandha | ★★★★★ | Low |
| Melatonin | ★★★★★ | Very Low / None |
| Lecithin | ★★★★★ | Low |
| Chromium | ★★★★★ | Low |
| Flaxseed Oil | ★★★★★ | Very Low / None |
| Acetyl-L-Carnitine | ★★★★★ | Very Low / None |
Studies
Find individual evidence reviews for supplements sorted by DEX Score.
11 supplements for and rated at least stars. All purchase bands. No minimum star filter.
Vitamin B9 (Folate)View supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is unclear if taking folic acid helps improve symptoms when added to usual medicine for bipolar disorder.
- Most research shows that folic acid does not boost the antidepressant effect of lithium.
- However, folic acid added to valproate medicine during a manic episode has been shown to reduce mania symptoms more than valproate alone.
- Taking folic acid by itself can help reduce manic symptoms in the short term but does not seem to help thinking problems.
- Vitamin B6 taken with folic acid might lessen folic acid’s benefits for mania.
- Overall, folic acid seems safe and helpful for treating mania, but more studies are needed to know the best way to use it.
Browse 3 studies·1 meta-analysis
MetaCausal relationship between B vitamins and neuropsychiatric disorders: A systematic review and meta-analysis2025
A meta-analysis found that this complexity underscores the importance of personalized supplementation in developing future therapeutic approaches for NPDs.
RCTShort-Term Effects of Folate Supplementation in Combination With Vitamin B6 for Treating Acute Manic Episodes in Bipolar I Disorder: A Randomized Controlled Trial2025n=43
A randomized trial of 43 patients with bipolar disorder found that 5 mg/day all groups demonstrated significant clinical improvements after the treatment period; however, the trends in MMSE scores showed no significant differences (p = 0.068).
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 5 mg/day
- Population
- Patients with bipolar disorder
- Participants
- 43
RCTFolic acid efficacy as an alternative drug added to sodium valproate in the treatment of acute phase of mania in bipolar disorder: a double-blind randomized controlled trial2009
A randomized trial in patients with bipolar disorder found that based on our findings, folic acid seems to be an effective adjuvant to sodium valproate in the treatment of the acute phase of mania in patients with bipolar disorder.
- Effect
- Benefit
- Duration
- 3 weeks
- Population
- Patients with bipolar disorder
InositolView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- In children with bipolar disorder, taking inositol alone or combined with omega-3 fatty acids for about 12 weeks may help reduce symptoms of mania and depression.
- The best results were seen when inositol and omega-3s were taken together, improving mood symptoms more than either supplement alone.
Browse 3 studies
RCTA Randomized, Double-Blind, Controlled Clinical Trial of Omega-3 Fatty Acids and Inositol as Monotherapies and in Combination for the Treatment of Pediatric Bipolar Spectrum Disorder in Children Age 5-122022
In children aged 5–12 with bipolar spectrum disorder, omega-3 fatty acids, inositol, and their combination produced modest symptom improvements versus control.
- Effect
- Benefit
- Population
- Adults
- Ages
- 5–12
RCTA randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study2015n=10
In a pilot RCT of 10 children (ages 5–12) with bipolar spectrum disorder, high-EPA omega-3 and inositol showed preliminary but limited efficacy over 12 weeks.
- Effect
- Benefit
- Population
- Children/adolescents
- Participants
- 10
- Ages
- 5–12
RCTInositol as an add-on treatment for bipolar depression2000n=12
In 24 adults with bipolar depression over 6 weeks, inositol add-on (12 g/day) improved depressive symptoms versus placebo when added to standard treatment.
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 12 g/day
- Population
- Adults
- Participants
- 12
AshwagandhaView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is uncertain if ashwagandha helps thinking in adults with bipolar disorder.
- One study found that taking ashwagandha for 8 weeks slightly improved some, but not all, thinking skills compared to placebo.
Browse 1 study
RCTRandomized placebo-controlled adjunctive study of an extract of Withania somnifera for cognitive dysfunction in bipolar disorder2013n=29
In 60 euthymic bipolar patients, adjunctive ashwagandha extract 500 mg/day improved auditory-verbal working memory versus placebo over 8 weeks.
- Effect
- Benefit
- Duration
- 8 weeks
- Dose
- 500 mg/day
- Population
- Patients with bipolar depression
- Participants
- 29
Branched Chain Amino Acids (BCAAs)View supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is uncertain if taking branched-chain amino acids (BCAAs) helps people with bipolar disorder.
- In one small study, people with mania took a special amino acid drink with BCAAs but no tyrosine, a building block for dopamine.
- This drink reduced manic symptoms within 6 hours, and daily use for a week helped symptoms improve over 2 weeks.
- It is thought that BCAAs reduce brain dopamine activity, which may calm mania.
- More research is needed to know if this is an effective treatment.
Browse 1 study
RCTEffects of a branched-chain amino acid drink in mania2003n=25
An RCT of 25 manic patients found 60 g/day BCAA lowered mania ratings over the first 6 hours and maintained an advantage at 1 week versus placebo.
- Effect
- Benefit
- Duration
- 7 days
- Dose
- 60 g/day
- Population
- Mania patients
- Participants
- 25
EleutheroView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- In teenagers with bipolar disorder, taking eleuthero root together with lithium for 6 weeks worked about as well as fluoxetine (an antidepressant) with lithium for improving mood symptoms.
- It is not known if eleuthero alone helps.
- More studies are needed.
Browse 1 study
RCTComparison of the Addition of Siberian Ginseng (Acanthopanax senticosus) Versus Fluoxetine to Lithium for the Treatment of Bipolar Disorder in Adolescents: A Randomized, Double-Blind Trial2007
In 76 Chinese adolescents with bipolar disorder on lithium over 6 weeks, adjunct Acanthopanax senticosus showed similar response (67.6% vs 71.8%) and remission rates to fluoxetine, with no switching to mania versus 3 fluoxetine cases.
- Effect
- Benefit
- Duration
- 6 weeks
- Population
- Children/adolescents
- Ages
- 12–17
N-Acetyl Cysteine (NAC)View supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Taking N-acetylcysteine (NAC) by mouth may help reduce depression symptoms in people with bipolar disorder when added to usual treatment.
- In some patients with bipolar II disorder, it helped more people get better from both depression and mania together.
- However, a higher dose did not work in another study and NAC does not seem to help keep people from relapsing or maintain remission over the long term.
Browse 1 study
RCTN-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial2008n=75
A 24-week double-blind RCT of 75 bipolar patients found NAC (1 g twice daily) significantly reduced depressive symptoms versus placebo.
- Effect
- Benefit
- Duration
- 24 weeks
- Dose
- 1 g 2×/day
- Population
- Bipolar patients
- Participants
- 75
LecithinView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- In a small study of six people with mania, taking lecithin 10 mg three times a day helped improve delusions, confused speech, and hallucinations compared with a placebo.
Browse 1 study
Clinical trialLecithin in the treatment of mania: double-blind, placebo-controlled trials1982
In six manic patients in double-blind trials, lecithin produced significantly greater improvement than placebo in five of six patients.
- Effect
- Benefit
- Population
- Patients with mania
MelatoninView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Early research suggests that taking melatonin may help people with bipolar disorder sleep longer and reduce manic symptoms in the short term.
- However, larger studies show that melatonin does not improve mania or other bipolar symptoms overall.
- One slow‑release form may help reduce side effects of antipsychotic medications, such as weight and blood pressure increases, but it does not reduce mania or depression.
- There is also some concern that melatonin could worsen depression in certain people with bipolar disorder.
Browse 5 studies
RCTMelatonin In Acute Mania Investigation (MIAMI-UK). A randomized controlled trial of add-on melatonin in bipolar disorder2021n=21
An RCT of 21 bipolar patients with acute mania found add-on melatonin did not reduce YMRS manic scores but significantly lowered depression scores on QIDS-SR16 vs placebo.
- Effect
- No Benefit
- Duration
- 3 weeks
- Population
- Adults
- Participants
- 21
- Ages
- 18–65
RCTMelatonin attenuates antipsychotic metabolic effects: an eight-week randomized, double-blind, parallel-group, placebo-controlled clinical trial2014n=24
An 8-week RCT of 24 patients on atypical antipsychotics found 5 mg/day melatonin attenuated weight gain (1.5 vs 2.2 kg) and reduced diastolic BP vs placebo, with greater fat-mass benefits in bipolar disorder.
- Effect
- Benefit
- Dose
- 5 mg/day
- Population
- Psychiatric patients
- Participants
- 24
Clinical trialMelatonin add-on in manic patients with treatment resistant insomnia2000n=11
A 1-month pilot of 11 manic patients with treatment-resistant insomnia found 3 mg/day melatonin add-on significantly lengthened sleep duration and reduced mania severity.
- Effect
- Benefit
- Duration
- 1 month
- Dose
- 3 mg/day
- Population
- ALL patients
- Participants
- 11
- Ages
- 22–43
RCTEffects of exogenous melatonin administration and withdrawal in five patients with rapid-cycling bipolar disorder1997
A 12-week double-blind study of 5 rapid-cycling bipolar patients found melatonin had no mood benefit and one patient developed a free-running sleep-wake cycle after withdrawal.
- Effect
- No Benefit
- Duration
- 12 weeks
- Dose
- 10 mg/day
- Population
- Bipolar patients
Controlled trialNegative effects of melatonin on depression1976
An early study of 6 depressed patients and 2 with Huntington's chorea found melatonin exacerbated dysphoric symptoms, caused weight loss, sleep disruption, and lowered oral temperature.
- Effect
- No Benefit
- Population
- Depression patients
ChromiumView supplement →
Do not purchase·★★★★★
How we scored this▸
- It is not yet clear whether taking chromium helps people with difficult-to-treat bipolar disorder.
- Early research in a small group of people with rapid mood cycling found that taking chromium chloride (600–800 mcg daily) for up to two years was linked to about three fewer mood episodes each year compared to before they started.
- However, this study did not include a comparison group, so we cannot be sure that chromium was responsible for the improvement.
Browse 1 study
Open-labelA 2-year, open-label pilot study of adjunctive chromium in patients with treatment-resistant rapid-cycling bipolar disorder2007
A 2-year open-label pilot in treatment-resistant rapid-cycling bipolar disorder suggested adjunctive chromium may stabilize mood in some patients, but evidence remains preliminary and uncontrolled.
- Effect
- Benefit
- Population
- Patients with bipolar disorder
Acetyl-L-CarnitineView supplement →
Do not purchase·★★★★★
How we scored this▸
- Taking acetyl-L-carnitine with alpha-lipoic acid does not seem to help depression in people with bipolar disorder.
- One small study found no improvement compared to placebo over 12 weeks.
Browse 1 study
RCTA placebo-controlled trial of acetyl-L-carnitine and α-lipoic acid in the treatment of bipolar depression2013n=20
A 12-week RCT in 40 patients with bipolar depression found acetyl-L-carnitine plus α-lipoic acid did not reduce depression scores versus placebo on the Montgomery-Åsberg Depression Rating Scale.
- Effect
- No Benefit
- Duration
- 12 weeks
- Dose
- 3000 mg/day
- Population
- Patients with bipolar depression
- Participants
- 20
Flaxseed OilView supplement →
Do not purchase·★★★★★
How we scored this▸
- Research in children and teens with bipolar disorder found that taking flaxseed oil for 16 weeks, in amounts providing up to 6.5 grams of omega‑3 (alpha‑linolenic acid) daily, did not improve symptoms of mania or depression compared with a placebo
Browse 1 study
RCTRandomized, placebo-controlled trial of flax oil in pediatric bipolar disorder2010n=51
In 51 youths with bipolar disorder over 16 weeks, flax oil up to 6.6 g alpha-LNA/day did not significantly change mania or depression rating scales versus olive oil, though higher omega-3 status correlated with lower symptom severity.
- Effect
- No Benefit
- Duration
- 16 weeks
- Dose
- 6.6 g alpha-LNA/day
- Population
- Children/adolescents
- Participants
- 51
- Ages
- 6–17
Evidence visualised
Same ratings as above, aggregated so you can see coverage and imbalance.
| Supplement | DEX | Studies | Meta-analyses | Share |
|---|---|---|---|---|
| Melatonin | ★★★★★40% | 5 | 0 | 26% |
| Inositol | ★★★★★48% | 3 | 0 | 16% |
| Vitamin B9 (Folate) | ★★★★★52% | 3 | 1 | 16% |
| Acetyl-L-Carnitine | ★★★★★32% | 1 | 0 | 5% |
| Ashwagandha | ★★★★★44% | 1 | 0 | 5% |
| Branched Chain Amino Acids (BCAAs) | ★★★★★44% | 1 | 0 | 5% |
| Chromium | ★★★★★36% | 1 | 0 | 5% |
| Eleuthero | ★★★★★44% | 1 | 0 | 5% |
| Flaxseed Oil | ★★★★★32% | 1 | 0 | 5% |
| Lecithin | ★★★★★40% | 1 | 0 | 5% |
| N-Acetyl Cysteine (NAC) | ★★★★★44% | 1 | 0 | 5% |