Condition
Bipolar Disorder
Bipolar disorder is a mood condition in which a person swings between depressive episodes and episodes of mania or milder hypomania, involving changes in brain circuits that regulate mood and energy. Among supplements, the evidence is strongest for fish oil rich in EPA, and five small trials found bipolar symptoms improved. Those trials included only about 260 people, and studies of inositol and CDP-choline found no clear difference, though each was very small.
Sources: PMID 16814257; PMID 15465995
- Supplements studied
- 8
- Graded outcomes
- 9
- Trials
- 12
- People studied
- 1,915
Evidence by supplement
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Anxiety Symptoms Moderate Improvement | Improves (the measure goes down) | Moderate effect | 5 studies | 60 people | ||
Studies that measured anxiety symptoms | ||||||
| Bipolar Disorder Symptoms | Improves (the measure goes down) | 1 study | 60 people | |||
Studies that measured bipolar disorder symptoms | ||||||
| Attention | Improves (the measure goes up) | 60 people | ||||
| Depression Symptoms | Improves (the measure goes down) | 60 people | ||||
| Executive Function | Improves (the measure goes up) | 60 people | ||||
| Memory | Improves (the measure goes up) | 60 people | ||||
| Processing Accuracy | Improves (the measure goes up) | 60 people | ||||
| Processing Speed | Improves (the measure goes up) | 60 people | ||||
Coenzyme Q10
- Anti-Oxidant Enzyme Profile: improves
- Oxidative Stress Biomarkers: improves
- Depression Symptoms: improves
Chromium
- Bipolar Disorder Symptoms: improves
- Depression Symptoms: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Bipolar Disorder Symptoms Small Improvement | Improves (the measure goes down) | Small effect | 30 people | |||
| Depression Symptoms | Improves (the measure goes down) | 4 studies | 30 people | |||
Studies that measured depression symptoms
| ||||||
Uridine
- Bipolar Disorder Symptoms: improves
- Depression Symptoms: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Bipolar Disorder Symptoms Small Improvement | Improves (the measure goes down) | Small effect | 7 people | |||
| Depression Symptoms Small Improvement | Improves (the measure goes down) | Small effect | 7 people |
CDP-Choline
- Bipolar Disorder Symptoms
- Cocaine Addiction Symptoms
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Bipolar Disorder Symptoms No significant effect on bipolar symptoms | NoneNo effect | 1 study | 44 people | |||
Studies that measured bipolar disorder symptoms | ||||||
| Cocaine Addiction Symptoms | ||||||
Inositol
- Bipolar Disorder Symptoms
- Depression Symptoms: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Bipolar Disorder Symptoms No effect | NoneNo effect | 1 study | 24 people | |||
Studies that measured bipolar disorder symptoms | ||||||
| Depression Symptoms | Improves (the measure goes down) | 5 studies | 24 people | |||
Studies that measured depression symptoms | ||||||
N-Acetylcysteine
- Anxiety Symptoms
- Depression Symptoms: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Anxiety Symptoms No effect | NoneNo effect | 315 people | ||||
| Depression Symptoms | Improves (the measure goes down) | 4 studies | 335 people | |||
Studies that measured depression symptoms
| ||||||
Key findings
- Bipolar Disorder SymptomsImproves (the measure goes down)
- Anxiety SymptomsImproves (the measure goes down)
- Anti-Oxidant Enzyme ProfileImproves (the measure goes up)
The Bipolar Disorder Nutritional Support protocol
2 primary supplements · 6 supporting supplements
- Omega-3 Fatty Acids (High EPA)1–2 g EPA daily (total omega-3: 2–4 g)
- N-Acetylcysteine (NAC)1,000–2,000 mg twice daily
Studies cited
55 studies from PubMed
- Effects of Coenzyme Q10 Supplementation on Depressive Symptoms and Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
- N-acetylcysteine as an adjunctive treatment for bipolar depression and major depressive disorder: a systematic review and meta-analysis of double-blind, randomized placebo-controlled trials.
- N-acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta-analysis of randomized controlled trials.
- The effect of N-acetylcysteine on bipolar depression: a systematic review and meta-analysis of randomized controlled trials.
- N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis.
- Inositol as an add-on treatment for bipolar depression
- Myo-inositol in the treatment of premenstrual dysphoric disorder
- Inositol addition does not improve depression in SSRI treatment failures
- Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone
- Double-blind, controlled trial of inositol treatment of depression
- Inositol for depressive disorders.
- The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA
- Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial
- Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study
- Omega-3 fatty acid treatment, with or without cytidine, fails to show therapeutic properties in bipolar disorder: a double-blind, randomized add-on clinical trial
- Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder
- Omega-3 fatty acid treatment and T(2) whole brain relaxation times in bipolar disorder
- Fish oil supplementation in the treatment of major depression: a randomised double-blind placebo-controlled trial
- A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs
- Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial
- Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial
- Efficacy of omega-3 for vasomotor symptoms treatment: a randomized controlled trial
- Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study
- The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial
- Supplementation of a low dose of DHA or DHA+AA does not prevent peripartum depressive symptoms in a small population based sample
- Omega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized, double-blind, placebo-controlled trial
- Omega-3 fatty acids as a treatment for perinatal depression: randomized double-blind placebo-controlled trial
- Omega-3 fatty acids for a better mental state in working populations - Happy Nurse Project: A 52-week randomized controlled trial
- Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing
- The effect of omega 3 fatty acid supplementation on premenstrual syndrome and health-related quality of life: a randomized clinical trial
- Coenzyme Q10 supplementation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders
- Coenzyme Q10 supplementation reduces oxidative stress and increase antioxidant enzyme activity in patients with coronary artery disease
- Effects of coenzyme Q10 supplementation on liver mitochondrial function and aerobic capacity in adolescent athletes
- Postprandial antioxidant effect of the Mediterranean diet supplemented with coenzyme Q10 in elderly men and women
- Effects of Coenzyme Q10 Supplementation on Biomarkers of Oxidative Stress in Adults: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.
- Evaluating the Effect of Coenzyme Q10 Augmentation on Treatment of Bipolar Depression: A Double-Blind Controlled Clinical Trial
- Influence of adjuvant Coenzyme Q10 on inflammatory and oxidative stress biomarkers in patients with bipolar disorders during the depressive episode
- The effects of coenzyme Q10 supplementation on cardiometabolic markers in overweight type 2 diabetic patients with stable myocardial infarction: A randomized, double-blind, placebo-controlled trial
- Coenzyme Q10 improves seminal oxidative defense but does not affect on semen parameters in idiopathic oligoasthenoteratozoospermia: a randomized double-blind, placebo controlled trial
- Effect of Coenzyme Q10 supplementation on antioxidant enzymes activity and oxidative stress of seminal plasma: a double-blind randomised clinical trial
- Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial
- Coenzyme Q10 supplementation alleviates pain in pregabalin-treated fibromyalgia patients via reducing brain activity and mitochondrial dysfunction
- Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q₁₀ effect on clinical improvement
- Oral coenzyme Q10 supplementation in patients with migraine: Effects on clinical features and inflammatory markers
- Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients
- Effectiveness of chromium in atypical depression: a placebo-controlled trial
- A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving
- A 2-year, open-label pilot study of adjunctive chromium in patients with treatment-resistant rapid-cycling bipolar disorder
- A randomized, placebo-controlled trial of citicoline add-on therapy in outpatients with bipolar disorder and cocaine dependence
- Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study
- Effect of Ashwagandha (Withania somnifera) extract on sleep: A systematic review and meta-analysis
- Randomized placebo-controlled adjunctive study of an extract of withania somnifera for cognitive dysfunction in bipolar disorder
- Safety and efficacy of Withania somnifera for anxiety and insomnia: Systematic review and meta-analysis.
- Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974
- A double-blind, placebo-controlled evaluation of the anxiolytic efficacy ff an ethanolic extract of withania somnifera