What supplements are recommended for a generally healthy adult to improve their mood?

Supplements for Mood Enhancement in Healthy Adults

Primary Recommendation

For a generally healthy adult seeking mood improvement without diagnosed depression, the evidence for supplement efficacy is limited and mixed, with omega-3 fatty acids showing the most promise only when used alongside antidepressant medication in clinical depression—not for general mood enhancement in healthy individuals. 1

Evidence-Based Supplement Options

Omega-3 Fatty Acids (EPA/DHA)

• Not recommended as monotherapy for mood enhancement in healthy adults 2
• A large-scale trial (VITAL-DEP) of 18,353 adults found omega-3 supplementation (1g/day fish oil) over 5.3 years actually showed a small but statistically significant increase in depression risk compared to placebo (HR 1.13,95% CI 1.01-1.26) 2
• The International Society for Nutritional Psychiatry Research guidelines support omega-3s only as adjunctive therapy with antidepressants for diagnosed major depressive disorder, not for general mood support 1
• If omega-3s are considered despite limited evidence, dosing would be 1-2 g/day of EPA (either pure or EPA/DHA ratio >2:1) 1
• Evidence is insufficient to support omega-3 monotherapy even in clinical depression 1

S-Adenosylmethionine (SAMe)

• Limited evidence for use in healthy individuals without depression 1
• The American College of Physicians recognizes SAMe as a complementary treatment option for major depressive disorder, but evidence quality is low 1, 3
• Therapeutic dosing for depression is 1-2 g/day, starting at 400-800 mg/day 3
• SAMe shows comparable efficacy to tricyclic antidepressants in clinical depression, but this does not translate to mood enhancement in healthy adults 3
• Important safety concern: SAMe should not be combined with other serotonergic agents without careful monitoring due to serotonin syndrome risk 3, 4

St. John's Wort

• Network meta-analyses show no significant differences in response, remission, or discontinuation rates compared to second-generation antidepressants in major depressive disorder 1
• Evidence pertains only to clinical depression, not general mood enhancement 1
• Not recommended for healthy individuals seeking mood improvement

Multivitamins

• Modest evidence for mood benefits in healthy older adults 5, 6, 7
• A 1-year trial found multivitamin supplementation (10x RDA of 9 vitamins) improved mood in healthy young adults, with females reporting feeling more agreeable, composed, and better mental health 5
• An 8-week trial in healthy men aged 50-69 showed reduced depression/anxiety/stress scores and improved alertness with multivitamin supplementation 7
• A 4-week trial in healthy women aged 50-75 showed improved stress ratings when assessed in real-time at home, though not in laboratory settings 6
• Effects appear subtle and may require several months to manifest 5

N-Acetylcysteine (NAC)

• Not recommended for mood enhancement 8
• Evidence for NAC in depression is substantially weaker than for omega-3 fatty acids 8
• Should only be used as adjunctive therapy (never monotherapy) in clinical settings, with typical doses of 1000-3000 mg daily for 8-24 weeks 8
• NAC demonstrates superior evidence in obsessive-compulsive disorder, not mood enhancement 8

Critical Caveats

Quality and Safety Concerns

• Supplement quality varies significantly—prescription products should be considered when available 3
• For omega-3 products, quality evaluation is essential for non-responders 1
• The American Diabetes Association notes there is no clear evidence that dietary supplementation with vitamins, minerals, herbs, or spices can improve outcomes in people without underlying deficiencies 1
• Long-term use of antioxidant supplements (vitamins E, C, carotene) may have safety concerns 1

When Supplements Are NOT Appropriate

• Supplements should never replace established treatments for diagnosed mood disorders 8
• Evidence for supplement efficacy in healthy individuals is substantially weaker than for clinical depression 1, 8
• Most high-quality evidence pertains to adjunctive use with antidepressants in diagnosed major depressive disorder, not general mood enhancement 1, 3

Practical Algorithm for Decision-Making

For a healthy adult seeking mood improvement:

1. First-line approach: Address lifestyle factors (exercise, sleep, stress management, nutrition) before considering supplements 1

2. If considering supplements despite limited evidence:

   • Multivitamin supplementation has the most favorable risk-benefit profile for healthy adults, with modest evidence for mood benefits and minimal safety concerns 5, 6, 7
   • Expect subtle effects that may take 3-12 months to manifest 5
   • Choose high-quality products with appropriate dosing 3

3. Avoid in healthy individuals:

   • Omega-3 fatty acids (evidence shows potential harm in healthy adults) 2
   • SAMe (insufficient evidence, drug interaction concerns) 3, 4
   • NAC (weak evidence for mood) 8
   • St. John's Wort (evidence limited to clinical depression) 1

4. Seek professional evaluation if:

   • Mood symptoms persist or worsen
   • Symptoms interfere with daily functioning
   • Clinical depression is suspected (requires formal diagnosis and evidence-based treatment) 1