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Which nutritional therapies are safe and effective for depression?
ST. JOHN’S WORT is effective for short-term relief of mild to moderate depression (strength of recommendation [SOR]: A; 1 systematic review). Its safety profile is superior to older antidepressants; data comparing it with newer antidepressants (such as selective serotonin reuptake inhibitors) are limited (SOR: A, 1 systematic review).
A small but statistically significant clinical benefit has been demonstrated for saffron, lavender, borage, dan zhi xiao yao (SOR: B, 1 systematic review and 3 randomized controlled trials), folate (SOR: A, 1 systematic review), and S-adenosylmethionine (SAMe) (SOR: A, 1 meta-analysis and 1 systematic review). Most trials of these preparations were short and small, limiting the ability to detect adverse effects.
Tryptophan (SOR: A, 1 systematic review) and 5-hydroxytryptophan (5-HTP) (SOR: A, 1 systematic review) have demonstrated superiority over placebo in alleviating symptoms of depression, but concerns exist about their safety.
N-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) and omega-3 fatty acids don’t appear effective in treating major depressive disorder (SOR: A, 1 systematic review.)
Evidence summary
TABLE W1 summarizes study results and recommendations for nutritional therapies for depression.1-16
St. John’s wort works as well as standard antidepressants
A recent Cochrane review suggested that St. John’s wort is more effective than placebo in patients with mild to moderate depression and as effective as standard antidepressants.1
Other supplements also have benefits
A systematic review of 4 small randomized controlled trials (RCTs) suggested that saffron (30 mg) is superior to placebo in treating short-term depression (6 weeks). Treatment and outcomes were equivalent to fluoxetine and imipramine.2 A later RCT yielded results consistent with the systematic review.3
Combined lavender tincture (60 drops per day) and imipramine were more effective than imipramine alone in 1 small RCT.4
Borage, a traditional Persian medicine, was superior to placebo in reducing depressive symptoms in 1 small RCT.2
Dan zhi xiao yao, a traditional Chinese medicine, was as effective as the tricyclic anti-depressant maprotiline in 1 small RCT.2
Three RCTs suggested that folate may be used to supplement conventional treatments for depression, but it isn’t clear whether this would help patients with normal folate levels.5
A meta-analysis of 13 controlled clinical trials and a later systematic review of 11 articles including 2 RCTs concluded that SAMe is more effective than placebo and as efficacious as tricyclic antidepressants in treating major depression in adults. However, further trials are needed to answer questions about absorption, mechanism of action, and bioavailability.6,7
Tryptophan’s benefit comes with risk
In a Cochrane review of 2 RCTs, tryptophan and 5-HTP were superior to placebo in alleviating symptoms of depression. However, some published case reports have linked tryptophan use to potentially fatal eosinophilia-myalgia syndrome.8
No clear evidence for inositol or n-3 PUFAs
A Cochrane review of 4 small double-blind RCTs investigating inositol as a nutritional supplement in depression treatment failed to find clear evidence of therapeutic benefit.9
Three RCTs demonstrated significantly higher red blood cell membrane levels of n-3 PUFAs in nondepressed patients compared with depressed patients.10 However, a systematic review of 12 RCTs failed to demonstrate any benefit of n-3 PUFA supplementation over placebo in treating depressed mood.11 The authors concluded that larger trials are needed to demonstrate efficacy because of marked heterogeneity among the RCTs.
Safety issues. A recent Cochrane review found fewer adverse effects for St. John’s wort than tricyclic antidepressants.1 The most common adverse reactions were sensitivity to light, skin symptoms, gastrointestinal symptoms, and agitation. Data comparing St. John’s wort with newer antidepressants are lacking.
St. John’s wort does have pharmacokinetic interactions and should not be taken concurrently with other antidepressants, immunosuppressants, anti-HIV drugs, cou-marin-type anticoagulants, or certain antineoplastic agents.17
Reviews of meta-analyses, case reports, population studies, RCTs, and other literature have reported virtually no adverse effects for PUFAs; 18 trials investigating saffron, lavender, borage, dan zhi xiao yao, folate, SAMe, and inositol also reported no safety concerns. However, the size and duration of these studies limit their ability to detect significant problems.2,5,6,9 As previously noted, concerns exist regarding an association between tryptophan and eosinophilia-myalgia syndrome.8
Recommendations
The World Federation of Societies of Biological Psychiatry doesn’t recommend St. John’s wort for moderate to severe depression, but suggests it can be considered for treating mild to moderate depressive episodes provided the prescriber considers potential pharmacokinetic interactions with other medications and understands possible variations in purity and potency of extracts.19 The Federation also states that St. John’s wort is an alternative for patients reluctant to take traditional antidepressants.
TABLE W1
What the studies say about nutritional therapies for depression
| Supplement | Study type | Number of subjects | Comparison group | Outcome measure | Results | Conclusion | SOR |
|---|---|---|---|---|---|---|---|
| Borage (Echium amoenum) | 1 small RCT | 352,16 | Placebo | HAM-D | Improved HAM-D scores significantly at week 4 (borage 18. 3±3. 9 vs placebo 21. 9±3. 9; t=2. 51; P=. 02); no significant difference at Week 62,16 | Superior to placebo in reducing symptoms of depression | B |
| Dan zhi xiao yao | 1 small RCT | 632 | Maprotiline | HAM-D, SDS, SAS, scale for traditional Chinese medicine syndrome and symptom differentiation | 87% depression reduction (dan zhi xiao yao) vs 84% depression reduction (maprotiline) | As effective as maprotiline in treating depression | B |
| Folate | Cochrane review of 3 RCTs | 2475 | Studies 1 and 2: folate vs folate + other treatment (Study 1: low folate levels; Study 2: normal folate levels) Study 3: folate vs trazodone (normal folate levels) | HAM-D | Superior to placebo (NNT=5, defined as 50% reduction in HAM-D); comparable to trazodone (RR=0. 97; 95% CI, 0. 14-2. 01)7 | May have role as supplement to other treatments for depression Efficacy unclear in patients with normal folate levels | A |
| Inositol | Cochrane review of 4 RCTs | 1419 | Studies 1-3: placebo plus conventional antidepressants Study 4: placebo only | HAM-D, MADRS | Pooled estimate of effect of all 3 studies (SMD= -0. 08; 95% CI, -0. 45 to 0. 30) | No clear evidence of therapeutic benefit | A |
| Lavender (Lavandula angustifolia) | 1 small RCT | 454 | Imipramine | HAM-D | Imipramine plus lavender showed significant effect compared with imipramine alone (f=26. 87; Df=3. 01; P<. 0001) | Synergistic effect suggested when used with imipramine | B |
| n-3 long-chain polyunsaturated fatty acids | Systematic review including 3 RCTs; 10 meta-analysis of 12 RCTs11 | 10210 103211 | Various comparison groups included | Serum SFAs, MUFAs, PUFAs; RBC membrane levels n-3 PUFAs2 HAM-D, BDI3 | Systematic review:10 Study 1: n=30; ES=3. 61 Study 2: n=24; ES=1. 2 Study 3: n=48; ES=2. 43 Meta-analysis:11 Pooled ES=0. 13; 95% CI, 0. 01-0. 25 | Significantly higher RBC membrane levels of n-3 PUFAs in nondepressed vs depressed patients10 No significant effect for supplementation11 Larger trials with adequate power needed2,3 | A |
| S-adenosyl-methionine (SAMe) | Meta-analysis of 13 RCTs,6 systematic review including 2 RCTs7 | 3996 787 | Placebo and conventional antidepressants | HAM-D | NNT=2. 5 for HAM-D decrease of >25%; 6 NNT=6. 25 for HAM-D decrease of >50%6 | May have role in treatment of major depression Further trials are needed to address unanswered questions about absorption, mechanism of action, and bioavailability7 | A |
| Saffron (Crocus sativus) | Systematic review of 4 small RCTs, 1 later RCT | 3012 4013 4014 4015 403 | Imipramine12 Placebo13,15 Fluoxetine5,14 | HAM-D | Systematic review: Study 1: imipramine and saffron equally efficacious (f=2. 91; P=. 09)12 Study 2: Improved HAM-D scores: -12. 20±4. 67 (saffron) vs -5. 10±4. 71 (placebo) (P<. 0001)13 Study 3: Improved HAM-D scores: saffron petal -12. 00±4. 10; fluoxetine -13. 50±4. 91; difference between 2 treatments not significant (P=. 27)14 Study 4: Improved HAM-D scores: -14. 01±5. 53 (saffron petal) vs -5. 05±4. 63 (placebo) (P<. 0001)15 Study 5:5 NNT=10 | Efficacy of extract and petal suggested to treat mild to moderate depression Large-scale trials are warranted | B |
| St. John’s wort (Hypericum perforatum L. ) | Cochrane review of 29 RCTs | 54891 | SSRIs, tri/tetracyclic antidepressants, placebo | Responder rate ratio | St. John’s wort vs placebo: 9 larger trials: RR=1. 28; 95% CI, 1. 10-1. 491 9 smaller trials: RR=1. 87; 95% CI, 1. 22-2. 871 St. John’s wort vs SSRIs: 12 trials: RR=1. 00; 95% CI, 0. 90-1. 111 St. John’s wort vs tricyclics: 5 trials: RR=1. 02; 95% CI, 0. 90-1. 151 | Effective for treating mild to moderate depression | A |
| Tryptophan and 5-hydroxy-tryptophan (5-HTP) | Cochrane review of 2 RCTs | 648 | Placebo | HAM-D | NNT=2. 78 vs placebo (OR=4. 1; 95% CI, 1. 28-13. 15 | Superior to placebo Insufficient evidence regarding safety | A |
| BDI, Beck Depression Inventory; CI, confidence interval; DF, degrees of freedom; ES, effect size; F, F statistic; HAM-D, Hamilton Depression Rating Scale; MADRS, Mont-gomery-Asberg Depression Rating Scale; MUFAs, monounsaturated fatty acids; n-3 PUFAs, n-3 long-chain polyunsaturated fatty acids; NNT, number needed to treat; OR, odds ratio; PUFAs, polyunsaturated fatty acids; RBC, red blood cell; RCT, randomized controlled trial; RR, relative risk; SAS, self-rating anxiety scale; SDS, self-rating depression scale; SFAs, saturated fatty acids; SMD, standard weighted mean difference; SOR, strength of recommendation; SSRI, selective serotonin reuptake inhibitor. | |||||||
1. Linde K, Bemer MM, Kriston L. St. John’s wort for major depression. Cochrane Database Syst Rev. 2008;(4):CD000448.-
2. Sarris J. Herbal medicines in the treatment of psychiatric disorders: a systematic review. Phytother Res. 2007;21:703-716.
3. Akhondzadeh Basti A, Moshiri E, Noorbala AA, et al. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients. Prog Neuropsychopharmacol Biol Psychiatry. 2006;31:439-442.
4. Akhondzadeh S, Kashani L, Fotouhi A, et al. Comparison of Lavandula angustifolia Mill. tincture and imipramine in the treatment of mild to moderate depression. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:123-127.
5. Taylor MJ, Carney S, Geddes J, et al. Folate for depressive disorders. Cochrane Database Syst Rev. 2003;(2):CD003390.-
6. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepres-sant. Acta Neurol Scand Suppl. 1994;154:7-14.
7. Williams AL, Girard C, Jui D, et al. S-adenosylmethionine (SAMe) as treatment for depression. Clin Invest Med. 2005;28:132-139.
8. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxy-tryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198.-
9. Taylor MJ, Wilder H, Bhagwager Z, et al. Inositol for depressive disorders. Cochrane Database Syst Rev. 2004;(2):CD004049.-
10. Williams AL, Katz D, Ali A, et al. Do essential fatty acids have a role in the treatment of depression? J Affect Disord. 2006;93:117-123.
11. Appleton KM, Hayward RC, Gunnell D, et al. Effects of n-3 longchain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr. 2006;84:1308-1316.
12. Akhondzadeh S, Fallah-Pour H, Afkham K, et al. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression. BMC Complement Altern Med. 2004;4:12.-
13. Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, et al. Crocus sativus L. in the treatment of mild to moderate depression. Phytother Res. 2005;19:148-151.
14. Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, et al. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression. J Ethnopharmacol. 2005;97:281-284.
15. Moshiri E, Basti AA, Noorbala AA, et al. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression. Phytomedicine. 2006;13:607-611.
16. Sayyah M, Sahhah M, Kamalinejad M. A preliminary randomized double blind clinical trial on the efficacy of aqueous extract of Echium amoenum in the treatment of mild to moderate major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:166-169.
17. Schulz V Safety of St. John’s wort extract compared to synthetic antidepressants. Phytomedicine. 2006;13:199-204.
18. Lee S, Gura KM, Kim S, et al. Current clinical applications of ome-ga-6 and omega-3 fatty acids. Nutr Clin Pract. 2006;21:323-341.
19. Bauer M, Bschor T, Pfennig A, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders in primary care. World J Biol Psychiatry. 2007;8:67-104.
ST. JOHN’S WORT is effective for short-term relief of mild to moderate depression (strength of recommendation [SOR]: A; 1 systematic review). Its safety profile is superior to older antidepressants; data comparing it with newer antidepressants (such as selective serotonin reuptake inhibitors) are limited (SOR: A, 1 systematic review).
A small but statistically significant clinical benefit has been demonstrated for saffron, lavender, borage, dan zhi xiao yao (SOR: B, 1 systematic review and 3 randomized controlled trials), folate (SOR: A, 1 systematic review), and S-adenosylmethionine (SAMe) (SOR: A, 1 meta-analysis and 1 systematic review). Most trials of these preparations were short and small, limiting the ability to detect adverse effects.
Tryptophan (SOR: A, 1 systematic review) and 5-hydroxytryptophan (5-HTP) (SOR: A, 1 systematic review) have demonstrated superiority over placebo in alleviating symptoms of depression, but concerns exist about their safety.
N-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) and omega-3 fatty acids don’t appear effective in treating major depressive disorder (SOR: A, 1 systematic review.)
Evidence summary
TABLE W1 summarizes study results and recommendations for nutritional therapies for depression.1-16
St. John’s wort works as well as standard antidepressants
A recent Cochrane review suggested that St. John’s wort is more effective than placebo in patients with mild to moderate depression and as effective as standard antidepressants.1
Other supplements also have benefits
A systematic review of 4 small randomized controlled trials (RCTs) suggested that saffron (30 mg) is superior to placebo in treating short-term depression (6 weeks). Treatment and outcomes were equivalent to fluoxetine and imipramine.2 A later RCT yielded results consistent with the systematic review.3
Combined lavender tincture (60 drops per day) and imipramine were more effective than imipramine alone in 1 small RCT.4
Borage, a traditional Persian medicine, was superior to placebo in reducing depressive symptoms in 1 small RCT.2
Dan zhi xiao yao, a traditional Chinese medicine, was as effective as the tricyclic anti-depressant maprotiline in 1 small RCT.2
Three RCTs suggested that folate may be used to supplement conventional treatments for depression, but it isn’t clear whether this would help patients with normal folate levels.5
A meta-analysis of 13 controlled clinical trials and a later systematic review of 11 articles including 2 RCTs concluded that SAMe is more effective than placebo and as efficacious as tricyclic antidepressants in treating major depression in adults. However, further trials are needed to answer questions about absorption, mechanism of action, and bioavailability.6,7
Tryptophan’s benefit comes with risk
In a Cochrane review of 2 RCTs, tryptophan and 5-HTP were superior to placebo in alleviating symptoms of depression. However, some published case reports have linked tryptophan use to potentially fatal eosinophilia-myalgia syndrome.8
No clear evidence for inositol or n-3 PUFAs
A Cochrane review of 4 small double-blind RCTs investigating inositol as a nutritional supplement in depression treatment failed to find clear evidence of therapeutic benefit.9
Three RCTs demonstrated significantly higher red blood cell membrane levels of n-3 PUFAs in nondepressed patients compared with depressed patients.10 However, a systematic review of 12 RCTs failed to demonstrate any benefit of n-3 PUFA supplementation over placebo in treating depressed mood.11 The authors concluded that larger trials are needed to demonstrate efficacy because of marked heterogeneity among the RCTs.
Safety issues. A recent Cochrane review found fewer adverse effects for St. John’s wort than tricyclic antidepressants.1 The most common adverse reactions were sensitivity to light, skin symptoms, gastrointestinal symptoms, and agitation. Data comparing St. John’s wort with newer antidepressants are lacking.
St. John’s wort does have pharmacokinetic interactions and should not be taken concurrently with other antidepressants, immunosuppressants, anti-HIV drugs, cou-marin-type anticoagulants, or certain antineoplastic agents.17
Reviews of meta-analyses, case reports, population studies, RCTs, and other literature have reported virtually no adverse effects for PUFAs; 18 trials investigating saffron, lavender, borage, dan zhi xiao yao, folate, SAMe, and inositol also reported no safety concerns. However, the size and duration of these studies limit their ability to detect significant problems.2,5,6,9 As previously noted, concerns exist regarding an association between tryptophan and eosinophilia-myalgia syndrome.8
Recommendations
The World Federation of Societies of Biological Psychiatry doesn’t recommend St. John’s wort for moderate to severe depression, but suggests it can be considered for treating mild to moderate depressive episodes provided the prescriber considers potential pharmacokinetic interactions with other medications and understands possible variations in purity and potency of extracts.19 The Federation also states that St. John’s wort is an alternative for patients reluctant to take traditional antidepressants.
TABLE W1
What the studies say about nutritional therapies for depression
| Supplement | Study type | Number of subjects | Comparison group | Outcome measure | Results | Conclusion | SOR |
|---|---|---|---|---|---|---|---|
| Borage (Echium amoenum) | 1 small RCT | 352,16 | Placebo | HAM-D | Improved HAM-D scores significantly at week 4 (borage 18. 3±3. 9 vs placebo 21. 9±3. 9; t=2. 51; P=. 02); no significant difference at Week 62,16 | Superior to placebo in reducing symptoms of depression | B |
| Dan zhi xiao yao | 1 small RCT | 632 | Maprotiline | HAM-D, SDS, SAS, scale for traditional Chinese medicine syndrome and symptom differentiation | 87% depression reduction (dan zhi xiao yao) vs 84% depression reduction (maprotiline) | As effective as maprotiline in treating depression | B |
| Folate | Cochrane review of 3 RCTs | 2475 | Studies 1 and 2: folate vs folate + other treatment (Study 1: low folate levels; Study 2: normal folate levels) Study 3: folate vs trazodone (normal folate levels) | HAM-D | Superior to placebo (NNT=5, defined as 50% reduction in HAM-D); comparable to trazodone (RR=0. 97; 95% CI, 0. 14-2. 01)7 | May have role as supplement to other treatments for depression Efficacy unclear in patients with normal folate levels | A |
| Inositol | Cochrane review of 4 RCTs | 1419 | Studies 1-3: placebo plus conventional antidepressants Study 4: placebo only | HAM-D, MADRS | Pooled estimate of effect of all 3 studies (SMD= -0. 08; 95% CI, -0. 45 to 0. 30) | No clear evidence of therapeutic benefit | A |
| Lavender (Lavandula angustifolia) | 1 small RCT | 454 | Imipramine | HAM-D | Imipramine plus lavender showed significant effect compared with imipramine alone (f=26. 87; Df=3. 01; P<. 0001) | Synergistic effect suggested when used with imipramine | B |
| n-3 long-chain polyunsaturated fatty acids | Systematic review including 3 RCTs; 10 meta-analysis of 12 RCTs11 | 10210 103211 | Various comparison groups included | Serum SFAs, MUFAs, PUFAs; RBC membrane levels n-3 PUFAs2 HAM-D, BDI3 | Systematic review:10 Study 1: n=30; ES=3. 61 Study 2: n=24; ES=1. 2 Study 3: n=48; ES=2. 43 Meta-analysis:11 Pooled ES=0. 13; 95% CI, 0. 01-0. 25 | Significantly higher RBC membrane levels of n-3 PUFAs in nondepressed vs depressed patients10 No significant effect for supplementation11 Larger trials with adequate power needed2,3 | A |
| S-adenosyl-methionine (SAMe) | Meta-analysis of 13 RCTs,6 systematic review including 2 RCTs7 | 3996 787 | Placebo and conventional antidepressants | HAM-D | NNT=2. 5 for HAM-D decrease of >25%; 6 NNT=6. 25 for HAM-D decrease of >50%6 | May have role in treatment of major depression Further trials are needed to address unanswered questions about absorption, mechanism of action, and bioavailability7 | A |
| Saffron (Crocus sativus) | Systematic review of 4 small RCTs, 1 later RCT | 3012 4013 4014 4015 403 | Imipramine12 Placebo13,15 Fluoxetine5,14 | HAM-D | Systematic review: Study 1: imipramine and saffron equally efficacious (f=2. 91; P=. 09)12 Study 2: Improved HAM-D scores: -12. 20±4. 67 (saffron) vs -5. 10±4. 71 (placebo) (P<. 0001)13 Study 3: Improved HAM-D scores: saffron petal -12. 00±4. 10; fluoxetine -13. 50±4. 91; difference between 2 treatments not significant (P=. 27)14 Study 4: Improved HAM-D scores: -14. 01±5. 53 (saffron petal) vs -5. 05±4. 63 (placebo) (P<. 0001)15 Study 5:5 NNT=10 | Efficacy of extract and petal suggested to treat mild to moderate depression Large-scale trials are warranted | B |
| St. John’s wort (Hypericum perforatum L. ) | Cochrane review of 29 RCTs | 54891 | SSRIs, tri/tetracyclic antidepressants, placebo | Responder rate ratio | St. John’s wort vs placebo: 9 larger trials: RR=1. 28; 95% CI, 1. 10-1. 491 9 smaller trials: RR=1. 87; 95% CI, 1. 22-2. 871 St. John’s wort vs SSRIs: 12 trials: RR=1. 00; 95% CI, 0. 90-1. 111 St. John’s wort vs tricyclics: 5 trials: RR=1. 02; 95% CI, 0. 90-1. 151 | Effective for treating mild to moderate depression | A |
| Tryptophan and 5-hydroxy-tryptophan (5-HTP) | Cochrane review of 2 RCTs | 648 | Placebo | HAM-D | NNT=2. 78 vs placebo (OR=4. 1; 95% CI, 1. 28-13. 15 | Superior to placebo Insufficient evidence regarding safety | A |
| BDI, Beck Depression Inventory; CI, confidence interval; DF, degrees of freedom; ES, effect size; F, F statistic; HAM-D, Hamilton Depression Rating Scale; MADRS, Mont-gomery-Asberg Depression Rating Scale; MUFAs, monounsaturated fatty acids; n-3 PUFAs, n-3 long-chain polyunsaturated fatty acids; NNT, number needed to treat; OR, odds ratio; PUFAs, polyunsaturated fatty acids; RBC, red blood cell; RCT, randomized controlled trial; RR, relative risk; SAS, self-rating anxiety scale; SDS, self-rating depression scale; SFAs, saturated fatty acids; SMD, standard weighted mean difference; SOR, strength of recommendation; SSRI, selective serotonin reuptake inhibitor. | |||||||
ST. JOHN’S WORT is effective for short-term relief of mild to moderate depression (strength of recommendation [SOR]: A; 1 systematic review). Its safety profile is superior to older antidepressants; data comparing it with newer antidepressants (such as selective serotonin reuptake inhibitors) are limited (SOR: A, 1 systematic review).
A small but statistically significant clinical benefit has been demonstrated for saffron, lavender, borage, dan zhi xiao yao (SOR: B, 1 systematic review and 3 randomized controlled trials), folate (SOR: A, 1 systematic review), and S-adenosylmethionine (SAMe) (SOR: A, 1 meta-analysis and 1 systematic review). Most trials of these preparations were short and small, limiting the ability to detect adverse effects.
Tryptophan (SOR: A, 1 systematic review) and 5-hydroxytryptophan (5-HTP) (SOR: A, 1 systematic review) have demonstrated superiority over placebo in alleviating symptoms of depression, but concerns exist about their safety.
N-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) and omega-3 fatty acids don’t appear effective in treating major depressive disorder (SOR: A, 1 systematic review.)
Evidence summary
TABLE W1 summarizes study results and recommendations for nutritional therapies for depression.1-16
St. John’s wort works as well as standard antidepressants
A recent Cochrane review suggested that St. John’s wort is more effective than placebo in patients with mild to moderate depression and as effective as standard antidepressants.1
Other supplements also have benefits
A systematic review of 4 small randomized controlled trials (RCTs) suggested that saffron (30 mg) is superior to placebo in treating short-term depression (6 weeks). Treatment and outcomes were equivalent to fluoxetine and imipramine.2 A later RCT yielded results consistent with the systematic review.3
Combined lavender tincture (60 drops per day) and imipramine were more effective than imipramine alone in 1 small RCT.4
Borage, a traditional Persian medicine, was superior to placebo in reducing depressive symptoms in 1 small RCT.2
Dan zhi xiao yao, a traditional Chinese medicine, was as effective as the tricyclic anti-depressant maprotiline in 1 small RCT.2
Three RCTs suggested that folate may be used to supplement conventional treatments for depression, but it isn’t clear whether this would help patients with normal folate levels.5
A meta-analysis of 13 controlled clinical trials and a later systematic review of 11 articles including 2 RCTs concluded that SAMe is more effective than placebo and as efficacious as tricyclic antidepressants in treating major depression in adults. However, further trials are needed to answer questions about absorption, mechanism of action, and bioavailability.6,7
Tryptophan’s benefit comes with risk
In a Cochrane review of 2 RCTs, tryptophan and 5-HTP were superior to placebo in alleviating symptoms of depression. However, some published case reports have linked tryptophan use to potentially fatal eosinophilia-myalgia syndrome.8
No clear evidence for inositol or n-3 PUFAs
A Cochrane review of 4 small double-blind RCTs investigating inositol as a nutritional supplement in depression treatment failed to find clear evidence of therapeutic benefit.9
Three RCTs demonstrated significantly higher red blood cell membrane levels of n-3 PUFAs in nondepressed patients compared with depressed patients.10 However, a systematic review of 12 RCTs failed to demonstrate any benefit of n-3 PUFA supplementation over placebo in treating depressed mood.11 The authors concluded that larger trials are needed to demonstrate efficacy because of marked heterogeneity among the RCTs.
Safety issues. A recent Cochrane review found fewer adverse effects for St. John’s wort than tricyclic antidepressants.1 The most common adverse reactions were sensitivity to light, skin symptoms, gastrointestinal symptoms, and agitation. Data comparing St. John’s wort with newer antidepressants are lacking.
St. John’s wort does have pharmacokinetic interactions and should not be taken concurrently with other antidepressants, immunosuppressants, anti-HIV drugs, cou-marin-type anticoagulants, or certain antineoplastic agents.17
Reviews of meta-analyses, case reports, population studies, RCTs, and other literature have reported virtually no adverse effects for PUFAs; 18 trials investigating saffron, lavender, borage, dan zhi xiao yao, folate, SAMe, and inositol also reported no safety concerns. However, the size and duration of these studies limit their ability to detect significant problems.2,5,6,9 As previously noted, concerns exist regarding an association between tryptophan and eosinophilia-myalgia syndrome.8
Recommendations
The World Federation of Societies of Biological Psychiatry doesn’t recommend St. John’s wort for moderate to severe depression, but suggests it can be considered for treating mild to moderate depressive episodes provided the prescriber considers potential pharmacokinetic interactions with other medications and understands possible variations in purity and potency of extracts.19 The Federation also states that St. John’s wort is an alternative for patients reluctant to take traditional antidepressants.
TABLE W1
What the studies say about nutritional therapies for depression
| Supplement | Study type | Number of subjects | Comparison group | Outcome measure | Results | Conclusion | SOR |
|---|---|---|---|---|---|---|---|
| Borage (Echium amoenum) | 1 small RCT | 352,16 | Placebo | HAM-D | Improved HAM-D scores significantly at week 4 (borage 18. 3±3. 9 vs placebo 21. 9±3. 9; t=2. 51; P=. 02); no significant difference at Week 62,16 | Superior to placebo in reducing symptoms of depression | B |
| Dan zhi xiao yao | 1 small RCT | 632 | Maprotiline | HAM-D, SDS, SAS, scale for traditional Chinese medicine syndrome and symptom differentiation | 87% depression reduction (dan zhi xiao yao) vs 84% depression reduction (maprotiline) | As effective as maprotiline in treating depression | B |
| Folate | Cochrane review of 3 RCTs | 2475 | Studies 1 and 2: folate vs folate + other treatment (Study 1: low folate levels; Study 2: normal folate levels) Study 3: folate vs trazodone (normal folate levels) | HAM-D | Superior to placebo (NNT=5, defined as 50% reduction in HAM-D); comparable to trazodone (RR=0. 97; 95% CI, 0. 14-2. 01)7 | May have role as supplement to other treatments for depression Efficacy unclear in patients with normal folate levels | A |
| Inositol | Cochrane review of 4 RCTs | 1419 | Studies 1-3: placebo plus conventional antidepressants Study 4: placebo only | HAM-D, MADRS | Pooled estimate of effect of all 3 studies (SMD= -0. 08; 95% CI, -0. 45 to 0. 30) | No clear evidence of therapeutic benefit | A |
| Lavender (Lavandula angustifolia) | 1 small RCT | 454 | Imipramine | HAM-D | Imipramine plus lavender showed significant effect compared with imipramine alone (f=26. 87; Df=3. 01; P<. 0001) | Synergistic effect suggested when used with imipramine | B |
| n-3 long-chain polyunsaturated fatty acids | Systematic review including 3 RCTs; 10 meta-analysis of 12 RCTs11 | 10210 103211 | Various comparison groups included | Serum SFAs, MUFAs, PUFAs; RBC membrane levels n-3 PUFAs2 HAM-D, BDI3 | Systematic review:10 Study 1: n=30; ES=3. 61 Study 2: n=24; ES=1. 2 Study 3: n=48; ES=2. 43 Meta-analysis:11 Pooled ES=0. 13; 95% CI, 0. 01-0. 25 | Significantly higher RBC membrane levels of n-3 PUFAs in nondepressed vs depressed patients10 No significant effect for supplementation11 Larger trials with adequate power needed2,3 | A |
| S-adenosyl-methionine (SAMe) | Meta-analysis of 13 RCTs,6 systematic review including 2 RCTs7 | 3996 787 | Placebo and conventional antidepressants | HAM-D | NNT=2. 5 for HAM-D decrease of >25%; 6 NNT=6. 25 for HAM-D decrease of >50%6 | May have role in treatment of major depression Further trials are needed to address unanswered questions about absorption, mechanism of action, and bioavailability7 | A |
| Saffron (Crocus sativus) | Systematic review of 4 small RCTs, 1 later RCT | 3012 4013 4014 4015 403 | Imipramine12 Placebo13,15 Fluoxetine5,14 | HAM-D | Systematic review: Study 1: imipramine and saffron equally efficacious (f=2. 91; P=. 09)12 Study 2: Improved HAM-D scores: -12. 20±4. 67 (saffron) vs -5. 10±4. 71 (placebo) (P<. 0001)13 Study 3: Improved HAM-D scores: saffron petal -12. 00±4. 10; fluoxetine -13. 50±4. 91; difference between 2 treatments not significant (P=. 27)14 Study 4: Improved HAM-D scores: -14. 01±5. 53 (saffron petal) vs -5. 05±4. 63 (placebo) (P<. 0001)15 Study 5:5 NNT=10 | Efficacy of extract and petal suggested to treat mild to moderate depression Large-scale trials are warranted | B |
| St. John’s wort (Hypericum perforatum L. ) | Cochrane review of 29 RCTs | 54891 | SSRIs, tri/tetracyclic antidepressants, placebo | Responder rate ratio | St. John’s wort vs placebo: 9 larger trials: RR=1. 28; 95% CI, 1. 10-1. 491 9 smaller trials: RR=1. 87; 95% CI, 1. 22-2. 871 St. John’s wort vs SSRIs: 12 trials: RR=1. 00; 95% CI, 0. 90-1. 111 St. John’s wort vs tricyclics: 5 trials: RR=1. 02; 95% CI, 0. 90-1. 151 | Effective for treating mild to moderate depression | A |
| Tryptophan and 5-hydroxy-tryptophan (5-HTP) | Cochrane review of 2 RCTs | 648 | Placebo | HAM-D | NNT=2. 78 vs placebo (OR=4. 1; 95% CI, 1. 28-13. 15 | Superior to placebo Insufficient evidence regarding safety | A |
| BDI, Beck Depression Inventory; CI, confidence interval; DF, degrees of freedom; ES, effect size; F, F statistic; HAM-D, Hamilton Depression Rating Scale; MADRS, Mont-gomery-Asberg Depression Rating Scale; MUFAs, monounsaturated fatty acids; n-3 PUFAs, n-3 long-chain polyunsaturated fatty acids; NNT, number needed to treat; OR, odds ratio; PUFAs, polyunsaturated fatty acids; RBC, red blood cell; RCT, randomized controlled trial; RR, relative risk; SAS, self-rating anxiety scale; SDS, self-rating depression scale; SFAs, saturated fatty acids; SMD, standard weighted mean difference; SOR, strength of recommendation; SSRI, selective serotonin reuptake inhibitor. | |||||||
1. Linde K, Bemer MM, Kriston L. St. John’s wort for major depression. Cochrane Database Syst Rev. 2008;(4):CD000448.-
2. Sarris J. Herbal medicines in the treatment of psychiatric disorders: a systematic review. Phytother Res. 2007;21:703-716.
3. Akhondzadeh Basti A, Moshiri E, Noorbala AA, et al. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients. Prog Neuropsychopharmacol Biol Psychiatry. 2006;31:439-442.
4. Akhondzadeh S, Kashani L, Fotouhi A, et al. Comparison of Lavandula angustifolia Mill. tincture and imipramine in the treatment of mild to moderate depression. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:123-127.
5. Taylor MJ, Carney S, Geddes J, et al. Folate for depressive disorders. Cochrane Database Syst Rev. 2003;(2):CD003390.-
6. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepres-sant. Acta Neurol Scand Suppl. 1994;154:7-14.
7. Williams AL, Girard C, Jui D, et al. S-adenosylmethionine (SAMe) as treatment for depression. Clin Invest Med. 2005;28:132-139.
8. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxy-tryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198.-
9. Taylor MJ, Wilder H, Bhagwager Z, et al. Inositol for depressive disorders. Cochrane Database Syst Rev. 2004;(2):CD004049.-
10. Williams AL, Katz D, Ali A, et al. Do essential fatty acids have a role in the treatment of depression? J Affect Disord. 2006;93:117-123.
11. Appleton KM, Hayward RC, Gunnell D, et al. Effects of n-3 longchain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr. 2006;84:1308-1316.
12. Akhondzadeh S, Fallah-Pour H, Afkham K, et al. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression. BMC Complement Altern Med. 2004;4:12.-
13. Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, et al. Crocus sativus L. in the treatment of mild to moderate depression. Phytother Res. 2005;19:148-151.
14. Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, et al. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression. J Ethnopharmacol. 2005;97:281-284.
15. Moshiri E, Basti AA, Noorbala AA, et al. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression. Phytomedicine. 2006;13:607-611.
16. Sayyah M, Sahhah M, Kamalinejad M. A preliminary randomized double blind clinical trial on the efficacy of aqueous extract of Echium amoenum in the treatment of mild to moderate major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:166-169.
17. Schulz V Safety of St. John’s wort extract compared to synthetic antidepressants. Phytomedicine. 2006;13:199-204.
18. Lee S, Gura KM, Kim S, et al. Current clinical applications of ome-ga-6 and omega-3 fatty acids. Nutr Clin Pract. 2006;21:323-341.
19. Bauer M, Bschor T, Pfennig A, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders in primary care. World J Biol Psychiatry. 2007;8:67-104.
1. Linde K, Bemer MM, Kriston L. St. John’s wort for major depression. Cochrane Database Syst Rev. 2008;(4):CD000448.-
2. Sarris J. Herbal medicines in the treatment of psychiatric disorders: a systematic review. Phytother Res. 2007;21:703-716.
3. Akhondzadeh Basti A, Moshiri E, Noorbala AA, et al. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients. Prog Neuropsychopharmacol Biol Psychiatry. 2006;31:439-442.
4. Akhondzadeh S, Kashani L, Fotouhi A, et al. Comparison of Lavandula angustifolia Mill. tincture and imipramine in the treatment of mild to moderate depression. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:123-127.
5. Taylor MJ, Carney S, Geddes J, et al. Folate for depressive disorders. Cochrane Database Syst Rev. 2003;(2):CD003390.-
6. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepres-sant. Acta Neurol Scand Suppl. 1994;154:7-14.
7. Williams AL, Girard C, Jui D, et al. S-adenosylmethionine (SAMe) as treatment for depression. Clin Invest Med. 2005;28:132-139.
8. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxy-tryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198.-
9. Taylor MJ, Wilder H, Bhagwager Z, et al. Inositol for depressive disorders. Cochrane Database Syst Rev. 2004;(2):CD004049.-
10. Williams AL, Katz D, Ali A, et al. Do essential fatty acids have a role in the treatment of depression? J Affect Disord. 2006;93:117-123.
11. Appleton KM, Hayward RC, Gunnell D, et al. Effects of n-3 longchain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr. 2006;84:1308-1316.
12. Akhondzadeh S, Fallah-Pour H, Afkham K, et al. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression. BMC Complement Altern Med. 2004;4:12.-
13. Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, et al. Crocus sativus L. in the treatment of mild to moderate depression. Phytother Res. 2005;19:148-151.
14. Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, et al. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression. J Ethnopharmacol. 2005;97:281-284.
15. Moshiri E, Basti AA, Noorbala AA, et al. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression. Phytomedicine. 2006;13:607-611.
16. Sayyah M, Sahhah M, Kamalinejad M. A preliminary randomized double blind clinical trial on the efficacy of aqueous extract of Echium amoenum in the treatment of mild to moderate major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:166-169.
17. Schulz V Safety of St. John’s wort extract compared to synthetic antidepressants. Phytomedicine. 2006;13:199-204.
18. Lee S, Gura KM, Kim S, et al. Current clinical applications of ome-ga-6 and omega-3 fatty acids. Nutr Clin Pract. 2006;21:323-341.
19. Bauer M, Bschor T, Pfennig A, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders in primary care. World J Biol Psychiatry. 2007;8:67-104.
Evidence-based answers from the Family Physicians Inquiries Network
How do exercise and diet compare for weight loss?
Exercise alone produces short-term weight loss that is comparable with that induced by diet, after which a plateau in weight loss appears to occur (strength of recommendation [SOR]: B). Exercise in combination with diet promotes maintenance of weight loss above either intervention alone in both obese and overweight men and women (SOR: A). Exercise-induced weight loss has been shown to preferentially reduce abdominal fat and increase lean skeletal muscle compared with that induced by diet (SOR: B).
Multiple short bouts of exercise per day are as effective as a single long bout in producing weight loss (SOR: B). Adherence improves when exercise can be completed at home or home equipment is used (SOR: B).
The real challenge: Motivating patients to exercise
Henry Domke, MD
St. Mary’s Health Center, Jefferson City, Missouri
The evidence is pretty clear. The real challenge is motivating patients to start and maintain an exercise plan. The key points I make with my patients are: Aim for 5 to 7 times each week. Start slowly (10 minutes per session) and gradually build (at least to 20 minutes within a few months). Walking is often preferred, but do what you enjoy. Having a “buddy” work out with you may help you stick with it.
Evidence summary
Exercise vs diet: Some conflicting results
Studies comparing the effectiveness of exercise and diet in weight reduction have yielded conflicting results. Earlier studies, including a meta-analysis and randomized (noncontrolled) study, favored interventions that included caloric restriction (diet alone or diet plus exercise).1,2
However, subjects on caloric restriction regained a significant amount of weight over time (0.9 kg±7.7 at 2-year follow-up). Subjects who did aerobic exercise but did not diet lost less weight initially (0.7 kg±2.8) but maintained their weight loss better than those who dieted or dieted with exercise.
These earlier studies failed to control for the confounding variable of energy balance—that is, ensuring the amount of calories reduced was comparable with the amount of calories burned through exercise between groups. A more recent randomized controlled trial suggests that aerobic exercise and caloric restriction are equally beneficial in reducing weight for obese men when controlling for negative energy balance.3 However, those who exercised experienced greater fat reduction and maintenance of skeletal muscle mass than those who only restricted calories. Similar findings regarding fat reduction have been reported elsewhere.4
Combining diet and exercise appears to be superior to diet alone, based on the results of a recent meta-analysis of randomized controlled trials.5 However, this meta-analysis did not specify type of exercise, so it is unclear whether outcomes varied by activity.
Exercise: Is there a dose-response relationship?
Several studies have looked at the relationship between duration and intensity for exercise and weight loss. A dose-response relationship has been observed between the amount of time spent in aerobic exercise per week and the amount of weight lost for overweight women.6,7
There appears to be no significant difference in weight loss based on duration of a single aerobic exercise episode; rather, weight loss is similar whether completed in short or long bouts.7,8 One study found that at 12 months, individuals exercising more than 200 minutes per week lost 7.8 kg more (P<.01) than those exercising less than 150 minutes per week.7 Another study noted that at 18 months, subjects exercising more than 200 minutes per week lost 9.6 kg more than subjects exercising less than 150 minutes per week (P<.05).6
Studies with energy expenditure, rather than time spent exercising, as the independent variable had similar results. At 18 months, individuals with higher energy expenditure (2500 kcal/week) lost 6.7 kg±8.1 compared with a mean loss of 4.1±8.3 in subjects with lower energy expenditure (maximum of 1000 kcal/week).9
Recommendations from others
The National Institutes of Health’s National Heart, Lung and Blood Institute,10 the US Department of Health and Human Services,11 the Centers for Disease Control and Prevention’s Healthy People 201012 recommend between 30 to 90 minutes of daily moderate physical activity, and that this activity be done at least 5 days a week—or even 7 days per week—depending on whether a person’s goal is weight maintenance or weight loss.
Another option, offered by the CDC, is that people do 20 minutes of vigorous activity 3 days or more per week. All of the groups recommend staying within caloric intake requirements (TABLE).
TABLE
How much exercise is best? Government agencies weigh in
| AGENCY | PHYSICAL ACTIVITY LEVEL | ACTIVITIES | DURATION | FREQUENCY | NOTES |
|---|---|---|---|---|---|
| CDC12 | Moderate | Bicycling 5–9 mph, level terrain or with a few hills, brisk walking, golf, mowing lawn, recreational swimming, scrubbing floors/washing windows, tennis (doubles), weight lifting/Nautilus machines/free weights | 30 min | 5 or more days/week | All adults |
| CDC12 (alternative) | Vigorous | Bicycling more than 10 mph (alternative) or on steep uphill terrain, circuit training, moving/pushing furniture, mowing lawn (hand mower), racewalking, jogging, running, swimming laps, tennis (singles) | 20 min | 3 or more days/week | All adults |
| DHHS11 | Moderate | Bicycling (<10 mph), dancing, golf, hiking, light gardening/yard work stretching, walking (3.5 mph), weight lifting (general light workout) | 60–90 min | Daily | All adults attempting to lose weight |
| NHLBI10 | Moderate | Basketball, bicycling 5 miles/30 min, gardening, running 10 min/mile, social dancing, swimming laps, walking 15–20 min/mile | 30 min | Daily | All adult |
1. Miller WC, Koceja DM, Hamilton EJ. A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention. Int J Obes 1997;21:941-947.
2. Skender M, Goodrick G, Del Junco D. Comparison of 2 year weight loss trends in behavioral treatments of obesity: Diet, Exercise, and Combination interventions. J Amer Diet Assoc 1996;96:342-346.
3. Ross R, Freeman JA, Janssen I. Exercise alone is an effective strategy for reducing obesity and related comorbidities. Exerc Sport Sci Rev 2000;28:165-170.
4. Tsai A, Sandretto A, Chung Y. Dieting is more effective in reducing weight but exercise is more effective in reducing fat during the early phase of a weight-reducing program in healthy humans. J Nut Biochem 2003;14:541-549.
5. Curioni C, Lourenco P. Long-term weight loss after diet and exercise: a systematic review. Internat J Obes 2005;29:1168-1174.
6. Jakicic J, Marcus B, Gallagher K, Napolitano M, Lang W. Effect of exercise duration and intensity on weight loss in overweight, sedentary women, a randomized trial. JAMA 2003;290:1323-1330.
7. Jakicic J, Winters C, Lang W, Wing R. Effects of intermittent exercise and use of home exercise equipment on adherence, weight loss, and fitness in overweight women—a randomized trial. JAMA 1999;282:1554-1560.
8. Schmidt W, Biwer C, Kalscheuer L. Effects of long versus short bout exercise on fitness and weight loss in over-weight females. J Am Coll Nutr 2001;20:494-501.
9. Jeffrey RW, Wing RR, Sherwood NE, Tate DF. Physical activity and weight loss: does prescribing higher physical activity goals improve outcome? Am J Clin Nutr 2003;78:684-689.
10. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Obes Res 1998;6:6-26.
11. Department of Health and Human Services Dietary guidelines for Americans 2005 [Internet monograph]. Washington, DC: Department of Health and Human Services; 2005. Available at: www.health.gov/dietaryguidelines/dga2005/document/html/chapter4.htm. Accessed on September 4, 2007
12. Healthy People 2010 [Web site] Rockville, Md: Office of Disease Prevention and Health Promotion, US Department of Health and Human Services; 2002. Available at: www.healthypeople.gov/document/html/volume2/22physical.htm. Accessed on September 4, 2007.
Exercise alone produces short-term weight loss that is comparable with that induced by diet, after which a plateau in weight loss appears to occur (strength of recommendation [SOR]: B). Exercise in combination with diet promotes maintenance of weight loss above either intervention alone in both obese and overweight men and women (SOR: A). Exercise-induced weight loss has been shown to preferentially reduce abdominal fat and increase lean skeletal muscle compared with that induced by diet (SOR: B).
Multiple short bouts of exercise per day are as effective as a single long bout in producing weight loss (SOR: B). Adherence improves when exercise can be completed at home or home equipment is used (SOR: B).
The real challenge: Motivating patients to exercise
Henry Domke, MD
St. Mary’s Health Center, Jefferson City, Missouri
The evidence is pretty clear. The real challenge is motivating patients to start and maintain an exercise plan. The key points I make with my patients are: Aim for 5 to 7 times each week. Start slowly (10 minutes per session) and gradually build (at least to 20 minutes within a few months). Walking is often preferred, but do what you enjoy. Having a “buddy” work out with you may help you stick with it.
Evidence summary
Exercise vs diet: Some conflicting results
Studies comparing the effectiveness of exercise and diet in weight reduction have yielded conflicting results. Earlier studies, including a meta-analysis and randomized (noncontrolled) study, favored interventions that included caloric restriction (diet alone or diet plus exercise).1,2
However, subjects on caloric restriction regained a significant amount of weight over time (0.9 kg±7.7 at 2-year follow-up). Subjects who did aerobic exercise but did not diet lost less weight initially (0.7 kg±2.8) but maintained their weight loss better than those who dieted or dieted with exercise.
These earlier studies failed to control for the confounding variable of energy balance—that is, ensuring the amount of calories reduced was comparable with the amount of calories burned through exercise between groups. A more recent randomized controlled trial suggests that aerobic exercise and caloric restriction are equally beneficial in reducing weight for obese men when controlling for negative energy balance.3 However, those who exercised experienced greater fat reduction and maintenance of skeletal muscle mass than those who only restricted calories. Similar findings regarding fat reduction have been reported elsewhere.4
Combining diet and exercise appears to be superior to diet alone, based on the results of a recent meta-analysis of randomized controlled trials.5 However, this meta-analysis did not specify type of exercise, so it is unclear whether outcomes varied by activity.
Exercise: Is there a dose-response relationship?
Several studies have looked at the relationship between duration and intensity for exercise and weight loss. A dose-response relationship has been observed between the amount of time spent in aerobic exercise per week and the amount of weight lost for overweight women.6,7
There appears to be no significant difference in weight loss based on duration of a single aerobic exercise episode; rather, weight loss is similar whether completed in short or long bouts.7,8 One study found that at 12 months, individuals exercising more than 200 minutes per week lost 7.8 kg more (P<.01) than those exercising less than 150 minutes per week.7 Another study noted that at 18 months, subjects exercising more than 200 minutes per week lost 9.6 kg more than subjects exercising less than 150 minutes per week (P<.05).6
Studies with energy expenditure, rather than time spent exercising, as the independent variable had similar results. At 18 months, individuals with higher energy expenditure (2500 kcal/week) lost 6.7 kg±8.1 compared with a mean loss of 4.1±8.3 in subjects with lower energy expenditure (maximum of 1000 kcal/week).9
Recommendations from others
The National Institutes of Health’s National Heart, Lung and Blood Institute,10 the US Department of Health and Human Services,11 the Centers for Disease Control and Prevention’s Healthy People 201012 recommend between 30 to 90 minutes of daily moderate physical activity, and that this activity be done at least 5 days a week—or even 7 days per week—depending on whether a person’s goal is weight maintenance or weight loss.
Another option, offered by the CDC, is that people do 20 minutes of vigorous activity 3 days or more per week. All of the groups recommend staying within caloric intake requirements (TABLE).
TABLE
How much exercise is best? Government agencies weigh in
| AGENCY | PHYSICAL ACTIVITY LEVEL | ACTIVITIES | DURATION | FREQUENCY | NOTES |
|---|---|---|---|---|---|
| CDC12 | Moderate | Bicycling 5–9 mph, level terrain or with a few hills, brisk walking, golf, mowing lawn, recreational swimming, scrubbing floors/washing windows, tennis (doubles), weight lifting/Nautilus machines/free weights | 30 min | 5 or more days/week | All adults |
| CDC12 (alternative) | Vigorous | Bicycling more than 10 mph (alternative) or on steep uphill terrain, circuit training, moving/pushing furniture, mowing lawn (hand mower), racewalking, jogging, running, swimming laps, tennis (singles) | 20 min | 3 or more days/week | All adults |
| DHHS11 | Moderate | Bicycling (<10 mph), dancing, golf, hiking, light gardening/yard work stretching, walking (3.5 mph), weight lifting (general light workout) | 60–90 min | Daily | All adults attempting to lose weight |
| NHLBI10 | Moderate | Basketball, bicycling 5 miles/30 min, gardening, running 10 min/mile, social dancing, swimming laps, walking 15–20 min/mile | 30 min | Daily | All adult |
Exercise alone produces short-term weight loss that is comparable with that induced by diet, after which a plateau in weight loss appears to occur (strength of recommendation [SOR]: B). Exercise in combination with diet promotes maintenance of weight loss above either intervention alone in both obese and overweight men and women (SOR: A). Exercise-induced weight loss has been shown to preferentially reduce abdominal fat and increase lean skeletal muscle compared with that induced by diet (SOR: B).
Multiple short bouts of exercise per day are as effective as a single long bout in producing weight loss (SOR: B). Adherence improves when exercise can be completed at home or home equipment is used (SOR: B).
The real challenge: Motivating patients to exercise
Henry Domke, MD
St. Mary’s Health Center, Jefferson City, Missouri
The evidence is pretty clear. The real challenge is motivating patients to start and maintain an exercise plan. The key points I make with my patients are: Aim for 5 to 7 times each week. Start slowly (10 minutes per session) and gradually build (at least to 20 minutes within a few months). Walking is often preferred, but do what you enjoy. Having a “buddy” work out with you may help you stick with it.
Evidence summary
Exercise vs diet: Some conflicting results
Studies comparing the effectiveness of exercise and diet in weight reduction have yielded conflicting results. Earlier studies, including a meta-analysis and randomized (noncontrolled) study, favored interventions that included caloric restriction (diet alone or diet plus exercise).1,2
However, subjects on caloric restriction regained a significant amount of weight over time (0.9 kg±7.7 at 2-year follow-up). Subjects who did aerobic exercise but did not diet lost less weight initially (0.7 kg±2.8) but maintained their weight loss better than those who dieted or dieted with exercise.
These earlier studies failed to control for the confounding variable of energy balance—that is, ensuring the amount of calories reduced was comparable with the amount of calories burned through exercise between groups. A more recent randomized controlled trial suggests that aerobic exercise and caloric restriction are equally beneficial in reducing weight for obese men when controlling for negative energy balance.3 However, those who exercised experienced greater fat reduction and maintenance of skeletal muscle mass than those who only restricted calories. Similar findings regarding fat reduction have been reported elsewhere.4
Combining diet and exercise appears to be superior to diet alone, based on the results of a recent meta-analysis of randomized controlled trials.5 However, this meta-analysis did not specify type of exercise, so it is unclear whether outcomes varied by activity.
Exercise: Is there a dose-response relationship?
Several studies have looked at the relationship between duration and intensity for exercise and weight loss. A dose-response relationship has been observed between the amount of time spent in aerobic exercise per week and the amount of weight lost for overweight women.6,7
There appears to be no significant difference in weight loss based on duration of a single aerobic exercise episode; rather, weight loss is similar whether completed in short or long bouts.7,8 One study found that at 12 months, individuals exercising more than 200 minutes per week lost 7.8 kg more (P<.01) than those exercising less than 150 minutes per week.7 Another study noted that at 18 months, subjects exercising more than 200 minutes per week lost 9.6 kg more than subjects exercising less than 150 minutes per week (P<.05).6
Studies with energy expenditure, rather than time spent exercising, as the independent variable had similar results. At 18 months, individuals with higher energy expenditure (2500 kcal/week) lost 6.7 kg±8.1 compared with a mean loss of 4.1±8.3 in subjects with lower energy expenditure (maximum of 1000 kcal/week).9
Recommendations from others
The National Institutes of Health’s National Heart, Lung and Blood Institute,10 the US Department of Health and Human Services,11 the Centers for Disease Control and Prevention’s Healthy People 201012 recommend between 30 to 90 minutes of daily moderate physical activity, and that this activity be done at least 5 days a week—or even 7 days per week—depending on whether a person’s goal is weight maintenance or weight loss.
Another option, offered by the CDC, is that people do 20 minutes of vigorous activity 3 days or more per week. All of the groups recommend staying within caloric intake requirements (TABLE).
TABLE
How much exercise is best? Government agencies weigh in
| AGENCY | PHYSICAL ACTIVITY LEVEL | ACTIVITIES | DURATION | FREQUENCY | NOTES |
|---|---|---|---|---|---|
| CDC12 | Moderate | Bicycling 5–9 mph, level terrain or with a few hills, brisk walking, golf, mowing lawn, recreational swimming, scrubbing floors/washing windows, tennis (doubles), weight lifting/Nautilus machines/free weights | 30 min | 5 or more days/week | All adults |
| CDC12 (alternative) | Vigorous | Bicycling more than 10 mph (alternative) or on steep uphill terrain, circuit training, moving/pushing furniture, mowing lawn (hand mower), racewalking, jogging, running, swimming laps, tennis (singles) | 20 min | 3 or more days/week | All adults |
| DHHS11 | Moderate | Bicycling (<10 mph), dancing, golf, hiking, light gardening/yard work stretching, walking (3.5 mph), weight lifting (general light workout) | 60–90 min | Daily | All adults attempting to lose weight |
| NHLBI10 | Moderate | Basketball, bicycling 5 miles/30 min, gardening, running 10 min/mile, social dancing, swimming laps, walking 15–20 min/mile | 30 min | Daily | All adult |
1. Miller WC, Koceja DM, Hamilton EJ. A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention. Int J Obes 1997;21:941-947.
2. Skender M, Goodrick G, Del Junco D. Comparison of 2 year weight loss trends in behavioral treatments of obesity: Diet, Exercise, and Combination interventions. J Amer Diet Assoc 1996;96:342-346.
3. Ross R, Freeman JA, Janssen I. Exercise alone is an effective strategy for reducing obesity and related comorbidities. Exerc Sport Sci Rev 2000;28:165-170.
4. Tsai A, Sandretto A, Chung Y. Dieting is more effective in reducing weight but exercise is more effective in reducing fat during the early phase of a weight-reducing program in healthy humans. J Nut Biochem 2003;14:541-549.
5. Curioni C, Lourenco P. Long-term weight loss after diet and exercise: a systematic review. Internat J Obes 2005;29:1168-1174.
6. Jakicic J, Marcus B, Gallagher K, Napolitano M, Lang W. Effect of exercise duration and intensity on weight loss in overweight, sedentary women, a randomized trial. JAMA 2003;290:1323-1330.
7. Jakicic J, Winters C, Lang W, Wing R. Effects of intermittent exercise and use of home exercise equipment on adherence, weight loss, and fitness in overweight women—a randomized trial. JAMA 1999;282:1554-1560.
8. Schmidt W, Biwer C, Kalscheuer L. Effects of long versus short bout exercise on fitness and weight loss in over-weight females. J Am Coll Nutr 2001;20:494-501.
9. Jeffrey RW, Wing RR, Sherwood NE, Tate DF. Physical activity and weight loss: does prescribing higher physical activity goals improve outcome? Am J Clin Nutr 2003;78:684-689.
10. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Obes Res 1998;6:6-26.
11. Department of Health and Human Services Dietary guidelines for Americans 2005 [Internet monograph]. Washington, DC: Department of Health and Human Services; 2005. Available at: www.health.gov/dietaryguidelines/dga2005/document/html/chapter4.htm. Accessed on September 4, 2007
12. Healthy People 2010 [Web site] Rockville, Md: Office of Disease Prevention and Health Promotion, US Department of Health and Human Services; 2002. Available at: www.healthypeople.gov/document/html/volume2/22physical.htm. Accessed on September 4, 2007.
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3. Ross R, Freeman JA, Janssen I. Exercise alone is an effective strategy for reducing obesity and related comorbidities. Exerc Sport Sci Rev 2000;28:165-170.
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5. Curioni C, Lourenco P. Long-term weight loss after diet and exercise: a systematic review. Internat J Obes 2005;29:1168-1174.
6. Jakicic J, Marcus B, Gallagher K, Napolitano M, Lang W. Effect of exercise duration and intensity on weight loss in overweight, sedentary women, a randomized trial. JAMA 2003;290:1323-1330.
7. Jakicic J, Winters C, Lang W, Wing R. Effects of intermittent exercise and use of home exercise equipment on adherence, weight loss, and fitness in overweight women—a randomized trial. JAMA 1999;282:1554-1560.
8. Schmidt W, Biwer C, Kalscheuer L. Effects of long versus short bout exercise on fitness and weight loss in over-weight females. J Am Coll Nutr 2001;20:494-501.
9. Jeffrey RW, Wing RR, Sherwood NE, Tate DF. Physical activity and weight loss: does prescribing higher physical activity goals improve outcome? Am J Clin Nutr 2003;78:684-689.
10. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Obes Res 1998;6:6-26.
11. Department of Health and Human Services Dietary guidelines for Americans 2005 [Internet monograph]. Washington, DC: Department of Health and Human Services; 2005. Available at: www.health.gov/dietaryguidelines/dga2005/document/html/chapter4.htm. Accessed on September 4, 2007
12. Healthy People 2010 [Web site] Rockville, Md: Office of Disease Prevention and Health Promotion, US Department of Health and Human Services; 2002. Available at: www.healthypeople.gov/document/html/volume2/22physical.htm. Accessed on September 4, 2007.
Evidence-based answers from the Family Physicians Inquiries Network