Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients
Abstract
:1. Introduction
2. MDD, Stress, and Neuropsychoimmunity
3. The Interplay between Depression, Obesity, and Metabolic Dysregulation
4. Personalized Omega-3 Polyunsaturated Fatty Acids (n-3 PUFAs) Intervention in Depression
5. Omega-3 Polyunsaturated Fatty Acids (n-3 PUFAs) for Depression Treatment in Obese and Metabolically Dysregulated Patients
6. Future Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Biological specificity | Population | Study Design | Intervention | Main Findings | References | |
| ||||||
IFN-induced depression | n = 152, HCV patients | Double-blind, RCT | 2-week treatment with EPA (3.5 g/day) (n = 50); DHA (1.75 g/day) (n = 51); placebo (n = 50) | EPA-treated, not DHA-treated significantly decreased the incidence of IFN-α-induced depression in HCV patients (10%, 28%, respectively, compared to 30% placebo, p = 0.037). | [101] | |
Cardiovascular disease comorbidity | n = 59, CVD patients with comorbid MDD | RCT | 2-week treatment with n-3 PUFAs (EPA 2.0 g/day and DHA 1.0 g/day) (n = 30); placebo (n = 29) | No significant differences between groups in HAMD and BDI-II total scores, but n-3 PUFAs significantly reduced HAMD cognition at week 8 (p < 0.05) and the HAMD core subscale in very severe MDD at week 12 (p < 0.05). | [104] | |
n = 108, CHF patients with comorbid MDD | Double-blind, RCT | 2-week treatment with n-3 PUFAs (2:1 EPA/DHA 2.0 g/day) (n = 36); EPA (2 g/day) (n = 36); placebo (n = 36) | No significant differences between groups in HAMD and BDI-II total scores. BDI-II cognitive depressive subscales were strongly associated with the high EPA group (p < 0.05). | [103] | ||
n = 92, CAD patients with comorbid MDD | Double-blind, RCT | 2-week treatment with n-3 PUFAs (1.9 g/day) (n = 45); placebo (n = 47) | Plasma EPA and DHA levels increased (p < 0.01), but no significant differences between groups in HAMD (p = 0.20) and BDI-II (p = 0.50) total scores. | [105] | ||
Pain comorbidity | n = 46, Breast cancer survivor | Prospective, RCT | 6-week diet intervention with high n-3 PUFAs (2040 mg, 12 ounces/week wild-caught Alaskan salmon) (n = 24) and low PUFAs (1020 mg, 6 ounces/week) (n = 15) | High n-3 PUFA group significantly decreased pain (p < 0.01), perceived stress (p < 0.05), sleep (p < 0.001), depression (p < 0.001), and fatigue (p < 0.01). | [106] | |
Obesity and metabolic comorbidity | n = 25, Diabetes patients with MDD | Double-blind, RCT | 12-week treatment with EPA (1 g/day) (n = 13), placebo (n = 12) | No significant impact on BDNF (p = 0.887) and no significant association between changes in BDNF levels and depression severity (p = 0.593). | [107] | |
n = 45, Obese patient with MDD | Double-blind, RCT | 12-week treatment with n-3 PUFAs (1.08 g/d EPA and 0.72 g/d DHA) (n = 24); placebo (n = 21) | Significantly reduced depression (p = 0.05) in n-3 treatment groups. | [108] | ||
n = 61, Obese patient with MDD | Double-blind, RCT | 12-week treatment with EPA (1 g/d, n = 15; 2 g/d, n = 15; 4 g/day, n = 16); placebo (n = 15) | EPA 4 g/d produced a sustained effect on IDS-30 scores at both weeks 8 and 12. A potential dose-response relationship between EPA dose and change in IDS-C30 scores, but this was not statistically significant. | [26] | ||
| ||||||
Parkinson’s disease comorbidity | n = 29, Parkinson’s disease with MDD | Double-blind, RCT | 12-week treatment with n-3 PUFAs (1200 mg/d) (n = 14); placebo (n = 15) | Significant decrease in MADRS and CGI-Depression scores but not in BDI in the n-3 PUFAs group. | [109] | |
Alzheimer’s disease comorbidity | n = 26, Patients with MCI or AD | Double-blind, RCT | 24-week treatment with n-3 PUFAs (1080 mg/d EPA and 720 mg/d DHA) (n = 20); placebo (n = 15) | No associations were found between the randomization group and ADAS-cog, MMSE, or HDRS scores. | [110] | |
n = 204, Patient with AD | Double-blind, RCT | 6-month treatment with n-3 PUFAs (0.6 g/d EPA and 1.7 g/d DHA) (n = 103); placebo (n = 103) | No overall n-3 PUFA effect on neuropsychiatric symptoms. Possible positive effects of MADRS in non-APOEv4 carriers (p = 0.005). | [111] | ||
Late-life depression | n = 18,353, Adults aged 50 years or older without depression | RCT | Median of 5.3 years of treatment with n-3 PUFAs (65 mg/d EPA and 375 mg/d DHA) (n = 9171), placebo (n = 9182) | No significant improvement in the n-3 PUFA group in the prevention of depression. | [112] | |
| ||||||
Perinatal depression | n = 59, Perinatal and postpartum women | Double-blind, RCT | 8-week treatment with n-3 PUFAs (1.9 g/d) (n = 28), placebo (n = 23) | Both groups experienced significant decreases in EPDS and HAM-D scores (p < 0.0001) from baseline. | [113] | |
n = 36, Perinatal women with MDD | Double-blind, RCT | 8-week treatment with n-3 PUFAs (3.4 g/d) (n = 18), placebo (n = 18) | Significantly lower EDPS and BDI were observed in the n-3 PUFA group. | [22] | ||
Safety consideration | Special populations | |||||
Children and adolescents with depression | n = 60, Children with DD or MADD | Double-blind, RCT | 12-week treatment n-3 PUFAs (2.4 g/d) (n = 30), n-6 PUFAs (n = 30) | Significant reductions in CDI scores were observed in the n-3 PUFAs group and the DD subgroup compared to the n-6 PUFAs and MADD subgroup. No serious side effects were observed, except for increased defecation reported by one participant in the n-3 PUFA group. | [114] | |
High-risk psychosis | n = 81, Patients with an ultra-high risk of psychotic disorder | Double-blind, RCT | 12-week treatment with n-3 PUFAs (1.2 g/d) (n = 41), placebo (n = 40) | Significant improvement was observed in PANSS and GAF scores but not in MADRS scores. No significant adverse effects between the treatment groups. | [115] | |
n = 50, Patients with schizophrenia-spectrum or bipolar disorders on medication | RCT | 16-week n-3 PUFAs (740 mg/d EPA and 400 mg/d DHA) (n = 27), placebo (n = 26) | The n-3 PUFA group showed significant improvement in BPRS scores compared to placebo among a subgroup of patients (n = 23) who did not receive lorazepam. Lower rates of confusion, anxiety, depression, irritability, and tiredness/fatigue in the n-3 PUFAs group as compared to those on placebo. | [116] | ||
n = 110, Injured patients with PTSD | Double-blind, RCT | 12-week n-3 PUFAs (1470 mg/d DHA and 147 mg/d EPA) (n = 53), placebo (n = 57) | Serum BDNF and pro-BDNF changes at week 12 were linked to depression severity, but DHA had no specific effect on these levels. Adverse events, including loose stool and constipation, were reported, but there were no significant differences between the two groups. | [117] | ||
Pregnant women with MDD | n = 36, Perinatal women with MDD | Double-blind, RCT | 8-week treatment with n-3 PUFAs (3.4 g/d) (n = 18), placebo (n = 18) | Well tolerated, and there were no adverse effects on the subjects or newborns. | [22] |
References | Sample | Study Design | Intervention | Outcome Scale | Main Findings | Notes and Limitations |
---|---|---|---|---|---|---|
Bot et al. (2011) [107] | n = 25, Women with MDD and diabetes on antidepressants | Double-blind, RCT | 12-week treatment with EPA (1 g/day) (n = 13), placebo (n = 12) | MADRS, Serum BDNF | No significant impact on BDNF (p = 0.887) and no significant association between changes in BDNF levels and depression severity (p = 0.593). | First clinical study to examine the effects of n-3 PUFAs on BDNF. Small sample size. One patient reported an allergic reaction and discontinued using EPA; no other severe adverse events were reported. |
Keshavarz et al. (2018) [108] | n = 45, Women with depression and comorbid obesity (BMI ≥ 25 kg/m2) without antidepressants | Double-blind, RCT, | 12-week treatment with n-3 PUFAs (EPA 1.08 g/day and DHA 0.72 g/day) (n = 24); placebo (n = 21) | Body weight, height, BMI, waist and hip circumferences, total body fat, muscle percentage, BDI, food craving questionnaire, appetite, and food abstinence visual Analogue scales | Reduced depression (p = 0.05) and body weight (p = 0.049) in n-3 treatment groups | Weight regains after a one-month follow-up. Side effects include nausea, skin rash, hemorrhagia, and increased appetite, which were reported in both groups. |
Mischoulon et al. (2022) [26] | n = 61, Patient with MDD comorbid overweight/obese (BMI ≥ 25 kg/m2), without antidepressants | Double-blind, RCT | 12-week treatment with EPA (1 g/d, n = 15; 2 g/d, n = 15; 4 g/day, n = 16); placebo (n = 15) | IL-6, LPS-stimulated TNF level, plasma hs-CRP level, IDS-C30 | EPA 4 g/d produced a sustained effect on IDS-30 scores at both weeks 8 and 12. A potential dose-response relationship between EPA dose and change in IDS-C30 scores, but this was not statistically significant. | 1st dose-finding trial of EPA in MDD to focus on inflammatory biomarkers as a primary outcome among overweight/obese subjects with elevated hs-CRP |
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Wu, S.-K.; Chen, W.-J.; Chang, J.P.-C.; Guu, T.-W.; Hsin, M.-C.; Huang, C.-K.; Mischoulon, D.; Capuron, L.; Su, K.-P. Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients. J. Pers. Med. 2023, 13, 1003. https://doi.org/10.3390/jpm13061003
Wu S-K, Chen W-J, Chang JP-C, Guu T-W, Hsin M-C, Huang C-K, Mischoulon D, Capuron L, Su K-P. Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients. Journal of Personalized Medicine. 2023; 13(6):1003. https://doi.org/10.3390/jpm13061003
Chicago/Turabian StyleWu, Suet-Kei, Wei-Jen Chen, Jane Pei-Chen Chang, Ta-Wei Guu, Ming-Che Hsin, Chih-Kun Huang, David Mischoulon, Lucile Capuron, and Kuan-Pin Su. 2023. "Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients" Journal of Personalized Medicine 13, no. 6: 1003. https://doi.org/10.3390/jpm13061003
APA StyleWu, S.-K., Chen, W.-J., Chang, J. P.-C., Guu, T.-W., Hsin, M.-C., Huang, C.-K., Mischoulon, D., Capuron, L., & Su, K.-P. (2023). Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients. Journal of Personalized Medicine, 13(6), 1003. https://doi.org/10.3390/jpm13061003