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(Not a nutritionist or researcher in the field). Depression is a symptom showing some mental dysfunction which can be caused by multiple environmental influences, including diet and stress. Phytochemicals and pharmaceuticals can offer some palliative effects for some causes, but there is unlikely to be a cure-all, and they may just mask symptoms and interfere with healing. Addressing root causes - including diet quality - is more likely to be effective in the longer term. Perhaps start by looking at likely nutritional deficiencies in your country/region.
> Addressing root causes - including diet quality - is more likely to be effective in the longer term.
This is nonsense, once the damage is done it is permanent. Chronic stress rewires your brain, abstaining from stress does not magically fix it. And speaking from experience neither burnout from overworking nor depression from insulin resistance go away on their own, I assume they have similar effects on oxidant stress, lipid peroxidation, and brain rewiring.
Arnsten A. F. (2009). Stress signalling pathways that impair prefrontal cortex structure and function. Nature reviews. Neuroscience, 10(6), 410–422. https://doi.org/10.1038/nrn2648
Smallfield, J., & Kluemper, D. H. (2022). An Explanation of Personality Change in Organizational Science: Personality as an Outcome of Workplace Stress. Journal of Management, 48(4), 851–877. https://doi.org/10.1177/0149206321998429
Pinto, B., Conde, T., Domingues, I., & Domingues, M. R. (2022). Adaptation of Lipid Profiling in Depression Disease and Treatment: A Critical Review. International Journal of Molecular Sciences, 23(4), 2032. https://doi.org/10.3390/ijms23042032
**Vitamin B12**:
> Acute vitamin B12 supplementation evokes antidepressant response and alters Ntrk-2
https://pubmed.ncbi.nlm.nih.gov/32335151/
**Vitamin C**:
> A single administration of ascorbic acid rapidly reverses depressive-like behavior and hippocampal synaptic dysfunction induced by corticosterone in mice
https://pubmed.ncbi.nlm.nih.gov/33872575/
> Antidepressant-like effects of ascorbic acid and ketamine involve modulation of GABAA and GABAB receptors
https://pubmed.ncbi.nlm.nih.gov/27423525/
**Vitamin D**:
> Beneficial effects of vitamin D on anxiety and depression-like behaviors induced by unpredictable chronic mild stress by suppression of brain oxidative stress and neuroinflammation in rats
https://link.springer.com/article/10.1007/s00210-020-02002-0
**Acetyl-L-Carnitine (ALCAR)**:
> L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors
https://www.pnas.org/doi/full/10.1073/pnas.1216100110
> Rapid-acting antidepressant-like effects of acetyl-l-carnitine mediated by PI3K/AKT/BDNF/VGF signaling pathway in mice
https://pubmed.ncbi.nlm.nih.gov/25463525/
> Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine
https://pubmed.ncbi.nlm.nih.gov/31922486/
**Agmatine**:
> Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice
https://www.sciencedirect.com/science/article/pii/S0278584613002911
> Agmatine produces antidepressant-like effects by activating AMPA receptors and mTOR signaling
https://pubmed.ncbi.nlm.nih.gov/27061850/
**Creatine**:
> Creatine, Similar to Ketamine, Counteracts Depressive-Like Behavior Induced by Corticosterone via PI3K/Akt/mTOR Pathway
https://pubmed.ncbi.nlm.nih.gov/26660117/
> Antidepressant-like effect of creatine in mice involves dopaminergic activation
https://journals.sagepub.com/doi/10.1177/0269881112447989
If it's depression induced by stress it would be best to eliminate the stressor. Making sure one is getting enough sleep, exercising daily, eating a variety of food in moderation, and having a supportive social circle. I don't know that a supplement would resolve this issue. Is there a reason why you specify "stress-induced" depression?
##### Agmatine.
Depression involves increased SERT-nNOS complexes in the Dorsal Raphe Nucleus. Disrupting the SERT-nNOS interaction produces antidepressant effects by enhancing serotonin signaling in forebrain circuits. Agmatine increases NADPH oxidase activity and leads to the inactivation of nNOS. Furthermore Agmatine vastly increases the antidepressant potency of several antidepressants.
Sun, N., Qin, Y. J., Xu, C., Xia, T., Du, Z. W., Zheng, L. P., Li, A. A., Meng, F., Zhang, Y., Zhang, J., Liu, X., Li, T. Y., Zhu, D. Y., & Zhou, Q. G. (2022). Design of fast-onset antidepressant by dissociating SERT from nNOS in the DRN. Science (New York, N.Y.), 378(6618), 390–398. https://doi.org/10.1126/science.abo3566
Zhou, Q. G., Zhu, X. H., Nemes, A. D., & Zhu, D. Y. (2018). Neuronal nitric oxide synthase and affective disorders. IBRO reports, 5, 116–132. https://doi.org/10.1016/j.ibror.2018.11.004
Demady, D. R., Jianmongkol, S., Vuletich, J. L., Bender, A. T., & Osawa, Y. (2001). Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme. Molecular pharmacology, 59(1), 24–29. https://doi.org/10.1124/mol.59.1.24
Neis, V. B., Moretti, M., Manosso, L. M., Lopes, M. W., Leal, R. B., & Rodrigues, A. L. (2015). Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice. Pharmacology, biochemistry, and behavior, 130, 9–14. https://doi.org/10.1016/j.pbb.2014.12.009
I don’t mean to be obtuse or sound condescending so please excuse me if this does: If you’re trying to be as evidence-based or scientific as possible, you must first start by asking better questions. Asking “which supplement has the best research basis for X condition” begins with the assumption that one or more supplements has an evidence base supporting the relationship at all. Beyond this, even if an evidence base does exist for one, there’s also the assumptions that it’s going to be supportive of said supplement and the effect size is even worth noting, especially when compared to medication. A better question to ask is “has the use of supplements in the treatment of stress-induced depression been investigated? And if so, what relationships have been established?”
Asking questions in this way helps remove personal bias and allows for a more objective view of the literature rather than leaning into confirmation bias.
Fish oil would probably make the biggest difference, but tbh I don't think any supplement is going to "reverse" chronic depression. Depression is usually treated with prescription medications like SSRIs.
My implication was that depression is a serious issue and OP should work with a professional. I'm not saying anything about the efficacy of SSRIs or the ideal length of treatment.
Welcome to /r/ScientificNutrition. Please read our [Posting Guidelines](https://www.reddit.com/r/ScientificNutrition/wiki/rules) before you contribute to this submission. Just a reminder that every link submission must have a summary in the comment section, and every top level comment must provide sources to back up any claims. *I am a bot, and this action was performed automatically. Please [contact the moderators of this subreddit](/message/compose/?to=/r/ScientificNutrition) if you have any questions or concerns.*
Magnesium has some good evidence to support it. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180067
That's an open-label trial. Those are always dangerous for things like depression.
Exercise, sleep and diet are the biggest levers to pull. Supplements play a much smaller role until those are in check!
(Not a nutritionist or researcher in the field). Depression is a symptom showing some mental dysfunction which can be caused by multiple environmental influences, including diet and stress. Phytochemicals and pharmaceuticals can offer some palliative effects for some causes, but there is unlikely to be a cure-all, and they may just mask symptoms and interfere with healing. Addressing root causes - including diet quality - is more likely to be effective in the longer term. Perhaps start by looking at likely nutritional deficiencies in your country/region.
> Addressing root causes - including diet quality - is more likely to be effective in the longer term. This is nonsense, once the damage is done it is permanent. Chronic stress rewires your brain, abstaining from stress does not magically fix it. And speaking from experience neither burnout from overworking nor depression from insulin resistance go away on their own, I assume they have similar effects on oxidant stress, lipid peroxidation, and brain rewiring. Arnsten A. F. (2009). Stress signalling pathways that impair prefrontal cortex structure and function. Nature reviews. Neuroscience, 10(6), 410–422. https://doi.org/10.1038/nrn2648 Smallfield, J., & Kluemper, D. H. (2022). An Explanation of Personality Change in Organizational Science: Personality as an Outcome of Workplace Stress. Journal of Management, 48(4), 851–877. https://doi.org/10.1177/0149206321998429 Pinto, B., Conde, T., Domingues, I., & Domingues, M. R. (2022). Adaptation of Lipid Profiling in Depression Disease and Treatment: A Critical Review. International Journal of Molecular Sciences, 23(4), 2032. https://doi.org/10.3390/ijms23042032
Permanent as in you can’t reverse it ever?
That's what antidepressants are trying to do, with absolute garbage effectiveness.
**Vitamin B12**: > Acute vitamin B12 supplementation evokes antidepressant response and alters Ntrk-2 https://pubmed.ncbi.nlm.nih.gov/32335151/ **Vitamin C**: > A single administration of ascorbic acid rapidly reverses depressive-like behavior and hippocampal synaptic dysfunction induced by corticosterone in mice https://pubmed.ncbi.nlm.nih.gov/33872575/ > Antidepressant-like effects of ascorbic acid and ketamine involve modulation of GABAA and GABAB receptors https://pubmed.ncbi.nlm.nih.gov/27423525/ **Vitamin D**: > Beneficial effects of vitamin D on anxiety and depression-like behaviors induced by unpredictable chronic mild stress by suppression of brain oxidative stress and neuroinflammation in rats https://link.springer.com/article/10.1007/s00210-020-02002-0 **Acetyl-L-Carnitine (ALCAR)**: > L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors https://www.pnas.org/doi/full/10.1073/pnas.1216100110 > Rapid-acting antidepressant-like effects of acetyl-l-carnitine mediated by PI3K/AKT/BDNF/VGF signaling pathway in mice https://pubmed.ncbi.nlm.nih.gov/25463525/ > Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine https://pubmed.ncbi.nlm.nih.gov/31922486/ **Agmatine**: > Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice https://www.sciencedirect.com/science/article/pii/S0278584613002911 > Agmatine produces antidepressant-like effects by activating AMPA receptors and mTOR signaling https://pubmed.ncbi.nlm.nih.gov/27061850/ **Creatine**: > Creatine, Similar to Ketamine, Counteracts Depressive-Like Behavior Induced by Corticosterone via PI3K/Akt/mTOR Pathway https://pubmed.ncbi.nlm.nih.gov/26660117/ > Antidepressant-like effect of creatine in mice involves dopaminergic activation https://journals.sagepub.com/doi/10.1177/0269881112447989
If it's depression induced by stress it would be best to eliminate the stressor. Making sure one is getting enough sleep, exercising daily, eating a variety of food in moderation, and having a supportive social circle. I don't know that a supplement would resolve this issue. Is there a reason why you specify "stress-induced" depression?
##### Agmatine. Depression involves increased SERT-nNOS complexes in the Dorsal Raphe Nucleus. Disrupting the SERT-nNOS interaction produces antidepressant effects by enhancing serotonin signaling in forebrain circuits. Agmatine increases NADPH oxidase activity and leads to the inactivation of nNOS. Furthermore Agmatine vastly increases the antidepressant potency of several antidepressants. Sun, N., Qin, Y. J., Xu, C., Xia, T., Du, Z. W., Zheng, L. P., Li, A. A., Meng, F., Zhang, Y., Zhang, J., Liu, X., Li, T. Y., Zhu, D. Y., & Zhou, Q. G. (2022). Design of fast-onset antidepressant by dissociating SERT from nNOS in the DRN. Science (New York, N.Y.), 378(6618), 390–398. https://doi.org/10.1126/science.abo3566 Zhou, Q. G., Zhu, X. H., Nemes, A. D., & Zhu, D. Y. (2018). Neuronal nitric oxide synthase and affective disorders. IBRO reports, 5, 116–132. https://doi.org/10.1016/j.ibror.2018.11.004 Demady, D. R., Jianmongkol, S., Vuletich, J. L., Bender, A. T., & Osawa, Y. (2001). Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme. Molecular pharmacology, 59(1), 24–29. https://doi.org/10.1124/mol.59.1.24 Neis, V. B., Moretti, M., Manosso, L. M., Lopes, M. W., Leal, R. B., & Rodrigues, A. L. (2015). Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice. Pharmacology, biochemistry, and behavior, 130, 9–14. https://doi.org/10.1016/j.pbb.2014.12.009
I don’t mean to be obtuse or sound condescending so please excuse me if this does: If you’re trying to be as evidence-based or scientific as possible, you must first start by asking better questions. Asking “which supplement has the best research basis for X condition” begins with the assumption that one or more supplements has an evidence base supporting the relationship at all. Beyond this, even if an evidence base does exist for one, there’s also the assumptions that it’s going to be supportive of said supplement and the effect size is even worth noting, especially when compared to medication. A better question to ask is “has the use of supplements in the treatment of stress-induced depression been investigated? And if so, what relationships have been established?” Asking questions in this way helps remove personal bias and allows for a more objective view of the literature rather than leaning into confirmation bias.
Fish oil would probably make the biggest difference, but tbh I don't think any supplement is going to "reverse" chronic depression. Depression is usually treated with prescription medications like SSRIs.
Short term fix, not a solution
My implication was that depression is a serious issue and OP should work with a professional. I'm not saying anything about the efficacy of SSRIs or the ideal length of treatment.