So depression is an inflammatory disease, but where does the inflammation come from?
BMC Med. 2013 Sep 12;11:200. doi: 10.1186/1741-7015-11-200.
Berk M, Williams LJ, Jacka FN, O'Neil A, Pasco JA, Moylan S, Allen NB, Stuart AL, Hayley AC, Byrne ML, Maes M.
IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia. mikebe at barwonhealth.org.au.
BACKGROUND: We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is 'what is the source of this chronic low-grade inflammation?'
DISCUSSION: This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency.
SUMMARY: The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder.
Clipped section from PDF which discusses Vitamin D
Vitamin D
Low levels of Vitamin D, particularly 25-hydroxyvitamin D are widespread among Western populations [219], making it the most prevalent deficiency state. Low Vitamin D is linked to a diversity of adverse health outcomes, such as osteoporosis and cancer [220]. Notably, the physiology of vitamin D overlaps with the patho-physiology of depression. Vitamin D receptors are expressed in key brain areas; and vitamin D has a role in circadian rhythms and sleep, affects glucocorticoids and influences neuronal growth, cell proliferation in the developing brain and embryogenesis [221]. There is a growing epidemiological evidence-base linking depressive symptoms to low levels of serum 25-hydroxyvitamin D. These studies include both cross-sectional studies, as well as prospective data suggesting that low levels are associated with increased risk for the development of depression. There are positive trials of the potential anti-depressant effects of vitamin D [222], although there are equally negative trials [223].
Vitamin D has well documented modulatory effects on immunity. It modulates immune responses to infections, such as tuberculosis [224]. In rats given a high fat diet, 1a, 25-dihydroxyvitamin D3 (calcitriol) treatment reduced concentrations of various inflammatory markers, including TNF-a, CRP and IL-6, and protected the liver from inflammatory damage [225]. In human studies, supplementation robustly reduces inflammatory markers in people with cystic fibrosis, including TNF-a and IL-6, but not other cytokines. Curiously, those two cytokines are the most robustly associated with depression in meta-analyses [226]. In multiple sclerosis, vitamin D reduces markers of inflammation and attenuates disease progression [227]. A one-year clinical trial of supplementation with Vitamin D in obese individuals reduced TNF-a levels, but increased hsCRP. The implications of these changes are unclear [225]. Inflammation and oxidative stress are tightly interlinked, and in human studies, vitamin D supplementation additionally reduced oxidative stress markers [228]. Vitamin D is a proxy of sunlight exposure, and it is useful to note that sunlight may suppress immunity via pathways other than via vitamin D. In fact, vitamin D derived from safe sunlight exposure may reduce systemic inflammation. There are additional skin photoreceptors that absorb ultraviolet light, and play a role in immunoregulation, that include DNA and lipids in skin cells and fra#s-urocanic acid found in the stratum corneum [229].
 Download the PDF from VitaminDWiki.
See also VitaminDWiki
- Anti-depression medication about as good as big increase in vitamin D – meta-analysis of flawless data April 2014
- Depression and low Vitamin D – review 2014
- Mental health problems cut in half when have adequate level of vitamin D – Jan 2013
- Much less depression if higher than 43 ng of vitamin D – Oct 2012
- Teens no longer depressed after vitamin D raised to 36 ng – Feb 2012
- Magnesium and Vitamin D - similar, different and synergistic
- Magnesium in depression 2013 file, not webpage
- Depression category listing has
268 items along with related searches - The Single Vitamin That's a Double Whammy Against Both Depression and Dementia (Mercola) – Aug 2014
See several more items from Mercola on Inflammation and Depression in web section below- Depression leads to many other diseases if vitamin D level not restored
Depression ==> Fragile bones- Depression ==> Cognitive Decline
Pages listed in BOTH the categories Depression and Omega-3
- Overweight needed more EPA (4 grams) to fight depression – RCT Aug 2022
- Anxiety, depression, and suicide have recently surged (Note: Vitamin D, Omega-3, and Magnesium help) – May 2022
- Omega-3 did not prevent depression (they failed to reduce Omega-6, which blocks Omega-3) – RCT Dec 2021
- Mental health not helped by vitamin D monotherapy (adding Omega-3 and Magnesium help) – review Nov 2021
- Benefits of Omega-3 plus Vitamin D were additive – RCT Sept 2021
- Depression treatments: diet, exercise, bright light, Vitamin D, B12, Omega-3, Zinc, Music, etc. – May 2019
- Omega-3 helps treat Major Depression – International Consensus Sept 2019
- Mental disorders fought by Omega-3 etc. - meta-meta-analysis Oct 2019
- Omega-3 reduces Depression. Anxiety, Stress, PTSD, etc. – Aug 2018
- Depression treated by Omega-3 (again) – meta-analysis Aug 2019
- Depression after childbirth 5 X less likely if good Omega-3 index – April 2019
- Occupational burnout reduced after 8 weeks of Omega-3 – RCT July 2019
- Anxiety severity reduced if more than 2 grams of Omega-3 – meta-analysis Sept 2018
- Psychotic disorders not treated by Omega-3 when patents take anti-depressants and get therapy – June 2018
- Happy Nurses Project gave Omega-3 for 3 months – reduced depression, insomnia, anxiety, etc for a year – RCT July 2018
- Depression – is it reduced by Vitamin D and or Omega-3 – RCT 2019
- Benefits of Omega-3 beyond heart health - LEF Feb 2018
- Omega-3 improves gut bacteria, reduces inflammation and depression – Dec 2017
- Unipolar depression treated by Omega-3, Zinc, and probably Vitamin D – meta-analysis Oct 2017
- Omega-3 reduces many psychiatric disorders – 2 reviews 2016
- Omega-3 does not consistently treat depression if use small amounts for short time period – review Oct 2016
- How Omega-3 Fights Depression – LEF July 2016
- Depression due to inflammation reduced by Omega-3 (children and pregnant) – Nov 2015
- Depression treated somewhat by Omega-3 (St. John's Wort better) – RAND org reviews 2015
- Depression substantially decreased with Omega-3 – Sept 2015
- Omega-3 for just 3 months greatly reduced psychosis for 80 months – RCT Aug 2015
- Omega-3 prevents PTSD and some mood disorders - Aug 2015
- Omega-3, Vitamin D, and other nutrients decrease mental health problems – March 2015
See also web
- Is Depression a Disease—or a Symptom of Inflammation? Chris Kresser Aug 2014
Mentions Vitamin D, but not Magnesium - Depression ==> Heart Disease 40% increase,, Forbes 2014
- Advances in Understanding of Depression Offers New Hope Mercola Jan 2015
Discusses depression and inflamation. The phrase "Vitamin D" occurs 20 times. - Depression’s Link to Inflammation Gains StrengthMercola Oct 2016
Includes video interview of Interview with Dr. Hyla Cass with transcript
Vitamin D occurs 21 times, and others such as Omega-3, nuts, and arthritis anti-inflammation drugs
References in Mercola 2016
1 Neuropsychopharmacology 2012 Jan;37(1):137-62
2 Brain, Behavior and Immunity 2013 Jul;31:1-8
3 Neurodegener Dis Manag. Dec 1, 2012; 2(6): 609–622
4 Psychosom Med. 2009 Feb;71(2):171-86
5 Translational Psychiatry (2014) 4, e344
6 Geriatric Bioscience (PDF)
7 Neuropsychiatr Dis Treat. 2011; 7: 431–439
8 BBC August 24, 2016
9 American Journal of Clinical Nutrition July 27, 2016, doi: 10.3945/ ajcn.116.134205
10 American Council on Science and Health August 1, 2016
11 Science Daily July 29k, 2016
12 Reuters August 24, 2016
13, 14 Journal of the American College of Nutrition 2011 Dec;30(6):502-10.
15 New England Journal of Medicine November 21, 2013: 369:2001-2011
16 NPR.org November 21, 2013
17 Time magazine November 20, 2013
18 Boston.com November 20, 2013
19 University of Maryland Medical Center, Omega-3 Fatty Acids
20 Omega-3 Institute, Differentiation of ALA (plant sources) from DHA + EPA (marine sources) as Dietary Omega-3 Fatty Acids for Human Health
21 NutraIngredients.com April 10, 2006Inflammation causes Depression, perhaps this is why vitamin D helps with depression – Sept 201313552 visitors, last modified 09 Oct, 2016, This page is in the following categories (# of items in each category) - The Single Vitamin That's a Double Whammy Against Both Depression and Dementia (Mercola) – Aug 2014