Vitamin D prevents cortisol-induced depression and...inflammation


Mar 18, 2013
USA / Europe
A great study for a number of reasons. First, it discussed openly that in animal research circles cortisol administration is considered an official and reliable method of causing major depression. As the article states, for some reason human medical circles have been unwilling to accept the stress-depression causal link and continue to argue that stress is just a risk factors that ultimately depends on genetic predispositions to actually cause depression.
More importantly, the study also demonstrated that oral vitamin D (D3, a.k.a. cholecalciferol) administration for just 7 days concurrently with the cortisol administration (which was given to cause the depression) was able to fully prevent the depressive symptoms. Another finding was that vitamin D administration was also able to upregulate the expression of the glucocorticoid receptors (GR), which were downregulated as a result of the chronic administration of cortisol. These findings suggest, yet again, that vitamin D acts as a direct glucocorticoid antagonist and corroborates it not only as a rapidly-acting antidepressant (which GR antagonists are known to be), but also as an anti-catabolic / anabolic substance. Let's just hope that FDA won't take action and either ban vitamin D3 (cholecalciferol) as an "unapproved drug", or put it in the category of prescription chemicals such as vitamin D2. The latter is know known to have only about 30% of the effects of vitamin D in equivalent doses and has a much higher risk of side effects such as kidney disease, hypercalcemia, etc.
But what's up with the contradictory title? Isn't cortisol a powerful anti-inflammatory steroid/treatment, as our doctors keep telling us? Well, as they say in the movies - "life is stranger than fiction", and so it seems to be in medicine as well. As the study explains, cortisol, while directly anti-inflammatory itself, sets the stage for a pro-inflammatory systemic response that starts even while cortisol is still being administered. So, at best cortisol is an inflammatory symptom "masker" with the trade-off of drastically higher inflammation down the road, even if cortisol administration continues! One of the likely mechanisms for cortisol's pro-inflammatory effects is that being a highly catabolic hormone, cortisol administration floods the blood stream with cellular / tissue debris and those are known to trigger potent inflammatory reactions that persist for as long as there is a sufficient amount of debris left in the bloodstream. In a sense, the systemic inflammatory response can never stop as long as cortisol is being administered, and the longer cortisol is administered the worse systemic health becomes.

Vitamin D Supplementation Ameliorates Severity of Major Depressive Disorder - PubMed
Effects of cholecalciferol on behavior and production of reactive oxygen species in female mice subjected to corticosterone-induced model of depression - PubMed
Cholecalciferol abolishes depressive-like behavior and hippocampal glucocorticoid receptor impairment induced by chronic corticosterone administration in mice - PubMed

"...Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric disorder that affects > 350 million people, causing a high personal and socioeconomic burden (World Health Organization, 2017). It is well reported that chronic stress and hypothalamic-pituitary-adrenal (HPA) axis dysfunction are risk factors for MDD (Goodyer et al., 2000; Nowacki et al., 2020). Chronic stress can induce increased levels of glucocorticoids, namely cortisol in humans and corticosterone in rodents, which may damage the hippocampus, a region that presents a high density of glucocorticoids receptor (GR) crucial for HPA axis autoregulation and mood modulation (Anacker et al., 2011; Lee et al., 2002)."

"...In keeping with these premises, exogenous corticosterone (CORT) administration in rodents has been proposed as a pharmacological stress model of depression that mimics the behavioral and neurochemical alterations associated with HPA dysfunction in the depressive state (Pazini et al., 2016; Rosa et al., 2014; Zhao et al., 2008). Despite the numerous studies reporting that chronic stress underlies the genesis of MDD, the mechanisms by which glucocorticoids contribute to the depressive symptoms have not been entirely established. Compelling evidence indicates that glucocorticoids may induce a peripheral and central pro-inflammatory state that involves the stimulation of the nod-like receptor pyrin domain containing 3 (NLRP3), an intracellular multiprotein complex responsible for the inflammatory response (Busillo et al., 2011; Kaufmann et al., 2017). Importantly, NLRP3-driven pro-inflammatory response culminates in neuronal damage and death remarkably in brain regions involved with mood modulation, and these events are thought to underlie depressive symptoms (Miller et al., 2009)."

"...In the present study, we showed that a low dose of cholecalciferol abrogates the depressive- and anhedonic-like behavior induced by chronic corticosterone administration, confirming a previous study from our group (Camargo et al., 2018). We extend these findings providing evidence that these behavioral effects were accompanied by the reestablishment of GR immunocontent impaired by corticosterone. Additionally, the ability of cholecalciferol in reducing NLRP3 inflammasome-related proteins ASC, TXNIP, and caspase-1 in the hippocampus of mice was also demonstrated."

"... In the present study, we reinforced the notion that repeated administration of cholecalciferol (2.5 μg/kg, p.o.) for 7 days is effective to reduce the immobility time, in a way similar to fluoxetine, in vehicle-treated mice submitted to the TST (Camargo et al., 2018; Souza et al., 2020). We also showed the cholecalciferol's ability to prevent corticosterone-induced depressivelike behavior evaluated in the TST, when administered in the last 7 days of corticosterone protocol. This result agrees with previous reports of our research group carried out in male Swiss mice (Camargo et al., 2018) and female Swiss mice (Souza et al., 2020). Of note, previous studies showed that administration of cholecalciferol (5 mg/kg, s.c.) or α-calcidiol (1 μg/kg, p.o.) caused an antidepressant-like effect in the forced swim test in rodents (Fedotova et al., 2016; Kawaura et al., 2017), in agreement with our results."

"...Collectively, our results show that repeated administration of cholecalciferol has an antidepressant-like effect, confirming previous findings (Camargo et al., 2018; Fedotova et al., 2016; Kawaura et al., 2017; Souza et al., 2020), an effect associated with the reestablishment of hippocampal GR immunocontent impaired by chronic corticosterone administration. Although we did not ascertain the causal relationship between GR and behavioral outcomes, further experiments could be carried out in future studies to shed light on this issue."
Similar threads
Thread starter Title Forum Replies Date
H DHEA Alters Vitamin E Status Prevents Lipid Peroxidation In Vitamin E-Deficient Rats DHEA 0
B Landmark Study - Vitamin B3 Aka Niacin Aka NAD Prevents Miscarriages And Birth Defects Scientific Studies 3
P Vitamin B3 Modulates Mitochondrial Vulnerability And Prevents Glaucoma In Aged Mice Articles & Scientific Studies 0
R Vitamin E Prevents Exercise-induced DNA Damage Scientific Studies 1
P Vitamin B3/NAD Fully Prevents The Development Of Glaucoma In Mice And Halts Its Progression If Alrea Scientific Studies 16
Drareg Vitamin K Prevents Oxidative Cell Death By Inhibiting Activation Of 12-lipoxygenase In Developing Ol Scientific Studies 0
DaveFoster Vitamin C Prevents Lipid Peroxidation Scientific Studies 5
G Vitamin B3 Prevents And Reverses Skin Cancer Cancer 2
J Vitamin E Prevents Calcium Oxalate Stones Articles & Scientific Studies 1
D Vitamin D Always High! Blood Work, Labs 7
Q Is Vitamin D induced serotonin syndrome possible? Please hear me out... Ask For Help or Advice 47
T VItamin D Megadose accident, what to do Supplements, Pharmaceutical Drugs 6
N Home made vitamin D... Supplements, Pharmaceutical Drugs 1
bzmazu Why politicians and doctors keep ignoring the medical research on Vitamin D and Covid Rant or Rave 2
S I think vitamin K2 ruined my life. Vitamins 75
S Fluorescent pee after b vitamin supp, Normal?! Ask For Help or Advice 15
Hirri Suddenly lower Vitamin D question Vitamins 9
Pistachio Vitamin K2's effect on Lunulae (fingernail crescents) Supplements, Pharmaceutical Drugs 0
Ras How can Vitamin K2 MK-4 be Price's Activator X? K 10
R Interesting podcast on dangers of vitamin E supplementation E 1
Mauritio Cistanche more effective at decreasing lipid peroxidation and free radicals than Vitamin E and Caffeine Science 29
J Vitamin d powder Ask For Help or Advice 8
Mito The efficacy of Vitamin K in the treatment of cancer K 1
Brandin vitamin e to balance eggs pufa. Polyunsaturated Fats, Seed Oils 15
G How many of you have gotten Vitamin D injections? D 10
Mito Vitamin D Supplementation Ameliorates Metabolic Dysfunction in Patients with PCOS D 0
deliciousfruit Does liver from grain-fed animals contain vitamin A? Meat, Organ Meat, Gelatin, Seafood 2
C Vitamin D lamp? D 17
M Vitamin D3 makes me feel cold D 16
Lokzo Vitamin B6 Increases Serotonin, Regardless of Serotonin Levels - PUBMED Supplements, Pharmaceutical Drugs 2
P Vitamin B12 Facilitates the Retroconversion of Estrogens into Androgens by Bacteria Scientific Studies 3
R Is vitamin K2 required when taking Vitamin D? Vitamins 16
Charger Blunted Emotions from Vitamin K2? K 8
bzmazu Hey Drinkers....The case for Vitamin-Enriched Alcohol Alcohol, Tobacco, Drugs 3
Mito The efficacy of vitamin E in reducing non-alcoholic fatty liver disease E 0
ecstatichamster how do you oxidize vitamin C safely? C 8
Mito The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification K 0
haidut Fasting ups estrogen & cortisol, decimates vitamin D, may cause diabetes Scientific Studies 11
haidut Vitamin D is anti-catabolic / anabolic, protects liver from cortisol injury Scientific Studies 2
metabolizm Vitamin D Supplementation is Improving my Sleep D 23
Lokzo This B-Vitamin Can Raise Dopamine (Thiamine tetrahydrofurfuryl disulfide - TTFD) Supplements, Pharmaceutical Drugs 58
A Cheap Vitamin C products, any contamination risk? Ask For Help or Advice 8
J Interesting study claims Vitamin K2 should be classified as a hormone Supplements, Pharmaceutical Drugs 9
Lokzo The Ameliorating Effects Of Vitamin E On Hepatotoxicity Of Ecstasy Scientific Studies 0
M I’m Not Convinced Vitamin D Should Be Supplemented D 152
Mito 7-fold Higher COVID-19 Mortality In Vitamin D Deficient Subjects D 2
ursidae How To Make Vitamin D Work? Ask For Help or Advice 52
A Pufa Detox - Vitamin E Polyunsaturated Fats, Seed Oils 6
ddjd Is Vitamin A (retinol Palmitate/acetate) Dangerous During Pregnency? Ask For Help or Advice 1
Mito Vitamin D Supplementation During Winter: Effects On Stress Resilience D 10

Similar threads