Quote from Jenny on October 13, 2020, 10:59 am

I am just like the rats. I can clearly see now how I poisoned myself with vA & this resulted in weight gain. Then I calmed the vA down & weight became stable (I never lost the extra weight gained). Then summer 2018 I supplemented vA again & weight shot up. Very clear correlation. I could never understand it. It seemed so illogical & unfair. 

2 years low vA & my weight is slowly reducing back to pre-poisoning days. Thank you Grant for providing the answer for me. 

Quote from r on October 14, 2020, 1:39 am

we should try to bring these researchers in this forum , would greatly help us and they would also have lot of experimental data here from people who are trying this diet  

Quote from rockarolla on March 19, 2021, 3:15 pm

steroidal effect.. weight gain just like from corticosteroids or antidepressants 

Quote from Navn on March 20, 2021, 3:50 am

@ rockarolla  , does this means it is more of water weight ? I had taken a very high dose of dexamethasone in the past and put on a lot of weight , after the dose was reduced very slowly I was given lasix to get rid of the water weight . 

Quote from rockarolla on March 20, 2021, 10:50 am

Quote from Navn on March 20, 2021, 3:50 am

@ rockarolla  , does this means it is more of water weight ? I had taken a very high dose of dexamethasone in the past and put on a lot of weight , after the dose was reduced very slowly I was given lasix to get rid of the water weight . 

probably - could be a mix of water and fat

when  corticosteroids or antidepressants block TLR receptors the immune cells start to compete far less for glucose leading to its upregulated conversion into fats and fat deposits partly because of the chronically full liver glycogen deposits.

also gaining weight and inability to drop it is one if the first signs of chronic unproductive inflammation and inhibited immune system.

At the end, feeding of the vitamin A-enriched diet resulted in increased body weight gain/obesity and retroperitoneal white adipose tissue (RPWAT)

https://pubmed.ncbi.nlm.nih.gov/23086657/
Our results showed that retinol suppressed the expression of various inflammatory cytokines in bone marrow-derived macrophages stimulated with ligands of TLR2, TLR3, or TLR4. 

Antidepressants normalize elevated Toll-like receptor profile in major depressive disorder
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828490/
Abnormalities in Toll-like receptor (TLR) expression in depression have been inferred in part from observed increases in TLR4 levels in peripheral blood mononuclear cells (PBMCs) and postmortem brains of depressed and suicidal patients. Our previous study found differences in the TLR expression in PBMCs between healthy controls and patients with major depressive disorder. Normalization of increased TLR4 in PBMCs by cognitive behavior psychotherapy has been reported.
...
TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9 were expressed at elevated levels in patients with MDD(major depressive disorder) and were significantly decreased by treatment with antidepressants for 4 weeks. Antidepressant treatment completely normalized TLR3, TLR5, TLR7, TLR8, and TLR9 levels, whereas TLR1, TLR2, TLR4, and TLR6 were decreased to below normal levels.
...
These findings suggest that antidepressant treatment exerts anti-inflammatory effects in patients with MDD(major depressive disorder) and identify TLR profiles as a predictor of response to antidepressant therapy. Further studies investigating the effects of manipulating individual TLRs on depression are needed to fully elucidate the underlying mechanism.
...
This study has provided novel insights into relationships among TLR expression, antidepressants, and clinical response for a well-characterized MDD. Beyond confirming that the expression levels of certain TLRs are decreased in PBMCs among MDD patients, we have also described—to the best of our knowledge for the first time—distinctive effects of antidepressants on TLRs. In summary, the observed decrease in TLR expression and its association with treatment outcome in depressive patients implies a link between inflammation, depression, and treatment. Further animal studies are needed to test antidepressive effects using antagonists of specific TLRs.

 

Glucocorticoids downregulate TLR4 signaling activity via its direct targeting by miR-511-5p
https://pubmed.ncbi.nlm.nih.gov/28776644/

https://journals.sagepub.com/doi/10.1177/1721727X17721829?icid=int.sj-full-text.similar-articles.1
This revealed that dexamethasone treatment can significantly reduce the expression levels of TLR4 and MyD88. 

Anti-inflammatory effect of lycopene on endotoxin-induced uveitis in rats
https://pubmed.ncbi.nlm.nih.gov/28076559/

Methods:: Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS) [TLR4 agonist]. Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically.

Results:: Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone.

 

Quote from Navn on March 20, 2021, 11:18 am

Thanks , I went back to my original weight pretty quickly then , but that was 30 years ago ! Now at 55 although I have lost significant edema which came with the A supplements , I need to loose a few more pounds 

Quote from rockarolla on June 3, 2021, 4:12 pm

Retinoic acid as a proxy steroid(acts as an alternative to obesity-inducing dex and pred):

Effect of retinoic acid on human adrenal corticosteroid synthesis
https://www.sciencedirect.com/science/article/pii/S0024320516301771

Aims

Retinoic acid has recently yielded promising results in the treatment of Cushing's disease, i.e., excess cortisol secretion due to a pituitary corticotropin (ACTH)-secreting adenoma. In addition to its effect on the tumoral corticotrope cell, clinical results suggest an additional adrenal site of action. Aim of this study was to evaluate whether retinoic acid modulates cortisol synthesis and secretion by human adrenals in vitro.

Main methods

Primary cultures from 10 human adrenals specimens were incubated with 10 nM, 100 nM and 1 μM retinoic acid with and without 10 nM ACTH for 24 h. Cortisol levels were measured by radioimmunoassay and CYP11A1, STAR and MC2R gene expression analyzed by real-time PCR.

Key findings

Retinoic acid increased cortisol secretion (149.5 ± 33.01%, 151.3 ± 49.45% and 129.3 ± 8.32% control secretion for 10 nM, 100 nM and 1 μM respectively, p < 0.05) and potentiated STAR expression (1.51 ± 0.22, 1.56 ± 0.15 and 1.59 ± 0.14 fold change over baseline, for 10 nM, 100 nM and 1 μM respectively, p < 0.05). Concurrently, retinoic acid markedly blunted constitutional and ACTH-induced MC2R expression (0.66 ± 0.11, 0.62 ± 0.08 and 0.53 ± 0.07 fold change over baseline, for 10 nM, 100 nM and 1 μM respectively, p < 0.05; 0.71 ± 0.10, 0.51 ± 0.07 and 0.51 ± 0.08 fold change over ACTH alone, for 10 nM, 100 nM and 1 μM respectively, p < 0.05). No effect on CYP11A1 was observed.

https://www.medchemexpress.com/Prednisolone.html
[..]Prednisolone is a potent, orally active corticosteroid and a glucocorticoid. Prednisolone possesses about four times the anti-inflammatory activity of hydrocortisone[..]

https://hmdb.ca/metabolites/HMDB0014998
[..]Prednisolone is a glucocorticoid receptor agonist.[..]

https://en.wikipedia.org/wiki/Glucocorticoid
Dexamethasone - a synthetic glucocorticoid binds more powerfully to the glucocorticoid receptor than cortisol does.

Quote from ggenereux on June 3, 2021, 8:10 pm

Thanks for sharing this information. 

A common treatment given for eczema, and other inflammatory diseases are the corticosteroids. 

They work great in suppressing the symptoms; I know this from first hand experience. However, with longer term use they can be a disaster. When my doctor prescribed corticosteroids, he warned me to go easy with it as they can have long term “side-effects”. What he did not tell me is that one of the more common known “side-effects” is cancer.

What’s also interesting is that corticosteroids bind to the same hormone receptors as do vit A and vit D. So, I think their real mechanism of action is to rate limit the uptake of vit A into the cell. 

In a crisis situation the corticosteroids could be used to buy time. It functions by suppressing the aggressive immune response and thus allowing the tissue to heal (somewhat). However, prolonged “suppression” of the immune response can obviously lead to cancer.

I also have no doubt that elevated cortisol levels is why I experience the weird chronic fatigue / insomnia; that of being dead tired and still not able to sleep. Seeing that cortisol secretion is increased with retinoic acids explains that chronic fatigue / insomnia and  I guess in an indirect way, it sure points to cancer causation too.

So, it's hard for me to agree with their claim of: "Retinoic acid has recently yielded promising results"

 

Quote from Orion on June 4, 2021, 8:40 am

This also sheds some light on how after accutane my sleep has never returned to normal.