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"Vitamin D" - Marshall Protocol perspective
Probably the same could be said for vit A(normalization/deficiency of A as a contributor to IRIS):
Is vitamin D deficiency involved in the immune reconstitution inflammatory syndrome?
https://aidsrestherapy.biomedcentral.com/articles/10.1186/1742-6405-6-4
Background
About 20–30% of persons with HIV infection, especially those living in countries with limited resources, experience an immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral treatment. The active form of vitamin D, 1,25-dihydroxyvitamin D, is a key player in the clearance of pathogens and influences the level of inflammation and macrophage activation.
Presentation of the hypothesis
We hypothesize that low availability of 1,25-dihydroxyvitamin D, either due to vitamin D deficiency or due to polymorphisms in the vitamin D receptor or in its activating/inactivating enzymes, contributes to the appearance of IRIS. Furthermore, drug interactions with the enzymatic pathways of vitamin D could favour the development of IRIS.
Testing the hypothesis
Our hypothesis could be explored by a case-control study to assess the prevalence of vitamin D deficiency in HIV-infected patients on antiretroviral treatment who develop and do not develop IRIS.
Role of vitamin D locally at the inflammation site – example based on Mtb infection. 1,25-(OH)2D, the active form of vitamin D produced by macrophage-CYP27B1 at the inflammation site, has many local actions leading to a negative feedback loop avoiding macrophage overstimulation. 1,25-(OH)2D reduces T helper (Th1) lymphocyte-mediated macrophage activation, (a) by activating regulatory T-cells (Treg) which inhibit the activation of Th1 lymphocytes by antigen-presenting cells (APC) [36], (b) by directly inhibiting activation of Th1 lymphocytes and thus their interferon-γ (IFN-γ) production, and (c) by preventing antigen presentation by APC to Th1 lymphocytes [34]. 1,25-(OH)2D acts also directly on macrophages (d) by reducing expression of Toll-like receptor (TLR) to Mycobacterium tuberculosis (Mtb) [34], and (e) by inducing intracellular Mtb destruction via the cathelicidin-mediated system. If macrophages are overstimulated, high local level of 1,25-(OH)2D could lead to systemic spill over and thus hypercalcemia, as has been described in Mtb-IRIS [39], since no systemic negative feedback by the parathyroid axis exists on macrophage-1,25-hydroxylase (CYP27B1) [15].
Enhanced LL-37 expression following vitamin D supplementation in patients with cirrhosis and spontaneous bacterial peritonitis
https://pubmed.ncbi.nlm.nih.gov/26058412/
Background & aims: The morbidity and mortality of spontaneous bacterial peritonitis (SBP) are high among patients with cirrhosis; however, the mechanisms of SBP pathogenesis are poorly understood. This study aimed to determine the role of the vitamin D-LL-37 pathway in the pathogenesis and treatment in patients with cirrhosis and SBP.
Methods: Serum 25-hydroxyvitamin D concentrations of 119 patients with chronic liver diseases were tested. Vitamin D receptor (VDR) and LL-37 in peritoneal leucocytes of cirrhotic and ascitic patients with SBP were detected and compared with those without SBP. Then the peritoneal macrophages of non-infected patients were cultured and activated by lipopolysaccharide (LPS) to analyse the changes of VDR and LL-37 expressions after incubation with vitamin D.
Results: Vitamin D deficiency or insufficiency was found in all of patients with cirrhosis. LPS inhibited VDR and LL-37 expression in peritoneal macrophages [1.3-fold decrease (P = 0.003) and 20-fold decrease (P = 0.010) respectively]. However, vitamin D could reverse the inhibition of both VDR and LL-37 [1.5-fold increase (P = 0.001) and 2000-fold increase (P < 0.001) respectively]. The effect of the incubation time following vitamin D supplementation was significant for LL-37 expression, with a peak expression found at 36 h (P < 0.001).
Conclusions: When vitamin D levels were low, bacteria inhibited VDR and LL-37 responses in peritoneal macrophages as a mechanism to evade antibacterial defence. Vitamin D supplementation could up-regulate peritoneal macrophage VDR and LL-37 expressions, which resulted in an enhanced immunological defence against SBP in patients with cirrhosis and ascites.
Key points:
• All of patients with cirrhosis were in a state of vitamin D deficiency or insufficiency.
• Under low vitamin D circumstances, bacteria inhibited VDR and LL-37 responses in peritoneal macrophages as a mechanism to evade antibacterial defence.
• Vitamin D supplementation could reverse the inhibition effect of LPS to up-regulate peritoneal macrophage VDR and LL-37 expressions, which resulted in an enhanced immunological defence against SBP in patients with cirrhosis and ascites.
• The results of this study suggest that vitamin D could be an adjunct to antibiotic therapy in the prevention and treatment of SBP.
In our study, we found that in low vitamin D conditions, various concentrations of LPS down-regulated both VDR and LL-37. Pramanik et al. (30) also found that LPS could decrease VDR proteins levels and inhibit VDR functions in the human leukaemic cell line in the absence of 1,25(OH)2D3 stimuli. Furthermore, other researchers have reported that bacterial exotoxins down-regulate LL-37 expression in the intestinal epithelial cells (31) and Neisseria gonorrhoea down-regulated LL-37 expression in cervical epithelial cell line ME180 (32). We speculate that this may be a new bacterial mechanism against antibacterial immunity, which could explain the reasons why cirrhosis and ascites patients with low vitamin D levels are more likely to suffer from bacterial infections, which are often considered serious.
When vitamin D was sufficient, VDR and LL-37 were up-regulated in the peritoneal macrophages, indicating that appropriate levels of vitamin D are necessary for the complete functions of the vitamin D-VDR-LL-37 pathway. This pathway may be a mechanism against bacterial invasion. In particular, LL-37 expression improved with increased vitamin D, indicating that the LL-37 response was vitamin D concentration-dependent. These results are consistent with the results of Adams et al. (33). Furthermore, for the first time, we characterized the time-dependent effect of 1,25(OH)2D3 on LL-37 up-regulation. The maximum LL-37 expression under 1,25(OH)2D3 stimuli was found at 36 h.
Because LL-37 not only worked as a broad antibacterial effector but also had the effect of immunomodulation and chemotaxis, we hope to use it in the prevention and treatment of SBP. It has been shown that transient cutaneous adenoviral gene therapy with LL-37 was 10 times more effective for the treatment of burn wound infections than the administration of the LL-37 peptide in second-degree scald burn Sprague-Dawley rats (34). These results illustrated that increasing endogenous LL-37 expression was more efficient than the simple application of an antimicrobial peptide in terms of antibacterial immunity. Hata et al. designed a single-centre, controlled study of atopic dermatitis and showed that LL-37 in involved skin biopsy samples increased significantly following oral vitamin D supplementation at 4000 IU per day for 21 days (35). This result provided theoretical evidence for vitamin D supplementation, which was later applied to clinical treatment to improve the endogenous LL-37 in peritoneal macrophages against infectious diseases in the abdominal cavities in cirrhosis and ascites patients.
In conclusion, vitamin D deficiency as universal in patients with cirrhosis and ascites, and the degree of vitamin D deficiency was more severe with more serious liver diseases. When vitamin D levels are low, bacteria can inhibit the LL-37 response of peritoneal macrophages as a mechanism to evade antibacterial immune defence. However, this inhibition can be corrected by vitamin D supplementation (the higher concentration of vitamin D, the stronger the corrective activity). Therefore, adequate vitamin D is vital for the body to improve antimicrobial immune defence response. The results of this study suggest that vitamin D could be an adjunct to antibiotic therapy in the prevention and treatment of SBP. Our next step is to conduct animal experiments to investigate the effects of vitamin D and LL-37 on the prevention and treatment of SBP in a cirrhosis rat model.
...
Administration of oral vitamin D induces cathelicidin production in atopic individuals
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659525/
After supplementation with 4000 IU/d oral vitamin D for 21 days, AD lesional skin showed a statistically significant increase in cathelicidin expression from a median of 3.53 relative copy units (RCU) before supplementation to a median of 23.91 RCU post supplementation (P <.01; Fig 1).
Serum calcium and vitamin D levels were measured in atopic and normal subjects at baseline and after 3 weeks of supplementation with 4000 IU/d of oral vitamin D3. 4000 IU of vitamin D3 has been well documented to effectively increase 25-hydroxyvitamin D levels while maintaining normal serum calcium levels, suggesting that the current recommendation for vitamin D supplementation may be too conservative. Indeed, serum calcium in our normal control subjects did not rise but actually decreased from a median of 9.8 mg/dL to a median of 9.4 mg/dL post supplementation (P > .05). During this time, their serum 25-hydroxyvitamin D levels rose from a median of 24.5 mg/mL to 37 mg/mL (P > .05). Similarly, atopic subjects’ serum calcium levels also decreased from a median of 9.6 mg/dL to a median of 9.4 mg/dL post supplementation (P > .05), and their serum 25-hydroxyvitamin D levels rose from a median of 22.5 mg/mL to 35.5 mg/mL (P > .05). No subject complained of any adverse event during supplementation.
...
Vitamin D deficiency has been linked to increased rates of multiple cancers, autoimmune diseases, infectious diseases, cardiovascular diseases, and hypertension.8 We believe our study has shown that supplementation of oral vitamin D can result in correction of defects in cathelicidins in the innate immune system of atopic subjects.
Breast milk - mystery. It contains very little VE, VK, VB1, VB6, VB9. But tons of VA :/
Breast milk is a detox for the Mum (Dr Jenny Goodman environmental toxicology expert). Oldest child gets the most toxicity. We evolved in less toxic times. Breast milk now also contains heavy metals, pesticides etc.
Quote from Jenny on July 30, 2021, 8:40 amBreast milk is a detox for the Mum (Dr Jenny Goodman environmental toxicology expert). Oldest child gets the most toxicity. We evolved in less toxic times. Breast milk now also contains heavy metals, pesticides etc.
Interesting.
Looking at my family, I can say it seems to be the opposite in our case. Oldest brother never really had any health issues, never needed dental braces like me and my younger brother. Worst thing he had was poor vision once he hit adolescence. I also needed corrective lens. My younger brother did not.
I'm the middle child and seem to have had most of the health issues. I've had wild dreams ever sense I was young, eczema, RA, anxiety, raynauds, chronic fatigue.
My younger brother, aside from missing adult teeth, never really had any issues either.
Maybe my mom had my older brother and then thought about taking prenatal vitamins/etc before I was born. Not sure. But I was born with eczema.
Quote from Jenny on July 30, 2021, 8:40 amBreast milk is a detox for the Mum (Dr Jenny Goodman environmental toxicology expert).
> Dr Jenny Goodman environmental toxicology expert
plz avoid referencing any so called "health" "experts" - there is enough BS on other forums already
It's funny, I was thinking along those lines (be careful about giving them too much credit) for medical studies. Because if VA is really toxic, that is so foundational that we have to take almost anything the medical profession says with a grain of salt.
It's almost like a religion to believe that VA is good for you. You can't build a house on sand, you must build a house on rock.
For example: lets say they still believed (as many did in the olden days) that drinking all day was healthy. Even children did it. You woke up, had your morning draft of ale and made sure the wife was well provided with alcohol all day: it would make her work harder. Well, every study would be tainted with the fact that the people were poisoned with alcohol. They would make all sorts of excuses for the bad health --ANYTHING but the alcohol .
Quote from lil chick on July 31, 2021, 9:26 amIt's funny, I was thinking along those lines (be careful about giving them too much credit) for medical studies. Because if VA is really toxic, that is so foundational that we have to take almost anything the medical profession says with a grain of salt.
It's almost like a religion to believe that VA is good for you. You can't build a house on sand, you must build a house on rock.
For example: lets say they still believed (as many did in the olden days) that drinking all day was healthy. Even children did it. You woke up, had your morning draft of ale and made sure the wife was well provided with alcohol all day: it would make her work harder. Well, every study would be tainted with the fact that the people were poisoned with alcohol. They would make all sorts of excuses for the bad health --ANYTHING but the alcohol .
VA is toxic, I can assure you. Today I read a study:
"Aldehyde dehydrogenase (ALDH) is an enzyme that is expressed in the liver and is required for the conversion of retinol (vitamin A) to retinoic acids. ALDH is also highly enriched in hematopoietic stem cells (HSCs) and is considered a selectable marker of human HSCs, although its contribution to stem cell fate remains unknown. In this study, we demonstrate that ALDH is a key regulator of HSC differentiation. Inhibition of ALDH with diethylaminobenzaldehyde (DEAB) delayed the differentiation of human HSCs that otherwise occurred in response to cytokines. Moreover, short-term culture with DEAB caused a 3.4-fold expansion in the most primitive assayable human cells, the nonobese diabetic/severe combined immunodeficiency mouse repopulating cells, compared with day 0 CD34(+)CD38(-)lin(-) cells. The effects of DEAB on HSC differentiation could be reversed by the coadministration of the retinoic acid receptor agonist, all-trans-retinoic acid, suggesting that the ability of ALDH to generate retinoic acids is important in determining HSC fate. DEAB treatment also caused a decrease in retinoic acid receptor-mediated signaling within human HSCs, suggesting directly that inhibition of ALDH promotes HSC self-renewal via reduction of retinoic acid activity. Modulation of ALDH activity and retinoid signaling is a previously unrecognized and effective strategy to amplify human HSCs."
Are you seriously questioning my referencing of Dr Jenny Goodman? She is an expert in environmental toxicity. I have learnt a lot from her!!! There is a lot of bullshit out there. However, there is also some highly intelligent and highly educated people, with lifelong experience who are talking a lot of sense. She is the latter.
I have a very honed bullshit radar. I would never reference someone who hadn’t passed it.
Please share your opinions with kindness and respect. Your response was unnecessarily incredibly rude in my opinion. We are all trying to recover from toxicity here on this forum. One of the key things is to reduce stress. Rudeness is not required.
@rockarolla It’s fine to express skepticism towards authors like Dr. Goodman if that’s how you feel, but insulting another forum member’s intelligence in order to control discussion crosses the line from good-natured disagreement into bullying.