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PubMed research papers
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415385/pdf/nihms858446.pdf
References a study that links RBP4 to macrophage foam-cell formation, experimental atherosclerosis and human CVD risk. It's interesting how obvious things are when Dr. Silverstein, a senior investigator at the Blood Research Institute at the Medical College of Wisconsin's Blood Center, comments on the Liu, et.al., paper titled Retinol Binding Protein-Dependent Cholesterol Uptake Regulates Macrophage Foam Cell Formation and Promotes Atherosclerosis. He says, "This study also suggests that macrophage derived RBP4 acts ….". That was a full-stop for me, especially in that the rest of what he narrates, in this mini-review of 8 papers, doesn't ask the essential question: Why is the macrophage cell creating Retinol Binding Protein in the first place?
His last paragraph gives it away. More questions, more study, and "potential targets for therapeutic intervention".
J Diabetes Res. 2018 Aug
Involvement of RBP4 in Diabetic Atherosclerosis and the Role of Vitamin D Intervention.
The purposes of this study were to evaluate the expression of retinol-binding protein 4 (RBP4) in diabetic rats with atherosclerosis and to investigate the role of vitamin D intervention.
After 8 weeks of vitamin D supplementation in group DM3, the levels of 25(OH)D and HOMA-β increased and the levels of LDL-c, TC, HOMA-IR, FINS, CRP, RBP4, AI1, AI2, and SBP decreased significantly when compared with group DM2 (P < 0.05); Pearson analysis showed that serum RBP4 was positively correlated with TG, FINS, HOMA-IR, SBP, CRP, and AI and negatively correlated with 25(OH)D.
In addition, multivariable logistic regression analysis showed that serum RBP4, SBP, and HDL-c were predictors for the presence of diabetic atherosclerosis. These findings suggested that RBP4 could involve in the improvement of diabetic atherosclerosis; vitamin D had the ability to decrease the level of RBP4 and eventually played an important role in preventing atherosclerosis in diabetes. PMID:30186876 Free PMC Article
Wonder if hormone-D helps drive retinol lower, thus less need for RBP4? That's probably way too simple, considering the complexity of lipid-metabolism, but it is interesting that here again, it's all about RBP4 and not retinol. What's up with that? Would it be too out-there to think that RBP4 is a code-word for retinol in some of these studies? Guess I need to go look for studies that correlate both of them in some fashion.
I plan to do the serum-RBP4 test each time I do a serum-retinol, just to see if there's a pattern over time. I got my D3-level up to 52 ng/ml in one month and am tapering into the 60-80 level with lower dosing, so the next retinol/rbp4 tests should be kind of interesting on the question of whether D3 has an impactful effect for me.
J Clin Med. 2019
Plasma Levels of Retinol Binding Protein 4 Relate to Large VLDL and Small LDL Particles in Subjects with and without Type 2 Diabetes.
Retinol binding protein 4 (RBP4) carries retinol in plasma, but is also considered an adipokine, as it is implicated in insulin resistance in mice. Plasma RBP4 correlates with total cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides, and may confer increased cardiovascular risk. However, controversy exists about circulating RPB4 levels in type 2 diabetes mellitus (T2DM) and obesity. Here, we analyzed the relationships of RBP4 and retinol with lipoprotein subfractions in subjects with and without T2DM.
RESULTS:
Plasma RBP4 and retinol were strongly correlated (r = 0.881, p < 0.001). RBP4, retinol and the RBP4/retinol ratio were not different between T2DM and non-diabetic subjects (all p > 0.12), and were unrelated to body mass index. Notably, RBP4 and retinol were elevated in subjects with metabolic syndrome (p < 0.05), which was attributable to an association with elevated triglycerides (p = 0.013). Large VLDL, total LDL and small LDL were increased in T2DM subjects (p = 0.035 to 0.003).
Taking all subjects together, RBP4 correlated with total cholesterol, non-HDL cholesterol, LDL cholesterol, triglycerides and apolipoprotein B in univariate analysis (p < 0.001 for each). Age-, sex- and diabetes status-adjusted multivariable linear regression analysis revealed that RBP4 was independently associated with large VLDL (β = 0.444, p = 0.005) and small LDL particles (β = 0.539, p < 0.001). Its relationship with large VLDL remained after further adjustment for retinol. RBP4 did not co-elute with VLDL nor LDL particles in FPLC analyses.
CONCLUSIONS:
Plasma RBP4 levels are related to but do not physically interact with large VLDL and small LDL particles. Elevated RBP4 may contribute to a proatherogenic plasma lipoprotein profile.
PMID:31717719
@hillcountry Are you feeling better this last month with the higher D3 level? I've been trying to raise mine, which is extremely low with the Sperti Vitamin d lamp, but continue to get such horrible detox it's miserable! Are you experiencing detox with high dose oral D3?
that first study is interesting, just lowering the retinol bind ing protein s would be bad right? But, could that be the horrible detox reactions to the sun? Without the retinol wrapped up it would be able to real havoc. Or maybe I'm not understanding the study. That's why I was wondering about the effect of oral Vit D -you are trying the high dose method correct?
Thanks!
Quote from Curious Observer on March 7, 2020, 2:58 pm@hillcountry Are you feeling better this last month with the higher D3 level? I've been trying to raise mine, which is extremely low with the Sperti Vitamin d lamp, but continue to get such horrible detox it's miserable! Are you experiencing detox with high dose oral D3?
that first study is interesting, just lowering the retinol bind ing protein s would be bad right? But, could that be the horrible detox reactions to the sun? Without the retinol wrapped up it would be able to real havoc. Or maybe I'm not understanding the study. That's why I was wondering about the effect of oral Vit D -you are trying the high dose method correct?
Thanks!
Hi Curious Observer - sorry to hear of your reactions to the light. Yes, I've had better sleep and energy levels, and overall mood is up, almost cheery in fact. Normally I'd be on-the-edge by this time of year. No detox noted so far. My dose was 15,000 IU, which took me from 19 ng/ml to 52 ng/ml in 5 weeks. I took the dose down to 5,000 IU the other day, for this next month, and I'll test again in April, with another dose-reduction based on those results. I think the high-dose B-50 complex is too much for my system, so I've been playing around with that part of the Dr. Gominak protocol.
The way I'm reading the studies about RBP4 is more of a between-the-lines approach. I think researchers uncover useful data and then tend to misinterpret it, or just plain miss the elephant in the room. So, I'm not really sure about the meaning (or validity) of their observation/contention that Vitamin D decreases RBP4. I'm still looking for confirmation that Vitamin D3 is doing something major to help handle or mitigate our retinoid-load. I'm hoping consistent blood-testing might point that way.
As for detox reactions to sunlight, I think Grant has covered a lot of that somewhere. I don't know that bound or unbound is the main issue, but more the absorption of wavelengths and thermal effects. I don't even know if it's more of a retinol or retinoic acid thing with skin reactions. Grant could much better elucidate on that part of the toxicity, but I get your logic that less RBP4 doesn't seem like a positive. And that's not to mention that we don't really know what a serum-RBP4 level is really telling us, particularly when RBP4 is created inside of cells, likely to protect themselves from our favorite molecule. When they measure it in the serum, does it always have retinol bound inside it? Is there such a thing as un-liganded RBP4? As always, there's a lot more that I don't know about this subject, than what I do. I find myself mostly looking for discrepancies and potential clues. I'll sign off for now and keep on sleuthing in the stacks for something useful.
Epstein-Barr Virus Lytic Infection Induces Retinoic Acid-responsive Genes through Induction of a Retinol-metabolizing Enzyme, DHRS9
https://www.sciencedirect.com/science/article/pii/S002192582063842X
Lytic Epstein-Barr virus (EBV) replication occurs in differentiated, but not undifferentiated, epithelial cells. Retinoic acid (RA) induces epithelial cell differentiation. The conversion of retinol into its active form, retinoic acid, requires retinol dehydrogenase enzymes. Here we show that AGS gastric carcinoma cells containing the lytic form of EBV infection have enhanced expression of a gene (DHRS9) encoding an enzyme that mediates conversion of retinol into RA. DHRS9 expression is also increased following induction of lytic viral infection in EBV-positive Burkitt lymphoma cells. We demonstrate that the EBV immediate-early protein, BZLF1, activates the DHRS9 promoter through a direct DNA binding mechanism. Furthermore, BZLF1 expression in AGS cells is sufficient to activate DHRS9 gene expression and increases the ability of retinol to induce the RA-responsive gene, CYP26A1. Production of RA during the lytic form of EBV infection may enhance viral replication by promoting keratinocyte differentiation.
[..]
Given the critical roles that RA plays in cell growth and differentiation, it is not surprising that a variety of viruses are regulated by RA and/or have developed mechanisms for regulating RA signaling (6). For example, treatment of undifferentiated human embryonal carcinoma cells with RA results in the cells becoming permissive for cytomegalovirus (CMV) infection (7, 8).
[..]
Most importantly, we show that BZLF1 dramatically enhances the ability of retinol to activate the RA-dependent cellular gene, CYP26A1, in cells. These results suggest that EBV has hijacked the retinol metabolizing machinery to promote cellular differentiation and thus favor lytic viral replication.
[..]
In this report, we demonstrate that an Epstein-Barr virus lytic protein, BZLF1, enhances expression of DHRS9 and increases the ability of retinol to active RA-responsive cellular genes. As EBV lytic replication is induced by epithelial cell differentiation (17), this ability of the virus to stimulate RA production presumably helps the virus to promote its own replication.
[..]
Given the close association between efficient lytic EBV infection and epithelial cell differentiation, our finding that the EBV IE viral protein, BZLF1, enhances expression of a retinol metabolizing enzyme is particularly interesting and relevant to viral pathogenesis. By increasing DHRS9 expression, the virus likely increases the amount of cellular retinoic acid and thus enhances transcription of retinoic acid-responsive genes. In support of this, our results in AGS cells showed that BZLF1 greatly increases the ability of retinol to induce a well known RA target gene, CYP26A1. Enhanced production of RA in virally infected cells may allow EBV to replicate more efficiently by promoting epithelial cell differentiation. In addition, RA released from virally infected cells could potentially affect neighboring cells through a paracrine mechanism, promoting their differentiation and enhancing cell to cell spread of virus.
In addition to promoting lytic viral replication in epithelial cells, BZLF1 induction of DHRS9 gene expression may also promote lytic EBV replication in B cells.
The ability of BZLF1 to enhance retinol-mediated expression of the cytochrome P450 enzyme, CYP26A1, may also benefit the virus by inhibiting cellular apoptosis and preventing early death of the host cell before infectious viral particles can be released. CYP26A1 has been shown to protect cells from an array of apoptotic stimuli including TRAIL, oxidative stress, genotoxic drugs, and γ-irradiation (44). Furthermore, elevated levels of CYP26A1 are found in cancers such as acute promyelocytic leukemia (45) and squamous cell carcinomas of the head and neck (46).
[Chronic fatigue syndrome associated with Epstein-Barr virus infection]
https://pubmed.ncbi.nlm.nih.gov/2545980/
Epstein-Barr virus (EBV) infection is ubiquitous and may result in multiple and widely different clinical features; the most common of these is infectious mononucleosis (IM). Recently, a group of patients has been included in the chronic EBV infection syndrome (EBVIS), with a sustained nonspecific syndrome consisting of asthenia, anorexia, low grade fever and changes in mood, associated with a viral infection not necessarily caused by EBV; this has been called chronic fatigue syndrome (CFS). We report a patient who fulfilled the criteria for CFS associated with EBV after an acute, well documented EBV infection. We discuss its etiological and pathophysiological implications, emphasizing the need for extreme caution in the diagnosis of CFS. A merely clinical diagnosis may hide severe mistakes.
@rockarolla So because I take 4x250mg of apolactoferrin and I feel nothing I really want to try low dose antibiotics. So what type should I buy from this website? https://lekarna-eshop.com/antibiotika
Howdy y'all - hope everyone is hale and hearty!!
Imagine the implications of this one. Haven't had time to cross-reference it with confirmatory studies but sure will soon.
PMID: 26620317
Not sure if there's a better place for this video, but we just finished watching it and I thought it timely. We've been supporting the FLCCC Alliance and spreading the word about their work for quite a while now.
https://odysee.com/@FrontlineCovid19CriticalCareAlliance:c/FLCCC-WEBINAR-120121_FINAL:f
Hi @hillcountry,
Thanks for sharing that. I think it's an important finding.
Here's a related paper:
Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503269/
Quote from Jiří on November 26, 2021, 11:54 pmI really want to try low dose antibiotics.
Check out this 2 links:
https://web.archive.org/web/20130713102749/http://mpkb.org/home/protocol/mp_antibiotics
https://web.archive.org/web/20130624190613/http://mpkb.org:80/home/protocol/mp_antibiotics/dosing
Additionally 100mg minocycline could be overkill - I'd limit it by 10mg..25mg every 2..4 days, as for other abx .. azithromycin could be limited by 40..60mg every 8..12 days and clindamycin by up to 75mg every 2..4 days
Micro dosing like this will not damage/inhibit your immune system to fight persistent infections while being enough to keep on cleaning out bugs from leukocytes(they got constantly re-infected).