Thread by @GPR109A

“It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms.”

ncbi.nlm.nih.gov/pmc/articles/P…

^ "Next, carbamoyl phosphate synthetase and ATP convert carbamate to carbamoyl phosphate. This enzymatic reaction is activated by N-acetyl glutamine, which is a metabolite of the amino acid glutamine”

ncbi.nlm.nih.gov/pmc/articles/P…

“In addition to our findings of changes of urea cycle and glucose metabolism in COVID-19, Shen et. al. uncovered dysregulated metabolites in lipid metabolism, suggesting their significant regulation in signal transduction and immune activation process [9]. Kimhofer et al. also…

… determined the metabolic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on human blood plasma using multiplatform metabolic phenotyping. They also observed key discriminant metabolites including elevated α-1-acid glycoprotein and an…

… increased kynurenine/ tryptophan ratio (low niacin) in COVID-19 patients, indicating that liver dysfunction was one of the potential pathological mechanisms [31]. In another study on plasma metabolomic and lipidomic alterations associated with COVID-19, carbamoyl…

… phosphatase, which participates in the urea cycle, was shown to be reduced in patients [36]. This finding is particularly consistent with our finding that the level of citrulline, which is formed from carbamoyl phosphate, was significantly downregulated in mild and severe…

… patients. These data collectively indicated that the dysregulated urea cycle was involved in the potential pathological mechanisms of COVID-19 disease progression.”

erj.ersjournals.com/content/early/…

^ Yuuuup!

^ Don’t make me do diabetes next…. #epitwitter and #medtwitter would literally explode…. Should I?

71.5% difference in the incidence of diabetes between those with higher versus lower N-acetglutamine (2nd to only low LDL)
...
“In Aalen additive hazard models, the greatest differences in incident type 2 diabetes rates comparing the 90th to the 10th percentiles of metabolites...

... distributions were observed for small LDL in the lipoprotein particles subclasses and contents group (78.19 [16.82, 139.56]); for N-acetylglutamine in the amino acids group (− 71.46 [− 109.9, − 33.01]); for acetone in the energy metabolism group (72.26 [29.49, 115.03]);...

... for trimethylamines in the products of bacterial co-metabolism group (− 68.58 [− 112.14, − 25.01]); and for albumin in the fluid balance group (− 70.49 [− 116.19, − 24.78])”

ncbi.nlm.nih.gov/pmc/articles/P…

Triglycerides 3rd, HDL 4th

...

Again: N-acetylglutamine in fact holds the second-highest independent influence on diabetes....

Low N-acetylglutamine levels have more independent influence on predicting diabetes than triglycerides (VLDL cholesterol) and than HDL; only less than small LDL numerically speaking..

... “Immediate-release niacin has been shown to significantly decrease small LDL-P.”

medscape.com/viewarticle/71…

...

... “Nicotinic acid reduces the production of triglycerides and VLDL (very low-density lipoprotein, which is converted to LDL in the blood).”

stlukesonline.org/health-service…

...

... “Niacin has more moderate LDL cholesterol-lowering efficacy, but this change is associated with an increase in LDL particle size and a shift from small LDL to the less atherogenic, large LDL subclasses”

pubmed.ncbi.nlm.nih.gov/15539965/

...

^ Again: From order of most influence on incident diabetes to least of the top 4:

#1 more Small LDL (78.2%)
#2 more N-acetylglutamine (-71.5%)
#3 higher VLDL triglycerides (56.6%)
#4 higher (medium) HDL (-46.4%)

...

... "This meta-analysis involved 2,110 patients with T2DM from 8 RCTs across a wide range of patients’ characteristics. The results of this study suggested that niacin supplementation significantly reduced TC, TG, & LDL, and increased the level of HDL"
journals.lww.com/md-journal/ful…
...

Effect of FLUSH niacin supplementation on

triglycerides -37%

low-density lipoprotein -42%

high-density lipoprotein +33%

plasma glucose [null; but with 3.5x NAG + flush niacin will improve, along with HOMA-IR rapidly, as well as more so the other three]

Shall I keep going?

High triglyceride to HDL-cholesterol ratio as a biochemical marker of severe outcomes in COVID-19 patients
clinicalnutritionespen.com/article/S2405-…

Low HDL and high triglycerides predict COVID-19 severity
nature.com/articles/s4159…

Triglyceride/High-Density Lipoprotein Cholesterol Ratio is Associated with the Mortality of COVID-19
dovepress.com/triglyceridehi…

High-density lipoproteins may play a crucial role in COVID-19
virologyj.biomedcentral.com/articles/10.11…

HDL cholesterol levels and susceptibility to COVID-19
thelancet.com/journals/ebiom…

Causal Inference for Genetically Determined Levels of High-Density Lipoprotein Cholesterol and Risk of Infectious Disease
ahajournals.org/doi/10.1161/AT…

“This meta-analysis involved 2,110 patients with T2DM from 8 RCTs across a wide range of patients’ characteristics. The results of this study suggested that niacin supplementation significantly reduced TC, TG, & LDL, and increased the level of HDL.”

journals.lww.com/md-journal/ful…

“Niacin use significantly increased HDL-C by 29% and 29% and decreased triglycerides by 23% and 28% and LDL-C by 8% and 9%, respectively, in participants with and without diabetes.”

jamanetwork.com/journals/jama/…

“niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q < 0.01; LDL-C − 20%, q < 0.01; and triglyceride − 15%, q = 0.1)”

Effect of niacin monotherapy on high density lipoprotein composition and function
lipidworld.biomedcentral.com/articles/10.11…

“niacin retains an FDA-approved indication as monotherapy for treating dyslipidemia, a main risk factor for cardiovascular events & myocardial infarction”

Stratified meta-analysis showed an association of niacin monotherapy with reduction of some cardiovascular events among...

... patients WITHOUT statins (acute coronary syndrome: relative risk, 0.68; 95% CI, 0.58-0.96; stroke: 0.69; 95% CI, 0.59-0.94; revascularization: 0.51; 95% CI, 0.37-0.72). These results were mainly derived from 2 trials conducted in the 1970s and 1980s”

jamanetwork.com/journals/jaman…

“Our study concludes that lipid-modifying dosages of niacin can be safely used in patients with diabetes and that niacin should be used for patients with diabetes to sufficiently correct hypertriglyceridemia or low HDL-C levels.”

read.qxmd.com/read/10979113/…

"concluded from many clinical trials using statins, lowering LDL-C alone is no longer regarded to be sufficient to treat CVD
comprehensive lipid management, in which raising HDL is an important target, a new standard. Niacin is UNSURPASSED in raising HDL”

ahajournals.org/doi/10.1161/at…

"Here, we demonstrated that oral supplementation of niacin resulted in a significant reduction in body weight and fat mass without affecting food intake in highfat diet-fed”

"Additionally, we demonstrated that niacin treatment stimulated thermogenesis in brown adipose tissue...

... induction of thermogenic genes via GPR109A”

“GPR109A deficient animals display obesity”

"niacin exhibited a MARKEDLY decrease in HOMA-IR values, suggesting the beneficial role of niacin in insulin sensitivity"

papers.ssrn.com/sol3/papers.cf…

“The findings suggest that niacin exerts beneficial effect on adiposity, glucose tolerance and insulin sensitivity, and plasma lipids, and that it specifically modulates the level of serum adiponectin under obese condition.”

sciencedirect.com/science/articl…

“Our research demonstrated that intake of niacin prevents the prevalence rate of cardiovascular disease by inhibiting low HDL-cholesterol and hyperglycemia”

“In conclusion, all the results from this research show the highest prevalence rate of cardiovascular diseases from...

... physiological factors: hypertension, waist size, low HDL-cholesterol, and the nutrient that was related to the abnormal rate of physiological factors was niacin.”

Relationship of Niacin with Cardiovascular Disease
kjcls.org/journal/view.h…

“The findings reveal that macrophage GPR109a deficiency accelerates the development of T1D [Type 1 Diabetes]. Activation of GPR109a on macrophage by nicotinic acid may provide a new strategy for preventing or treating T1D.”

onlinelibrary.wiley.com/doi/10.1002/mn…

“Participants in an open label study at Kaiser Permanente in San Francisco received an average of 3000mg a day. After a mean duration of one year, 81% of patients had experienced reductions in intra-abdominal fat as measured by a single slice abdominal CT scan (the method...

... agreed to provide an objective measure of changes in body fat). The average reduction in those who experienced improvement was 27%, and the degree of fat loss was significantly associated with the degree of increase in HDL cholesterol (niacin is given to people with...

... elevated cholesterol to increase levels of good HDL cholesterol), and a reduced Total Cholesterol/HDL cholesterol ratio.”

Niacin reduces abdominal fat: pilot study
aidsmap.com/news/feb-2002/…

DO YOU REALLY WANT ME TO KEEP GOING!?!?!?!?

… “each unit increase in niacin intake was associated with a 3.5% reduction in diabetes risk (OR = 0.965; 95% CI 0.944-0.986; P = 0.001)”

jhpn.biomedcentral.com/articles/10.11…

Don’t make me show you the COVID intersecting research more… you fuckin bioterrotists on #epitwitter and #medtwitter would have to call the Gestapo on me - kinda like the Nazis at UNC tried to 3+ years ago when my causally inferring models confirmed all this before IVM pandemic