Inflammation is one of the two principle drivers of “The Hallmarks of Cancer” which are the common drivers of progression of cancer from initiation to invasion and spread, to developing resistance to treatments and ultimately to end stage metastasis. (The other main driver being genomic instability: the accumulation of mutations). So the reduction of unnecessary baseline inflammation as well as DNA protection and repair are of paramount importance.
aacrjournals.org/cancerdisc...
Inflammation is also one of the main drivers of the diseases of aging (‘Hallmarks of Aging'), of Type 2 diabetes and metabolic syndrome, and of cardiovascular disease.
Colchicine is a medication derived from the plant autumn crocus that has been used for millennia. Most commonly now, to manage the inflammation associated with gout. It is taken by those with gout at 0.6mg/day to prevent repeat attacks. Anti-inflammatory effects of colchicine include reductions in CRP (34%), IL-6 (15%), MMP9 (30%), Resistin (21%) LOX-1 (33%), and in TNFa and TGFb1.
Last month “Lodoco”, a branded low-dose colchicine (0.5mg rather than 0.6mg but otherwise identical), was approved by the FDA for the treatment of those with high risk atherosclerotic cardiovascular disease. This was based upon the results of the LoDoCo2 Trial which showed a 31% (mean) further decrease in major CVD events (heart attack, stroke, coronary surgery or death) compared to placebo in patients with ASCVD who were already on lipid lowering regimens.
nejm.org/doi/pdf/10.1056/NE...
Colchicine also has some anti-cancer properties, perhaps beyond the anti inflammatory effects. Patients with gout who take colchicine have a lower incidence of all cancers than gout patients who do not take it. In vitro cell studies have show it can cause G2/M cell cycle arrest and apoptosis and microtubule disruptions among other effects. But it has not been developed as a anti-cancer therapy due to toxicity at the higher doses used.
I personally take several agents to decrease my baseline inflammation as measured by my high sensitivity hsCRP tests. This is in attempt to decrease inflammation as a driver of cancer progression, for metabolic health, for risks of the diseases of aging, and cardiovascular disease. Basically all of my major health risks in life outside of infectious diseases!
My regimen includes the medicines: Celecoxib, Atorvastin, Metformin, Sirolimus and low dose aspirin. ( I do not take doxycycline because of adverse effects on gut microbiome). My supplements that have anti-inflammatory actions include: Quercetin, Fisetin, Resveratrol, Co Q10, Alpha-lipoic acid, Curcumin, ECGC, Sulforaphane, Omega3 FAs, Melatonin and Pro-biotics. Perhaps I will consider adding low dose colchicine. I would just get the generic 0.6mg and cut them in half to take a very conservative dose of 0.3mg/day. Or perhaps the 0.6mg 3 times per week. We do not want to block ALL inflammation as it is necessary to fight infections and for healing wounds and injuries. Paul/MB
nature.com/articles/s41366-...
“Colchicine, an anti-inflammatory medication used for gout, has garnered considerable interest for its potential metabolic and cardiovascular benefits. Colchicine can reduce fasting insulin resistance in adults with obesity and has been suggested to reduce the risk of incident T2D. Among individuals with CVD, colchicine also decreased the incidence of major adverse cardiovascular events.”
“Multiple inflammatory molecules were decreased by colchicine [Fig. 1]. Among them, seven have specific roles with regards to neutrophil function: alpha 1-antichemotrypsin, bactericidal/permeability-increasing protein, CD177, matrix metalloproteinase 9 (MMP9), myeloperoxidase, proteinase 3, and S100A12. Other mediators of the innate immune system were also suppressed, including complement components C5a and C9, cyclooxygenase-2, haptoglobin, serum amyloid P, and surfactant protein D. In addition, oxidized LDL receptor (LOX-1) and phosphodiesterase 5A concentrations were decreased in the colchicine arm. Conversely, colchicine significantly increased several molecules involved in metabolism and tissue repair (growth/differentiation factor 15 [GDF15], heart-type fatty acid binding protein [hFABP], hepatocyte growth factor activator) as well as an anti-thrombotic molecule, protein C.”
A Reason why Checkpoint Inhibitors may not be effective has been found...
My Recent and Temporary BAT failure and it's relation to High Uric Acid (Kidney Stone and Gout)
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