Colchicine and Inflammation Revisited

[MateoBeach]

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.”

[Tall_Allen]

Be careful. You are talking about a VERY toxic substance:

"Ingestion of colchicine typically leads to profuse vomiting and diarrhea, which can be bloody, followed by hypovolemic shock and multisystem organ failure within 24-72 hours. Coma, convulsions, and sudden death might also occur. Subsequent complications include bone marrow suppression with resultant leukopenia, thrombocytopenia (nadir in 4-7 days), and possibly sepsis (1)."

emergency.cdc.gov/agent/col....

[MateoBeach in reply to Tall_Allen]

And you are talking about severe overdose not low dose. No one is advocating overdosing on anything

[MateoBeach in reply to MateoBeach]

From LoDoCo2 study. Only adverse signal was non-CV death, (1.9% vs 1.3%, basically 1 extra non CV death per 500 person years). No other significant toxicity from the colchicine appeared at this dose in study population vs placebo.

Adverse Events in the Intention-to-Treat Population.

Noncardiovascular deaths occurred more frequently among the patients who received colchicine than among those who received placebo, with incidence rates of 0.7 and 0.5 events, respectively, per 100 person-years (hazard ratio, 1.51; 95% CI, 0.99 to 2.31) (Table 2 and Table S7). We observed similar rates of cancer diagnosis, hospitalization for infection, hospitalization for pneumonia, and hospitalization for a gastrointestinal reason in the two trial groups, in both the intention-to-treat analysis and the on-treatment analysis (Table 2 and Table S8). Gout occurred in 38 patients (1.4%) in the colchicine group and in 95 patients (3.4%) in the placebo group (cumulative incidence ratio, 0.40; 95% CI, 0.28 to 0.58). Neutropenia and myotoxic effects were uncommon in both trial groups. Among the patients from the Netherlands, myalgia was reported in 384 (21.2%) in the colchicine group and 334 (18.5%) in the placebo group (cumulative incidence ratio, 1.15; 95% CI, 1.01 to 1.31). Dysesthesia was reported in 143 patients (7.9%) in the colchicine group and in 150 patients (8.3%) in the placebo group (cumulative incidence ratio, 0.95; 95% CI, 0.76 to 1.18).

[Tall_Allen in reply to MateoBeach]

No one takes a toxic dose on purpose, of course. You should also be aware that it can have toxic interactions with CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy.

[MateoBeach in reply to Tall_Allen]

I always check any new drug or supplement for interactions with any other in my regimen, as we all should do.

[London441 in reply to MateoBeach]

Just be sure you have your exercise habits together. Otherwise it's all just cart before the horse.

[kainasar in reply to Tall_Allen]

What are safe OTC or herbal anti-inflammatories?

[Tall_Allen in reply to kainasar]

ibuprofen - with omeprazole if taken for more than 2 weeks.

[kainasar in reply to Tall_Allen]

Oh I see. IB stomach issues offset by omeprazole. Thanks.

[swwags]

MateoBeach, I always enjoy your posts. I was reading your regimen and the first and overwhelming thought I had, was holy moly the cost of your self care must be impressive. This is in no way intended as a criticism. Cheers to your health good sir.

[MateoBeach in reply to swwags]

Thank you. And to yours.

[ragnar2020]

Hi Paul,

As always, great information. Thank you.

[Papillon2]

Many thanks MateoBeach and TA. Because I have prescriptions for Atorvastatin and Colchicine, this topic was very informative for me.

[Medline]

Microtubules are structures in cells that play a crucial role in cell division and movement. They are made up of protein subunits called tubulin, and drugs that target microtubules can be used in cancer therapy. Docetaxel and Colchicine are both microtubule-targeting agents, Docetaxel is a microtubule-stabilizing agent, while Colchicine is a microtubule-destabilizing agent. Studies have shown that Docetaxel-resistant cancer cells may be more sensitive to microtubule-destabilizing agents such as Colchicine!

[85745 in reply to Medline]

Microtubules are in good cells as well as bad cells

[GeorgeGlass]

Paul, how often do you get your CRP levels checked? What is your score on the recent CRP test? Mine is usually 0.1 or 0.2.

George

[Seasid in reply to GeorgeGlass]

What is the unit of your 0.1 or 0.2 CRP test?

[85745]

Thanks, If I might add what is in our diet triggers or adds to inflamation, Since cutting out all sugar, carbs and follow a strict diet coupled with periodic prolonged fasting and intermitent, my symptoms have gone. And yes I take many alt sups as well . Most important for me is digestion and detox for that I take Tudca, MCP, and fermented foods. Big time improvement from before. I walk into a grocery store now and realize just how toxic 90% of the items are and that it's getting worse now that food shortages are upon us. Thank God I have a garden and can compensate . wish you the best

[RayF]

A little story about my experience with colchicine, not relevant to the post. I had feet problems in my 30's, sometimes knee problems with swelling and intense pain. I was fit and thin, and gout was always ruled out. I went on a trip to the Midwest, and had a fried liver dinner. When I got home my feet ballooned, and I was in agony. I had to crawl up and down the stairs. Couldnt sleep more than an hour at a time. Docs finally said it was gout. New, young doc said take colchicine until you can't take it any more. I did that and thought I was going to die. I've never been so sick. So I had the pain in my feet and was poisoned. Very rough time.

I personally will not touch the stuff.

[kainasar]

I know its been a while, since this was posted. But wanted to ask if anyone has tried "Sweet Suranjan Powder Colchicum Luteum Hiranyatuttha Autumn Crocus Hiran Tutiya" from India and how much did they safely take?