#9

I consume mountains of dark chocolate and cocoa powder so that’s good.

As far the others go, cool results. I just wish we got more results for things many of us routinely take (taurine, creatine, etc.). Just have to be a little more patient.

#10

FWIW: I have been a heavy consumer of chocolate for my entire life without regard to brand. I ate any chocolate that tasted good. Now I consume mainly dark chocolate exclusively, not because it is better but because my tastes have changed. I haven’t put Navitas cacao powder in my coffee yet, but maybe I will give it a try. IMO: The health hazards of heavy metals in chocolate have been overblown.
In my mid-80s, my mind is functioning quite well, and I don’t have cancer.

1 Like
#11

For those interested, if minimizing heavy metals is your priority, prefer cacao/cocoa powders sourced from West Africa or labeled “West African origin” (or blends tilted that way). On average they’re lower in cadmium. Unfortunately, Navatos cacao powder is not in this group.
Back of the Navatos cacao powder that I have.

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A better choice would be Cacao Powder By Juka’s Organic Co. (Non-GMO, Gluten-Free, Unrefined, Authentic, All Natural From West Africa) 16oz (16)

Brand: Juka’s Organic Co.

4.7 4.7 out of 5 stars (21) Available from Amazon, and it is slightly cheaper.

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#12

Mitoglitazone = MSDC-160 ( https://www.nia.nih.gov/research/dab/interventions-testing-program-itp/supported-interventions ). It’s not even approved. And after that, the ITP decided to test pioglitazone. I wonder why they chose mitoglitazone in the first place, but they were right anyway.

1 Like
#13

Yes, the ITP folks seem to make choices - or the folks who submit the requests - based on some pretty good knowledge. That makes me wonder all the more about which specific drugs they pick - like cana and not dapa or empa, and mito and not pio. With empa/dapa and pio being so much more popular and widely used, they had to undertake a very specific choice to forego them in favor of the less common. In a way that’s somewhat deflating for those of us who use the more common drugs, lol.

1 Like
#14

They picked pioglitazone (link above).

#15

Wow, you’re right. Can’t wait for the results. It’s been 2+ years, so likely soon.

#16

I’m just learning about this drug, looks interesting.

Here is a summary of the commercial history of pioglitazone — key patent milestones, regulatory approvals, launches, genericization, safety/regulatory changes, and current status.

Origins & Patenting

  • Pioglitazone is a thiazolidinedione class drug, developed by Takeda and co-developed with Eli Lilly in some markets. (PMC)
  • It was patented in 1985. (Wikipedia)

Regulatory Approval & Market Launch

  • In the United States, the Food and Drug Administration (FDA) approved Actos (pioglitazone hydrochloride) on July 15, 1999 for the treatment of type 2 diabetes mellitus. (FDA Access Data)
  • In Europe, approval through the European Medicines Agency (EMA) came about a year later, on October 13, 2000. (PMC)
  • Its launched brand name in the U.S. is Actos. (Wikipedia)

Commercial Performance / Sales

  • Early expectations: when it was launched, pioglitazone was seen as a safer thiazolidinedione than its predecessor drugs (such as troglitazone, withdrawn for liver toxicity), with hopes of considerable sales. (WIRED)
  • It in fact became a blockbuster drug; at various points, its sales were in the billions per year. For example, in 2008, it was among the top-10 drugs by revenue in the U.S. with sales exceeding US$2.4 billion. (Wikipedia)

Genericization

  • The first generic versions of Actos were approved in the U.S. on August 17, 2012. (Medscape)
  • Multiple manufacturers now supply generic pioglitazone tablets (15 mg, 30 mg, 45 mg) in the U.S. (Drugs.com)

Combination Products

  • Pioglitazone has been combined with other agents to broaden its therapeutic use; for example: • ACTOplus Met (pioglitazone + metformin) was approved by FDA on August 29, 2005. (Drugs.com) • Duetact (pioglitazone + glimepiride) approval came in the U.S. around 2006. (Wikipedia) • Oseni (pioglitazone + alogliptin) is another fixed-dose combination with FDA approval in 2013. (Drugs.com)

Safety, Regulatory Concerns, and Withdrawals / Market Limitations

  • Over time, safety concerns emerged, particularly regarding risks such as bladder cancer, heart failure, weight gain, edema, etc. Some markets (France, Germany) suspended or withdrew Actos in 2011 over cancer risk concerns. (Wikipedia)
  • Regulatory labeling was updated to reflect such risks. (Wikipedia)

Current Status

  • Pioglitazone remains an approved, generic drug in many countries, widely prescribed for type 2 diabetes as an insulin sensitizer. (Wikipedia)
  • It is no longer under brand-exclusive patent (in many markets), so generic competition has lowered price and broadened access. (Drugs.com)
#17

Two threads about it:

Ralph DeFronzo interview about it on Peter Attia’s podcast was interesting.

2 Likes
#18

I feel like sulforaphane should be on the itp list, but not seeing it there yet https://www.nia.nih.gov/research/dab/interventions-testing-program-itp/supported-interventions

3 Likes
#19

It’s very interesting, the consistent male bias of favorable interventions, at least in lower life forms. In humans my bet is that rapamycin and estrogen will be the biggest levers for women. These other things might be hit or miss, but the decline in estrogen seems to set off the master cascade of decline for women and replenishing it seamlessly seems to set things right — even helps men. Rapamycin among the organism wide changes also seems to be an anti fibrotic and good at particularly rejuvenating ovaries so that it also delays the orchestrated obsolescence.

#20

(post deleted by author)

#21

Pioglitazone (another TZD) is one of my all time favorite longevity compounds. It’s readily available and I shared about it quite a bit in the Facebook Rapamycin group. E.g. Pioglitazone

Cocoa is turning out to be a no brainer supplement for longevity. Because it has numerous human trials showing benefits now! Plus ITP life extension. Further reading Cocoa

1 Like
#22

Very nice writeup on pioglitazone, though notably lacking in one of the biggest concerns: increased incidence of bladder cancer, which is strongly correlated both dose and time dependent. I too have explored pioglitazone (Work In Progress) in this thread:

I also think it’s pretty important to look at combining use of pioglitazone and other drugs. Statins, which you mention, but also telmisartan which has several possible synergies while possibly alleviating some of the undesirable side effects, such as weight gain. Also, SGLT2i, such as empagliflozin which might reduce edema and perhaps lower the HF danger.

As always, healthy aging and life prolongation is complex and unlikely for any single drug to have optimal effectiveness alone. Instead, carefully calibrated polypharmacy is called for, adjusted depending on one’s particular phenotype.

Atm, I’m doing lipid lowering therapy (pitavastatin, bempedoic acid, ezetimibe), glucose control (empagliflozin), BP control (telmisartan), and soon low dose (7.5mg/day) pioglitazone. Epicatechin I’m hoping to cover through dietary sources, daily cacao and green tea. And of course, rapamycin - 6mg/1-week. To the degree that I could, I’ve explored the possible interactions of these various molecules, but naturally, it’s a continuing and never ceasing work in progress (WIP).

2 Likes
#23

Great! Any reason you’re doing pitvastatin over other statins?

I’m currently on rosuvastatin + bempedoic acid & ezetimibe.
But always keeping an eye out for the safest in class among the statins.

#24

As bladder cancer (BC) is very rare, a modest increase in BC risk is probably not very significant.

The best cardiometabolic drug for NASH, today, is retatrutide (stage 3 clinical trials about to be finished). I’ve been on it for 2 yrs or so. It’s amazing – next gen tirzepatide. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial | Nature Medicine

I’ve been on Rosuvastatin (2.5mg), Lisinopril 10mg, Aspirin 80mg. Added ezetimibe on and off (still trying to get used to it). Pio 7.5mg is great but I think I’m getting too much bone marrow supression these days (so I’m not on it).

Nice group on heart disease risk: Redirecting...

Supplements:

  1. Daily green tea + hibiscus tea (1 mug)
  2. Daily coffee (1 mug)
  3. Vitamin D3 (2k-4k IU/day)
  4. Fish oil (1.2g-4g/day)
  5. Alpha ketoglutarate (AKG) 250mg/day
  6. Beta alanine 400mg/day
  7. Alpha lipoic acid 300mg/day
  8. Cucumber + Celery juice (1/2-1 cup)
  9. Aged Garlic Extract
  10. Magnesium, Calcium, Chromium, Fiber

Plus mediterrenean keto diet recently.

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#25

I’m glad to see epicatechin had a life-extending effect after all, however small. Maybe there’s a similar compound with even more potent effects.

I’m looking forward to hearing how GlyNAC turns out. Neuro-NAC might be an even more powerful supplement to try for life-extending purposes.

I also will test out black ginger to see its effects. (A personal n=1 test).

#26

I wonder about EGCG, also. It has been claimed to inhibit DYRK1A, one of the genes of the DREAM Network (so does EGCG result in an increase in DNA repair?), though I’m not sure the same is true of plain epicatechin.

#27

Interesting

  1. it improves mitochondrial dysfunction, potentially even more than aerobic training
  2. redistributes fat from muscles and beta cells to subcutaneous fat
  3. is the only drug that increases insulin sensitivity
1 Like
#28

The results from the ITP (Intervention Testing Program) can absolutely be seen as a strong signal that excessive insulin signaling (hyperinsulinemia) is a key accelerator of mammalian aging. This aligns very well with Dr. Ben Bikman’s reasoning and the broader scientific understanding of the insulin/IGF-1 signaling pathway in aging. Insulin levels can be seen as the canary in the coal mine.

ITP, some of us here and biogerontologists know that the Insulin/Insulin-like Growth Factor 1 Signaling pathway is one of the most evolutionarily conserved pathways regulating aging. Reduced signaling in this pathway is strongly associated with increased lifespan and healthspan in species from worms and flies to mice. And some say that, low insulin signals is strongly associated with increased lifespan and healthspan even in long lived humans.

Excessive signaling is associated with accelerated aging and age-related diseases.Insulin is Not the Enemy, Hyper-insulinemia Is. Insulin is an essential anabolic hormone. We need it to live. The problem is the chronic, excessive levels. The ITP provides strong correlative signal for this reasoning.

But these drugs (drugs for type 2 diabetes) have other proposed anti-aging effects, like effects on mitochondria, AMPK activation, that may be independent of insulin. Lower insulin likely contributes to these other beneficial effects. High insulin activates besides IGF also mTOR.