Gemfibrozil, a lipid-lowering drug, improves damage in a mouse model of aging

[RapAdmin]

Gemfibrozil is a drug that Dr. Brian Kennedy of National University of Singapore, has identified as a probable longevity drug and one which they are working to test at their university in clinical trials with humans. New data is also suggesting a possible 60% reduction in Alzheimers with fibroid medications like Gemfibrozil (see down by post #19).

Here is some new research on this drug that has just come out:

Gemfibrozil (GFZ) is a medication of the fibrate category with agonistic effects on PPAR-α and is effective for hypertriglyceridemia and mixed dyslipidemia. This agent also has anti-inflammatory and antioxidant properties. The current study investigated the effects of GFZ on hepatorenal (Kidney/Liver) damage in a D-galactose (D-gal)-induced aging model. We used twenty-eight male mice, which were equally and randomly divided into four groups as follows: Normal, D-gal (150 mg/kg/day; i.p., for 6 weeks), GFZ (100 mg/kg/day GFZ, p.o. for 6 weeks) and the combined D-gal + GFZ. Liver and kidney function indices were measured as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase. Oxidative stress in hepatic and renal tissue was evaluated through malondialdehyde, superoxide dismutase, and glutathione peroxidase levels. Finally, the liver and kidney tissues were assessed for histopathological lesions. The results showed that D-gal induced aging leads to abnormalities in liver and kidney function indices. D-gal also induced significant oxidative stress and histopathological lesions in these organs. GFZ improved function indices and oxidative stress compared to the D-gal -treated animals. Histological evaluations of the liver and kidney also confirmed these results. These data provide evidence for the potential therapeutic of GFZ in clinical practice for mitigating the hepatorenal damages of aging.

Paper (Paywalled)

Gemfibrozil, a lipid-lowering drug, improves hepatorenal damages in a mouse model of aging

https://onlinelibrary.wiley.com/doi/10.1111/fcp.12865

Other related research:

Gemfibrozil, a lipid-lowering drug, reduces anxiety, enhances memory, and improves brain oxidative stress in d-galactose-induced aging mice

Gemfibrozil, a lipid-lowering drug, reduces anxiety, enhances memory, and...

Gemfibrozil Protects Dopaminergic Neurons in a Mouse Model of Parkinson's...

Dr. Brian Kennedy on AKG and Gemfibrozil:

AKG & Gemfibrozil - 2 Promising Geroprotectors For Slowing Aging | Dr Brian Kennedy Interview Clips

Gemfibrozil

Related Reading

From: For Researchers | Cognitive Vitality | Alzheimer's Drug Discovery Foundation

Fenofibrate.pdf (465.2 KB)

[LeeJohn]

I highly recommend people take a look of the list of PDFs by Alzheimer’s Drug Discovery Foundation. Many drugs and supplements which have been discussed in this site also are included in these PDFs.

Such as:
Acarbose, GLP-1 Receptor Agonists, Lithium, Metformin, Methylene Blue, Naltrexone low-dose(LDN), PDE5 Inhibitors, Rapamycin, Selegiline, SGLT2 inhibitors, 17α-Estradiol, Cocoa, Alpha-ketoglutarate, Apigenin, Astaxanthin, Fisetin, L-Serine, Medium Chain Triglycerides, Magnesium, Melatonin, N-Acetylcysteine, Palmitoylethanolamide, NDGA, Selenium, Trehalose, ISRIB, Vitamin K2…

Of my surprise, I thought molecular hydrogen was a hype, but here is their summary of molecular hydrogen:

Evidence Summary
Hydrogen can protect against minor oxidative stress and inflammation-associated tissue damage, but
cannot repair existing damage.

Aging and related health concerns:
Hydrogen-rich water is protective against mild oxidative
stress, has anti-inflammatory properties, and may regulate blood lipids and metabolism. May
help protect the liver.

Molecular-Hydrogen-Cognitive-Vitality-For-Researchers.pdf

There are also many drugs&supplements I’ve never heard of, I think it’s a great resource, maybe our members can find some interesting gem and discussed here.

[RapAdmin]

Latest update by Brian Kennedy on his work with Gemfibrozil (video pre-set to the part of the discussion about gemfibrozil):

Prof. Brian Kennedy at Rejuvenation Startup Summit 2022

[Neo]

Interesting that its aging effects may be through amino acid and perhaps mTOR regulation.

[forceofnature]

Looks like Gemfibrozil shouldn’t be taken with Zetia

ezetimibe

[RapAdmin]

Gemfibrozil looks to be a pretty inexpensive drug, from the typical Indian online pharmacies:

About $2.50 to $3.50 US for a stripe / strip of 10 pills.

I wonder if this might be a good drug to use in addition (or replacement) for statins… since it seems to address more fundamental causes of aging in addition to the lipid issue…

[RapAdmin]

related to this drug (Gemfibrozil is a type of fibrate drug)… this is extremely interesting; 60% lower risk of Alzheimers in early data:

Being Patient: In your recent study, you looked at fibrates, which are primarily used for triglycerides, right?

Jicha: That’s correct. You know, what we’ve really known about these and the data from those European studies suggest that if you have ever been on a fibrate in your life, your risk for Alzheimer’s disease is reduced by about 60 percent. Now, that’s pretty darn good. That would take our 6 million people with Alzheimer’s in the United States and bring it down to two and a half. Sparing three and a half million people, that would be incredible…

Being Patient: Do you predict more people will be on fibrates for prevention in the future?
Jicha: That’s a very good question. Right now, we have our preliminary data. The study that we did was a relatively small study of 74 people, with 36 to 38 people in each group. With that, we saw very directional changes in everything. We saw in microRNA a 107 increase, we saw an amyloid decrease in its production, and we saw benefits in memory and thinking…"

Source:

An Alzheimer's Expert on Cholesterol, Statins, and Brain Health

Dr. Gregory Jicha: The Link Between Cholesterol and Brain Aging | Being Patient

[AnUser]

Fibrates slightly increase apoA1, which lends slight credence to the apoA1-alzheimer’s link.

[RapAdmin]

You’re talking about this line of research?

What’s good for the heart may be good for the brain. Apolipoprotein A-I is the major component of high-density lipoprotein (HDL, or “good cholesterol”) in the blood, and is under intensive investigation by cardiovascular researchers for its ability to protect against heart disease. New evidence suggests that it might also help defend the brain against the cognitive deficits associated with Alzheimer’s-like pathology.

https://www.alzforum.org/news/research-news/apoa1-does-good-cholesterol-protect-brain

and

Apolipoprotein A1, the neglected relative of Apolipoprotein E and its...

[AnUser]

I heard it first from John Kastelein with Peter Attia from NewAmsterdam Pharma.
For APOE-e4 carriers, apoA1 can take over function of APOE to remove oxidized sterols in neurons etc according to him, which is not functioning properly. I haven’t looked at the research but I saw some MR studies apoA1 can be protective, etc.

[RapAdmin]

Here, I assume:

255-Latest therapeutics in CVD, APOE’s role in Alzheimer’s disease, familial hypercholesterolemia

[AnUser]

Yes it starts at 1:41:30 and runs for about 10 minutes.

[RapAdmin]

I think I’ll include some Gemfibrozil in my next order… just to try out. At $10/month (typical cost from Indian pharmacies) it seems worth a try (I have high cholesterol already so I’m looking to try some different approaches), will report back with pre and post testing.

[DeStrider]

My pharmacist just recommended Gemfibrozil to me. The generic is made here in HK and costs 0.25 USD for 600 mg. Cheaper than India. A Malaysian generic is 0.18 USD for 300 mg. Dirt cheap.

Gemfibrozil enhances the effects of ezetimibe.

Just got the prescription. Dr. said the side effects would be much milder.

[Neo]

@DeStrider

Gemfibrozil enhances the effects of ezetimibe.

Haven’t read the link, but make sure you read if considering that combo (zetia = ezetimibe I think?)

@forceofnature

Looks like Gemfibrozil shouldn’t be taken with Zetia

ezetimibe

[RapAdmin]

Its interesting, three different medical websites and three different takes on using this combination of drugs…

the Kaiser website says definitely don’t take Ezetimbe at the same time as Gemfibrozil:

But the WebMD says there is only minor risk of interaction

and then the Drugs.com Interaction checker says “Moderate” risk:

Source: Drug Interaction Report: ezetimibe, gemfibrozil

[RapAdmin]

There has to be new data after the 2002 product information from Schering-Plough.

Here is Some newer research on gemfribrozil and ezetimibe I found:

The efficacy of Ezetimibe added to ongoing Fibrate-Statin therapy on postprandial lipid profile in the patients with type 2 Diabetes mellitus

Conclusion

Adding ezetimibe to gemfibrozil has no additional effect on reducing postprandial TG but ezetimibe can potentiate the effect of low-dose atorvastatin on lowering TG and LDL-c.

The efficacy of Ezetimibe added to ongoing Fibrate-Statin therapy on...

What are effective medication combinations for dyslipidemia?

Some physicians are reluctant to prescribe statin/fibrate combinations due to the interaction of
gemfibrozil with statins; plus, patients must forego grapefruit juice with fibrates to avoid toxicity.

Full document here: https://cdn.mdedge.com/files/s3fs-public/Document/September-2017/5501JFP_ClinicalInquiries4.pdf

Perhaps other people can look for more information and studies.

[Radiata]

Gemfibrozil reduces Lp(a) by about 18%, but had a wide error band of +/- 15% and wasn’t considered statistically significant. They took pretty high doses, of 2400 mg, which is a bit concerning from a gallstone risk.

[Gemfibrozil reduces elevated lipoprotein (a) levels in hypercholesterolemic...

Gemfibrozil treatment in patients with elevated lipoprotein a: a pilot study...

[DeStrider]

Well the not working well with grapefruit is a non starter. I could solve this whole lipid issue if I just stopped taking Rapa. But that seems counterproductive.

Any interaction between ezetimibe and grapefruit or anything else???

[ben_nichols]

Hey RapAdmin, interested to hear what you think of this stuff. You can take it with Ezetimibe, I took fenofibrate w it for a cpl yrs… it actually DECREASES the risk of gallstones by adding Zetia/Ez….

what I found, though is that it really increased my fatigue and muscle pain. I experimented with adding a Statin and even rosuvastatin 5 mg twice a week was too much w the combo… I dropped the fenofibrate and Statin was still too much. Took a one or two month break from all of it, and then tried pravastatin by itself and still too much muscle pain…

I then went back to Fenofibrate after having been off it for a few months and it was just too much fatigue/muscle pain also. I rechallenged a couple times and still too much. I might try it again, when I first started taking it I had the same thing slightly but it went away, the last couple times it did not.

I actually really wanted to take bezafibrate over the years, that one doesn’t just hit PPAR Alpha, but Delta and Gamma as well, and it causes greater increase in Apo-A1, greater metabolic effects, etc… but it always caused me way too much fatigue and I’ve tried it for the last 20 years off and on a couple times… I think for me hitting the PPAR pathway lowers blood sugar/pressure or something… interested to see how you feel on it, people seem to do fine for the most part