Paul's self experimentation

Adrian M agelessrx.com is USA source. The doctors there will decide your dose. Or you could use one of the international sources such as AlldayChemist.com or one of the others discussed in these forums. Agelessrx prescribed 1000 mg/day for me but I am twice your age.

Adrian M you could try to convince a local primary care doctor to prescribe it.  I don’t believe that insurance will pay for unless you are diabetic but the cost is quite low.

David H Thanks very much for the quick response. Isn't David Sinclair taking 1000 a day also? Pretty sure I've heard him say he takes 500 twice a day. PS I'm in Europe and AlldayChemist don't ship here. I'll try asking around.

I think GP's in my jurisdiction are quite conservative about prescribing drugs compared with the US but I'll certainly give it a shot.

Any side effects you've had from it? I know an upset stomach is quite common. I suppose the question is how upset...

Adrian M Yes David Sinclair takes 500gm morning and night.  I didn't know you were in Europe.    I have not had even a hint of side effects with metformin and I have taken as much of 2000mg per day, often before meals.  I am not diabetic but without metformin and being very careful about what carbs I eat, my blood glucose gets higher than I like. 

My desire is to keep the after meal glucose spikes at 1 and 2 hours no higher than 120. Dr. Peter Attia (peterattiamd.com) believes under 100 is best. (I am using the units commonly used in the USA.). I check the effects of the carbs I eat with a glucose meter. As examples, because of the glucose meter, I no longer eat bananas or oatmeal. I eat brown rice for breakfast but eat it with red lentils which keeps the blood glucose down.

I have quite a bad metabolic history - my mother added sugar to just about everything we ate - lettuce, tomatoes, rice, strawberries, etc.  By age 16, I weighed 168 pounds - by 35,  I weighed 310 pounds.  Later I lost weight so that by age 50, I weighed around 200 pounds.  I am now 69 and by being careful about my diet (and taking metformin and rapamycin and doing Fasting Mimicking Diet monthly), my current weight is 160 pounds. 

David H Many thanks for this fascinating information, David!

Yes, in the British Isles. That is great to hear, you had no side effects. I often have mildly upset stomach as is (I suffer from chronic reflux) but it's very treatable with heartburn pills, so I'm not sure what to expect.

The most dangerous side effect from metformin I've read about is hypoglycemia. An (older) friend of mine actually died hitting his head when he had a fit and collapsed as a result of this condition (he wasn't taking any metformin).

If you're no diabetic, how did you convince your doctor to prescribe metformin for you? I'm hoping for some tips haha.

Yes, I pay close attention to my carb intake and have completely eliminated processed/added sugars from my diet. I also try to do the 8/16 intermittent fasting as often as I can. I'd love to get a glucose monitor, been thinking of it for a while but due to the pandemic I avoid visiting my doctor for non-essential purposes. Which glucose monitor as you using? 

So Attia recommends to test at 1 and 2 hours after feeding? Is the ideal value of 100 the same for both? I wonder if this varies by gender (females may have a different ideal value).

The fasting mimicking diet sounds fascinating, is there a reason you prefer to do it over intermittent fasting (other than convenience, of course)? Kind regards

Adrian M YMMV, but I don't believe that hypoglycemia is a problem with metformin.  Metformin works by reducing absorption of carbohydrates and by reducing the amount of fat converted into glucose.  It's not like taking insulin or other diabetic drugs.

You will need to convince your doctor that the anti-aging benefits are sufficient reason to take metformin.  In the USA, a doctor prescribing metformin for anti-aging is said to be prescribing it "off label" which means a purpose for which it is not FDA approved.  Anytime a doctor prescribes off label, I presume that they have more risk to themselves (from legal liability and from problems with the medical boards). Yet, some do prescribe metformin for anti-aging.

Here's a link from these forums about how to approach MD's about anti-aging:

https://forum.age-reversal.net/t/18csjj/faq-how-to-work-with-the-medical-system

I bought a Bayer Contour Next EZ Glucose Meter.  It is very inexpensive but the test strips are expensive. You prick yourself with a little device and put a little of the blood on a test strip.

According to this link https://twitter.com/PeterAttiaMD/status/1207363088325976064 I misunderstood Dr. Attia. This twitter posting he made in December 2019 says an average of 100. Not max of 100.

Here is another link for Dr. Attia's view on the subject:

https://podcastnotes.org/the-drive-with-dr-peter-attia/the-drive-with-peter-attia-ask-me-anything-edition/

Goals = Fasting glucose below 90, 1 hour post prandial <120-130, 2 hour glucose below 100 (post prandial means after a meal or eating)

David H David and others on this thread, you should be aware that metformin can significantly reduce testosterone in some seniors. I tried it several years ago when it was first being recommended for its antiaging properties. It reduced my testosterone by ~ 50 % even though I use androderm.  As a consequence my cholesterol increased due to feed back for need to produce more testosterone.  for  Calorie restriction does the same. There are multiple references to both if you google. 

See attached for example:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296448/#:~:text=significant%20p%3D0.001.-,Conclusion,sex%20drive%20and%20erectile%20function.

Senior men need testosterone, some say estradiol due to aromatiztion may be even more important, to prevent dementia, osteoporosis, sarcopenia and other senior related disabilities. There are multiple reference to these benefits also.

Peter H. Howe Thank you for the warning.  Before I started metformin my testosterone was fine but I haven't had a test for 13 months.  First due to being in SE 5 months and then we came back home in Florida due to Covid19.  I will test as soon as my wife and I agree it is safe.

Peter H. Howe The study reports ED, lower T, etc., in patients with type II diabetes.  Not sure if the effect of metformin use would be similar in people non-diabetic.

Dorian Gray Dorian, this is probably due to the fact that most studies are done on diabetic men. I googled the the issue, and after considerable effort, found study on non diabetic, non obese men which concluded,  after short term metformin use, that testosterone (T) was decreased. See attached:

https://www.researchgate.net/publication/11156121_Effects_of_short_term_metformin_administration_on_androgens_in_normal_men

As indicated in E-Mail to David H., my testosterone was reduced by about 50 %,  and I supplement with androderm, a testosterone patch. My serum concentration was below an acceptable level based on LEF recommendations.

In the Google search I found paper on PCOS treatment with metformin in women to reduce testosterone. The reduction in testosterone was due to reduction in LH . This is the hormone produced by the pituitary in men to stimulate the  the Leydig cells in testes to produce testosterone. Paper is attached.

https://rbej.biomedcentral.com/articles/10.1186/1477-7827-12-98

Metformin is also used to lower testosterone in women with breast cancer.

Testosterone generally decreases significantly in senior men and this is well documented. This reduction contributes  to a number of issues like dementia, osteoporosis, sarcopenia, anemia, etc., etc. There are a multitude of peer reviewed papers on these topics. Attached is one on osteoporosis. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376477/#:~:text=7.-,Conclusions,both%20primary%20and%20secondary%20hypogonadism.

Attached is another "general" article on dementia in both men and women

https://www.issm.info/sexual-health-qa/is-there-a-connection-between-testosterone-

In summary, senior men may not want to use metformin if their T is in unacceptable range.  I did not go into detail, but estrogens are also important to senior men and need to be maintained. Some research suggests that estrogens may be more important that T in preventing late onset problems.  A previous commenter  on this topic indicated he used T injections to offset the negative impacts.  My androderm patch is inadequate for this purpose.

A final comment is that calorie restriction will also significantly reduce T and is another issue discussed on this blog. This can be readily documented with google search.  

Apologize for the wordiness but I believe this is important topic for senior men and probably women.

David H David just sent long response to a Dorian Gray comment on my first comment to you. You might find it interesting.

If you do a blood sample would you compare Ts to see if it changed due to your metformin use.

Thanks

Peter H. Howe "...Apologize for the wordiness but I believe this is important topic for senior men and probably women..."  

I agree completely, Peter.  I've just started Metformin and intend to monitor, all hormones closely.  And let us not forget T3, TSH, also can be impacted by testosterone (vice versa).

Peter H. Howe Thank you for the information. I did not know that metformin can decrease T.

Staffan Olsson Steffan, Dave H and Dorian, just got the attached overview on metformin fr om Longevity right after my last correspondence with Dorian. Note toward end are comments that unpublished studies from Germany indicate that metformin may decrease life expectancy in older organisms by disrupting mitochondria function. This has also been a subject of discussion for past 2-3 years by several researchers. Barry Sears, in his most recent book "The Resolution Zone" mentioned this without reference. Note also the Longevity overview mentioned the use of metformin in treatment of PCOS. This is done by disrupting testosterone production as mentioned in my previous post. 

https://mail.google.com/mail/u/0/#inbox/FMfcgxwJXftRfJJzcTBvwpSGTcdWGMQf

If you are a senior, you may want to give use of metformin careful consideration and do periodic blood work. 

Peter H. Howe Hi Peter, seems like you've done a deep dive on Testosterone. I assume you believe it extends lifespan in males? Can I ask your age, and what does your doctor target for free testosterone? I am 55, and my functional medicine doctor who I took on, started me on topical cream (needle aversion onset), but it didn't work, switched to self biweekly injections. My doc targets 500 pmol/L at TROUGH, namely, the level on the morning prior to next injection. I am also on DHEA, no other meds, but a whack of targeted supplements. I am strict ketogenic diet (plant fats based), OMAD (one meal a day), high daily exerciser, both aerobic and resistance. The ghrelin signal throughout the day is very strong, especially amplified by the exercise pre meal. My blood BHB ketones average around 2 mmol/L at peak, very strong signal (ketones are a lifespan extending metabolite, ancestral preserved pathway, and a huge separate subject on its own). I am lean, very muscular, and super fit. The muscles come purely from the amount of daily resistance exercise I do. I watched my dad become frailer and frailer as he aged, associated sarcopenia, eventually succumbing to Parkinsons. I swore I would do everything possible to avoid that fate. I feel like a teenager again, super energy, high mobility, resilient. No cardio concerns (have had a CCAC), and super high aerobic exerciser. Neuro-cognitive health is my main goal, and I've had a volumetric MRI (measure volumes of different brain regions, especially MTL hippocampi), SPECT scan, and deep neuropsychological baseline testing this past year so I can track my evolution over time. My DNAage result this past July came back 52.

MAC Mac, I am 80 and have been on androderm ( patch) for almost 30 years following an emergency bypass.  I am hypogonadal - not just age related- and this contributed to my cardiovascular event. Note, if you are hypogonadal, this results in high cholesterol as part of feed back to increase testosterone. A second indication is anemia. If you are in your mid 40's and have anemia and high cholesterol this combination is strongly suggestive of low testosterone. I can go on for pages on this, but it sums it up. I may be 80 but I do not feel any older than when I was middle age.

You should be aware that there is substantial number of studies that have concluded that health benefits of T therapy in senior males may in fact be due in large part to estradiol that arises from aromatization of testosterone in the liver.

If you have a copy, suggest that you review LEF's HRT protocols in its Encyclopedia of treatment of of age related diseases. 

I also supplement with DHEA ( as I see you do) and pregnenolone, and keep my DHEAS near the upper recommended level of 500 as recommended by LEF. This also has a number of anti aging benefits.  Note that your percentage free T  will increase from 1-2 to 4-5 % if you supplement with DHEA. This is all explained in the LEF guidance document HRT protocol.

I also supplement with a number of other over the counter supplements. I am of the opinion that high dose fish oil is also critical to maintaining your health. It has a beneficial impact on almost all of your systems. 

Finally, suggest you review the fisetin thread on this forum. You will note that several members have reported immediate benefits following its use-- typically at levels in the Mayo protocol. I started in June and the results were fantastic in terms of color vision and increase in strength as was reported by others. I do not know the reason as the effect was immediate and unlikely due to removal of senescent cells.

Good luck!!!

MAC Forgot to emphasize that I follow LEH's recommendations on optimum hormone levels. This includes free testosterone. I only use a Dr. for a script for androderm. Most of them, including endocrinologists, don't have a clue.

Peter H. Howe Thanks Peter. No CVD, cholesterol or anemia issues. In fact, I started donating 500mL blood religiously every 8 weeks (free to donate here) 2 years ago for the express purpose of reducing my blood iron stores (Ferritin: I happen to be homozygous H63D, so mild raised Ferritin level) as iron is HIGHLY toxic and correlated with many bad pathways (including CVD and neurodegenerative) and secondly, for the rejuvenation benefits of dumping blood and creating new white/red blood cells (you know about the parabiosis type work).

See "Dumping Iron" https://roguehealthandfitness.com/dumping-iron/ as one good reference on why men should not have a ferritin level over 50.

Sorry, what specific link and actionable med/supplement interventions are you referring to "LEF HRT protocol".

This one?: 

https://www.lifeextension.com/protocols/male-reproductive/male-hormone-restoration#SectionTestosteroneReplacementTherapies

My doc has not measured or put me on pregnenolone. 

You didn't comment on your actual level of free testosterone?

Yes, I take 3 g/day of DHA/EPA fish oil...my blood squirts when I do pin pricks. My RBC Omega 3 index last check was over 12%. Along with ZINC, essential Vitamins, Resveratrol, Curcumin, Choline, B supplements.

Glad to hear you feel so young!

MAC 

MAC Title is "Disease Prevention and Treatment", Fifth Ed.  It is large book  and  has 130 protocols.  I try for 20 - 25 pg/ml free testosterone  per text of Male HRT section. The book is my first go to when I start investigating a new issue such as BPH. I got it with my membership in LEF. It is out of date with new issues such as a mTOR, epigenetics and senescent cells. It does have excellent chapter on DHEA benefits. Pregnenolone is not covered directly. It is "grandmother of all steroids and gives rise to DHEA and progesterone.  The latter is recognized as important in preventing dementia and neurogenesis.

Am having some problem with free as my Total T is declining. Am looking at using chlomiphene which stimulates pituitary to release leutenizing hormone to stimulate Leydig cells in testes to produce testosterone. My current level of free is12-15.This procedure  is not covered in the book.

My ferritin is 50 and I still have occasions when I am anemic and supplement with low levels  of iron sulfate.

I basically supplement with all of those that you are using.

Fisetin is remarkable and am looking at  plasmaphoresis and replacing plasma. This is a couple years off. See what happens to someone on this forum who tries it as I did with fisetin. 

In terms of my overall health, I think it is excellent. My chinups went from 20 to 25 the day after my first fisetin treatment. I hope these positive statements do not come back to bite me. Will knock on biggest tree I see tomorrow.

stay safe

Peter H. Howe Free testosterone of 12-15 ng/dL is a good number, puts you in the range of a 25 yr old! Replacing plasma and such like interventions sound VERY promising indeed...I'll have to settle for 8 week phlebotomies, which according to CONBOY, he said this exchange protocol represents about 10% of the full exchange therapeutic. 25 chinups as an 80 yr old, amazing. What are you doing for diet?