These Molecules Reversed Aging by... YEARS! [TRIIM Study Explained - Study 216]

[@ivanverdian1]

The aging reversal cocktail is: 1. 0.015 mg of HGH 2. 50 mg of DHEA 3. 500 mg of Metformin 4. 3000 iu of Vit D 5. 50 mg of Zinc

[@Benny-dv7xm]

Thanks get past the ad sense you tube requirements to see if there is anything new to fact check and there ISN'T!

[@leebid1626]

Cheers man. This really should be in the description but hey ho 👍

[@Batmicheal]

I have the metformin, D3 and Zinc. What’s DHEA and what safe source of HGH?

[@Zhdhcjen]

@@BatmichealDHEA is Dihyedeoandrosterone, which is a hormone. You cam just buy it as an OTC supplement. HGH is Growth Hormone, so you’ll need to get it at a hormone clinic.

[@asqs9071]

❤

[@Physionic]

Notes: 1. [Amendment] I should have mentioned this (a mistake on my part), but the study was not a double blind, randomized controlled trial. It was an intervention trial, however it did not have a control group. I still believe the results of the study, but that belief is not grounded on any foundation of evidence beside the fact that other studies have shown effects of these molecules in other trials. So, up to you if you believe the results to be non-placebo driven. My apologies for not adding it - it completely failed me, and it’s important information. 2. People have been confused on the metformin part - the idea in this study isn’t to use metformin for its life extension properties, but to maintain insulin sensitivity. I’ll look at metformin independently (and berberine) in the future. 3. DHEA was added to control insulin release. So, both metformin and DHEA were added to mitigate potential negative effects of HGH alone.

[@sarrazin5]

Berberine please!

[@tomg5405]

But why are the numbers going up again after 9-12 months?

[@tomg5405]

But how to get metformin and the growth hormone? 😅

[@capnkirk5528]

@@tomg5405 Yeah THIS ... BUT if it's INSULIN SENSITIVITY a carefully managed keto diet can help using HOMA-IR if you have a cooperative doctor (I DON'T 🤬). HGH may be possible to be stimulated by resistance (weight) training. DHEA is banned in Canada which I find INCREDIBLY interesting as Canada doesn't ban a number of things that SHOULD be, why is THIS banned?

[@JazenValencia]

@@tomg5405 You can mimick GH and Metformin with GH mimiicking peptides, CJC-1295 and Ipamorelin used together as a replacementfor pure HGH, Di-hydro Berberine replaces Metformin, and Ironmag Labs has a great topical DHEA that's very powerful. This protocol IMHO is a great replacement for the prescription stuff you can't get.

[@ivarhakuse8572]

12:38 1. HGH 2. DHEA 3. METFORMIN 4. Vit D 5. Zinc

[@jonnitrea]

Thank you

[@joebartles3986]

You spoiled the video for me.

[@joebartles3986]

@MrGriff305 I have to. It’s a disease. Don’t be hating on me.

[@joebartles3986]

@MrGriff305 Don’t be swearing at me now. That’s rude and uncalled for. Reading the comments first is a clinical condition I am subject too. I can’t help it so don’t be a hater.

[@joebartles3986]

@MrGriff305 it’s called Griffism…

[@lucycooper55]

I absolutely love every time he says glomerular filtration rate ! ❤ I’m a dialysis nurse so makes me smile to hear that struggle. So hilarious. Love this guy

[@mcy1122]

A great example of how superb Nicolas is when translating rather complex science to engaging and useful content. Thank you!

[@druvaciam5407]

Would be great to see separate videos describing how all these 5 components are working inside our bodies.

[@barbararitam7355]

1:57 1:59

[@homesignup]

Fantastic study!! I will have to share this with my friend who is interested in reversing thymic aging. Thanks for the study. 😃 To boost HGH naturally, all you need to do is lose body fat, decrease insulin levels (which is why they likely used metformin), increase arginine, lysine (unless you have cancer or pre-CA lesions), get enough sleep, HIIT exercise (anaerobic exercise that stimulates HGH by up to 450% during the 24 hours after you finish your intense fast workout.), resistance exercises in a load-dependent manner (aerobic exercise), and do more intermittent fasting (those who do 24-48h can increase HGH 3 to 5-fold. But do at least 12hrs if you want to see a bit of a raise, 18-20h is optimal for those who like doing it daily). DHEA is useful in old age due to lower levels. My friend takes pregnenolone instead which is the master precursor hormone of all your hormones. I am not taking of these yet till I get older. Right now don't need it. Berberine may be used in place of metformin because it will decrease both insulin levels + triglycerides + lipid levels in a safer natural way, besides activating AMPK. D and Zn are a no brainer. Thanks again for this cool video!! :D

[@wallstreet_au]

12mg of melatonin before bed also helps.

[@amperage8032]

Excellent comment!! How closed do you think these natural ways will get you vs if you had supplemented? Supplementation doesn’t even seem like an option. Wonder how they equate to each other in how much they impact HGH, which ones work best?

[@dewdew34]

I’d never wake up … stuff is like a 24 hour interrogation for me lol

[@PrestonTalbott]

​@@wallstreet_auThat's way too much melatonin.. you saturate receptors at like 3mg.

[@wallstreet_au]

@@PrestonTalbott i think youre right.

[@suj1201]

Congrats on 100K, Nicolas! Proud of ya, man. That’s awesome and very well-deserved! 👏👏🥳🎉

[@stasstarcha]

Just a week ago youtube suggested Greg Fahy and his trim-x study and now it's all here with details we love physionics for. Amazing!

[@HarrySerpanos]

metformin is raising the ALP, an alternative to metformin would be taurine supplementation.

[@lauraw.7008]

Ooh, think I like that better!

[@Libertas_P77]

Extended fasting over 48hrs dramatically increases HGH, and I have been taking 25mg DHEA for 5yrs now (I’m in my mid-40’s), along with Berberine in place of Metformin. Great results from my own side, this study merely reinforced my stack and protocol was potentially on the right track to have a positive impact on aging. I recall when this came out at the time, and was surprised to see DHEA in the trial, but it nonetheless left some quite interesting epigenetic results - I just take all of those clocks with a huge pinch of salt.

[@UNKLELUKE86]

Thanks for sharing. DHEA √

[@waltermagee2305]

DHEA+HGH+Metformin, in addition to other components mentioned in this video have yielded signifigant results increasing athletic performance within three months. Nascent iodine supplementation is another important consideration as well as vitamin E. Staggering supplementation times should be considered in order to avoid antagonistic influence that could diminish absorbtion and temporary metabolic enzyme depletion.

[@Libertas_P77]

@@waltermagee2305 I’m 48hrs into my monthly fast and HGH levels are currently 5x normal. I up my DHEA to 50mg for the next two days with berberine, to further mimic the conditions of this trial and in theory maximise the longevity benefits of the fasted state.

[@Helene_experience]

@libertas_p77 are you a man or a woman ?

[@Libertas_P77]

@@Helene_experience Man

[@timothydavis2568]

Nice to see the channel taking off, never thought there would be so many nerds on KZbin. In the end, science will prevail!

[@Santa-ny1yp]

If you want budget fixes, they are as follows. 1 red light therapy for hgh. 2 apeginen for cd38 reduction. 3 Berberine instead of metfomin. You could always sun blast yourself for vitamin d. Happy living!

[@incognitotorpedo42]

Don't sunblast yourself to save a few pennies. Vitamin D is cheap. We know sun ages/damages the skin. You'll never get rid of those wrinkles.

[@jons2447]

Thank you for this! I just bought a Mito red light & already take berberine daily w/ zinc (pyroluria) & vit. D (& others).

[@lauraw.7008]

Living in Seattle, sun blasting won’t work 😢

[@lauraw.7008]

@Santa-ny1yp Unless one lives in Seattle or other similar places along northern latitudes.

[@Schnelllll]

How much Apigenin would it have to be? I bet 1500mg of berberine would be fine...

[@verunchik1065]

Thank you very much! I really appreciate your work, Nicolas!

[@keng7758]

Your analysis of these studies is soooo helpful and appreciated! Your well researched work is incredibly well done. On the study molecules…I was on Metformin by request as I’m close to being pre diabetic, but have changed to Berberine to minimize the impact that Metformin has on VO2 max (workout) reductions and the effect it has on reducing testosterone. Berberine has helped reduce my A1c and lipid readings. As a 68 yr old male, I really want to keep my workouts to be as effective as possible and no male wants testosterone reduced by medication.

[@IanRushtonMusic]

What I find interesting about the stack used is that it didn't appear to include any of the popular and more widely promoted anti-aging supplements like NMN, GlyNAC etc and also the likes of omega3, collagen etc.

[@IanRushtonMusic]

@@WhyteHorse2023 While true, I was also thinking of things that decline with age: NAD+, glutathione etc. and popular supplements that have been shown to be of some benefit e.g. NMN, GlyNAC etc.

[@tracymullane8818]

I just read the article last night where Peter Attia who is writing about the particulars about this TRIIM study (Thymus Regeneration Immunorestoration and Insulin Mitigation) mentioned it was a weak study because there were 9 or 10 people (the article says 9, the study shows 10) only men (as NV laments during a podcast) and there was no control group. They added the DHEA because the HGH increases cholesterol and the main author of the study, Fahy, added it in based on a hunch- he was right- the cholesterol went back down on the DHEA. Thymus seems very important as the study cites roughly at about age 63 is when cancer, infectious disease, autoimmune conditions, generalized inflammation, arthrosclerosis and all cause mortality increase due to lack of T cell production which happens in the thymus gland as well as lack of t cell receptors. As @physionic points out in his recent podcast, adipose tissue collected around the thymus gland basically kills it off and removing the fat enables it to function again. This was shown in diagrams of the gland in the study! So the conclusion was to mitigate insulin production, and restore immune function by regenerating the thymus gland. (Sorry, I'm very good at stating the obvious.) Regarding the epigenetic effect mentioned, it only gained about 2 and 1/2 years. I'm wondering how that can be true because earlier in the study they mentioned that the immune response in centenarians is still apparent and this was part of their goal. Maybe if we could see a comparison with the blood markers of a centenarian we could measure the effect more accurately. So the goal was to keep the vibrancy of the immune function in order to prolong life. If this is so, why not also prescribe thymosin alpha 1 to everyone? There are no poor side effects. This has the effect of increasing hematopoiesis which is the goal here. Keep everyone strong, apo B and LDL low, a nice low body fat percentage (BMI can be higher because of muscle weight) and take higher amounts of B vitamins for the NAD effect, especially B12 for higher RBC count? I think that would solve many of the problems along with keeping low insulin- very significant because it was perceived to contribute to depositing fat, which needs to be controlled to liberate the thymus gland so it can do its job. A few things I noticed about the study is that exercise is not mentioned at all. The weight of the men or weight change is not mentioned. And diet is not mentioned at all. With no control group and only measuring the blood markers, I am wondering what the real significance is of a study like this could be without other measurements and records. Interesting study but I'm sniffing stacks as opposed to lifestyle changes. I think the focus should be on the function of the thymus gland, and what we need to optimize the whole body response to that which is much broader, and not the stack.

[@chuckm2405]

Well thought, logical, brilliant

[@tracymullane8818]

Thank you​@@chuckm2405

[@ThiagoBenazziMaia]

So, that's what I found out so far and why you probably see this "coincidently result". - Epigenetic clocks are sometimes based on "whole blood". - Many times are using something like a "Random forest regression". - The problem of whole blood is that you take a mix of cells, including B and T cells, and make an average of the epigenetics. - Now let's take for example the methylation of cg02162324. - in a sample I have here, the methylation of B cell for this CpG is 0.25 where the methylation of T cell for the same CpG is 0.61 in the same sample from the same patient. - As we age, the proportion of T and B cells change, and probably that's what's happen on this research when they start to play with the immune system. - So when you apply an aging clock like horvath clock trained on whole blood, you are possibly (at least is the conclusion I'm arriving on my study), not calculating the age, you are calculating the proportion of B and T cells and therefore estimating the age. - So although multi tissue ageing clock are great for a lot of things, I believe that for epigenetic ageing must be calculated using single cell methylation.

[@herculeholmes504]

Thankyou! This sounds like a very good explanation to me.

[@kenswanston820]

Does the ratio remain consistent for both types of cells, or have you determined that one is a better representative of age change/reversal? These detailed blood tests are not normally done in Canada (USA too?) and in Canada a doctor appears to be the only way to even get a 'normal' blood test. How can this information be acquired by a regular citizen not in a study?

[@ThiagoBenazziMaia]

​@@kenswanston820 I still need more data to find something more conclusive. I can see so far that the different population of blood type is enough to change in around 8-14% the prediction of the age. On the other side I couldn't use only the blood population to predict the age of the patient. So, is like, helps to predict the age, but doesn't help enough to be used alone to predict the age. (how much of 8-14% influence the result) NK 100.000% T 76.560% B 65.663% CD4T 60.902% CD8T 28.086% So, this little change in age in the paper could be related to this variation. In many countries a standard blood test can be done directly in the lab, without the need of a doctor for very cheap price, you just need to tell what type of blood test you want to be done.

[@tomb8430]

As a 58 year old, now understanding more about keto/carnivore, and the benefits it has given me in the last 6 months, I would love to be involved in trials. Experimenting on myself and doing analysis has been a really good and positive experience.

[@Facetime_Curvature]

Have you learned about how ketoacidosis is you polluting your blood with ketones, which are cellular waste, and turning it acidic which is an environment that cancer grows best due to messenger proteins, that tumors send out to get more blood from their environment, don't function in alkaline/ basic pH? You are poisoning yourself for temporary muscle growth. Muscle mass is not an indicator of organ health.

[@MsTatli]

I deffinately need that coctail....

[@IjzermanPieter]

Funny, 57 here and changed to same diet, no more alcohol and sports routine that totally changed my life. So the additional supplements would be interesting indeed. I am looking into it. This particular study needs to be redone with larger population and blinded etc..

[@dallysinghson5569]

May want to get your test levels checked bro, carbophobia is not optimal for the man hormones.

[@StKrane]

Nice one! The protocol seems realistically feasible. Excited for the data of phase 2!

[@adamscottv]

Except HGH ...

[@lymphomasurvive]

There are ways to naturally increase it. ​@@adamscottv

[@philsorensen6277]

Feasible? Have you seen the price of HGH therapy?

[@lv1985aa]

Just to clarify, that HGH dose of 0.015 mg/kg was done 3-4x per week and not daily? From what I recall reading the study when it first came out.

[@redberries8039]

..and the others daily?

[@lv1985aa]

@@redberries8039 yea the others are definitely daily dosages

[@Quietword]

Haha...love your sense of humor. This really hits home. Been very close pulling this protocol... Also adding a Khavinson bioregulator peptide called Thymogen to heal the gland. Thank you & Happy Holidays!

[@TheMaui2020]

My grandfather lived to 104, never took a supplement in his life. He was an MD and advised people to eat a wide variety of wholesome foods, but not too much. Sounds a lot like Michael Pollan.

[@MorrisLess]

Cool. Where can I get some of this "wholesome food" stuff? When I go to the store, all I see are chemical concoctions, mineral and vitamin depleted produce laced with pesticides and herbicides, and antibiotic laced meat raised in feedlots.

[@TheMaui2020]

@@MorrisLess You can actually see pesticides on produce and the amount of minerals and vitamins in them? Amazing! I'm sure the FDA and USDA would love to have your services so they can do these measurements without expensive equipment. When I go into a food market I see carrots, melons, bananas, lettuce and dozens of other wholesome foods. What "chemical concoctions" do you see? You need to get help about your paranoia or you will starve to death.

[@OP-lk4tw]

@@TheMaui2020that's not a convincing argument, you have 1 subject, 1, you didn't even specify his health state at that age and previous, maybe he could have lived up to 125 years but he died earlier because of his diet, maybe he could have been healthier at those ages as well, he probably had good genetics, and avoiding processed foods is already a big deal, that doesn't mean he was achieving anything close to an optimal diet

[@TheMaui2020]

Yes, he could have lived to 200. Sure. @@OP-lk4tw

[@pambaughman1579]

@@TheMaui2020how do u see it

[@matrixfull]

what you do is so precious. I could not reach this knowledge without you translating it for me. My brain can't handle complicated stuff. You make transform information into bearable to understand.

[@SAOSIN987]

ALP levels can be elevated during periods of rapid growth, such as childhood or adolescence, due to increased bone remodeling so this rejuvenation stack could be improving bones.

[@Critterpal]

I came here to say this also!

[@Yogiraj1969]

I'm wondering if the increase in ALP was statistically significant given the low power (low sample size)?

[@michelezimmerman6430]

And during pregnancy APL is normally high.

[@davea136]

I was curious, with what frequency was the cocktail administered? Thank you for the video.

[@barbarashirland9078]

Would fasting help reduce the fat in the thymus? During fasting, interstitial fat in the organs tends to go first.

[@todayipaint4667]

Excellent suggestion.

[@kenswanston820]

​@@WhyteHorse2023...so for a 71 yr. old male, do you know if fasting (1, 3, 7 days?) would sufficiently boost HGH to eliminate the need for an injection (assuming it is even available in Canada on request)? Does a One Meal A Day regimen of usually a Keto diet generate an adequate amount of HGH?

[@danaustin5869]

Increased HGH can come from exercise and/or fasting. DHEA, D, and Zinc can come from easily available supplements. Metformin isn't easy for non-diabetics to get, but Berberine is easily available, has some similar effects, and may work anywhere from less well in this concoction to better than the Metformin. It seems likely that the measured antiaging effects seen in this study are the simple sum total of the effects of the individual substances rather than some 'magical' interaction between them. Anyone else have thoughts on this?

[@SkyRiver1]

I believe you are correct, and metformin will obviate any physical exercise you do, gains will plummet or become negative especially aerobic performance, and muscle gain.

[@ilevitatecs2]

Metformin is extremely easy to get…there are a few online sources that will fill a script within minutes and not having to officially see a physician…and outside of the US it’s even OTC

[@andrewrivera4029]

Yea I agree with the exercise and fasting part to increase HGH, the study was done with 50-65 year olds which I am one. I’m trying to stay nattie so will do that before I take a prescription. We also have control over insulin sensitivity by not eating carbs so I try to do these things to stay healthy and all my inflammatory markers are low. Just did a CAC test and advanced lipid cardiac panel and am waiting for the results to compare with the ones I did 5 years ago.

[@wiczus6102]

The ammount of hgh administered is a hundred milion times higher than what you can get from exercise. Even if by mg they meant micrograms, spread it over 7 days and if I would assume that HGH is extremely short lived (high turnover means that the same elevated baseline is equivalent to higher dosage), that would still be way more than what exercise can give you.

[@Fullmoonrisingtarot]

One thought that rose to the top while reading your post, and I have many to ponder right now:) . My understanding is The body produces human growth hormone while you sleep and on an empty stomach . so not eating a few hours before bed gives your body more time to produce it while you sleep . It begins producing it 6 hours after your last meal and only while you sleep and there are Other benefits as well to sleeping on an empty stomach.

[@Dan-dg9pi]

Very intriguing topic. Like some other commenters, I was surprised at the zinc dosing. It also raises questions about whether the mixture of molecules should change over time and based on other medical conditions.

[@statementmark2131]

I've read before about high doses of zinc causing poor absorption of iron

[@alrivers2297]

​@@statementmark2131I'm not sure about iron, but too much zinc causes poor absorption of copper.

[@karlhanso]

Zinc is bullshit you only need 11 miligram per day magnesium dialy requirement is 410mg per day 37 times more that zinc

[@Dan-dg9pi]

@@karlhanso Using this "logic", would you say that magnesium is bullshit relative to protein because we all need a lot more than 410mg of protein a day? Alternatively, is it just possible that we need all minerals within certain ranges and my question had to do with whether the mention of zinc (not a bullshit mineral) in the video was out of this ideal range?

[@karlhanso]

@@Dan-dg9pi try to live without magnesium if you can. when heart relaxes uses magnesium-potasium and when it contrancs uses calcium. How they treat torsades despointes with magnesium sulfate. and torsades despointes can lead to suddent dead. I mean you dont need a lot of zinc to function correctly meanwhile magnesium is need to function correcly..

[@MrRockrobstr]

Fascinating! In my mid to late 20’s I was a participant in the human growth hormone study and have since taken three of the other four compounds (excluding metformin) used in this cocktail at various times.

[@franciscochacon5542]

That's amazing! Do you feel that it has kept you young? And what clinic or Doctor prescribes HGH? I'm looking to start taking it along with DHEA, Berberine (in place of Metformin), Zinc, and Vitamin D.

[@Web3Dre]

Thank you for the video Physionic! I learn so much from your channel

[@InvestigadorTJ]

Can you replace BERBERINE FOR METFORMIN as an alternative? For reversal?

[@requetevision]

I think the key molecules are Vitamin D3 (should be taken together with Vitamin K2) and Zinc (3 types). The zinc is a well known Thymus gland enhancer

[@xemtuvi-nhiettinh-az]

A great conclusion how did you come up to this find out?

[@HAOS5HD]

​@@xemtuvi-nhiettinh-azCommon Sense .

[@LenHealsU]

I just love your videos! So professionally done in every manner way shape and form! I, myself, try to retard the aging process by eating a (mostly whole organic) plant based diet, with lots of antioxidants, with just 1 organic pasture raised egg daily. I do also take organic nutritional supplements. At 75, I still mountain bike, hike, swim, etc. Most people thing I'm around 59 or 60.

[@jons2447]

Plant based diets may not be as "healthy" as claimed considering how carnivore has solved some health issues.

[@LenHealsU]

@@jons2447 It works for me and all my allergies disappeared, etc., etc. . But you are right that it may not work for some people.

[@Ash-m7l]

The longest living people on earth eat in a very similar way (mostly plant foods, add in fish). Carnivore diet doesn't convince me as populations which eat the highest amount of animal protein and fat have some of the lowest lifespans (even when looking at populations which do not eat excess processed foods).

[@thierryvidal63]

very nice. The fact that the thymus density increased is certainly something. Personally I would love to see a similar study but complemented with Thyroid, gonadal and adrenal hormones. Not just growth hormone, dhea and vit D. All hormones are abruptly down after 50. The production stops, the glands are old. Doesn't matter what you do to stimulate "naturally". Why not supplement everything that is available ? Sterling work Nicolas, as always. Thanks !

[@jamesthompson7282]

Well, supplements aren't necessarily benign. Most aren't. In some cases the dose is important: too little provides no therapeutic benefit; too much is toxic. And we're still in early days when it comes to research into long-term side effects & benefits. There's little/no research on conflicts & interactions between supplements, and just the beginnings of research into interactions between them & pharmaceuticals. It's a minefield & most people don't realize just how significant a danger this represents. Worse, there are non-trivial issues with sourcing (synthetic vs natural, environmental toxins &/or unanticipated impurities...) & with production (supplement manufacturing isn't much regulated and is anyhow almost entirely outsourced to China & India, where FDA oversight even of pharmaceutical manufacturing is non-existent & manufacturing standards are, to be polite, highly variable. People assume that the availability of supplements everywhere indicates they're perfectly safe. Not so. They're potentially a powerful aid but also a bit of a minefield.

[@reggaespiritdance]

Started Thymus Gland extract a couple months ago and at 41 I noticed a difference in my vitality. But excellent presentation of information, definitely sharing this with my clients who comment on my youthfulness. Most say I look 30 or younger…

[@MadHatter11371]

Hi what type did you use?

[@zuikis]

That's very cool, so when and where can i buy this cocktail 😂?

[@mustafanaser9789]

Just one question about DHEA in general. There are some fertility clinics pretending on their websites that DHEA shut down Testosterone and Sperm production. Now are they right? What is you opinion on these claims? From my point of view it doesn't make any sense since it is just the testosterone or hormones similar to testosterone (like exogenous steroids for bodybuilding) that can do it or is DHEA also quite the same?

[@Kevin_Street]

Hello! KZbin recommended this video to me, and I'm glad it did. You do a superb job of explaining the results of the study. Definitely coming back to this channel.

[@Physionic]

Glad it was helpful!

[@ryuuguu01]

same thing for me. just subscribed.

[@helmutwilhelm8918]

Ditto

[@studygodsword5937]

@@Physionic You need to go into hiding from the Democrats and big pharma, you mentioned zinc on social media

[@towerace1238]

glad i found your site.. dealing with doctors and trying to self educate is a shameful dispute that should never take place,, but it does sadly

[@good4ud]

Do you think it would be feasible to have a conversation/friendly debate with Dr Anthony Chaffee? he seems to be doing podcasts/interviews everyday but most the people he speaks to arent well versed in the medical literature or already have their mind made on carnivore etc. Would love to see you discuss the topic with him as I really think he is the most eloquent and coherent speaker on this.

[@jtk5867]

Could you please provide comment on the potential efficacy of Berberine vs Metformin, as it relates to this application?

[@Physionic]

Will do.

[@jons2447]

@@Physionic "Thank you", in advance.

[@lindapestridge3073]

Oh good you asked the question that I wanted to know Metformin vs Berberine I take Bererine hoping it is as good as metformin without any side affects

[@Boiing008]

I think the way you put things across is a gift & really easy to understand. It's a pleasure to listen too :-)

[@Physionic]

That's incredibly kind of you to say, B. Thank you.

[@rookandpawn]

I'm a new subscriber and I love your simple but informed communication. Thanks for covering these stories on health and wellness with detail. ❤

[@jaykent1836]

GH-->IGF1-->'new' skeletal muscle and bone growth (reflected to a degree by increased serum ALP level); there's your 'connection'...you're welcome!

[@Jeffreymart]

hgh bennefit?

[@jaykent1836]

@@Jeffreymart Yes...but, the highest quartile of IGF1 levels are associated with 'better' healthevity (somewhat elevated cancer risk though); but, the lowest quartile IGF1 levels are associated with the 'best' longevity...sooo...???

[@Jeffreymart]

@@jaykent1836 quality over quantity every time

[@ConradJupiter77]

My secret to reverse aging. I drink from the cup of the Holy Grail. I chose wisely.

[@jmc8076]

Brilliant. Smart man. 😉

[@Unsensitive]

Searching for the holy Grail alone would keep your mind active, and require exercise. You're n=1 is clearly biased. Please invent a time machine and clone yourself then have them live the exact same lifestyle, but doesn't care about the holy grail to correct for this. It's the only way we can know for sure.

[@joeont]

@@Unsensitivefor sure, did you see how jacked and ripped indiana Jones is in the latest movie?

[@Unsensitive]

@@joeont and he only searched for 2-3 hours while I watched the movie over 30 years ago! Those are some lasting gains there! Imagine an entire life searching... Then again.. he did drink from it so this might bias the study using him as a reference.

[@Physionic]

It’s not the shiny one, Indiana… :)

[@ExtaTer]

The immune modulation and thymus restoration was probably entirely due to HGH inducing IGF-1. The metformin was added to reduce insulin secretion due to HGH, because DHEA could not do it. The increase of the liver enzyme is most probably due to the high dose of zinc - probably toxic over long term. Epigenetic clocks correlate with aging, but that doesn't mean that reducing methylation translates in actual age reversal - Bryan Johnson has an epigenetic age of 20 years old, yet doesn't look like it.

[@ivydune4185]

Exactly. That's my quest. One thing is to be internally younger, another is to actually be younger. If your skin, muscles and bones are still sagging and shrinking, then you're still aging normally. Healthier, but aging. I can accept living for 80 years, but I can't deal with looking old(er). There's got to be a way to make our tissue, our skin, muscles, bones to regenerate to the stage of 25, the "end" of growth and the start of decaying.

[@ExtaTer]

@@ivydune4185 Contemporary medicine is not there yet, at all. They constantly confuse correlation with causation. Just because aging correlates with epigenetic aging, doesn't mean that reversing the epigenetic aging will rejuvenate you on microbiology level. Apparently aging is not only about epigenetic clocks.

[@ivydune4185]

@@ExtaTer so far, I think the scientists closer to that (and it will take years) is Michael Levin-s team. I wish we got at least some temporary fix until a real cure is found.

[@MJ-ge6jz]

Your dry humor is spot on!

[@Maxumized]

I am in a study. I’ve been in it for over 40 years now. It involves exercising 3-4 days a week, conscious healthy diet, low alcohol intake, no smoking, have a career working inside, maintain healthy body weight throughout life, partake in hobbies that make you feel good, avoid drama. I’m almost 60 and I weight same as high school…the clothes still fit me. I have a few friends who say I sleep in a freezer. The muscle mass I’ve gained above baseline since a teen makes all the difference I think. I keep my muscles (every body part) working and in turn they demand fuel. This fuel is of course is the little body fat I have and other toxins that build up in the body. The turnover of fat in the body and increased blood perfusion to the entire body keeps the aging process at bay. I’m convinced of my personal “study.”

[@frankblakley8249]

Anecdotal evidence isn't a study. Your delusional.

[@Maxumized]

@@frankblakley8249 …and you’re the drama that ages people when you can’t take a joke…Franky boy

[@frankblakley8249]

@@Maxumized I'm not aging you fast enough if your still alive.

[@Maxumized]

@@frankblakley8249 you’re exactly right. You’re like my daily constitutionals. I flush and forget…Franky Boy

[@JeffMcDuffie72MeridianGate]

Bs. Lots of people have followed what you said and get cancer. Get realistic.

[@starxcrossed]

Love your videos (and humor)

[@Physionic]

Thanks!

[@SkyRiver1]

I used metformin for a half year or so. My work out results nose dived to negative results, and I began having cramps in muscles that had never cramped before, like incredibly painful diaphragm cramping that was so bad I thought it was a hernia. Stopped metformin -- work out result returned to normal, cramping decreased significantly. In my seventies I question if the results are more positive than the loss of muscle mass production is negative. Addendum: When investigating the cramping was told by a very experienced nurse that the cramping indicated that I did not need metformin. Which I knew, but I think it did indicate that I was already insulin stable. This may be due to continual benign twitching of muscles in my legs for decades. This will keep blood sugar stable, strangely enough.

[@thierryvidal63]

Same thing here. I stopped after a few weeks because the metformin triggered what I suppose was an atrophy of the pyriform muscle. This was giving me an excruciating sciatica pain when I've never had any problem.It was totally depressing. Fortunately it disappeared completely when I stopped the metformin and reinforced this muscle.

[@Physionic]

A great point. I’d argue maintaining muscle mass is more important.

[@SkyRiver1]

@@thierryvidal63 I was also quite disappointed. Was told by a nurse that had vast experience, that the cramping indicated I did not need metformin.

[@jons2447]

Twitching could be a deficiency, prolly minerals.

[@SkyRiver1]

@@jons2447 Probably is in most cases. But I had all that and every test they could think of checked long ago and again and again recently. I forget the exact term that my neurologist used, but it amounts to benign mild involuntary contractions. Someone probably would not even notice it until I pointed it out. Very subtle, but a near continuous kind of rippling of the muscles in my calf and thighs. I can neither feel or control it at all. Can't reproduce it or stop it. Huberman once advised subtle leg movements, if forced to remain seated for long periods as a method of regulating blood sugar, in other words burning glucose in the calf muscles. I believe this constant rippling has done the same for me.

[@JenP2776]

I wonder if 7-KETO DHEA could have the same effect? I wonder the same thing about using berberine instead of Metformin.

[@michael-bell]

I think the simplest way a person at home can measure if their age is reversing, given that they already have visible signs of aging, is when their gray hair regains its color, when their wrinkles start to disappear, when their skin begins to become more taut, when their thinning hair begins to thicken, and when their receding hairline begins to fill in

[@todayipaint4667]

..and when they rise from their deathbed.

[@Al-vw8qt]

very well said

[@michael-bell]

@@Al-vw8qt Thank you 🤝

[@errebusaether]

@@todayipaint4667 Indeed. Hahaha. 😅

[@UniDocs_Mahapushpa_Cyavana]

What if those things don't happen, but internal mechanisms get much stronger, decreasing biological age? 🤔

[@PandaPunch]

Mg/kg meaning?

[@jtk5867]

Could you please comment on any studies which identify the amount of HGH increase experienced by "Intermittent Fasting", i.e. 36-48 hours? Could this amount approach the 1.05 mg of HGH given to a 70 kg man?

[@jtk5867]

@@ptinvite7942 Thanks, greatly, for the comprehensive analysis...fascinating stuff, really.

[@errebusaether]

Interesting. For me, this information is really important because I am aiming to find a way to stop or prolong aging. Thanks a lot for this video, it’s easy to understand and you didn’t skip any major details while focusing on the main point of the topic.

[@jimstormcrow]

Bloody fascinating!

[@VeganLinked]

With a list of like five different variables there that they're implementing (HGH, DHEA, D, Zinc...) How do they know that it's this particular combination and not just one of these interventions? Between the various interventions and doses it could be any one or combination of those things. Surely they parsed this out and controlled for each variable?

[@0chuklz0]

There was another study done in a university somewhere in the NW United States (sorry, I can't remember the one) that was working on an experiment with NMN and NAD. The idea was to check the cell maintenance processes, and they had an amazing response as well that apparently reversed several aging metrics. Are you familiar with this study? This would have been a few years ago.

[@sabymondal]

Harvard, Dr Sinclair.

[@0chuklz0]

@@sabymondal Thanks, for some reason I thought it was in the Northwest.

[@tracymullane8818]

Cool. I'm doing the stack already, except for the metformin. Wondering if I can substitute berberine or fasting days for the metformin.

[@Velvet_hippo]

Are these things synergistic with one another? I wish they studied each individually. HGH, metformin, and DHEA seem like big steps for someone to add to their supplement list.

[@drunvert]

Skip metformin unless you are fat. Just quit sugar and starch

[@jessicasanchez5765]

My Alk Phos is always elevated. They did a differential, and it's not coming from my bones. It's my liver. Would this be considered a high "normal" for me?

[@TheFarmacySeedsNetwork]

Man, I would love to see a study where they drop the metformin and increase the vitamin d to 30000 IU, and add some good sunlight exposure, and a few cold shocks. Are so hard to do without extremely technical lab equipment. Just discover your channel, excellent information and by far the best explanation I've seen yet that was short, simple and sweet about epigenetics! Subscribe and thank you!

[@cakesteak]

Yeah, and don't forget a few slaps in the face with a rainbow trout! Should be part of every stack.

[@shirleytimms7914]

Hi I take NAC and Glycine after listening to your podcast. I have osteoporosis in my knees and have just heard another podcast that it causes this? Can you reassure me ty. Love your work

[@phillipcowan1444]

I know that taking melatonin at night is supposed to cause a pulse of HGH. I take a 5mg sublingual dose at night but have no idea if the pulse rises to the level mentioned in the study. Does anyone out there know?

[@petercallison5765]

Taking melatonin long term may be a problematic issue you should look into.

[@phillipcowan1444]

@@petercallison5765 I haven't been able to find any credible research that says long term use of melatonin in the0.5-5mg range is harmful. In addition it seems that melatonin is such a primative hormone that there is no negative feedback loop ie. taking a supplemental form won't decrease the bodies natural production. A calcified pineal gland is the usual problem with decreased natural production. The K2 form of vitamin K is supposedly good for decalcification.

[@idiotsavant53]

And doesn't metformin blunt MTOR for muscle growth to counter sarcopenia?

[@salvadorslim3234]

This guy’s great 👍🏽

[@EdwardHansen-e9v]

Just a week ago youtube suggested Greg Fahy and his trim-x study and now it's all here with details we love physionics for. Amazing!

[@thebigpicture2032]

Thanks for posting.A few questions - how often was the stack given? Why did they chose that particular combo? I didn’t see a link to the study, were there similar studies that helped them hone in on this combo. I’m thinking the growth hormone alone would have the greates effect.

[@codematrix]

Can I replace 500 mg of metformin with berberine instead?

[@alisaw4076]

Interesting review, thanks for sharing. My question is once the reversal is achieved is it locked in or like most things has to be consistently maintained?

[@danmcmurry1203]

I want to live forever or die in the attempt. Kudos to you Doc Nic for this presentation, looking forward to the follow up. One caveat, in lieu of Metformin, I wanna use Berberine for my cocktail. Your thoughts?

[@EduardQualls]

@0:53 You say, "This study was performed at the Stanford Medical School" and my knee-jerk reaction (arthritis?) is immediately, "Uh-oh. Was Marc Tessier-Lavigne involved?" So, I listen on... @12:36 For some years, I've been taking 3 of the 5, substituting exercise for #1, and, this year, went keto for #3. So, the question I've faced is what am I supposed to do when someone thinks I'm in my 50's and they're 15 to 20 years too low? (Unfortunately, at the gym, in this condition, one goes from being "hot" to being "an inspiration." [Sigh of {age-enlightened} frustration...])

[@davidhammer7410]

Just a thought - Alkaline phosphatase is produced in several organs - not just the liver - this includes kidneys and bones. HGH and vitamin D3 both affect bone turnover. Perhaps the rise in ALP represents bone (or kidney) metabolic changes rather than liver?

[@Physionic]

Certainly a possibility. :)

[@greggcobb8701]

I’m pretty much using this stack now. Good thing I’m a somewhat older man. Losing weight and exercise combined with fasting for the HGH, Berberine in place of Metformin, Vit D, zinc, DHEA all easy to get without RX. You mentioned the rise in Alkaline Phosphatase . For me has always been an elusive marker- could be taking Vit D without K2 could monkey with the calcium blood levels and in turn push AP all over the place. Subclinical - parathyroiditis messed with my calcium & AP for most of my life. PSA is another marker that is easy to push around- Salmon oil - mine is always under 1.0. Good stuff- thanks for the news. 1:16

[@kdub7490]

@greggcobb8701 - how is this protocol working out for you so far?

[@janesjourney9564]

Question. Are 2 on the list to help mitigate HGH side effects? Metformin (to prevent diabetes) and DHEA (prevent gynecomastia)

[@janesjourney9564]

@@WhyteHorse2023 Thanks!

[@jswets5007]

I would be interested in seeing this study continued for another 18 months. I would also like to know why a certain number of the cohort only went to 12 months instead of 18. It is very suspicious that no reason for this was given.

[@imhere8380]

BE your own experiment...try water fasting and document the progress. Click over to Doctor Predip, a Florida Cardiologist to get info there. Good luck.

[@Nightraven26]

Also, 10 people is extremely small sample size, we can’t really infer any recommendations from that. Compared to something like CRASH-3 trial which has a sample size of 12 thousand patients. Also, reversing of thymus involution and changing fat cells back to thymus cells begs the question if the thymus tissue regenerated from fat cells is healthy or not and whether there would be a higher risk of thymomas (thymus tumors) further down the line.

[@jswets5007]

@@Nightraven26 Agreed. It would be exciting if this represented something beneficial that could be replicated for the population. However, the many issues with the methodology of the trial make this particular result sound like quackery to me. Ineffective at best and potentially harmful at worst.

[@r3drum3k92]

Is metformin available as a supplement anywhere without prescription?

[@tommasobonvicini7114]

Metformin usage always makes me raise an eyebrow: it's known for its reduction in mythocondrial function, that to me seems a big no, at every age.

[@RichardAMorris]

It's effect inhibiting complex 1 of the ETC chain in the mitochondria may be overblown. That only happen at large doses. I mean, it's not cyanide. Metformin's role as an activator of AMPK is likely more relevant. AMPK is a mitochondrial energy shortfall signal and it's effect on acetyl-CoA carboxylase in the cytosol is to disinhibit fatty acid transport into the mitochondria to be used to make more energy. More metformin = more AMPK = more fatty acids allowed into the mitochondria = less buffering of fatty acids in tissue like the thymus.

[@Nightraven26]

Why? There was a study which showed that people who take metformin live longer, although whether that’s because usually they’re diabetics who go to regular checkups so any potential lethal diagnoses are caught sooner compared to people who don’t take metformin or not remains to be seen. I think there’s a prospective study about that in progress.

[@Anjanya1948]

You didn't say what's on the cocktail tisk tisk. 😞

[@jayalanlife5926]

Cool job my friend

[@adampepin9944]

Clearly this works. Buddy Holly here looks no older than he did in 1958.

[@joshhart8722]

I’ve been following this study for a while, and the results are very exciting. With regards to the elevated ALP enzymes, I have not heard the team mention anything as a suspected cause. That said, exogenous DHEA is converted to DHEA-S during first pass metabolism in the liver. So, this could be the culprit?

[@Physionic]

That's a great point, Josh. I wonder if that's a contributor; although, other liver enzymes showed no negative effects, so is there a specific interaction with this metric? I don't know. They added DHEA to control the insulin released by the pancreas, so maybe if they found an alternative, they'd be able to see if that's the cause for the rise.

[@janesjourney9564]

Good luck getting HGH legally. It took 2 yrs to find a competent endocrinologist willing to screen me. He measured a large number of hormones, many labs, a 24 hour urine, and performed adrenal function IV stimulation test, as well as a several hour long IV GH stim test. Poor GH results began the “application” process. Including a full (rule out) cancer screening (colonoscopy, mammography etc) and body composition/bone density etc etc. Results are submitted for “approval”. HGH is more expensive than many people’s house payments. Which began another process - submitting my 1040s tax forms to be approved for financial assistance. HGH treatment was extremely beneficial on the short term. But it’s no panacea - adverse (painful) side effects had me beginning to wean within a year- until I stopped taking it altogether in 2 yrs. That’s the reality. The need for HGH treatment is NOT for the faint hearted...

[@Portia620]

What type of side effects?

[@janesjourney9564]

@@Portia620 Carpal tunnel syndrome is a common side affect. Hands going to sleep would be more of a "nuisance" compared to something like tenosynovitis that I experienced in my wrist - very inflamed feeling - rendering my thumb useless in grasping and in pain. It went away with dialing back HGH and splinting my thumb. Repeat...reduce again...until HGH treatment stopped. My thumb is fine now.

[@janesjourney9564]

@@Portia620 It also affects "metabolism". HGH treatment can push a per-diabetic into full blown diabetes. (it pushed my A1C over 6. Keto helped to keep that in check - high 5s.

[@redberries8039]

I think there are peptides that boost HGH ...sounds a bit flaky tho' it was that Huberman guy that mentioned it

[@janesjourney9564]

@@redberries8039 I just listened to one vid by Huberman. It’s the usual advice...for healthy people. Here’s the caveat - adults that actually need HGH treatment are not well. Here’s an example. Huberman spoke of sleep hygiene. And mine was restless, even while taking HGH. It gets itself into a circular argument. lol! Then, after HGH treatment, I found a nutritional supplement that has me sleeping like a baby - which helps anyone feel better! Sermorelin Peptide was never got discussed with my doc. (I’ve had pituitary issue, not hypothalamus) I’ve seen other OTC HGH stimulants that are cost prohibitive. Arginine, alone, may help Joe 6pack at the gym. But, for me? - nutritional support has been paramount. Canned cod liver has become my new super food. But, I do need more “building blocks” than I can eat, that I supplement. My doc does well to monitor some vits - like D and B etc. All that, does not seem like bad advice for the elderly - whose HGH is waning. : - )

[@charlesdowning5899]

Can you cover blood flow restriction training and lactate increase?

[@jeffreybritton3338]

It would be interesting to know the participants initial vitamin D levels and Zinc levels, since I hear most people are deficient. However one wouldn’t really expect any benefit unless one was initially deficient.

[@farnio]

can you replace metformin with berberine?

[@Stevieboy38]

I believe so, asked Chat GPT's latest model and it seemed convincing in this regard. "Yes, berberine does act similarly to metformin in several ways. Both berberine and metformin are known to activate an enzyme called AMP-activated protein kinase (AMPK), which plays a crucial role in regulating energy balance at the cellular level. Activation of AMPK leads to improved insulin sensitivity, enhanced glucose uptake by cells, and reduced glucose production in the liver. These effects contribute to better regulation of blood sugar levels and metabolic health."

[@farnio]

@@Stevieboy38 thanks mate

[@MrBottlecapBill]

The most interesting thing about all of this data you show, but that you never comment on is that the positive effects seem to reverse around the 10-12 month mark in every case.

[@raffaelecorrente1123]

the reverse aging process went to baseline after 9 months. But patients held what they got.

[@ki4npx]

I started and read Sinclair book,love the concepts, I use some of the Ideas , first year , my blood work was , perfect , my cardiologist, was blown away ...I was 70, now 75 my strength, is real good , I ride bike 25 miles a week , and weight lift , I take NMN , nac, tmg,,,,, some others too...

[@Kim-vf7rw]

I am a woman. I take all of this except HGH and I take 25 mg. Of DHEA and 50 mg. Pregnenolone. I take 25 mg. of Zinc.3000 Vitamin D Seems to work! I am 65 and people think I am 55.... thank you for this!

[@lindapestridge3073]

@@WhyteHorse2023 could you tell me how you get you HGH checked My dr would say I don't know what you are talking about and could you tell me please What nasty things you get from thymic involution and advice would be appreciated.

[@michellenotherday1482]

Very interesting and I really want to follow up next year with the Phase 2 study. Curious though: I noticed the graphs almost all show increases (or decreases depending how you look at it)…reversals in the improvements. Does this indicate the participants may have to continue taking the cocktail, or increase the portions, or does it stop working after about 12 months? Thank you, and as interesting as you made this, I subscribed!

[@upendo2]

Waiting for more info on this ALP rise as I am currently trying to biohack my way out of stage 4 breast cancer with prolonged fasting, keto, methylene blue, tons of supplements, etc. and recently all my labs were good yet ALP was elevated just over 140. I am also dealing with bone metastases, so hoping that elevation might be from healing bones, because I look and feel younger and better than ever!

[@jons2447]

Best wishes to you.

[@momoasraf3348]

Hey! I will pray for you sister, stay strong my friend. You WILL beat this!!!!! ❤❤❤❤

[@karenf9137]

I truly, sincerely wish you the best! Win!!!!

[@upendo2]

@@jons2447 thank you!

[@upendo2]

@@momoasraf3348 thank you 🙏🏽

[@mercedesfoster8257]

Question: the study was just on men where DHEA was part of the formula used. Would the effectivness hold true for menopausal women as I read females are at higher risk for depression side effect from DHEA ( the information did not specify the age group they got this result from) It interests me because it seems like DHEA would be helpful for menopausal women but this side effect concerns me

[@kdw75]

I couldn't even fathom the wealth a company could acquire if they were able to stop or reverse aging.

[@ortcloud99]

Survey says most people dont want to live longer, so not much money there. However another survey says high net worth people would pay half of their assets for another healthy 10 years, so that is alot of money

[@kdw75]

@@ortcloud99 That is surprising. About 80% of the people in my family I asked say they would like to live at leat another 50 years, but only if they were healthy. My wife and I only have a household income of $145k and we live in a town outside of Kansas City. Both of us would do anything to live longer and see our kids and grandchildren longer. Family is everything.

[@ortcloud99]

@@kdw75 There is an assumption that people do want to live longer, but I cant find any. I have asked around to everyone and cant find anyone who wants to live longer. I have also read articles on life extension and people in the comments are all negative. I would like to see a formal study and get this solidified. I think it would be surprising

[@kdw75]

@@ortcloud99 it’s funny because I would do almost anything to live longer, yet living to long would be one of the worst fates imaginable. :)

[@iraklimgeladze5223]

​@@ortcloud99people just afraid, when it's become common people will adopt in new reality

[@WholeEd]

If you want to apply these findings to your own n=1 health regimen "study" using GRAS supplements, you could use creatine to increase HGH, and berberine in lieu of metformin. I'm already taking most of this stuff, but I'm going to add DHEA to complement the collagen supplement I already take. It is generally better to obtain nutrients from whole foods, but if you have been on the standard American diet for years (or decades!) supplementation may be appropriate for a corrective phase as you transition to a more natural maintenance routine. You can't remove thymic fat that's already gone.

[@threeone6012]

I wonder if most/all of this could be accomplished with excellent diet/sleep/exercise.

[@joefarrow1599]

How are they giving growth hormone? It must have been injected?

[@CJWass09]

TMG could be added to offset the liver abnormalities

[@teddybearroosevelt1847]

Sure, if you take any b vitamin or nmn/nr it makes sense to take that as well

[@shoppinmadnesz22]

What about rapamycin?

[@aanchaallllllll]

0:21: 🧪 A study conducted at Stanford Medical School showed promising results in reversing aging in a small group of men. 3:27: 🧪 The researchers investigated the effects of time-restricted feeding on immune health and found that blood insulin and glucose levels did not change, but they were more interested in thymic involution. 5:27: ✅ Intervention increases thymic fat-free fraction in most participants, but not all. 12:07: 🔬 The study found that people who experienced a six and a half year reversal of epigenetic age also experienced improvements in several indices of clinical health. 8:42: 🧬 Epigenetic clocks are a way to measure and track aging based on changes in epigenetic tags on our genes. Recap by Tammy AI