Everything Tesamorelin

[madhacker]

*Repost from Madman, very interesting.

I have polyglandular autoimmune syndrome 1 (APS-1) and is possibly why I notice such a positive improvement with exogenous GH. IGF-1 has an even greater improvements in myself.

Abstract

Introduction

The GH/IGF-1 axis affects multiple metabolic pathways, and animal models demonstrate that it also modulates immune function. Little is known, however, regarding the effects of augmenting GH secretion on immune function in humans. This study used proteomics and gene set enrichment analysis to assess the effects of a GH releasing hormone (GHRH) analog, tesamorelin, on circulating immune markers and immune-related gene pathways in the liver in people with HIV (PWH) and NAFLD. We hypothesized that tesamorelin would decrease circulating markers of immune activation in conjunction with previously reported reductions in visceral fat and hepatic triglyceride.

Methods

92 biomarkers associated with immune function (Olink Immuno-Oncology panel) were measured in plasma samples from 61 PWH with NAFLD who participated in a double-blind, randomized, 12-month trial of tesamorelin versus identical placebo. Proteins differentially altered by tesamorelin at a false discovery rate < 0.1 were considered significantly changed. Gene set enrichment analysis targeted to immune pathways was subsequently performed on liver tissue from serial biopsies.

Results

Compared to placebo, tesamorelin decreased circulating concentrations of 13 proteins, including four chemokines (C-C Motif Chemokine Ligands 3 [CCL3, effect size -0.38 Log2 fold change], 4 [CCL4, -0.36 Log2 fold change], and 13 [CCL13 or MCP4, -0.42 Log2 fold change] and interleukin-8 [-0.50 Log2 fold change]), two cytokines (interleukin-10 [-0.32 Log2 fold change] and cytokine stimulating factor 1 [-0.22 Log2 fold change]), and four T-cell associated molecules (CD8A [-0.37 Log2 fold change], Cytotoxic And Regulatory T Cell Molecule [CRTAM, -0.47 Log2 fold change], granzyme A [-0.53 Log2 fold change], and adhesion G protein-coupled receptor G1 [ADGRG1, -0.54 Log2 fold change]), as well as arginase-1 [-0.95 Log2 fold change], galectin-9 [-0.26 Log2 fold change], and hepatocyte growth factor [-0.30 Log2 fold change]. No proteins in the panel were significantly increased by tesamorelin. Network analysis indicated close interaction among the gene pathways responsible for the reduced proteins, with imputational analyses suggesting downregulation of a closely related cluster of immune pathways. Targeted transcriptomics using tissue from liver biopsy confirmed an end-organ signal of down-regulated immune pathways, including pathways involved in antigen presentation, complement activation, toll-like receptor, and inflammatory signaling, and T-cell activation.

Conclusions

Long-term treatment with tesamorelin decreased circulating markers of T-cell and monocyte/macrophage activity, with corresponding downregulation of immune pathways in the liver. These findings suggest that augmenting pulsatile GH may ameliorate immune activation in a population with metabolic dysregulation and systemic inflammation.

 

[Tlow]

Hi guys,

Where are some good reputable places to buy tesamorelin and has anyone had any interfernce using it while on trt? And my objective is to lose belly fat that as I get older is getting harder to lose.

 

[JimGainz]

I’ve been wanting to try Tesamorelin but I’ve read in multiple studies that most people develop antibodies to the drug, which concerns me. Although the antibodies do not lower the effectiveness of the drug, it can’t be a good thing having these in your system,no? I already suffer from am anitibody related disease, Hashimotos Thyroid disease, and would not want to risk any more.

 

[BigTex]

Here is a lot of research on tesamorelin:

Mangili A, Falutz J, Mamputu JC, Stepanians M, Hayward B. Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat. PLoS One. 2015 Oct 12;10(10):e0140358. doi: 10.1371/journal.pone.0140358. PMID:

Julian Falutz, M.D., Soraya Allas, M.D., Ph.D., Koenraad Blot, M.D., Diane Potvin, M.Sc., Donald Kotler, M.D., Michael Somero, M.D., Daniel Berger, M.D., Stephen Brown, M.D., Gary Richmond, M.D., Jeffrey Fessel, M.D., Ralph Turner, Ph.D., M.P.H., and Steven Grinspoon, M.D. Metabolic Effects of a Growth Hormone–Releasing Factor in Patients with HIV. December 6, 2007
N Engl J Med 2007; 357:2359-2370. DOI: 10.1056/NEJMoa072375

Stanley TL, Falutz J, Marsolais C, Morin J, Soulban G, Mamputu JC, Assaad H, Turner R, Grinspoon SK. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis. 2012 Jun;54(11):1642-51. doi: 10.1093/cid/cis251. Epub 2012 Apr 10. PMID: 22495074; PMCID: PMC3348954.

Baker, L. D., Barsness, S. M., Borson, S., Merriam, G. R., Friedman, S. D., Craft, S., & Vitiello, M. V. (2012). Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Archives of neurology, 69(11), 1420–1429. Effects of Growth Hormone–Releasing Hormone on Cognitive Function in Adults With Mild Cognitive Impairment and Healthy Older Adults: Results of a Controlled Trial

Adrian, S., Scherzinger, A., Sanyal, A. et al. The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV. J Frailty Aging 8, 154–159 (2019). The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV - The Journal of Frailty & Aging

Dhillon, S. Tesamorelin. Drugs 71, 1071–1091 (2011). https://doi.org/10.2165/11202240-000000000-00000

Clinical Review Report: Tesamorelin (Egrifta) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Aug. Executive Summary. Available from: Executive Summary - Clinical Review Report: Tesamorelin (Egrifta) - NCBI Bookshelf

Friedman SD, Baker LD, Borson S, et al. Growth Hormone–Releasing Hormone Effects on Brain γ-Aminobutyric Acid Levels in Mild Cognitive Impairment and Healthy Aging. JAMA Neurol. 2013;70(7):883–890. doi:10.1001/jamaneurol.2013.1425

Dhillon S. Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy. Drugs. 2011 May 28;71(8):1071-91. doi: 10.2165/11202240-000000000-00000. PMID: 21668043.

Patel A, Gandhi H, Upaganlawar A. Tesamorelin: A hope for ART-induced lipodystrophy. J Pharm Bioallied Sci. 2011;3(2):319-320. doi:10.4103/0975-7406.80763

Clinical Review Report: Tesamorelin (Egrifta) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Aug. Executive Summary. Available from: Executive Summary - Clinical Review Report: Tesamorelin (Egrifta) - NCBI Bookshelf

Sami H. Tuffaha, Prateush Singh, Joshua D. Budihardjo, Kenneth R. Means, James P. Higgins, Jaimie T. Shores, Roberto Salvatori, Ahmet Höke, W.P. Andrew Lee & Gerald Brandacher (2016) Therapeutic augmentation of the growth hormone axis to improve outcomes following peripheral nerve injury, Expert Opinion on Therapeutic Targets, 20:10, 1259-1265, DOI: 10.1080/14728222.2016.1188079

 

[SteveCleves]

Just bumping this to see if anyone has any real world, non HIV lipodystrophy, experience with Tesamorelin? Anyone use it see real VAT reduction beyond what you could have achieved with diet?

 

[Jim Marlowe]

Just bumping this to see if anyone has any real world, non HIV lipodystrophy, experience with Tesamorelin? Anyone use it see real VAT reduction beyond what you could have achieved with diet?

Yes, I would fall in that category. Visible VAT reduction relatively quickly - I believe in the 15-18% range anticipated. 1mg at night, six nights on, one off since middle of last year. Continue to work out - barbell lifts. Weight on the scale is virtually unchanged, and I assume there is body recomposition happening to some degree. The only confounder is that I have transitioned from a strict Keto diet to a "Bio Energetic" (Ray Peat) diet. Trying to eliminate all PUFA, still consuming plenty of saturated fat, but increased carbs and decreased protein. Definitely my total calorie consumption is up if that means something to anyone.

 

[SteveCleves]

Yes, I would fall in that category. Visible VAT reduction relatively quickly - I believe in the 15-18% range anticipated. 1mg at night, six nights on, one off since middle of last year. Continue to work out - barbell lifts. Weight on the scale is virtually unchanged, and I assume there is body recomposition happening to some degree. The only confounder is that I have transitioned from a strict Keto diet to a "Bio Energetic" (Ray Peat) diet. Trying to eliminate all PUFA, still consuming plenty of saturated fat, but increased carbs and decreased protein. Definitely my total calorie consumption is up if that means something to anyone.

TY. Helpful.

I am still not really sure though how much Tesamorelin is actually doing that regular GH wouldn't do just as effectively. I guess it's probably an impossible question to answer.

 

[Gman86]

Yes, I would fall in that category. Visible VAT reduction relatively quickly - I believe in the 15-18% range anticipated. 1mg at night, six nights on, one off since middle of last year. Continue to work out - barbell lifts. Weight on the scale is virtually unchanged, and I assume there is body recomposition happening to some degree. The only confounder is that I have transitioned from a strict Keto diet to a "Bio Energetic" (Ray Peat) diet. Trying to eliminate all PUFA, still consuming plenty of saturated fat, but increased carbs and decreased protein. Definitely my total calorie consumption is up if that means something to anyone.

Quick question. Does eliminating PUFA’s include cutting out fatty fish/ fish oil supplements?

 

[Jim Marlowe]

Quick question. Does eliminating PUFA’s include cutting out fatty fish/ fish oil supplements?

Yes. My focus was originally on eliminating the non-Omega 3 PUFAs, but I'm going for everything, including all Omega 3s and Omega 6s. What I have discovered is that consumption of pork and chicken is responsible for a significant amount of my current PUFA intake due to modern farming practices. Apparently that can be mitigated by avoiding fatty cuts, so that means lean cuts of pork and chicken breast without the skin--basically everything I hate about modern pork and poultry. I love bacon and chicken thighs with skin. The only alternative is to go with organic pasture raised, non-grain fed pork and chicken. I've tried some products from a producer of low-PUFA pork (Aspey farms - that I found on the internet). It's fine stuff, but I will hemorrhage money if I eat that way regularly. So basically, keeping low PUFA is a gigantic PIA. When PUFA is consumed, the deleterious effects (from oxidizing PUFA) can supposedly be mitigated by also consuming saturated fat and tocopherols at the same time.
(I don't blame any commenters for judging me harshly, but I'm in it for the full effort).

 

[Jim Marlowe]

TY. Helpful.

I am still not really sure though how much Tesamorelin is actually doing that regular GH wouldn't do just as effectively. I guess it's probably an impossible question to answer.

Two reasons that you likely already know. The first is that it is half the cost of GH if using a compounding pharmacy with a proper script. And it can be as low as 1/4 of the cost if you are going with "research only" peptides. The second reason is that if you have pituitary function, then you are having your own body release GH rather than simply substituting it through an exogenous source. That said, I'm doing 1mg whereas Nelson in earlier post noted he was doing 2mg which is what was dosed in the trials IIRC.

 

[FunkOdyssey]

My focus was originally on eliminating the non-Omega 3 PUFAs, but I'm going for everything, including all Omega 3s and Omega 6s. What I have discovered is that consumption of pork and chicken is responsible for a significant amount of my current PUFA intake due to modern farming practices.

Allow me to introduce you to...

 

[Jim Marlowe]

Allow me to introduce you to...

View attachment 40515

I hear you. Of course beef is the primary protein in our household. But I am in a family of five, and I will have to pay for a divorce if we only eat beef. I cannot afford that.

 

[Gman86]

Yes. My focus was originally on eliminating the non-Omega 3 PUFAs, but I'm going for everything, including all Omega 3s and Omega 6s. What I have discovered is that consumption of pork and chicken is responsible for a significant amount of my current PUFA intake due to modern farming practices. Apparently that can be mitigated by avoiding fatty cuts, so that means lean cuts of pork and chicken breast without the skin--basically everything I hate about modern pork and poultry. I love bacon and chicken thighs with skin. The only alternative is to go with organic pasture raised, non-grain fed pork and chicken. I've tried some products from a producer of low-PUFA pork (Aspey farms - that I found on the internet). It's fine stuff, but I will hemorrhage money if I eat that way regularly. So basically, keeping low PUFA is a gigantic PIA. When PUFA is consumed, the deleterious effects (from oxidizing PUFA) can supposedly be mitigated by also consuming saturated fat and tocopherols at the same time.
(I don't blame any commenters for judging me harshly, but I'm in it for the full effort).

Don’t want to derail the thread, but ur 100% on the right track, are clearly very knowledgeable on what’s actually healthy for us, and what is not, and I couldn’t agree more with everything u said. Very impressed with ur knowledge on these subjects.

u definitely don’t want to be regularly eating any meat/ fat from a monogastric animal that’s being fed grains/ “a vegetarian feed”, and not eating it’s evolutionary appropriate diet. Once in a while isn’t gonna kill u, but eating it regularly just isn’t ideal, if optimal health is the goal, especially if u eat fatty cuts of these meats, like u were saying. And I LOVE bacon and chicken thighs, so I’m right there with u about being bummed that pasture raised pork and chicken is so difficult to get/ so expensive. I don’t even bother trying to find/ buy either. Luckily pasture raised eggs are very easily accessible, and fairly affordable

I can see vitamin E being beneficial, in regards to mitigating the effects of consuming PUFA’s, but check out Barrie Tan’s work, he has tons of interviews on YouTube. He’s spent his life studying vitamin E, and claims that it’s tocotrienols that we want to consume, and tocopherols can actually inhibit the positive effects of tocotrienols, or something along those lines. Check out his stuff if u have time. Very interesting. Been taking his Annatto-E product for a few years now. I’ll link it below

Annatto-E™ 150 mg, 60 softgels

<p>Annatto-E™ is a unique tocopherol-free, tocotrienols-only product, featuring tocotrienols sourced from the annatto tree. Annatto is the richest known source of tocotrienols, containing 100% tocotrienols (90% delta and 10% gamma isomers), with no tocopherols.<br /><br />Commercial vitamin E...

arn.ehealthpro.com

So what‘s ur views on PUFA’s from fish, vs from other sources, based on all the research u’ve done so far? Are they different/ better, or are no different, and basically all PUFA’s should be avoided? Obv farm raised fish is absolute crap, and nobody should be consuming that stuff in a regular basis, but what about wild caught fatty fish? Should be consumed here and there, in ur opinion, or should be avoided like all other PUFA’s? TIA

Feel free to DM me with ur response. Feel bad derailing the original topic of the thread