SS-31 Peptide Guide – Benefits, Dosage, Side Effects

SS-31 is a Peptide that can enhance your mitochondrial function and optimize your energy levels so that you can always feel energized!

Do you frequently feel tired and out of energy while working out?

While there can be a whole lot of reasons for the lack of sufficient energy, you don’t have to worry anymore because peptides like SS-31 peptide can boost your energy levels and will help you get back to your exercise routine in no time! 

SS-31 is a peptide that accumulates in the inner mitochondrial membrane and modulates the mitochondrial function. It then regenerates adenosine triphosphate (ATP) production, which brings the energy levels back up. 

Other functions of SS-31 include the repair of cognitive function, protection from anti-oxidative damage, and the reduction in apoptosis. 

Even though this might sound a little complex, I got you like always, as I have tried my best to break down the working of SS-31 for you! Stay with me till the end to find out about this peptide and to decide if it fits your requirements. 

Warning: The content on Muscleandbrawn.com and the information included in this article is intended for entertainment and informational purposes only. It is not intended nor implied to be a substitute for professional medical advice. Prior to buying anything, check that it is compliant where you live with your current government laws. We frequently mention research chemicals that are not made for human consumption. Therefore, before purchasing any product for personal use, consult with your doctor or healthcare provider first.

Key Takeaways:

  1. SS-31 is a potent therapeutic peptide that treats mitochondrial disorders and reverses mitochondrial damage.
  2. SS-31 mitigates the risk of oxidative damage by reducing oxidative stress manifested in mitochondria.
  3. SS-31 is also known to improve neurodegenerative diseases as well as cardiovascular disease.

What is SS-31?

The Sczeto-Schiller peptide (SS-31), also known as Elamipretide, is an aromatic synthetic tetrapeptide that is primarily aimed at correcting mitochondrial dysfunction, It has a molecular weight of 639.8 g/mol and is made up of the following sequence: D-Arg- dimethyl-Tyr-Lys-Phe-NH2.  (1

It consists of a series of small water-soluble peptides, and at physiological pH, it carries a net charge of 3+. (2

How Does SS-31 Work?

SS-31 is primarily a mitochondria-targeted peptide that is responsible for repairing dysfunctional mitochondria. Therefore, its mechanism of action mostly revolves around modulating mitochondrial biogenesis and function. 

To understand its mechanism of action, we must first look at the way that this peptide is transported within the cell. Its delivery inside the cell is not dependent upon mitochondrial energy, receptors, or other transporter-protein mediated processes and is thus rapidly absorbed by cells within 15-30 minutes. (3

Once it is inside the cell, it accumulates only in the inner mitochondrial membrane and does not travel to the mitochondrial matrix, even at high concentrations. It must be noted that SS-31 is relatively stable to peptidases which allow for a longer duration of action and only acts upon isolated mitochondria.

SS-31 has dimethyl tyrosine residues that scavenge reactive oxygen species and then form unreactive tyrosine radicals. This inhibits the oxidative phosphorylation of linoleic acid and low-density lipoprotein and thus allows SS-31 to act as an antioxidant. (2

Cardiolipin is an anionic phospholipid that is found on the inner membrane of mitochondria and is essential for the maintenance and functioning of the mitochondrial structure. When cardiolipin binds to cytochrome c, it can change cytochrome c from an electron carrier to a peroxidase which impedes the electron carrier function of cytochrome c.   

SS-31 peptide selectively binds with cardiolipin and therefore inhibits the peroxidase activity of cytochrome c. This restores the electron transport chain of the mitochondria, which allows for ATP synthesis as well. (4

The mitochondrial membrane has cristae, and the degradation of these is associated with aging. SS-31 is responsible for remodeling these mitochondrial cristae structures by enhancing the activity of cardiolipin, and it, therefore, produces anti-aging effects. (5

Proton leak is another phenomenon that is observed in aged mitochondria, which is usually prevented by peroxisomal adenine nucleotide transporter 1 (ANT1) protein. SS-31, in conjunction with ANT1, has the ability to prevent excessive mitochondrial proton entry and thus helps in restoring mitochondrial function. (6

Benefits of SS-31

Research done on mice has yielded positive results, supporting the efficacy of SS-31 treatment for mitochondrial dysfunction. This goes on to show that the benefits of SS-31 can be observed in all diseases that are caused by mitochondrial abnormalities. 

Fig 1. SS-31 reverses mitochondrial functioning in mitochondrial cardiomyopathy 

People with disrupted mitochondrial functioning may suffer a lack of energy and lethargy on physical exertion due to a lack of adequate ATP. In such cases, SS-31 not only restores the function of mitochondria but also consequently improves skeletal muscle function and exercise tolerance. 

Barth syndrome is a genetic disorder that is caused by defects in the TAZ gene, which is responsible for the maturation of cardiolipin. In this case, by mediating the effect of cardiolipin, SS-31 can prevent skeletal muscle weakness and dilated cardiomyopathy that follows Barth syndrome. (7

Mitochondrial dysfunction may eventually lead to mitochondrial swelling and cell death through the activation of the intrinsic apoptotic pathway. 

A study proved that the administration of SS-31 in mouse islet cells reduces apoptosis and the inflammatory response that ensues, thus increasing islet cell yield by preserving the mitochondria. This paves the way for SS-31 to be used in overcoming insulin resistance by preserving transplanted islet cells in humans. (8)  

The antioxidant effects of SS-31 make it a potent peptide for alleviating mitochondrial oxidative stress in older people, which directly contributes to cognitive dysfunction. A study on mice reported cerebral microvascular dilation and improved memory, motor skills, and gait coordination after treatment with SS-31. (9

Fig 2. Effects of SS-31 on mitochondrial dysfunction, synaptic transmission, and memory impairment 

Furthermore, SS-31 can be used for treating neurodegenerative diseases. This peptide specifically counters hippocampal oxidative stress and thus can be considered as a treatment for Alzheimer’s disease, in which the hippocampus is affected in the early stages. (10)

Findings suggest that SS-31 is also applicable in cardiovascular diseases such as diastolic dysfunction. By maintaining the proton leak mechanism in the heart, SS-31 can reduce reactive oxygen species and, therefore, any damage that may occur. 

By regenerating the levels of ATP, SS-31 has proven to be effective in countering ischemia-reperfusion injury in chronic kidney disease. (11). 

Is SS-31 Legal?

The efficacy and safety of SS-31 have only been established by trials conducted on animals. Therefore, it has not been approved by the FDA as of yet, due to the ambiguity in its effect on humans.

Who Should Use SS-31?

SS-31 is just the right peptide for bodybuilders who might feel that they lack energy and want to improve their skeletal muscle tolerance while exercising. 

This peptide is also effective for people who are suffering from any disease due to mitochondrial dysfunction, such as Barth’s syndrome. A study has also even proven SS-31 as a novel treatment for Amyotrophic lateral sclerosis. (12)   

Due to its antioxidant effects on the body, SS-31 can be used as a protective agent in diastolic dysfunctions, wherein the presence of mitochondrial ROS may become a cause of damage.

SS-31 employs antiaging effects and is, therefore, suitable for anyone looking forward to improving their physical and cognitive health with time.

Forms of SS-31

SS-31 is available in an injectable form that has been widely used in clinical trials as well and is most popularly administered.

Intranasal sprays of SS-31 are also available, which are much easier to use. Similarly, pre-mixed pens of this peptide have been recently introduced, which are highly portable.

How To Use SS-31?

SS-31 can be very conveniently injected subcutaneously or intramuscularly

Intranasal sprays are sprayed within the nostrils, and it is recommended to generally have a cleaned nostril before administering the spray.  

SS-31 Dosage

A dose of 40mg is considered safe and well-tolerable in human subjects. 

However, it is important to note that the dose may vary according to the condition that you want to get treated for, and thus a healthcare practitioner must be consulted.

SS-31 Cycling

Since the dosage of SS-31 varies according to the condition, it’s cycling also differs. 

Some research does conclude that SS-31 can be injected until the problem resolves, but it is always better to consult a health practitioner first. 

SS-31 User Reviews

Honestly, it is very hard to find any legitimate user experiences solely because of the fact that this peptide is so DAMN expensive.

What I have learnt so far from Reddit discussions is that people prefer alternate options such as Mots-c, which have proven to be really effective.

πŸ’‰Become a Peptide Expert (Protect your Health) πŸ’‰

Take our FREE 25-email course to learn everything you need to know about the scientific application of peptides. Discover how to protect your health, avoid sketchy peptide vendors, and stop wasting your hard-earned money. πŸ”₯ πŸ§ͺ πŸ’Š πŸ’ͺ πŸ’‰ 🩸πŸ₯ πŸ₯Ž

SS-31 Side Effects

The most common side effect of SS-31 pertains to the method of its delivery through an injection. This includes itching and redness at the site of injection.

Other mild side effects are headache and dizziness. 

Where Can I Buy SS-31?

SS-31 peptide for sale is nowhere to be seen, quite frankly.

There are not many trusted online vendors offering this peptide, so what I would recommend is getting your hands on any of the stores offering SS-31.

SS-31 vs. Other Peptides

SS-31 vs. Humanin 

SS-31 and Humanin are both peptides that have the ability to improve mitochondrial function and, therefore, age-related processes and life span.

However, SS-31 is a synthetic peptide that accumulates in the inner mitochondrial membrane, whereas Humanin is a naturally occurring peptide that is derived from the mitochondria and has various other functions as compared to SS-31. 

SS-31 vs. MOTS-C

SS-31 and MOTS-C are both regulators of mitochondrial function and help in regulating mitochondrial bioenergetics and metabolism, but their area of localization differs greatly.

SS-31, on the one hand, is a synthetic peptide that is used for its anti-aging properties and in improving cognitive functions. On the other hand, MOTS-C is specifically used to improve insulin resistance and, therefore, glucose metabolism.  

Is SS-31 Legit?

SS-31 is considered to be a novel peptide for the treatment of mitochondrial dysfunction and its related diseases. Its limited side effects also make it extremely user-friendly!

From improving energy levels to increasing exercise tolerance, SS-31 can work wonders for gym enthusiasts and bodybuilders.

While scientific literature has provided evidence with regard to its efficacy, the only barrier that this peptide faces is the lack of research on human subjects as well as any considerable user experiences.

People Also Search For

What are the effects of SS-31?

SS-31 protects the mitochondrial structure, scavenges ROS, increases ATP supply, reduces cytochrome C release, and inhibits mPTP opening and calcium overload by binding to cardiolipin in the inner membrane of mitochondria, thereby exerting anti-oxidative stress as well as anti-inflammatory, antifibrotic, antiapoptotic effects.

What are the peptides for mitochondrial support?

Abstract. Mitochondria-derived peptides (MDPs) are small peptides hidden in the mitochondrial DNA, maintaining mitochondrial function and protecting cells under different stresses. Currently, three types of MDPs have been identified: Humanin, MOTS-c, and SHLP1-6.

What is the best vitamin for mitochondria?

The most commonly used dietary supplement ingredients for PMDs include antioxidants, such as vitamin C, vitamin E, and alpha-lipoic acid, as well as electron donors and acceptors, such as CoQ10 and riboflavin.

What are mitochondria-derived peptides?

Mitochondria contain DNA with small open reading frames (sORFs) that encode functional microproteins called mitochondria-derived peptides (MDPs).
These MDPs can stay inside mitochondria, enter the cytosol, translocate to the nucleus, or be secreted extracellularly to target tissues.

SS-31 Reconstitution and Dosage Calculator

Comments and questions?

Join our closed Facebook group and get custom answers from the community.

Drop us a comment down below and one of our expert coaches will respond to it.

1)Nashine, S. (2021). Potential Therapeutic Candidates for Age-Related Macular Degeneration (AMD). Cells, 10(9), 2483. https://doi.org/10.3390/cells10092483

2)Zhao, K., Zhao, G., Wu, D., Soong, Y., Birk, A. V., Schiller, P. W., & Szeto, H. H. (2004). Cell-permeable Peptide Antioxidants Targeted to Inner Mitochondrial Membrane inhibit Mitochondrial Swelling, Oxidative Cell Death, and Reperfusion Injury. Journal of Biological Chemistry, 279(33), 34682–34690. https://doi.org/10.1074/jbc.m402999200

3)Siegel, M. A., Kruse, S. E., Percival, J. M., Goh, J., White, C. L., Hopkins, H., Kavanagh, T. J., Szeto, H. H., Rabinovitch, P. S., & Marcinek, D. J. (2013). Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell, 12(5), 763–771. https://doi.org/10.1111/acel.12102

4)Birk, A. V., Chao, W., Bracken, C., Warren, J. D., & Szeto, H. H. (2014). Targeting mitochondrial cardiolipin and the cytochromec/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. British Journal of Pharmacology, 171(8), 2017–2028. https://doi.org/10.1111/bph.12468

5)Szeto, H. H., & Liu, S. (2018). Cardiolipin-targeted peptides rejuvenate mitochondrial function, remodel mitochondria, and promote tissue regeneration during aging. Archives of Biochemistry and Biophysics, 660, 137–148. https://doi.org/10.1016/j.abb.2018.10.013

6)Zhang, H., Alder, N. N., Wang, W., Szeto, H. H., Marcinek, D. J., & Rabinovitch, P. S. (2020). Reduction of elevated proton leak rejuvenates mitochondria in the aged cardiomyocyte. eLife, 9. https://doi.org/10.7554/elife.60827

7)Sabbah, H. N. (2021). Barth syndrome cardiomyopathy: targeting the mitochondria with elamipretide. Heart Failure Reviews, 26(2), 237–253. https://doi.org/10.1007/s10741-020-10031-3

8)Thomas, D., Stauffer, C. A., Zhao, K., Yang, H. G., Sharma, V., Szeto, H. H., & Suthanthiran, M. (2007). Mitochondrial Targeting with Antioxidant Peptide SS-31 Prevents Mitochondrial Depolarization, Reduces Islet Cell Apoptosis, Increases Islet Cell Yield, and Improves Posttransplantation Function. Journal of the American Society of Nephrology, 18(1), 213–222. https://doi.org/10.1681/asn.2006080825

9)Tarantini, S., Valcarcel-Ares, N. M., Yabluchanskiy, A., Fulop, G. F., Hertelendy, P., Gautam, T., Farkas, E., Perz, A., Rabinovitch, P. S., Sonntag, W. E., Csiszar, A., & Ungvari, Z. (2018). Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice. Aging Cell, 17(2), e12731. https://doi.org/10.1111/acel.12731

10)Reddy, P. H., Manczak, M., Yin, X., & Reddy, A. P. (2018). Synergistic Protective Effects of Mitochondrial Division Inhibitor 1 and Mitochondria-Targeted Small Peptide SS31 in Alzheimer’s Disease. Journal of Alzheimer’s Disease, 62(4), 1549–1565. https://doi.org/10.3233/jad-170988

11)Birk, A. V., Liu, S., Soong, Y., Mills, W. C., Singh, P. K., Warren, J. D., Seshan, S. V., Pardee, J. D., & Szeto, H. H. (2013). The Mitochondrial-Targeted Compound SS-31 Re-Energizes Ischemic Mitochondria by Interacting with Cardiolipin. Journal of the American Society of Nephrology, 24(8), 1250–1261. https://doi.org/10.1681/asn.2012121216

12)Petri, S., Kiaei, M., Damiano, M., Hiller, A., Wille, E., Manfredi, G., Calingasan, N. Y., Szeto, H. H., & Beal, M. F. (2006). Cell-permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosis. Journal of Neurochemistry, 98(4), 1141–1148. https://doi.org/10.1111/j.1471-4159.2006.04018.x

Contributors

Kumar Rathi

Kumar Rathi | Writer

Kartik is a medical student with a passion for anatomy and physiology. He writes research papers, articles and blogs to raise awareness and also has a strong interest in teaching and public speaking. Aspiring to be a successful cardiologist, Kartik believes in connecting with people on a personal level and is an expert in peptides.

Read all articles
Subscribe
Notify of
guest

0 Comments
Inline Feedbacks
View all comments

SS-31

Chemical Structure

Mechanism of Action

SS 31 is an synthetic, aromatic tetra-peptide which exerts its effects by targeting the mitochondria. Once it is inside the cell, it accumulates in the inner mitochondrial membrane where it binds to cardiolipin, which is the main phospholipid that is responsible for the maintenance and functioning of mitochondria. Through this process, SS 31 inhibits the cytochrome c peroxidase and activates its electron carrier function which subsequently results in the production of ATP. This raises the energy levels in the body allowing people to carry out intensive exercise. SS 31 therefore also has an anti-aging effect and some of its free radical scavenging properties make it a potent antioxidant.

Class of Compound

Peptide

Street Names

SS 31, Szeto-Schiller peptide, Elamipretide

Effects

Restores mitochondrial function , Anti-oxidant ,Anti-aging

Side Effects and Dangers

Dizziness , Headache , Itching at site of injection

WANT TO BUY PEPTIDES?

Check out our best peptide company rankings comparing 🏷️costs, πŸ“¦ delivery times, πŸ“„ πŸ§ͺtesting methods, and ⭐️ public reviews!