Last Updated February 17, 2024

 February 17, 2024

Due to increased interest in mitochondrial-derived peptides, researchers are now inquiring about how to establish an appropriate MOTS-c dosage for their next experiment. 

MOTS-c is a short, mitochondrial-derived peptide that has been garnering the attention of researchers for potential applications, including: 

  • Weight loss 
  • Improved physical performance 
  • Anti-aging 

In this MOTS-c dosage calculator and guide, we cover what researchers may need to know about this peptide, including a reference dosing protocol and our recommendation on where to buy research-grade MOTS-c online.

Buy MOTS-c from our top-rated vendor...

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MOTS-c Dosage Chart | Quick Breakdown

Timeline 20-Day Research Protocol For Weight Loss and Metabolism
20 days Four doses of 5-10mg taken subcutaneously every five days
6-12 months 7-20mg
20 days Four doses of 5-10mg taken subcutaneously every five days

What is MOTS-c?

MOTS-c (mitochondrial open-reading-frame of the twelve S rRNA-C) is a 16 amino acid peptide naturally produced in the human body and classified as a mitochondria-derived peptide (MDP).

It has been found to play an important role in regulating metabolism and weight loss, improving athletic performance, and enhancing longevity [1]. Above all, mitochondria-derived peptides like MOTS-c play a “cytoprotective role in maintaining mitochondrial function and cell viability under pressure” [2].

MOTS-c is found in skeletal and muscle tissue, and in various organs such as the liver and brain. It helps to regulate metabolic functions in the body, including the conversion of glucose into usable energy. MOTS-c increases glucose uptake in muscle cells by activating the AMP-activated protein kinase (AMPK) pathway, without increasing insulin. AMPK is a key energy-sensing kinase and a master metabolic regulator that is triggered by metabolic stress [1, 3, 4].

The peptide is sometimes referred to as an exercise‐mimetic, meaning it can imitate the mechanism of exercise on the body; exercise itself induces endogenous MOTS-c expression in both skeletal muscle and circulation in humans [5].


mots-c dosage calculator


MOTS-c Benefits

MOTS-c has been found to produce varied benefits in test subjects, including facilitating weight loss, improving longevity, and reducing insulin resistance.

MOTS-c and body composition

MOTS-c works by increasing the body’s usage of energy by targeting the skeletal muscle and enhancing glucose metabolism. In the skeletal muscle, the peptide’s cellular actions slow down the folate cycle and result in AMPK activation.

A 2015 study conducted on mice being administered a high-fat diet showed that MOTS-c prevented diet-induced obesity [3, 6]. Researchers have also found that increasing AMPK can affect the expression of genes associated with inflammation, which typically contributes to weight gain [3].

MOTS-c and longevity

Research on MOTS-c has revealed possible properties related to aging phenomena. In a 2015 study, researchers found that the m.1382A>C polymorphism, located in the MOTS-c encoding mtDNA, may play a role in the longevity of the Japanese—the population with the longest average life expectancy in the world. Based on this study, the researchers proposed a “biological link between MOTS-c and extended lifespan through the putative endocrine action of this mitokine” [7].

MOTS-c attenuates insulin resistance

Researchers have found that MOTS-c is important to promoting insulin sensitivity. MOTS-c treatment has been shown to prevent both diet-induced and age-dependent muscle insulin resistance in mice, acting as a regulator of metabolic homeostasis [4].

In a 2012 human study, researchers investigated whether there was a relationship between plasma MOTS-c levels and insulin sensitivity surrogates, in both lean and obese subjects. The researchers found that MOTS-c was positively associated with insulin sensitivity in the lean subject group, but not in the obese individuals [8].

MOTS-c and muscle atrophy

Myostatin is responsible for limiting the amount of skeletal muscle mass on the body. It also mediates insulin resistance-induced skeletal muscle wasting.

A 2021 study found an inverse correlation between plasma MOTS-c and myostatin levels in human subjects. The researchers observed that by elevating AKT phosphorylation, MOTS-c inhibits the activity of myostatin and other muscle wasting genes. They proposed MOTS-c as a potential treatment of insulin resistance-induced skeletal muscle atrophy and other muscle wasting conditions [9].

MOTS-c and bone health

A 2018 study found that MOTS-c treatment could stimulate the formation of calcified nodules in the bone marrow stromal cells (BMSC) of rats afflicted with osteoporosis. The researchers found that MOTS-c administration upregulated the TGF-β/Smad pathway-related genes, leading to osteogenic differentiation and improvement of symptoms of osteoporosis [10].

Another 2016 study sought to evaluate whether MOTS-c could protect mice from osteoporosis after an ovariectomy. Following ovary removal, the rodents were injected with a MOTS-c dose of 5 mg/kg once daily for 12 weeks. The researchers found that MOTS-c administration greatly alleviated bone loss in the test subjects [11].


MOTS-c Side Effects

MOTS-c is a research peptide and has not undergone any large-scale safety studies in humans.

However, there is data on the safety profile of CB4211, a novel analog of MOTS-c. This mitochondria-based therapeutic has been evaluated for safety in a phase 1a/1b double blind, placebo-controlled clinical trial in healthy adults, with the researchers finding it safe and well-tolerated [12, 13, 14].

There may also be sex-based differences in how MOTS-c works. Compared to females, male subjects have been shown to exhibit a greater disruption in MOTS-c in contexts of metabolic disease. Researchers have proposed that the protective properties of estrogen may inhibit the decline of MOTS-c in premenopausal women [15].

For this reason, researchers believe that MOTS-c therapy may be more effective in males than in females [16].

Since MOTS-c works by activating AMPK, the peptide interacts with other AMPK-activating drugs like metformin [16].


MOTS-c Dosage Calculator and Guide

MOTS-c must be reconstituted with bacteriostatic water prior to being administered via subcutaneous injection.

Follow the below steps to reconstitute MOTS-c for injection:

  1. Remove the tops of the MOTS-c and bacteriostatic vials and wipe their surfaces with an alcohol swab to prevent contamination and infection.
  2. Insert a sterile drawing syringe into the bacteriostatic water vial and draw the desired amount, typically 1-2 ml, but dependent on the dose.
  3. Slowly transfer the bacteriostatic water into the MOTS-c vial, allowing it to trickle down the side of the vial while dissolving the powder.
  4. Do not shake or stir MOTS-c vials, as doing so may compromise the peptide. The solution to be injected should appear clear when fully mixed.
  5. Place the unused solution in refrigeration for future use.

Based on the research available, researchers are advised to administer MOTS-c in the morning as it may interfere with the research subject’s sleep.

Sample MOTS-c Protocol for Weight Loss

Currently, there is a lack of clinical data to suggest a potential dosing regime. The available data from mice studies suggest dosing of up to 15mg/kg/day for three days a week, while a potential experimental dose in human trials should be more than 10-fold lower [5, 17].

Thus, researchers are recommended to administer doses no greater than 5-10mg/day and no more frequently than 1-3 times a week. At Peptides.org, we recommend applying up to 5mg/day once every 5 days for up to 20 days.

Here is a reference MOTS-c protocol that researchers may administer to observe fat loss in subjects:

  • MOTS-c Dosage: 5mg in the morning, preferably before exercise.
  • Frequency: Administer every five days.
  • Study Duration: 20 days.
  • Repeat: It is advisable to administer a second identical cycle within six months of completing the initial study.
  • Notes: Researchers require two MOTS-c 10mg vials to complete the one-month weight loss protocol described above.

mots-c dosage calculator


Where to Buy MOTS-c Online? | 2024 Edition

Given increased research interest in mitochondria-derived peptides and MOTS-c, several vendors now sell this compound online.

While peptide researchers certainly have options of where to buy MOTS-c online, it can also be challenging to determine which online vendors sell legitimate, research-grade peptides.

Our team has placed orders with numerous peptide suppliers and is well aware of which companies meet standards of quality and service, and which do not.

Based on our expert survey, here are the two top online sources of MOTS-c.

Limitless Life

We endorse Florida-based Limitless Life for their MOTS-c and other research peptides. The vendor operates with several important features:

  • Research-Grade MOTS-c: Limitless Life stocks only the finest quality compounds that are backed by HPLC-MS test results furnished by an independent laboratory.
  • Easy Payments: To accommodate its diverse clientele, the vendor facilitates a range of payment methods like credit cards, Cash App, and eCheck.
  • Resourceful Site: The product pages for each Limitless Life peptide contain useful research summaries and guidance for professionals looking to kick off their work in peptide research.
  • Top Service and Care: Limitless Life’s care team earns top marks for their responsiveness, professionalism, and deep product knowledge.

Limitless Life is now offering first-time customers an extra 10% discount. To take advantage, enter the following coupon code at checkout:

peptidesorg10

Buy MOTS-c from our top-rated vendor...


Xcel Peptides

Xcel Peptides is a new entrant within the research chemicals industry, but ships high-purity MOTS-c to researchers at a fair price.

Here’s why we endorse them:

  • USA-Made MOTS-c: All Xcel Peptides peptides are sourced in the United States in partnership with certified manufacturers who follow industry best practices.
  • Fair Pricing & Discounts: Researchers can purchase research-grade MOTS-c at $59 per 10mg vial from this vendor, and the shipping fee is waived on order of $200+.
  • Support and Service: Xcel Peptides’s dedicated service team has a policy of leaving no question unanswered and they usually respond to inquiries within one business day.

And last but not least, researchers can enjoy a 10% discount off their first order by signing up to the Xcel Peptides email newsletter!

Buy research peptides from Polaris Peptides today...


Bacteriostatic Water and MOTS-c

To successfully administer MOTS-c and other peptides, researchers need to have certain materials at their disposal.

From peptide reconstitution to proper storage, items like bacteriostatic water, sterile vials, and insulin syringes are necessary for proper completion.

Overall, a research lab may need supplies and materials like:

  • Bacteriostatic Water
  • Insulin Syringes
  • Alcohol Prep Pads
  • Sterile Empty Glass Vials
  • Large Needles + Syringes

For researchers without the needed supplies available, it is recommended to source from authorized vendors.


MOTS-c Dosing | Verdict

There is limited human data on mitochondria-derived peptide MOTS-c, but it has been shown to promote outcomes like weight loss, greater insulin sensitivity, inhibited myostatin, and improved bone health in animal models.

Studies conducted on this peptide have indicated that it is safe and well-tolerated, and its analog CB4211 has recently completed a Phase 1a/1b clinical study

Researchers should note that MOTS-c may be more effective in male subjects compared to female subjects, believed to be due to the influence of ovarian hormones like estrogen on MOTS-c based therapeutics.

Researchers planning to explore the applications of MOTS-c are advised to visit our top-rated vendor to place an order.


References

  1.  Lee C, Kim KH, Cohen P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 2016;100:182-187. doi:10.1016/j.freeradbiomed.2016.05.015
  2. Yang Y, Gao H, Zhou H, Liu Q, Qi Z, Zhang Y, Zhang J. The role of mitochondria-derived peptides in cardiovascular disease: Recent updates. Biomed Pharmacother. 2019 Sep;117:109075. doi: 10.1016/j.biopha.2019.109075. Epub 2019 Jun 8. PMID: 31185388.
  3. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015 Mar 3;21(3):443-54. doi: 10.1016/j.cmet.2015.02.009. PMID: 25738459; PMCID: PMC4350682.
  4. Kim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab. 2018 Sep 4;28(3):516-524.e7. doi: 10.1016/j.cmet.2018.06.008. Epub 2018 Jul 5. PMID: 29983246; PMCID: PMC6185997.
  5. Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021 Jan 20;12(1):470. doi: 10.1038/s41467-020-20790-0. PMID: 33473109; PMCID: PMC7817689.
  6. Elko Randrianarisoa, Angela Lehn-Stefan, Johannes Krier, Anja Böhm, Martin Heni, Martin Hrabě De Angelis, Andreas Fritsche, Hans-Ulrich Häring, Norbert Stefan, Harald Staiger, AMPK Subunits Harbor Largely Nonoverlapping Genetic Determinants for Body Fat Mass, Glucose Metabolism, and Cholesterol Metabolism, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 1, January 2020, Pages 14–25, https://doi.org/10.1210/clinem/dgz020
  7. Fuku, Noriyuki & Pareja-Galeano, Helios & Zempo, Hirofumi & Alis, Rafael & Arai, Yasumichi & Lucia, Alejandro & Hirose, Nobuyoshi. (2015). The mitochondrial-derived peptide MOTS-c: A player in exceptional longevity?. Aging cell. 14. 10.1111/acel.12389.
  8. Cataldo LR, Fernández-Verdejo R, Santos JL, et alPlasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individualsJournal of Investigative Medicine 2018;66:1019-1022.
  9. Kumagai, H, Coelho, AR, Wan, J, Mehta, HH, Yen, K, Huang, A et al.. MOTS-c reduces myostatin and muscle atrophy signaling. Am J Physiol Endocrinol Metab. 2021;320 (4):E680-E690. doi: 10.1152/ajpendo.00275.2020. PubMed PMID:33554779
  10. Hu BT, Chen WZ. MOTS-c improves osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via TGF-β/Smad pathway. Eur Rev Med Pharmacol Sci. 2018 Nov;22(21):7156-7163. doi: 10.26355/eurrev_201811_16247. PMID: 30468456.
  11. Ming W, Lu G, Xin S, Huanyu L, Yinghao J, Xiaoying L, Chengming X, Banjun R, Li W, Zifan L. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. Biochem Biophys Res Commun. 2016 Aug 5;476(4):412-419. doi: 10.1016/j.bbrc.2016.05.135. Epub 2016 May 26. PMID: 27237975.
  12. A phase 1A/1B study of CB4211 in healthy non-obese subjects and subjects with nonalcoholic fatty liver disease – full text view. Full Text View – ClinicalTrials.gov. (n.d.). Retrieved September 18, 2022, from https://clinicaltrials.gov/ct2/show/NCT03998514
  13. BioSpace. (2019, November 5). CohBar completes phase 1a and initiates phase 1b stage of clinical trial of CB4211 under development for Nash and ObesityMilestone for first mitochondrial based therapeutic in humans. BioSpace. Retrieved September 18, 2022, from https://www.biospace.com/article/releases/cohbar-completes-phase-1a-and-initiates-phase-1b-stage-of-clinical-trial-of-cb4211-under-development-for-nash-and-obesitymilestone-for-first-mitochondrial-based-therapeutic-in-humans/
  14. Cundy KC, Grindstaff K, Magnan R et al. (2017) CB4209 and CB4211 Reduce the NAFLD Activity Score in the STAM Model of NASH, Reduce Triglyceride Levels, and Induce Selective Fat Mass Loss in DIO Mice. Poster AASLD Meeting 2017.
  15. Du, C, Zhang, C, Wu, W, et al. Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance. Pediatr Diabetes. 2018; 19: 1058– 1064. https://doi.org/10.1111/pedi.12685
  16. Mots-C – alzdiscovery.org. (n.d.). Retrieved September 18, 2022, from https://www.alzdiscovery.org/uploads/cognitive_vitality_media/MOTS-c.pdf

Scientifically Fact Checked by:

David Warmflash, M.D.

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