Titus Thorne

Last Updated November 6, 2022

Titus Thorne

 November 6, 2022

Looking for the ideal MOTS-c dosage? Inside, researchers will find everything they must know about dosing this powerful peptide.

MOTS-c is a mitochondria-derived peptide that has recently garnered the attention of researchers for potential uses including weight loss, improved physical performance, and anti-aging.

Due to increased research and development involving this peptide, peptide researchers are now inquiring about how to establish an appropriate MOTS-c dosage for their next experiment.

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

Buy MOTS-c from our #1 recommended vendor...

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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 anti-aging properties. 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 your MOTS-c vial, as doing so may compromise the peptide. The solution to be injected should appear clear when fully mixed.
  5. Place the unused solution in your 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

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? | 2022 Edition

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

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

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

Based on our expert survey, Peptide Sciences is the top source of MOTS-c online. They ship high-purity MOTS-c to researchers at fair prices, around the globe.

Here is why this vendor stands out:

  • Lab-Tested Peptides: Peptide Sciences submits each batch of MOTS-c for quality and purity testing via methods of mass spectrometry (MS) and high performance liquid chromatography (HPLC). The vendor then posts the lab results online to its website, which researchers may consult prior to placing an order.
  • Fair Pricing: Researchers can purchase research-grade MOTS-c at $110 per 10mg vial, with discounts available for bulk purchasers.
  • USA-made MOTS-c: All Peptide Sciences peptides are sources in the United States in partnership with WHO/GMP and ISO 9001:2008 approved manufacturers who follow industry best practices.
  • Quick Shipping: Domestic orders usually arrive within two to three business days and qualify for free shipping if over $200. International orders usually take seven to ten business days to arrive, depending on the destination.
  • Customer Service: Peptide Sciences’ dedicated customer service team has a policy of leaving no question unanswered and they usually respond to customer inquiries within one business day.

Researchers looking to buy high-quality MOTS-c for their next study are advised to check out Peptide Sciences, an established leader of the research chemicals industry.

Buy MOTS-c from our #1 recommended vendor...


Bacteriostatic Water for Injection

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

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

But what is the best source to buy the full set of research materials?

Because it can be challenging to find a single trusted retailer for all your research supplies, we at Peptides.org have surveyed the market to give you our top recommendation.

BacteriostaticWater.org

This online vendor is the only source you need to stock up on the full range of essentials for peptide research. It is our first choice due to its convenient supply kits that efficiently supply all the requisite materials and eliminate the hassle of assembling the necessary products from multiple sites.

The BacteriostaticWater.org starter research kit supplies you with:

  • Bacteriostatic Water (30mL) – 3x
  • Insulin Syringes (0.5 cc/mL x 29g x ½) – 100x
  • Alcohol Prep Pads – 200x
  • Sterile Empty Glass Vial (10mL) – 1x
  • Large Needles + Syringes Combo (3cc x 21g x 1) – 10x

Its premium research kit delivers:

  • Bacteriostatic Water (30mL) – 5x
  • Insulin Syringes (0.5 cc/mL x 29g x ½) – 200x
  • Alcohol Prep Pads – 200x
  • Sterile Empty Glass Vial (10mL) – 2x
  • Large Needles + Syringes Combo (3cc x 21g x 1) – 20x

Boost the speed and efficiency of your research with an unbeatable supply kit from this winning vendor.

Buy Bacteriostatic Water from our #1 recommended vendor...


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 top vendor Peptide Sciences 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

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