7 Game-Changing Peptides for Fat Loss

What This Article Will Cover:

1. Quick Intro to Peptides

2. Reasons For Weight Gain

2. What Are The 6 Best Peptides for Fat Loss?

3. Fat Loss Peptides That Don’t Require A Needle

4. Peptides Beyond Fat Loss

5. Dose Ranges for Fat Loss Peptides

6. How To Put Together a Peptide Stack

6. What Should You Know Before Adding Them To Your Routine?

Quick Intro to Peptides

Peptide therapy has been a treatment option for decades in other countries and used within the world of bodybuilding for over 20 years. It has now become a viable option to the general public for their ability to help with a variety of chronic and acute issues. Given peptides are highly specific to function but not location and well-tolerated by most, they have taken the health and wellness world by storm. As of January 2015, there were more than 60 US FDA-approved peptides, 140 peptides being evaluated in clinical trials, and 500 in pre-clinical development.

So what are peptides? Peptides reproduce what the body already knows to do through its signaling, neurotransmitters, hormones, and enzymes, making them complementary protocols to a healthy lifestyle. Think of it this way; our cells are intelligent, we’re just giving them the ability to show their intelligence.

Simply put, peptides are a string of amino acids, which can then bind together to form a protein. A well-known peptide in fitness and longevity is, of course, growth hormone, which is actually quite large and consists of 191 amino acids. [1] The peptides we work with are usually 50 amino acids or smaller. 

Reasons for Weight Gain

Interested in how and why you gain weight or store fat? That’s a massive topic we’ll cover in an upcoming article, but for now, let’s look at it from the perspective of metabolism, glucose regulation, and hormones.

Eating excessive sugar and carbs increases your blood sugar levels. It triggers the pancreas to subsequently release insulin, which in turn switches on the transportation of glucose into the cells, particularly the liver and muscle cells. Your body keeps storing excess sugar as fat, and if your diet is carbohydrate-dominant, it becomes difficult for the body to burn fat and more likely to hang on to it. 

Another potential reason for weight gain is the progressive decline of endogenous growth hormone (GH) by 15% for every decade of adult life. The growth hormone’s role is vast in that it is directly correlated with healthy metabolism, lower levels of fat accumulation, heart health, exercise capacity, maintenance of muscle, as well as cognitive function. [2] The decline of GH results in reduced production of insulin-like growth factor (IGF-1), which typically works in tandem to manage and modulate our fat, protein, and glucose metabolism. However, decreases in both show increased abdominal and visceral adiposity[3], which is not exactly ideal if you have specific physique goals.

Genetics, lifestyle, age, and environment all play a role in one’s GH secretion. Natural stimulators of GH include: decreased blood glucose, fasting, protein deficiency, decreased free fatty acids, trauma, stress, excitement, exercise; so, those are options if you decide peptides aren’t for you.  

Thankfully, some peptides help our body upregulate hGH production, helping sustain or correct our metabolic health. These peptides are listed below and can be an essential part of boosting your general health and helping you get the desired physique. [4] Reminder: there is no “magic pill” and no “magic peptide,” however, used in combination with low hanging fruit like diet, exercise, and simple lifestyle modifications, a lot is possible!

In the following article, we are going to cover the top fat loss peptides based on clinical studies and dive into how they work inside the body. 

What Are the 7 Best Peptides for Fat Loss?

MOTS-C

MOTS-c is a mitochondrial-derived peptide and what is called an exercise mimetic. Considering that mitochondria are one of the most important organelles in our cells, it is not surprising that the benefits are vast with this peptide. MOTS-c activates at the cellular and systemic level, and the benefits are exceptionally far-reaching. They include implications in the regulation of longevity, obesity, diabetes, and physical performance. 

MOTS-c can translocate into the nucleus in response to metabolic stress and regulation of adaptive nuclear gene expression. This allows the peptide to promote resistance to metabolic stress by upregulating the mitochondrial genome. 

Multiple studies have demonstrated MOTSc’s ability to enhance lipid beta-oxidation, increase thermogenic brown fat, decrease fat gain on a high-fat diet, and improve glucose uptake during glycolysis. [28,29,30] 

MOTS-c can be used for the benefit of weight loss, improving insulin sensitivity, energy production, neuro-protection, and longevity. Given, Mots-C improves intracellular NAD+ and AMPk, which are associated with metabolism and longevity, it’s an exciting multi-purpose peptide for those seeking optimization. [31] 

Tesamorelin

Tesamorelin is a growth hormone-releasing hormone analog that has been shown to increase IGF-1 levels in men and women, and decrease adipose tissue. It can also reduce c-reactive proteins which are created in the liver in response to inflammation and inversely associated with general biomarkers of health. [8] Although the main focus is on weight loss, Tesamorelin can improve the cognitive function in healthy adults with an increased risk of Alzheimer’s disease. [9]  It is an option to explore for people carrying ApoE4 gene, which is a strong genetic risk factor for developing this condition. A controlled study of 152 adults who self-administered subcutaneous injections of Tesamorelin or a placebo for 20 days, showed extremely favorable effects on their cognitive state despite their disease state. [10] Tesamorelin has been used actively under the brand name Egrifta[11] for a decade for a specific subset of the population with disease complications that include excess abdominal fat. [12] It can be useful in reducing visceral adiposity, positively affecting insulin resistance, and lowering triglyceride levels in healthy people. [13]  Additionally, the benefits demonstrated the reduction in visceral abdominal fat that remained for upwards of 52 weeks according to a double-blind placebo clinical trial. [14]

AOD9604

AOD9604 is a peptide fragment of the human growth hormone’s (hGH) C-terminus, which harbors the fat reducing activity of hGH without the negative effects. [5]

A trial conducted in 2004 on 300 obese patients by a Melbourne-based biotechnology company, states that they recorded successful weight loss over the course of 12 weeks. Patients were subjected to different doses of it once a day, and the group given the 1mg dose lost the most weight, triple that of the control group, and showed small but consistent improvement in cholesterol levels too. [6]

Similar to the human studies, studies in animals showcase both the effectiveness and safety of this peptide in reducing body weight, increasing fat oxidation, and increasing lipolysis in obese animals. [7] AOD9604 has the potential to result in more significant weight loss in a shorter period than diet and exercise alone. Results are often seen prior to 12 weeks, but of course, lifestyle choices impact the speed of progress as do genetics and innate metabolism. Given the safety, it’s a perfect peptide to start if you’re seeking to drop fat with little side effects. 

Tesamorelin also improves the overall framework of the body. This peptide works well for individuals 30+ since the production of GH naturally begins to lower as we age and it helps improve it. Physical activity supports the release of GH as well. 

This peptide is the mildest growth hormone-releasing peptide and also the most versatile one. It is said to be the most suitable peptide as it doesn’t induce these side effects like desensitization, hunger stimulation, or unnecessary plasma growth, like other peptides. [5]

CJC 1295 (with & without DAC)

Since a lot of peptide companies are producing CJC 1295 with and without DAC I thought it would be helpful to review both. CJC 1295 with DAC (aka Drug Affinity Complex) is known as a long-acting GHRH (growth hormone stimulating hormone). However, regardless. of whether CJC 1295 is the DAC version or not its primary purpose is to boost protein synthesis levels and help fuel the growth of muscle tissue in the body.

Some claim CJC 1295 with DAC has an advantage over CJC 1295 (without DAC) given it does not have a limited duration of action. However, others believe we should be concerned about unregulated and inconsistent hGH release associated with DAC’s extended release. I fall into the latter group based on my functional medicine foundation.

A study of healthy participants between the ages of 21 and 61 found that CJC 1295 with DAC prolonged elevated levels of growth hormone as well as IGF-1 with no increase in prolactin, leading to fat loss and increased muscle mass via improved protein synthesis. [15] 

CJC 1295 DAC can be used for relatively short periods since it lengthens the duration of the body’s natural hGH secretion. However, your dose timing doesn’t impact your body’s decision when those natural GH peaks occur, which isn’t exactly advantageous. So, for example, if your blood sugar is high during one of those hGH peaks, then hGH will not convert to IGF-1, and you will lose the benefits. Another thing to be cautious of with CJC 1295 DAC is that its effects on longevity are not thoroughly understood. In a podcast with Ben Greenfield, Jean Tremblay mentioned that the university team who discovered the peptide had seen the mice who were on CJC 1296 DAC die a horrible death. [16] There is a working theory this is due to the irregularity of hGH spikes. 

CJC 1295 without DAC, on the other hand, does not come with the same warning and is the preferred compound clinically. A reminder that it’s essential to do your research and work with a member of the International Peptide Society to make sure you are safe while working towards your health goals. 

CJC 1295 stimulates growth hormone secretion and will keep a steady increase of hGH and IGF-1, leading to fat loss and muscle growth. With no increase in prolactin and better stimulation and release of hGH, clinical results showcase fat loss, increased lean muscle mass, and better lipid profiles. Another benefit of this peptide is its ability to promote slow-wave sleep (e.g. Delta sleep), which is the sleep stage associated with muscle recovery and memory formation. 

Interested in skin elasticity and collagen? CJC 1295 has demonstrated skin repair capabilities, as well. [17] 

Interested in how to maximize the efficacy of CJC 1295? CJC 1295 actually works synergistically with Ipamorelin for improved fat loss and the promotion of lean body mass. More below. 

Ipamorelin

Ipamorelin is within a class of what are called growth hormone secretagogues, which aid the body’s production of endogenous growth hormone. [18] Users report accelerated fat loss, improved sleep, mood, increased energy, as well as long term growth hormone production. That is especially evident when programmatically combined with CJC 1295. After a cycle, the body sees a prolonged boost in hGH production far beyond their initial dose, thus allowing longer-term maintenance of benefits. 

Ipamorelin does this by stimulating the pituitary gland to release growth hormone naturally by its action as an analog to the well-known hunger hormone ghrelin. [19] Unlike a lot of other GHRP’s, however, Ipamorelin does not have a laundry list of negative side effects like elevated cortisol or increased appetite, which allows patients to use it for a broad range of issues and goals. Many patients use Ipamorelin for a short amount of time (~3 months) for fat loss benefits, increased metabolism, and general improvements in their body composition. 

Growth hormone production decreases by about 15% with each decade of life, resulting in decreased mental and physical function. Thus, why hGH secretagogues may be beneficial for those seeking to maximize performance in sports, the gym or for aesthetics. [20]

GHRP-6

GHRP-6 stands for Growth Hormone-Releasing Hexapeptide that contains 28 amino acids. This HGH secretagogue promotes GH secretion that increases body mass on account of muscles, with a substantial reduction in body fat. [21]

It increases both GH and insulin-like growth factor (IGF-1), which makes it an optimal choice for athletes and bodybuilders, and also for people who are just looking to improve their general stamina during workouts. 

A study published in The New England Journal of Medicine showed that male participants over 60 years old, who took hGH for six months gained on average 8.8% lean body mass and lost 14% fat mass. [22] In a hypothyroid population, GHRP-6 was found to increase the hGH response, which could lead to similar results of increased muscle mass and reduced body fat. [23

Tesofensine

Tesofensine is a serotonin-noradrenaline-dopamine reuptake inhibitor that was initially researched for its effect on Alzheimer’s and  Parkinson’s disease. Tesofensine’s caused the trial participants to lose too much weight while in the trials. [24] Soon after investigation began into its ability to modulate satiety and appetite. Tesofensine is currently in phase 3 clinical trials with the FDA and supported by further research at Johns Hopkins University School of Medicine. [25] 

A two-week study of 203 obese patients hinted that Tesofensine could have the ability to reduce weight two times more than any weight-loss drug currently on the market. [26] During a six-month clinical trial, participants lost on average 25 lbs each. Tesofensine has even been called a “novel potent weight loss medicine” by the Queensland University of Technology and has shown minimal side effects. [27] 

Are you a little nervous about subcutaneous injections but still want the fat-loss benefits? 

Well, you’re in luck. I put together a list of needle-free peptide options to help you lose weight, improve your energy and improve your physique. 

Fat Loss Peptides That Don’t Require A Needle  

There are quite a few peptides that don’t involve subcutaneous injections. My favorite science-backed peptides for fat loss that come in needle-free options include:

  1. Amlexanox 
  2. Glycyrrhetinic Acid 
  3. Tesofensine 
  4. AOD9604 
  5. 5-Amino-1MQ 

For fat loss, there are also MIC injections, Naltrexone and various other treatments that are non-peptides but can benefit a practitioner-led fat loss protocol. 

Amlexanox

With an atypical history, Amlexanon has traditionally been used as an  anti-inflammatory to treat canker sores and even asthma in Japan. However, several years ago, it was shown to reverse obesity, diabetes, and fatty liver disease in mice without subjecting them to any changes in diet and exercise. [32] 

How? That’s the exciting part. 

Amlexanox has multiple mechanisms of action. It can inhibit inflammation by preventing the release of histamine and leukotrienes but also change the activity of genes that control metabolism. [33] It does that by increasing the rate at which cells burn fat via a messenger molecule called CAMP and reducing the level of glucose by improving insulin sensitivity. One of the reasons many calorie restriction diets are so ineffective in producing weight loss for some is because the human body naturally wants to adjust to the reduced calories by also reducing metabolism. Amlexanox mitigates that response by increasing one’s energy expenditure and fat oxidation independent of calorie consumption and exercise. 

Dose format: Capsule

Peptide Therapy helps you drop fat, not just weight, in a matter of weeks, not months.

Glycyrrhetinic Acid

It is the active ingredient in licorice root that has been shown to reduce subcutaneous thigh fat in a group of healthy 20-33-year-old women, making it one of the best peptides for female weight loss given this is an area that is extremely resistant to fat loss. [34]

The effects of Glycyrrhetinic Acid combined with Aminophylline display even greater fat loss in both men and women. Over 12 weeks, participants in one study lost 11 cm in waist circumference, showcasing the best results through topical application. 

Dose format: Capsule or Transdermal Cream

Tesofensine

This peptide works as an inhibitor of the presynaptic reuptake of noradrenaline, dopamine, and serotonin. Blocking these neurotransmitters results in the suppression of appetite and thus weight loss. [35, 36, 37]

Dose format: Capsule or Transdermal Cream

AOD9604

This is one of the few peptides that has received FDA approval as a food supplement in the United States with results in 12 weeks or less. 

AOD9604 has the potential to: 

  • Stimulates fat release from obese fat cells 
  • Reduce body fat by stimulating lipolysis 
  • Support the repair of cartilage via its regenerative properties, especially when paired with BPC 157

Dose format: Transdermal Cream

5-Amino -1MQ

The benefits of NMN have been widely discussed but 5-Amino-1MQ is more of a new kid on the block and is a small, selective membrane-permeable molecule that blocks the NNMT enzyme.[38] This compound has mostly been studied in the setting of obesity but works on our mitochondria so energy production comes along for the ride. 5-Amino-1MQ being explored in the prevention of adipogenesis, type II diabetes and in its potential to reverse diet-induced obesity. 5-Amino -1MQ is best supplemented alongside NAD+ or an NAD+ precursor. 

I combine 5-Amino-1MQ alongside NAD+ IV’s, injections and/or patches at my practice for greatest efficacy. 

Dose format: Capsule 

Peptides Beyond Fat Loss  

It is now crystal clear that peptides work by stimulating the pituitary gland to release more human growth hormone in the bloodstream.  As mentioned above, some of the peptides also elevate the production of insulin-like growth factor, which is perfect for improving lean muscle and restricts some neurotransmitters that are responsible for weight gain. Besides helping you lose weight, peptides help in solving other medical conditions, as well. AOD9604 has the potential to repair cartilage and be used as a treatment for muscle and joint conditions such as Osteoarthritis. [39] Tesofensine can improve your sleep cycle, mood, bone density, immune function, and body composition. [40] Tesamorelin could help improve cognition in older adults over the age of 60. A study showed that GHRP-6 could reduce lung and renal damage and could be used for the prevention of multiple organ failure.[41] Peptides are also being used as therapeutic anti-inflammatory agents, as well as anti-tumor treatments given they offer minimal immunogenicity and excellent tissue penetrability. [42,43]

Dose Ranges for Fat Loss Peptides

Peptide protocols and dosings should be crafted with both short term and long term goals and effects in mind. And, due to their efficacy, it’s important to work with a practitioner who can guide you safely based on your bioindividuality. That said, there is no “average peptide cycle” or across the board dose that will work for everyone. There are ranges that one could work within, and I’ll share below, however, there are many variables to work with (weight, age, hormones, other RX’s, peptides, underlying conditions, etc.) to consider. 

  • AOD9604: 300 mcg – 1mg
  • Ipamorelin: 100 – 500 mcg
  • Tesamorelin: 1 – 2 mg
  • CJC 1925 (DAC): 2 mg
  • GHRP-6: 100 – 150 mcg
  • Tesofensine: 1 mg

How to Put Together a Peptide Stack?

For optimal results, you should align your peptide stack in the correct order, dosing, compliment, and cycle based on your goals and bioindividuality. Again, it’s strongly advised to consult a member of the International Peptide Society versus going at it on your own. If interested in scheduling a Peptide Consult with Dr. Paulvin you can do that here.

What you should know before adding them to your routine?

Peptides are extremely safe but in order to get the results you want there is often an order of operations to layering in peptides. Often that starts with Thymosin Alpha 1. If you’re interested in learning more about how peptides, in general, subscribe to my newsletter for updated research and information on peptides, human optimization & more.

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Medical Disclaimer:

The Information in this guide is designed to complement, not replace, the relationship between a patient and his/her own physician and is for informational purposes only. The information is not intended to be medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you saw or read on my website.

References:

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