Summary of Rapid Rebound
- Promotes rapid recovery and reduction of pain after intense workouts.
- Accelerates the healing of musculoskeletal injuries by inducing angiogenesis, increasing nitric oxide production and reducing inflammation.
- Promotes healthier digestion by healing stomach ulcers and reducing intestinal inflammation (ex: in leaky gut or IBS).
- Accelerates the healing of skin wounds and burns by promoting collagen production and angiogenesis.
- Has neuroprotective effects and may promote healing after traumatic brain injury.
Pentadecapeptide BPC-157, composed of 15 amino acids, is a partial sequence of body protection compounds (BPC) isolated from human gastric juice in the stomach. It has been demonstrated to accelerate the healing of many different wounds, including tendon-to-bone healing and superior healing of damaged ligaments by increasing Growth Hormone receptors in ligaments and tendons. In addition, this peptide has shown to have Osteogenic properties on the healing of segmental bone defects in in vivo experiments (13).
Recently, the peptide has also been used as a remedy for CNS disorders and a neuroprotective agent acting through the brain-gut axis (10); even improving the healing course of spinal cord injuries leading to functional recovery (14). Daily use could promote cognitive longevity and aid in the prevention of neurological afflictions such as Alzheimer Disease. Additionally, BPC-157 has been shown to protect organs and prevent ulcers of the stomach, acting systemically in the digestive tract to combat leaky gut, IBS, cramps, and Crohn’s disease.
This peptide is also shown to decrease pain in damaged areas, decreasing
inflammatory mediators such as MPO, Leuktrienes B4, Tx B2, etc., and shows promising results for counteracting NSAID toxicity (16). Those who suffer from discomfort due to muscle sprains, tears and damage may benefit from treatment with this peptide. Lastly, BPC-157 can also help aid skin burns to heal at a faster rate and increase blood flow to damaged tissues making it a viable option for cosmetic recovery (11). In addition to the versatile and multi-faceted uses of BPC-157, it also exhibits a high safety profile in which the lethal dose to 1% of the population (LD1) was not achieved in vivo (17).
Palmitoylethanolamide (PEA, N‐(2‐hydroxyethyl) hexadecanamide, palmidrol; is a natural fatty acid amide found in a variety of foods, which was initially discovered in 1957 as an active anti‐inflammatory agent in chicken egg yolk. In mammals, PEA is produced on demand from the lipid bilayer and is ubiquitous. Indications for its use as an anti-inflammatory and analgesic date from before 1980. Preclinical and clinical
studies involving PEA suggest a wide range of therapeutic areas including the following: eczema, pain and neurodegeneration, atherosclerosis, mast cell hyperactivity, stroke, and infectious disease prevention, Alzheimer’s, and GI Health (9). PEA’s actions on multiple molecular targets while modulating multiple inflammatory mediators also provide therapeutic benefits for applications such as immunity, brain health, allergy, pain modulation, joint health, sleep and recovery (24).
The main conclusions of the many studies involving PEA provide evidence
showing that PEA may act as both an anti-inflammatory and antinociceptive agent. In 2012, a triple-blind randomized clinical trial was conducted on patients suffering from TMJ osteoarthritis or arthralgia (2). The results of the study indicated that pain decrease after 2 weeks was significantly higher in PEA treated patients than in ibuprofen treated patients. In addition, the maximum mouth opening improved more in PEA treated patients than in ibuprofen treated patients (P = .022) (2).
PEA has also been shown as an alternative treatment for chronic pain. In an
article published by Gatti, Antonio et al, “PEA treatment significantly decreased the mean score pain intensity evaluated in all patients who completed the study. The PEA effect was independent of the pain-associated pathological condition. PEA-induced decrease of pain intensity was present also in patients without accompanying analgesic therapy. Importantly, PEA showed no adverse effects.” (6).
In addition, PEA has other clinical applications including the following: improving clinical indices in stroke patients (neurological status, the degree of spasticity, cognitive abilities, pain and independence in daily living activities) (19), down-regulating hyperactive mast cells in a dose-dependent manner (8), promoting atherosclerotic plaque stability in ApoE−/− mice (20), acting as a prophylactic treatment against viral respiratory infections (including COVID-19) (7), and rescuing behavioral impairments that can mimic some traits of Alzheimer’s disease (9).
The mechanism of action for mediating anti-inflammatory, analgesic, and
antipruritic effects is still unspecified as more research will need to be completed to confirm or deny the current hypotheses. Overall, PEA is generally considered a safe medication unaccompanied by adverse drug reactions or drug interactions. A study from 2016 assessing the safety claims in clinical trials, case reports, pilot studies, and a meta-analysis, performed by Gabrielsson, Linda et al., concluded that “treatment times up to 49 days, the current clinical data argue against serious adverse drug reactions (ADRs) at an incidence of 1/200 or greater.” (18)
AOD 9604 is a modified form of amino acids 176-191 of the GH polypeptide. Investigators at Monash University discovered that the fat-reducing effects of GH appear to be controlled by a small region near one end of the GH molecule. This region, which consists of amino acids 176-191, is less than 10% of the total size of the GH
molecule and appears to have no effect on growth or insulin resistance. It works by mimicking the way natural Growth Hormone regulates fat metabolism but without the adverse effects on blood sugar or growth that is seen with unmodified Growth Hormone. Like Growth Hormone, AOD 9604 enhances lipolytic sensitivity (the breakdown or destruction of fat) and inhibits lipogenesis (the transformation of nonfat food materials
into body fat) both in laboratory testing and in animals and humans (23). “Chronic administration of AOD9604 in mice results in a marked decrease in fat accumulation, decreased body weight gain, and an improvement in circulating metabolites, such as triglycerides and cholesterol” (22; 23).
Recent findings have shown, in addition to its fat loss properties, AOD 9604
possesses many other regenerative properties associated with growth hormone. Currently more trials are underway to further pursue the application of AOD 9604 in osteoarthritis, hypercholesterolemia (23), bone and cartilage repair. AOD 9604 has an excellent safety profile, recently obtaining FDA approval and Human GRAS status in the USA. Since then, AOD 9604’s role continues to evolve.When it was first discovered, it was used for weight loss and while the results were encouraging, they were not spectacular. As of recently it is being used with increasing success in treating pain conditions caused by tendonitis, osteoarthritis. A 2015 in vivo study showed that after chemical destruction of the articular cartilage of the knee, AOD 9604 and Hyaluronic Acid were able to significantly regenerate new cartilage and relieve lameness. (1)
In vitro, AOD 9604 has been shown to stimulate bone differentiation and
mineralization in adipose derived mesenchymal stem cell cultures. AOD9604 had effects on its own and in combination with osteogenic growth media. It also promotes Myoblast differentiation in vitro and chondrocyte production of collagen and proteoglycan-indicators of potential for muscle and cartilage repair.
According to a 2014 article addressing the safety and metabolism of AOD 9604, AOD9604 was found to be generally safe after chronic oral application in rats and cynomolgus monkeys. There was no evidence of any genotoxic activities of AOD9604, as examined in an Ames test, a chromosomal aberration assay, or a bone micronucleus assay. Rat whole-body radiography revealed similar organ distribution after IV or oral application.(21)
(1) Kwon, Dong Rak, and Gi Young Park. “Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model.” Annals of clinical and laboratory science 45,4 (2015): 426-32.
(2) Marini, Ida et al. “Palmitoylethanolamide versus a nonsteroidal anti-inflammatory drug in the treatment of temporomandibular joint inflammatory pain.” Journal of orofacial pain 26,2 (2012): 99-104.
(3) Calabrò, Rocco Salvatore et al. “Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of ” Pain medicine (Malden, Mass.) vol. 11,5 (2010): 781-4. doi:10.1111/j.1526-4637.2010.00823.x
(4) Hesselink, Jan M Keppel, and Thecla Am Hekker. “Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series.” Journal of pain research 5 (2012): 437-42. doi:10.2147/JPR.S32143
(5) Jaggar, S I et al. “The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain.” Pain 76,1-2 (1998): 189-99.doi:10.1016/s0304-3959(98)00041-4
(6) Gatti, Antonio et “Palmitoylethanolamide in the treatment of chronic pain caused by different etiopathogenesis.” Pain medicine (Malden, Mass.) vol. 13,9 (2012): 1121-30. doi:10.1111/j.1526-4637.2012.01432.x
(9) D'Agostino, Giuseppe et al. “Palmitoylethanolamide protects against the amyloid-β25-35-induced learning and memory impairment in mice, an experimental model of Alzheimer disease.” Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology vol. 37,7 (2012): 1784-92. doi:10.1038/npp.2012.25
(10) Sikiric, Predrag et al. “Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications.” Current neuropharmacology 14,8 (2016): 857-865. doi:10.2174/1570159x13666160502153022
(11) Bilic, M et al. “The stable gastric pentadecapeptide BPC 157, given locally, improves CO2 laser healing in mice.” Burns : journal of the International Society for Burn Injuries vol. 31,3 (2005): 310-5. doi:10.1016/j.burns.2004.10.013
(12) Chang, Chung-Hsun et al. “Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts.” Molecules (Basel, Switzerland) vol. 19,11 19066-77. 19 2014, doi:10.3390/molecules191119066
(13) Sebecić, B et al. “Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone ” Bone vol. 24,3 (1999): (a) 202. doi:10.1016/s8756-3282(98)00180-x
(14) Perovic, Darko et al. “Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in ” Journal of orthopaedic surgery and research vol. 14,1 199. 2 Jul. 2019, doi:10.1186/s13018-019-1242-6
(15) Vuksic, Tihomir et al. “Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia) heals ileoileal anastomosis in the rat.” Surgery today 37,9 (2007): 768-77. doi:10.1007/s00595-006-3498-9
(18) Gabrielsson, Linda et al. “Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy.” British journal of clinical pharmacology 82,4 (2016): 932-42. doi:10.1111/bcp.13020
(19) Caltagirone, Carlo et “Co-ultramicronized Palmitoylethanolamide/Luteolin in the Treatment of Cerebral Ischemia: from Rodent to Man.” Translational stroke research vol. 7,1 (2016): 54-69. doi:10.1007/s12975-015-0440-8
(20) Rinne, Petteri et al. “Palmitoylethanolamide Promotes a Proresolving Macrophage Phenotype and Attenuates Atherosclerotic Plaque ” Arteriosclerosis, thrombosis, and vascular biology vol. 38,11 (2018): 2562-2575. doi:10.1161/ATVBAHA.118.311185
(21) Moré, Margret, & David "Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health." Journal of Endocrinology and Metabolism [Online], 4.3 (2014): 64-77. Web. 8 Sep. 2021
(23) Heffernan, M et “The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice.” Endocrinology vol. 142,12 (2001): 5182-9.doi:10.1210/endo.142.12.8522
|Tendon and Ligament repair||12||23|
|Accelerated Skin Healing||11|
|Pelvic/Neuropathic pain||3, 4, 8|
|Chronic, Visceral and Somatic Pain||2, 4, 5, 6|
|Gastric Ulcers||15, 10|
|Central Nervous System|
|Improvements in Sleep||24|
|Improvement in Mood/Cognition||24|
|TBI/Stroke/CNS disorders||10, 14||9|
|Neuroprotective/Neural Recovery||10, 14|
|Improves Immune Function||7|
|Contact Allergic Dermatitis||8|
|Prevents Respiratory Infections
|Decreasing Mast cells||8|
|Stabilizes Blood pressure||10|
|Benefits in Hypercholesteremia||20||23, 24|
|Break down of Fat||23|