Cardarine: Cardarine & Cancer
Conclusion: inconclusive. There are too many unanswered questions that I just don't have the education to address. Exercise (heh) caution with this compound if you choose to use it, with short cycle lengths (<4 weeks).
On the other, it causes cancer. At least it did in rats (Page 189):
GW501516, a non-genotoxic PPARδ agonist, was assessed for carcinogenic potential by daily administration (oral gavage) to Han Wistar rats for a period of 104 weeks. Males were given 0, 5, 15 or 30 mg/kg/day for the first 6 weeks of the study. For the remainder of the study males were given 0, 5, 20 or 40 mg/kg/day. Females were given 0, 3, 10 or 20 mg/kg/day for the entire study. GW501516 produced test article-related neoplastic findings in multiple tissues at all doses.
Increased mortality was seen with females given GW501516 at all doses and uterine endometrial adenocarcinoma contributed to death in a high proportion of these animals. Neoplasms considered test-article related occurred in the liver (hepatocellular adenoma at ≥ 10 mg/kg/day), urinary bladder (transitional cell carcinoma in males given 20 and 40 mg/kg/day), thyroid (follicular cell adenoma at ≥ 3 mg/kg/day and carcinoma in males at ≥ 20 mg/kg/day), tongue (squamous cell papilloma in males at 5 mg/kg/day and 40 mg/kg/day), stomach (squamous cell papilloma in males at ≥ 5 mg/kg/day and a female at 20 mg/kg/day, and carcinoma in a male at 40 mg/kg/day and a female at 3 mg/kg/day), skin (inverted squamous cell papilloma in males at ≥ 5 mg/kg/day and females at 3 or 20 mg/kg/day), Harderian glands (adenoma in males at ≥ 5 mg/kg/day and adenocarcinoma in a male at 40 mg/kg/day), testes (interstitial cell adenoma at 40 mg/kg/day), ovary (Sertoli cell adenoma at ≥ 10 mg/kg/day) and uterus (polyp and endometrial adenocarcinoma at ≥ 3 mg/kg/day). Some of the tumor types observed in this study have not been reported with either PPARα or PPARγ agonists and may reflect tumor promotion mediated through PPARδ agonism.
In the /r/PEDs wiki we reference that it's not worth it, none of us are smarter than GSK, and they would have considered the high dosage as the reason for the development of cancer. Perhaps they did, but it's also possible they dropped it because they knew with such a result it would never get to human trials, even at lower doses.
And speaking of doses, let's look at the doses given, since that's an oft cited reason as why the study was flawed.
Human Equivalent Dose (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]
= Animal Dose (mg/kg) x [Animal Km / Human Km]
= 3 x (6/37)
= 0.48 mg/kg
Where Animal Km is 6 for rats, and 37 for humans, and 3mg is the lowest dose where neoplastic findings were found.
For a 200 pound / 90 kg male, this is the equivalent 43.2mg per day. Study was ran for 104 weeks.
This raises a lot of questions that I just don't have the expertise to answer, and will need to get time with someone in pharmaceuticals.
- Why did GSK run a study where the lowest dose was 4 x what would commonly be taken for performance enhancement, and ~8x what would be taken for health benefits? For comparison, acetaminophen toxicity in a single dose for an adult starts at 7.5g, just 2x the maximum dose of 4g/day when used under supervision by a medical professional.
- Why run the study continuously for 2 years?
- Why not run a new trial at lower doses given what we know now from anecdotal experience?
Without any further R&D on this compound and its tainted reputation, it's likely we'll never know for sure if this compound can be utilized safely.