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Erythropoietin, Versatile Player

 EPO activity has been linked to angiogenesis, neuroprotection, cardioprotection, stress protection, anti-inflammation and especially the energy metabolism regulation that is recently revealed.


The primary physiological function of EPO system is to stimulate erythroid progenitor cell production to provide adequate red blood cells and oxygen delivery. However, emerging evidences revealed previously less realized roles of EPO and EpoR(receptor) signaling beyond hematopoietic system. For example, EPO stimulated angiogenesis via endothelial cells in cardiovascular system contributes to cardioprotection to ischemic injury. EPO also provides neuroprotection during ischemic/hypoxic stress or disease via stress induced EPO production and EpoR expression in the brain to exert the antiapoptotic, oxygen delivery and anti-inflammatory effects. 
The protective function and the wound healing and repair role of EPO in skeletal muscle during ischemic/injury were also demonstrated.
These pleiotropic activities of EPO in non-erythroid system strongly suggest therapeutic potential of EPO beyond its traditionally primary clinical application in hematopoietic system. More interestingly, recently published data confirm the tight link between EPO/EpoR signaling and energy metabolism and homeostasis. 

EPO administration could protects us from diet induced obesity, promotes energy expenditure, reduces fat mass accumulation and improves glucose intolerance and insulin resistance. The loss of EPO activity in non-hematopoietic system leads to glucose intolerant and insulin resistant with the development of obesity. EPO activity is also demonstrated to play a role in central regulation of appetite. The crosstalk between EPO and other important energy sensors including PGC-1α, Sirt1 and AMPK further provides a mechanism for EPO regulating energy homeostasis. Although these novel findings highlight the possible therapeutic potential of EPO in non-hematopoietic diseases. Further studies are required to uncover the detailed mechanism by which EPO regulates central control of energy homeostasis and energy metabolism in multiple tissues.

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Reconstituting powder vials and risks of multi-dosing

The manufacturer of the EPO powder vials we usually sell recommends reconstituting the powder with 1ml sterile water for injection (WFI, 0.9% sodium chloride) and using the contents of the vial *immediately*. Any leftover EPO should be discarded. Likewise a sterile WFI vial or ampoule must never be re-used. Tips for reconstituting EPO powder vials can be found further down this post.

Recommended WFI product (supplier not affiliated to us)

The potency of any pharmaceutical EPO brand may vary significantly from the IU declared on the label. An EPO vial or syringe may in some cases contain 150%+ of the labelled IU (this was once reported for the brand of powder vials we usually sell). Likewise much lower than the labelled IU is possible. Even significant variations in labelled vs actual IU for different batches of the same product have previously been reported for more than one brand. Closely monitoring blood values including hemoglobin and hematocrit is always crucial for any person using EPO, even when repeating a past schedule of doses with the same brand…even if blood values were closely monitored on that past schedule!

Multi-dosing from a vial

– Vials could be multi-dosed for up to 21 days after reconstitution by instead using sterile bacteriostatic saline (contains 0.9% sodium chloride + 0.9% benzyl alcohol). However, doing this may lead to detrimental changes to the EPO protein, reducing potency and increasing health risks to an end user (e.g. increased chance of an immune response due to increased aggregation of the EPO). These changes may occur at the time when bacteriostatic saline is first introduced into the vial and/or during subsequent storage. The potency and safety profile of the liquid may be vastly reduced by the 20th day after reconstitution.*
– Between doses, keep liquid EPO refrigerated at a stable temperature (4-5 Celsius).
– Multi-dosing also greatly increases the risk of coring.**
– Multi-dosing without bacteriostatic saline would not be advisable due to the high risk of bacterial growth inside the vial (even if using up the vial over a short timespan).
– Medications containing benzyl alcohol are contraindicated in newborns and infants as fatal reactions have previously occurred. They are also contraindicated in pregnant or lactating women, as fetuses and infants exposed to benzyl alcohol in utero or in breast-fed milk are also at risk of fatal reaction.
– We only recommend using bacteriostatic saline drawn from vials made by Hospira. Available from here (supplier not affiliated to us).

*EPO produced in the USA (Epogen and Procrit brands) is available in multi-dose liquid vials containing 1.1% benzyl alcohol, however this does not mean that adding bacteriostatic saline to powder vials will have an equal or similar effect on the EPO as the benzyl alcohol does in Epogen/Procrit multi-dose vials. This is due to a different manufacturing process for the Epogen/Procrit multi-dose vials, which contain ready-to-use liquid. The patient instructions for Epogen/Procrit multi-dose vials state that the vials should be discarded within 21 days of initial needle entry.

**There is a longstanding recommended technique of needle insertion into a medication vial that reduces the risk of coring. The needle should be inserted at a 45–60° angle with the opening of the needle tip facing up (i.e., away from the stopper). A small amount of pressure is applied and the angle is gradually increased as the needle enters the vial. The needle should be at a 90° angle just as the needle bevel passes through the stopper.

Tips for reconstituting EPO powder vials:
(This is NOT a complete instructional)

– Always disinfect the vial rubber top with a sterile pre-injection wipe (70% isopropyl alcohol) and allow to dry completely before inserting needle.
– Reconstitute each vial with the exact volume specified by the manufacturer (1ml for our usual brand).
– Do not reconstitute a vial until ready to use it.
– Use the technique above** to minimize risk of coring.
– Add the sterile WFI or bacteriostatic saline to the powder vial very slowly (drop by drop down the vial wall rather than directly onto the powder). Then leave it to sit dissolving for several minutes before gently swirling and rotating/inverting the vial to *completely* dissolve the powder. Do NOT shake the vial.
– Draw the EPO liquid into syringe very slowly. Transferring the liquid quickly may damage the EPO.

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Buy EPO here with credit or debit card

ALL PRODUCTS SHIPPED FROM EUROPE! Pay with any credit or debit card. We ship worldwide, with many customers in USA, Canada, UK, France, Germany, Spain, Italy, Australia and many more.

Click on product name to go to product page.
EPO – 3 x 10,000iu powder vials – $299.99
EPO – 6 x 10,000iu powder vials – $569.99

EPO – 10 x 4000iu pre-filled syringes – $339.99
EPO – 20 x 4000iu pre-filled syringes – $639.99

EPO – 6 x 4000iu powder vials – $239.99
EPO – 12 x 4000iu powder vials – $455.99
EPO – 24 x 4000iu powder vials – $893.99

FG-4592 (Roxadustat) – 1000mg – $429.99
FG-4592 (Roxadustat) – 2000mg – $829.99
Triamcinolone Acetonide (“KENACORT”) – 40mg vial – $24.99

Vintor 4000iuEpofer 40,000iu

 

 

 

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Where to buy EPO online? Advice for avoiding scams.

Admittedly we are biased when it comes to this, but nonetheless we figured this would be a useful exercise for our existing and potential customers looking to buy any research chemical online via a Google search. Or any product whatsoever for that matter.

A simple search for “buy epo” or “buy erythropoietin” will yield several web shops, included those listed below. Some very basic checks on these domains could save you from ending up empty handed after spending your hard earned money.

For each of the following, we conducted a WHOIS check, did a quick search around for customer reviews and made a basic common sense analysis regarding the legality of the products being sold.

24hoursppc.org – Clearly an illegal web shop, these kind of sites are liable to being shut down without warning by a regulatory authority, after which your order is unlikely to ever be fulfilled. This site is hosted on a server controlled by MSC Hosting, a UK based company under the jurisdiction of the UK courts, the laws of which are clearly violated by this website. We also found a negative review from 2007 here. Anyone website who truly values their reputation would surely address a complaint of this nature within a reasonable timeframe, especialy as the same complaint was referred to on this high ranking review site.

drs-labs.com – Likewise liable to being shut down due to selling controlled substances (HGH and HCG) without a licence on a Canadian registered and hosted domain name. Also their erythropoietin and other products are not made in GMP facilities, or at least can’t be verified as such. Perhaps the products are genuine but it throws the purity and dose accuracy into question. Although one absolutely shocking review here reports that “They mixed the labels on GHRP-6 and apparently mislabeled with Ipamorelin” and includes a response that the “ACE 031 from drs is fake”. As above, DRS Labs did not publicly address this review on the page in question, despite having the opportunity to do so for 2 years.

Erythropoietin.org – The WHOIS check reveals the domain was registered by [email protected], a Google search of which would lead one to the safe conclusion that this is a scam website. Unlikely that you will receive any product let alone EPO.

Stay safe out there and remember that here at Erythrobio we are more than happy to fulfil low cost sample orders so you can test our genuine, pharmaceutical grade, GMP manufactured products!

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EPO-Boost, the probable placebo

EPO-Boost, a supplement containing various vitamins, minerals and herbal extracts, promises much through it’s name alone, but we decided to ask the questions: does it really boost endogenous EPO levels in human subjects? If so, by how much? Does it represent good value for money?

Without any double-blind randomized placebo-controlled clinical trial results to directly back their claims, we can only analyze the presence of individual ingredients as follows:

Vitamin C – low plasma levels linked to erythropoietin resistance(1), intake increases absorption of oral non-heme iron(2), improves utilization of high ferritin stores(7)(8)

Vitamin B-3 – Deficiency a.k.a. Pellagra may lead to anemia, though a direct effect is unclear(10)

EPO-BoostVitamin B-6 (Pyridoxine HCl) – red cell B6 known to be depleted by increased RBC count as a result of erythropoietin treatment(3)

Folic Acid – red cell folic acid levels known to be depleted in the same way as B6(3), plus supplementation can significantly enhance the response to erythropoietin treatment in anemic patients with chronic renal disease(4). Anemia due to folate deficiency possible.

Vitamin B12 – deficiency can lead to pernicious anemia or increase resistance to EPO(5)(6)

Iron – apart from anemia brought about by a serious deficiency, supplementation of iron is required to achieve optimal response to erythropietin treatment(8)

BodyEndurance(TM) Complex and Alpha-Lipoic Acid – the primary ingredient here, echinacea purpurea extract, was shown to increase serum EPO levels by up to 63% during a 4wk study of oral supplementation at 8g/day.(9) Out of the remaining ingredients, we are unaware of any that directly stimulate EPO levels, but the addition of these may increase the total iron content and absorption as well as oxidative stress that may limit the effectiveness of any EPO increase.

It is immediately clear that there is only one ingredient that has been clinically proven to increase serum EPO levels and that is echinacea purpurea extract. Based on a generous assumption of 2g per capsule (we are kept in the dark regarding the exact dosage, but it is the main ingredient of the BodyEndurance(TM) Complex which totals 2.1g per capsule), we can see that the total echinacea purpurea dose is in line with that of the study referenced above.

Unfortunately this study did not result in ANY change in Hemoglobin, Hematocrit or RBC count!! Although erythropoietin has other benefits which we will address in later articles, it is safe to conclude that the purpose of injecting recombinant human erythropoietin or boosting EPO levels by other means (e.g. hypoxic exposure) is normally a resultant increase in the oxygen carrying capacity of the blood via enhanced hemoglobin content.

As for the remaining ingredients, these very well might increase the effectiveness of this echinacea purpurea stimulated EPO production, but to an extent capable of significantly increasing hemoglobin content seems unlikely, unless the user is already anemic due to iron/B6/B12/folate deficiency.

When one considers the relatively cheap cost of echinacea purpurea extract bought separately and the incredibly low content of iron in EPO-Boost, we struggle to reach any conclusion other than this product is very poor value for what can only be described as a mild effects.

(1) Intravenous vitamin C can improve anemia in erythropoietin-hyporesponsive hemodialysis patients
(2) Enhancers of iron absorption: ascorbic acid and other organic acids
(3) Vitamin levels in the serum and erythrocytes during erythropoietin therapy in hemodialyzed patients
(4) Folic acid supplementation improves erythropoietin response
(5) Erythropoietin resistance due to vitamin B12 deficiency. Case report and retrospective analysis of B12 levels after erythropoietin treatment.
(6) Hydroxocobalamin supplementation and erythropoisis stimulating agent hyporesponsiveness in haemodialysis patients.
(7) Efficacy and Safety of Oral Versus Intravenous Vitamin C in Hemodialysis Patients with Functional Iron Deficiency
(8) Erythropoietin hyporesponsiveness: from iron deficiency to iron overload.
(9) The effect of 4 wk of oral echinacea supplementation on serum erythropoietin and indices of erythropoietic status.
(10) Spivak JL, Jackson DL: Pellagra: An analysis of 18 patients and a review of the literature. Johns Hopkins Med J 140:295, 1977.

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Darbepoetin: Maybe not so “Novel”

Since first appearing on the market, Recombinant Erythropoietin preparations have called for 2-3x weekly dosing schedules. And at first glance this appears to be a logical approach, particularly considering the half life of intravenous preparations being limited to ~8.5 hours(1).

With the arrival of NESP (Novel Erythropoiesis Stimulating Protein, a.k.a. Darbepoetin alfa) and an IV half-life 3x longer, an obvious opportunity to market an alternative to Epoetin, one that didn’t need to be injected more than once a week.Darbepoetin Alfa

The fact remains however that subcutaneous Epoetin administration results in a large half-life range(2) of 16-67h. In other words a median half-life of 41.5h. Barely differing to the 48.8h half life of subcutaneous NESP(3)!

And yet subcutaneous NESP is recommended for 1x weekly dosing. Why not take Epoetin 1x weekly instead?
Well that question has since been answered by a 2000 Swedish study who found NO difference between 1x versus 2-3x weekly Epoetin (same total weekly dose).(4)

In fact, as far back as 1992 a study conducted by the Chinese University of Hong Kong uncovered “similar responses” between 1x and 2x weekly subcutaneous administration.(5)

Furthermore it was since revealed that as little as once MONTHLY Darbepoetin alfa was effective at maintaining Hemoglobin levels in stable dialysis patients.(6)

One might conclude that any patient considering 1x weekly subcutaenous Darbepoetin alfa in the interests of convenience may very well reduce their costs considerably by opting for 1x weekly rhEPO instead.

(1) Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients
(2) Drugs.com profile of Epoetin Alfa
(3) An overview of the efficacy and safety of novel erythropoiesis stimulating protein (NESP)
(4) The efficacy of once weekly compared with two or three times weekly subcutaneous epoetin beta: results from a randomized controlled multicentre trial. Swedish Study Group.
(5) Once weekly versus twice weekly subcutaneous administration of recombinant human erythropoietin in haemodialysis patients
(6) Darbepoetin alfa administered once monthly maintains haemoglobin levels in stable dialysis patients