Part 1 of this article explored some traditional methods of increasing the oxygen-carrying capacity of the blood, and the consequent performance and endurance benefits. Part 2 discusses some less well-known erythropoietic drugs, and looks at whether boldenone could conceivably – as many have long suspected – increase red blood cell count more than other steroids.
In 1967, boldenone undecyclenate was being clinically evaluated by Ciba. At that time the drug was known by its internal moniker of BA-29038. Elderly men and women (aged 70-95) were given BA-29038 at a dosage of 50mg every two weeks for a period of 16 weeks. The expected increase in hematocrit (the percentage of blood made up of red blood cells) turned out to be relatively minor (from 41.74±3.1 to 43.3:±4.1), and was not statistically significant.  That the effects on erythropoiesis were so mild is not too surprising, given the extremely modest dosages involved (bodybuilders often inject doses 20 or more times greater than that used in this study on a weekly basis).
Another study, conducted in 1973 on horses by Squibb (makers of EquipoiseTM) also failed to show an increase in hematocrit in the study period (although again, it was injected at a low dose – so low that no statistically relevant anabolic effect was noted). 
If the clinical studies don’t support an erythropoietic effect, is there any good reason to suspect one? To understand the answer to this question it’s necessary to understand a little advanced steroid metabolism.
Most readers will be aware that testosterone is metabolized in tissues such as skin, scalp, prostate, and liver, by the enzyme 5alpha-reductase to 5α-dihydrotestosterone (DHT), a more potent androgen. Less well-known is that in the liver, there is also a 5beta-reductase enzyme (encoded by the AKR1D1 gene) that catalyzes reduction of the double bond to form 5β-reduced, or 5β-H metabolites.
Relatively small structural changes can significantly change the way steroids are metabolized.
Unsaturation (the addition of a double bond) of a delta-4 steroid between C1 and C2 favours 5β-reduction of the delta-4 double bond over the 5α-H isomer.
This observation is important because it means that for those compounds with a “1,4-diene” structure – such as boldenone – reduction of the Δ4 double bond proceeds in favour of 5β-H metabolites.
“The reduction of the C-4,5-double bond [of boldenone] is stereospecific and yields the 5β-configuration. No 5α-metabolite is detected.” – Wilhelm Schänzer 
So what does this have to do with erythropoiesis?
In the late 1960s and early 1970s a number of experiments were conducted to determine the erythropoietic effects of a series of steroids. Some Δ4, 5α-H and 5β-H steroids of the androstane and pregnane series were found to be erythropoietic. The erythropoietic effects of testosterone and 5α-H steroids was found to be reversible by the co-administration of anti-erythropoietin antibodies – indicating that their effects are mediated directly by an increase in erythropoietin. Conversely, the erythropoietic effects of the 5β-H steroids were not adversely affected by the addition of anti-erythropoietin, which suggested that their erythropoietic effects were achieved by a different mechanism of action. 
The enzyme δ-aminolevulinic acid synthase (ALA synthase) is the rate-limiting step in heme synthesis, both in the liver and in erythroid tissues. In these experiments the researchers found that 5β-H steroid metabolites were more effective at stimulating the induction of δ-aminolevulinic acid synthase than 5α-H steroids.
When radioactively-labelled iron uptake was used to measure hemoglobin production in mice, it was observed that “compounds with a 5β-H configuration produced a significant increase in Fe59 incorporation relative to the control while those with a 5α-H configuration did not.” 
5β-H steroids of the pregnane series were also observed to increase hemoglobin synthesis in chick blastoderm  and in human bone marrow cultures,  and increase red cell mass in squirrel monkeys.  Of the steroids studied, the progesterone metabolite pregnanedione was among the most effective at inducing erythropoiesis.
Since boldenone produces almost exclusively 5β-H steroid metabolites, it could be that boldenone acts as a metabolic precursor to a pool of erythropoietic 5β-H steroids (though boldenone’s major metabolites have not been tested for this activity). In its unchanged form it is also expected to also elicit the same erythropoietin-mediated effects found with other anabolic steroids.
The reasons outlined above lend some credibility to the theory (already widely-held among bodybuilders) that boldenone could have an erythropoietic effect greater than that experienced with other steroids.☨
☨This is a theoretical exposition, and neither a statement of fact nor opinion.
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