Mauro Di Pasquale Q & A

Dear Andrea:

Here's my take on the supplements you asked about. 

All the best,

Mauro
______________________

Methoxyflavone 

This isoflavone (Methoxyflavone is 5-methyl 7-methoxyisoflavone) is a phytoestrogen and has weak estrogenic activity. Theoretically, some phytoestrogens, because they may inhibit the aromatase enzyme and thus decrease estrogen formation from testosterone and androstenedione, and because they may act as inhibitors of estrogen by competitively binding to the estrogen receptor, [1] may increase testosterone production much the same way that anti-estrogens (such as clomiphene – Clomid) and the newer aromatase inhibitors (such as anastrazole – Arimidex), by decreasing the inhibitory effects of estrogen on GnRH and LH (resulting in LH driven increased testicular steroidogenesis and subsequently increased testosterone production). 

Many animal studies and studies on postmenopausal women, however, have shown, that while the various phytoestrogens vary somewhat in their properties in general they have a dampening effect on the hypothalamic-pituitary-testicular axis and result in decreased levels of both total and, due also to increased levels of SHBG, bioavailable testosterone. [2] As well, isoflavones (such as Methoxyflavone) are significantly poorer inhibitors of aromatase than flavones (such as chrysin – the ingredient I use in my TestoBoost product).

The bottom line is that phytoestrogens, while they may have specific health benefits, [3] and may act to control endogenous sex hormone levels in both men and women, [4] are generally counterproductive for athletes wishing to increase muscle mass and strength. 

On the other hand, as already mentioned, some bioflavonoids (a somewhat loose umbrella term that includes isoflavones, anthocyanins, flavans, favonols, flavones, flavanones hesperidin, rutin, and citrus bioflavonoids), however may be useful under certain circumstances. For example, in one study, quercetin and fisetin, two naturally occurring bioflavonoids were shown to mobilize lipids and enzymes in the absence or presence of epinephrine in intact rat adipocytes [5]. The results of this study suggest that some flavonoids act synergistically with epinephrine on beta-adrenergic receptors to stimulate adipocyte lipolysis. Thus these bioflavonoids may be especially useful in the high fat, high protein, low carbohydrate anabolic diet. I included quercetin in both Thermo and ReNew, two of the three formulations in Cellusol, my weight and fat loss product). Quercetin also has significant immune system and antioxidant effects [6] [7] (another reason why it’s particularly useful in ReNew – for info on ReNew check it out on my web site www.MetabolicDiet.com.) 

Ecdysterone 

I wrote about ecdysterone (also known as ß-ecdysterone and 20-hydroxyecdysone, but also commonly referred to as ß-ecdysone or ecdysone, wrongly so since ecdysone is the precursor of ecdysterone – the enzyme ecdysone 20-monooxygenase converts ecdysone to ecdysterone) and related plant and animal sterols over two decades ago (I saw the first mention of the possible hormonal action of ecdysterone in mammals, [8] including plant sources, [9] over three decades ago even though it wasn’t until 1991 that the structure determinations were made of both ecdysone and 20-hydroxyecdysone). And taking into account the available information and research since then, my views are still basically the same. First a brief intro. 

Ecdysterone (a phytoecdysteroid) is an insect molting hormone with other phytoecdysteroids (ecdysteroids) implicated in the molting seen in crabs and lobsters. [10] A variety of phytosteroids, both agonists and to a lesser extent, antagonists, and are found in many plant species. [11] [12] In fact the presence of ecdysone-like molecules, molecules that act as ecdysteroid agonists, in the plant kingdom is nearly universal and new ones, such as the phytoecdysteroid, 3-epi-20-hydroxyecdysone, are constantly being discovered. [13] Plants use ecdysteroids as natural insecticides, yet it appears that phytoecdysteroids are completely innocuous in mammals. Despite their steroidal skeleton, they seem to have no teratogenic, sex-hormonal, anabolic, or analgesic properties. 

Because of their ready availability in plants, humans consume large amounts of dietary ecdysteroids (mostly ecdysterone agonists) without significant beneficial or detrimental effects. For example, fresh spinach contains over 100 µg/g (over 50mg per pound) of polypodine B and 20-hydroxyecdysone. [14] Ingested ecdysteroids survive the acidic conditions of the stomach, are quickly taken up, are promptly removed from the bloodstream, and are disposed of primarily through biliary excretion into the intestine. [15]

So what does it do? Ecdysterone has effects on RNA and protein synthesis in molting insects [16], [17], and birds [18], and has antioxidant properties [19], and anti-histaminic effects. There are also possible structural similarities between ecdysteroid and vertebrate steroid receptors [20]. As well, a Russian study has shown that ecdysterone in animals prevents the development of arrhythmias induced by aconitine and calcium chloride [21]. The authors felt that the mechanism of the antiarrhythmic action is related to the membrane stabilizing effect and the improvement of the hemodynamic parameters and the heart contractility is due to an increase of the adaptative possibilities of the myocardium. 

The part that’s of interest to bodybuilders and other athletes is that the ecdysteroids, especially ecdysterone, has in a series of studies spanning almost two decades, been favorably compared in a number of ways to the anabolic steroid methandrostenolone (other generic names include metandronstenolone, metandienone, and methandienone - trade names include Dianabol and Nerobol). I’ve included the citations and abstracts for 11 of those studies at the end of this email. All of these studies involved VN Syrov, a Russian scientist who’s only published papers are the eleven listed below and who obviously has spent his scientific career, as reflected by the papers he published, examining the effects of ecdysterone and comparing these effects to the anabolic steroid methandrostenelone. 

If you look at the studies in detail, however, a number of things stand out. 

· The studies were all done using rats. 
· The authors contend that the ecdysteroids are anabolic (as measured by their effects on protein synthesis, but not androgenic (as evidenced by their different effects on the thymus gland). 
· All but two of the studies dealt with the comparative effects on liver (similar effects), kidney (similar effects) and thymus (different effects). 
· Of the two remaining studies one dealt with their similar effects on insulin-dependent processes. In this study the authors used the fatty tissue of rats that were either insulin resistance via injections of hydrocortisone or were made insulin insufficient by the use of alloxan. The study looked at the modifying effects of methandrostenelone and ecdysterone on the reactivity of the isolated fatty tissues to insulin infusion, and found that both caused an increase in this reactivity. The authors concluded that “the above effects of steroids were determined by nonspecific synthesis of total proteins in cells rather than by an increase in insulin secretion”, which I gather is their way of saying that insulin sensitivity was increased. 
· The remaining study compared their effects on physical endurance and protein metabolism, stating that “The results of the comparative study on the myotropic activity of methandrostenolone and ecdysterone and their effects on physical endurance of animals suggested that ecdysterone possessing a wider spectrum of the anabolic action on the contractile proteins of the skeletal muscles exerts a more pronounced influence on physical endurance of animals without their preliminary training.” They seem to be saying that ecdysterone is more anabolic than methandrostenelone when measuring endurance in untrained animals. However, this statement, or anything that points to a significant anabolic effect of ecdysterone, is not substantiated by the study itself, which is also so poorly done that no such conclusions can be made. 

All in all, these studies do not show that ecdysteroids have any significant anabolic effects. They also do not look at any possible adverse effects although in general it’s felt that these compounds are innocuous. On the other hand, a recent study has shown that, while inducible gene expression systems in mammalian cells use as inducible reagents, compounds that are thought to be neutral and devoid of physiological or biologically undesirable effects in mammalian cells, that may not be the case with ecdysone analogs. [22] This study using the ecdysone inducible gene expression system in hematopoietic cells and looking at the effects of two inducer analogs of ecdysone, muristerone A and ponasterone A , found these analogs altered the signaling pathways induced by IL-3 in the pro-B cell-line, Ba/F3. The results of the study showed that these two analogs potentiate the IL-3-dependent activation of the PI 3-kinase/Akt pathway, which could ultimately interfere with the growth, and/or survival of these cells. Another factor to consider is that one of the main functions of the ecdysteroids in molting insects is to cause programmed cell death (apoptosis) given the appropriate genetic makeup. [23] 

The bottom line here, contrary to the misinformation offered by the those who are marketing these compounds that ecdysterone is as anabolic as anabolic steroids but without any side effects, is that the ecdysteroids do not have any significant ergogenic, hormonal, or anabolic effects on humans and may in fact be counter productive because of their possible androgen receptor and signaling pathways effects. In my experience I’ve seen neither positive nor negative effects in the many people who have tried ecdysterone. 

That’s not to say that combinations of one of the ecdysteroids with some other substances might not be beneficial. For example a recent study found that there was a significant anabolic effect of a combination of both blow fly maggot extract (not a pretty sight but then again this just might be parlayed into the next nutritional supplement superstar) and ecdysterone on epidermal growth factor stimulation of resting mammalian fibroblast tissue cultures. [24] 

HumanoVar (Humanofort)

This is a chicken embryo oligopeptide extract (read protein) that's supposed to stimulate the adrenal glands to produce testosterone. First of all this product is basically chicken protein (I guess that's why they call it HUMANovar and HUMANofort??), and I can’t see how it will do what they say it does. 

And even if by some miracle it did stimulate the adrenals, then it still wouldn't do much as far as testosterone production and the anabolic drive. That's because testosterone is mainly produced in the testicles with insignificant amounts produced in the adrenal glands. So even if it did stimulate the adrenals, which it doesn't, then it would produce more DHEA and androstenedione, and contrary to what they say in their ads, it would also produce more cortisol. The cortisol in turn would decrease testosterone production. The increased DHEA and androstenedione would increase estrogen production peripherally and would likely decrease testicular steroidogenesis and subsequently testosterone production, because of the inhibiting effect of estrogens on luteinizing hormone, the hormone that drives the testicles to produce testosterone. 

Bottom line is that first of all it doesn't work and taking it would likely be no different than eating Kentucky Fried. And, in the unlikely event that it did stimulate the adrenals, it would be counter productive. 

HumanPro Performance Protein.

HumanoPro Performance Protein contains:

HumanoVar™ - 50 mg
MX-7™ Methoxyflavone - 100 mg
Beta-Ecdysterone 30 mg
Whey Protein – 20-22 g
Glutamine Peptides – 1.5 g

In my view, any effect you're getting from the product comes from the whey protein and glutamine peptides. Unfortunately, there's not that much of the glutamine peptides (1.5 grams per serving) in each serving, and the protein is not the best since the label lists it as whey protein concentrate/isolate. This usually means a lot more of the much cheaper whey protein concentrate and less (sometimes just a sprinkling) of the more expensive whey protein isolate. In my view it’s not worth the extra bucks for the ineffective ingredients and an inferior protein mix. If you compare the protein mix with my Myosin Protein Complex that contains 16 grams of ion exchange whey protein isolate and 10% (3.8 grams) of glutamine peptides per 38 gram serving) at just over half the price of HumanoVar. 



1: Eksp Klin Farmakol 2001 Jul-Aug;64(4):56-8

[Experimental study of pharmacotherapeutic effect of phytoecdisteroids and nerobol in toxic liver damage]

[Article in Russian]

Syrov VN, Khushbaktova ZA.

Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, ul. Kh. Abdulaeva 77, Tashkent, 700170 Uzbekistan.

Phytoecdysteroids ecdysteron and turkesteron isolated from Ajuga turkestanica (Rgl.) Brig. decrease the manifestations of uremic intoxication in rats with experimental renal pathology induced by a nephrotoxic mixture (containing uranyl acetate and glycerol). Injected in a dose of 5 mg/kg, the drugs restore glomerular filtration level, favor the disappearance of the albuminuria and normalize urinary sediments. The nephroprotector effect of the phytoecdysteroids studied resembles the action of a steroidal anabolic drug nerobol.

PMID: 11589113 [PubMed - indexed for MEDLINE]

2: Eksp Klin Farmakol 1997 May-Jun;60(3):41-4

[The results of experimental study of phytoecdysteroids as erythropoiesis stimulators in laboratory animals]

[Article in Russian]

Syrov VN, Nasyrova SS, Khushbaktova ZA.

Phytoecdysteroids alpha-ecdysone, 2-desoxyecdysterone, ecdysterone, sileneoside A, and turkesterone isolated from Rhaponticum carthamoides (Willd.) IIjin, Silene brahuica Boiss and Ajuga turkestanica (Rgl.) Repeated administration of brig increased the content of erythrocytes and hemoglobin in the blood of intact rats. The most active of them--ecdysterone, sileneoside A, and, particularly turkesterone, cause also a marked effect on red blood regeneration in hemotoxic phenylhydrazine anemia. In its capacity for simulating erythropoiesis turkesterone resembles the well-known steroidal anabolic drug nerobol.

PMID: 9324397 [PubMed - indexed for MEDLINE]

3: Ukr Biokhim Zh 1992 Jul-Aug;64(4):61-7

[Effect of phytoecdysteroids and nerobol on parameters of carbohydrate and lipid metabolism and phospholipid spectrum of liver mitochondrial membrane in experimental diabetes mellitus of rats]

[Article in Russian]

Syrov VN, Tashmukhamedova MA, Khushbaktova ZA, Mirtalipov DT, Mamatkhanov AU.

Phytoecdysteroids: ecdysterone and turkesterone, introduced orally to male rats with the body mass 180-120 g in a dose of 5 mg/l kg of mass and nerobol in a dose of 10 mg per 1 kg of the mass for 15 days against a background of the developed alloxan diabetes cause a considerable decrease in the content of free fatty acids of the blood serum, sharply increased after the subcutaneous injection of alloxan to the animals (150 mg per 1 kg of the mass). The content of glycogen, malonic dialdehyde, pyruvic acid and calcium transporting function of the liver mitochondria are also normalized. These changes are closely interrelated (and may be mutually conditioned) with the preparation-induced reduction of phospholipid spectrum of the liver mitochondrial membranes pathologically changed owing to insulin insufficiency. In this case phytoecdysteroids in the first turn normalize the fractions of phospholipids which play the structural role in the mitochondrial membranes, and nerobol normalizes the level of minor and monoacylic phospholipids.

PMID: 1448876 [PubMed - indexed for MEDLINE]

4: Eksp Klin Farmakol 1992 May-Jun;55(3):61-5

[An experimental study of the hepatoprotective properties of phytoecdysteroids and nerobol in carbon tetrachloride-induced liver lesion]

[Article in Russian]

Syrov VN, Khushbaktova ZA, Nabiev AN.

The phytoecdisteroids ecdisterone, turkesterone and cyasterone were administered in a dose of 5 mg/kg per os to rats with hepatitis induced by subcutaneous injections of CCl4. Similarly to the anabolic drug nerobol (10 mg/kg), the above agents not only interfere with the manifestation of the hepatic action of CCl4 (in this case the effect of the phytoecdisteroids is more remarkable) but also favour a more rapid normalization, as compared to the control, of functional and metabolic disorders in the liver. The phytoecdisteroids and nerobol noticeably stimulate the recovery of bile secretion, the synthesis of bilirubin and bile acids, cholesterol excretion.

PMID: 1458171 [PubMed - indexed for MEDLINE]

5: Biull Eksp Biol Med 1991 Oct;112(10):393-5

[The effect of anabolic steroids on proliferative activity of thymocytes]

[Article in Russian]

Sergeev PV, Semeikin AV, Dukhanin AS, Solov'eva EV.

Testosterone, methandrostenolone during ten-day injections to mice 50 mg/kg decrease mass, quality of DNA and 3H thymidine in Thymus. In vitro these drugs loss 3H-thymidine incorporation at 10(-5) M. Ecdysthene do not influence proliferative activity of thymocytes in vitro and thymolytyc effect in vivo. The present results indicate, that proliferative process may have a functional significance in thymolytycal effects of anabolic steroids.

PMID: 1804354 [PubMed - indexed for MEDLINE]

6: Farmakol Toksikol 1991 Jul-Aug;54(4):37-8

[The mechanism of the thymolytic action of anabolic steroids]

[Article in Russian]

Semeikin AV, Stanevskaia TIu, Chermnykh NS, Sergeev PV.

The administration of testosterone and metandrostenolone to male rats in doses of 10 and 20 mg/kg for 10 days produced a decrease of the thymus mass and a reduction of the thymic serum factor content. A phytoecdisteroid ecdisterone not possessing the androgenic activity fails to influence the thymus mass and the content of the thymic serum factor.

PMID: 1786821 [PubMed - indexed for MEDLINE]

7: Probl Endokrinol (Mosk) 1989 Sep-Oct;35(5):77-81

[The effect of nerobol and ecdysterone on insulin-dependent processes linked normally and in insulin resistance]

[Article in Russian]

Kosovskii MI, Syrov VN, Mirakhmedov MM, Katkova SP, Khushbaktova ZA.

The effect of substances with anabolic activity (metandienone and ecdysterone phytoecdysteroid) on the manifestation of insulin effects was studied on a model of insulin resistance in rats induced by injections of hydrocortisone or by insulin insufficiency caused by alloxan. The sensitivity of the body to i. v. infusion of insulin and the reactivity of isolated fatty tissue to the hormone were increased after administration of these substances to test animals. The above effects of steroids were determined by nonspecific synthesis of total proteins in cells rather than by an increase in insulin secretion.

PMID: 2685804 [PubMed - indexed for MEDLINE]

8: Farmakol Toksikol 1988 Nov-Dec;51(6):57-60

[The action of methandrostenolone and ecdysterone on the physical endurance of animals and on protein metabolism in the skeletal muscles]

[Article in Russian]

Chermnykh NS, Shimanovskii NL, Shutko GV, Syrov VN.

The results of the comparative study on the myotropic activity of methandrostenolone and ecdysterone and their effects on physical endurance of animals suggested that ecdysterone possessing a wider spectrum of the anabolic action on the contractile proteins of the skeletal muscles exerts a more pronounced influence on physical endurance of animals without their preliminary training.

PMID: 3234543 [PubMed - indexed for MEDLINE]

9: Vopr Med Khim 1986 Sep-Oct;32(5):24-8

[Comparative study of the effect of ecdysterone, turkesterone and nerobol on the function of rat liver mitochondria in experimental diabetes]

[Article in Russian]

Tashmukhamedova MA, Almatov KT, Syrov VN, Sultanov MB, Abidov AA.

Oxidative phosphorylation and Ca2+-transport functions of liver mitochondria were normalized in rats with alloxane diabetes after peroral administration of phytoecdisteroids - ecdisterone and turkesterone (5 mg/kg) or nerobol (10 mg/kg) within 15 days. These drugs normalized the activity of NADH dehydrogenase and succinate dehydrogenase in respiratory chain of mitochondria, increased distinctly stability of the enzymes to the effect of such factors as heating, effect of phospholipase A2 or trypsin.

PMID: 3776112 [PubMed - indexed for MEDLINE]

10: Vopr Med Khim 1986 Jan-Feb;32(1):81-4

[Effect of phytoecdysteroids and steranobols on the activity and stability of membrane-bound enzymes of liver mitochondria in experimental hepatitis]

[Article in Russian]

Tashmukhamedova MA, Almatov KT, Khushbaktova ZA, Syrov VN.

After administration of phytoecdisteroids (ecdisterone, turkesterone) at a dose of 5 mg/kg and the anabolic steroid preparation nerobol at a dose of 10 mg/kg into rats with experimental hepatitis caused by CCl4 poisoning, positive alterations were found in activity of the polyenzymatic systems in membranes of liver mitochondria simultaneously with an increase in their stability and resistance to the effect of exogenous factors producing the mitochondria degradation (controlled heating, treatment with phospholipase A2 or trypsin). These alterations, which appear to occur due to development of strong binds between phospholipids and proteins of inner mitochondrial membrane, promoted normalization of the respiratory chain and the outer pathway of electron transport in hepatocytes of rats with hepatitis.

PMID: 3953017 [PubMed - indexed for MEDLINE]

11: Nauchnye Doki Vyss Shkoly Biol Nauki 1985;(9):37-9

[Effect of phytoecdisteroids and anabolic steroids on liver mitochondrial respiration and oxidative phosphorylation in alloxan diabetic rats]

[Article in Russian]

Tashmukhamedova MA, Almatov KT, Syrov VN, Sultanov MB, Abidov AA.

Administration of phytoecdisteroides ecdisterone and turkesterone in the dose of 5 mg/kg and anabolic steroid preparation nerobol in the dose 10 mg/kg in rats with experimental diabetes removes the activation of respiration under all metabolic conditions of rats liver mitochondria revealing at given pathology. The normalized effect of phytoecdisteroides on the cells energetic processes is observed on the 7th day of the administration. The same effect of nerobol is revealed at more prolonged (15 days) administration.

PMID: 4063413 [PubMed - indexed for MEDLINE]

Hi Phillip,

In my opinion, my Creatine Advantage is the best one out there. It's the one that EAS and the new creatines with delivery systems not based on carbs, are all trying to copy but can't because they don't really understand why I did what I did when I formulated it and they're not willing to put out the bucks since they have such a high markup compared to my products). Creatine Advantage is based on real science and my expertise instead of hype and false promises. I've attached some info on it in a Word file. It has a very low carb based insulin boosting system (glutamine in the form of glutamine peptides - more stable in liquid form and more effective than free glutamine) and compounds to increase insulin sensitivity (chromium and alpha lipoic acid) and thus make the insulin more effective. It also contains all the necessary products for the synthesis of both high energy phosphate compounds, creatine phosphate and ATP (including the inorganic phosphorus and phosphates, creatine, inosine, and ribose), as well as the compounds needed for the efficient salvage of ATP after it's been metabolically degraded. 

On top of that it contains gluconeogenic compounds (glutamine peptides) and other nutrients to fascilitate the glycolytic and TCA cycle energy processes (biotin - a cofactor in many energy reactions involving glycolytic and TCA anapleurotic enzymes, magnesium - which has also been shown to increase energy systems, insulin sensitivity, protein synthesis and serum testosterone, GH and IGF-I levels, and calcium - which has been shown to fascilitate muscle contraction and decreasing fatigue), and volumizing agents (taurine and sodium), that along with creatine, which is also a volumizing agent, increase protein synthesis and the anabolic processes in the body. 

I hope that this information helps. Let me know if the attached file on Creatine Advantage gets through. 

Best of luck,

Mauro