Growth factors

As discussed else where it is the unique and synergistic balance of many nutrients and co-factors that make up a truly natural anabolic formula. There is no one element that works alone and there is also potential for elements that may appear inactive in isolation to be critical factors when other co-factors are present.

Known growth factors such as creatine are widely understood and excepted and the effect of glutamine and agrinine discussed below, when brought together in an environment where nutrient absorption is optimised and nutrient synergy is present the Growth factor is maximized.

  • Growth factors such as:
  • Arginine & Glutamine
  • Methoxyflavone and Beta ecdysterone

Arginine and Glutamine

As far as supplementation before exercise is concerned, it has been shown that ingestion of 1.5g of arginine will increase human growth hormone (hGH) secretion by blocking release of the hGH-inhibitor somatostatin, although some studies have suggested this causes gastric disturbance. However, 2g of glutamine will lead to elevation of human growth hormone (hGH) 90 minutes later without side effects. It may also be a good idea to ingest some amino acids after exercise, as this has been shown to enhance human growth hormone (hGH) secretion too.

References

Growth hormone and IGF Research 8(suppl B): 127-9, 1998

Journal of Clinical Endocrinology and Metabolism, 76(6): 1418-22, 1993

Metabolism 48(9): 1152-6

European Journal of Endocrinology, 45(4): 445-50, 2001

American Journal of Physiology; Regulative and Integrative Comparative Physiology 279(4):R1455-66, 2000

American Journal of Clinical Nutrition, 61: 1058-1061, 1995

Medicine and Science in Sports and Exercise, 31(12): 1748-54, 1999

Journal of Endocrinology and Metabolism, 75: 157-162, 1992

Journal of Applied Physiology, 83(5): 1756-1761, 1997

European Journal of Applied Physiology, 72: 460-467, 1996

Methoxyflavone and Beta ecdysterone

Whilst there is a lot of controversy with regard to these two elements we have found that used in a synerstic balance they offer only positive enhancement and work particularly well with in this product to enhance and optimise the anabolic environment naturally.

It is no doubt that some of the benefits and claims for these ingredients have been over hyped and had some outrageous claims associated with them such as "so powerful it's guaranteed to help you pack on up to 10 pounds of rock-hard mass in just 30 days!". One study very good study by International Society of Sports Nutrition found ‘we conclude that supplementation of methoxyisoflavone, ecdysterone, and/or sulfo-polysaccharides (CSP3) do not have any affect on training adaptations and/or anabolic/catabolic status in resistance-trained subjects’. http://www.jissn.com/content/3/2/19.

Yet many informed performance specialist and individuals report many positive effects when methoxyflavone and betaecdysterone with in their nutritional regimes. In fact in the trial development of Anabolic Egg with in a small trial group the effects were felt to be positive for increased lean mass whether this came from anabolic properties or positive interaction with the unique proteins and polysaccharides with in the blend a nitrogen positive balance was obtained or improved tendon strength. The overall feeling was one of positive improvement. As there are no negative with regard to the inclusion of such a synergistic stack of ingredients we felt that the inclusion was highly positive. In the presence of a highly bio-available protein and an otimised hormonal state it would appear that these sleeping factors become active participants in a regime for increased muscle mass.

Below are a collection of perspectives and research on these now mythical ingredients.

What is Beta Ecdysterone?

Beta-ecdysterone (ecdysterone, or, 20-Hydroxyecdysone) is a type of ecosteroid, a naturally occurring steroid like compound. Over a 150 ecdysteroids have been identified in many plants and insects. Most commercial ecdysteroids come from plants such as Leuzea carthamoides. Some studies suggest that that Beta-ecdysterone is a powerful anabolic agent, that may enhance protein synthesis and thereby increase lean muscle mass.

Why consider Beta Ecdysterone? Beta-ecdysterone may be of benefit to people looking to increase lean muscle mass.

Summary of Beta Ecdysterone's Phyiological Effects:

  • Appears to have an anabolic effect when taken at a dose of around 5mg per kg (i.e. 350mg for a 70kg man)
  • May enhance weight loss and muscle size
  • Appears to control blood sugar levels
  • Appears to act as an antioxidant

Beta Ecdysterone Research research by Russian researchers Syrov and Kurmukov (1976) found that ecdysterone showed anabolic activity and increased protein synthesis. Animal studies in both rats and Japanese quail have demonstrated significant anabolic effects (Slama et al., 1996; Dinan, 2001). Ecdysterone is also believed to have an anabolic effect in humans (Chermynkh et al., 1988; Simakin et al., 1988; Bizec et al., 2002; Chen et al., 2005).

A Russian research study (Chermynkh et al., 1988) compared the muscle building activities of methandrostenolone, a powerful anabolic steroid, and ecdysterone. They demonstrated that ecdysterone had a wider anabolic action on contractile proteins of the muscle than methandrostenolone.

That year another group of Russian of researchers (Simakin et al., 1998) looked at the combined effects of ecdysterone and a high protein diet. They found that when athletes combined a high protein diet with ecdysterone, lean muscle mass increased by 6-7% and body-fat decreased by 10%.

Research also found that ecdysterone can assit to lower blood glucose levels without altering insulin levels (Yoshida et al., 1971; Chen et al., 2005). One recent study ecdysterone lowered blood sugar levels when they were in the normal (5.5mmol/l) and moderate range (11.1-16.7mmol/l) but not when it was in the high range (22.2mmol/l). Therefore, it could be of benefit in the treatment of type-II diabetes, and may aid weight loss.

Despite these positive findings by Russian researchers, there has been no research, performed outside of Russia, that looks at the effects of ecdysterone on human performance. Therefore, ecdysterone cannot be confirmed as an effective anabolic agent, in humans, until further research is performed, in a well-controlled trial and on a large scale, that is widely available for review purposes.

References

Bizec, B. L., Antigna, J-P., Monteau, F. and Andre, F. (2002) Ecdysteroids: one potential new anabolic family in breeding animals. Analytica Cimica Acta. 473, 89-97.

Chermynkh, N. S., Shimanovskii, N. L., Shutko, G. V. and Syrov, V. N. (1988) The action of methandrostenolone and ecdysterone on the physical endurance of animals and on protein metabolism in the skeletal muscles. Farmakologia I Toksikogia. 51 (6), 57-60.

Chen, Q., Xia, Y., and Qui, Z. (2005) Effect of ecdysterone on glucose metabolism in Vitro. Life Sciences. Article In Press.

Dinan, L (2001) Phytoecdysteroids: biological aspects. Phytochemistry. 57 (3), 325-39.

Konovolova, N. P., Mitrokhin, I. And Volkova, L. M. (2002) Ecdysterone modulates antitomour activity of cytostatics and biosynthesis of macromolecules in tumour-bearing animals. Izvestiya Akademic Nauk, Seriya Bilogicheskaya. 6, 650-658.

Kuzmenko, A. I., Morozova, R. P. and Nikolenko, I. A. (1997) Effects of vitamin D3 and ecdysterone on free-radical lipid peroxidation. Biochemistry (Mosc). 62 (6), 609-612.

Kuz’menko, A. I. (1999) Also a very strong adaptogen and antioxidant: antioxidant effect of 20-hydroxyecdysone in a model system. Ukranskii Biokhimicheskii Zhumal. 71 (3), 35-38.

Simakin, S. Yu. et al., (1998) The combined use of ecdisten and the product ‘Bodrost’ during training in cyclical types of sports. Scientific Sports Bulletin. No 2.

Slama, K., Koudela, K., tenora, J. and Mathova, A. (1996) Insect hormones in vertebrates: anabolic effects of 20-hydroxyecdysone in Japanese quail. Experientia 52 (7), 702-706.

Syrov, V. N. and Kurmukov, A. G. (1976) Anabolic activity of phytoecdyserone-ecdysterone isolated from Rhaponticum carthamoides. Farmakologia I Toksikogia. 39 (6), 690-693.

Yoshida, T., Otaka, T., Uchiyama, M. and Ogawa, S. (1971) Effect of ecdysteone on hyperglycemia in experimental animals. Biochemical Pharmacology. 20, 3263-3268.

Methoxyflavone

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

A number of animal studies and studies on postmenopausal women have shown, that while the various phytoestrogens vary somewhat in their properties in general they have a suppressing effect on the HTP axis and the result is decreased levels of both total bioavailable testosterone. Isoflavones (such as Methoxyflavone) are poor inhibitors of aromatase than flavones such as chrysin. [2]

Phytoestrogens, may have specific health benefits, [3] and may act to control endogenous sex hormone levels in both men and women, [4] are generally not productive for athletes wishing to increase muscle mass and strength.

But as already mentioned, some bioflavonoids (a loose term that includes isoflavones, anthocyanins, flavans, favonols, flavones, flavanones hesperidin, rutin, and citrus bioflavonoids), however may be very useful under certain circumstances. One study found 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]. 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.

References

[1] Kuiper GGJM, Lemmen JG, Carlsson B, et al. 1998 Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 139:4252-4263.

[2] McGarvey C, Cates PA, Brooks A, Swanson IA, Milligan SR, Coen CW, O'Byrne KT. Phytoestrogens and gonadotropin-releasing hormone pulse generator activity and pituitary luteinizing hormone release in the rat. Endocrinology 2001 Mar;142(3):1202-8.

[3] Tham DM, Gardner CD, Haskell WL. 1998 Potential health benefits of dietary phytoestrogens-a review of the clinical epidemiological and mechanistic evidence. J Clin Endocrinol Metab. 83:2223-2235.

[4] Sudhir K, Komesaroff PA. Cardiovascular Actions of Estrogens in Men Journal of Clinical Endocrinology and Metabolism Volume 84, Number 10. October 1, 1999.

[5] Kuppusamy UR. Das NP. Potentiation of beta-adrenoceptor agonist-mediated lipolysis by quercetin and fisetin in isolated rat adipocytes. Biochemical Pharmacology. 47(3):521-9, 1994 Feb 9.

[6] Formica JV, Regelson W. Review of the biology of Quercetin and related bioflavonoids. Food Chem Toxicol 1995;33:1061-1080.

[7] Lamson DW, Brignall MS. Antioxidants and Cancer III: Quercetin. Altern Med Rev 2000 Jun; 5(3):196-208."

Ipriflavone / Methoxyflavone

So what about Ipriflavone and/or 5-methyl-7-methoxy-isoflavone? What are the claims? What is the mechanism of action?

Most people familiar with Ipriflavone know that it has been extensively studied with respect to bone metabolism, or more specifically, osteoporosis. For instance, one representative animal study found ipriflavone inhibited parathyroid hormone-, vitamin D-, PGE2-, and interleukin 1 stimulated bone resorption (1). The effects of Ipriflavone on bone loss have also been demonstrated in humans. The same protocol was used throughout most of these studies (i.e. 200 mg ipriflavone or placebo three times daily). Several two-year studies looked at women immediately postmenopause (age 50-65) and found bone mass was maintained or improved slightly in the ipriflavone groups while those in the placebo groups experienced significant bone loss (2,3,4,5).

Ipriflavone acts as an estrogen "sensitizer" in several tissues:

While Ipriflavone does not have any significant direct estrogenic effects, it does enhance the effects of estrogen, particularly in bone, the thyroid gland, and the gastrointestinal tract (6,7). In bone, ipriflavone makes estrogen's bone sparing effect more potent. Ipriflavone, like the soy flavone genistein, has decent affinity for the estrogen receptor-beta (8).

Ipriflavone's effects on Ca2+:

In the heart, ipriflavone has been shown to prevent Ca2+ ions from building up in the mitochondria (9). Ca2+ builds up in mitochondria when there is insufficient oxygen. Ipriflavone actually enables heart muscle tissue to survive longer without oxygen. This means less damage due to hypoxia (lack of oxygen). No studies have been performed looking at skeletal muscle function during ipriflavone supplementation however, it is not unreasonable to assume a similar function in skeletal muscle. More research is needed in this area.

"Test of anabolic effect: The investigation was carried out with castrated rats by means of the musculus levator ani test and vesicula seminalis test. The preparations were administered orally for a period of three weeks. The tests were performed by the method of Eisenberg and Gordan (Eisenberg, E., Gordan, G. S. J.: J. Pharmacol. 99, 38, 1950). In addition to that, also the weight of the prepared diaphragm of the animals was established. According to these tests, the weight of musculus levator ani rose by a Student significance of p 0.01, the weight of vesicula seminalis did not increase while the weight of the prepared diaphragm of the animals increased by a Student significance of p 0.05. On the basis of these results the preparations proved to possess the anabolic activity free from androgen effect".

The patent goes on to relate:

"The weight yield increasing effect induced by doses of 2 g/100 kg of feed was in the various animal species as follows:
  • 8 to 15% in calves
  • 7 to 10% in cattle
  • 7 to 10% in hogs
  • 8 to 20% in poultry
  • 10 to 20% in rabbits
  • 8 to 12% in guinea pigs"

The amount of feed given to these animals did not increase, only their body weights increased. They did test their new compound on ill humans as well:

"The anabolic effect of the composition was tested on thinned (asthenic), reconvalescent, dystrophic patients suffering from pathological thinness. It has been found that as a result of a treatment lasting for some weeks the patients have gained 2-3 kg of weight. According to our experiments the physical condition of the patients has also improved."

In the patent on 5-methyl-7-methoxy-isoflavone (U.S. patent 4,163,746), the details on increasing ipriflavone's effectiveness are outlined. Several compounds are mentioned, namely 5-methyl-7-methoxy-isoflavone; 5-methyl-7-ethoxy-isoflavone; 5-methyl-7-(2-hydroxy-ethoxy)-isoflavone; and 5-methyl-7-isopropoxy-isoflavone. The same guys filed the 5-methyl-7-methoxy-isoflavone patent some 3 years after they filed the ipriflavone patent. Basically, all this patent does is show that when you methylate the isoflavone, you make it nearly twice as anabolic compared to ipriflavone. The claims are the same except that I noticed the claim that the "compounds are useful as anorexigenic agents. A significant advantage of these compounds over known catabolic agents is that they do not exhibit a central stimulating effect." Now this is quite a claim to add to the fact that they profess that it is an anabolic, as well. So not only does it cause a shift towards more muscle, it also decreases appetite at the same time. Thus far, no manufacturers that I have seen make the claim that ipriflavone or 5-mthyl-7-methoxy-isoflavone is a good appetite suppressants. But if they wanted to I guess they could, based on this patent.

In conclusion we do feel that ipriflavone/methoxyflavone is a valuable supplement to anybody who trains regularly. It "should" help to strengthen bones and tendons and even enhance cellular metabolism. If the patents are true, it may even increase muscle mass and decrease fat mass if used long enough. Keep in mind that we only answered the first question completely. There is still NO good explanation of how ipriflavone or its methylated derivatives could produce non-hormonal, or hormonal for that matter, anabolic effects.

References

1. Tsutsumi N, Kawashima K, Nagata H, et al. Effects of KCA-098 on bone metabolism: comparison with those of ipriflavone. Jpn J Pharmacol 1994;65:343-349.

2. Adami S, Bufalino L, Cervetti R, et al. Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteoporos Int 1997;7:119-125.

3. Gennari C, Adami S, Agnusdei D, et al. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int 1997;61:S19-S22.

4. Agnusdei D, Crepaldi G, Isaia G, et al. A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int 1997;61:142-147.

5. Valente M, Bufalino L, Castiglione GN, et al. Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass. Calcif Tissue Int 1994;54:377-380.

6. Effect of ipriflavone on the response of uterus and thyroid to estrogen. Life Sci 1986 Feb 24;38(8):757-764.

7. Yamazaki I, Kinoshita M. Calcitonin secreting property of ipriflavone in the presence of estrogen. Life Sci 1986;38:1535-1541.

8. Arjmandi BH, Khalil DA, Hollis BW. Ipriflavone, a synthetic phytoestrogen, enhances intestinal calcium transport In vitro. Calcif Tissue Int. 2000 Sep;67(3):225-9.

9. Feuer L, Barath P, Strauss I, Kekes E. Experimental studies on the cardiological effects of ipriflavone on the isolated rabbit heart and in rat and dog. Arzneimittelforschung 1981;31(6):953-8 www.mesomorphosis.com/supplement-profiles/ipriflavone-methoxyflavone.htm