Forskolin-95 What you always wanted to know

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  1. Forskolin-95 What you always wanted to know


    Forskolin-95
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    Forskolin-95 is a pure 95% forskolin agent intended to deliver the plethora of potent effects associated with this compound. In particular, Forskolin-95 delivers:

    - Powerful lipolytic and thermogenic effects
    - Regulation of insulin signaling
    - Potent cyclic AMP activation devoid of hormonal down-regulation
    - Enhanced synthesis of steroid hormones such as testosterone
    - Significant anabolic and anti-catabolic effects

    So, what exactly is the key active in Forskolin-95, and how does it induce its effects?

    A diterpene, forskolin is the key active principle of the Ayurvedic herb, Coleus forskohlii, and has been demonstrated to have a variety of powerful effects. [1] Forskolin’s focal mechanism of action is the stimulation of adenylate cyclase, the enzyme responsible for the downstream activation of the second messenger, cyclic AMP (3,5 cyclic adenosine monophosphate (cAMP)) in cells. [2,6,8] A central cell-regulating compound, cyclic AMP activates a range of other enzymes and membrane proteins involved in diverse cellular actions, such as stimulating anabolic and anti-catabolic effects, promoting the oxidation of fatty acids, inducing an increase in the body’s basal metabolic rates, boosting the levels of serum free testosterone, and promoting an increase in lean mass. [9,10]

    Cyclic-AMP Activation

    Although hormones, neurotransmitters and adrenergic receptor agonists are capable of activating cyclic AMP, the pathways they employ for this cyclic AMP stimulation might lead to a negative feedback effect, in which receptor or hormonal down-regulation occurs during prolonged or chronic expression of these hormones or stimulation of these agonists. Herein lies the advantage of forskolin: It can not only work in concert with these hormones and agonists, but can also activate adenylate cyclase (and consequently stimulate cAMP) completely independently of these hormones and receptors, averting the risk of hormonal or receptor down-regulation.

    Protein Kinase A and Hormone Sensitive Lipase Activation

    As is well known, the rate-limiting step in lipolysis is mediated by a cyclic-AMP mechanism. In particular, in this initial step, adenylate cyclase is hormonally activated, leading to an elevated synthesis of cyclic AMP and cyclic-AMP-dependent protein kinase (PKA), as well as the downstream phosphorylation and activation of enzyme hormone sensitive lipase (HSL). [3] Forskolin has been demonstrated to activate adenylate cyclase action (forskolin directly activates the catalytic subunit of adenylate cyclase), devoid of any upstream hormonal intervention, and increase cyclic AMP accumulation, leading to the release of fatty acids from adipose stores, and ultimately to thermogenesis and lipolysis in fat cells. [4,5,7,8]

    Non-Stimulant Thermogenesis and Thyroid-Gland Stimulation

    So, by activating cyclic AMP in adipose cells, completely independently of hormonal intervention, Forskolin-95 ultimately activates HSL, inducing potent lipolytic action by liberating free fatty acids in adipocytes to be used as substrates for energy regulation. Forskolin-95 induces this effect without the incorporation of any stimulant. Beyond this, Forskolin-96 enhances human and animal thyroid activity (comparable in strength to thyrotropin or thyroid-stimulating hormone (TSH)) by potently activating adenylate cyclase in the thyroid gland. [11,12] In particular, Forskolin-95 achieves this effect not only by stimulating the production of the thyroid hormones, T4 and T3, but also by stimulating the conversion of T4 into the metabolically more active T3. This thyroid stimulation supports increased basal metabolic rate and promotes thermogenesis.

    Insulin Signaling

    In another line of exploration relevant to body composition and fat loss, forskolin has been reported, in a rodent trial, to be involved in the beneficial modulation of insulin signaling, influencing macronutrient metabolism for preferential body compositional effects. [13]

    Anabolic Effects

    Furthermore, studies have demonstrated that forskolin not only induced a statistically significant reduction of adipose mass, but also stimulated increased bone mass and serum free testosterone levels, supporting forskolin’s anti-catabolic and anabolic effects. [9,10]

    Synthesis of Steroid Hormones

    Protein kinases (activated by cyclic AMP) play a crucial role in steroidogenesis or the synthesis of steroid hormones. [14] Trophic hormones, such as luteinizing hormone (LH) or adrenal corticotrophic hormone activate cyclic AMP, leading to the activation of protein kinase A (PKA) and the downstream phosphorylation of transcription factors that regulate the steroidogenic acute regulatory (StAR) protein transcription. StAR, a Leydig-cell cholesterol-transfer protein, is a critical protein in the biosynthesis of steroid hormones. In particular, StAR facilitates the transfer of cholesterol, the key substrate for all steroid hormones, to the inner mitochondrial membrane where cholesterol is converted to pregnenolone by the P450 side chain cleavage enzyme (P450scc), initiating the crucial formation of steroids. [15,16,17,18,19] This cascade is important, because the activation of the steroidogenic enzymes involved in the synthesis of testosterone from cholesterol cannot occur without the prior activation of the StAR protein by cyclic AMP. By activating cyclic AMP independently of trophic hormones, forskolin activates PKA and stimulates increased expression of the StAR protein, ultimately leading to steroidogenesis. [14] The steroids, including testosterone, produced in this process typically bind to intra-cellular androgen receptors, specifically activating so-called transcription genes. These steroidal molecules instruct the genes to induce specific effects, for instance, delivering anabolic effects such as increasing nitrogen retention and protein synthesis, reducing cortisol, and increasing IGF.

    Further Anabolic Effects

    Relatedly, as hypothalamic-pituitary-testicular axis (HPTA) shutdown is partly due to low levels of cyclic AMP, forskolin-induced elevation of cyclic AMP expression can stimulate the pituitary gland to increase the secretion of luteinizing hormone (LH), which in turn signals the Leydig cells of the gonads to boost the production of steroid hormones such as testosterone by stimulating the activity of the StAR protein, a Leydig cell cholesterol-transfer protein that plays a foundational role in the synthesis of testosterone. So, by potently elevating cyclic AMP levels, Forskolin-95 exerts a powerful anabolic effect via cyclic AMP-induced steroid biosynthesis.

    Calpains, Calpastatin Gene Transcription and Anti-Catabolic Effects

    Forskolin-95 also exerts an anti-catabolic effect, an effect that is also cyclic-AMP-dependent. Catabolism, in the sense of skeletal muscle mass, is the breakdown of muscle tissue, and reflects the hydrolytic degradation of muscle proteins, partially into peptides or completely into amino acids. This process, also called proteolysis, unlike other posttranslational modifications or changes (such as protein methylation, protein phosphorylation, and so on), is completely irreversible. Under normal circumstances, muscle mass is regulated by a balance between protein synthesis and protein degradation, and muscle breakdown can result when this equilibrium is impaired. [23]

    The breakdown of muscle tissue is predominantly governed by calcium-dependent enzymes, known as calpains. Calpains are calcium-activated proteases that are involved in myofribrillar disassembly and channel the resulting myofibrillar structures into the ubiquitin-proteosome pathway (UPP), the primary proteolytic system in skeletal muscle, for degradation. [21] Apart from injury and calcium leak, calpains can be activated by physiological mechanisms in intact cells. [22] Calpain activity can be regulated by the endogenous inhibitor, calpastatin. Calcium, beyond being an important activator of calpains, also regulates the binding of calpastatins to caplains, leading to inhibition of calpain activity. [22] As it turns out, the activation of calpastatin is cyclic-AMP-dependent. As such, by activating cyclic AMP, Forskolin-95 exerts considerable anti-catabolic action by stimulating calpastatin gene transcription, thus inhibiting caplain activity, and ultimately promoting the preservation of lean muscle mass. [24]

    Summary

    So, Forskolin-95, predominantly via cyclic AMP activation, recruits a variety of pathways to elicit considerable thermogenic and lipolytic activity (and stimulate noticeable fat loss), exert powerful anabolic and anti-catabolic effects, induce thyroid-gland stimulation, boost steroid-hormone biosynthesis, and modulate beneficial insulin signaling.

    A truly powerful and versatile compound, Forskolin-95 is a safe, reliable and effective agent that delivers a spectrum of results consistent with the different goals of bodybuilders, as well as fitness and sports enthusiasts.

    References
    1) Agarwal KC, Parks RE (1983).Forskolin: a potential antimetastic agent. Int J Cancer 32, 801-804.
    2) Leamon KB, Padgett W & Daly, JW (1981). Forskolin: Unique diterpene activator of adenylate cyclase in membrane and intact cells. Proc. Natl. Acad. Sci 78, 3363-3367.
    3) Belfrage P, Fredrikson G, Olsson H & Strilfors P (1982). Hormonal regulation of adipose tissue lipolysis by reversible phosphorylation of hormone-sensitive lipase. Prog. Clin. Biol. Res 102, 213-223.
    4) Mooney RA, Swicegood CL & Marx RB (1986). Coupling of adenylate cyclase to lipolysis in permeabil- ized adipocytes: direct evidence that an antilipolytic effect of insulin is independent of adenylate cyclase. Endocrinology 119, 2240-2248.
    5) Daly, JW (1984). Forskolin, adenylate cyclase and cell physiology: an overview. Adv. Cyclic Nucleotide Protein Phospholylution Res 17, 81-89.
    6) De Souza NJ, Dohadwalla AN & Reden J (1983). Forskolin, A Labdane Diterpenoid with Antihypertensive, Positive Inotropic, Platelet Aggregation Inhibitory, and Adenylate Cyclase Activating Properties. Medicinal Research Reviews 3, 201-219.
    7) Girardier L (1983). “Brown Fat: An Energy Dissipating Tissue”; In: Mammalian Thermogenesis; Girardier L, Sock M.J. Eds, Chapman and Hall Ltd, 50-98.
    8) Burns TW, Langley PE, Terry BE, Bylund DB, Forte LR Jr (1987). Comparative effects of forskolin and isoproterenol on the cyclic AMP content of human adipocytes. Life Sci 40,145-154.
    9) Godard MP, Johnson BA, Richmond SR (2005). Body Composition and Hormonal Adaptations Associated with Forskolin Consumption in Overweight and Obese Men. Obesity Research 13, 1335-1343.
    10) Srivasta SK, Khatoon CS, Mehrotra SR (2002). Pharmacognostic evaluation of coleus forskohlii. Pharmaceutical Biology 40, 129-134.
    11) Haye, B. et al. (1985) Chronic and acute effects of forskolin on isolated thyroid cell metabolism. Molecular and Cellular Endocrinology 43, 41-50.
    12) Lauerberg P (1984). Forskolin stimulation of thyroid secretion of T4 and T3. FEBS Lett. 21, 273-276.
    13) Yajima H. et al (1999). cAMP enhances insulin secretion by an action on the ATP-sensitive K+ channel-independent pathway of glucose signaling in rat pancreatic islets. Diabetes 48, 1006-12
    14) Jones PM, Sayed SB, Persaud SJ, Burns CJ, Gyles S & Whitehouse BJ (2000). Cyclic AMP-induced expression of steroidogenic acute regulatory protein is dependent upon phosphoprotein phosphatase activities. Journal of Molecular Endocrinology 24, 233–239.
    15) Clark BJ, Wells J, King SR, Stocco DM (1994). The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR). J. Biol. Chem. 269, 28314–28322.
    16) Lin D, Sugawara T, Strauss JF III, Clark BJ, Stocco DM, Saenger P, Rogol A, Miller WL (1995). Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science 267, 1828–1831.
    17) Stocco DM (1997). The steroidogenic acute regulatory (StAR) protein two years later. Endocrine 6, 99–109.
    18) Wang X, Liu Z, Eimerl S, Timberg R, Weiss AM, Orly J, Stocco DM (1998). Effect of truncated forms of the steroidogenic acute regulatory protein on intramitochondrial cholesterol transfer. Endocrinology 139, 3903–3912.
    19) Reinhart AJ, Williams SC, Stocco DM (1999). Transcriptional regulation of the StAR gene. Mol. Cell. Endocrinol 151, 161–169.
    20) Averna M, De Tullio R, Capini P, Salamino F, Pontremoli S, Melloni E (2003). Changes in calpastatin localization and expression during calpain activation: a new mechanism for the regulation of intracellular Ca2+-dependent proteolysis. Cellular and Molecular Life Sciences 60, 2669-2678.
    21) Hasselgreen PO, Wray C, Mammen J (2002). Molecular regulation of cachexia: it may be more than the proteasome. Biochem Biophys Res Common 290, 1-10.
    22) Goll DE, Thompson VE, Li H, Wei W, Cong J (2003). The calpain system. Physiol Rev 83, 731–801.
    23) Lang CH, Frost RA, Vary CV (2007). Regulation of muscle protein synthesis during sepsis and inflammation. Am J Physiol Endocrinol Metab 293, E453–E459.
    24) Cong M, Goll DE, Antin PB (1998). cAMP responsiveness of the bovine calpastatin gene promoter. Biochem Biophys Acta. 1443, 186-92.
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  2. Awesome write up Dan! Very informative
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  3. Awesome. Thanks for putting this together Dan.
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  4. AnabolicMinds Site Rep
    Driven2lift's Avatar

    Great write up!
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  5. great info!
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  6. f-95 is one of my favorite supplements, thanks for the write up...

  7. I have 15 bottles of forskolin 95, but none of the forskolin 96.

  8. as a diterpene how's solubility?

    to be taken with or without food?

  9. Quote Originally Posted by DAdams91982 View Post
    Cyclic-AMP Activation

    Although hormones, neurotransmitters and adrenergic receptor agonists are capable of activating cyclic AMP, the pathways they employ for this cyclic AMP stimulation might lead to a negative feedback effect, in which receptor or hormonal down-regulation occurs during prolonged or chronic expression of these hormones or stimulation of these agonists. Herein lies the advantage of forskolin: It can not only work in concert with these hormones and agonists, but can also activate adenylate cyclase (and consequently stimulate cAMP) completely independently of these hormones and receptors, averting the risk of hormonal or receptor down-regulation.
    Soooo no reason to cycle off then, yea? My stash of F-95 and I are about to get real cozy

  10. Quote Originally Posted by kdubson14 View Post
    Soooo no reason to cycle off then, yea? My stash of F-95 and I are about to get real cozy

    With many supplements, they should be cycled but don't NEED to be. With that said, we recommend running for 12 weeks and cycling off for 4 weeks.
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  11. What you guys running? How many caps per day? I've seen different suggestions

  12. Quote Originally Posted by digitalducki View Post
    What you guys running? How many caps per day? I've seen different suggestions
    Coop said their is no additional benefit going over 100mg per day. So I run 4 caps spread throughout the day.

  13. Quote Originally Posted by digitalducki View Post
    What you guys running? How many caps per day? I've seen different suggestions
    Most use 2-4 caps (50-100mg) daily. I wouldn't jump right in at 100mg. I'd recommend starting with 50mg and working up from there if you'd like.
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  14. Ok cool thanks.

  15. Quote Originally Posted by digitalducki View Post
    Ok cool thanks.
    No problem man.
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  16. Quote Originally Posted by digitalducki View Post
    What you guys running? How many caps per day? I've seen different suggestions
    Something you need to work up to (100) slowly or your spending a lot of time on the toilet
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  17. Quote Originally Posted by Geoforce View Post
    Something you need to work up to (100) slowly or your spending a lot of time on the toilet
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  18. Quote Originally Posted by digitalducki View Post
    ^^awful
    Lol... She got over 20M views on youtube.. that is a pretty penny right there in ads to her bank.
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  19. Pretty sad really, what is rewarded in today's world.

  20. Whats the best way to dose this?

  21. Quote Originally Posted by EMPIREMIND View Post
    Whats the best way to dose this?
    25-50mg twice per day. If possible dosed with beta agonists (synergistic combo for fat loss).
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  22. Quote Originally Posted by EMPIREMIND View Post
    Whats the best way to dose this?
    Will you be stacking with anything or running solo?
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  23. Probably ABE and Alphamine...

  24. Just curious as to the timing, fasted or not, pre workout, pre bed etc...
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