Here is a write up about the ingredients in thunderbolt!
Kallidinogenase
Kallidinogenase, also known as kallikrein, is a natural human enzyme and the only pharmaceutical-strength vasodilator legally available as a supplement. Thunderbolt contains kallikrein in recombinant form, and while sensitive to degradation by low pH from stomach acid, we have encapsulated Thunderbolt with enteric-coating to ensure high bioavailability.
Mechanism of action: Kallikrein is a serine protease, which cleaves kininogen to release the potent vasoactive kinin peptides bradykinin or kallidin. Kallidin is very similar, and can be converted to bradykinin. Within skeletal muscle, bradykinin promotes glucose uptake and improves blood flow. [1]The pharmaceutical class of drugs known as ACE Inhibitors act on bradykinin to keep it active longer which leads to the normalization of blood pressure and nitric oxide release. Boosting bradykinin also increases vascular permeability, which allows for better nutrient delivery to tissues.
Kinins have a very short half-life, as they are destroyed in less than 20secs by through the action of kininases (aminopeptidases) present in the tissues and blood. Hence, kinins are unsuitable for use as exogenously administered agents. In plasma, kininogen is in excess, leaving kallikrein as the limiting factor in kinin formation. Therefore, kallikrein is a far better choice for activating the kinin–kallikrein system.
Kallidinogenase is stable for 28 months at room temperature, and about five years if kept refrigerated. [2]
Primary effects: Kallidinogenase is a peripheral vasodialator, causing an increase in bloodflow and nutrient delivery to skeletal muscle. [3]
Other beneficial effects: Kallidinogenase has significant pro-fertility effects, [4,5,6] is nephroprotective, has diuretic effects via activation of the Bradykinin B2 receptor, and increases bloodflow to the brain. [7] Constitutive over-activation of the Bradykinin B2 receptor has been shown to increase the anabolic response to exercise, so Kallidinogenase may also impart a directly anabolic effect. [8]
Arginine Butyrate
Mechanism of action: Arginine Butyrate is a histone deacetylase (HDAC) inhibitor, and also activates the nitric oxide pathway.
Primary effects: In mouse models of muscular dystrophy arginine butyrate demonstrated beneficial effects including increased muscle strength and increased utrophin expression. [9]
Exposure of myoblasts to HDAC inhibitors results in upregulation of follistatin expression. In turn, follistatin binds to and suppresses the activity of myostatin, a TGF-β family member that negatively regulates muscle mass. [10]
Other beneficial effects: Arginine’s NO-mediated functions are fairly well known. L-arginine is converted into NO by the enzyme NO synthase (eNOS). Nitric oxide causes relaxation vascular smooth muscle by binding to and activating guanylate cyclase and increasing intracellular levels of cyclic-guanosine 3’,5’-monophosphate, causing vasodilation which lowers arterial pressure. [11] This improves blood flow, which increases the “pump”. Nitric oxide also inhibits platelet aggregation and adhesion. [12] Arginine is also a precursor of creatine, and plays a role in accelerating tissue repair following injuries. [13]
S-Nitrosoglutathione
S-Nitrosoglutathione (GSNO) mediates the cellular signalling effects of nitric oxide (NO). To date, GSNO has been tested in almost 20 clinical trials, examining its efficacy in treating a variety of conditions – including topical use as a treatment for female sexual dysfunction. [14]
Mechanism of action: Although GSNO is often described as a “NO donor”, rather than being denitrated like traditional nitrate drugs (e.g. glyceryl trinitrate) which decompose to produce NO, GSNO is capable of donating the nitroso moiety to other molecules, though a reaction called S-nitrosylation. [15] This ability to directly transfer NO+ protects the NO moiety from attack by free radicals. [16]
Primary effects: GSNO has vasodilatory effects on the vasculature, specifically of the arteries. [17] Unlike nitrates, S-nitrosothiols do not cause tolerance with long-term continuous use. [18] While NO itself is very short lived, GNSO acts as a stable intracellular pool of NO which allows the beneficial effects of NO stimulation to sustain over a longer period of time.
Other beneficial effects: GSNO, and associated nitrosothiols like S-nitrosocysteine, contribute to the regulation of breathing, heart rate, blood pressure, and vascular muscle tone. [19,20,21] GSNO inhibits platelet aggregation, [22] probably via degradation to NO and glutathione disulfide by the cell-surface protein disulfide isomerase (csPDI). [23] GSNO also has neuroprotective properties (via up-regulation of the antioxidative thioredoxin system), and may encourage wound repair through enhanced collagen formation. [24,25] Copper Copper potentiates the vasodilatory and antiplatelet actions of GSNO.
Mechanism of action: Copper ions are important catalysts in the decomposition of low molecular weight nitrosothiols (like GSNO) by superoxide dismutase (Cu/Zn SOD). [26]
Primary effects: Copper enhances the anti-platelet aggregation properties of GSNO. [27]
Other beneficial effects: Copper deficiency has been shown to block acetylcholine-mediated vascular smooth muscle relaxation. [28,29,30]
