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Cardenosine - Liquid Product For R&D

  1. Our new product is finally here and it is "all about the ATP". I mentioned quite a few times on the forum and over email that we plan on releasing an ATP product and people have been asking me about it for the last few months. It seems a very simple task at first but we thought that we can do a bit better than just release a plain ATP supplement. So, without further ago here is what it contains and why.

    Adenosine Triphosphate (ATP) is the cardinal adsorbent in Gilbert Ling's theory of the cell. While mainstream medicine claims that the data on oral administration of ATP is inconclusive, there are several human studies showing that oral ATP is absorbed and has several beneficial effects on muscle health. In addition, an animal study in the references section below shows striking reduction of tumor growth, reversal of cachexia and mortality in animals administered ATP. While tumor are known to produce ATP in amounts similar to normal cells, they do it through glycolysis. So, providing exogenous ATP seems to reduce the excessive glycolysis, lactic acid buildup, and thus the breakdown of tissues (cachexia) in order to feed the tumor. This suggests (once again) that tumor cells are not evil but simply cells under a lot of stress, and reduction of this stress through the provision of beneficial chemicals is therapeutic. So, I think the addition of ATP to Cardenosine does not really need much justification given it is billed as a pro-ATP product.

    As a testament to the importance of ATP in every cell and especially cells highly sensitive to energy deprivation, recent human clinical trials found that increasing ATP levels in the scalp promotes hair growth in male androgenic alopecia, also known as male pattern baldness (MPB). Hair follicles are among the cellular systems most sensitive to ATP depletion, perhaps second only to the brain. The human trials actually used a saturated fatty acid called pentadecanoic acid topically on the scalp and found that the effectiveness of that fatty acid in restoring hair growth was due to its effects on raising scalp levels of succinic acid, and succinic acid then dramatically increased ATP levels. This is not surprising as succinic acid is a very efficient precursor of ATP. So, by using Cardenosine on the scalp, it may be able to deliver ATP directly to those hair follicles and restore hair growth. Cardenosine also contains succinic acid, for an additional ATP boost, and even if there are some doubts about transdermal ATP absorption effectiveness it has been confirmed numerous times (in animals and humans) that succinic acid absorbs through the skin.

    http://onlinelibrary.wiley.com/doi/10.1111/j.1468-2494.1993.tb00592.x/abstract
    "...The effect of the glyceride of pentadecanoic acid (PDG) in treating male pattern alopecia has already been confirmed in a double blind controlled clinical test. In order to study the mechanism of the hair growing effect of PDG, ATP levels were measured in the hair follicles of rabbits. The ATP levels in telogen hair follicles increased remarkably with the application of PDG. To examine this effect, the metabolic properties of pentadecanoic acid (PDA) were investigated using the mitochondrial fraction prepared from guinea-pig hair follicles. It was shown that PDA could be metabolized in hair follicles, and succinic acid, which was formed in the degradation process of PDA, had a remarkable ATP producing ability. These results suggest that the hair growing effect of PDG depends on the efficient supply of energy to hair follicles, and this mechanism seems to be derived from the metabolic property of the odd numbered carbon fatty acid, PDA."

    Based on the above study, pentadecanoic acid (another SFA) is now approved in Japan as topical treatment for hair loss.
    Clinical Evaluation of The Product Containing Glyceride of Pentadecanoic Acid on Male Pattern Alopecia in Women

    A combination of SolBan + Cardenosine (SolBan - Liquid Aspirin/Caffeine/Niacinamide Mix) may be even more beneficial due to the additional antiinflammatory and antifibrotic effects of caffeine, niacinamide, aspirin, inosine, B6, etc.

    But I am jumping the gun here, so let's get back to the story on how I got around to releasing Cardenosine. About a year ago I stumbled upon a product sold in Europe and Latin America as an anti-alcohol and liver health remedy. The product is known as Metadoxine, and it is a simple combination of L-pyroglutamic acid (L-PGA) and vitamin B6 (pyridoxine Hcl).
    Metadoxine - Wikipedia
    As a side note, despite its (unfortunate) common name suggesting it is a variation of glutamic acid, L-PGA is actually just an oxidized version of the amino acid proline (which Peat has written many times about comparing it to glycine). The chemical name of L-PGA is 5-oxo-proline (5-keto-proline) and its properties are much more similar to proline than to glutamic acid. In fact, L-PGA has been shown to act as a glutamate antagonist, at least in the brain.
    The main effect of Metadoxine, observed across many human and animal studies, is to accelerate alcohol metabolism (by speeding up BOTH alcohol dehydrogenase and aldehyde dehydrogenase) and reduce the negative effects of acetaldehyde on the entire organism. While initially it was thought that increase of activity in the alcohol metabolizing enzymes was the main mechanism of action for Metadoxine, more recent studies discovered that the chemical also prevents the depletion of ATP that alcohol consumption induces. This prevention of ATP depletion is likely at least as important for the observed benefits of Metadoxine, as speeding up the activity of the alcohol-metabolizing enzymes.

    "...Metadoxine is an ion pair salt of pyridoxine and pyrrolidon carboxilate (PCA).[1] Pyridoxine (vitamin B6) is a precursor of coenzymes including pyridoxal 5’-phosphate (PLP), which accelerates the metabolic degradation of ethanol and prevents adenosine triphosphate (ATP) inactivation by acetaldehyde. Pyridoxal phosphate dependent enzymes also play a role in the biosynthesis of four important neurotransmitters: serotonin (5-HT), epinephrine, norepinephrine and GABA: see vitamin B6 functions. L-PGA is present in the diet and is produced endogenously by enzymatic conversion of gamma-glutamyl amino acids to L-PGA and free amino acids. In the central nervous system (CNS), L-PGA was found to have a role in composition of neuro-active molecules. Its production has been linked to hepatic gamma-glutamyl transferase activity and levels of reduced glutathione (GSH). Lastly, it was shown that L-PGA facilitates ATP synthesis by stimulating de novo synthesis of purines."

    And since the metabolism of alcohol requires ATP, the current theory is that Metadoxine exerts most of its protective effects on the liver by preventing the decline of ATP when alcohol is consumed. This makes sense and matches the recent posts about inosine ameliorating fatty liver by raising levels of ATP. Furthermore, other studies found that Metadoxine (or more specifically its component L-PGA) increases de novo synthesis of ATP from purines (e.g. inosine) and thus prevents ATP depletion systemically as a result of other toxic assaults including carcinogens, radiation, and various chronic conditions. So, all in all, the combination of L-PGA and vitamin B6 has been shown to prevent ATP depletion from a number of assaults that organisms encounter every day.
    As if that was not good enough, Metadoxine is known as serotonin antagonist at the 5-HT2B receptor. This second effect is probably why it has shown beneficial results for liver fibrosis, secondary to alcohol consumption. Studies that have tried to elucidate the mechanism of antagonism point to L-PGA as the most likely active ingredient.
    5-HT2B receptor - Wikipedia
    "....Metadoxine: a 5ht2b antagonist and GABA-activity modulator [33]"

    As you can see from the Wikipedia pages, Metadoxine is currently being evaluated for ADHD - a condition associated with dopamine deficiency and currently treated with dopaminergic stimulants like Ritalin and Adderall. Furthermore, studies are being conducted with Metadoxine for Fragile X syndrome, which is a subset of autism thought to be genetically driven. Given the role of dopamine deficiency in ADHD and serotonin excess (i.e. hence dopamine deficiency as well) in autism, I did some digging and it turns out that Metadoxine does indeed raise dopamine and lower serotonin (see study in the references section). Thus, the rational for including the ingredients of Metadoxine in our product are the prevention of ATP depletion by various assaults as well as its anti-serotonin and pro-dopamine effects.

    Now, given that Metadoxine raises ATP levels by accelerating de-novo purine synthesis as well as the purine salvage pathway,its effects will be even more pronounced if there was enough raw material for ATP synthesis floating around. One such raw material is of course inosine, and that is why the product includes inosine as another ingredient. In addition to the studies I posted on inosine ameliorating fatty liver. I also posted about the ability of inosine to raise the NAD/NADH ratio, as well as increase mitochondrial biogenesis, oxidative respiration, and lower lactate/NO/LPO. Yet another post showed that an immediate metabolite of inosine lowers both serotonin and cortisol synthesis.
    Inosine Powerfully Stimulates Mitochondriogenesis, Oxidative Metabolism & Cell Differentiation
    Inosine Increases NAD/NADH Ratio And Reduces Systemic Inflammation
    Inosine As A Powerful Inhibitor Of Serotonin And Cortisol Synthesis

    The benefits of inosine are numerous and it enjoys a widespread use in Europe as an immunostimulant, cardioprotector, anti-ischemic, anti-hypoxic, anti-inflammatory, anti-anemic, anabolic, and in general actoprotector substance. I collected a decent number of studies on inosine in the references section below, but these are just scratching the surface. There are thousands of studies in Russian available through various Russian-labguage databases, and I can provide additional references for those who can read in Russian or are interested in messing around with Google Translate.

    While reading all those studies on inosine going back to the early 1950s, I noticed that in Europe inosine is commonly administered in combination with succinic acid. In fact, there are several patented drugs containing inosine and succinic acid, the most famous ones being Cytoflavin and Reamberin (amber acid is the common name for succinate).
    Cytoflavin generic. Price of cytoflavin. Uses, Indications and Description
    Reamberin - Drugs.com

    Succinic acid had been studied for even longer than inosine and it has a myriad of health effects, many of them overlapping with inosine. As a Krebs cycle intermediate, its main metabolic effect is the stimulation of the Krebs cycle activity as well as the flow of electrons along the electron transport chain (ETC). In fact, the enzyme that metabolizes succinic acid (Succinic Acid Dehydrogenase) is an enzyme that is part of both the Krebs cycle and ETC. The final effects of these stimulations is of course the increase in ATP synthesis. So, the presence of succinic acid in Cardenosine is due to its role as a stimulator (and an indirect source) of ATP synthesis.

    Finally, a word on potential synergy of Cardenosine with some other chemicals. Succinic acid stimulates succinic dehydrogenase and the electrons succinic acid provide subsequently flow along the ETC, assuming the ETC is working properly. However, if somebody takes succinic acid and their ETC is not functioning well for some reason then there won't be as much boost in ATP synthesis, compared to if the ETC was operating well (and the electrons from succinic acid were able to flow to O2 at the end). One way to circumvent a malfunctioning ETC is using MB (e.g. Oxidal). It provides an alternative electron acceptor for that electron flow originating from succinic acid, and it has been shown to restore electron flow along the ETC in various pathologies. And in case of well-working ETC it can speed up ATP synthesis even more than succinic acid would on its own.
    Another chemical that can speed up the process of succinic acid oxidation is riboflavin (e.g. Energin) as it is the precursor of FAD, and FAD is the cofactor for succinic dehydrogenase (which metabolizes succinic acid). In fact, the drug Cytoflavin I mentioned above, contains riboflavin for that very reason. The active form of riboflavin (R5P) would work even better. However, rifoblavin/R5P/FAD will not help in case of ETC damage/malfunction. It would only speed up the Krebs cycle side of the reaction.
    Bypassing the compromised mitochondrial electron transport with methylene blue alleviates efavirenz/isoniazid-induced oxidant stress and mitochondria-mediated cell death in mouse hepatocytes - ScienceDirect
    Mitochondrial pharmacology: Electron transport chain bypass as strategies to treat mitochondrial dysfunction
    Alternative Mitochondrial Electron Transfer as a Novel Strategy for Neuroprotection

    Finally, as mentioned at the beginning of the thread, a combination of Cardenosine and SolBan may be synergistic in providing benefits to optimal hair growth. The caffeine and niacinamide present in SolBan may actually increase the transdermal absorption of the ingredients of Cardenosine and thus help deliver pre-formed ATP (from Cardenosine) directly to the hair follicles.

    That's pretty much it. The idea of Cardenosine is thus very simple - increase ATP levels by exploiting various pathways. Those pathways include providing ATP directly (duh), preventing its degradation (Metadoxine), or increasing its synthesis through the Krebs cycle / ETC (succinic acid) and through the purine salvage pathway (inosine). If somebody is aware of any other pathways to ATP please let me know. Maybe @Travis can shed some light??
    As far as the name Cardenosine - it is just an old and forgotten name for ATP. It is the same idea as the name Calcirol we picked for the vitamin D3 supplement.

    The units listed on the label are just for measurement purposes. They do not indicate suggested or optimal dose. Please note that similar to the products sold by companies like BluePeptides, this product is for lab/research use only. The product can be ordered from the link below:
    www.idealabsdc.com/lab

    *******************************************************************************
    Cardenosine is a product with the main purpose of raising ATP levels in an organism. Besides raising ATP, the ingredients in Cardenosine have been studies separately over a period of several decades. Those ingredients and have been found to possess a number of desirable properties - including anti-inflammatory, anti-serotonin, pro-dopamine, anti-glucocorticoid, anti-inflammatory, anti-endotoxin, anti-viral, anti-mutagenic, antimicrobial, anti-cancer, anxiolytic, antidepressant, cardioprotective, anti-ischemic, neuroprotective, and generally anti-aging.

    Serving size: 40 drops
    Servings per container: about 15
    Each serving contains the following ingredients:

    Adenosine Triphosphate (ATP): 200mg
    Succinic acid: 200mg
    L-Pyroglutamic acid: 200mg
    Inosine: 100mg
    Vitamin B6 (P5P): 10mg

    Other ingredients: distilled water
    *******************************************************************************

    References:

    ATP:
    Anticancer activities of adenine nucleotides in tumor bearing hosts (very important!)
    http://jpet.aspetjournals.org/content/jpet/294/1/126.full.pdf
    A Single Dose Of Oral Atp Supplementation Improves Performance And Physiological Response During Lower Body Resistance Exercise In Recreational Res... - PubMed - NCBI
    Oral Adenosine-5'-triphosphate (ATP) Administration Increases Postexercise ATP Levels, Muscle Excitability, and Athletic Performance Following a Re... - PubMed - NCBI
    Treatment with Oral ATP decreases alternating hemiplegia of childhood with de novo ATP1A3 Mutation. - PubMed - NCBI
    Oral adenosine-5'-triphosphate (ATP) administration increases blood flow following exercise in animals and humans. - PubMed - NCBI
    Adenosine-5'-triphosphate (ATP) supplementation improves low peak muscle torque and torque fatigue during repeated high intensity exercise sets. - PubMed - NCBI
    Cardiovascular and pulmonary response to oral administration of ATP in rabbits. - PubMed - NCBI


    L-Pyroglutamic acid:

    1. Misc
    [Reproductive toxicity of metadoxine in rats]. - PubMed - NCBI
    Brain penetration of orally administered sodium pyroglutamate. - PubMed - NCBI
    Neurotoxic effects of endogenous materials: quinolinic acid, L-pyroglutamic acid, and thyroid releasing hormone (TRH). - PubMed - NCBI
    [Metadoxine in the treatment of vomiting in uremic patients under dialysis treatment]. - PubMed - NCBI
    Pyroglutamate kinetics and neurotoxicity studies in mice. - PubMed - NCBI


    2. Anti-cancer
    Isolation of an anti-angiogenic substance from Agaricus blazei Murill: its antitumor and antimetastatic actions. - PubMed - NCBI


    3. Insulin resistance / diabetes
    Anti-diabetic effect of pyroglutamic acid in type 2 diabetic Goto-Kakizaki rats and KK-Ay mice. - PubMed - NCBI
    Metadoxine, an ion-pair of pyridoxine and L-2-pyrrolidone-5-carboxylate, blocks adipocyte differentiation in association with inhibition of the PKA... - PubMed - NCBI


    4. Vision / eyes / retina
    Pyroglutamic acid promotes survival of retinal ganglion cells after optic nerve injury. - PubMed - NCBI
    Reduction of enhanced rabbit intraocular pressure by instillation of pyroglutamic acid eye drops. - PubMed - NCBI


    5. Pro-dopamine / anti-prolactin
    Effect of metadoxine on striatal dopamine levels in C57 black mice. - PubMed - NCBI
    Isolation of pyroglutamic acid from hypothalamic tissue and significance of its inhibition of prolactin release. - PubMed - NCBI


    6. Mood / Mental Health / Cognition
    Pyroglutamic acid improves the age associated memory impairment. - PubMed - NCBI
    A randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of extended-release metadoxine ... - PubMed - NCBI
    Alternative pharmacological strategies for adult ADHD treatment: a systematic review. - PubMed - NCBI
    Attention benefits after a single dose of metadoxine extended release in adults with predominantly inattentive ADHD. - PubMed - NCBI
    Efficacy of metadoxine extended release in patients with predominantly inattentive subtype attention-deficit/hyperactivity disorder. - PubMed - NCBI
    Capillary electrophoresis for caffeine and pyroglutamate determination in coffees study of the in vivo effect on learning and locomotor activity in... - PubMed - NCBI
    Pyroglutamic acid improves learning and memory capacities in old rats. - PubMed - NCBI


    7. Neuroprotective
    [The central vascular and metabolic effects of pyroglutamic acid]. - PubMed - NCBI
    Protection by pyroglutamic acid and some of its newly synthesized derivatives against glutamate-induced seizures in mice. - PubMed - NCBI
    [Molecular mechanisms of pidolate magnesium action and its neurotropic affects]. - PubMed - NCBI
    Effect of pyrrolidone-pyroglutamic acid composition on blood flow in rat middle cerebral artery. - PubMed - NCBI
    [Correlations of pharmacokinetics and pharmacodynamics of a combined preparation containing pyrrolidone and pyroglutamic acid]. - PubMed - NCBI
    Pyroglutamate stimulates Na+ -dependent glutamate transport across the blood-brain barrier. - PubMed - NCBI
    [Neuroprotective and cerebrovascular effects of GABA mimetics]. - PubMed - NCBI
    [Evolution of the neuroprotection concept]. - PubMed - NCBI
    [Neuroprotective properties of pyroglutamic acid in combination with pyrrolidone]. - PubMed - NCBI
    [Effect of a drug composition containing pyroglutamic acid and pyrrolidone on the cerebral circulation]. - PubMed - NCBI
    L-pyroglutamic acid protects rat cortical neurons against sodium glutamate-induced injury. - PubMed - NCBI
    Role of oxoproline in the regulation of neutral amino acid transport across the blood-brain barrier. - PubMed - NCBI
    Investigations on the binding properties of the nootropic agent pyroglutamic acid. - PubMed - NCBI
    Pyroglutamic acid administration modifies the electrocorticogram and increases the release of acetylcholine and GABA from the guinea-pig cerebral c... - PubMed - NCBI
    Is glutamate a trigger factor in epileptic hyperactivity? - PubMed - NCBI


    8. Anti-alcohol / liver health / hepatitis
    Pyroglutamic acid stimulates DNA synthesis in rat primary hepatocytes through the mitogen-activated protein kinase pathway. - PubMed - NCBI
    Identification of a hepatoprotective peptide in wheat gluten hydrolysate against D-galactosamine-induced acute hepatitis in rats. - PubMed - NCBI
    Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis. - PubMed - NCBI
    Metadoxine Versus Placebo for the Treatment of Non-alcoholic Steatohepatitis: A Randomized Controlled Trial. - PubMed - NCBI
    Treatment with metadoxine and its impact on early mortality in patients with severe alcoholic hepatitis. - PubMed - NCBI
    Preliminary findings on the use of metadoxine for the treatment of alcohol dependence and alcoholic liver disease. - PubMed - NCBI
    [Capsule metadoxine in the treatment of alcoholic liver disease: a randomized, double-blind, placebo-controlled, multicenter study]. - PubMed - NCBI
    Acute alcohol intoxication. - PubMed - NCBI
    Combined metadoxine and garlic oil treatment efficaciously abrogates alcoholic steatosis and CYP2E1 induction in rat liver with restoration of AMPK... - PubMed - NCBI
    A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence. - PubMed - NCBI
    [The therapeutic effect of metadoxine on alcoholic and non-alcoholic steatohepatitis]. - PubMed - NCBI
    Metadoxine in the treatment of acute and chronic alcoholism: a review. - PubMed - NCBI
    Fibrosis and glycogen stores depletion induced by prolonged biliary obstruction in the rat are ameliorated by metadoxine. - PubMed - NCBI
    Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study. - PubMed - NCBI
    Efficacy of metadoxine in the management of acute alcohol intoxication. - PubMed - NCBI
    Metadoxine prevents damage produced by ethanol and acetaldehyde in hepatocyte and hepatic stellate cells in culture. - PubMed - NCBI
    Treatment of alcoholic fatty liver: is the metabolic effect of metadoxine the only reason for improved liver function? - PubMed - NCBI
    Long-term ethanol administration enhances age-dependent modulation of redox state in central and peripheral organs of rat: protection by metadoxine. - PubMed - NCBI
    Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for t... - PubMed - NCBI
    Effects of Metadoxine on cellular status of glutathione and of enzymatic defence system following acute ethanol intoxication in rats. - PubMed - NCBI
    Effects of metadoxine on cellular formation of fatty acid ethyl esters in ethanol treated rats. - PubMed - NCBI
    Changes in expression of the albumin, fibronectin and type I procollagen genes in CCl4-induced liver fibrosis: effect of pyridoxol L,2-pyrrolidon-5... - PubMed - NCBI
    [Therapeutic use of metadoxine in chronic alcoholism. Double blind study of patients in a department of general medicine]. - PubMed - NCBI
    Effects of metadoxine on cellular free fatty acid levels in ethanol treated rats. - PubMed - NCBI
    Metadoxine (pyrrolidone carboxylate of pyridoxine) antagonizes the locomotor-stimulatory effect of ethanol in mice. - PubMed - NCBI
    [Effects of metadoxine on main biohumoral changes induced by chronic alcoholism]. - PubMed - NCBI
    Pyridoxol L,2-pyrrolidon-5 carboxylate prevents active fibroplasia in CCl4-treated rats. - PubMed - NCBI
    Action of metadoxine on isolated human and rat alcohol and aldehyde dehydrogenases. Effect on enzymes in chronic ethanol-fed rats. - PubMed - NCBI
    Alcoholic abstinence syndrome: short-term treatment with metadoxine. - PubMed - NCBI
    [Metadoxine in alcohol-related pathology]. - PubMed - NCBI
    https://www.ncbi.nlm.nih.gov/pubmed/2972505
    https://www.ncbi.nlm.nih.gov/pubmed/3828134
    https://www.ncbi.nlm.nih.gov/pubmed/3539468
    https://www.ncbi.nlm.nih.gov/pubmed/7192694


    Succinic Acid:

    1. Misc.
    https://www.ncbi.nlm.nih.gov/pubmed/14968174
    https://www.ncbi.nlm.nih.gov/pubmed/27141637
    https://www.ncbi.nlm.nih.gov/pubmed/25076754
    https://www.ncbi.nlm.nih.gov/pubmed/24555229
    https://www.ncbi.nlm.nih.gov/pubmed/25790698
    https://www.ncbi.nlm.nih.gov/pubmed/23457968
    https://www.ncbi.nlm.nih.gov/pubmed/27502960
    https://www.ncbi.nlm.nih.gov/pubmed/27072777
    https://www.ncbi.nlm.nih.gov/pubmed/28974722
    https://www.ncbi.nlm.nih.gov/pubmed/14816255
    https://www.ncbi.nlm.nih.gov/pubmed/14137425
    https://www.ncbi.nlm.nih.gov/pubmed/3756230
    https://www.ncbi.nlm.nih.gov/pubmed/23901465

    2. Cancer
    https://www.ncbi.nlm.nih.gov/pubmed/29412795
    https://www.ncbi.nlm.nih.gov/pubmed/16746008


    3. Reproductive/menopause
    https://www.ncbi.nlm.nih.gov/pubmed/23767097
    https://www.ncbi.nlm.nih.gov/pubmed/23323329
    https://www.ncbi.nlm.nih.gov/pubmed/27759458


    4. ATP/Metabolism/insulin/diabetes/obesity
    https://www.ncbi.nlm.nih.gov/pubmed/29211771
    https://www.ncbi.nlm.nih.gov/pubmed/11109530
    https://www.ncbi.nlm.nih.gov/pubmed/10965352
    https://www.ncbi.nlm.nih.gov/pubmed/9580367
    https://www.ncbi.nlm.nih.gov/pubmed/8865105
    https://www.ncbi.nlm.nih.gov/pubmed/7857680
    https://www.ncbi.nlm.nih.gov/pubmed/3202180
    https://www.ncbi.nlm.nih.gov/pubmed/3571215
    https://www.ncbi.nlm.nih.gov/pubmed/3032929
    https://www.ncbi.nlm.nih.gov/pubmed/16315979
    https://www.ncbi.nlm.nih.gov/pubmed/17537413
    https://www.ncbi.nlm.nih.gov/pubmed/16910316
    https://www.ncbi.nlm.nih.gov/pubmed/16694665
    https://www.ncbi.nlm.nih.gov/pubmed/13525390
    https://www.ncbi.nlm.nih.gov/pubmed/13242564
    https://www.ncbi.nlm.nih.gov/pubmed/13898070
    https://www.ncbi.nlm.nih.gov/pubmed/7181923
    https://www.ncbi.nlm.nih.gov/pubmed/6289887
    https://www.ncbi.nlm.nih.gov/pubmed/7269512


    5. GI/liver/digestion/endotoxin/Kidney
    https://www.ncbi.nlm.nih.gov/pubmed/9178284
    https://www.ncbi.nlm.nih.gov/pubmed/7944393
    https://www.ncbi.nlm.nih.gov/pubmed/15856914
    https://www.ncbi.nlm.nih.gov/pubmed/17855829
    https://www.ncbi.nlm.nih.gov/pubmed/18649657
    https://www.ncbi.nlm.nih.gov/pubmed/18055880
    https://www.ncbi.nlm.nih.gov/pubmed/23536947
    https://www.ncbi.nlm.nih.gov/pubmed/21516854
    https://www.ncbi.nlm.nih.gov/pubmed/20919557
    https://www.ncbi.nlm.nih.gov/pubmed/19529856
    https://www.ncbi.nlm.nih.gov/pubmed/27411015
    https://www.ncbi.nlm.nih.gov/pubmed/27030185
    https://www.ncbi.nlm.nih.gov/pubmed/26118088
    https://www.ncbi.nlm.nih.gov/pubmed/14771029
    https://www.ncbi.nlm.nih.gov/pubmed/7256925
    https://www.ncbi.nlm.nih.gov/pubmed/7364086
    https://www.ncbi.nlm.nih.gov/pubmed/44392
    https://www.ncbi.nlm.nih.gov/pubmed/730417


    6. Neuroprotective/CNS
    https://www.ncbi.nlm.nih.gov/pubmed/15206559
    https://www.ncbi.nlm.nih.gov/pubmed/12910308
    https://www.ncbi.nlm.nih.gov/pubmed/12230956
    https://www.ncbi.nlm.nih.gov/pubmed/9027260
    https://www.ncbi.nlm.nih.gov/pubmed/7893078
    https://www.ncbi.nlm.nih.gov/pubmed/16242831
    https://www.ncbi.nlm.nih.gov/pubmed/15565840
    https://www.ncbi.nlm.nih.gov/pubmed/17523453
    https://www.ncbi.nlm.nih.gov/pubmed/17369903
    https://www.ncbi.nlm.nih.gov/pubmed/18856206
    https://www.ncbi.nlm.nih.gov/pubmed/25699017
    https://www.ncbi.nlm.nih.gov/pubmed/23887452
    https://www.ncbi.nlm.nih.gov/pubmed/22665728
    https://www.ncbi.nlm.nih.gov/pubmed/22379879
    https://www.ncbi.nlm.nih.gov/pubmed/20517221
    https://www.ncbi.nlm.nih.gov/pubmed/26781419
    https://www.ncbi.nlm.nih.gov/pubmed/28432362
    https://www.ncbi.nlm.nih.gov/pubmed/13141885
    https://www.ncbi.nlm.nih.gov/pubmed/13119037
    https://www.ncbi.nlm.nih.gov/pubmed/14833533
    https://www.ncbi.nlm.nih.gov/pubmed/15393012
    https://www.ncbi.nlm.nih.gov/pubmed/18133082
    https://www.ncbi.nlm.nih.gov/pubmed/20247549
    https://www.ncbi.nlm.nih.gov/pubmed/20292325


    7. Stress/Mood/Cognition
    https://www.ncbi.nlm.nih.gov/pubmed/3410024
    https://www.ncbi.nlm.nih.gov/pubmed/14561530
    https://www.ncbi.nlm.nih.gov/pubmed/26081324
    https://www.ncbi.nlm.nih.gov/pubmed/26016320
    https://www.ncbi.nlm.nih.gov/pubmed/25894772
    https://www.ncbi.nlm.nih.gov/pubmed/13458496
    https://www.ncbi.nlm.nih.gov/pubmed/13533639
    https://www.ncbi.nlm.nih.gov/pubmed/13288815
    https://www.ncbi.nlm.nih.gov/pubmed/1158629


    8. Antibacterial/antiviral/antipathogen
    https://www.ncbi.nlm.nih.gov/pubmed/28635832
    https://www.ncbi.nlm.nih.gov/pubmed/14352463


    9. Asthma/Allergies/histamine/inflammation/pulmonary
    https://www.ncbi.nlm.nih.gov/pubmed/10227065
    https://www.ncbi.nlm.nih.gov/pubmed/3325978
    https://www.ncbi.nlm.nih.gov/pubmed/13010407
    https://www.ncbi.nlm.nih.gov/pubmed/14926567
    https://www.ncbi.nlm.nih.gov/pubmed/14868262
    https://www.ncbi.nlm.nih.gov/pubmed/14852365
    https://www.ncbi.nlm.nih.gov/pubmed/18870246
    https://www.ncbi.nlm.nih.gov/pubmed/7375465


    10. CVD/circulation/hypoxia
    https://www.ncbi.nlm.nih.gov/pubmed/9607905
    https://www.ncbi.nlm.nih.gov/pubmed/7819559
    https://www.ncbi.nlm.nih.gov/pubmed/19145322
    https://www.ncbi.nlm.nih.gov/pubmed/22866305
    https://www.ncbi.nlm.nih.gov/pubmed/21846056
    https://www.ncbi.nlm.nih.gov/pubmed/22420162
    https://www.ncbi.nlm.nih.gov/pubmed/19803215
    https://www.ncbi.nlm.nih.gov/pubmed/27475675
    https://www.ncbi.nlm.nih.gov/pubmed/4670508
    https://www.ncbi.nlm.nih.gov/pubmed/4076420
    https://www.ncbi.nlm.nih.gov/pubmed/1023969


    11. Muscle/anabolism/ergogenic/actoprotective
    https://www.ncbi.nlm.nih.gov/pubmed/28944867
    https://www.ncbi.nlm.nih.gov/pubmed/7773089
    https://www.ncbi.nlm.nih.gov/pubmed/25016753
    https://www.ncbi.nlm.nih.gov/pubmed/6498320


    11. Radiation/EMF
    https://www.ncbi.nlm.nih.gov/pubmed/2251365
    https://www.ncbi.nlm.nih.gov/pubmed/3495507


    Inosine:

    1. Misc.
    https://www.ncbi.nlm.nih.gov/pubmed/11912550
    https://www.ncbi.nlm.nih.gov/pubmed/8940895
    https://www.ncbi.nlm.nih.gov/pubmed/26903141
    https://www.ncbi.nlm.nih.gov/pubmed/7079571
    https://www.ncbi.nlm.nih.gov/pubmed/720586
    https://www.ncbi.nlm.nih.gov/pubmed/1583701


    2. Cancer
    https://www.ncbi.nlm.nih.gov/pubmed/8732102
    https://www.ncbi.nlm.nih.gov/pubmed/1963839
    https://www.ncbi.nlm.nih.gov/pubmed/3689353
    https://www.ncbi.nlm.nih.gov/pubmed/2423256


    3. Reproductive/menopause
    https://www.ncbi.nlm.nih.gov/pubmed/15061652
    https://www.ncbi.nlm.nih.gov/pubmed/6654752


    4. ATP/Metabolism/insulin/diabetes/obesity
    https://www.ncbi.nlm.nih.gov/pubmed/10917906
    https://www.ncbi.nlm.nih.gov/pubmed/10737175
    https://www.ncbi.nlm.nih.gov/pubmed/18562629
    https://www.ncbi.nlm.nih.gov/pubmed/2448739
    https://www.ncbi.nlm.nih.gov/pubmed/6198929
    https://www.ncbi.nlm.nih.gov/pubmed/474465
    https://www.ncbi.nlm.nih.gov/pubmed/186586
    https://www.ncbi.nlm.nih.gov/pubmed/186035
    https://www.ncbi.nlm.nih.gov/pubmed/2650958
    https://www.ncbi.nlm.nih.gov/pubmed/2601579


    5. GI/liver/digestion/endotoxin/Kidney
    https://www.ncbi.nlm.nih.gov/pubmed/14767733
    https://www.ncbi.nlm.nih.gov/pubmed/12947007
    https://www.ncbi.nlm.nih.gov/pubmed/12443716
    https://www.ncbi.nlm.nih.gov/pubmed/12388199
    https://www.ncbi.nlm.nih.gov/pubmed/10623851
    https://www.ncbi.nlm.nih.gov/pubmed/7909375
    https://www.ncbi.nlm.nih.gov/pubmed/16394918
    https://www.ncbi.nlm.nih.gov/pubmed/23660094
    https://www.ncbi.nlm.nih.gov/pubmed/23232950
    https://www.ncbi.nlm.nih.gov/pubmed/20868668
    https://www.ncbi.nlm.nih.gov/pubmed/19906119
    https://www.ncbi.nlm.nih.gov/pubmed/19375788
    https://www.ncbi.nlm.nih.gov/pubmed/19103461
    https://www.ncbi.nlm.nih.gov/pubmed/18643723
    https://www.ncbi.nlm.nih.gov/pubmed/16531145
    https://www.ncbi.nlm.nih.gov/pubmed/3663162
    https://www.ncbi.nlm.nih.gov/pubmed/7317735
    https://www.ncbi.nlm.nih.gov/pubmed/7233650
    https://www.ncbi.nlm.nih.gov/pubmed/6998075
    https://www.ncbi.nlm.nih.gov/pubmed/534819
    https://www.ncbi.nlm.nih.gov/pubmed/369092
    https://www.ncbi.nlm.nih.gov/pubmed/55837
    https://www.ncbi.nlm.nih.gov/pubmed/3188198
    https://www.ncbi.nlm.nih.gov/pubmed/1350772


    6. Neuroprotective/CNS
    https://www.ncbi.nlm.nih.gov/pubmed/16317421
    https://www.ncbi.nlm.nih.gov/pubmed/15976325
    https://www.ncbi.nlm.nih.gov/pubmed/15692110
    https://www.ncbi.nlm.nih.gov/pubmed/15026152
    https://www.ncbi.nlm.nih.gov/pubmed/15019271
    https://www.ncbi.nlm.nih.gov/pubmed/14744912
    https://www.ncbi.nlm.nih.gov/pubmed/12676349
    https://www.ncbi.nlm.nih.gov/pubmed/12440381
    https://www.ncbi.nlm.nih.gov/pubmed/12084941
    https://www.ncbi.nlm.nih.gov/pubmed/11930165
    https://www.ncbi.nlm.nih.gov/pubmed/10557347
    https://www.ncbi.nlm.nih.gov/pubmed/9691220
    https://www.ncbi.nlm.nih.gov/pubmed/9681443
    https://www.ncbi.nlm.nih.gov/pubmed/8863513
    https://www.ncbi.nlm.nih.gov/pubmed/28294142
    https://www.ncbi.nlm.nih.gov/pubmed/27497459
    https://www.ncbi.nlm.nih.gov/pubmed/27130268
    https://www.ncbi.nlm.nih.gov/pubmed/26805433
    https://www.ncbi.nlm.nih.gov/pubmed/26529505
    https://www.ncbi.nlm.nih.gov/pubmed/26365718
    https://www.ncbi.nlm.nih.gov/pubmed/25382017
    https://www.ncbi.nlm.nih.gov/pubmed/24913204
    https://www.ncbi.nlm.nih.gov/pubmed/24502983
    https://www.ncbi.nlm.nih.gov/pubmed/24366103
    https://www.ncbi.nlm.nih.gov/pubmed/24312612
    https://www.ncbi.nlm.nih.gov/pubmed/21643997
    https://www.ncbi.nlm.nih.gov/pubmed/21508223
    https://www.ncbi.nlm.nih.gov/pubmed/19553458
    https://www.ncbi.nlm.nih.gov/pubmed/17406376
    https://www.ncbi.nlm.nih.gov/pubmed/17293357
    https://www.ncbi.nlm.nih.gov/pubmed/16923353
    https://www.ncbi.nlm.nih.gov/pubmed/3924588
    https://www.ncbi.nlm.nih.gov/pubmed/2985162
    https://www.ncbi.nlm.nih.gov/pubmed/6264499
    https://www.ncbi.nlm.nih.gov/pubmed/6784145
    https://www.ncbi.nlm.nih.gov/pubmed/6275442
    https://www.ncbi.nlm.nih.gov/pubmed/6252561
    https://www.ncbi.nlm.nih.gov/pubmed/37602
    https://www.ncbi.nlm.nih.gov/pubmed/286337
    https://www.ncbi.nlm.nih.gov/pubmed/284422
    https://www.ncbi.nlm.nih.gov/pubmed/2390879


    7. Stress/Mood/Cognition
    https://www.ncbi.nlm.nih.gov/pubmed/28695335
    https://www.ncbi.nlm.nih.gov/pubmed/27966087
    https://www.ncbi.nlm.nih.gov/pubmed/24569499
    https://www.ncbi.nlm.nih.gov/pubmed/23613131
    https://www.ncbi.nlm.nih.gov/pubmed/3003762


    8. Immunomodulation/Antibacterial/antiviral/antipathogen
    https://www.ncbi.nlm.nih.gov/pubmed/27821093
    https://www.ncbi.nlm.nih.gov/pubmed/16358878
    https://www.ncbi.nlm.nih.gov/pubmed/16055398
    https://www.ncbi.nlm.nih.gov/pubmed/14978744
    https://www.ncbi.nlm.nih.gov/pubmed/8876359
    https://www.ncbi.nlm.nih.gov/pubmed/8788123
    https://www.ncbi.nlm.nih.gov/pubmed/1283173
    https://www.ncbi.nlm.nih.gov/pubmed/1384023
    https://www.ncbi.nlm.nih.gov/pubmed/27476281
    https://www.ncbi.nlm.nih.gov/pubmed/26591662
    https://www.ncbi.nlm.nih.gov/pubmed/26011933
    https://www.ncbi.nlm.nih.gov/pubmed/2446760
    https://www.ncbi.nlm.nih.gov/pubmed/2429908
    https://www.ncbi.nlm.nih.gov/pubmed/24272839
    https://www.ncbi.nlm.nih.gov/pubmed/6209193
    https://www.ncbi.nlm.nih.gov/pubmed/1693173
    https://www.ncbi.nlm.nih.gov/pubmed/1693065
    https://www.ncbi.nlm.nih.gov/pubmed/2482585
    https://www.ncbi.nlm.nih.gov/pubmed/3150993
    https://www.ncbi.nlm.nih.gov/pubmed/1726683


    9. Asthma/Allergies/histamine/pulmonary
    https://www.ncbi.nlm.nih.gov/pubmed/15579626
    https://www.ncbi.nlm.nih.gov/pubmed/11923614
    https://www.ncbi.nlm.nih.gov/pubmed/11712075
    https://www.ncbi.nlm.nih.gov/pubmed/11673212
    https://www.ncbi.nlm.nih.gov/pubmed/23355189
    https://www.ncbi.nlm.nih.gov/pubmed/22456813
    https://www.ncbi.nlm.nih.gov/pubmed/20472668
    https://www.ncbi.nlm.nih.gov/pubmed/19174745


    10. CVD/circulation/hypoxia
    https://www.ncbi.nlm.nih.gov/pubmed/8240456
    https://www.ncbi.nlm.nih.gov/pubmed/1462898
    https://www.ncbi.nlm.nih.gov/pubmed/21059208
    https://www.ncbi.nlm.nih.gov/pubmed/19902663
    https://www.ncbi.nlm.nih.gov/pubmed/16730445
    https://www.ncbi.nlm.nih.gov/pubmed/3503988
    https://www.ncbi.nlm.nih.gov/pubmed/3830217
    https://www.ncbi.nlm.nih.gov/pubmed/3737656
    https://www.ncbi.nlm.nih.gov/pubmed/3956572
    https://www.ncbi.nlm.nih.gov/pubmed/3591170
    https://www.ncbi.nlm.nih.gov/pubmed/3922025
    https://www.ncbi.nlm.nih.gov/pubmed/6705907
    https://www.ncbi.nlm.nih.gov/pubmed/6347379
    https://www.ncbi.nlm.nih.gov/pubmed/6888082
    https://www.ncbi.nlm.nih.gov/pubmed/6847795
    https://www.ncbi.nlm.nih.gov/pubmed/6368998
    https://www.ncbi.nlm.nih.gov/pubmed/7094228
    https://www.ncbi.nlm.nih.gov/pubmed/6889939
    https://www.ncbi.nlm.nih.gov/pubmed/7326684
    https://www.ncbi.nlm.nih.gov/pubmed/7449820
    https://www.ncbi.nlm.nih.gov/pubmed/7423093
    https://www.ncbi.nlm.nih.gov/pubmed/7377330
    https://www.ncbi.nlm.nih.gov/pubmed/7224845
    https://www.ncbi.nlm.nih.gov/pubmed/7370243
    https://www.ncbi.nlm.nih.gov/pubmed/435683
    https://www.ncbi.nlm.nih.gov/pubmed/445523
    https://www.ncbi.nlm.nih.gov/pubmed/347135
    https://www.ncbi.nlm.nih.gov/pubmed/910962
    https://www.ncbi.nlm.nih.gov/pubmed/28559
    https://www.ncbi.nlm.nih.gov/pubmed/1242314
    https://www.ncbi.nlm.nih.gov/pubmed/125181
    https://www.ncbi.nlm.nih.gov/pubmed/2594615
    https://www.ncbi.nlm.nih.gov/pubmed/2923227
    https://www.ncbi.nlm.nih.gov/pubmed/3068401
    https://www.ncbi.nlm.nih.gov/pubmed/3355562
    https://www.ncbi.nlm.nih.gov/pubmed/3688262
    https://www.ncbi.nlm.nih.gov/pubmed/1711609
    https://www.ncbi.nlm.nih.gov/pubmed/1991356


    11. Muscle/anabolism/ergogenic/actoprotective
    https://www.ncbi.nlm.nih.gov/pubmed/11469903
    https://www.ncbi.nlm.nih.gov/pubmed/26875616
    https://www.ncbi.nlm.nih.gov/pubmed/16643789


    12. Radiation/EMF
    https://www.ncbi.nlm.nih.gov/pubmed/19280464
    https://www.ncbi.nlm.nih.gov/pubmed/17179648
    https://www.ncbi.nlm.nih.gov/pubmed/16776063
    https://www.ncbi.nlm.nih.gov/pubmed/16669708
    https://www.ncbi.nlm.nih.gov/pubmed/2809455
    https://www.ncbi.nlm.nih.gov/pubmed/2685869
    https://www.ncbi.nlm.nih.gov/pubmed/1811724
     
  2. "Servings per container: about 15"

    sounds a bit low. so once a week could work ?
     
  3. Very cool. Perhaps the most generally beneficial mechanism of action.
     
  4. as a typ 1 Diabetic i am very interested in this
     
  5. On the halloweenish picture on your site I read "serving size 40 drops".
    Any comments on the difference of effects between this and MB?
     
  6. Every other day, if you want it to last 30 days. For me at least, using every day at these doses was a bit too stimulating. I think the dopaminergic effects of pyroglutamic acid really build up if used every day. So, I thought it was a good compromise.
     
  7. Thanks. That is my hope. I don't think there is a cell in any tissue that cannot use a bit of help with ATP, especially when stress/assault of some kind.
     
  8. Great catch! The correct dose is 40 drops, so the label is right. I updated the original thread description.
    Oxidal complements this greatly! So, thanks so much for bringing this up. In fact, I will update the original thread and mention this.
    The reason for synergy is that methylene blue (MB) helps the ETC function better if there is block anywhere in the stages I - IV. So, if somebody takes succinic acid and their ETC is not functioning well for some reason then there won't be as much boost as the ETC was operating well and the electrons from succinic acid were able to flow to O2 at the end. MB proides this alternative electron acceptor, which has been shown to restor electron flow along the ETC in case of damage. And in case of well working ETC it can speed it up even more.
    Bypassing the compromised mitochondrial electron transport with methylene blue alleviates efavirenz/isoniazid-induced oxidant stress and mitochondria-mediated cell death in mouse hepatocytes - ScienceDirect
    Mitochondrial pharmacology: Electron transport chain bypass as strategies to treat mitochondrial dysfunction
    Alternative Mitochondrial Electron Transfer as a Novel Strategy for Neuroprotection

    Another chemical that can speed up the process of succinic acid oxidation is riboflavin (e.g. Energin) as it is the precursor of FAD and FAD is the cofactor for succinic dehydrogenase which metabolizes succinic acid. In fact, riboflavin is present in the drug cytoflavin I mentioned above, for that very reason. The active form R5P would work even better. However, riboflavin/R5P/FAD will not help in case of ETC damage/malfunction. It would only speed up the Krebs cycle side of the reaction.
     
  9. I love your creativity in these supplements man

    Curious about a couple things:

    The "glutamic" in pyroglutamic acid worries me a bit as any time I have taken glutamic acid I get super ADHD and depressed. Cannot handle MSG or anything like that. Is L-PGA similar to glutamic acid or different?

    Can you outline what kind of effects you saw from your experimentation of this? Or the test group's experiences?

    Also ,other then Inosine, will any of the ingredients raise Uric Acid? I don't think so, but want to make sure.

    Thanks man!
     
  10. @haidut exciting! any evidence for topical administration of inosine increasing its relatively short half life ?
     
  11. Haidut, I'm wondering if, given the neuroprotective properties of this supplement, it might be of help systemically to those with Parkinson's, particularly if taken with Oxidal/MB?
     
  12. so this is anti-hang-over product you were mentioning as well or will you release another product specific for that purpose??
     
  13. I gotta ask...is this legal?

    I’m assuming this isn’t FDA approved, in which case is it enough to just declare ‘for R&D purposes’ in the title, even though it’s clear and obvious from the accompanying marketing language that it is being recomended, marketed and distributed for general use as a supplement by whoever orders it? Is it really that easy to bypass the regulations?

    I’m not questioning the effectiveness or safety of this thing, just the legality of making it and selling it.
     
  14. Research is perfectly legal. Thank goodness we are still able to do research.
     
  15. So what you’re saying is that “research” *wink*, *wink* is perfectly legal?
     
  16. According to a study perforemed by a major skincare and chemical-actives enterprise, at least in aged skin cells not ATP in itself is the major probelem, but mitochondrial Creatinkinase (mtCK).
    I'll find the study meanwhil I'll losely translate the major bit:

    In Skin cells of aged probands, function of mtCK is diminished and malfunctioning leading to less stimulation of mitochondrial OXPHOS,
    Phospho-creatine pool maintenance is slowed down and local supply of PCr is insufficinet.
    Cytosolic Creatinkinase is no longer bal to maintain and stabilize ATP-Concentration in that cells. Higher ADP-concentration leads to glycolysis to maintain ATP-concetration and functioning of local ATPasen.

    The study further sais that ATP needs Creatinkinases to "leave" the mitochondria and be recycled from the cytosols?
    Anybody ever thought about that angke.

    The said PhD thesis is in german only, but the main synopsis is that things like Q10 and so forth are not significantly different in aging skin but for the insufficnnet couplin of Creatinkinase to mito ATP-synthesis - leading to many detrimental consequences in skin energy metabolism. (Not surprisingly, old skin cells use Glycolysis for ATP as said, wih a lot of lactate then damaging the skin)

    Is this not of importance when supplementing ATP in therory? How to increase mtCK? Creatine? In the Diss at least they provide evidence for enrichng skincreams with Creatine
     
  17. So, pyroglutamic acid actually has several names including 5-oxo-proline / 5-keto-proline. In other words, it is proline with an extra oxygen atom and Peat has written about the beneficial effects of proline along with those of glycine. I think the choice of name "pyroglutamic" is unfortunate as it confuses people. In reality, L-PGA seems to act like an antagonist to glutamate and seems to increase GABA signalling (where it is needed). The Wiki link in regards 5-HT2B antagonism mentions that. Another glutamate analog is the amino acid theanine and it is also known to antagonize glutamate and promote GABA.
    Theanine - Wikipedia
    Inosine may raise uric acid but human studies showed that only chronic daily doses of 3g or more led to elevations of uric acid beyond the acceptable range.
    The only side effects I had when testing this was overstimulation and trouble sleeping, which is a known side effect of ATP administered through infusion. Hence, the design of the product to be used every other day instead of daily like the other products we have.
     
  18. Why would this not be legal...you can get all these ingredients on Amazon if you wanted.
     
  19. Don't know if it would prolong half life, but it makes it better as an ATP precursor because it avoids the hydrolysis of inosine to hypoxanthine and ribose (which occurs in the GI tract).
     
  20. Thank you!
     
  21. Can't speak about specific conditions but the combination of L-PGA + B6 does seem to raise dopamine quite a bit, so in theory should help dopamine deficiency states. That is why it is used for ADHD, which is also a dopamien deficiency state.
     
  22. Yes, the combination of L-PGA and B6 is the antihangover product I had in mind. Originally, I thought of adding succinic acid to it and releasing as a separate AlcoBan product but then I realized the effects are due to raising ATP and since I had an ATP product in the works I thought it would be best to combine them both because of synergistic effects and to not have people spend money on two separate supplements that actually work best together.
     
  23. Why wouldn't it be legal? None of the ingredients is a controlled substance and how people use it is their business. We are just not advertising it for human consumption. As you probably know, you can buy liquid aromatase inhibitors like letrozole / anastrozole, SARMs, SERMs (tamoxifen, clomiphene), etc from various US-based vendors and they market their products for "R&D purposes only". Ultimately, it comes down to safety and potential for abuse. In this product, everything is substance that exists in the organism naturally or in the diet, and none of the ingredients is a controlled substance like those SARM/SERM, AI or designers steroids which also available legally.
     
  24. I suppose adding creatine could help improve ATP, but in my experience succinic acid is a much better and more direct precursor. Creatine is more of a buffer that can be used to provide emergency ATP source. On the other hand, succinic acid HAS to be metabolized into ATP as that is the ultimate destination of all food we eat and that food (after a few steps) always goes through the succinic acid step.
     
  25. copy that
     
  26. Ok cool! Some people don't tolerate MB, could you briefly compare the difference in effects betweenMB and this new supplement or even inosine?
    By the way I've been wondering if exercise lowers BP (you were a former athlete and love your MB) then perhaps exercise would be a nice supplement to a MB regimen ?
     
  27. Oral ATP raises uric acid as well, although the acute doses were high

    Adenosine 5'-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans.

    "A single dose of orally administered ATP is not bioavailable, and this may explain why several studies did not find ergogenic effects of oral ATP supplementation. On the other hand, increases in uric acid after release of ATP in the proximal part of the small intestine suggest that ATP or one of its metabolites is absorbed and metabolized. Uric acid itself may have ergogenic effects, but this needs further study. Also, more studies are needed to determine whether chronic administration of ATP will enhance its oral bioavailability."​

    Oral bioavailability of ATP after prolonged administration.

    "ATP supplementation for 4 weeks did not lead to changes in blood or plasma ATP concentrations. Of all ATP metabolites, only plasma uric acid levels increased significantly after the administration of 5000 mg of ATP. Prolonged administration of ATP was safe as evidenced from liver and kidney parameters. We conclude that oral administration of ATP only resulted in increased uric acid concentrations."
    Screen Shot 2018-02-10 at 7.55.22 AM.png Screen Shot 2018-02-10 at 7.55.57 AM.png
     
  28. How is ribose metabolized?
     
  29. how much would you take in order to prevent hangover?before or after heavy night out?
     
  30. I've seen that even a mild dietary phosphorous deficiency can impair cell ATP levels. Creatine will also increase phosphate requirements and uptake - potentially a mechanism for creatine induced muscle cramps if that mild dietary phosphate deficiency is present and/or if there is insulin resistance. Important to consider, especially for athletes, considering the general emphasis on reducing phosphate intake here. ATP in this product comes with its own phosphate, but I assume ramping up ETC or utilizing the purine salvage pathways could increase phosphate requirements further.
     
  31. Thank you!
     
  32. I notice that distilled water is the only additional ingredient so does that mean this product is designed for oral intake. There appear to be no topical absorption enhancers.

    Also, it appears to me that this product does not have to be limited to the lab chemical section. Why not also include it in the supplement section, since
    Or, technically, should it only be in the supplement section?
     
  33. want :hearteyes:
     
  34. Well, MB is just an electron carrier, an oxidizing agent. So, it is the spark that helps burn the fuel. However, if the Krebs cycle is not working well and not enough electrons reach the ETC then MB probably won't do much for ATP even tough it has other benefits such as lowering inflammation (as per my other recent post). Succinic acid and inosine are kind of like pre-formed ATP precursors, which have been shown to raise ATP in humans and animals, and MB can make that process even more efficient. So, Oxidal and Energin would be the spark and Cardenosine the fuel in my analogy.
    Exercise seems to lower BP due to keeping blood vessels flexible, and it also lowers heart rate. If MB raises BP then I would try some taurine, and/or vitamin K/D as it could be an issue with vascular calcification and those have been shown to reverse it. Exercise may help too, so I would use whatever works best for the specific person.
     
  35. The human studies in the ATP section of the thread show positive effects from oral ATP administration. Yes, most of it breaks down into adenosine and phosphate but the purine salvage pathway seems to be pretty efficient in regenerating that ATP using the resulting adenosine. In addition, rodent studies show that about 10% of orally administered ATP enters circulation unchanged (i.e. without breakdown). Furthermore, one of the rodent studies, also in that ATP section, shows that chronic feeding of ATP orally made the rodents really efficient at converting food into ATP, so the positive effects may be more related to how exogenous ATP changes the physiology than its direct contribution as a purine.
    So, exogenous ATP definitely has effects and I hoping that further human studies will elucidate the mechanism.
     
  36. I would use a single dose (40 drops) about 1 hour before drinking. I don't think a second dose is needed. Higher doses, equivalent to 2 servings (80 drops) daily have been used to treat cirrhosis and other liver diseases.
     
  37. Ribose actually shares a common pathway with inosine for re-generating ATP. Ribose gets converted into ribose-5-phosphate, then this ribose-5-P gets converted into phosphoribosyl pyrophosphate (PRPP), then PRPP gets converted into phosphoribosylamine, which then gets converted into inosine-5-monophosphate (IMP). Inosine also replenishes ATP through conversion into IMP. But inosine already contains ribose within its structure, so I don't think there is need to add even more ribose as a separate ingredient in this product.
     
  38. True, good points. I may actually change the inosine to inosine-5-monophosphate (IMP) since that way it will also have its own phosphate supply, leaving only succinic acid competing for phosphate groups. IMP is harder to source, but I will see what can be done. It is more water-soluble than inosine so I may be able to dissolve more per dose and make this even more effective.
     
  39. Succinic acid is a transdermal enhancer and so is pyroglutamic acid.
    [Oleyl pyroglutamate for use as transdermal enhancer and its enhancing mechanism]. - PubMed - NCBI
    http://www.pharmtech.tu-bs.de/files/muegoy/JFokuhlJena0910.pdf

    We may move it to the supplement section. I am waiting on our lawyer to opine on the matter.
     
  40. Hey @charlie - Haidut blew up the pubmed title script again
     
  41. Feels like Christmas all over again :). It's in the queue and looking forward to trying !
     
  42. Is this the most dopaminergic product from Idealabs? How stable is it? Shelf life?
     
  43. Anyone got this yet then? Must be some initial impressions..
     
  44. @haidut Would this be a good alternative for lowering prolactin for someone who isn't comfortable using something like lisuride or bromo? What is a good starting dose for someone who is typically prone to overstimulation?
     
  45. Anyone got this yet then? Must be some initial impressions..

    I ordered on friday night , hoping it would start shipping Saturday, but he didnt ship it till Monday, 3 days estimate...I should get it today.
     
  46. Just dropped twenty drops onto my tongue. Will check back in when I'm levitating.
     
  47. This looks great. Excited to try it out.
     
  48. So should I put this on my rats skin or administer orally?
     
  49. I can attest that proline is great and highly underrated IMO. Alpha tocopherol succinate has been superior to every other E product I have tried and maybe the succinic acid has something to do with it. Smart combination overall.
     
  50. Since ATP has a high affinity for magnesium, would this supplement increase the need for dietary (or supplemental) magnesium?
     
  51. Don't know if it is the most dopaminergic, but when I use it over several days it is very reminiscent to dopamine agonists like lisuride or pramipexole. ATP is stable in solution as long as it does not become too acidic or basic. So, ideal pH is in the 5-7 range. Shelf life is mandated by the FDA to be no more than 12 months, as the product is liquid.
     
  52. It is only sanctioned for topical use.
     
  53. If anything, it would probably decrease the need it as it would help retain it from the dietary sources you consume it from.
     
  54. Possibly, since the two studies on dopamine/prolactin showed that the L-PGA/B6 combo both lowered prolactin and increased dopamine. I would start with the recommended dose, every other day. You can try every day but if you notice headache and overstimulation I would back off and try a lower dose or every other day.
     
  55. Regarding the dopamine boost, is there any reason to believe it is more sustainable long term (no down regulation) than other dopaminergic compounds ?
     
  56. Yesterday afternoon I used 25 drops topically. I didn't notice anything obvious until about 4-5 hours later, when I started having some heart palpitations off and on for maybe 20 minutes. Just prior to this, I did start feeling an extreme sense of well-being, but I'm not sure how much of this to chalk up to the Cardenosine and how much to chalk up to the fact that I'd just had an amazingly good evening with my husband. It may have been a mix of both. Today, the few times I've needed to walk briskly (like to get in out of the rain), I've felt it in my heart/chest more than usual. Also, I woke up at 3:30 from a bad dream, and when I woke up for work, I was again having a stressful dream (I haven't been recalling dreams recently at all).

    I'll probably wait a couple days and try a half dose first thing in the morning, to see if the response is the same.
     
  57. So far so good for me. Had a nice dopaminergic boost and heightened sense of well being throughout the day. Slept like a baby. Took the full dose orally.
     
  58. The mouse study showed that even a tiny dose of 1 mg/kg Metadoxine, which is equivalent to 0.08mg/kg for a human, elevated dopamine more than 24 hours after taking it. Since Metadoxine is used for ADHD in humans, I suspect the effects is persistent enough to matter. And since the effect is increase in actual endogenous dopamine synthesis vs. dopamine agonism on receptors, I am hoping that there would be less risk of downregulation.
     
  59. Interestingly succinic acid is taken as a menopause "remedy". And RP says that:

    "Filatov found that stressed tissues of both plants and animals produce protective and stimulating substances, which can be extracted for medical use. He identified succinic acid as a component of his extracts. Szent-Gyorgyi found that succinic acid stimulates respiration, which might explain why it promotes synthesis of pregnenolone and related steroids. It and fumaric acid are now considered to be adaptogens. Since succinic acid safely chelates toxic heavy metals out of mitochondria, it might also safely carry copper into the mitochondria."
     
  60. Interesting, thanks. Please keep us posted.
     
  61. Great, thanks for the feedback Dan!
     
  62. Yes, and it seems to work rather well. Look at the studied in the "Reproductive/menopause" section in the original thread.
     
  63. How would one know if there ETC is not working properly?
     
  64. Most people with malfunctioning ETC have high lactate, and symptoms of MELAS.
    MELAS syndrome - Wikipedia

    I don't know if there is a specific easily obtainable test to see if just ETC is working properly. Maybe @Travis / @Koveras / @Kyle M would know.
     
  65. Perhaps indirectly through lactic acid would be the best bet, but it is actually possible to measure the mitochondrial membrane potential (ψ) which is probably the most direct measure of mitochondrial activity. Determining the activity of the electron transport chain in this way is tantamount to measuring the electrons themselves; the value for ψ is generally around −180‧mV. Obviously, this is not a routine clinical test but this has been done.
     
  66. Hello haidut
    Along 1g of inosine, what topical dose of cardenosine would I need for a muscle imbalance? And does it mix with other SFA esters-ethanol products?
     

  67. This product would definitely be a benefit to people with MELAS syndrome!
     
  68. The problem is in isolating someone's biopsied mitochondria, lots of variables. A crude test off the top of my head would be disappearance time of methylene blue, using the assumption that problem respiration is linked to a well-oxidized cell potential.
     
  69. Did anybody ever ask Peat about his opinion on using oral methylene blue as a health test? I wonder if he thinks it's reliable and what doses would indicate good health. What do you think?
     
  70. What would be the outcome you look for? I've only read him about the disappearance of MB color on skin is indicative of the oxidative potential of cells. That would only be at the skin though, and there may be many confounders such as extracellular reducing agents and extracellular oxidants competing with the MB.

    My gut feeling is that it's worth trying if someone has MB and doesn't mind a bit of blue on their skin for a while, but it would be more qualitative than quantitative.
     
  71. Yeah, the skin test is nice but it can be skewed by local conditions not indicative of systemic health. I was thinking that maybe ingesting up to a certain amount of MB and checking for urine discoloration would be more indicative of systemic health as it has to pass through the GI, liver and then kidneys. Human studies with oral MB show that the bioavailability is pretty stable and does not vary much. I think it was around 70%. I have seen very young children get blue pee from 1mg oral MB doses and I am inclined to think it signifies their high oxidative state, while I have seen adults not get any change in urine color from even 15mg doses. This can't be a coincidence and as such could be developed into a more robust test with "normal" ranges where say a person ingests increasing MB doses once daily for several days until the pee turns blue. The lowest dose at which this happens can be compared to the results of a large number of other adults and this could gauge redox status. I suppose the same can be achieved with a simple blood test for pyruvate and lactate and then the pyruvate/lactate ratio can be checked against known pathological ranges for which data already exists. But the MB test would be better since it would be non-invasive and everybody can do at home without doctors getting involved.
     

  72. Wow. Love this ❤️
     
  73. Hey, interestingly enough, I got blue pee a few days ago. And it corresponded with feeling much better overall.
    I have been taking MB for many months now. 3 drops oxidal on the back of my tongue in the am and another dose at night. Maybe totalling 8 - 10 drops per day.
     
  74. Goes to buy more oxidal :).
     
  75. Interesting, thanks for sharing. So, this means about 5mg MB daily right?
     
  76. Yes that would be better, but for any kind of rigor you would need a spectrophotometer to measure differences in "blueness" outside of eye perception. The other hues of urine, which vary by what you're consuming and your metabolism, would obfuscate small to moderate blues. At best this could be a safe and easy qualitative test, but I still don't see potential for quantitative results.
     
  77. Yes. I think so.
     
  78. Yes, and that's why I was thinking of switching the test into trying different doses until ANY hint of blue is seen, not trying to determine how blue it is. In my experience, a person who sees any change in urine color from say 5mg is healthier than somebody who has no change from 5mg but very deep blue from 10mg. It's almost like a threshold test, since any amount of unused MB is enough to indicate sufficiently oxidative state. Checking the blue saturation would be better but would probably only become necessary when a large amount of people fall into a specific group where say 1,000 of them see urine changes form 5mg and these people need to be segregated further. However, even that group can be subtested with 4mg, 4.5mg, etc in order to get an even finer breakdown. But I think that much of granularity may not be needed since we are only looking for a few categories like "unhealthy", "borderline/OK", "healthy". And the dose would need to be on a mg/kg basis, not set to 5mg since a massive person like a NLF linebacker will probably not react much to 5mg while a baby would get oversaturated with the same dose.
    Anyways, I will ask Peat and see what he says.
     
  79. Well, inspired O₂ cannot be reduced (+4e⁻) to water without flux through the electron transport chain. Of course you'd expect some O₂ to be consumed in the body during enzymatic reactions (i.e. cyclooxygenase, glycine oxidase), become a hapless bystander of incidental non-energy-yielding reductions (i.e. NADH, vitamin C), and participate in spontaneous peroxides with polyunsaturated lipids—all of which are probably negligible; I think it would be safe to say that over 90% of inhaled oxygen not expired becomes converted to H₂O and trapped within the body. If you could accurately estimate the total amount of mitochondrial heme groups within the body, then you could perhaps divide oxygen consumption by that to yield an efficiency ratio rate—or mol·O₂ per mitochondrial heme group per second. Of course this neglects the O₂ transport efficiency in the blood, so wouldn't be 'perfect,' but there should be enough data on this to quickly find out its applicability. Since O₂ is directly coupled to the electron transport chain, I think it would be provide a better indicator than expired CO₂—which can be produced from non-respirative glycolysis. But expired CO₂ is also a useful thing to know, as that would allow the calculation of The Meyerhof–Warburg quotient (the cancer quotient):

    ➞ Otto Warburg & Dean Burk: "On respiratory impairment in cancer cells." Science (1956)

    'the higher the malignancy, the greater the fermentation and the smaller the respiration...' ―Warburg

    'The more cancer cells a tumor contained, the higher was the fermentation and the lower was the respiration.' ―Warburg

    'If there is a disturbance in respiration that leads to an accumulation of lactic acid, it can occur only at or beyond the pyruvic acid stage and. must be due either to some aberration in carbon transport through the citric acid cycle or to some "bottleneck" in electron transport.' ―Weinhouse

    'When, in more extensive experimentation, ¹⁴C-marked substrates were tested (glucose, lactate, acetate, butyrate, octanoate, palmitate, and 2,4-acetoacetate), there was in general a relatively much greater aerobic production of ¹⁴CO₂ by the normal tissue groups than by the tumor groups employed.' ―Burk

    'On the basis of impairment type i, and as a confirmatory qualitative demonstration thereof, the following simple manometric test has been devised that permits investigators to distinguish cancer cells from virtually all normal body cells, growing or nongrowing. The cells under test are placed in a manometric vessel of any convenient size. The vessel is filled to one-third to one-half of its volume with physiological serum or other equivalent body fluid. The volume of cells is of the order of ¹⁄₃₀₀ the volume of serum. Cancer cells cause the manometer to register a steady and notable increase in pressure with time, whereas normal body cells cause a negative (or zero) change in pressure with time. The few-if any exceptions extant are only apparent, or are readily ruled out on other bases; thus, use of nonphysiological media (for example, unfortified saline ) may vitiate the test for normal cells, and omission of the carbohydrate glucose certainly will for cancer cells. [...] Thus, the sign and magnitude of the pressure change can be expressed as an exact mathematical function of the ratio of the absolute magnitude of aerobic glycolysis to the absolute magnitude of respiration for any given conditions of experimental arrangement. ―Burk

    'The impaired respiration may involve any combination-usually at least three-of the following experimental quantities readily measurable under appropriate conditions: (i) a high ratio of glycolysis to respiration; (ii) a low absolute value for oxygen consumption (QO₂); (iii) an inefficient or uncoupled respiration; or (iv) a low paraphenylenediamine (succinate) oxidative response (3). This list could be expanded.' ―Burk
     
  80. What about RMR testing through CO2 production and O2 usage?

    You think too expensive to make it useful? Ie a good capnometet seems to cost $500
     
  81. What do think about urinary metabolites as an indicator of mitochondrial efficiency?
    B003EAAD-57F8-4F6A-9BF9-547A1C74DE08.jpeg
     
  82. Urine tests can offer some insight but I would combine them with a blood test as by themselves they can be unreliable. Similar to the cortisol and serotonin tests, which combined blood with urine 24-hour test to obtain a complete picture.
     
  83. Yes, a threshold test makes sense to me.
     
  84. I noticed the product is a bit sticky. If I put in my forearms, it sticks to my sweater. Any recommendations on places of application?
     
  85. If it is surface sticky, consider swallowing?
     
  86. If you eat for example vitamin C with the methylene blue, the pee results will be skewed
     
  87. I think it is the ATP and succinic acid causing this. Spreading on wider area should reduce the stickiness.
     

  88. On your note of urine discoloration. I use 1mg of MB and the next day my urine is a dark green color!
     
  89. I've been taking Cardenosine for almost 2 weeks now, 40 drops every other day + 2 drops Oxidal. (Sidenote: I have been taking 2 tablets of Cynomel daily, divided into 4 doses of 1/2 tablet, since 2010. I tried all different adjustments to my diet etc. and for some reason this is the amount I need to function and keep my temps/pulse up. I was exposed to mold and insecticides on and off for the last 4 or so years, which impacted me further. I strongly suspect that my sister and I inherited some mitochondrial thing from my mother since we all have strong symptoms, even since childhood.) Effects: absence of quicksand-like fatigue, mental clarity/general cognitive improvement, emotional/mental lift, increased endurance/muscle weakness seems to be going away, increased appetite (I was only eating 2 small/med meals & 2 snacks per day, until I woke up ravenous at 3am a few nights ago, now I need 3 more substantial meals), premenstrual symptoms associated with estrogen were almost gone - fibrocystic sore breasts, super-heavy period sometimes lasting 2 weeks, irregular etc (I'm turning 51 next month, and perimenopausal), better digestion (had IBS-like symptoms, bloating, gas, diarrhea + slow transit, intolerant of milk proteins), my thumb nails that I had been unable to grow since 2014 due to vertical splitting are beginning to grow out finally. Facial puffiness is going away. Will report on my progress again soon.

    Edit: By the way, I experimented with 13mg doses of methylene blue a little over a year ago, and even at that dose, my pee was at best, green. Never blue.
     
  90. Is that all? That's underwhelming.
     
  91. I think that's a good sign. It would be nice to get Peat's take on it too.
     
  92. What were you expecting in < 10 days?
     
  93. Oh wow, this is amazing! Thanks so much for sharing!
     
  94. I think Wagner was being sarcastic :):. Thanks for the report!
     
  95. .
     
  96. I am happy to be a guinea pig. Always been open to experimentation of this sort.
     
  97. I guess the only thing I'd suggest is to try with methylene blue (1mg) or B-complex vitamins. Either one, and together probably much more, should be synergistic with Cardenosine.
     
  98. Hard to tell with no accompanying emojis!
     
  99. The emoticon wouldn't be fun.
     
  100. Of course not, how much fun could they possibly be? :clown::dead::depressed::jimlad::bucktooth::vamp: