Norvaline
Does anybody here have experience from the use of Norvaline? in that case did you notice any cognitive effects?
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I couldnt understand why research on such a promising supplement seemed to show no follow up. I found this on Medical Express:
"People taking the protein supplement L-norvaline should be aware of its potential for harm, scientists say. L-norvaline is an ingredient widely used in body building supplements and is promoted as a compound that can boost workouts and aid recovery. Similar compounds have been linked to neurodegenerative diseases and a study on human cells, by scientists from the University of Technology Sydney, suggests L-norvaline may also cause damage to brain cells.
The study, published in Toxicology in Vitro showed that even at relatively low concentrations the amino acid L-norvaline could make cells unhealthy and eventually kill them."
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chuck stanley
Norvaline has several interesting effects that is related to antiaging and to disease prevention. And yes I have also seen what is written in medical express. Which focus on potential negative effects of norvaline.
There is a focus on Arginase and on nitric oxide. Another substance that acts on arginase is epicatechin, which by the way is tested in the ITP cohort of 2021, so it will take some time until we can have results coming out from the labs.
Norvaline, Citrulline, epicatechin all act on arginase. (And of course also on other targets.) Tadalafil (Cialis) and Sildenafil (Viagra) also show promise for being repurposed for other conditions than erectile dysfunction. These substances are all related to circulatory health.
“ Growing evidence highlights the role of arginase activity in the manifestation of Alzheimer’s disease (AD). Upregulation of arginase was shown to contribute to neurodegeneration. Regulation of arginase activity appears to be a promising approach for interfering with the pathogenesis of AD.”
There is much interesting research about Nitic oxide and arginase
Arginase inhibition by (−)-Epicatechin reverses endothelial cell aging - ScienceDirect
https://www.frontiersin.org/articles/10.3389/fphar.2020.584669/full
L-Citrulline Supplementation Increases Plasma Nitric Oxide Levels and Reduces Arginase Activity in Patients With Type 2 Diabetes.
"Twenty-five patients received L-citrulline supplements (2000 mg/day) for 1 month. Arginase activity decreased by 21% in T2DM patients after taking L-citrulline supplements. Additionally, plasma NO levels increased by 38%. There was a modest improvement on H1Ac levels in these patients, though not statistically significant. The effect of L-citrulline on arginase activity was also studied in bovine aortic endothelial cells (BAECs) grown in high glucose (HG) conditions. HG (25 mM, 72 h) caused a 2-fold increase in arginase activity in BAECs and decreased NO production by 30%. L-citrulline (2.5 mM) completely prevented the increase in arginase activity and restored NO production levels. These data indicate that L-citrulline can have therapeutic benefits in diabetic patients through increasing NO levels and thus maintaining vascular function possibly through an arginase inhibition related pathway"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073798/
l-Citrulline Supplementation: Impact on Cardiometabolic Health
https://journals.physiology.org/doi/full/10.1152/physrev.00037.2016
Arginase: A Multifaceted Enzyme Important in Health and Disease
The involvement of excessive activity of the arginase/ornithine pathway in cardiovascular and renal dysfunction and injury has been well documented by research in experimental models and human disease conditions. The involvement of these pathways in CNS disease and cancer has also been clearly demonstrated. Targeting specific elements in the arginase/ornithine pathways offers immense potential for the treatment of cardiovascular, renal, and CNS diseases as well as cancer. Studies in patients with cardiovascular disease have shown beneficial effects of local delivery of arginase inhibitors. As has been explained in the previous sections, the two arginase isoforms are 100% homologous in the areas critical for their activity. In addition, both isoforms are clearly involved in dysregulation of NOS function. However, A1 and A2 are encoded by different genes and localized to different intracellular compartments. Both isoforms are widely expressed in many cell types, and both are involved in multiple cellular functions. Analyses using mutant mice and specific gene knockdown have clearly demonstrated the differential involvement of the two isoforms in disease conditions. However, extensive evidence substantiates a positive role for A1 activity in maintaining normal cell growth, collagen synthesis, and neuronal development as well as tissue repair from injury. Therefore, the global inhibition of arginase activity for extended periods could be detrimental.
There are som interesting effects from Tadalafil (Cialis) and Sildenafil (Viagra) .
”Diabetes-induced kidney cell injury involves an increase in matrix protein expression that is only partly alleviated by current treatment, prompting a search for new modalities. We have previously shown that hydrogen sulfide (H2S) inhibits high glucose-induced protein synthesis in kidney podocytes. We tested whether tadalafil, a phosphodiesterase 5 inhibitor used to treat erectile dysfunction, ameliorates high glucose stimulation of matrix proteins by generating H2S in podocytes. Tadalafil abrogated high glucose stimulation of global protein synthesis and matrix protein laminin γ1. Tadalafil inhibited high glucose-induced activation of mechanistic target of rapamycin complex 1….”
”According to findings published in Nature Aging, the research team, led by Feixiong Cheng, Ph.D., of Cleveland Clinic’s Genomic Medicine Institute, used computational methodology to screen and validate FDA-approved drugs as potential therapies for Alzheimer’s disease. Through a large-scale analysis of a database of more than 7 million patients, they determined that sildenafil is associated with 69% reduced incidence of Alzheimer’s disease, indicating the need for follow-up clinical trial testing of the drug’s efficacy in patients with the disease.”
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