This has been very interesting.
Lyme Disease is something that effects many people in my area.
ACG Glutathione spray x 3 a day
Ingredients
Acetyl L-Cysteine (NAC), Acetyl L-Carnitine, L-Glutamine, L-Glutathione Tripeptides (Reduced), Lipoic Acid (R-Fraction), TMG (trimethylglycine), Peppermint Leaf (Mentha x Piperita), Ascorbic Acid and Natural Trace Minerals
https://www.ncbi.nlm...les/PMC3651682/
Safety Survey of Intranasal Glutathione
Glutathione depletion has been documented in several disease states, and exogenous administration has been hypothesized to have therapeutic potential for some conditions. In an effort to reach target tissues of the sinuses and central nervous system (CNS), glutathione is being prescribed as an intranasal spray, although no literature exists to support this mode of administration.
Seventy (70) individuals returned the survey (23.3% response rate) from 20 different states. Reported indications for (in)GSH prescriptions were multiple chemical sensitivity (MCS) (n=29), allergies/sinusitis (n=25), Parkinson disease (PD) (n=7), Lyme disease (n=3), fatigue (n=2), and other (n=10). Of the respondents, 78.8% (n=52) reported an overall positive experience with (in)GSH, 12.1% (n=8) reported having experienced adverse effects, and 62.1% (n=41) reported having experienced health benefits attributable to (in)GSH use. Over 86% of respondents considered the nasal spray to be comfortable and easy to administer.
https://www.ncbi.nlm...les/PMC5877983/
Role of glutathione metabolism in host defense against Borrelia burgdorferi infection.
Supporting the in vitro analysis, we identified a cluster of GSH-related metabolites, the γ-glutamyl amino acids, specifically altered in patients with Lyme disease, and not in other infections. Lastly, we performed in vitro experiments to validate the role for GSH metabolism in host response against Bb. We found that the GSH pathway is essential for Bb-induced cytokine production and identified glutathionylation as a potential mediating mechanism. Taken together, these data indicate a central role for the GSH pathway in the host response to Bb GSH metabolism and glutathionylation may therefore be important factors in the pathogenesis of Lyme disease and potentially other inflammatory diseases as well.
https://www.ncbi.nlm...pubmed/31785327
BBE31 from the Lyme disease agent Borrelia burgdorferi, known to play an important role in successful colonization of the mammalian host, shows the ability to bind glutathione.
Abstract
Lyme disease is a tick-borne infection caused by Borrelia burgdorferi sensu lato complex spirochetes. The spirochete is located in the gut of the tick; as the infected tick starts the blood meal, the spirochete must travel through the hemolymph to the salivary glands, where it can spread to and infect the new host organism. In this study, we determined the crystal structures of the key outer surface protein BBE31 from B. burgdorferi and its orthologous protein BSE31 (BSPA14S_RS05060 gene product) from B. spielmanii. BBE31 is known to be important for the transfer of B. burgdorferi from the gut to the hemolymph in the tick after a tick bite. While BBE31 exerts its function by interacting with the Ixodes scapularis tick gut protein TRE31, structural and mass spectrometry data revealed that BBE31 has a glutathione (GSH) covalently attached to Cys142 suggesting that the protein may have acquired some additional functions in contrast to its orthologous protein BSE31, which lacks any interactions with GSH. In the current study, in addition to analyzing the potential reasons for GSH binding, the three-dimensional structure of BBE31 provides new insights into the molecular details of the transmission process as the protein plays an important role in the initial phase before the spirochete is physically transferred to the new host. This knowledge will be potentially used for the development of new strategies to fight against Lyme disease.
https://www.ncbi.nlm...pubmed/29673413
Epidemiol Infect. 2018 May;146(7):931-934. doi: 10.1017/S0950268818000420. Epub 2018 Apr 20.
Seven cases of probable endotoxin poisoning related to contaminated glutathione infusions.
Abstract
We report seven cases of probable endotoxin poisoning linked to contaminated compounded glutathione. Five of the cases were using the infusions for treatment of Lyme disease highlighting the risks of using compounded sterile preparations for unapproved indications, especially if the quality of source products cannot be assured.
https://www.fda.gov/...ile-injectables
FDA highlights concerns with using dietary ingredient glutathione to compound sterile injectables
FDA warned compounders on February 1, 2019, not to use glutathione L-reduced powder (L-glutathione) distributed by Letco Medical located in Decatur, Alabama, to compound sterile injectable drugs. FDA received a report concerning seven patients who received an injectable drug compounded with L-glutathione and experienced adverse events due to potentially high levels of endotoxins, a substance that may cause unintended health consequences ranging from fever to death. Exposure to inappropriate levels of endotoxin in a drug intended for injection raises safety concerns. As part of the investigation into the adverse events, FDA collected and analyzed samples of the L-glutathione powder. The following are the details on the adverse events the agency has received to date and the findings from FDA’s investigation.
https://www.ehealthm...e/side-effects/
Most common side effects over time *:
< 1 month:
⦁ Alanine aminotransferase increased
⦁ Blood albumin decreased
⦁ Bone marrow failure
⦁ Chest discomfort
⦁ Liver injury
1 - 6 months:
⦁ Actinomycosis (infection that causes sores, or abscesses)
⦁ Amylase increased
⦁ Blood glucose increased
⦁ Blood pressure fluctuation
⦁ Cystitis haemorrhagic (blood in the urine and painful voiding)
⦁ Drug ineffective
⦁ Drug-induced liver injury (diseases of the liver that are caused by physician-prescribed medications)
⦁ Febrile neutropenia (fever with reduced white blood cells)
pharmacokinetic properties:
⦁ There may be some absorption of glutathione intact from the intestines, but it cannot enter cells intact. It must be metabolized to form L-cystine (two molecules of L-cysteine bound together) before being taken up.
⦁ Provision of L-cysteine within the cell is all that is needed to increase glutathione synthesis, and ⦁ N-Acetylcysteine does this efficiently at a lower financial cost than glutathione.
In effect, glutathione is an indirect and expensive way to provide dietary L-cysteine. Dietary protein itself, including L-cysteine rich sources such as Whey Protein, are effective but inefficient ways to increase L-cysteine intake in the diet and N-Acetylcysteine is both more efficient and cheaper than glutathione.
Selenium supplementation increases the production of L-Cysteine however it only takes small amounts of selenium to cause a toxic reaction. Routine blood analysis is needed to monitor serum blood levels of selenium if supplements are used.
Alpha-lipoic acid (ALA) appears to have a role in promoting the synthesis of glutathione.
Glutathione, along with oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO), bind to the glutamate recognition site of the NMDA and AMPA receptors (via their γ-glutamyl moieties). GSH and GSSG may be neuromodulators.[21][22][23] At millimolar concentrations, GSH and GSSG may also modulate the redox state of the NMDA receptor complex.[22] Glutathione binds and activate ionotropic receptors, potentially making it a neurotransmitter.[24] Wiki
N-Acetylcysteine
https://www.healingw...?f=30&m=2806900
http://flash.lymenet...=1;t=089458;p=0
https://www.dcnutrit...ylcysteine-nac/
https://www.ncbi.nlm...m=Selenium Lyme
Crystallization and preliminary crystallographic analysis of BbCRASP-1, a complement regulator-acquiring surface protein of Borrelia burgdorferi.
Borrelia burgdorferi is the causative agent of Lyme disease. Serum-resistant strains of the pathogen are able to reduce the host's immune response to infection by recruiting fluid-phase complement regulators from the serum. Crystals of native and selenomethionine-substituted BbCRASP-1 have been obtained and a native data set to 2.7 A as well as selenomethionine MAD data to 3.2 A resolution have been collected. The selenium substructure has been solved and initial phases have been refined to 3.0 A by density-modification methods. Model building and refinement are under way.
Clarification. Lyme disease tends to complex with selenium making it less bioavailable.
https://www.ncbi.nlm...les/PMC3719580/
Manganese and Zinc Regulate Virulence Determinants in Borrelia burgdorferi
Abstract
Borrelia burgdorferi, the causative agent of Lyme disease, must adapt to two diverse niches, an arthropod vector and a mammalian host. RpoS, an alternative sigma factor, plays a central role in spirochetal adaptation to the mammalian host by governing expression of many genes important for mammalian infection. B. burgdorferi is known to be unique in metal utilization, and little is known of the role of biologically available metals in B. burgdorferi. Here, we identified two transition metal ions, manganese (Mn2+) and zinc (Zn2+), that influenced regulation of RpoS. The intracellular Mn2+ level fluctuated approximately 20-fold under different conditions and inversely correlated with levels of RpoS and the major virulence factor OspC. Furthermore, an increase in intracellular Mn2+ repressed temperature-dependent induction of RpoS and OspC; this repression was overcome by an excess of Zn2+. Conversely, a decrease of intracellular Mn2+ by deletion of the Mn2+ transporter gene, bmtA, resulted in elevated levels of RpoS and OspC. Mn2+ affected RpoS through BosR, a Fur family homolog that is required for rpoS expression: elevated intracellular Mn2+ levels greatly reduced the level of BosR protein but not the level of bosR mRNA. Thus, Mn2+ and Zn2+ appeared to be important in modulation of the RpoS pathway that is essential to the life cycle of the Lyme disease spirochete. This finding supports the emerging notion that transition metals such as Mn2+ and Zn2+ play a critical role in regulation of virulence in bacteria.
Clarification - Increased presence of Mn+2 increases the Lyme disease activity and Zinc+2 decreases the activity of Lyme disease. I would assume that is because zinc competes with Mn so any increase in zinc will lower Manganese levels. I will do more research on this.
https://www.ncbi.nlm...pubmed/23376276
J Biol Chem. 2013 Mar 22;288(12):8468-78. doi: 10.1074/jbc.M112.433540. Epub 2013 Feb 2.
A manganese-rich environment supports superoxide dismutase activity in a Lyme disease pathogen, Borrelia burgdorferi.
Abstract
The Lyme disease pathogen Borrelia burgdorferi represents a novel organism in which to study metalloprotein biology in that this spirochete has uniquely evolved with no requirement for iron. Not only is iron low, but we show here that B. burgdorferi has the capacity to accumulate remarkably high levels of manganese. This high manganese is necessary to activate the SodA superoxide dismutase (SOD) essential for virulence. Using a metalloproteomic approach, we demonstrate that a bulk of B. burgdorferi SodA directly associates with manganese, and a smaller pool of inactive enzyme accumulates as apoprotein. Other metalloproteins may have similarly adapted to using manganese as co-factor, including the BB0366 aminopeptidase. Whereas B. burgdorferi SodA has evolved in a manganese-rich, iron-poor environment, the opposite is true for Mn-SODs of organisms such as Escherichia coli and bakers' yeast. These Mn-SODs still capture manganese in an iron-rich cell, and we tested whether the same is true for Borrelia SodA. When expressed in the iron-rich mitochondria of Saccharomyces cerevisiae, B. burgdorferi SodA was inactive. Activity was only possible when cells accumulated extremely high levels of manganese that exceeded cellular iron. Moreover, there was no evidence for iron inactivation of the SOD. B. burgdorferi SodA shows strong overall homology with other members of the Mn-SOD family, but computer-assisted modeling revealed some unusual features of the hydrogen bonding network near the enzyme's active site. The unique properties of B. burgdorferi SodA may represent adaptation to expression in the manganese-rich and iron-poor environment of the spirochete.
Clarification. High manganese activates Lyme Disease. Higher iron levels lowers manganese levels and deactivates activity of Lyme disease. As iron can collect to toxic levels in the blood easily routine blood sampling would been to be done to monitor serum iron levels.
https://www.ncbi.nlm...pubmed/25709405
Drug Des Devel Ther. 2015 Feb 11;9:805-16. doi: 10.2147/DDDT.S77063. eCollection 2015.
Borreliacidal activity of Borrelia metal transporter A (BmtA) binding small molecules by manganese transport inhibition.
Abstract
Borrelia burgdorferi, the causative agent of Lyme disease, utilizes manganese (Mn) for its various metabolic needs. We hypothesized that blocking Mn transporter could be a possible approach to inhibit metabolic activity of this pathogen and eliminate the infection. We used a combination of in silico protein structure prediction together with molecular docking to target the Borrelia metal transporter A (BmtA), a single known Mn transporter in Borrelia and screened libraries of FDA approved compounds that could potentially bind to the predicted BmtA structure with high affinity. Tricyclic antihistamines such as loratadine, desloratadine, and 3-hydroxydesloratadine as well as yohimbine and tadalafil demonstrated a tight binding to the in silico folded BmtA transporter. We, then, tested borreliacidal activity and dose response of the shortlisted compounds from this screen using a series of in vitro assays. Amongst the probed compounds, desloratadine exhibited potent borreliacidal activity in vitro at and above 78 μg/mL (250 μM). Borrelia treated with lethal doses of desloratadine exhibited a significant loss of intracellular Mn specifically and a severe structural damage to the bacterial cell wall. Our results support the possibility of developing a novel, targeted therapy to treat Lyme disease by targeting specific metabolic needs of Borrelia.
Comment - Desloratadine (trade name Clarinex and Aerius) is a tricyclic H1 antagonist that is used to treat allergies. It is an active metabolite of loratadine. Loratadine, sold over the counter under the brand name Claritin among others, is a medication used to treat allergies This includes allergic rhinitis (hay fever) and hives. An over the counter treatment for Lyme Disease by a common safe otc drug?
https://www.ncbi.nlm...pubmed/31271863
Protein Expr Purif. 2019 Nov;163:105447. doi: 10.1016/j.pep.2019.105447. Epub 2019 Jul 1.
Expression, purification and metal utilization of recombinant SodA from Borrelia burgdorferi.
A coupled enzyme assay demonstrates SOD activity in the presence of Mn, but not Fe.
Comment - Mn activates the infection by stimulating the metabolism and Fe (iron) lowers the metabolic rate.
https://www.ncbi.nlm...MC3828560/FrontCell Infect Microbiol. 2013 Nov 15;3:79. doi: 10.3389/fcimb.2013.00079. eCollection 2013.
Metal-dependent gene regulation in the causative agent of Lyme disease.
Bb is a unique bacterial pathogen because it does not require iron (Fe(2+)) for its metabolism. Bb encodes a ferritin-like Dps homolog called NapA (also called BicA), which can bind Fe or copper (Cu(2+)), and a manganese (Mn(2+)) transport protein,
Recent evidence demonstrates that Bb modulates the intracellular Mn2+ and zinc (Zn2+) content and, in turn, these metals regulate gene expression through influencing the Ferric Uptake Regulator (Fur) homolog Borrelia Oxidative Stress Regulator (BosR).
https://www.ncbi.nlm...pubmed/26480895
Mol Microbiol. 2016 Feb;99(3):586-96. doi: 10.1111/mmi.13251. Epub 2015 Nov 19.
The salt-sensitive structure and zinc inhibition of Borrelia burgdorferi protease BbHtrA.
Examination of the influence of transition metals on the activity of BbHtrA revealed that this protease is inhibited by Zn(2+) > Cu(2+) > Mn(2+).
