F-actin and cholesterol sulfate; video by David Diamond about history of cholesterol research & statins.
More acidic body pH may be a direct cause of arthritis pain. Low cholesterol also plays a role. Magnesium and functioning methylation cycles & reducing any other stress, also needed.
Research is exploring a chemical found to bind with F-actin, a structural protein of cell matrix and/or extracellular matrix. The hope with research like that always tends to be… so that we can use a medication targeting that chemical or use that chemical as a targeted medication for osteoarthritis.
F-Actin Protein Could Be Key for Osteoarthritis Prevention, August 8, 2023, by
Molly Campbell. (technologynetworks.com) Healthy tissue has plenty of adseverin and lack of it (in a knockout mouse model) was found to negatively effect articular chondrocyte function by a reduction in F-actin levels.
Looking very briefly at ‘glyphosate and F-actin’ we see early research saying problems are observed and more recent research saying no problems exist here. (google search 'glyphosate effect on F-actin')
Moving on, more conclusively we see that lower pH levels, more acidic conditions in the body, are a direct cause of increased breakdown of actin and collagen. (Wioland, Jegou, Romet-Lemonne, 2019) This suggests osteoarthritis joint pain may in part simply be due to having a more acidic diet and lifestyle. Anything promoting inflammation is adding to a more acidic body environment as inflammation is acid producing.
“Oxidative hotspots” on actin have been observed in Rh. arthritis and an animal model of arthritis, in the same locations on the actin protein, and were similarly associated with muscle weakness in the area of the inflamed joint. “…these areas, here coined “hotspots,” are important for the stability of the actin molecule and its capacity to generate filaments and interact with myosin [in muscle].” (Steinz, et al., 2019) Muscle mass may be the same while muscle strength is reduced in arthritis.
Actin plays a large role in muscle tissue, both the filamentous and globular types: “A major component of myofibrils is filamentous actin (F-actin) (29), which is formed by polymerization of monomeric actin (G-actin). The polymerization process results in formation of asymmetric helical actin filaments, each characterized by a fast (barbed) and slow (pointed) polymerizing end (30) and by extensive structural cooperativities coupled to ATP hydrolysis and interaction with filament-binding proteins (30–33).” (Steinz, et al., 2019)
Taking a side road down memory lane with David Diamond to review the history of cholesterol research in nutrition and heart health.
Deception has played too large of a role in nutrition and medical research in the past and present. The history of cholesterol research is reviewed in a video talk by David Diamond - Demonization and Deception in Cholesterol Research. (Youtube) Fraudulent or misleading research, by Ancel Keys, a person who didn’t even have a medical or nutrition degree, led to the demonization of fats and cholesterol as causes of heart disease and eventually to the quite harmful but widely used statin medications. Statin drugs block our own cholesterol production and frequently cause joint and muscle pain in the patients prescribed the drug as a prevention against heart attacks.
It was already known in the early 1900s that a low carbohydrate diet made a big difference for heart disease or weight control. Other new foodtech risks to heart health were invented and popularized as ‘healthy and new’ but weren’t healthy, just new. Instead, the invention of margarine and later high-fructose corn syrup led to more heart disease and type 2 diabetes and non-alcholic fatty liver disease.
Ancel Keys had an Economics undergrad degree and an Oceanography PhD. He first became known as a nutrition focused scientist due to a study he led with conscientious objectors during WWII - he starved them and studied the effects of acute malnutrition on their health. Not very nice for the men who didn’t want to take part in killing other people. Why was an oceanographer allowed to use human war objectors as starvation research guinea pigs?
Coincidentally, Ancel Keys, is on a list of scientists who were atheists: “Ancel Keys (1904–2004): American scientist who studied the influence of diet on health. He examined the epidemiology of cardiovascular disease (CVD) and was responsible for two famous diets: K-rations and the Mediterranean diet.” (newageislam.com) My guess is that he had lots of friends in high places who wanted natural foods to be demonized while manmade replicas were being introduced as innovative and healthier for us. Margarine is a bad product. We were conned. High fructose corn syrup is also very bad for health. (Aside - this future food tech infographic presents what is in the works or already available and is generally upbeat and excited about it. Truthful information about the reduced nutritional value of the engineered foods versus real meat, dairy or plant based foods is included.
More coincidentally - at the time of his ‘groundbreaking’ research regarding the role of a high fat diet and heart risk, other scientists debunked his work for its misleading use of data and very wrong results. Statin drug use and muscle and joint pain are based on research that was debunked when it was newly published.
Ancel Keys saw the slimness of post WWII Italians who were eating a low-fat diet and based on a paper on his theory that they had less heart disease because of a low fat diet. He used data from Italy and five other nations which when plotted formed a graph suggesting a clear correlation between increased heart risk and a higher fat national diet.
The problem with the paper - there was data available for 22 nations and when all 22 were plotted on the graph it showed no pattern - a random scatter plot. That suggests that the total fat level in a diet is not directly associated with heart disease risk. Yet he went on to get a Time cover photo and is still lauded as ‘helping’ our collective health with his major work in nutrition (K-Rations for the military and Mediterranean Diet based on post WWII rationed skinny Italians). He and others since have ignored the French high fat diet and their lack of heart disease.
Ancel Keys must have had highly placed connections within the military to have been able to do a starvation study with Conscientious objectors to the draft and then to have developed the military’s K-rations - a standardized boxed meal designed to support health, last a long time and not cost too much. Keep the soldiers moving. It did include a chocolate bar. The economics degree may have been in play. It was an early step in the creation of US nutrient guidelines.
Fibrinogen is a factor that is directly associated with risk of cardiovascular disease.
Physiologically, what is seen in cardiovascular illness is increased levels of fibrinogen - clotting factors in the blood that increase ‘stickiness’ of the blood cells. Risk factors for platelet aggregation/clotting were known in early days of health research and include being a smoker or being stressed and with obesity.
Related information: “Platelet-dependent thrombosis is significantly higher in patients with stable coronary artery disease with low intracellular magnesium…” (DiNicolantonio, O’Keefe, Wilson, 2018)
Low cholesterol levels created by medications was linked to increased risk of Type 2 diabetes developing and cancer risk seems to be increased in statin users.
Statins reduce cholesterol and CoQ10 which leads to increased muscle damage and potentially heart risks. Vitamin K2 is also needed to keep calcium in the bones. Cholesterol is used to repair damage caused by calcium and inflammation. «< Yeah! nice to hear it even if not from mainstream doctors.
Summary points based on the video lecture by David Diamond - Demonization and Deception in Cholesterol Research. (Youtube)
Addition - a more recent video has a few new points in the opening and then I think it is the same presentation in the later part. The video has Chinese subtitles. David Diamond - An Update on Demonization and Deception in Research on Saturated Fat... (6 years ago) (Youtube)
So, what does F-actin have to do with cholesterol and statin drug use?
It turns out that they have a lot to do with each other. Our cell membranes are really more of a ‘brain’ and a perceptive control organ than early science has given them credit for. (Bruce Lipton theory.) Cholesterol and sphingolipids within the membranes work with the globular and filamentous actin in the cell and outside of the cell in a way that seems to stabilize and support G-protein coupled receptors.
“Membrane lipids such as cholesterol and sphingolipids, along with the underlying actin cytoskeleton, assume significance owing to their ability to nonrandomly organize into domains in membranes that serve as hubs for cellular signaling originating from the plasma membrane (25, 41, 42). Importantly, cholesterol and the actin cytoskeleton have been shown to modulate the organization, dynamics, and function of membrane proteins such as G protein-coupled receptors (GPCRs) (43) which serve as major drug targets (44).” (Sarker, et al., 2022)
G-protein coupled receptors include the cannabinoid and niacin/butyrate receptors and taste and odor receptors and many others. They are special in the way they cross the cell membrane and can perceive/receive a signaling chemical on the outside of the cell which causes an action to take place within the cell - like ringing a doorbell that can then release food for a cat inside the apartment - or make a ringing sound inside.
Statins are bad, um kay - they block a major enzyme in acetyl-CoA metabolism. Reminder - acetyl-CoA is critical in the Citric Acid/Kreb’s/tricarboxylic acid cycle which is the quantumly fast way for mitochondria to burn glucose for the release of energy in the form of ATP.
“Biosynthesis of cholesterol begins with acetyl-CoA that feeds into the mevalonate pathway to generate lanosterol. Cholesterol is synthesized from lanosterol either via desmosterol (the Bloch pathway) or via 7-dehydrocholesterol (the Kandutsch-Russel pathway) as immediate precursors (35, 37). It is noteworthy that one of the best-selling drugs in clinical history, statins, are cholesterol-lowering agents that act as competitive inhibitors of HMG-CoA reductase, the crucial enzyme catalyzing the rate-limiting step in the cholesterol biosynthesis pathway (38, 39, 40).” (Sarker, et al., 2022)
Chronically low cholesterol is associated with increased amounts of actin - but is that a good thing? Or is it an excess of proteins that become disorganized and tangled? Acutely low cholesterol does not appear to effect concentration of actin. (Sarker, et al., 2022)
“Our results show that F-actin content significantly increases upon chronic cholesterol depletion, but not during acute cholesterol depletion.” […]
“Our results suggest that F-actin content increases in response to chronic cholesterol depletion as a result of synergy between multiple pathways that are parallelly associated with cellular cholesterol biosynthesis.” (Sarker, et al., 2022)
In previous posts…
Standing on one leg - a life lengthening skill. (post 1, risk factors for Metabolic Syndrome and lifestyle and nutrient factors that might help)
Rest in peace Dr. Zelenko. (post 2, focus on nutrients that may help with schizophrenia)
…we learned that cholesterol sulfate has an important role to play in helping remove misfolded proteins from an overloaded endoplasmic reticulum - and therefore it helps prevent Alzheimer’s and other neurocognitive conditions involving excess amyloid protein tangles (which seen in autism too). Avoiding hypoxia and not getting too overheated in order to prevent Heat Shock Proteins from forming is part of the care plan for improvement in addition to having cholesterol or saturated fats in the diet. Vegans would need coconut or palm oil products or dark cocoa as possible saturated fat precursors. (post 1) (post 2)
Cholesterol sulfate has a protective role against bone breakdown as it affects osteoclast differentiation. (Park, et al., 2023)
“Cholesterol sulfate (CS) is an activator of retinoic acid-related orphan receptor α (RORα). CS treatment or RORα overexpression attenuates osteoclastogenesis in a collagen-induced arthritis mouse model. […]
Collectively, these results indicate that CS inhibits osteoclast differentiation and survival by suppressing NF-κB via the AMPK-Sirt1 axis in a RORα-independent manner. Furthermore, CS protects against bone destruction in lipopolysaccharide- and ovariectomy-mediated bone loss mouse models, suggesting that CS is a useful therapeutic candidate for treating inflammation-induced bone diseases and postmenopausal osteoporosis.” (Park, et al., 2023)
Ischemia/heart attack or stroke, and atherosclerosis may involve a deficiency of cholesterol sulfate, which would involve low cholesterol and problems with sulfate deficiency or sulfur metabolism within the methylation cycles. (Seneff, et al., 2015)
A previous post about chimeric spike and CoV risks (scroll to the second part, section C - membranes) discussed the role of actin as our scaffolding and hook and crane that can move equipment where it needs to go to connect with a receptor or other cell part - and that glyphosate seems to disrupt the hook end of the crane or scaffolding like filamentous F-actin. This more recent post has an excerpt of the section in the spike post: Genes - some of mine & F-actin, glyphosate, microtubules & conception. (Substack)
The scaffolding and control functions of actin plays a large role in cell division and the creation of new life. To build life we need our miniature construction crew to be fully equipped and not bogged down in toxins or excess material or damaged, old material that needs to go to the dump - if there was a dump truck to haul it away (white blood cell with adequate niacin and mitochondrial function).
Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.
(DiNicolantonio, O’Keefe, Wilson, 2018) DiNicolantonio JJ, O’Keefe JH, Wilson W, Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis, Open Heart 2018;5:e000668. doi: 10.1136/openhrt-2017-000668, https://openheart.bmj.com/content/5/1/e000668
(Park, et al., 2023) Park JH, Lee J, Lee GR, Kwon M, Lee HI, Kim N, Kim HJ, Lee MO, Jeong W. Cholesterol sulfate inhibits osteoclast differentiation and survival by regulating the AMPK-Sirt1-NF-κB pathway. J Cell Physiol. 2023 Jun 19. doi: 10.1002/jcp.31064. Epub ahead of print. PMID: 37334825. https://pubmed.ncbi.nlm.nih.gov/37334825/
(Sarker, et al., 2022) Sarkar P, Kumar GA, Shrivastava S, Chattopadhyay A. Chronic cholesterol depletion increases F-actin levels and induces cytoskeletal reorganization via a dual mechanism. J Lipid Res. 2022 May;63(5):100206. doi: 10.1016/j.jlr.2022.100206. Epub 2022 Apr 4. PMID: 35390404; PMCID: PMC9096963. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096963/
(Seneff, et al., 2015) Seneff, S., Davidson, R.M., Lauritzen, A. et al. A novel hypothesis for atherosclerosis as a cholesterol sulfate deficiency syndrome. Theor Biol Med Model 12, 9 (2015). https://doi.org/10.1186/s12976-015-0006-1 https://tbiomed.biomedcentral.com/articles/10.1186/s12976-015-0006-1
(Steinz, et al., 2019) Steinz MM, Persson M, Aresh B, Olsson K, Cheng AJ, Ahlstrand E, et al., Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis. JCI Insight. 2019 Mar 28;5(9):e126347. doi: 10.1172/jci.insight.126347. PMID: 30920392; PMCID: PMC6538353. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538353/
(Wioland, Jegou, Romet-Lemonne, 2019) Hugo Wioland, Antoine Jegou, Guillaume Romet-Lemonne, Quantitative Variations with pH of Actin Depolymerizing Factor/Cofilin’s Multiple Actions on Actin Filaments, Biochemistry 2019, 58, 1, 40–47, Pub: November 30, 2018, https://doi.org/10.1021/acs.biochem.8b01001 https://pubs.acs.org/doi/10.1021/acs.biochem.8b01001
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