paymanz

Member
Joined
Jan 6, 2015
Messages
2,693
Was surprised when saw a study showing statins have positive effects on bones, did a bit of searching and it turned out that it has some positive action,generally, through inhibiting rho kinase, which also is protective against heart disease.

Im not promoting statin use at all(for obvious reasons,q10,cholesterol) , but there is other natural rho kinase inhibitors like vitamin d,taurine and maybe other substances , i will post some studies on this subject here.

Im not sure what ray thinks about inhibiting rho kinase but many peat friendly stuff inhibit this, seems peaty but im curious to know his view ,and also more studies.

Effects of Randomized Rosuvastatin Compared to Placebo on Bone and Body Composition among HIV-Infected Adults
Statins have a beneficial effect on bone mineral density (BMD) and lean mass in some studies of HIV-uninfected adults, however this has never been investigated in the setting of HIV infection.
Pitavastatin enhanced BMP-2 and osteocalcin expression by inhibition of Rho-associated kinase in human osteoblasts. - PubMed - NCBI
Hydroxyfasudil, a specific inhibitor of Rho-kinase, increased BMP-2 and osteocalcin expression .......Rho-kinase inhibitor may be a new therapeutic reagent for the treatment of osteoporosis such as glucocorticoid-induced osteoporosis.

Rho-associated protein kinase - Wikipedia
Recent research has shown that ROCK signaling plays an important role in many diseases including diabetes, intracerebral hemorrhage,[14]neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis,[15] pulmonary hypertension[16] and cancer. It has been shown to be involved in causing tissue thickening and stiffening around tumours in a mouse model of skin cancer, principally by increasing the amount of collagen in the tissue around the tumour.[17]

Researchers are developing ROCK inhibitors for treating disease. For example, such drugs have potential to prevent cancer from spreading by blocking cell migration, stopping cancer cells from spreading into neighbouring tissue.[1]
Its a mediator of histamin actions
RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock

It may involve in erectile dysfunction
Understanding and targeting the Rho kinase pathway in erectile dysfunction

Statins Inhibit Rho Kinase Activity in Patients with Atherosclerosis
Lipid-Independent Actions of Statins
Evidence for the lipid-independent “pleiotropic” effects of statins derives partly from statistical analyses of clinical trials demonstrating that improved outcomes correlate as much with anti-inflammatory actions of statins as with LDL-C lowering [1113]. Furthermore, when similar reductions in LDL-C are achieved, only statins but not ezetimibe, a drug that lowers LDL-C without inhibiting HMG-CoA reductase, reverse endothelial dysfunction [14], reduce platelet reactivity [15], and inhibit pro-inflammatory cytokines [15].

Rho/Rho Kinase Pathway
In experimental studies, inhibition of Rho/ROCK has been implicated as a potential mechanism for many of the lipid-independent “pleiotropic” benefits of statins. By reducing mevalonate synthesis, statins prevent the formation of isoprenoid intermediates required for the membrane translocation and GTP binding activity of small GTPases such as Rho, Ras, and Rac [2]. Direct inhibition of Rho or ROCK is anti-atherogenic by augmenting endothelial nitric oxide synthesis [16], decreasing vascular smooth muscle cell contraction and proliferation [17], decreasing cytokine formation and inflammatory cell trafficking and proliferation [18,19], and reducing thrombogenicity of the vessel wall [20]. Statins replicate these vascular benefits of selective Rho/ROCK inhibitors in vitro via inhibition of Rho [19,2123]. Yet in vivo in animals, doses of statins reported to inhibit Rho/ROCK are far higher than those used by clinicians raising legitimate concerns about the relevance of these experimental findings to practice [4]. The development of a quantitative assay of ROCK activity in our laboratory has facilitated investigations of this pathway in humans [5,6].

Consequences of Rho Kinase Inhibition by Statins in Humans
In this study, atorvastatin 80 mg/d inhibited ROCK activity by approximately 49% compared to placebo. What might be the consequences of this magnitude of ROCK inhibition? Previously, we have treated atherosclerotic subjects with the direct ROCK inhibitor, fasudil, and have observed improved brachial artery endothelial function associated with 59% inhibition of ROCK activity [5]. This degree of ROCK inhibition was similar to that achieved in the present study with atorvastatin 80 mg/d. In the present study, we found a modest correlation between ROCK inhibition and an anti-inflammatory effect measured as reduction in hs-CRP (r=0.6, p=0.07). Although not conclusive, these results support the hypothesis that Rho/ROCK inhibition mediates the anti-inflammatory effects of statins and potentially explains the clinical benefit observed in the JUPITER study in patients with elevated CRP levels treated with intensive statin therapy
-------------------------------

Chronic treatment with taurine ameliorates diabetes-induced dysfunction of nitric oxide-mediated neurogenic and endothelium-dependent corpus cavern... - PubMed - NCBI
Taurine treatment improves NO-mediated relaxations of corpus cavernosum in diabetic rats probably by inhibiting NADPH oxidase/Rho kinase pathways.
Antenatal taurine improves neuronal regeneration in fetal rats with intrauterine growth restriction by inhibiting the Rho-ROCK signal pathway. - PubMed - NCBI
The Rho-ROCK signal pathway is an important mediator of inhibitory signals that blocks central nervous cell regeneration............Thus, antenatal taurine supplementation inhibited the expression of key Rho-ROCK signal molecules and improved IUGR fetal brain development

The vitamin D receptor agonist elocalcitol upregulates L-type calcium channel activity in human and rat bladder. - PubMed - NCBI

-------------
One interesting stuff, 1,25ohd3 ,the active form of d3 apparently activates rho kinase, so its another reason for having decent calcium intake , as it lowers conversion of 25oh to 1,25oh.
---------


Aspirin
Salicylates dilate blood vessels through inhibiting PYK2-mediated RhoA/Rho-kinase activation

I will probably update this post and add more stuff if i found more...

------------

Rho kinase and depression
The ROCK inhibitor Fasudil prevents chronic restraint stress-induced depressive-like behaviors and dendritic spine loss in rat hippocampus — University Andrés Bello
 
Last edited:

AMK

New Member
Joined
Jun 27, 2018
Messages
3
Hi Paymanz, this is interesting to me because I am trying to treat my connective tissue disorder, and the enzyme that is causing me trouble is the same one that statins inhibit. It is a defect in cholesterol synthesis. Long story. But in short, I see that you have some experience or knowledge of benfotiamine and manganese.I am looking for ideas on a starting dose of manganese and benfotiamine (antagonising each other as they do, if body ratio is wrong).
Do you mind me asking if you take Benfothiamine and manganese and if so, what dose and how you got there?
Cheers, AngelA
 

paymanz

Member
Thread starter
Joined
Jan 6, 2015
Messages
2,693
Hi @AMK

I never used benfotiamine ,just normal thiamine. But maybe benfotiamine is better ,i dont know.

I took manganese up to 50mg a day for some periods but i dont think high dose like that is necessary, lower doses like 5-10 mg if taken everyday is enough to correct a deficiency.

Also took high doses thiamine hcl for some periods with good results.but again i dont think high doses in long term is good idea.

Best way for both manganese and thiamin is to monitor how your body reacts to it , your energy level especially.

We need 3-5 mg of manganese a day ,and phytates can block its absorption.

Vitamin k is also a cofactor for Mn.

Sometimes low dose of tetracyclines like doxycycline can help to improve connective tissue problems, because they are anti-inflammatory, search forum for them you can find some good info.
 
Last edited:

AMK

New Member
Joined
Jun 27, 2018
Messages
3
Many thanks Paymanz.
Can I ask what dose of thiamine hCl you took and did you go down or off it.....because your condition cleared up?
Angela
 

paymanz

Member
Thread starter
Joined
Jan 6, 2015
Messages
2,693
I think it was around 1500-2000mg a day , after a while its effects wasnt as strong as the beginning of supplementation,they are a bit expensive and also i dont think its normal to get hundreds time more than required amount of a vitamin for long time. So i stopped.
because your condition cleared up?
And yes my energy level is better than that time.
 

AMK

New Member
Joined
Jun 27, 2018
Messages
3
Yes I think that even though it is a water soluble vitamin, you can still take too much of it (and relative to other vitamins).
That whole area of dosing of Vitamins is so difficult.

What is the dose you currently take? That you stabilised on.

(I want to take more THCL than they give you in the standard multivitamin from the shop. Just asking others what they take so that I can find a range to experiment it)?
 

paymanz

Member
Thread starter
Joined
Jan 6, 2015
Messages
2,693
Currently ,some days i take no supplement at all , some days just a normal standard DRI dosage of b complex multivitamin.

Start with a dosage and judge it by how it effects you.
 
Similar threads
Thread starter Title Forum Replies Date
haidut Statins May Cause Insulin Resistance By Depleting Vitamin K Scientific Studies 1
forterpride Is this drug healthier than statins? Ask For Help or Advice 12
Mito 20-Year Follow-up Of Statins In Children With Familial Hypercholesterolemia Articles & Scientific Studies 0
haidut Statins More Than Double The Risk Of Diabetes Compared To Non-users Scientific Studies 0
haidut PUFA/Statins Promote UV Damage & Skin Cancer (melanoma), Cholesterol Is Protective Scientific Studies 4
Hugh Johnson "Hypercholesterolaemia Caused By Glyphosate Is Now Treated By Statins" Health 3
D Statins And Bone Growth Cholesterol 0
haidut Lowering Cholesterol Increases CVD Deaths, Benefits Of Statins Exaggerated Scientific Studies 12
charlie Statins: Heart Disease Drug Speeds Up Ageing Process, Warns New Research Articles 6
haidut Aspirin Better Than Statins For Cholesterol And Triglycerides Scientific Studies 16
haidut Safety And Efficacy Of Statins Deliberately Exaggerated Articles 4
charlie Parkinson's Link To Statins: Calls To End Widespread Use Of The Drug Miscellaneous Health Discussions 2
charlie Statins Stimulate Atherosclerosis And Heart Failure: Pharmacological Mechanisms Scientific Studies 17
haidut Statins cause fat buildup, adrenergic activation causes muscle wasting Scientific Studies 0
J KMUD: PUFA, Heart Health, Statins KMUD Radio-The Herb Doctors 4
G Cholesterol is Protective (Statins, Thyroid, Metabolic Rate, Kmud Interview: Oct.10, 2010 - Sugar II [Clipped.I 0
haidut Vitamin B1 and/or biotin may treat Huntington Disease (HD) Scientific Studies 35
H Circumcision may increase STI rates Scientific Studies 5
haidut Vitamin A may treat anosmia (loss of smell) due to COVID-19 Scientific Studies 8
GorillaHead Vaccines may not be required anymore in the future. Pills are coming. Thoughts? Supplements, Pharmaceutical Drugs 20
haidut PUFA required for periodontal disease, aspirin may help Scientific Studies 12
ecstatichamster Yes, Nick Minaj may be right: swollen balls are entirely possible after the "vaccine" Vaccines 24
ImprovingDaily Almost fully recovered from Covid pneumonia, here are some tips for anyone who may need them. Viruses, Parasites, Fungus, Vaccines 16
Apollo Is lactose free milk safe ? (galactose may be toxic) Dairy 20
haidut Having SARS-CoV-2 confers MUCH stronger immunity than vaccines, and it may last a lifetime Scientific Studies 33
haidut Vitamin D, reducing fat oxidation may treat lung fibrosis, COVID-19 Scientific Studies 10
haidut How lipolysis may damage organs such as the heart Scientific Studies 0
OccamzRazer Income idea for anyone who's lost or may lose their job Miscellaneous 57
A Https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250771/ Mortality From Coronavirus Disease 2019 Increases With Unsaturated Fat and May Be Reduced by Metabolism 1
J Think I may have vitamin D toxicity Skin 15
RenaissanceMan Omega-3 EPA and DHA may be the solution to "male pattern baldness" / hair loss in men Polyunsaturated Fats, Seed Oils 29
G CDC may be preparing internment camps Ask For Help or Advice 54
G The COVID Vaccine May Induce COVID Sensitivity Vaccines 0
D New article frames SIBO as a gender specific disease; anabolic steroids may be useful treatment Articles & Scientific Studies 3
haidut COVID-19 vaccines may cause 82%+ miscarriage rate Scientific Studies 81
haidut Iron supplementation may not cure anemia, unless nutrition is also improved Scientific Studies 1
haidut Damaged mitochondria may cause 90%+ of Parkinson Disease (PD) cases Scientific Studies 4
haidut Aging is an energy deficiency problem, taking cardiolipin may reverse it Scientific Studies 8
haidut It's official: COVID-19 vaccination may be stemming evolution of “fitter” SARS-CoV-2 variants Scientific Studies 15
A How teen marijuana use may alter the shape of the brain Scientific Studies 0
D Theory, which may explain copper toxicity/deficiency/low cerruloplasmin Minerals 86
charlie Like night and day: Animal studies may not translate to humans if time of day is disregarded Scientific Studies 2
P Progesterone Suppresses GAD enzyme MRNA (If progesterone excites you, it may be glutamate) Progesterone 2
haidut Mitochondrial dysfunction may be the cause of anemia Scientific Studies 0
haidut Blocking the endotoxin receptor (TLR4) may prevent / treat hearing loss Scientific Studies 8
haidut Upregulated serotonin synthesis may be a biomarker for breast cancer Scientific Studies 0
haidut Vitamin B6, lowering stress, may treat schizophrenia Scientific Studies 3
haidut Many people may suffer from chronic serotonin syndrome Scientific Studies 65
haidut Endocrine disruptors in cosmetics may cause postpartum depression, premature births Scientific Studies 1
haidut Endotoxin (LPS) may be the cause of fatal lung damage in COVID-19 Scientific Studies 0

Similar threads

Top