MS as a disease of endothelial dysfunction

[cheerleader]

Lots of new research showing the connection between a dysfunction in the cellular lining of the 60,000 miles of blood vessels in the human body, called the endothelium, and multiple sclerosis. The endothelium is the largest secreting organ in our bodies, and when it doesn't work, diseases of neurodegeneration can occur, due to hypoperfusion (slowed cerebral blood flow.)

The aim of the study was to assess endothelial function in patients with MS and in healthy controls.
METHODS:
We enrolled 46 patients with diagnosis of relapsing-remitting MS and age-matched population of 31 healthy subjects. Endothelial function was assessed using peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI).
RESULTS:
RHI in MS population was significantly lower than in controls (1.77 vs 2.30; p=0.001), even though control population seemed to have higher burden of known vascular risk factors (significantly higher portion of male sex and significantly higher body mass index; p≤0.001 for both parameters). The presence of MS was the only significant independent variable associated with the RHI (beta=0.396, p<0.001) in multiple linear regression model.
CONCLUSION:
Results of our study suggest significant impairment of endothelial function in MS population compared to age matched control population with low burden of vascular risk factors.

http://www.ncbi.nlm.nih.gov/pubmed/25789590

So----even though controls had higher burden of vascular "risk factors"---pwMS had worse endothelial dysfunction, as expressed by reperfusion hyperemia index, a measurement of how blood flows after a blockage of a blood vessel. We see this same high index response in ischemic stroke.

Here's more recent research connecting the endothelium and blood flow to MS. Published the last couple of months.
http://ccsviinms.blogspot.com/2015/03/t ... s-new.html

The heart and brain are connected....as neurovascular experts are discussing this week at the 5th annual. International Society for Neurovascular Disease conference.
http://ccsviinms.blogspot.com/2015/03/2 ... racts.html

get to know your endothelium, and take care of it---
http://ccsvi.org/index.php/helping-myse ... ial-health
cheer

[tedhutchinson]

Dietary Vitamin D and Its Metabolites Non-Genomically Stabilize the Endothelium

This paper explains the role of CHOLECALCIFEROL Vitamin D3 in it's basic form, is more than just the precursor of the circulating form calcidiol, which is converted to the active hormonal form but is active in it's own right as a signalling molecule that maintains endothelial function.

Because Cholecalciferol only has a half life of 19-25hours in the body in that form it's vital to take it daily and in sufficient quantities to have measurable amounts of cholecalciferol in tissue.
The image below shows you can only measure significant amounts of cholecalciferol in tissue if you keep 25(OH)D at or above 50ng/ml 125nmol/l
Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status

[PointsNorth]

Thanks Ted. Bump. Dirt cheap vitamin. Maybe Coimbra stumbled on something 12+ years ago? He has CURED 100's of people with MS and MANY other autoimmune diseases using relatively high doses of vitD. I have not heard of anyone having difficulty with his protocol.

[CureOrBust]

I have not heard of anyone having difficulty with his protocol.

But it does not work for everyone. And the actual % of people it does actually work for, over simply an improvement over a higher than normal MS D3 level is unknown.

[PointsNorth]

I have not heard of anyone having difficulty with his protocol.

But it does not work for everyone. And the actual % of people it does actually work for, over simply an improvement over a higher than normal MS D3 level is unknown.

I have read a figure of 95% efficacy in several places. But we don't know as there has not been any trials. but the trial for high dose vitamin D in psoriasis/vitiligo had a pretty high success rate: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897595/

[tedhutchinson]

But there is a huge difference between the Coimbra protocol which uses 60,000iu daily or more vitamin D3 (in the context of drinking 2.5 liters water daily and eliminating dietary calcium foods) and using DAILY amounts of vitamin D3 that would naturally be made in human skin if we were able to spend 30 minutes in midday summer sunshine near naked daily or a few minutes under a uvb light source.
If we measure 25(OH)D levels in indigenous peoples who average about 125nmol/l (50ng/ml) with up to 200nmol/l (80ng/ml) in pregnancy/lactation.
Simply trying to mimic what happens naturally with DAILY VITAMIN D3 supplementation at amounts aiming to attain/maintain a high stable 25(OH)D that enbles vitamin D3 in the basic unchanged natural form to be measurable in tissue, is different from Coimbra's protocol where he is trying to reset the immune response and reverse autioimunity.
There is a difference between trying to achieve the natural levels human DNA is set to achieve given the circumstances human DNA evolved with, and trying to experiment with higher than natural amounts of vitamin D3 daily.

[vilnietis]

There is also interesting coincidence regarding various biomakers occuring naturally and then on vitamin D huge dose. Women with MS are doing much better while they are pregnant. Hormones plays a big part, but I found one interesting relation . Vitamin D huge dose reduces PTH and here:

http://www.ncbi.nlm.nih.gov/pubmed/3047164
Our findings suggest, in contrast with the results of most previous studies, that serum intact PTH may decline during pregnancy.

High vitamin D - better outcome, pregnancy - better outcome. PTH is suppressed in both cases. Is there any other option to suppress parathyroid hormone without taking vitamin D?

[tedhutchinson]

High vitamin D - better outcome, pregnancy - better outcome. PTH is suppressed in both cases. Is there any other option to suppress parathyroid hormone without taking vitamin D?

Why would anyone want to achieve optimal PTH levels by anything other than having natural optimal 25(OH)D levels?
PTH and 25(OH)D are inversely correlated. Surely that is an indication that optimal vitamin D levels lead to optimal PTH levels.



It's amazing isn't it that the level at which human milk is a vitamin D3 replete food for human babies is also the level at which vitamin D3 is most effective at resolving inflammation and is linked to the lowest levels of PTH and the lowest incidence of cancer and other chronic diseases.
http://www.grassrootshealth.net/media/d ... -24-12.pdf

[1eye]

Regardless of high-dose Vitamin D and parathyroid, it is important to stay on track with this new work http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607301/, Dietary Vitamin D and Its Metabolites Non-Genomically Stabilize the Endothelium, on the value of Vitamin D in general, in the context of endothelial dysfunction. This problem is not limited to MS. It is associated, at least, with the most common cause of death, ischaemic heart disease.

My immediate (siblings and parents) family is full of chronic autoimmune problems - arthritis, reynauds, lupus, MS, vitaligo, type II diabetes, CLL. We endured leaded gas and atmospheric nukes, and lived in an area where 3 sibling girls died of leukemia. We spent a year in the low sunshine of the UK. Nature or nurture, the deck was stacked.

But this discovery concerns what effect low (not high) vitamin D has on endothelial problems. Vitamin D stabilizes the endothelium. Without it, you get problems -- leaks, stenosis, lack of tone, etc. It is not just a Vitamin. It is very biologically active. In doses as low as "100 pM to 10 μM".

One of the figures:

D3 abrogates inflammatory leak

Blood-brain barrier:

a key role in the destabilization of vascular endothelial cadherin (VE-Cadherin) cell-cell junction proteins

anywhere you see `junctions` they might be talking about the Blood-brain barrier.

Importantly, we also show that the barrier-enhancing function of vitamin D3 is not limited to what is commonly referred to as the “active metabolite” 1,25(OH)2D3, but this activity is present in the “inactive” dietary and mono-hydroxylated forms of the vitamin as well.

(released by UVA...)

Vascular instability is a hallmark of such inflammatory diseases

Inflammation is a hallmark of MS. Therefore, following hallmarks down the hall...

...might lead to another recent study by Paulo Zamboni: http://www.thisisms.com/forum/chronic-c ... 27291.html

Journal of Multiple Sclerosis
ISSN: 2376-0389
Journal of Multiple Sclerosis
Open Access

from the first paper in this thread: Note the comparison is with healthy controls without risk factors for vascular disease.

The presence of MS was the only significant independent variable associated with the RHI (beta=0.396, p<0.001) in multiple linear regression model.

http://www.ncbi.nlm.nih.gov/pubmed/25789590