Table Salt - Inflammation and Cardiovascular Health

[nishka]

I have found some interesting studies about problems of excess dietary salt

As I couldn't find anything on the JoS forum, I decided to do some research myself.
I noticed that salt is a rather controversial subject, so I ended making a summary of everything I could find.

My goal is to spark a healthy discussion
Further findings, coincidences with traditional medicine, even links with Satanism etc.




Introduction

In its solid state, common salt is a molecule comprising sodium and chloride.
When the sodium-chloride molecule is solved in water, it is split into its respective ions: Sodium ( Na+ ) and chloride ( Cl- ).

Sodium regulates the blood volume. The 'cellular voltage' and the transduction of signals from the central nervous system
are facilitated by both sodium and chloride ( alongside other ions: e.g. potassium, anionic proteins, calcium ).

Salt is a popular additive found in many processed foods. It enhances flavor and increases the product's shelf life.


Salt has come under heavy scrutiny for causing high blood pressure; leading to heart failure,
kidney diseases, strokes and many other ailments.

Ironically, excess dietary salt could increase the incidence of strokes independently of blood pressure, or promote cognitive impairment.


It is known that a decreased blood supply of the cerebral arteries leads to lethargy, somnolence, cognitive problems and even coma.

You will notice that overextending your neck will result in a feeling of discomfort, or even dizziness.
This is the direct result of obstructing the two vertebral arteries inside your neck.

The 2 vertebral arteries are indirectly linked with the 2 internal carotid arteries.
A chronic obstruction ( e.g. atherosclerosis ) of one artery can be offset by the 3 remaining arteries ( unlike in an acute obstruction ).

So how exactly could salt lead to strokes, or - may the Gods forbid for a lack of better words - 'dumbness'?



Summary

The culprit is a certain protein produced by immune cells belonging to the adaptive immune system.
Simplified, there are two types of cells in the adaptive immune system ( in contrast to the innate immune system ).

- CD8-positive T cells
- CD4-positive T cells

-> 'CD' refers to a type of protein cluster on the cell's surface:

When CD4-positive T cells are activated, they expand, and split into three subclasses:
- Th1 cells, Th2 cells and Th17 cells


The Th17 cells produce interleukin-17 ( short: IL-17 ), the protein I mentioned at the beginning of this paragraph.
When Th17 cells come into contact with salt, they start expanding, causing a higher level of plasma IL-17.
IL-17 expression is also boosted by salt.

IL-17 itself is a pro-inflammatory protein, a cytokine. It is not exclusively produced by Th17 cells, though.
The promotion of inflammation helps to attract other immune cells.
An inflammation itself is a reaction of the innate immune system. Since Th17 cells belong to the adaptive immune system, this is one the many links between the two systems.

The cytokine IL-17 interferes with the widening of blood vessels. In case of the cerebral blood vessels,
this can lead to the aforementioned problems: strokes, cognitive impairment, etc.


Interestingly, elevated levels of IL-17 are also observed in autoimmune diseases ( e.g. rheumatoid arthritis and multiple sclerosis ),
with some studies claiming that they are directly caused by IL-17 ( e.g. psoriasis ).



Mechanism

In order to better understand the mechanism, the structure of a blood vessel needs to be understood first.
A blood vessel comprises three vascular walls:

- Tunica interna: the inner layer, formed by 'endothelial cells' ( often summarized as the 'endothelium' )
- Tunica media: the middle layer, comprising muscle cells
- Tunica externa: the outer layer, made of connective tissue

The endothelium contains an enzyme for the production of nitric oxide, a molecule that is crucial for vasodilatation.
Vasodilatation refers to the increase of vascular diameter. Nitric oxide relaxes the muscle cells by inhibiting
the entry of calcium into the muscle cell. Calcium is required for the contraction of muscle cells.

Increasing the vascular diameter yields a lower vascular resistance, making it easier for the blood to flow through ( Hagen–Poiseuille law ).

The enzyme for nitric oxide is called 'endothelial nitric oxide synthase' ( eNOS ).
Endothelial NOS synthesizes nitric oxide from L-arginine.

The activity of eNOS can be modulated by means of phosphorylation; meaning: the addition of a phosphoryl group to specific locations.

In the case of eNOS, there are two amino acid side chains that can be targeted:

- the serine side chain ( Ser1177 ) to increase the enzyme's activity
- the threonine side chain ( Thr495 ) to stop the synthesis of nitric oxide

For the phosphorylation of either target, we need another enzyme: the Rho kinase. The Rho kinase needs to be activated by the RhoA-GTPase protein.
This is called the RhoA/Rho-kinase pathway. This pathway is crosslinked with yet another enzyme called p38 MAPK.
p38 MAPK can be triggered in the presence of high salt levels.

p38 MAPK itself is responsible for the production of cytokines inside every CD4-positive T cell, including IL-17.



tl;dr

- high saline levels trigger P38 mitogen-activated protein kinases, facilitating the expression of interleukin-17 by CD4+ Th17 helper cells
- interleukin-17 phosphorylates eNOS Thr495 by activating the RhoA/Rho-kinase pathway, suppressing the expression of endothelial nitric oxide
- eNO is required for vasodilatation, thus increasing the risks of cardiovascular diseases





I think finding a healthy balance is key here. We're talking about extreme levels here.
What makes me wonder, though: Can a controlled intake of salt influence autoimmune diseases?
Or, in case of sweating, ameliorate inflammations? What do you think?


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Sources:

https://www.ncbi.nlm.nih.gov/pubmed/24192502?dopt=Abstract
http://grantome.com/grant/NIH/R01-NS095441-03
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526596/

 

[Centralforce666]

This model assumes two things:

A) that inflammation is bad and the ameriolation of inflammation will assist in the curing of diseases and,

B) that strokes and other cardiovascular problems are caused by salt.

Neither of the above statements are true in isolation, however in occasion and in some instances they are depending on the person's syndrome pattern.

Inflammation in an extreme form, such as asthma can kill a person however simply quashing the inflammation (which is what steroidal interventions do) does not rid the person of the disease, it only drives it deeper.

Cardiovascular problems caused by salt intake are from over cooling of the heart fire by kidney yin, and related to the formation of phlegm. Salt actually preserves the kidney structure and function, including the juxtagloremular apparatus which is responsible for the regulation of blood pressure. Damage to this apparatus is responsible for irreversible blood pressure changes (increases).

Therefore the sodium restrictive diet, whilst useful in reducing inflammatory mediators which may reduce symptoms of disease does not fix the inherent problem.

Sweating therapy however is a legitimate and useful tool in clearing phlegm and damp from the superficial layers and the lung and heart (which is a part of the salt-cooling-phlegm cardiovascular disease pathway) and infectious illness from the lung such as influenza and the common cold.

 

[nishka]

...
A) that inflammation is bad and the ameriolation of inflammation will assist in the curing of diseases..
....
Inflammation in an extreme form, such as asthma can kill a person however simply quashing the inflammation (which is what steroidal interventions do) does not rid the person of the disease, it only drives it deeper.

Also including the suppression of the hypothalamic-pituitary-adrenal-axis, the effects on the thyme parenchyma and the enforced catabolism? Yes, it's mere symptom treatment.
The rigidness of school medicine can be mind-blowing, an eosinophilia is not triggered without cause. On a more personal note, there are special classes and educational events for children with asthma. Basically, it's a psychologist explaining the boons and 'exaggerations' of corticosteroids without having any medical foundation whatsoever. Amazing, right?

B) that strokes and other cardiovascular problems are caused by salt.

Shame on me, yes, you are right on that one. I have misphrased it, I should have written something like 'excessive intake of dietary salt could be one factor in the increase of such incidences'.
The papers describe one of possibly many pathological mechanisms caused by the excessive consumption thereof. If memory serves me right, a glucocorticoid-based kinase was also involved in the p38 MAPK pathway, but it belonged to the domain of sodium transport. I just find it interesting to establish links with wider or more isolated cases. Call it the fanatic belief in scientific explanations for every phenomenon.

Another thing I should have mentioned is that studies should generally be approached with caution. But in human biology, nothing is for sure, even in the case of anatomy, a more conservative subject ( e.g. the discovery of the M. tensor vastus intermedius, pulmonary ionocytes in cystic fibrosis, etc. ).

Cardiovascular problems caused by salt intake are from over cooling of the heart fire by kidney yin

Concerning the 'cardiorenal' link, this also makes sense on a more strictly anatomic level. Blood volume is not only regulated b the auriculae cordis that produce atrial natriuretic peptide,
but also the nephrogenic renin-angiotensin-aldosterone system, with ACE being provided by endothelial cells, etc.

Therefore the sodium restrictive diet, whilst useful in reducing inflammatory mediators which may reduce symptoms of disease does not fix the inherent problem.

That is correct, although an inflammation can escalate by triggering a cascade, leading to a plethora of other problems. Still, an inflammation itself IS a reaction of the innate immune system, and an obvious
sign that everything is in working order ( as long as we remain on normal levels, think of Gaussian distribution ).
Perhaps it's something I can keep in mind for later on.

By the way, I find this conversation rather enjoyable. I appreciate it that you have taken the time to answer in depth.
I find the 'salt-cooling-phlegm cardiovascular disease pathway' you described rather interesting, do you have any personal recommendations for
a selection of good books on topics like these?