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Thiamine, endothelial cells and nitric oxide

Mary

Moderator Resource
Messages
17,334
Location
Southern California
Okay, this study has to do with diabetes patients but it might have some relevance for ME/CFS:
http://www.ncbi.nlm.nih.gov/pubmed/21288652

It states in part:

Nitric oxide (NO) is synthesized by the endothelial cell and is also an important element for the viability and functionality of this cell type. However, in the DM patient, a deficient synthesis of NO has been reported. It is relevant to mention that recent evidences have led to propose mitochondrial activity as an important regulator of nitric oxide synthesis (ON). We consider that the exogenous administration of TPP facilitates the utilization of this molecule, regulating some metabolic processes such as phosphorylation of thiamine by TPPK, energy consumption (ATP), as well as mitochondrial activity, inducing eventually NO synthesis. If this is confirmed, the administration of TPP to the diabetic patient would provide additional protection to endothelial cells, reducing the risk of vascular damage, to which the diabetic patient is highly susceptible.
 

Gondwanaland

Senior Member
Messages
5,092
I was going to start a new thread on endothelial health but then found this one which is a great start. I wasn't aware about the role of B1 in it.

In my early 40s I had endothelial rupture (due to thoracic outlet syndrome) followed by DVT and was put on rat poison (warfarin) for 1.5 years. Warfarin inhibits endogenous conversion of vitamin K1 into K2, which leads to brittle endothelium. Today I have plaque in both carotids and am not 50yo yet. So I am looking into how to limit my rampant endothelial damage.

There sure is a genetic component since I have close family members with this problem, but their issues have been diagnosed much later in life (because no dr looked into it earlier?).

So in addition to B1, I would like to list:

- Vitamin K2 redirects calcium from plaque to the bones. there will be holes. When the calcium deposited in plaques is stripped off - there will be holes. What is needed to repair the endothelium?
- Vitamin C (which I do not tolerate in any amount in supplemental form - I suspect because it is an aromatase inhibitor and I have very low estrogen)
- Lysine + Copper + Silica for collagen formation (Biotin is needed)
- B6 to reduce homocysteine (will require B9 & B12 as well)
- I just experienced B2 is needed for healthy skin (reversed a rosacea-like flare with it - perhaps due to B6 activation? Glutathione regeneration?)
- Glutamine: I have found studies (e.g., 1, 2, 3) stating that it inhibits NO synthesis by the endothelium and therefore is recommended for vascular health. This confused me. My experience with it is that, despite raising my RBC and WBC counts (which I suppose is a good thing since they are usually below range) it generates higher ammonia creating a higher need for B2 + B6.

Steve Gundry's approach is undoable for me since I quickly become salicylate intolerant if I take pycnogenol (perhaps I need more copper), and because I can't afford to exclude beans from my diet again (I need to gain weight).

In my experience, coconut oil quickly and reliably reduced homocysteine, but the natural and added sulfites in coconut products are toxic to lymphocytes and lead to food intolerance build up (salicylates) + interfers with nitric oxid functions.

http://www.inchem.org/documents/jecfa/jecmono/v21je15.htm
Sulfur dioxide reacts irreversibly with thiamine to yield
pyrimidine sulfonic acid and 4-methylhydroxyethyl thiazole (Dwivedi &
Arnold, 1973) and, at high concentrations, may destroy cobalamins via
the formation of photolabile complexes (Gunnison et al., 1981a;
Gunnison & Jacobsen, 1983).

Sulfite forms adducts with nicotinamide adenine dinucleotide
(NAD), flavins, and with cytosine and uracil, their nucleosides, and
nucleotides (Gunnison, 1981, Shapiro, 1983).
....
Sulfite is oxidized in vivo to sulfate, catalysed by the enzyme
sulfite oxidase (sulfite;ferricytochrome C oxidoreductase, EC 1.8.2.1)
located in the mitochondrial intramembranous space. This enzyme has
been well-characterized as a dimer with subunits containing a
molybdenum atom, a cytochrome b5 type of haemoprotein, and a pterin
cofactor. The enzyme is inhibited by tungstate both in vitro and
in vivo (Cohen & Fridovich, 1971; Johnson et al., 1980).
....
sulfate
formed metabolically from sulfite may serve to increase the loss of
calcium in urine and faeces of man

http://www.inchem.org/documents/jecfa/jecmono/v042je06.htm
The possibility that the adverse effects attributed to ingestion
of sulfites, including bronchoconstriction, are mediated through
effects on nitric oxide as part of the parasympathetic pathway was
tested in a series of experiments in vitro. Sulfites were shown to
react in solution with nitric oxide and with biological carriers of
nitric oxide (S-nitrosylated bovine serum albumin and
S-nitrosoglutathione) and to interfere with the effects of nitric
oxide in biological processes such as inhibition of platelet
aggregation. The results suggest that sulfites interfere with the
biological effects of nitric oxide at physiologically realistic
concentrations (Harvey & Nelsestuen, 1995).
...which brings Molybdenum to the dance, making it a constant juggle between Mo & Cu (one antagonizes the other)

The link above is an extensive review on sulfite detrimental effects on health.

@prioris @Lolinda @aaron_c @alicec @adreno @alex3619
 
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Gondwanaland

Senior Member
Messages
5,092
Drink 1 or 2 glasses of red wine.
Wine causes me non-stop vomiting (natural and added sulfites) and insomnia. I think I need to permanently take a B complex, but it has been causing me a severe tension in shoulders and neck. Perhaps a copper deficiency? (have you looked into that @picante ?). Resveratrol supplementation feels awful (estradiol antagonizer?)
 

aaron_c

Senior Member
Messages
691
I have recently gone off of molybdenum entirely. As you might recall, I used to take quite high doses of Mo, 1500 mcg per day. I no longer need to: Boron appears to help with SUOX in some way. I don't know if it this is by directly helping SUOX or by doing something to mobilize molybdenum.

I know boron binds to B2 and they both get excreted, but I've had success compensating by using a borax foot-bath and increasing my b2 intake a little. The only issue (currently) is that boron seems to cause insomnia. On the other hand, it seems to help me function with less sleep (on boron I can function ok with eight or nine hours of sleep, whereas without I need at least 11 to not feel extra-shitty).

My current theory is that the boron insomnia is caused by some kind of interaction between the boron and the excess molybdenum. Hopefully time will tell.

PS. Boron is particularly useful for fungal infections, at least for me. I use dandruff as a rough yardstick to see when I need more boron. Perhaps ideally I should be taking more, but with the insomnia and b2 stuff I'm walking a fine line.
 

Wishful

Senior Member
Messages
5,679
Location
Alberta
Interesting. I recently discovered that peroxynitite scavengers worsen my symptoms. Peroxynitrite is formed from NO and superoxide.

B1 did reduce my symptoms slightly when I tried it years ago, but then it stopped working.
 

prioris

Senior Member
Messages
622
Supplements that promote nitric oxide are very limited in what they can do due to the rate limiting factor. In studies, supplementation did not stop arteriosclerosis. It will make the arteries a little more flexible hence bring down blood pressure so take some stress off arteries but does not stop the underlying disease progression. It's just buying a little more time at best I think. It works well superficially in that it brings blood pressure down but for me, that just doesn't cut it if not stopping progression.

I have started another thread to talk about heart disease in a larger context
http://forums.phoenixrising.me/inde...lerosis-arteriosclerosis-calcification.51321/
 

Gondwanaland

Senior Member
Messages
5,092
New research into NO
https://www.ncbi.nlm.nih.gov/pubmed/28511731
Nutr Res Rev. 2017 May 17:1-12. doi: 10.1017/S0954422417000063. [Epub ahead of print]
Dietary nitrate and blood pressure: evolution of a new nutrient?

Abstract

Dietary nitrate is mainly obtained from vegetables, especially green leafy vegetables and beetroot. As a result of early research, dietary nitrate is currently viewed as a contaminant linked to increased risks of stomach cancer and methaemoglobinaemia. Consequently, nitrate levels are restricted in certain vegetables and in water supplies to ensure exposure levels remain below an acceptable daily intake of 3·7 mg/kg per d. The average nitrate intake in the UK is approximately 70 mg/d, although some population groups, such as vegetarians, may consume three times that amount. However, recent studies in the last decade suggest that dietary nitrate can significantly reduce systolic blood pressure via the nitrate-nitrite-NO pathway. A small, downward shift in systolic blood pressure across the population could significantly reduce the incidence of hypertension and mortality from CVD such as stroke. Interestingly, vegetarians tend to have lower levels of blood pressure than omnivores and epidemiological studies suggest that vegetarians have lower risks of CVD. Recent evidence is mainly focused on the acute effects of dietary nitrate supplementation and there is a lack of data looking at the chronic effects of high nitrate consumption in humans. Nevertheless, due to potential health benefits, some authors are recommending that nitrate should be considered as a nutrient necessary for health, rather than as a contaminant which needs to be restricted. This review will discuss the emerging role of dietary nitrate in the control of blood pressure and whether there is sufficient evidence to state that nitrate is a 'new' nutrient.
 

aaron_c

Senior Member
Messages
691
I don't know @Gondwanaland , It smells like something the fertilizer industry would push--aren't they the source of higher nitrates in vegetables?

I don't know a lot about this. Maybe nitrates really aren't dangerous if they haven't been turned into nitrosamines. But it sounds like they are sort of saying "hey we accidentally found our product makes vegetables produce this drug, so we propose this drug is good for everyone."
 

prioris

Senior Member
Messages
622
nitrate do increase nitric oxide levels but there are rate limiting factors which make it difficult to raise it in body after a certain point. nitrate has been tried and it has no effect on arterosclerosis progression so dead end.
 

Little Bluestem

All Good Things Must Come to an End
Messages
4,930
Dietary nitrate is mainly obtained from vegetables, especially green leafy vegetables and beetroot.
But I thought that beetroot was good for the liver. I try to eat it 3-4 times/week. :confused:
 

ScottTriGuy

Stop the harm. Start the research and treatment.
Messages
1,402
Location
Toronto, Canada
I had endothelial rupture (due to thoracic outlet syndrome) followed by DVT and was put on rat poison (warfarin) for 1.5 years.

Yikes.

That's concerning for me - I was recently diagnosed with TOC (the artery / vein type) and the vascular surgeon asked why I wasn't on statins after my carotid ultrasound - presumably because he saw some plaque build up - I told him about endothelial dysfunction in ME and asked about its potential relationship to TOC, he had nothing helpful to say and didn't seem interested in discussing - I have not seen his actual report yet for the details.

What were your TOC symptoms? (My vascular surgeon said my symptoms were not typical, and other than asking about statins, made no suggestion for treatment. I'm going to ask my GP for a 2nd opinion.)

What were you symptoms when you experienced endothelial rupture? And DVT?

How come you were only on warfarin for 1.5 years?

Thanks!
 

Gondwanaland

Senior Member
Messages
5,092
after my carotid ultrasound - presumably because he saw some plaque build up
I did carotid US last year: both carotids with plaque.
What were your TOC symptoms?
It has only been discovered because I had a vein rupture damage (holes covered by clots, not plaque), but my previous symptoms were essentially extreme tiredness from lifting my arms above my head for a few seconds - like hanging laundry for instance, or like playing volleyball in my childhood (which I never enjoyed).
What were you symptoms when you experienced endothelial rupture? And DVT?
I had the rupture damage in the 1st place because I was involved in an activity that required me to reach stuff above my head for 5 days in a row.

I had extreme pain at my shoulder and the 1st dr that saw me at the ER concluded it was a bursitis. He prescribed anti-inflammatory + painkiller.

2 days later my upper arm looked like a ballon and another dr at the ER sent me to an emergency US where they found 3 DVTs in my left shoulder/upper arm.

I didn't even left the hospital and I spent 3-4 days there taking heparin injections. When I left, I had a warfarin prescription to take it daily.

A couple of months later I was dignosed with Hashimoto's by an endo. The hematologist found I am +/- Factor V Leiden and said that being heterozygous is meaningless for clotting tendency.

In my personal view, I think the culprit was my stupid GYN who prescribed my a pill that was clearly harming me: migraines, ovary cysts, etc. Another stupid one was my dermatologist who prescribed me Accutane the year before for rosacea (which actually was B2 deficiency probably triggered by the pill). I assume my homocysteine was very high at that time, but no dr was checking for it. It is the marker of endothelial damage.

How come you were only on warfarin for 1.5 years?
I told my vascular dr about what the hemato said and he agreed that I didn't need to be on warfarin for life. If I hadn't talked with him about it, I would still be on it...

EDITED TO ADD - follow-up US showed complete resorption of the 3 clots.

I went off of warfarin in 2012, and started studying supplements in 2013. Then I spent about a year on Omega 3 + Gamma E and enjoyed its anti-inflammatory + blood thinning effects, but it added up with the Xdermal progesterone my new GYN put me on and suppressed my estrogen almost completely.
 
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prioris

Senior Member
Messages
622
Warfarin inhibits vitamin K. Causes more calcification. YIKES

nattokinase and serrapeptase taken together is a much better alternative to warfarin. there will not be any studies funded to prove that either.
 

prioris

Senior Member
Messages
622
What dosage of Omega 3 were you using and what was omega 6 omega 3 ration. What was dosage and brand for Gamma E.