High Serum LDH But Low CRP

[Ella]

It seems like I'm deficient in antidiuretic hormone or vasopressin.

What is your cortisol level like? Have your read the following two papers.

https://onlinelibrary.wiley.com/doi/full/10.1111/joim.12649

Vasopressin regulates renal calcium excretion in humans

You need further investigation - 24 hr urinary tests monitoring calcium etc., to decipher exactly what your status is. You may need to work with an endocrinologist as your GP may not be able to do the required testing. I don't how your medical system works in Manilla.

Is your vitamin D level in the good range and do you do muscle work? Do you spend time in the sun?
This brings us back to PTH and aldosterone - also inflammatory markers.

ResearchGate | Share and discover research

 

[yerrag]

What is your cortisol level like? Have your read the following two papers.

https://onlinelibrary.wiley.com/doi/full/10.1111/joim.12649

Vasopressin regulates renal calcium excretion in humans

You need further investigation - 24 hr urinary tests monitoring calcium etc., to decipher exactly what your status is. You may need to work with an endocrinologist as your GP may not be able to do the required testing. I don't how your medical system works in Manilla.

Is your vitamin D level in the good range and do you do muscle work? Do you spend time in the sun?
This brings us back to PTH and aldosterone - also inflammatory markers.

ResearchGate | Share and discover research

My cortisol levels look good, as based on my a.m. and p.n. tests on August 2017:

a.m. 398.60 nmol/L (ref 172-497)
p.m. 150.60 nmol/L (ref 74 -286)

As of Sep 2016, my 24 hr urine calcium was at 3.36 mmol/24hr (range of 2.50-7.50); my urine phosphorus at 31.42 (range 12.90-42.00)
As of Sep 2015, my 25-OH Vitamin D was 47.32 ng/mL (range >30).

I noticed, however, something odd, which was my serum ammonia levels are low: at <9 umol/L (range 9-30). I looked at www.labtestsonline.org, and it says low ammonia is related to hypertension. But that's all I can find about low serum ammonia in my searches.

My PTH has been within range at 40.06 pg/mL (range 15-65) as of Sep 2016. My ionized calcium is fine as well.

I haven't taken aldosterone test or vasopressin test. Both are expensive. Aldosterone at $72 and vasopressin at $160.

If vasopressin tests low, it would mean my pituitary is producing low levels of vasopressin and this may be related to a concussion I suffered from a car accident 30 years ago. But it isn't likely as it took twenty years for my hypertensive condition to show up. If vasopressin tests normal, it could mean that my kidneys aren't responsive to the signal from vasopressin, and still keeps urinating when vasopressin is telling it not to.

As for aldosterone, I'm so far drawing a blank on understanding it.

 

[yerrag]

And yes, elevated RBC can also cause slight elevations of LDH.

It turns out I'm not hypovolemic, but there is hypoxia in my kidneys. Hypoxia leads to producing EPO, and EPO leads to RBC production. In hypoxia, metabolism goes the anaerobic glycolytic pathway, and LDH enzyme is used. This could be why my LDH is borderline high. But since there's no inflammation, hsCRP and ESR shows negative for inflammation.

 

[Hans]

Elevated nitric oxide maybe? It can also cause hypoxia, then angiogenesis and fibrosis.
It also inhibits CO2 production and can create other toxic radicals such as peroxynitrite.

 

[yerrag]

It turns out I'm not hypovolemic, but there is hypoxia in my kidneys. Hypoxia leads to producing EPO, and EPO leads to RBC production. In hypoxia, metabolism goes the anaerobic glycolytic pathway, and LDH enzyme is used. This could be why my LDH is borderline high. But since there's no inflammation, hsCRP and ESR shows negative for inflammation.

Just got my EPO tests results and it's within range: 9.70 mIU/mL (ref 2.59-18.50). Although I'm not sure where the optimal range stands.

I was hoping this would confirm hypoxia, as would corroborate with my high uric acid levels (which is needs hypoxia to be high).

Elevated nitric oxide maybe? It can also cause hypoxia, then angiogenesis and fibrosis.
It also inhibits CO2 production and can create other toxic radicals such as peroxynitrite.

I did a salivary test for nitric oxide, and my nitric oxide is low. I would even think my nitric oxide is low also, because isn't nitric oxide a vasodilator, and my blood pressure is high, athough there are other factors affecting my blood pressure.

 

[Hans]

I did a salivary test for nitric oxide, and my nitric oxide is low. I would even think my nitric oxide is low also, because isn't nitric oxide a vasodilator, and my blood pressure is high, athough there are other factors affecting my blood pressure.

Infection, inflammation, endotoxins, stress, estrogen, serotonin, etc, etc, increases nitric oxide production. NO promotes vasodilation yes, but then also promotes vascular leakage, angiogenesis and then fibrosis over the long term. It difficult to test NO because its half life is very short and it get rapidly converted into other radicals. When NOS becomes uncoupled due to oxidative stress it creates mainly superoxide and a little NO. The NO binds with the superoxide and creates peroxynitrite. Peroxynitrite damages protein, lipids, DNA, etc., and can be rapidly converted to nitrate. So maybe NO could have been elevated for quite a while and then it started causing too much oxidative stress and then the situation flips where there are too little NO and mainly reactive oxygen species. Studies show that NO is low in people with CVD, hypertension, diabetes and so on, but there were always high NO at the start. They call it the NO/O2- ratio. First the ratio is high, but when NO has been doing damage for too long, the ratio starts to decline and superoxide predominates. That's why people think NO is low in hypertension. NOS is still very active, it's just mainly creating superoxide and the NO it's creating is converted to peroxynitrite.

 

[yerrag]

Infection, inflammation, endotoxins, stress, estrogen, serotonin, etc, etc, increases nitric oxide production. NO promotes vasodilation yes, but then also promotes vascular leakage, angiogenesis and then fibrosis over the long term. It difficult to test NO because its half life is very short and it get rapidly converted into other radicals. When NOS becomes uncoupled due to oxidative stress it creates mainly superoxide and a little NO. The NO binds with the superoxide and creates peroxynitrite. Peroxynitrite damages protein, lipids, DNA, etc., and can be rapidly converted to nitrate. So maybe NO could have been elevated for quite a while and then it started causing too much oxidative stress and then the situation flips where there are too little NO and mainly reactive oxygen species. Studies show that NO is low in people with CVD, hypertension, diabetes and so on, but there were always high NO at the start. They call it the NO/O2- ratio. First the ratio is high, but when NO has been doing damage for too long, the ratio starts to decline and superoxide predominates. That's why people think NO is low in hypertension. NOS is still very active, it's just mainly creating superoxide and the NO it's creating is converted to peroxynitrite.

That's very interesting and thank you for explaining it. I've really never understood NO as it appears to be a very elusive subject to really understand. I feel like it is a two-faced chimera that I have to try to get on its good side, or else I'm effed! So I'm getting to think that NO in itself is good, but when it becomes NOS it's bad. But only as far as my blood vessels losing the ability to dilate. But it's good in that it converts to NOS because it's needed to do same damage to pathogens. But there's also bad in that good because in the process of killing the pathogens there's some collateral damage on the good guys. And so some antioxidants, such as uric acid or albumin or glutathione, are needed to counter the 'mini' bad effect on NOS.

So, at my state I'm low in NO as NO, and this could affect my virility, and it could also affect my hair growth, given how a constricted vessel can affect the penis and the scalp's hair growth. As it certainly would affect my blood pressure. And if I'm high in NOS, I have to find out where this need for NOS comes from. But I'm at a loss, since hsCRP and ESR values are low, and it basically rules out the presence of inflammation.

If fibrosis in itself is constricting my blood vessels, would the hypoxia it induces be a cause of NOS, rather than the other way around (where NOS induces hypoxia)? Hypoxia would make the metabolic pathway into anaerobic glycolysis, and produce lactic acid, and turn it into a mini environment of high acidity. Would an acidic environment induce NOS?

 

[Hans]

That's very interesting and thank you for explaining it. I've really never understood NO as it appears to be a very elusive subject to really understand. I feel like it is a two-faced chimera that I have to try to get on its good side, or else I'm effed! So I'm getting to think that NO in itself is good, but when it becomes NOS it's bad. But only as far as my blood vessels losing the ability to dilate. But it's good in that it converts to NOS because it's needed to do same damage to pathogens. But there's also bad in that good because in the process of killing the pathogens there's some collateral damage on the good guys. And so some antioxidants, such as uric acid or albumin or glutathione, are needed to counter the 'mini' bad effect on NOS.

So, at my state I'm low in NO as NO, and this could affect my virility, and it could also affect my hair growth, given how a constricted vessel can affect the penis and the scalp's hair growth. As it certainly would affect my blood pressure. And if I'm high in NOS, I have to find out where this need for NOS comes from. But I'm at a loss, since hsCRP and ESR values are low, and it basically rules out the presence of inflammation.

If fibrosis in itself is constricting my blood vessels, would the hypoxia it induces be a cause of NOS, rather than the other way around (where NOS induces hypoxia)? Hypoxia would make the metabolic pathway into anaerobic glycolysis, and produce lactic acid, and turn it into a mini environment of high acidity. Would an acidic environment induce NOS?

Well I think it would be important to remove any NOS stimulators such as hypoxia, endotoxins, a virus, stress, etc, to stop any overproduction of NO or superoxide. So the problem might not be low NOS, but only low NO because its get converted to something else, or it binds to heme and inhibits a wide variety of enzymes.
Eeevated NOS is not something we want. CO2 should be the primary vasodilator, but we obviously do need a little NO. To enhance the bioavailability of NO, you want to reduce other free radical and provide BH4 for proper NO production. Too little BH4 will uncouple NOS to create superoxide instead of NO.

But like I mentioned, an excess of NOS will generate an excess of NO and in the short term it will cause vasodilation, but if it becomes chronic, it causes fibrosis and then hypertension.
So in both cases NOS stimulators should be removed and NOS should be inhibited if in excess to reduce superoxide production. You might have already have resolved any NOS stimulators, but now you still struggle with the consequence. NO will provide little vasodilation if there is fibrosis, so stimulating NOS might not help. It might help to have enough arginine around as well as BH4 so that if the body wants to make NO it can, and not make superoxide instead.
Nitrotyrosine is a marker that will indicate tissue damage from peroxynitrite.

 

[yerrag]

Well I think it would be important to remove any NOS stimulators such as hypoxia, endotoxins, a virus, stress, etc, to stop any overproduction of NO or superoxide. So the problem might not be low NOS, but only low NO because its get converted to something else, or it binds to heme and inhibits a wide variety of enzymes.
Eeevated NOS is not something we want. CO2 should be the primary vasodilator, but we obviously do need a little NO. To enhance the bioavailability of NO, you want to reduce other free radical and provide BH4 for proper NO production. Too little BH4 will uncouple NOS to create superoxide instead of NO.

But like I mentioned, an excess of NOS will generate an excess of NO and in the short term it will cause vasodilation, but if it becomes chronic, it causes fibrosis and then hypertension.
So in both cases NOS stimulators should be removed and NOS should be inhibited if in excess to reduce superoxide production. You might have already have resolved any NOS stimulators, but now you still struggle with the consequence. NO will provide little vasodilation if there is fibrosis, so stimulating NOS might not help. It might help to have enough arginine around as well as BH4 so that if the body wants to make NO it can, and not make superoxide instead.
Nitrotyrosine is a marker that will indicate tissue damage from peroxynitrite.

Thanks Hans. I think the only NOS stimulator I have left is hypoxia. And to resolve it I have to do away with fibrosis. And I'll be using a combination of fasting and the use of proteolytic enzymes to remove the fibrosis in the extracellular matrix in my kidneys. And then perhaps rebuild the ECM with the help of intake of collagen and vitamin C. And if these aren't enough, I would resort to CO2 bath therapy in the hope that CO2 can permeate the cells and provide vasodilatory action in antagonizing NOS. This I detailed here: "Essential" Hypertension And Appreciating It For What It Really Is

 

[yerrag]

Thanks Hans. I think the only NOS stimulator I have left is hypoxia. And to resolve it I have to do away with fibrosis. And I'll be using a combination of fasting and the use of proteolytic enzymes to remove the fibrosis in the extracellular matrix in my kidneys. And then perhaps rebuild the ECM with the help of intake of collagen and vitamin C. And if these aren't enough, I would resort to CO2 bath therapy in the hope that CO2 can permeate the cells and provide vasodilatory action in antagonizing NOS. This I detailed here: "Essential" Hypertension And Appreciating It For What It Really Is

Hans, glad you gave me some ideas to pursue.

Now I've arrived at a hypothesis for what ails me, and what's vexed me is because it involves a vicious cycle. Hypoxia causes high lactate (anaerobic glycolysis, evidenced by high serum LDH). High lactate at the proximal tubule of kidneys interferes with renal excretion of uric acid. With low renal UA excretion, serum uric acid increases. High uric acid causes low nitric oxide, and low nitric oxide causes vasoconstriction, and this leads to hypoxia.

This cycle would explain why my serum LDH is high (just high enough to be above range), but since it does not involve inflammation, my hsCRP and ESR stays low.

I also don't think the hypoxia is from fibrosis. This is because my serum EPO tests normal, and this would not indicate that HIF-1a levels are high, and since HIF-1a levels are low, this would make the chances for fibrosis to develop to be less likely. With low HIF-1a, VEGF is likely low as well, as this makes angiogenesis less likely to occur. If fibrosis is less likely, then hypoxia is less likely to originate from fibrosis.

This leaves me to focus on pinning down the vicious cycle outlined above as the cause of hypoxia that leads to hypertension.

When I did one day of dry fasting, I noticed my heart rate increasing significantly (from 70 to 91) and my blood pressure going down (from 201/121 to 181/123). While one day doesn't make a trend, it makes me wonder if the increased heart rate is the result of the hypoxic condition being ameliorated, as hypoxia would cause the downregulation of mitochondrial oxygen consumption. The lower blood pressure may also indicate less hypoxia and increased NO. During the fast, was it possible that uric acid production was downregulated, such that uric acid levels went down?

HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. - PubMed - NCBI
High Altitude Renal Syndrome (HARS)
Inactivation of Nitric Oxide by Uric Acid

 

[yerrag]

I'm now suspecting that hemolytic anemia is what's causing my LDH (at around 225) to be above range. Hemolytic anemia, technically, is a condition where red blood cells are being destroyed faster than they are being made. I don't technically fall under that classification yet, as my RBC, hemoglobin, and hematocrit are actually high. But I think, though, that they are high because as some red blood cells are being destroyed, new red blood cells (reticulocytes) are already produced and ready to replace them. With the dying and their replacement still being counted, it makes it appear that my RBC is high.

I just had a reticulocyte count blood test to determine if indeed I have a high level of reticulocytes. Tomorrow, I'll know the results.

Hemolytic anemia may explain why LDH is high, as the enzyme is being released as the red blood cells are being destroyed. Why I think my red blood cells are being destroyed? I think it's caused by a deficiency of an enzyme called G6PD. This enzyme helps red blood cells work properly. A deficiency leads to the destruction of red blood cells. Why is there a deficiency of G6PD? Excess aldosterone, or hyperaldosteronism, is the cause. I tested 2.44 ng/dL on my serum aldosterone (supine), but I can't use that information enough to tell if I have high aldosterone. No one in this forum seems to know. Nor is this information available in my searches. Giving up on getting that information, I have to get a test on G6PD next week. This way, I will know the most likely cause of my high LDH, and it may also help to confirm that my aldosterone is high (Aldosterone Impairs Vascular Reactivity By Decreasing Glucose-6-phosphate Dehydrogenase Activity).

Knowing my aldosterone is high may lead to me finding the real cause of my hypertensive condition.

My hsCRP is at 0.8, which would seem low, but it is high enough to indicate there is a tiny bit of inflammation going on, and the finger of blame points to G6PD deficiency. This deficiency leads to oxidative stress, and this oxidative stress would be the reason why nitric oxide is low, and why my blood vessels can't dilate, and why my blood pressure is high.

G6PD is the rate-limiting enzyme of the pentose phosphate pathway. I am sure there are other implication to this, but I have to read up on this.

 

[yerrag]

I just had a reticulocyte count blood test to determine if indeed I have a high level of reticulocytes. Tomorrow, I'll know the results.

Oddly enough, my reticulocyte count turned out lower than range, at 0.45, with optimal range being 0.5 -1 . This blows my guess of hemolytic anemia away, as well as it being the cause of slightly high LDH away as well.

I'm left to have a G6PD test next week. I'll also do a peripheral blood smear, together with a CBC w/differential. This would allow me to examine my red blood cells to give me a clue as to what's wrong with my red blood cells. Having the G6PD test adds context to it. It doesn't seem though that I would have G6PD deficiency, as my RBC and hemoglobin values are higher than optimal. If anything, a G6PD would more likely lead to low RBC, hemoglobin, and hematocrit values.

 

[yerrag]

Oddly enough, my reticulocyte count turned out lower than range, at 0.45, with optimal range being 0.5 -1 . This blows my guess of hemolytic anemia away, as well as it being the cause of slightly high LDH away as well.

I'm left to have a G6PD test next week. I'll also do a peripheral blood smear, together with a CBC w/differential. This would allow me to examine my red blood cells to give me a clue as to what's wrong with my red blood cells. Having the G6PD test adds context to it. It doesn't seem though that I would have G6PD deficiency, as my RBC and hemoglobin values are higher than optimal. If anything, a G6PD would more likely lead to low RBC, hemoglobin, and hematocrit values.

I didn't do the 6GPD test, but got the results for my CBC and my peripheral blood smear. I didn't do the 6GPD because it's more expensive, and would do it if my peripheral blood smear had bad findings. But my peripheral blood smear gave very good results :

Peripheral blood smears show normochromic,normocytic red blood cells. White blood cells seen are mostly neutrophils. No blast seen. Platelet number and morphology within normal.

My CBC continues to show my RBC, hemoglobin to be high, although my hemotocrit is now optimal (optimal values are from Dr. Weatherby)-

RBC - 5.43 ref 4.63 - 6.08; optimal 4.2 - 4.9 (male)
Hgb - 160 ref 137 - 175; optimal 140 - 150 (male)
Hct - 0.46 ref 0.40 - 0.51; optimal 0.40 - 0.48 (male)

The only thing that explains this is dehydration (although my low albumin, normal total protein, normal sodium, normal potassium, normal BUN) suggests otherwise.
Be that as it may, dehydration may simply mean low blood volume, and the low blood volume could cause my LDH to be higher, enough to tip it slightly above optimal range.

I still have problems with waking up at night to urinate, and the heavy urination is a sign I'm not holding enough water in my blood/ecf. And my hypertension lends weight to the possibility that I have low blood volume.

Other than LDH being slightly above optimal range, I also have serum aldosterone level at 24.4 ng/dL, which is above the 15 ng/dL mark upon which primary aldosteronism can be considered. This may explain my heavy urination.

I suppose my focus has to be on increasing blood volume, and a sign my blood volume has become normal would be when I stop urinating so much, to be confirmed by optimal values in RBC, hemaglobin, and hemotocrit, and by lower LDH readings. Also, my hsCRP could stand to be go down to 0.6 from its current 0.8.

@Hans I have two bottles of Pansterone (pregnenolone and DHEA) and a bottle of Progestene. Since you mentioned DHEA as helpful in reducing CRP, how much DHEA would you recommend? I think the next step for me is to use some of these hormones to assist my adrenals by way of reducing the production of aldosterone. I'll also be taking more salt to help bring my blood volume up.

It would be helpful if I took an ARR (aldosterone renin ratio) test to see if my high aldosterone is the result of renin causing it to be high. A value of 50 would establish that my aldosterone is high on its own, without renin causing it. Then it would be a matter of something wrong with the adrenals causing the high production of aldosterone. But ARR costs $220, so I'm not ready yet to part with it.

 

[Hans]

@Hans I have two bottles of Pansterone (pregnenolone and DHEA) and a bottle of Progestene. Since you mentioned DHEA as helpful in reducing CRP, how much DHEA would you recommend? I think the next step for me is to use some of these hormones to assist my adrenals by way of reducing the production of aldosterone. I'll also be taking more salt to help bring my blood volume up.

I'd advise just the regular Peat dose of 5-15mg daily for DHEA. :) Topically could be best because oral dose achieves only 3% that of subcutaneous injection and 33% that of topical. So topical is much more potent.

 

[yerrag]

I'd advise just the regular Peat dose of 5-15mg daily for DHEA. :) Topically could be best because oral dose achieves only 3% that of subcutaneous injection and 33% that of topical. So topical is much more potent.

Thanks Hans. I'll use Pansterone, and the added pregnenolone wouldn't hurt.

 

[yerrag]

In my opinion, this is a highly probable cause of the high LDH (although it's just barely above range) I'm experiencing:

Iron is an essential growth factor for most bacteria. Unlike many other microorganisms, P. gingivalis does not produce siderophores to sequester and transport iron. Instead, the bacterium utilizes specific proteases such as gingipains and surface-associated proteins to acquire iron from host heme [43]. Proteolytic gingipains Kgp and Rgp play an important role in the acquisition of iron by releasing heme from hemoglobin [43].

Surface-expressed hemagglutinins mediate the acquisition of heme through erythrocyte binding [47].

From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405727/pdf/zjom-9-1300366.pdf#page=3

Finally, I'm able to find the cause of my high LDH.

I was perplexed why this marker of inflammation is high, as my hsCRP and ESR values are normal, and they don't confirm there is presence of high inflammatory conditions. Now, I think I can lay this question to rest.

It makes sense now, as my ferritin is high also. And it's because the body is keeping iron away from p. gingivalis bacteria, and the bacteria has to acquire iron from red blood cells.