High dose folate, B2 and elevation of ammonia and uric acid (for dummies)

[Gondwanaland]

I will not elaborate, I think this info speaks for itself...

Some individuals are more susceptible than others, but the basic physiology is the same for everyone.

Open for discussion!

Source: http://www.health-science-spirit.com/HF5-2.html (modified)

(Previously posted here )

Ammonia
In physiology
Ammonia also plays a role in both normal and abnormal animal physiology. It is biosynthesised through normal amino acid metabolism and is toxic in high concentrations.[63] The liver converts ammonia to urea through a series of reactions known as the urea cycle. Liver dysfunction, such as that seen in cirrhosis, may lead to elevated amounts of ammonia in the blood (hyperammonemia). Likewise, defects in the enzymes responsible for the urea cycle, such as ornithine transcarbamylase, lead to hyperammonemia. Hyperammonemia contributes to the confusion and coma of hepatic encephalopathy, as well as the neurologic disease common in people with urea cycle defects and organic acidurias.[64]
Ammonia is important for normal animal acid/base balance. After formation of ammonium from glutamine, α-ketoglutarate may be degraded to produce two molecules of bicarbonate, which are then available as buffers for dietary acids. Ammonium is excreted in the urine, resulting in net acid loss. Ammonia may itself diffuse across the renal tubules, combine with a hydrogen ion, and thus allow for further acid excretion.[65]

Excretion
Main article: Excretion
Ammonium ions are a toxic waste product of the metabolism in animals. In fish and aquatic invertebrates, it is excreted directly into the water. In mammals, sharks, and amphibians, it is converted in the urea cycle to urea, because it is less toxic and can be stored more efficiently. In birds, reptiles, and terrestrial snails, metabolic ammonium is converted into uric acid, which is solid, and can therefore be excreted with minimal water loss.[66]

Don't miss the excellent chart "Reference ranges for blood tests, comparing blood content of ammonia (shown in yellow near middle) with other constituents" in the link above

How salicylates can worsen high ammonia (they also need to be neutralized with bicarbonate):

The origin and secretion of pancreatic juice bicarbonate

Abstract

1. The rate of secretion from a saline-perfused preparation of the cat's pancreas is directly proportional to the perfusate bicarbonate concentration. When all bicarbonate is omitted, secretion completely or almost completely ceases.

2. Incorporation of [14C]bicarbonate into the perfusion fluid results in its prompt appearance in the juice. The radioactive label is concentrated four to five times in the juice just as the total juice bicarbonate is four to five times greater than perfusate bicarbonate.

3. These two observations suggest that about 95% of pancreatic juice bicarbonate is derived from perfusate (plasma) bicarbonate.

4. The inhibition of pancreatic secretion from the perfused gland by acetazolamide is similar to that observed in the intact animal.

5. There is a fall in pH and rise in PCO2 in the perfusion fluid leaving the gland which is greater during secretion than at rest.

6. It is therefore suggested that during secretion, hydrogen ions pass from the gland into the perfusate (plasma), thus increasing the production of carbon dioxide from circulating bicarbonate. This carbon dioxide diffuses into the cell, is rehydrated (partly under the influence of carbonic anhydrase) and finally is secreted, thus establishing the necessary gradient for the continued diffusion of carbon dioxide into the cell.

Looking further into it:

Pancreatic Bicarbonate Secretion Involves Two Proton Pumps

Abstract

Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express H+/HCO3− transporters, which depend on gradients created by the Na+/K+-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and non-gastric H+-K+-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H+-K+ pump inhibitors and ion substitutions. Gastric and non-gastric H+-K+ pumps were demonstrated on RNA and protein levels, and pumps were localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H+/HCO3− and fluid transport shows that the H+-K+ pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely other epithelia. Furthermore, because pancreatic ducts play a central role in several pancreatic diseases, it is of high relevance to understand the role of H+-K+ pumps in pathophysiology.

 

[Martial]

so based on this information it is suggested to keep b 9 and b 2 at lower or balanced levels?

 

[Gondwanaland]

so based on this information it is suggested to keep b 9 and b 2 at lower or balanced levels?

I don't make any suggestion in that area since I am a dummy on that but transdermal bicarb (plus oral magnesium oxide) reversed all my issues with salicylate intolerance, high acid uric and ammonia build up.

 

[Sherlock]

magnesium

Did you find that Mg raised body temp? Not just night sweats, but overall more warm?

 

[Martial]

I don't make any suggestion in that area since I am a dummy on that but transdermal bicarb (plus oral magnesium oxide) reversed all my issues with salicylate intolerance, high acid uric and ammonia build up.

Thanks for the tips on the magnesium again, I don't really know if I have ammonia or salicylate issues but good stuff to know.

 

[Gondwanaland]

This is how I gauged for bicarb need:
dissolve 1/8 tsp of sodium bicarb in one glass of water and make mouth swishes. You will know if you need more.
I actually never drank it, but it was a great relief for constant dry mouth and tongue.

Next step is to do a foot bath (alternatively you can also soak your hands).

Shower scrub.

Bicarb bath. Before a full immersion I recommend to test your urine pH. I jumped in the bathtub when mine was 4.5 in the evening.

I must thank @ahmo who taught me all this months ago.

 

[Gondwanaland]

Did you find that Mg raised body temp? Not just night sweats, but overall more warm?

I am sure I posted a list of symptoms relieved by magnesium oxide. Magnesium fixed temperature, intolerances, sleep, breathlessness, depression etc. After the tipping point it caused nightsweats to return.

 

[Gondwanaland]

WARNING:

Successful management of uric acid nephrolithiasis with potassium citrate

Abstract
Successful management of uric acid nephrolithiasis with potassium citrate. Eighteen patients with uric acid nephrolithiasis (six with uric acid stones alone and 12 with both uric acid and calcium stones) underwent long–term treatment (1 to 5.33 years, mean of 2.78 years) with potassium citrate (30 to 80 mEq/day, usually 60 mEq/day). Urinary pH increased from low (5.30 0.31 SD) to normal (6.19 to 6.46) during treatment. Urinary content of undissociated uric acid, which was high to begin with at 204 82 mg/day, decreased to the normal range (64 to 108 mg/day) following treatment. Urinary citrate rose from 503 225 mg/day to 852 to 998 mg/day. Urinary saturation of calcium oxalate significantly declined with potassium citrate treatment. New stone formation rate declined from 1.20 1.68 stones/year to 0.01 0.04 stones/year (P < 0.001 by chi square). Remission was experienced in 94.4% of patients, and the group stone formation rate declined by 99.2%. Detailed case reports were obtained in five patients showing different responses between sodium alkali and potassium alkali treatment. All five patients had persistently low urinary pH (typically < 5.5) and normouricosuria, and four had hyperuricemia. Before treatment, they had stones surgically removed or spontaneously passed, which were pure uric acid in composition. When sodium alkali was give (as bicarbonate or citrate, 60 to 118 mEq/day), new stone formation continued in four patients, and a radiolucent (uric acid) calculus become "calcified" in the remaining patient. The stone analysis disclosed calcium oxalate in five patients and calcium phosphate in three patients. When potassium citrate (in four cases) or potassium bicarbonate (in one case) was offered instead over 1 to 3.5 years (at a dosage of 60 to 80 mEq/day), no new stones were formed. The results provide physiological and physicochemical rationale, as well as therapeutic efficacy for potassium citrate treatment in the management of uric acid lithiasis presenting with/without calcium stones.

 

[Gondwanaland]

WARNING:

Sodium and potassium urate crystals differ in their inflammatory potential.
Abstract
Uric acid (UA) is identified as a danger signal released from dying cells. It precipitates in sodium-rich extracellular fluid and in potassium-rich intracellular fluid as monosodium urate (MSU) and monopotassium urate (MPU), respectively. Here, we examined the structural and functional features of these crystals. In contrast to MPU MSU crystals induced reactive oxygen species production and release of pro-inflammatory cytokines in whole blood ex vivo assays. These results show that the cation of urate crystals determines the response of innate immune cells, indicating that the micromilieu at the site of crystal formation is important for their inflammatory potential.

 

[ahmo]

OK, here's my contribution. I've only just found this page, not spent any time with it, but maybe it can contribute to our understanding of ammonia....not that me staring at the page would make me any less of a dummy!
http://themedicalbiochemistrypage.org/nitrogen-metabolism.php#regulation

 

[Gondwanaland]

Thanks, @ahmo ! Understanding the Urea Cycle is crucial for me.

With my previous post with the research published in the "Autoimmunity" journal I have reached a new understanding of my pain. Also, now I know WHY potassium can help. Unfortunately potassium on its own either upsets my stomach (any form), gives me severe brain fog / electrolyte imbalances (KCl), or lowers my BP too much (K bicarb). I find that if I take a fraction of an electrolyte capsule it helps a little

 

[Gondwanaland]

Urea cycle
The urea cycle is a metabolic pathway that results in the formation of urea using two ammonium molecules and one bicarbonate molecule.[1] This route commonly occurs in the hepatic cell of the liver. (The reactions related to the urea cycle produce NADH). This NADH can be produced in two different ways. One of these uses oxaloacetate. In the cytosol there are fumarate molecules. Fumarate can be transformed into malate by the actions of the enzyme fumarase. The malate suffers the actions of malate dehydrogenase enzyme and it becomes oxaloacetate and producing a molecule of NADH. After that, oxaloacetate will be recycled to aspartate, as transaminases prefer these keto acids over the others. This recycling maintains the flow of nitrogen into the cell.

Apparently the transdermal bicarbonate is loosing its effectiveness with me to counteract uric acid and the probable causes could be related to the warnings I posted above.

I have been taking a B complex in the morning which turns me into a zombie for a few hors (pain + anesthesia at the same time) and then it starts to subside around noon and I get well after taking my multimin (Se + Zn + Cu + Mn + Boron). Tomorrow I will try the Multimin in the morning and perhaps skip the Bcompl.

Next I am looking into antagonizing / reducing Molybdenum rich foods due to its role in xanthine oxidase and uric acid formation. AND stay away from prebiotics.

Molybdenum Antagonists / Inhibitors:
Copper, fluoride, magnesium, zinc, tungsten, tin, phosphorus, selenium.

Molybdenum Sources:
Legumes, lentils, beans and soybeans, cauliflower, grains, nuts, organ meats.

Uric acid / gout sufferers, biochem literates out there please help!

@Peyt @adreno @Sidereal @alex3619 @Vegas @pone @Sherlock @drob31 @Mya Symons

 

[ahmo]

FWIW someone has just forwarded me this comprehensive molybdenum page. The left hand column lists various biological functions. The site is about molybd in the broadest sense. http://www.imoa.info/HSE/environmental_data/biology/copper.php

 

[alex3619]

I can understand not wanting to take molybdenum supplements in this position, but I am not sure why avoiding molybdenum rich foods is desirable. Molybdenum deficiency can result in severe neurological symptoms, sometimes fatal, and problems with sulphur containing foods. It may also lead to decreased mitochondrial function. Indeed molybdenum became popular in the late 90s in some circles for treating CFS.

Do you have active gout?

It was unclear from the first post why salicylates are a problem in this context (though there are plenty of other reasons) nor why bicarbonate helps. A healthy gut starts alkaline in the mouth, goes acidic in the stomach, and then becomes alkaline again in the small intestine. Manipulating intestinal pH with bicarbonate is not a good idea. Bicarbonate to correct acidity in the blood may be of use though, particularly during active periods, and a growing number of patients find it is helpful with PEM. It is not clear to me its useful while resting.

Gout was one of my early (wrong) diagnoses due to high serum uric acid. I did not have gout. My pains were more muscular than typical gouty joint pains.

Uric acid is an antioxidant. It is as likely to be helping as hindering unless there are other reasons. If you have gout crystals causing inflammation then that is a good reason.

I have not investigated ammonia issues in depth, so I cannot currently advise on this.

 

[Gondwanaland]

@alex3619 Thanks for your input. I know this thread lacks coherence, sorry. I just keep losing my thread of thought lately.

I am right in the midlle of a pain crisis after having taken 250mcg of vitamin K2-MK4 on Jan 1st. I don't know how it raises uric acid. Counter-intuitively, it felt like taking heparin (still have to research about heparin and uric acid). I have joint and bone (?) pain.

I do not have gout, but my serum uric acid levels have always been top of or a little above range (and this runs in my father's family).

I forgot to tag @aaron_c to this thread!

 

[alex3619]

@Gondwanaland, don't be concerned about lacking coherence. There are times I cannot even compose a single sentence. With ME we have to live with this every day. Fortunately threads give us an opportunity to expand and extend our discussion.

I am not sure highish uric acid is an issue. As I said earlier I cannot comment on ammonia though.

 

[Gondwanaland]

At this point I am not sure anymore it I am hurting still due to the K2 or due to something else I am taking or eating.

I found the sodium (bicarb) conexion intriguing. So today no bicarb scrub for me. Let's see how I wake up tomorrow.

 

[Gondwanaland]

TMI alert

Some other ideas for dealing with uric acid buildup, I am currently working my way through various xanthine oxidase inhibitors. Cherry extract didn't do much but grape seed extract seems to actually be easing joint pain. I'm also going to try inositol and quercetin. I know many here don't do well with phenols so obviously caution is needed.

I started a trial with cherry extract ( @Sherlock ) and I fellt it pushing uric acid crystals out of the body (increased urination and salivation), bad taste under the tongue (detox?), but stopped after taking it only 2x due to a side effect - hemorrhoid felt like there was glass inside the swollen vein. (TMI I know) Back in 2010 I had to extract blood clots from the hemorrhoids 2x (in the year before my DVT).

I took the cherry extract at bed time and the following morning felt like my joint and back pains were still there, but a bit numb (which was good, or at least "better than bad").

I take Gamma E + fishoil to help with blood flow. My questions are:
- what is the cherry extract doing?
- what experience do you guys have with this and other supps for lowering uric acid?

The best one I took so far was mB12, but I can't take it while my T3 is still low. (trying to convince my dr. to prescribe me higher T3)

 

[Sidereal]

TMI alert

I started a trial with cherry extract ( @Sherlock ) and I fellt it pushing uric acid crystals out of the body (increased urination and salivation), bad taste under the tongue (detox?), but stopped after taking it only 2x due to a side effect - hemorrhoid felt like there was glass inside the swollen vein. (TMI I know) Back in 2010 I had to extract blood clots from the hemorrhoids 2x (in the year before my DVT).

I took the cherry extract at bed time and the following morning felt like my joint and back pains were still there, but a bit numb (which was good, or at least "better than bad").

I take Gamma E + fishoil to help with blood flow. My questions are:
- what is the cherry extract doing?
- what experience do you guys have with this and other supps for lowering uric acid?

The best one I took so far was mB12, but I can't take it while my T3 is still low. (trying to convince my dr. to prescribe me higher T3)

Wow, that sucks. I have no idea what's going on there. I had a bad taste in mouth when I was taking cherry extract now that I think about it. I tried various supplements for gout and they all caused some weird side effect. I am taking allopurinol now to try and deal with a very troublesome crystal in my right index finger that just won't go away.

 

[Gondwanaland]

crystal in my right index finger that just won't go away.

Have you tried hand soaks in bicarb or magnesium oxide?

DH took Tart Cherry Extract for 4 evenings in a row and is feeling increased joint pain. These supps surely mobilize uric acid. Apparently the trouble begins when they are deposited in undesireable places