HYPOXIA #24: IS GOUT PROTECTIVE FOR HYPOXIA?

Purines are a natural substance found in the body. They are also found in many foods such as liver, shellfish, and alcohol. They can also be formed in the body when DNA is broken down. When purines are broken down to uric acid in the blood, the body gets rid of it when you urinate or have a bowel movement.  This removal process allows humans and birds to conserve mitochondrial water.  

Parkinson's disease patients suffer from hypoxia of their pigmented neurons in the brain.  This leads to melanin breakdown and lowered levels of endogenous dopamine.  Uric acid, a metabolite of purine biochemistry protects neurons from melanin degeneration and dopamine loss.  In primates, having a higher level of uric acid is protective of hypoxia in dopamine producing neurons.  It appears evolution knew what it was doing when it altered the uric acid pathways in the big brained primate clade. 

Parkinson's Disease (PD) patients have been found to have significantly lower levels of serum Uric Acid than controls (p = 0.000) in published research.  This fact is not well known in clinical medicine.  In fact, in patients on L-dopa the situation is even more dire and shows us why Big Pharma solutions often run contrary to nature's recipes.  In patients with PD serum UA levels were mush lower in the groups under L-Dopa + dopamine agonist treatment.  

Uric acid (urate) is often referred to as a waste product of purine metabolism (Johnson et al., 2009; Rock et al., 2013) by people who just do not understand its impact in big brained primates. Normally, it circulates at high levels in humans and other hominoids due to mutations in the gene encoding the urate-catabolizing enzyme urate oxidase (UOx) during primate evolution (Wu et al. 1992, Oda et al. 2002). 

In our species its circulating concentrations are so high they approach the limits of solubility.  Urate is best known clinically for the pain and damage that results when these limits are exceeded and urate crystallizes. When this occurs in joints it results in gout, a form of inflammatory arthritis triggered by urate crystals. Similarly, when urate (or more typically its acid form, uric acid) crystallizes in the urine then it can cause kidney stones.  People who have gout usually have serious blue light toxicity and melanopsin damage that lead to PD.  In fact, anyone with gout is a serious clue to me the quantum clinician that they have serious risks in their environment for damage to all melanin regions of the brain and skin.  

To illustrate this point, I'd like to tell you about one of my Kruse Longevity Farm patients I treated in the last year.  This person had many symptoms of undiagnosed mild Parkinson's Disease.  They came to me with many unusual symptoms that functional medicine doctors could not make sense of.  This particular patient had went to the Kresser Institute and had 9300 dollars of testing over a 9 month period of time and never received an answer about their neurologic and gut issues he had.   

After my nurse performed a review of systems and asked 45 minutes of questions I set down to review all the labs/tests that were ordered by 4 other clinicians.  Once I reviewed the history, I noticed two things.  The patient complained of a 3 year history of tinnitus, biannual bouts of gout, and a significant ENT history of cerumin accumulation and pale skin.  This caused severe ear pain and reddened ear drums and multiple rounds of prescription antibiotics.  After the first year, the person changed jobs and worked at night as an IT professional.  During the first year of symptoms, gut issues and sleep became hugely disrupted no matter what interventions were done.  As sleep worsened so did his cognition and motor abilities.  He noticed changes to his emotions as well. He developed a worsening ringing in his ears and began to have balance issues.  

When the patient arrived at my facility I asked pointed questions about the patients work environment after looking in their ears.  Upon looking in the ears I saw cerumin accumulation on one side compared to the other but there was significant erythema of both ear drums.  He was also sensitive to artificial light.  I removed the ear wax and noted the area underneath it was pale.   I also noted the pinna and external auditory canal were very pale and devoid of pigment.  I examined his skin and noticed some uneven melanosis in places.    

Immediately I asked about their use of cell phones, blue tooth, and nnEMF.  Then I got my answer.  The patient told me he used to use his cell phone to the ear 100% of the time but then his ENT physician convinced him to use wireless earbuds because of his ear problems to avoid putting the cell phone to his affected ear.  Within 3 months of using the ear pods the patients symptoms of mild tinnitus progressed to mild Meniere's disease with vertigo hearing loss and balance issues.  This got worse when he shifted to night time consulting work.  During this time he developed abnormal white skin patches over his torso and legs.   

I asked him if he had the ear pods during his visit with me.  He did.  He told me he used them frequently in his car or when he traveled for business.   I had him put them in the ear and we measured the nnEMF they emitted.  The picture below shows you what I found.  On his labs done at the Kresser Institute I noted three draws where his uric acids levels were off the charts.  The patient also had high blood pressure every time he had his uric acid drawn according to the chart review. 

This level of nnEMF was unbelievable.  The amount of radiation delivered to the ear, ear drum, cochlea, and brainstem.  The brain stem is where the vagal nuclei are that control the flow of autonomic information from the brain to the gut.  His eye exam showed an abnormal blink reflex, and his pupils hardly reacted to blue LED during direct eye exam, while reacting briskly to red LED during the eye exam.  This told me that there was a serious lack of dopamine in the pupillary mechanism.  The eye exam revealed a pale retina.  There was no change in refraction noted by the patient.  When I consolidated all these findings, my advice to them were to eliminate the ear buds, quit the night shift, begin a serious increase of building the solar callus every AM, use of  PBM/LLLT to the ears and head, and begin using my survivor's soup patreon recipe every day.  I also got him to wear blue blocking glasses with 550 BI tints anytime he was around blue light or in indoors behind glass.  He has used Luciaeyes,com blue blockers for the last 7 months.

The remainder of the patients extensive work up at the Kruse Longevity Center under my care showed no other sigficant abnormalities.  The patient instituted all my protocols and advice the symptoms for the most part improved within 3 weeks.  His Bristol stool score went from a 7 to a 4 in two weeks and all the GI symptoms improved quickly when he eliminated tech use to his ears and used more light from the sun and his red light I recommended.  His tinnitus improved over 6 months.  He grade his tinnitus at 7 out of ten at his initial visit, and at his 6 month follow up he reported it was now a 1 of 10.    His Meniere's symptoms resolved in 4 months 100%.  The patient was taught how to improve his skin's melanosis with sensible solar behavioral change and I used my light hygiene protocol to augment this result.  That protocol is devoid of any Big Pharma solutions.  His cognition and sleep improved over 3 months, and his uric acid levels normalized over the last year.  This case illustrates how nnEMF can destroy melanosis and cause abnormal neurologic symptoms, skin changes, and gut issues that lead to many low dopamine symptoms and disease phenotypes. 

WHY DID ALL THIS MAKE SENSE TO ME? 

Most people think high uric acid levels are pathologic.  This is not always true.  Many times people with electromagnetic sensitivities have high levels of uric acid to compensate for cellular hypoxia.  

Uric acid has been studied in several cardiorespiratory processes that produce hypoxia since this condition leads to increased catabolism of purines. In this sense, uric acid has shown me to be a useful as a prognostic marker of hypoxia from many causes.  This includes electromagnetic hypersensitivity, blue light toxicity,  heart failure, pulmonary thromboembolism, viral illness,  and primary pulmonary hypertension.  A higher uric acid level is a subtle sign of significant mitochondrial heteroplasmy from an unknown source linked to hypoxia.  So is a higher level of homocysteine.  Tissue hypoxia contribute to a sequence of events by leading to the depletion of adenosine triphosphate (ATP) and activation of purine nucleotide degradation to uric acid.

It appears this patients previous care givers did not know about these links.  That is why they missed it.  Uric acid is vilified by functional medicine practitioners because they are ignorant of how evolution has used it in primates.  It carries a negative connotation for many clinicians, but as a neurosurgeon, I am acutely aware that high levels of uric acid also are protective in traumatic brain injury, CNS trauma, and this is best seen in people with Parkinson's disease.  Uric acid has a significant potential for helping people with Parkinson’s disease and other neurodegenerative diseases that are exploding in this tech driven world.

Despite the known and theoretical adverse effects of higher uric acid levels in medical books, the evolutionary biology and biochemistry of uric acid suggests that its salubrious actions has a deep evolutionary purpose for large brained primates.  Uric acid appears to offset and possibly outweigh its detrimental effects (Álvarez-Lario & Macarrón-Vicente, 2010). Gout maybe a disease Nature gives is because uric acid protects us from cognitive decline and motor degeneration of low dopamine states.  I have also noted uric acid levels being higher in those with depression and bipolar disorder.  I believe this is a protective evolutionary response to a poor environment.  It turns out the uric acid-elevating inactivation of the urate oxidase enzyme in chimpanzees, gorillas, and humans can be attributed to multiple independent mutations in UOx during the speciation of primates (Wu et al. 1992, Oda et al. 2002).  This is unique to our evolutionary family.  

This is why many doctors have reported acute gout flare ups in patients with PD who were put on receiving L-dopa in combination with a decarboxylase inhibitor. It appears blockade of decarboxylation leads to major changes in the pattern of L-dopa metabolites. 

As such, the Black Swan clinician should reasonably presume that uric acid elevation conveys a critical survival advantage to our ancestors, with respect to their large brains. The discovery that uric acid possesses strong antioxidant properties, with a comparable or greater activity than ascorbate at their physiological concentrations in humans (Ames et al., 1981), suggested potential benefits of protection against oxidative stress. Uric acid decreases neuro-degeneration risks and this is likely why all primates have traded the higher levels of gout to protect their larger brains.

Might this be linked to the Warburg metabolism via glutamine?  Yes.  Glutamine enters the Krebs uric acid cycle. This move generates excess uric acid, and ammonia-N is excreted as uric acid-N. When this occurs cells require large inputs of glycine into the urea acid cycle along with, serine, and threonine, which serve as glycine precursors.  This is why I recommended the use of the survivor soup recipe to this patient.  That soup recipe is a glycine replacement mechanism for those who are tech addicted.  It is also why I recommended something called an Optimal Cocktail that I created at Kruse Longevity Center at Destin.  

This is an oral trouche we've created with one of my pharmacist Farm member's to offset low glycine states that appears with low dopamine states by taking advantage of the serine glycine interconversion pathway.   

Every mole of uric acid synthesized as the end-product of N metabolism requires one mole of glycine, and the loss of glycine incurs a loss of 12.5 ATP molecules.  This amount of ATP stresses mitochondrial function which is underperforming in a low dopamine disease.  This increase need for ATP is why red light therapy helps the low dopamine state.  

Since mitochondrial energy in the form of ATP is required to dispose of excess ammonia, it is apparent that ATP must be available for the urea cycle to properly function in low dopamine states. Thus, the urea cycle has to be closely linked physiologically to the citric acid cycle, which derives one of its nitrogens from the transamination of oxaloacetate to form aspartate and returns fumarate to the cycle while recycling metabolic water.  It was discovered in biochemical research that urea cycle disorders not only disturbe the metabolism of amino acids involved in the urea cycle but it also induce the accumulation of ammonia detoxification, but also interfered with the metabolism of amino acids related to some nervous systems, such as pipecolic acid and N-acetylaspartic acid.  

SUMMARY

Is urea and uric acid the same thing?

In contrast, mammals (including humans) produce urea from ammonia; however, they also form some uric acid during the breakdown of their nucleic acids. In this case, uric acid is excreted in urine instead of in feces, as is done in birds and reptiles. Uric acid is a compound similar to purines found in nucleic acids.  Since the end product nitrogen metabolism is ammonia in birds, in which ammonia cannot be synthesized by urea; thus, birds and humans are prone to the accumulation of uric acid.  Birds, like humans have high mitochondrial capacity.  This is no coincidence.  What else does uric acid reserve for birds and humans?  Water.  Metabolic water to be exact.   In birds and reptiles, and in some desert dwelling mammals (such as the kangaroo rat), uric acid also is the end-product of purine metabolism, but it is excreted in feces as a dry mass on purpose to conserve water.. This involves a complex metabolic pathway that is energetically costly in comparison to processing of other nitrogenous wastes such as urea (from the urea cycle) or ammonia, but has the advantages of reducing water loss and preventing dehydration.  Water is the key electromagnetic capacitor in cells that have high mitochondrial capacity.  Recall that mitochondria make metabolic water from metabolism.  

Purines are found in high concentration in meat and meat products, especially internal organs such as liver, shellfish, and kidney. In general, plant-based diets are low in purines.  This is another reason why a vegan diet stresses primates with a large brain and massive mitochondrial capacity.  

Aside from the crucial roles of purines (adenine and guanine) in DNA and RNA, purines are also significant components in a number of other important biomolecules, such as ATP, GTP, cyclic AMP, NADH, and coenzyme A.

There are many naturally occurring purines. Adenosine is one of the major ones that signals the onset of sleep.  This is why the patient above could not sleep well.  Some common human purines are the nucleobases adenine  and guanine . In DNA, these bases form hydrogen bonds with their complementary pyrimidines, thymine and cytosine, respectively.  You saw those appear in the last blog.   This is called complementary base pairing. In RNA, the complement of adenine is uracil instead of thymine.  It is also a purine. 

Other notable purines are hypoxanthine , xanthine, theobromine, caffeine, uric acid  and isoguanine.

Hans Kornberg wrote a paper entitled ‘Krebs and his trinity of cycles' commenting that every school biology student knows of the Krebs cycle, but few know that Krebs discovered two other cycles in biology. These are (1) the ornithine cycle (urea cycle), (2) the citric acid cycle (tricarboxylic acid or TCA cycle), and (3) the glyoxylate cycle that was described by Krebs and Kornberg. Ironically, Kornberg, codiscoverer of the ‘glyoxylate cycle’, overlooked a fourth Krebs cycle – (4) the uric acid cycle.  This cycle is critical in low dopamine states.  Anytime dopamine levels are lowered by blue light and nnEMF we should expect higher levels of uric acid to protect dopamine stores in pigmented cells in our body.  

The patient spent over 20,000 dollars in 3 years and got no answers.  He became a Farm member and with in 6 months he found his answer and got better without any need of a drug.  His cost of membership was much lower than he spent to solve this problem.  

CITES:

• Association of serum uric acid levels with the progression of Parkinson's disease in Chinese patients.Sun CC, Luo FF, Wei L, Lei M, Li GF, Liu ZL, LE WD, Xu PY.Chin Med J (Engl). 2012 Feb;125(4):583-7.PMID: 22490478

     Ames BN, Cathcart R, Schwiers E, Hochstein P.  Uric acid provides an antioxidant defense   in humans against oxidant- and radical-caused aging and cancer: a hypothesis.Proc Natl Acad Sci U S A. 1981 Nov; 78(11):6858-62.

   Serum uric acid levels and freezing of gait in Parkinson's disease.Ou R, Cao B, Wei Q, Hou Y, Xu Y, Song W, Zhao B, Shang H.Neurol Sci. 2017 Jun;38(6):955-960. doi: 10.1007/s10072-017-2871-3. Epub 2017 Mar 1.PMID: 28251464

• Pharmacokinetic-pharmacodynamic modeling of levodopa in patients with advanced Parkinson disease.Adamiak U, Kaldonska M, Klodowska-Duda G, Wyska E, Safranow K, Bialecka M, Gawronska-Szklarz B.Clin Neuropharmacol. 2010 May;33(3):135-41. doi: 10.1097/WNF.0b013e3181d47849.PMID: 20216409 Clinical Trial.
• Four pioneers of L-dopa treatment: Arvid Carlsson, Oleh Hornykiewicz, George Cotzias, and Melvin Yahr.Lees AJ, Tolosa E, Olanow CW.Mov Disord. 2015 Jan;30(1):19-36. doi: 10.1002/mds.26120. Epub 2014 Dec 8.PMID: 25488030 Review.
• Elevated homocysteine levels in levodopa-treated idiopathic Parkinson's disease: a meta-analysis.Hu XW, Qin SM, Li D, Hu LF, Liu CF.Acta Neurol Scand. 2013 Aug;128(2):73-82. doi: 10.1111/ane.12106. Epub 2013 Feb 21.PMID: 23432663 Review.
• Kornberg H.L. Krebs and his trinity of cycles. Nat. Rev. Mol. Cell Biol. 2000; 1: 225-228