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Uric Acid: Part 1 of a 3-Part Series

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In 1904, Havelock Ellis found in his “A Study of British Genius” that there was an unusually high rate of gout among eminent men in his study.  Gout is associated with higher volumes of uric acid (or urate) in the blood.  He, therefore, suggested that it might have something to do with it. (R)

Later investigators have examined this relationship, and there is indeed a correlation.  A review found only a slight correlation between IQ and uric acid.  However, there was a stronger correlation between uric acid and scholastic achievement, even after controlling for IQ. (R)

Another study found a correlation (+.37) between uric acid and publication rates of university professors. This is extremely significant for just one measure tested.  Insane. (R)

Uric acid has a similar chemical structure to that of caffeine, and can maybe act as a natural stimulant. (R)

Other Benefits of Uric Acid

Uric acid levels correlate with longevity in monkeys and animals.  This is presumably because of urate’s antioxidant properties. (R)

Uric acid levels are much lower in people with Multiple Sclerosis (MS) and a study with 11 people found correcting these levels are therapeutic.  (R)

In fact, it prevented the progression of MS in all 11 patients tested and even improved the symptoms of some patients. (R)

Like MS, low uric acid also correlates with Parkinson’s, Alzheimer’s and Huntington’s. (R, R2)  Clinical trials are underway to determine if raising urate levels will slow the disease in people.  Animal models have

Uric acid reduced Th1 immune dominance in people with MS (R), which is good for me.

As a natural antioxidant, urate provides up to 60% of the antioxidant capacity in human blood.  It also provides protection from the free radicals that it doesn’t neutralize. (R)

However, recent studies indicate that these mechanisms couldn’t explain all of its beneficial effects in the brain. (R)

Studies have found that urate was neuroprotective by protecting neurons from glutamate-induced toxicity, a central cause of neuron degeneration. (R)

In mice with autoimmune conditions, urate was beneficial and increased the survival rate.  (R)

On a cautionary note, uric acid can increase Th17 inflammation if inflammation is present (IL-1b, IL-18). (R)  It can be inflammatory in general if you have too much.  (R)

Too high or too low levels of uric acid are not good. Too low leads to oxidative stress, but too high can also lead to inflammation, gout and kidney stones. (R)

This is why it’s important to measure your Uric acid levels before you embark on a journey to increase it.

Screenshot 2014-12-29 20.39.42(R)

How too much uric acid causes inflammation:

fig2

How to Increase Uric Acid

Zinc elevates uric acid if you’re deficient. (R)

Animal products increase uric acid in general. (R)   Fructose can also increase uric acid (R), but I don’t know at what dosage or if it does in humans.

Dairy and maybe calcium lower uric acid levels, which explains why vegans have higher levels than omnivores. Soy might also increase urate levels. (R)

Estrogen increases uric acid excretion, which explains why men have higher levels than women.  (R)

In general, diet was more of a factor in men in its ability to influence urate levels rather than women. (R)

Inosine, found in liver and fish, is the most powerful way to increase uric acid levels.  (R)  This is what’s used in studies with MS and Parkinson’s.

Inosine Effects

Inosine has been shown to have antidepressant effects in mice through increasing brain growth (via BDNF, MAPK, adenosine antagonism).

Inosine increases RNA and DNA production and blood oxygen carrying capacity, which preserves ATP levels.

In a clinical trial with MS patients, Inosine more than doubled uric acid levels (increased from 3.9 to 8.3).

It decreased Nitrotyrosine,a marker of cell damage and inflammation, by more than half (from 73 to 32). (R)

It increased IL-10 and IL-13, which are Th2 cytokines.  IL-10 is an anti-inflammatory cytokine.  Mac-1 is a marker of inflammation and it more than halved (from 2.7 to 1.2).

Screenshot 2015-01-03 09.30.03
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189001/

My Experience With Inosine: It’s Amazing

For my first dosage, I took 3 grams in one shot, as an experimental dosage.

For me, it certainly increases cognitive performance and is wakeful promoting.  It works.

However, it also caused some slight pain in random places, one of which was my kidneys.  Kidney stone formation is very common with inosine supplementation.

I’m still going to include 500mg 1X a day and see how that works in the long term.

Caution

There are some negatives to uric acid/inosine such as gout and kidney stones, so be careful.  In studies with MS and Parkinson’s, kidney stones were quite common from inosine treatment (up to 1/4 people got it).

However, in the studies that were in a  controlled environment,  the patients were properly hydrated and none of them got kidney stones. (R)

You need to drink a ton of water (over a gallon) and take potassium citrate to prevent kidney stones.

Uric acid is also capable of binding iron (R), so be careful if you’re anemic.

If you need to supplement with calcium because you’re not getting enough from your diet, it’s better to use the citrate form.  I also recommend magnesium citrate.

I’m still taking a risk, but I like the effect enough that it’s worth it for me.

Buying Inosine

Increasing Inosine

Uric Acid on SelfDecode

Genes that Control Uric Acid Levels

SLC2A9 Gene-The Absorptive Urate Transporter:

The SLC2A9 gene encodes the glucose transporter 9 protein (GLUT4). It transports fructose and aids in the reabsorption of filtered urate by proximal tubules in the kidney. Loss-of-function mutations in this gene can cause hereditary hypouricemia due to reduced urate absorption  (R).

  1. RS10017674 
  2. RS10018204 
  3. RS1014290 – The “G” allele is associated with a lower age at onset of Parkinson’s disease (R).Individuals with the TT genotype had higher blood uric acid levels after increasing their consumption of soft drinks (R).The GG genotype is associated with significantly higher serum uric acid levels when compared with the TT/TG genotypes (R).
  4. RS1079128 
  5. RS10805346
  6. RS11722228– The “T” allele is linked to higher blood uric acid levels in females compared to males (R).
  7. RS12498150 
  8. RS12498742 – Each copy of the minor “G” allele reduces the risk of gout (R).
  9. RS12498956 
  10. RS13103879 
  11. RS13129697 – The “C” allele is linked to lower blood urate levels in the Croation population (R).
  12. RS13131257 – The “T” allele is associated with lower blood uric acid levels in Mexican Americans (R).
  13. RS13328050 
  14. RS16868246 
  15. RS16890979 
  16. RS17185835 
  17. RS17185870 
  18. RS1850744 
  19. RS2018643 
  20. RS3733585 – The “G” allele is associated with cleft palate (R).
  21. RS3733591 -The “C” allele increases the risk of severe gout for some populations (R).
  22. RS3775948 -The “G” allele is associated with an increased risk of gout (R).
  23. RS4311316 
  24. RS4312757 
  25. RS4314284 
  26. RS4339211 
  27. RS4455410 
  28. RS4473653 
  29. RS4475146 – The “A” allele is associated with gout (R).
  30. RS4481233 
  31. RS4519796 
  32. RS4580649 
  33. RS4621431 
  34. RS6449157 
  35. RS6449159 
  36. RS6449171 
  37. RS6449172 
  38. RS6449174 
  39. RS6449176 
  40. RS6449178 
  41. RS6449201 
  42. RS6449213 -This variant is associated with higher blood urate levels (R).
  43. RS6814664 
  44. RS6815001 
  45. RS6823361 
  46. RS6832439 -The “A” allele is associated with decreasing blood uric acid levels (R).
  47. RS6834893 
  48. RS6836706 
  49. RS6838021 
  50. RS6839490 
  51. RS6843873 
  52. RS6844316 
  53. RS6849729 
  54. RS6852441 
  55. RS6855911 -The “G” allele is associated with less uric acid (R).
  56. RS733175 
  57. RS734553 – The “T” allele is associated with gout (R).
  58. RS737267  – The GG genotype is associated with 1.25 times higher risk of gout (R).
  59. RS7376948 
  60. RS7378305 
  61. RS7378340 
  62. RS7435196 
  63. RS7442295  – The more common “A” allele is associated with higher blood urate levels and hyperuricemia (R).
  64. RS7658170 
  65. RS7671266 
  66. RS7672947 
  67. RS7676733 
  68. RS7677710 
  69. RS7680126 
  70. RS7686538 
  71. RS938554 
  72. RS9993410 
  73. RS9994266 

ABCG2 Gene- The Multi-functional Transporter That Exports Urate:

This gene encodes a multifunctional transporter that belongs to the ATP-binding cassette family and controls the export of various compounds including urate using ATP (R).

  1. RS13120400 
  2. RS1481012 – The “A” allele is associated with an increased risk of gout (R). Heterozygous carriers of the minor allele “G” have a lower risk of colorectal cancer (R).
  3. RS17731538 
  4. RS2199936 – The “A” allele is associated with incident gout (R).
  5. RS2231137 -The T” (minor) allele is associated with:
    • Increased activity of the drug Pravastatin in patients being treated for hyperlipidaemia (R).
    • Increased risk of tophaceous gout (R). This results in joint pain and arthritis.
    • Possible increase in drug-induced toxicity (R).
    • An increased survival rate in patients undergoing chemotherapy to treat Acute Myeloid Leukemia (R).
    • Increased chance of toxic response following chemotherapy to treat Acute Myeloid Leukemia (R).

    The C (major) allele is associated with:

    • Higher resistance to imatinib therapy in chronic myeloid leukemia patients (CC) (R).
  6. RS2231142 -The T (minor) allele is associated with:
    1. Increased risk of gout (R).
    2. Frequent diarrhea in lung cancer patients taking gefitinib (R).
    3. Heightened response to statins (R).
  7. RS2622604 -The T (minor) allele is associated with:
    •  Increased risk of developing myelosuppression and diarrhea in colorectal and lung cancer subjects being treated with irinotecan (R). This is because Irinotecan can be toxic to cells if it is not removed properly.
  8. RS2728124 
  9. RS2728125 -The “G” allele is associated with gout (R).
  10. RS3114018 
  11. RS4148152 
  12. RS4148155 
  13. RS72552713 -The “A” allele is associated with an increased risk of gout (R).

SLC22A12 Gene-The Urate Transporter That Determines the Amount of Urate Present in the Blood:

This gene encodes a protein that is a member of the organic anion transporter (OAT) family, and it transports urate. Found in the epithelial cells of the proximal tubule of the kidney, this protein helps control the amount of urate present in the blood. This gene is thought to be the major luminal pathway for urate reabsorption in humans and mutations have been associated with raised blood urate levels and decreased fractional urate excretion (R).

  1. RS12800450 -The “T” allele is associated with reduced blood urate levels (R).
  2. RS505802 – The “A” allele is associated with gout arthritis in Han Chinese males (R).

SLC22A11 Gene-The Organic Anion Transporter That Reabsorbs Uric Acid:

The gene encodes a protein that is involved in the transport and excretion of organic anions. It also aids in the reabsorption of uric acid on the apical membrane of the proximal tubule in the kidneys (R,R2).

  1. RS17300741 – The minor “G” allele is associated with lower blood uric acid levels in women (R).

SLC17A1 Gene-The Renal Urate Exporter:

This gene encodes a sodium-dependent transporter that helps transport glucose and other sugars, bile salts and organic acids, metal ions and amine compounds, as well as urate. It is also associated with a higher risk of gout and hyperuricemia (R).

  1. RS1165196-The  allele “C” is associated with an increased risk of gout in patients with normal uric acid excretion (R). It is also associated with a low-/high-density lipoprotein cholesterol ratio (R).
  2. RS1183201 -The minor “A” allele is associated with a reduced risk of gout in European and western Polynesian populations (R).

SLC17A3 Gene-Transporter That Transports Intracellular Urate Out of the Cell:

The gene encodes a voltage-driven transporter that transports intracellular urate and organic anions from the blood into kidney tubule cells (R).

  1. RS1165205 -The “A” allele is associated with higher blood uric acid levels (R).
  2. RS13198474 – The “G” allele is associated with schizophrenia (R).
  3. RS1408272 -The “G” allele is associated with mean corpuscular hemoglobin (R).
  4. RS548987 The “C” is linked to homocysteine concentrations (R).
  5. RS6910741 -The “T” allele is associated with mean arterial pressure (R).

UMOD Gene: The Protein That Helps Control The Amount of Water in Urine:

This gene encodes uromodulin, a protein that is highly abundant in urine under physiological conditions. Defects in this gene are associated with various kidney diseases including glomerulocystic kidney disease with hyperuricemia (R).

  1. RS12444268 -The “A” allele linked to Type 1 Diabetes (R).
  2. RS12917707 – The minor “T” allele is associated with a lower risk of chronic kidney diseases (R).
  3. RS13333226 -The minor “G” allele is associated with a lower risk of hypertension (R).
  4. RS4293393 – The “T” allele is associated with kidney stones and chronic kidney disease. This SNP may also be associated with susceptibility to gout, hypertension, and diabetes (R).

HPRT1 Gene- The Enzyme That Recycles Purines:

This gene encodes hypoxanthine phosphoribosyltransferase 1, an enzyme that allows cells to recycle purines. Mutations in this gene can result in gout or Lesch-Nyhan syndrome (R).

PRPS1 Gene- The Enzyme That Helps Make Purines:

The PRPS1 gene encodes an enzyme called phosphoribosyl pyrophosphate synthetase 1, or PRPP synthetase 1. This enzyme helps produce phosphoribosyl pyrophosphate (PRPP), which is involved in making purine and pyrimidine nucleotides (R).

 Uric Acid: Part 1 of a 3-Part Series

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21 COMMENTS

  • bob

    Any info on selfhacked as far as taking RNA supplements?

  • Ken Rood

    Hi
    I was reading part 1 of your uric acid study. At the bottom of the part 1 report, I wanted to read part 2. I clicked on part 2, and part 3 came up. Why wasn’t I connected to part 2? …Ken (My email has 3 – o’s)

    1. Nattha Wannissorn, PhD

      Fixed. Here’s the link again http://selfhacked.com/blog/high-uric-acid/

  • blue

    ketogenic diet is a 2-in-1 way to boost brain as ketones are a more efficient energy source for brain than glucose and they compete with uric acid in kidneys for excretion.

  • K

    I was reading that cold showers lower uric acid is that true?

    1. Betsy

      In people with MS, where do you suppose all their uric acid is going. If they are eating any amount of foods with purines, they surely should not be showing such low uric acid levels.
      And PS: Cold showers lower blood uric acid levels because it makes the uric acid precipitate into the tissue.

  • Jae hee

    Nice job on this article. Thanks. Interestingly, doesnt inosine do the exact opposite of the drug used for autoimmunity: cellcept (and myforte)? Those drugs inhibit b cell proliferation by preventing purine metabolism. That may imply people with ai disease (except perhaps brain affected folk) steer clear of inosine. Also curious how ingestion ofasparagus might increase uric acid and do thesame thing more gently (doneone will probably point out u need 5lbs a day…). I guess measuring uric acid is a first step. Any home test kits for that?

  • Stuart

    How is the 500mg once or twice a day working? Is it still providing a positive effect?

  • sciman

    Great article!

    I am convinced to try it. However, is it possible to get the kidney stones before kidneys start to hurt? How do you know that you are all right taking it?

    1. Joseph M. Cohen

      I pee in a portable urinal and if it starts forming too much solids, it’s a warning sign. Otherwise, you can check the acidity of your urine, but that might not be a great indicator.

      Otherwise, when I took 3g, I felt some pain in my kidney area.

  • ella m

    Hi joe, took 1 g of Swanson inosine yesterday and while it did give me a clear cognitive boost it also made me really aggressive and moody – does if make sense with this supp?

    1. Joseph M. Cohen

      It’s possible. Make sure to consume a gallon of water daily if you take that dosage.

  • Joanna

    You know, I wonder if this has anything to do with the temporary boost in creativity and mental function people get from alcohol consumption, since alcohol temporarily increases levels of uric acid.

    I find that if I hit a “sweet spot” with drinking I get a pleasant afterglow effects the day after for a short time. It seems to go away after eating and/or drinking + urinating.

    Then of course, there is GABA modulation, but I feel like the afterglow feeling is most noticeable the day after, which would make uric acid make more sense.

    Maybe I’m wrong, but I just thought it was interesting.

    1. Joseph M. Cohen

      I thought the same

  • Santiago

    Hi Joseph,

    maybe you have an idea of this issue. In the morning, and with age (just turned 40) happens to me that I’m going to say a word and say another. For instance, wanting to say my wife, and I say my mother.

    Do you know what part or process in the brain can be wrong for this type of mistakes?.

    Thanks a lot. Santiago

    PS: you have created a very useful blog.

  • Chris

    Opinion?
    American Psychological Association. “High-normal Uric Acid Linked With Mild Cognitive Impairment In The Elderly.” ScienceDaily. ScienceDaily, 3 January 2007.

    1. Joseph M. Cohen

      maybe I recall reading uric acid increases in response to oxidative stress or perhaps its inflammatory action

  • Dylan

    Have you covered the benefits of the molecular hydrogen machine yet? This is new to me. Thanks.

    1. Joseph M. Cohen

      No, but I’m very happy I bought it

  • veganpaleoflux

    Interesting here that vegans have the highest uric acid levels.

    http://www.ncbi.nlm.nih.gov/pubmed/23418557

    Calcium seems to also be a part of the puzzle.

    1. Joseph M. Cohen

      That’s really interesting!

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