L. Amber O'Hearn - My case against uricase: a critical examination of hypotheses - AHS19

Humans, along with other apes, evolved a series of mutations preventing uricase activity. Uricase breaks down uric acid (UA), and so apes, especially humans, have higher levels of UA than other mammals. There are many hypotheses about the selective advantage of these mutations, including benefits for the brain. However, higher UA levels make us more susceptible to fructose-induced metabolic syndrome, common in the modern food environment, which in turn can cause UA levels to rise pathologically. This is associated with cognitive and psychiatric detriments. Nonetheless, UA levels transiently increase in response to a ketogenic diet, without apparent detriment. Experts differ in their interpretations of this phenomenon. In this presentation, I will review evolutionary theories about uricase, and the interplay between UA, carbohydrate metabolism, and other dietary factors. In addition, I will attempt to disentangle negative effects of UA associated with metabolic syndrome from neuroprotective and cognitive benefits.

[@quittenfee42]

It's perhaps the oxalate levels in combination with high blood sugar that trigger gout. That would explain why fasting improves gout.

[@ilyalevin9400]

Fascinating lecture. Thank you

[@Noegzit]

@34'55 : That's Dr. Paul Saladino (The Carnivore code) who asks a question about other factors contributing to gout.

[@rckindkitty]

Damned fascinating, great work, Amber! Thank you!

[@markiangooley]

Windover archeological site in Florida: swamp burials of hunter-gatherers. Bones show much evidence of near-starvation from time to time. I would count that as evidence of a case of pre-agricultural famine.

[@btudrus]

My theory is that UA is a systemic regulator of insulin resistance. Yes, I understand IR as a physiological process, not primarily pathogenic. E.g. after an vigorous exercise your UA level will be raised, which is a signal to "spare energy" which is exactly what IR is. Of course there is a chronic/pathological IR which is T2D, but that doesn't mean that IR per se is bad. It's a normal regulatory state in the body. And: what Fructose does is actually a state which is contradicting itself. You have a plenty of Energy but you are signalling to the body that it needs to spare energy. Usefull to survive the winter but other than that this contradiction is the reason why IR can be so detrimental...

[@IndyRickHikes]

Recently heard a fascinating conversation between Peter Attia and Richard Johnson on this topic. Nearly fell out of my chair because the fructose/uric acid pathways seem to fit nicely as an explanation of some of my own n=1 observations with kidney stones, high uric acid, metabolic syndrome, long-term ketosis, and seasonal variation with metabolic control. It also seems to explain the presence of gout in older age of family members who have suffered metabolic disregulation and who share my maternal ancestry. Loved your review of the knowns and speculations in this area. Two key takeaways I’m trying from Dr. Johnson: (1) be very careful with alcohol consumption during holidays or other times when otherwise occasional consumption tends to increase and (2) drink a glass of water prior to consumption of salted food. From Amber, the takeaway to think about is perhaps increased carnivory with lower salt added. 👏🙏

[@aaronsilver-pell411]

so a meat diet + alcohol = stones you think?

[@freetrailer4poor]

Well done.

[@oilscience9808]

Good presentation. Thanks.

[@InconnuGlitterBoy]

Slide at 26:26 hits really hard.

[@steakovercake3986]

Paul Saladino! I'd always be able to tell his voice .

[@DarthGohma]

lol I was about to say.

[@rasier101]

34:55

[@btudrus]

23:45 "idea that ... [UA and ketone bodies] compete for reabsorption and clearance in the kidney..." WRONG! URAT1 is an *exchange transporter* which means that excreting ketone bodies (along with lactate and the precursor of NAD/NADH which all have something to do with energy metabolism!) will cause reabsorption of UA! This is not a competition! This is a regulation: ketone bodies *rergulate* UA levels in the BS!

[@jamiewoolner485]

Who is the gentleman at the end talking about iron?

[@rasier101]

34:55 Is that you Dr. Paul Saladino?

[@robertdaymouse3784]

As to the discussion near the end, I have hyperuricemia (no gout, age 61, history of osteoarthritis), I have roughly doubled my urinary excretion of UA from 500mg/day to 1,000/day by alkalizing my urine and taking VitC. Unfortunately even though I have been alkalizing my urine for 14 weeks my serum UA levels have stayed at 6.5-8.5. I can only speculate that I have a high urate crystal load that needs to be further depleted.

[@adamshand]

Hey Robert, curious how you got on with this? Did your uric acid levels settle down over time?

[@yoso585]

Amber Alert! :)

[@soleprobe]

The most-forbidden documentary in history: “Europa The Last Battle” at archive dot org

[@Appleblade]

So... with the man's final comment... don't eat carbs with your high red meat diet (which will be high in uric acid and iron).

[@prins424]

It sounded as if he found out from experience. Did you have similar experiences or do you know if there is research on it?

[@lt2339]

Pink salt, just a pinch now and then, mostly a tap sprinkled on a corner of my plate makes an optional dip for a meat bite. It is the best stool softener if ever needed because fruits and veggies are out (spark arthritis pain).