Does anybody have GOUT? (Purine fans get in here)

S-VV

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New study:

Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases

"Abstract: Post-exertional malaise (PEM) is a cardinal predictive symptom in the definition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). If the cases overexert themselves they have what is termed “payback” resulting in a worsening of symptoms or relapse which can last for days, weeks or even months. The aim was to assess the changes in biochemistry associated with the cases self-reported PEM scores over a 7-day period and the frequency of reporting over a 12-month period. Forty-seven ME/CFS cases and age/sex-matched controls had a clinical examination, completed questionnaires; were subjected to standard serum biochemistry; had their serum and urine metabolomes analyzed in an observational study. Thirty-five of the 46 ME/CFS cases reported PEM in the last 7-days and these were allocated to the PEM group.

The principal biochemical change related to the 7-day severity of PEM was the fall in the purine metabolite, hypoxanthine. This decrease correlated with alterations in the glucose:lactate ratio highly suggestive of a glycolytic anomaly.

Increased excretion of urine metabolites within the 7-day response period indicated a hypermetabolic event was occurring. Increases in urine excretion of methylhistidine (muscle protein degradation), mannitol (intestinal barrier deregulation) and acetate were noted with the hypermetabolic event.

These data indicate hypoacetylation was occurring, which may also be related to deregulation of multiple cytoplasmic enzymes and DNA histone regulation. These findings suggest the primary events associated with PEM were due to hypoacetylation and metabolite loss during the acute PEM response"
 
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S-VV

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Hypoxanthine is obtained from adenosine, and is further metabolized into uric acid. My uric acid is very low.

Adenosine is formed as a breakdown product from ATP. In fact high adenosine is a signal for the body that it has exerted itself too much and it's time to relax. That's why caffeine is useful. Caffeine blocks adenosine P2Y receptors.

Does low hypoxanthine mean low ATP?
Could inosine supplementation help? The body can salvage inosine back into adenosine and back into ATP?
 

S-VV

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Plasma hypoxanthine and exercise

Abstract
During exercise, ATP is converted to ADP and AMP to supply energy for muscular contraction. It is then regenerated via various pathways of intermediary metabolism. However, with high levels of exercise, net ATP degradation in muscle occurs. In exercise and other clinical situations, adenine nucleotide degradation leads to an accumulation of degradative purine products including hypoxanthine. In an effort to monitor events of energy metabolism, we examined plasma hypoxanthine levels at various exercise intensities. Peak plasma hypoxanthine levels after maximal exercise (18.9 +/- 2.6 microM, mean +/- SEM) were significantly greater than resting levels (1.1 +/- 0.1 microM; p less than 0.001). Hypoxanthine levels after steady state exercise at 52, 76, and 97% of ventilatory threshold did not exceed resting levels. However, plasma hypoxanthine rose significantly after exercise at 124% of ventilatory threshold (6.3 +/- 1.0 microM; p less than 0.01) and at 152% of ventilatory threshold (17.0 +/- 3.6 microM; p less than 0.001). Exercise at subventilatory threshold intensity (74% of ventilatory threshold) for a prolonged time period, such that total work equaled that performed at 152% of ventilatory threshold, did not elevate hypoxanthine levels (0.46 +/- 0.1 microM) above resting values. We conclude that elevation of plasma hypoxanthine levels occur during exercise at intensities that exceed the ventilatory threshold and indicate that net adenine nucleotide degradation has occurred.
 

S-VV

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More from the original study:

In the whole group analysis, the 7-day severity PEM score and 12-month frequency PEM scores were positively correlated with serum glucose and negatively correlated with hypoxanthine, phenylalanine, lactate and threonine. No significant correlates were noted within the ME/CFS group. The absolute urine levels showed a significant correlation between the 7-day PEM score along with mannitol, serine, acetate, methylhistidine and glucose. The 12-month frequency of PEM correlated with a fall in acetate alone. The urine percentage data showed falls in urea, pyruvate and acetate with both the 7-day severity and 12-month frequency scores. The only fecal component to reach statistical significance was the percentage uracil. These data show a significant renal concentrating issue is occurring in the ME/CFS group during a PEM event and this was principally related to falls in urea and acetate. To check this, we calculated the serum to urine ratios of multiple metabolites. The 7-day severity of PEM correlated with the following ratios: serum acetate :urine acetate ratio (r = −0.44, p < 0.002), serum tyrosine :urine tyrosine ratio (r = −0.40, p < 0.006), serum serine :urine serine ratio (r = −0.39, p < 0.008), serum creatine :urine creatine ratio (r = −0.38, p < 0.009), and the serum leucine:urine leucine ratio (r = −0.37, p < 0.01). Thus, the 7-day severity of PEM was associated with an increased urinary excretion of metabolites within the ME/CFS group and this was associated with a reduction in multiple serum metabolites including the important protein synthesis regulating amino acid, leucine.
 

S-VV

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Could this be the next anti-PEM stack:

-inosine (for hypoxanthine)
-creatine

-threonine
-tyrosine
-phenylalanine
-serine
-leucine

-acetate