Thursday, March 10, 2016

Does Protein Increase Uric Acid?

In an earlier blog post I looked at the evidenced from clinical trials of whether fructose increases uric acid (blog).  In this post I want to do the same for protein (see table below).  The proposed mechanism here is more obvious – uric acid is a breakdown product of amino acid (and purine) metabolism: so higher protein intake would increase uric acid production, which is thought to lead to higher uric acid


Participants
Diet
Duration
Outcome of high protein group
[1]
With kidney stones
High vs. low animal protein
2 weeks
13% increase in urea, no change in uric acid
[2]
Healthy adults
200g/d red meat vs. whole grains
3 weeks
10% increase in uric acid
[3]
Type 2 diabetes
30% vs. 15% protein
5 weeks
Increase in GH, IGF-1 and urinary cortisol.  No change in uric acid, calcium excretion or thyroid hormones
[4]
Middle-aged healthy men
160g/d beef vs. 26g/d beef
6 weeks
No difference in uric acid.  Greater increase in triglycerides
[5]
Overweight adults (90% women)
32:28:41 vs. 15:21:66
6 weeks
Greater satiety.  No significant differences (including uric acid), except higher urinary nitrogen, calcium and uric acid)
[6]
Healthy adults
29:54:17 vs. 15:36:48
2 weeks
Lower triglycerides, higher 25(OH)D, no difference in uric acid, more acidic urine
[7]
Healthy young women
High vs. low acidic amino acid and purine diets
5 days
Non-significant increase in uric acid (~5%)
[8]
Postmenopausal women (aged 50 or over)
30g/d of dairy protein (+15g/d protein vs. baseline)
4 weeks
No change in uric acid or urea
[9]
Fairly healthy, mostly overweight adults (aged between 35-71)
27:26:47 vs. 16:26:59
(high protein from gluten, fibre held constant)
1 month
Decrease in triglycerides and uric acid.  Increase in urea and urea clearance
[10]
Type 2 diabetes
LoBAG30 diet (30:40:30) vs. 15:30:55
6 days
No change in plasma uric acid or cortisol.  Increase in urinary cortisol, sodium, nitrogen, uric acid but no change in pH.  Increase in glucagon

Most of the studies found that a higher protein diet lead to either no change or a modest increase (~10%) in fasting uric acid levels.  The few studies that measured it found high protein diets consistently increased uric acid excretion (higher urine uric acid).  This negative feedback system maintains normal uric acid levels in response to the greater uric acid production from higher protein diets

I struggled to find any studies in humans looking at whether higher protein diets increase postprandial uric acid.  However, I did find a study compared the postprandial uric acid response of haddock, liver and soybeans to look at how different purines affect postprandial uric acid, while keeping total protein and total purines constant [11].  The study concluded that hypoxanthine and adenine disproportionately increased postprandial uric acid, although I don’t think you could say this definitely as there were other differences in the meal and may be other differences in the components of those foods that could influence the postprandial uric acid response.  What you can see from those graphs is that uric acid levels would return to normal a couple to several hours after high protein and purine consumption and so wouldn’t really affect fasting uric acid levels as the trials have shown, but  the postprandial increase in uric acid may be a concern for people with gout or high uric acid levels


* Higher urine uric acid is a factor in the development of uric acid kidney stones.  Uric acid kidney stones account for about 10% of all kidney stones and other factors in their development include low urine pH (diet can influence this and insulin resistance also lowers urine pH (everything seems to come back to insulin resistance)) and low urine volume [12]

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