[ExI] More on gout
js_exi at gnolls.org
Thu Apr 21 23:51:20 UTC 2011
Now I'm going to spend some time with the study Harvey cited, because
it's instructive even though his claims about it are nonsense.
First, here's the original study cited in the BBC article I posted (full
"Soft drinks, fructose consumption, and the risk of gout in men:
prospective cohort study"
HK Choi, G Curhan
And here's the study Harvey claims supersedes it:
"Lack of association between dietary fructose and hyperuricemia risk in
SZ Sun*, BD Flickinger, PS Williamson-Hughes, MW Empie
Note that these are both associational studies, both use old data sets
-- and neither proves causation, contrary to Harvey's claim that the
second does but the first does not.
First, one might notice from the title of Sun et.al. that it is
measuring hyperuricemia, not actual cases of gout. AFAIK less than 10%
of hyperuricemic people develop gout. So even if we take Sun et.al. at
face value, it's still entirely possible for fructose to cause gout.
Second, there is the fact Dave Sill already noted: the Nut. Metab. paper
is authored entirely by employees of Archer Daniels Midland -- the
largest industrial producer of corn in the country. Continued sales of
HFCS are very important to their bottom line.
Moving on. I'll start by pointing to actual controlled studies that
show urate (= uric acid) rising in response to fructose administration:
"Effect of oral fructose on urate production"
"Stimulation of human purine synthesis de novo by fructose infusion"
"The rate of infusion appeared more important than total dose in
determining the magnitude of this effect. [increased rate of purine
synthesis]" This is important, because it shows that drinking soft
drinks between meals (= quick infusion of fructose) is likely far worse
than consuming fructose as part of a meal.
"Hyperuricemia and hypertriglyceridemia: Metabolic basis for the
Also note: "To examine whether hypertriglyceridemia leads to
hyperuricemia, IV Intralipid was given to three gouty patients.
Triglycerides increased from 169 to 700 mg/dl for three hours but caused
no change in serum urate level or urine uric acid and oxypurine excretion."
Furthermore, from "Relation between serum triglyceride level, serum
urate concentration, and fractional urate excretion"
"Serum triglyceride level was positively correlated with serum urate
concentration and inversely correlated with fractional urate excretion
in both simple and multiple linear regression analysis."
So a high-fat paleo diet removes things that raise blood urate
(fructose, alcohol, sugar and 'carbs' through their effect on
triglycerides) and replaces them with things that do not (fat).
Therefore, there is indeed a plausible mechanism by which high-fat paleo
benefits gout sufferers more than a standard low-fat, high-carbohydrate
I'll continue by pointing out that the studies the Nut. Metab. article
cites to claim no relationship between urate and fructose consumption
tend to do the following:
1) Sampling urine at a single point in time instead of collecting
24-hour urine or urine over a period of time. Uric acid levels
fluctuate both seasonally, over days, and dramatically within the course
of a day.
2) Same issue for blood sampling.
3) Comparing high to very high doses of fructose. One study cited by
Sun et.al. compared 63 mg/day to 99 g/day! 63 mg is roughly equivalent
to the fructose in three cans of Coca-Cola.
4) Not accounting for the rate of fructose absorption: conflating
fructose as part of a meal with soda or candy consumed in isolation
Then, read the "Estimation of dietary fructose intake" section. There
are a lot of guesstimates involved.
In contrast, Choi and Curhan measure a clinical outcome (gout) that
cannot be missed by sampling during the wrong time window, and directly
survey soft drink intake as opposed to attempting to indirectly impute
total fructose through several layers of estimation -- any of which is
easy to fudge in order to produce the desired result.
Furthermore, since infusion rate is apparently more important than total
amount, soft drink consumption is likely to be more strongly correlated
than total fructose intake, since soft drinks are likely to be consumed
You can check the footnotes in the BMJ paper for a list of references to
the fact that fructose increases uric acid levels. This is not
controversial science. And as the BMJ paper correctly points out, it
was understood that fruit and sugars contributed to gout even before we
knew what fructose was.
For an example of one mechanism by which this might be occurring, see
this paper, which identifies a transporter of both fructose and uric
And: "Multiple Genetic Loci Influence Serum Urate Levels and Their
Relationship With Gout and Cardiovascular Disease Risk Factors" (SLC2A9
is among them)
So it seems likely that some people have a greater problem with dietary
fructose than others.
Well, this went completely out of control...I should write an article
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