Transcript GOUT and FRUCTOSE

GOUT and FRUCTOSE
Fructose
 present in honey and fruit
 50% of sugar (sucrose = 1 glucose +
1 fructose molecule)
 55% of HFCS ( high fructose corn sryup)
History
 1893 – Osler prescribed diets low in fructose as
a means to prevent gout “ The sugar should be
reduced to a minimum. The sweeter fruits
should not be taken”
 1967- Perheentupa noted fructose induced
hyperuricaemia, when infused.
 Introduction of effective drugs, such as
probenicid (1950s) allopurinol (1960s) to treat
gout has decreased the interest in the effect of
diet
Metabolic Syndrome
 Insulin resistance
 Hypertriglyceridemia
 Hypertension
and
 Hyperuricaemia
Headline News
 Soft drinks 'bigger gout risk than alcohol'. The Daily
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Telegraph, February 1 2008
Fizzy drinks linked to gout. The Times, February 1 2008
Fizzy pop increases gout risk. The Sun, February 1 2008
Two fizzy drinks a day 'can give you gout'. Daily Mail,
February 1 2008
Fizzy drinks ‘cause gout’. Metro, February 1 2008
Gout surge blamed on sweet drinks. BBC News,
February 1 2008
Fizzy drinks link to gout. Channel 4 News, February 1
2008
Objective of study
 “To examine the relation between intake of
sweetened soft drinks and fructose , and
the risk of incident gout in men”
Method
 In 1986, 51,529 health professionals were
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mailed a questionnaire on diet , medical
history and drugs.
Male, aged 40 – 75ys
49,166 replied, but 2773 had gout (5.6%)
and were excluded
Dietary questionnaire repeated every 4yrs
Medical history and drugs every 2 years
Results
 After 12 years 46,393 men had provided
information
 755 new cases of gout were documented
 With increasing intake of sugar sweetened soft
drinks, intake of caffeine, fructose, meat and
high fat dairy food tended to increase. But mean
age and low fat diary intake tended to decrease.
 with increasing consumption of free fructose,
the BMI, alcohol intake, caffeine, meat and high
fat dairy food tended to decrease
Irrespective of Body Mass,
Alcohol use, and Dairy
Intake, there is an increased
risk of gout associated with
increased fructose intake.
(adjusted for age, total
energy intake, BMI, diuretic
use, history of hypertension
or renal failure, intake of
alcohol, intake of vit C, %of
energy from total
carbohydrate and protein)
Choi and Curhan, BMJ 2008
Results
1 servings a day increased
risk by 45%
BUT 2 or more servings a day
increased risk of gout by 85%
Suggests that the risk posed by free fructose intake , is as great as that of
the intake of purine rich food
Why does fructose affect uric acid.
1.infusion studies show
Decreasing Pi
levels remove
feedback on
ATP
fructose
Fructokinase
Fructose -1-
ADP
AMP
phosphate
AMP
Deaminase
IMP
URIC ACID
Liver Cell
Letter abstract
Nature Genetics 40, 437 - 442 (2008)
Published online: 9 March 2008 | doi:10.1038/ng.106
SLC2A9 is a newly identified urate transporter influencing serum urate
concentration, urate excretion and gout
Veronique Vitart1,14, Igor Rudan2,3,14, Caroline Hayward1,14, Nicola K Gray1,12, James Floyd4, Colin NA Palmer5, Sara A
Knott4, Ivana Kolcic6, Ozren Polasek2,6, Juergen Graessler7, James F Wilson2, Anthony Marinaki8, Philip L Riches9, Xinhua
Shu1, Branka Janicijevic11, Nina Smolej-Narancic11, Barbara Gorgoni1,12, Joanne Morgan1, Susan Campbell1, Zrinka
Biloglav6, Lovorka Barac-Lauc11, Marijana Pericic11, Irena Martinovic Klaric11, Lina Zgaga6, Tatjana Skaric-Juric11, Sarah H
Wild2, William A Richardson1, Peter Hohenstein1, Charley H Kimber5, Albert Tenesa10, Louise A Donnelly5, Lynette D
Fairbanks9, Martin Aringer7, Paul M McKeigue2, Stuart H Ralston9, Andrew D Morris13, Pavao Rudan11, Nicholas D Hastie1,
Harry Campbell2 & Alan F Wright1
Uric acid is the end product of purine metabolism in humans and great apes, which have lost
hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200–500 M)
compared with other mammals (3–120 M)1. About 70% of daily urate disposal occurs via the
kidneys, and in 5–25% of the human population, impaired renal excretion leads to
hyperuricemia2. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis
that results from deposition of monosodium urate crystals in the joint. We have identified genetic
variants within a transporter gene, SLC2A9, that explain 1.7–5.3% of the variance in serum uric
acid concentrations, following a genome-wide association scan in a Croatian population sample.
SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in
UK, Croatian and German population samples. SLC2A9 is a known fructose
transporter3, and we now show that it has strong uric acid transport activity in Xenopus laevis
oocytes.
Why does fructose affect uric acid.
2.
 Some fructose transporters in the kidney
may also be uric acid transporters and this
may affect the way the kidney handles uric
acid.
Why does fructose affect uric acid. 3
 Carriers of the defect hereditary fructose
intolerance also have high plasma uric
acid.
Hereditary Fructose Intolerance
Decreasing Pi
levels remove
feedback on
ATP
fructose
Fructokinase
Fructose -1-
ADP
AMP
AMP
Deaminase
phosphate
IMP
Aldolase B
DHA phosphate
URIC ACID
Liver Cell
Why does fructose affect uric acid. 3
 Defects in aldolase B, lead to increased
UA from fructose metabolism, and low Pi
stimulation of AMP deaminase ( Pi is
locked in Fructose 1-P)
 Increased levels of fructose ( as it cannot
be metabolised) lead to competition with
for the uric acid/ fructose transporters
Summary
 Too many non-diet soft drinks increases
plasma uric acid.
 Diet soft drinks are OK.
 Benefits gained from eating fruit probably
far outweight the risk of developing gout