1. GOUT and FRUCTOSE

2. Fructose present in honey and fruit
50% of sugar (sucrose = 1 glucose fructose molecule)
55% of HFCS ( high fructose corn sryup)

3. 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

4. Metabolic Syndrome Insulin resistance Hypertriglyceridemia
Hypertension
and
Hyperuricaemia

6. Headline News
Soft drinks 'bigger gout risk than alcohol'. The Daily Telegraph, February
Fizzy drinks linked to gout. The Times, February
Fizzy pop increases gout risk. The Sun, February
Two fizzy drinks a day 'can give you gout'. Daily Mail, February
Fizzy drinks ‘cause gout’. Metro, February
Gout surge blamed on sweet drinks. BBC News, February
Fizzy drinks link to gout. Channel 4 News, February

7. Objective of study “To examine the relation between intake of
sweetened soft drinks and fructose , and the risk of incident gout in men”

8. Method
In 1986, 51,529 health professionals were 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

9. 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

10. 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

11. 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

12. Why does fructose affect uric acid. 1.infusion studies show
Decreasing Pi levels remove feedback on
ATP
fructose
Fructokinase
Fructose -1-
phosphate
ADP
AMP
AMP Deaminase
IMP
URIC ACID
Liver Cell

13. Letter abstract
Nature Genetics 40, (2008) Published online: 9 March 2008 | doi: /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.

14. 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.

15. Why does fructose affect uric acid. 3
Carriers of the defect hereditary fructose intolerance also have high plasma uric acid.

16. Hereditary Fructose Intolerance
Decreasing Pi levels remove feedback on
ATP
fructose
Fructokinase
AMP Deaminase
Fructose -1-
phosphate
ADP
AMP
IMP
Aldolase B
DHA -
phosphate
URIC ACID
Liver Cell

17. 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

18. 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