GOUT and FRUCTOSE

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GOUT and FRUCTOSE
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Fructose

• present in honey and fruit
• 50 of sugar (sucrose 1 glucose 1
  fructose molecule)
• 55 of HFCS ( high fructose corn sryup)

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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

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Metabolic Syndrome

• Insulin resistance
• Hypertriglyceridemia
• Hypertension
• and
• Hyperuricaemia

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Headline News

• Soft drinks 'bigger gout risk than alcohol'. The
  Daily 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

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Objective of study

• To examine the relation between intake of
• sweetened soft drinks and fructose , and the
  risk of incident gout in men

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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

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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

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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
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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
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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
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Letter abstract Nature Genetics 40, 437 - 442
(2008) Published online 9 March 2008
doi10.1038/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 (200500 M) compared with other
mammals (3120 M)1. About 70 of daily urate
disposal occurs via the kidneys, and in 525 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 1.75.3 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.
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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.

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Why does fructose affect uric acid. 3

• Carriers of the defect hereditary fructose
  intolerance also have high plasma uric acid.

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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
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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

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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