Editing Hyperuricemia (section)

===Mixed type===
Causes of hyperuricemia that are of mixed type have a dual action, both increasing production and decreasing excretion of uric acid.{{citation needed|date=November 2021}}

[[Pseudohypoxia]] (disrupted NADH/NAD<sup>+</sup> ratio), caused by diabetic hyperglycemia and excessive alcohol consumption, results in hyperuricemia. The lactic acidosis inhibits uric acid secretion by the kidney, while the energy shortage from inhibited oxidative phosphorylation leads to increased production of uric acid due to increased turnover of adenosine nucleotides by the [[Adenylate kinase|myokinase reaction]] and [[purine nucleotide cycle]].<ref>{{Cite book |last=Coffee |first=Carole J. |title=Quick Look Medicine: Metabolism |publisher=Hayes Barton Press |year=1999 |isbn=1-59377-192-4}}</ref>

High intake of alcohol ([[ethanol]]), a significant cause of hyperuricemia, has a dual action that is compounded by multiple mechanisms. Ethanol increases production of uric acid by increasing production of [[lactic acid]], hence [[lactic acidosis]]. Ethanol also increases the plasma concentrations of hypoxanthine and xanthine via the acceleration of adenine nucleotide degradation, and is a possible weak inhibitor of xanthine dehydrogenase. As a byproduct of its fermentation process, [[beer]] additionally contributes purines. Ethanol decreases excretion of uric acid by promoting [[dehydration]] and (rarely) clinical [[ketoacidosis]].<ref name="Yamamoto+2005" /><!-- ref for whole paragraph -->

High dietary intake of [[fructose]] contributes significantly to hyperuricemia.<ref>{{cite journal |author=Nakagawa T |title=A causal role for uric acid in fructose-induced metabolic syndrome |journal=Am. J. Physiol. Renal Physiol. |volume=290 |issue=3 |pages=F625–31 |year=2006 |pmid=16234313 |doi=10.1152/ajprenal.00140.2005 |name-list-style=vanc|author2=Hu H |author3=Zharikov S |display-authors=3 |last4=Tuttle |first4=KR |last5=Short |first5=RA |last6=Glushakova |first6=O |last7=Ouyang |first7=X |last8=Feig |first8=DI |last9=Block |first9=ER|s2cid=2667982 }}</ref><ref>{{cite journal |author=Mayes PA |title=Intermediary metabolism of fructose |journal=Am. J. Clin. Nutr. |volume=58 |issue=5 Suppl |pages=754S–765S |year=1993 |pmid=8213607 |doi=10.1093/ajcn/58.5.754S|doi-access=free }}</ref><ref name="pmid18301272">{{cite journal|vauthors=Miller A, Adeli K | title = Dietary fructose and the metabolic syndrome| journal = Curr. Opin. Gastroenterol.| volume = 24| issue = 2| pages = 204–9|date=March 2008| pmid = 18301272| doi = 10.1097/MOG.0b013e3282f3f4c4| s2cid = 26026368}}</ref> In a large study in the United States, consumption of four or more sugar-sweetened [[soft drink]]s per day gave an odds ratio of 1.82 for hyperuricemia.<ref name="pmid18163396">{{cite journal|vauthors=Choi JW, Ford ES, Gao X, Choi HK | title = Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third National Health and Nutrition Examination Survey| journal = Arthritis Rheum.| volume = 59| issue = 1| pages = 109–16|date=January 2008| pmid = 18163396| doi = 10.1002/art.23245| doi-access = free}}</ref> Increased production of uric acid is the result of interference, by a product of fructose metabolism, in purine metabolism. This interference has a dual action, both increasing the conversion of [[adenosine triphosphate|ATP]] to [[inosine]] and hence uric acid and increasing the synthesis of purine.<ref name="pmid8213607">{{cite journal| author = Mayes PA| title = Intermediary metabolism of fructose| journal = Am. J. Clin. Nutr.| volume = 58| issue = 5 Suppl| pages = 754S–765S|date=November 1993| pmid = 8213607| doi =10.1093/ajcn/58.5.754S| doi-access = free}}</ref>  Fructose also inhibits the excretion of uric acid, apparently by competing with uric acid for access to the transport protein SLC2A9.<ref name="pmid18327257">{{cite journal|vauthors=Vitart V, Rudan I, Hayward C, Gray NK, Floyd J, Palmer CN, Knott SA, Kolcic I, Polasek O, Graessler J, Wilson JF, Marinaki A, Riches PL, Shu X, Janicijevic B, Smolej-Narancic N, Gorgoni B, Morgan J, Campbell S, Biloglav Z, Barac-Lauc L, Pericic M, Klaric IM, Zgaga L, Skaric-Juric T, Wild SH, Richardson WA, Hohenstein P, Kimber CH, Tenesa A, Donnelly LA, Fairbanks LD, Aringer M, McKeigue PM, Ralston SH, Morris AD, Rudan P, Hastie ND, Campbell H, Wright AF | title = SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout| journal = Nat. Genet.| volume = 40| issue = 4| pages = 437–42|date=April 2008| pmid = 18327257| doi = 10.1038/ng.106| s2cid = 6720464}}</ref> The effect of fructose in reducing excretion of uric acid is increased in people with a hereditary (genetic) predisposition toward hyperuricemia and/or gout.<ref name="pmid8213607"/>

[[Starvation]] causes the body to metabolize its own (purine-rich) tissues for energy. Thus, like a high purine diet, starvation increases the amount of purine converted to uric acid. A [[very low calorie diet]] lacking in [[carbohydrate]]s can induce extreme hyperuricemia;  including some carbohydrate (and reducing the protein) reduces the level of hyperuricemia.<ref name="pmid7024153">{{cite journal| author = Howard AN| title = The historical development, efficacy and safety of very-low-calorie diets| journal = Int J Obes| volume = 5| issue = 3| pages = 195–208| year = 1981| pmid = 7024153}}</ref> Starvation also impairs the ability of the kidney to excrete uric acid, due to competition for transport between uric acid and ketones.<ref name="pmid7405247">{{cite journal|vauthors=Kirch W, von Gicycki C | title = [Renal function in therapeutic starvation (author's transl)]| language = de| journal = Wien. Klin. Wochenschr.| volume = 92| issue = 8| pages = 263–6|date=April 1980| pmid = 7405247}}</ref>