Environmental Triggers of Hyperuricemia and Gout

Abstract

Gout is the most prevalent type of inflammatory arthritis worldwide and environmental factors contribute to hyperuricemia and risk for gout flare. Causes of hyperuricemia include increased purine consumption from meat, alcohol, and high fructose corn syrup as well as medications such as cyclosporine, low-dose aspirin or diuretics. Triggers for gout flares include increased purine consumption and medication use such as urate lowering therapy and diuretics. Environmental exposures including lead exposure, particulate matter exposure, temperature fluctuations and physiologic stress have been found to trigger flares. In the right clinical scenario, these factors should be considered when treating gout patients.

Historically, the first documented evidence of gout appeared in ancient Egypt. Egyptians are credited with the first use of the word “podagra” for descriptions of gout flares of the first metatarsophalangeal joint in 2640 BC [1]. In addition to the documentation of the term podagra on papyrus, there has been archaeological evidence of urate crystals in joints of Egyptian mummies. Although today we understand that gout can affect people of all racial and socioeconomic backgrounds, the disease was historically associated with an “indulgent” lifestyle of the upper class. Hippocrates was among the first to make this observation, describing gout as “arthritis of the rich” [2].

Throughout history, there have been several gout “epidemics”, each providing insight into environmental factors predisposing individuals to gout. A historical survey noted that over two-thirds of all Roman Emperors from 30 to 220 AD suffered from gout [3]. Heavy consumption of port wines, a preferred beverage of the Roman ruling class, was typically produced in lead-lined pots or kettles. Nriagu estimates that the daily consumption of lead for the average Roman Emperor approached 150ug, far exceeding thresholds deemed to be safe by contemporary standards. Chronic lead intoxication, in turn, led to the development of debilitating gout and neurologic disturbances in many, possibly contributing to the downfall of the Roman Empire [3]. These epidemics continued into the Renaissance period, most notably with King Henry VIII whose overindulgent nature supported the commonly used term for gout, “the Disease of Kings”. It has been speculated that Michelangelo suffered from gout, possibly related to chronic exposure to lead-based paints used in his masterpieces such as the Sistine Chapel [4]. More recently, the popularity of moonshine in the southeastern United States, made in part by running alcohol through a lead-lined car radiator, led to another gout epidemic related to lead toxicity and plumbism [5].

This review will examine modern environmental risk factors in the development of hyperuricemia and gout, some of which have persisted since historic times. We will first focus on triggers for the development of hyperuricemia such as diet, alcohol use, medications, and lead exposure. Additionally, we will review environmental factors associated with the occurrence of flares that in some cases may act independently of serum urate concentrations such as physiologic stress, trauma, temperature changes, and air pollution.

Triggers for Hyperuricemia Leading to Gout

Considered a “necessary but insufficient” risk factor for gout, hyperuricemia results as an imbalance between dietary intake of purines that serve as building blocks of uric acid or endogenous uric acid synthesis (produced during cell turnover) and its excretion via the kidneys or gastrointestinal tract. Defined by serum concentrations exceeding its solubility threshold (>6.8 mg/dl or 400 umol/L), hyperuricemia may result from environmental exposures that tip the balance, particularly those related to increased purine consumption (e.g., diet, alcohol) or factors leading to diminished urate excretion (e.g., lead intoxication, medications) (Figure 1).

Figure 1. Environmental factors associated with hyperuricemia, serum urate lowering, and gout flare risk.

Hyperuricemia results as an imbalance between uric acid its excretion via the kidneys or gastrointestinal tract and may result from environmental exposures that tip the balance, particularly those related to increased purine consumption (e.g., diet, alcohol) or factors leading to diminished urate excretion (e.g., lead intoxication, medications)

Diet

A number of foods are linked to the development of hyperuricemia and gout based on high purine content (Table 1). Red meat (a stable of the Western diet) is often implicated in the development hyperuricemia, although most cuts of beef contain only moderate quantities of purine (~100mg purine/100g) [6]. Veal, chicken breast with skin, and lamb have higher purine contents (~170–180mg purine/100g) with organ meats such as heart, liver, kidney, thymus demonstrating the highest purine content of any foods, with calf thymus yielding ~1260mg of purines/100g [6].

Table 1.

Selected studies examining associations of high-purine content food intake with hyperuricemia and gout

First Author, publication year	Study Design, population source	Dietary Exposure	Sample Size	Results
Choi, 2004 [77]	Prospective cohort, American Health Professionals Follow up Study	Meat, seafood, purine-rich vegetables, daily products	47,150	RR of gout when comparing highest and lowest quintiles of meat and seafood consumption were 1.41 and 1.51, respectively
Choi, 2005 [8]	Prospective cohort, NHANES	Meat, seafood, dairy	14,809	Uric acid difference when comparing highest and lowest quintiles of meat and seafood consumption was 0.48mg/dL and 0.16mg/dL, respectively
Villegas, 2012 [78]	Cross-sectional, Shanghai Men’s Health Study	Rice, poultry, red meat, fish, eggs,	3,978	OR of hyperuricemia when comparing highest and lowest quintiles of seafood consumption was 1.56, no association with meat or vegetable consumption
Schmidt, 2013 [79]	Cross sectional, European Prospective Investigation into Cancer and Nutrition Oxford Cohort	Meat, fish, dairy, eggs, alcohol, coffee, tea, fructose-rich drinks,	1,693	Vegans had the highest concentrations of uric acid followed by meat eaters; vegetarians and fish (but not meat) eaters had the lowest concentrations of uric acid
Teng, 2015 [80]	Prospective cohort, Singapore Chinese Health Study	Rice/noodles, meats, vegetables, fruits, soy, non-soy legumes, nuts/seeds, dairy, beverages, condiments, preserved food	51,114	HRs of gout when comparing highest and lowest quartiles of protein, poultry, and fish consumption were 1.27, 1.27, and 1.16, respectively
Rai, 2017 [81]	Prospective cohort, American Health Professional Follow up Study	Fruits, vegetables, nuts/legumes, dairy, whole grains, sodium, sweetened beverages, red and processed meats	44,444	RR of gout when comparing highest adherent DASH diet to lowest adherent DASH diet was 0.68. RR of gout when comparing highest adherent Western diet to lowest adherence Western diet was1.42
Aihemaitijiang, 2020 [82]	Cross sectional, China Health and Nutrition Survey	Red meat, poultry, seafood, legumes, vegetables, fungi	6,813	RRs of hyperuricemia when comparing each 10g increase of meat and legumes were 1.024 and 1.10, respectively
Yokose, 2022 [83]	Prospective cohort, US Nurses’ Health Study	DASH, Alternate Mediterranean Diet Score, AHEI, Prudent diet, Western diet	80,039, females	HRs of gout when comparing highest and lowest adherence quintiles to a particular diet included: DASH (0.68), Alternate Mediterranean Diet Score (0.88), AHEI (0.79), Prudent (0.75), and Western (1.49) diet; High adherence to DASH diet with normal BMI compared to low adherence to DASH diet and abnormal BMI lead to HR of 0.32 for the development of gout.

RR: Relative Risk, OR: Odds Ratio, HR: Hazards Ratio, NHANES: National Health and Nutrition Examination Survey, DASH: Dietary Approaches to Stop Hypertension, AHEI: Alternative Healthy Eating Index (AHEI), BMI: Body Mass Index

Fish and seafood consumption may also precipitate hyperuricemia, again due to elevated purine content. Like different meats, not all fish and seafoods have equal purine content. Anchovies, trout, mackerel, herring, tuna, salmon, sardines, and shellfish have substantially higher purine content. In general, processed, dried, and canned fish have a higher purine content than fresh fish, with dried anchovies containing ~1100mg of purines/100g [6]. Given potential cardiovascular protection and reduction in gout flare frequency observed with omega-3 fatty acid consumption, the choice of fish/seafood may be important to optimize overall health benefits [7]. Fish with lower purine content such as cod, haddock, perch, pike, and sole contain only ~110–130mg of purines/100g.

Using the National Health and Nutrition Examination Survey (NHANES), the link between increased dietary consumption of purines and increased serum urate has been shown. Individuals consuming <1 meat serving/day demonstrate serum urate concentrations approximately 0.5mg/dL lower than in those consuming >2 meat servings/day [8]. Likewise, daily fish consumption of >2 servings corresponds to modest serum urate elevations, 0.16mg/dL higher compared to individuals consuming <1 fish serving/day [8].

Although there are a number of vegetables containing high quantities of purine (e.g., asparagus, mushrooms, spinach, green peas, and cauliflower), there is little data to suggest that these purine-rich foods contribute to hyperuricemia or gout risk. Two prospective studies found that vegetarians had the overall lowest risk of developing gout when compared to both vegans and non-vegetarians [9]. These findings were echoed in a 12-year prospective cohort study demonstrating no increased risk of gout with ≥1 serving of high-purine vegetables per day [8]. An additional meta-analysis of 19 studies found no associations between consumption of high-purine vegetables and hyperuricemia [10]. The combination of this data indicates that purine content alone may not fully explain the association between diet and hyperuricemia. These studies would suggest that healthcare providers should avoid “blanket” recommendations of a low-purine diet in gout, and rather suggest one lower in foods such as high-purine meats or seafood that have been more strongly implicated to raise serum urate concentrations.

In addition to meat, another staple of the Western diet includes high-fructose corn syrup, an artificial sweetener introduced in 1967. This product is used in many heavily processed foods and beverages, most notably soft drinks. Increased consumption of high-fructose corn syrup has correlated with the increased prevalence of gout [11]. Mechanistically, fructose intake leads to uric acid production by increasing adenosine triphosphate (ATP) degradation to adenosine monophosphate (AMP), a precursor to uric acid. Indeed, intravenous fructose infusions significantly increased serum urate concentrations one small study [12]. A systematic review and meta-analysis subsequently supported the existence of a dose-dependent relationship between the consumption of high-fructose corn syrup and serum urate levels, with “high consumers” (≥2 servings/day) demonstrating a 62% higher rate of incident gout compared to “low consumers” (<1 serving/day) [11]. Interestingly, fructose occurring in its natural form (e.g., fruit) does not appear to confer the same risk as artificially manufactured fructose in the form of corn syrup. In fact, a study of male runners found that fruit consumption (≥2 servings/day) was associated with a 27% lower risk of incident gout compared to those with lower amounts of intake [13].

There are a number foods available which appear to decrease serum urate, subsequently lowering gout risk. Consumption of ≥1 daily serving of dairy products (i.e., milk/yogurt), for example, has been associated with significant, albeit modest decreases in serum urate approaching 0.25mg/dL [8]. Low in overall purine content, dairy products contain casein and lactalbumin which have uricosuric properties [8]. Along this same line, patients with Vitamin D insufficiency and deficiency have significantly higher serum urate levels (0.33mg/dL and 0.45mg/dL, respectively) based on a meta-analysis of 7 cross-sectional studies which specifically included studies which compared serum urate acid values between Vitamin D replete and Vitamin D insufficiency groups [14]. This data suggests (but does not prove) that supplementation with this vitamin could portend urate-lowering effects. A metaanalysis of 32 studies, which had less strict inclusion criteria than the prior study and included any studies that examined an association between serum urate and Vitamin D levels, reported a pooled odds ratio of 1.5 between Vitamin D deficiency and hyperuricemia [15]. Given the potential of bias in these observational studies, future randomized controlled trials (RCTs) are needed to adequately assess the potential utility of vitamin D supplementation in gout. One small randomized control trial has shown a small reduction in serum urate concentration in prediabetic patients with hyperuricemia [16].

In contrast to the more limited evidence for Vitamin D, several randomized controlled trials have shown that serum urate levels are reduced with Vitamin C supplementation [17–19] with a meta-analysis of 13 RCTs equating Vitamin C doses of 500mg/day to serum urate reductions approaching 0.35mg/dL [20]. Although cherry juice and/or extract are well-advertised as gout remedies, evidence supporting their use is mixed. A meta-analysis of 6 studies (including RCTs and observational studies) found that cherry consumption yields only modest urate-lowering effects [21]. More recently, Stamp and colleagues found no significant decrease in serum urate with varying amounts of cherry concentrate [22]. With reports of decreased rates of gout flares with cherry consumption, this effect may more likely be due to anti-inflammatory pathways rather than urate-lowering properties [23, 24].

The consumption of coffee, another staple of the Western diet, may also lead to decreased serum urate. A meta-analysis of 9 observational studies by Park and colleagues showed a dose-dependent relationship with the highest decrease in serum urate (0.36mg/dL) attributable to the consumption of 4–6 cups of coffee daily compared with those with no consumption [25]. In addition to coffee consumption, tea may also exert a urate-lowering effect. In a mouse model, both green and black teas were shown to have a hypouricemic effect [26], findings, however, that have not been consistently replicated in human subjects [27–30]. Although coffee and green tea contain many compounds including caffeine, it is speculated that polyphenols (which can inhibit xanthine oxidase) explain any urate-lowering effects [31–33].

Alcohol

Increased alcohol consumption may also contribute to elevated serum urate levels, an effect that likely relates to purine content in some alcohol products as well as reduced secretion of uric acid induced by lactate, a metabolic byproduct of alcohol [34]. Using NHANES, investigators have shown that compared to individuals reporting no alcohol intake, those consuming ≥1 daily serving of beer (0.46mg/dL higher) or liquor (0.29mg/dL higher) have higher serum urate concentrations, an association not seen with wine [35]. The potential for a differential impact of different forms of alcohol may relate to the highly variable purine content across products. A study leveraging high-performance liquid chromatography demonstrated that 1 beer serving contains up to 1000ug/L of purines, whereas whiskey, brandy, and wine each contain less than 100ug/L [36].

Lead

As noted above, historic gout epidemics may be at least partially explained by increased exposures to lead, leading to saturnine gout. Increased blood lead levels cause tubulointerstitial nephritis, subsequent decreases in the renal secretion of uric acid coupled with increased reabsorption, that together contribute to the development of hyperuricemia [37]. In addition to this mechanism, it is also proposed that increased blood lead levels cause glomerular disruption, albuminuria, chronic kidney disease and decreased renal urate filtration [37], all of which conspire to further exacerbate hyperuricemia [38–42].

A 2010 Nigerian study demonstrated a dose-dependent relationship between occupational exposures to lead and serum urate concentration [43]. Although current studies suggest that exposures resulting in blood lead levels <5–10ug/dL are considered “safe” [44], an NHANES study noted a dose-dependent relationship between blood lead concentrations considered “safe” and the risk of both gout and hyperuricemia [45]. Even after accounting for confounders, those in the highest quartile of blood lead concentration (concentrations deemed safe based on U.S. standards), had a 3.6-fold higher risk of gout and 1.9-fold higher risk of hyperuricemia when compared to those in the lowest quartile [45]. Additionally, a study done on U.S. adolescents 12–19 years of age showed a positive linear relationship with blood lead levels and serum urate, suggesting that no level of lead is likely “safe” and without adverse physiologic effects [46].

Medications

A number of different medications may contribute to hyperuricemia and gout risk (Table 2). The calcineurin inhibitor cyclosporine gained popularity as a post-transplant immunosuppressant in the 1980’s and has been correlated with both increased rates of hyperuricemia and an increased risk of gout [47]. More recently, there has been increased use of tacrolimus over cyclosporine for long-term immunosuppression in the setting of transplant. A 2020 study found that nearly 20% of patients on cyclosporine had a diagnosis of gout, whereas patients on tacrolimus had approximately half the rate of gout and this was similar to rates observed in the absence of immunosuppressant therapy [48].

Table 2.

Non-gout medications with documented effects on serum urate concentrations

Increased serum urate	Proposed Mechanism
Anti-tubercular  - Pyrazinamide  - Ethambutol	Reduces renal excretion of uric acid [84]
Aspirin (low-dose)	Inhibits tubular secretion, decrease GFR [85, 86]
Beta Blockers (e.g., metoprolol)	Increases intracellular glucose, increasing serum urate by the pentose phosphate pathway [51]
Cyclosporine	Decreases GFR, reduces uric acid secretion in proximal tubule [87, 88]
Cytotoxins (e.g., chemotherapies)	Increases cell turnover leading to increased purine burden
Diuretics	Decreases fractional excretion of urate [89]
Nicotinic Acid (Niacin)	Interacts with URAT1 and OAT2 transporters in the nephron leading to decrease urinary excretion of uric acid [90, 91]
Decreased serum urate	Proposed Mechanism
Aspirin (high-dose)	Inhibits tubular reabsorption of uric acid [92]
Calcium channel blocker, dihydropiridines (e.g., amlodipine)	Dilates afferent arterioles and increases GFR and subsequent uric acid filtration; vasodilates blood vessels causing hemodilution effect [52]
Losartan	Inhibits uptake of uric acid by URAT1 transporter in nephron [93]
SGLT2 inhibitor (e.g., empagliflozin)	Increases glycosuria stimulates uric acid excretion and inhibits reabsorption [94]

GFR: Glomerular Filtration Rate, URAT1: Urate Transporter 1, OAT2: Organic Anion Transporter 2

Other medications implicated in hyperuricemia and gout include diuretics, select antihypertensives, low-dose aspirin, anti-tubercular drugs (i.e., pyrazinamide, ethambutol), cytotoxins in the context of chemotherapy and resulting cell turnover, testosterone replacement, and nicotinic acid [49]. Of these, diuretics may pose the most meaningful impact given frequent use and potent effects on serum urate levels. In a study of nearly 6,000 hypertensive patients, the use of loop and thiazide diuretics were associated with a 2.3- and 1.4-fold increased risk, respectively, with gout risk [50]. Metoprolol, another commonly prescribed medication for hypertension and heart disease and used commonly in combination with diuretics has also been shown to increase serum urate, particularly among black or African American patients [51]. A study examining dihydropyridine calcium channel blockers (e.g., amlodipine) reported a serum urate-lowering effect for these agents, an association that was particularly strong when blood pressure was well controlled [52]. These findings were supported by results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), which found that amlodipine administration lowered gout risk by 37% [53]. A urate-lowering effect has previously been well attributed to the angiotensin II receptor blocker (ARB) losartan [54], an effect that does not seem to be shared by other ARBs or ACE inhibitors [53, 55]. Together, these data suggest that for patients with hyperuricemia or at high risk for gout, careful selection of antihypertensives could yield benefit.

The management of diabetes mellitus type II (DMT2), another common comorbidity in gout, has evolved over the past 10 years with several novel therapies available. In addition to glucose-lowering effects, sodium/glucose transporter-2 inhibitors (SGLT2) also reduce cardiovascular risk [56]. In addition, SGLT2 inhibitors appear to reduce gout risk compared to glucagon-like-peptide-1 (GLP1) receptor agonists or dipeptidyl peptidase inhibitors in the treatment of DMT2 [57, 58], a protective effect that may result from urate-lowering. A meta-analysis of 62 studies found that various SGLT2 inhibitors lowered serum urate by a mean of 0.6mg/dL with empagliflozin yielding the greatest effect with mean reductions approaching 0.8mg/dL [59].

Triggers for Gout Flares

Diet

In addition to contributing to hyperuricemia and increased risk for gout development, a select number of environmental exposures have also been examined as potential triggers of gout flare, an effect that in select circumstances may be attributable to resulting fluctuations in serum urate concentration. Using questionnaire data from more than 500 patients with gout, investigators found that over one-third of patients reported at least 1 such trigger for gout flare with the most frequent triggers including red meat or seafood consumption, alcohol use, dehydration, injury or excess activity, or ambient temperature/weather [60]. In addition to associations with increased serum urate concentrations in large epidemiological studies, the consumption of foods with high-purine content has been linked with the risk of experiencing recurrent gout flare in other observational studies. Using a novel internet-based case-crossover study design, investigators found that increasing purine intake (>3 gm over a two-day span vs. those consuming <1g over the same time period) increased the odds of experiencing a gout flare by almost five-fold [61].

Alcohol

Alcohol consumption may also act as a potential trigger for acute gout flares in addition to adversely affecting serum urate concentrations [62]. Again, using an internet-based case-crossover study, Neogi and colleagues observed a dose-dependent relationship between alcohol consumption over the preceding 24 hours and flare risk [63]. Compared to those reporting no alcohol consumption, there was a 36% (95% CI 1.00 to 1.88) increased risk of flare with >1–2 servings of any type of alcohol (beer, liquor, wine) and a 51% (95% CI 1.09 to 2.09) increased risk of flare with >2–4 servings, respectively [63]. Of note, this risk appeared to be independent of alcohol type, suggesting that the increased flare risk posed by alcohol intake may related to factors other than purine content.

Medications

In addition to affecting long-term changes in serum urate, the use of select medications that acutely raise or lower serum urate have been implicated as precipitants of gout flare. This has perhaps been best detailed with the initiation of gout treatments such as allopurinol or febuxostat where flares are considered to be a “physiologic” consequence of urate-lowering and serve as the basis for recommendations supporting anti-inflammatory prophylaxis [64, 65]. Likewise, acute urate increases accompanying therapies such as diuretics may also increase flare risk [66]. Adjusting for alcohol consumption and purine intake, investigators found that diuretic use over the previous 2-day period increased the risk of flare by 3.6-fold (95% CI 1.4 to 9.7) with a similar magnitude of risk between loop and thiazide diuretics [67].

Climate

In addition to the aforementioned, climate could also impact the natural course of gout, specifically the occurrence of flares. A study examining the frequency of Google searches for “gout” found that this search term was used most frequently during spring and early summer months [68], suggesting a seasonal or weather-based influence on gout-related symptoms. Cooler temperatures promote uric acid crystallization, a fact that might explain the predominance of gout in cooler body regions such as the first metatarsophalangeal joint. A meta-analysis by Park and colleagues found that gout flares were most likely to accompany extreme variations (particularly increases) in day-to-day temperatures, which are most common during spring months [69]. Besides ambient temperature, humidity may also play a role in flare occurrence, with one study showing that most flares occur under conditions of both high temperature and low humidity Although the precise association and potential mechanisms linking weather and ambient temperatures to flare risk remain unknown, current trends in global warming could significantly effect the burden posed by gout.

Air Pollution

Ambient air pollution has also recently been associated with an increased risk of gout flares. A 2021 study found that for every 1mg/m³ increase in carbon monoxide concentration, the rate of gout hospitalizations increased by almost 4% [70]. Another study reported that exposures to ozone and particulate matter increased the risk of gout-related emergency department visits by 7% and 2%, respectively [71]. An additional study found that particulate matter levels >100ug/m³ showed a positive linear relationship with number of gout flares [72]. Although mechanisms underpinning the associations of air pollution with flare risk are not well understood, there is speculation that inhalant particulate matter could potentiate activation of the NLRP3 inflammasome, which in turn facilitates interleukin-1β production and acts as a key inflammatory mediator in flares [73]. NLRP3 inflammasome activation has been shown, for example, to be increased following quartz dust inhalation in iron workers [74]. Of note, these studies did not adequately adjust for socioeconomic status, which may confound study findings.

Physiologic Stress

Physiologic stress (and its downstream consequences) also appears to act as a trigger of gout flares. For example, post-surgical gout flares are common in the inpatient setting. In a study of 70 gout patients undergoing surgery, nearly half experienced a flare with mean occurrence on day 4 post-operatively [75]. Flares in this study most often accompanied large serum urate fluctuations (pre- to post-operatively) as well as in patients not receiving urate-lowering therapy, suggesting prior control of gout and continuation of urate-lowering therapy during the peri-operative period are most important factors in preventing flare in this setting. Although empiric data is limited, joint trauma is anecdotally reported to precede flare in many. Dehydration may also be tied to flare risk. A study of primary care patients found that nearly 5% reported dehydration prior to a gout flare [60]. Neogi and colleagues reported nearly a 50% reduction in gout flare risk in individuals consuming >8 glasses of water/day vs. those drinking only 0–1 glasses of water [76].

Summary

In summary, there are several environmental factors that promote hyperuricemia, increase gout risk and predispose patients to recurrent flares. In this review, we have summarized dietary patterns, medication use, and other select environmental exposures that have been implicated in the pathogenesis of gout. In general, the influence of individual environmental exposures on serum urate concentration or gout risk often cluster and thus are difficulty to tease apart. Moreover, the effect of individual factors appears to be modest, suggesting that interventions targeting these exposures may be best suited as part of a holistic approach to disease prevention or as adjuvant therapies among patients with established gout.

Key Points.

• Hyperuricemia results as an imbalance between purine intake, endogenous uric acid synthesis, and its excretion via the kidneys or gastrointestinal tract; an imbalance that may relate to a number of different environmental exposures.

• Increased purine consumption from meat, alcohol, and high fructose corn syrup contributes to both hyperuricemia leading to gout, as well as the risk of flare.

• Medications such as cyclosporine, low-dose aspirin, diuretics, and other select treatments contribute to hyperuricemia, while calcium channel blockers, losartan, and SGLT2 inhibitors demonstrate urate-lowering effects.

• Environmental exposures to lead, air pollution, and ambient temperature increases may also act as triggers for gout flares.

Gout, characterized by hyperuricemia and recurrent episodes of an acute painful inflammatory arthritis separated by asymptomatic inter-critical periods, is the most common type of inflammatory arthritis. Gout incidence has increased in recent decades, an increase that appears to be due in part to changes in several environmental factors including dietary patterns, medication use, and other select environmental toxins and exposures.

Clinical Care Points.

• High-purine content foods in the form of meat, alcohol, and high-fructose corn syrup contribute to hyperuricemia, gout, and gout flare risk, whereas high purine content vegetables and fruit do not appear to contribute to this risk.

• Medications such as amlodipine, losartan, and SGLT2 inhibitors have shown serum urate and gout risk lowering effects, whereas diuretics and beta blockers contribute to these risks.

• Lead exposure may serve as a relevant environmental risk factor for hyperuricemia and gout, even at levels that are typically considered safe by regulatory bodies.