Introduction
- Recently, large-scale studies [e.g. the Health Professionals
Follow-up Study (HPFS) and the Third National Health and Nutrition Examination
Survey (NHANES III)] have clarified a number of long-suspected relations
between lifestyle factors, hyperuricemia, and gout
Pathophysiologic
considerations in lifestyle recommendations for gout
- The amount of urate in the body, the culprit in the pathogenesis
of gout, depends on the balance between dietary intake, synthesis,
and excretion
- Hyperuricemia results
from the overproduction of uric acid
(10%), underexcretion of uric acid
(90%), or often a combination of the two
- Thus, while lifestyle factors such as oral purine load can
contribute to uric acid burden and the risk of gout to a certain level, factors that can affect renal uric acid
excretion or both production and excretion would likely have a substantially
higher impact on uric acid burden and the risk of gout.
- The first line of
lifestyle factors (e.g. meat, seafood, alcohol, fructose-rich food) that
affects serum uric acid levels can acutely lead to the risk of urate crystal formation and gout attacks.
- In comparison, the latter factors that affect insulin resistance (e.g. adiposity, dairy
intake, coffee, fructose) and the renal
excretion of urate can affect uric acid levels and the risk of gout in a long-term
manner.
- Traditional
lifestyle approaches have almost
exclusively focused on acute gout prevention with the first
line of risk factors
- However, since the insulin resistance syndrome is a highly
prevalent comorbidity among gout patients and has severe cardiovascular–metabolic
consequences it is important to consider the factors that can improve insulin
resistance, particularly in long-term lifestyle recommendation.
Gout is a metabolic
disorder associated with multiple associated comorbidities and cardiovascular-metabolic
sequelae
- Although gout’s cardinal feature is inflammatory
arthritis, gout is a metabolic condition associated with elevated uric acid
burden
- A number of associated cardiovascular–metabolic conditions
have been identified, including increased adiposity, hypertension,
dyslipidemia, insulin resistance, hyperglycemia, certain renal conditions and
atherosclerotic cardiovascular disorders
- The prevalence of the metabolic syndrome increased
substantially with increasing levels of serum urate, from 19% for serum urate
levels <6 mg/dl to 71% for levels of ≥10
mg/dl.
- Framingham Study: Gout was associated with a 60% increased
risk of CAD in men, which was not explained by clinically measured risk factors
- Multiple Risk Factor Intervention Trial (MRFIT): participants
with a history of gout had a 26% increased independent risk of myocardial
infarction, a 33% increased risk of peripheral arterial disease, and a 35%
increased risk of coronary heart disease (CHD) mortality; men with gout had a
41% increased risk for incident type 2 diabetes
- HPFS cohort: 59% increased risk for nonfatal myocardial
infarction and 55% for fatal myocardial infarction. Men with gout had a 28%
higher risk of death from all causes, a 38% higher risk of death from CVD, and a
55% higher risk of death from CHD
Low-purine diet vs. a dietary approach against the
metabolic syndrome
- Conventional dietary approach limits drinks or foods that are
known to potentially precipitate an acute gouty attack, such as large servings
of meat and heavy beers.
- However, a rigid
purine restricted diet has been thought to be of dubious therapeutic value and can rarely be sustained for long.
- Furthermore, low-purine
foods are often rich in both refined
carbohydrates (including fructose) and saturated fat.
- These tend to further
decrease insulin sensitivity, leading to higher plasma levels of insulin,
glucose, triglycerides, and LDL-C levels, and decreased HDL-C levels, thereby
furthering the risk of the metabolic syndrome and its complications.
- In contrast, a diet aimed to lower insulin resistance can
not only improve uric acid levels but also improve insulin sensitivity and
decrease plasma glucose, insulin, and triglyceride levels, which could lead to
a reduction in the incidence and mortality of CVD
- For example, from the HPFS data, weight loss, higher dairy
intake, lower fructose intake, and higher coffee intake that are known to
reduce insulin resistance have all been found to be protective against the risk
of developing new cases of gout
- Furthermore, the fact that previously tabooed items such as
purine-rich vegetables, nuts, legumes,
and vegetable protein, despite their high purine content, are not associated with an increase in gout
risk also supports their overall beneficial
effects in gout patients likely
through lowering insulin resistance
- In fact, individuals who consumed a larger amount of
vegetable protein (the highest quintile) had a 27% lower risk of gout compared
with the lowest quintile
- These approaches can not only lead to lower uric acid
levels and the risk of gout in the long run, but can also lower the major
consequences of insulin resistance
- In other words, the overall risk–benefit ratio of the diet approach against the metabolic syndrome
would likely yield a more favorable net
outcome in the long run than the traditional low-purine diet
- Furthermore, as compared with the less palatable low purine
diet, a dietary approach against the metabolic syndrome may achieve higher
long-term compliance
A prescription for
lifestyle change in patients with hyperuricemia and gout
- The goals of
lifestyle modifications are to help prevent
both gout attacks and complications of gout and its comorbidities, including
cardiovascular–metabolic sequelae and premature deaths.
- Thus, if certain factors can help prevent both recurrent
gout attacks and other major health consequences, such measures would be highly
preferred.
- In contrast, if certain factors can reduce the risk of
recurrent gout, but can increase the risk of major health outcomes such as
CVDs, type 2 diabetes, or cancer, it would be difficult to justify the
long-term implementation of such measures among gout patients, particularly
those with comorbidities.
- A simple pharmacologic analogy of this could be the use of
low-dose aspirin. Even though low-dose aspirin can increase the risk of gout,
it is difficult to justify stopping this medication given its cardioprotective benefits.
- The same holistic risk–benefit consideration would be
needed in determining appropriate lifestyle recommendations for gout patients
-Figure 1 summarizes this integration of the impacts of
identified factors on the risk of gout into a recent dietary recommendation for
the general public (i.e. Healthy Eating Pyramid)
- As discussed above, most of the identified factors affect
the risk of gout in the same direction as other major health outcomes, whereas
the potential exceptions include seafood, sugary fruits, and alcoholic beverages.
- Each identified risk factor in Table 3 is discussed with a
holistic risk–benefit recommendation considering both the risk of gout and
other major health outcomes below:
1) Exercise daily and
reduce weight
- Increased adiposity is associated with higher uric acid
levels and an increased future risk of gout, whereas weight loss is associated
with lower uric acid levels and a decreased risk of gout
- Many patients with gout are overweight or obese, and
weight reduction through gradual caloric restriction and exercise can
substantially help lower uric acid levels and the risk of gout attacks, in
addition to its beneficial effects on associated cardiovascular-metabolic commodities
and sequelae
2) Limit red meat
intake
- Red meat intake is associated with higher uric acid levels
and increased future risk of gout
- The mechanism behind this increased risk may be multifactorial.
- The urate-raising effect of artificial short-term loading
of purified purine has been well demonstrated by metabolic experiments in
animals and humans.
- Further, red meat is the main source of saturated fats,
which are positively associated with insulin resistance, which reduces renal excretion
of urate.
- These fats also increase LDL cholesterol levels more than
HDL cholesterol, creating a negative net effect
3) Tailor seafood
intake to the individual taking into account cardiovascular comorbidities, and
consider omega-3 fatty acid supplements
- Seafood intake has been linked to higher serum uric acid
levels and increased future risk of gout, which is likely due to its high
purine contents.
- Increased intake of oily fish, other fish, and shellfish
was associated with an increased risk of gout.
- However, given the apparent cardiovascular benefits from
fish products, particularly oily fish that are rich in omega-3 fatty acids, it
would be difficult to justify a
recommendation to avoid all fish intake considering only the risk of gouty
flares.
- Oily fish may be allowed while implementing other
lifestyle measures, particularly among gouty patients with cardiovascular
comorbidities.
- Furthermore, among patients with gout or hyperuricemia,
the use of plant-derived omega-3 fatty acids or supplements of eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA) could be considered in the place of
fish consumption
- Further, diets enriched in both linolenic acid and EPA
significantly suppress urate crystal induced inflammation in a rat model,
raising an intriguing potential protective role of these fatty acids against gout
flares.
4) Drink skim milk or
consume other low-fat dairy products up to two servings daily
- Low-fat dairy consumption has been inversely associated
with serum uric acid levels and also with a decreased future risk of gout
- Furthermore, low-fat dairy foods have been linked to a
lower incidence of CHD, premenopausal breast cancer, colon cancer, and type 2
diabetes
- Finally, low-fat dairy foods have been one of the main
components of the dietary approaches to stop hypertension (DASH) diet that has
been shown to substantially lower blood pressure
5) Consume vegetable
protein, nuts, legumes, and purine-rich vegetables, as they do not increase the
risk of gout
- These food items (especially, nuts and legumes) are
excellent sources of protein, fiber, vitamins, and minerals
- In fact, individuals who consumed vegetable protein in the
highest quintile of intake actually had a 27%
lower risk of gout compared with the lowest quintile
- Furthermore, nut consumption is associated with several
important health benefits including a lower incidence of CHD, sudden cardiac
deaths, gallstones, and type 2 diabetes.
- Legumes or dietary patterns with increased legume
consumption have been linked to a lower incidence of coronary heart disease, stroke,
certain types of cancer, and type 2 diabetes
- The healthy eating pyramid recommends 1-3 times daily consumption
of nuts and legumes, which appears readily applicable among patients with gout
or hyperuricemia
6) Reduce alcoholic
beverages
- Especially if you are drinking more than a moderate level
(i.e. one to two drinks per day for men, and no more than one drink per day for
women)
- The overall health benefits of sensible moderate drinking (1–2
drinks/day for men and ≤1
drink/day for women) likely outweigh the risks, as more than 60 prospective studies
have consistently indicated that moderate alcoholic consumption is associated
with a 25–40% reduced risk for CHD, and similar protective effect against other
CVD and deaths.
- These benefits may be particularly relevant to middle-aged
men, the demographic in whom gout occurs most often.
- However, starting
drinking is not generally recommended since
similar benefits can be achieved with exercise or healthier eating
7) Limit
sugar-sweetened soft-drinks and beverages
- Fructose
contained in these beverages increases serum
uric acid levels and the risk of gout
- Furthermore, fructose intake has been linked to increased
insulin resistance, a positive energy balance, weight gain, obesity, type 2
diabetes, an increased risk of certain cancers, and symptomatic gallstone
disease
- Multiple health benefits are expected by reducing or
eliminating sugary soft drinks from the diet of gouty patients.
- Sweet fruits (i.e. apples and oranges) have also been
linked to hyperuricemia and the risk of gout. However, given the other health
benefits of these food items, it appears difficult to justify restricting these
items even among gout patients.
8) Allow coffee drinking
if already drinking coffee
- Both regular and decaffeinated coffee drinking have been
associated with lower uric acid levels and a decreased risk of gout
- In addition, coffee drinking has been linked to a lower
risk of type 2 diabetes, kidney stones, symptomatic gallstone disease, and
Parkinson’s disease.
- However, caffeine tends to promote calcium excretion in
urine, and drinking a lot of coffee, about four
or more cups per day, may increase the risk
of fractures among women
- Caffeine, being a xanthine (i.e.
1,3,7-trimethyl-xanthine), likely exerts a protective effect against gout
similar to allopurinol through xanthine oxidase inhibition
- This means that intermittent use of coffee or acute introduction of a large amount coffee
may trigger gout attacks as allopurinol introduction does.
- So if a patient with gout chooses to try coffee intake to
help reduce uric acid levels and the risk of gout, its initiation may need to be similar to that of allopurinol.
9) Consider taking
Vitamin C supplements
- It has been found to reduce serum uric acid levels in
clinical trials and has recently been linked to a reduced future risk of gout
- Whereas these data suggest that total vitamin C intake of 500 mg/day or more is associated with a
reduced risk, the potential benefit of lower intake remains unclear.
- Furthermore, potential cardiovascular benefit of vitamin C
may also be relevant among gout patients, because of their increased risk of
cardiovascular morbidity and mortality.
- Given the general safety profile associated with vitamin C
intake, particularly within the generally consumed ranges (e.g. tolerable upper
intake level of vitamin C <2000mg
in adults according to the Food and Nutrition Board, Institute of Medicine),
vitamin C may provide a useful option in the prevention of gout.
Conclusion
- Lifestyle and dietary recommendations for gout patients should
consider other health benefits and risk, since gout is often associated with
major chronic disorders such as the metabolic syndrome and an increased risk
for CVD and mortality.
Summary in simple words (by ZYL):
- Traditionally, low purine diet is recommended for gout patients.
- However, recent studies found that a general healthy diet that reduce metabolic syndrome (a condition demonstrated by increased waist circumference, increased blood sugar level, increased blood 'fat' level, decreased good cholesterol level and/or high blood pressure) is more beneficial than traditional low purine diet.
- General healthy diet not only reduce the risk of gout, but also contribute to more favorable long-term health outcome, and is more sustainable in the long run.
- The dietary recommendations for gout patients are:
1) Exercise daily and reduce weight
2) Limit red meat intake
3) Moderate seafood (fish) intake is allowed because they are good for heart, although they are also associated with increased risk of gout.
The use of omega-3 fatty acids from plants or supplements of EPA and DHA may also be considered in place of (oily) fish consumption.
The use of omega-3 fatty acids from plants or supplements of EPA and DHA may also be considered in place of (oily) fish consumption.
4) Drink skim milk or consume other low-fat dairy products up to two servings daily
5) Consume vegetable protein, nuts, legumes, and purine-rich vegetables, as they do not increase the risk of gout
6) Reduce alcoholic beverages to 2 standard drink per day for men and 1 standard drink per day for women. For non-drinker, not recommend to start drinking.
[1 Standard drink: 360 ml beer (~5% alcohol), 150 ml wine (~12% alcohol), 45 ml hard liquor (~40% alcohol)]
7) Limit sugar-sweetened soft-drinks and beverages as fructose increase uric acid level. Sweet fruits (i.e. apples and oranges) may also increase uric acid level but given the other health benefits of these food items, they are allowed for gout patients. Personally, I recommend to consume variety of fruits.
8) Allow coffee drinking if already drinking coffee (up to 3 cups per day). For non-coffee drinker, do not consume large amount of coffee at a time as it may trigger gout attack
9) Consider taking Vitamin C supplements (at least 500 mg/day and not exceeding 2000 mg/day)
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