Health Professionals Follow-up Study on Gout: What Do We Now Tell Patients About Diet and Alcohol?

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American College of Rheumatology

Hotline

Health Professionals Follow-up Study on Gout: What Do We Now Tell

Patients About Diet and Alcohol?

Recent reports published in the New England Journal and the Lancet have

raised public interest and fueled controversy about a classic topic in

rheumatology; namely, relationship between diet, alcohol intake and

gout. This ACR Hotline provides a state of the art review of this topic

from an expert in the field.

The Bottom Line:

Dietary trends, increasing obesity and Metabolic Syndrome

prevalence are contributing to the increasing prevalence of gout in the

U.S.

Gout patients need to pay attention to weight management,

including moderation in the intake of meat and seafood rich in

cholesterol and saturated fatty acids and restraint in consumption of

foods and drinks with non-complex carbohydrates. High fat intake and

ketosis factoring into current, popular " low-carb " diets have a variety

of health risks including possible worsening of gout.

In the obese, controlled weight management and reduction in

alcohol consumption have the potential to lower serum urate in a

quantitatively similar way to relatively unpalatable " low purine " diets.

For patients with established gout, moderation in the consumption

of not only beer but also other forms of alcohol is essential. Moderate

beer consumption is acceptable in most patients with therapeutically

well-controlled hyperuricemia and gout.

Nonfat milk and low-fat yogurt have a variety of health benefits,

but dairy products have not yet been established to have clinically

meaningful antihyperuricemic effects for patients with established gout.

Introduction

Gout is well understood and usually one of the easiest of all common

rheumatic diseases to manage (1). At the same time, the prevalence of

gout has risen substantially over the last two decades in the U.S..

Insulin resistance (IR), a central factor in Metabolic Syndrome,

promotes hyperuricemia. Moreover, the dramatic rise in prevalence of

obesity and Metabolic Syndrome in the U.S. appears to be a major

contributor to increasing gout prevalence. Other factors in the rise of

gout prevalence include increases in hypertension and advanced renal

disease, steadily increasing use of diuretics, as well as greater

longevity of the population and more prolonged survival of subjects with

advanced forms of renal and cardiac disease. Significantly, gout

prevalence appears to be rising particularly rapidly among the elderly

and in postmenopausal women.

It is a broadly held clinical impression that an increase in numbers of

complex and refractory cases of gout is compounding the rise in gout

prevalence in the U.S. over the last few decades. Refractory gout often

reflects the limitations of an older generation of drugs for lowering

serum urate that includes allopurinol and probenecid (1). As a result,

there has been renewed attention to the importance for serum urate

lowering of dietary and lifestyle modifications beyond simple weight

management. Such modifications may serve as a primary measure to reduce

the risk of developing gout in predisposed subjects or as a

complementary approach to pharmacologic serum urate lowering in patients

with gout that is difficult to manage.

Background

The association of elevated alcohol consumption with gout is well

recognized, and physiologically consistent with the stimulatory effects

of alcohol intake on hepatic uric acid production and on renal urate

reabsorption. As such, it has generally been recommended that gout

patients limit consumption of all forms of alcohol.

In the past, relatively unpalatable " low purine " diets were employed as

an antihyperuricemic measure, with the expectation of a maximum of ~15%

reduction in serum urate (2). Importantly, recent years have seen a

surge in popularity of " low-carbohydrate, high protein diets " (e.g.,

Atkins, Zone, and South Beach diets). In a small, open study in

overweight male gout subjects, a calorically restricted diet designed

for IR management, with a 40/30/30 protein/carb/fat scheme and

customized for high contents of seafood and mono-unsaturated fat as well

as continued moderation in alcohol, achieved body weight lowering by ~17

pounds and also diminished hyperuricemia by 17 percent (3). But these

results cannot be directly extrapolated to popular " low-carbohydrate "

type diets, for which an adequately powered clinical trial in

hyperuricemia and clinical gout has not yet been done.

Summary Information

Findings have emerged that suggest changes in dietary patterns,

including increased meat and seafood consumption, and possibly decreased

dairy product consumption, are contributing to rising gout prevalence in

the U.S. and possibly other societies (4). Specifically, a prospective

12-year study by Choi et al at Harvard Medical School has been performed

that involved more than 47,000 male medical professionals aged 40 and

older without gout at baseline ( " The Health Professionals Follow-up

Study " ). Over the follow-up period, in which 730 new cases of gout

developed, there was a multivariate relative risk of 1.41 for incident

gout in the quintile with the highest meat intake compared to the

quintile with the lowest meat intake (4). Similarly, for seafood, the

multivariate relative risk was 1.51. In contrast, the multivariate

relative risk of incident gout was reduced to 0.56 for dairy products,

an association that on further analysis held up only for those regularly

consuming " low fat " dairy products (defined as frequent low fat yogurt

intake or drinking two or more glasses of skim milk per day as opposed

to less than one glass per month) (4). Interestingly, the levels of

dietary intake of purine-rich vegetables and total protein did not

correlate with risk of incident gout.

The Health Professionals study also found that even moderate regular

consumption of beer was associated with a high risk of development of

gout (multivariate relative risk of 1.49 per 12-oz beer serving per day)

(5). Consumption of alcohol spirit beverages was associated with a

multivariate relative risk of incident gout of 1.15 per shot (5). In

contrast, moderate wine consumption of 1-2 glasses per day was not

associated with significant change in the risk of incident gout in this

study (5).

Several of the aforementioned conclusions of the Health Professionals

study were previously suggested by smaller studies. But the prospective

design, long-term follow-up, and uniquely large size of the Health

Professionals study render the conclusions particularly compelling.

Limitations of the study include: 1) assessments were primarily

restricted to middle-aged male health professionals; 2) lack of

assessment of serum urate levels; 3) lack of requirement for

confirmation of gout diagnosis by synovial fluid crystal analysis; 4)

sole reliance on questionnaires for data on diet and hypertension; and

5) lack of data for Metabolic Syndrome (4). The linkage of greater meat

and seafood consumption to higher incident gout is not surprising (4).

But the apparent protective effects for incident gout of dairy products

remains to be proven. In this context, the milk proteins casein and

lactalbumin have been reported to have uricosuric effects, but directly

increased dietary milk protein did not have a therapeutically

significant effect on serum urate in a controlled study done in

postmenopausal nuns. Ascertainment bias may underlie the association of

low-fat dairy product consumption with less incident gout (4). In

effect, " skim milk drinkers " may be more attuned to health issues

including hyperlipidemia and weight management. Furthermore, recent

observations suggest dairy products assist in burning fat and promoting

weight loss, likely mediated in part by increased dietary calcium.

The striking differences in incident gout risk between beer and wine in

the Health Professionals study (5) need to be interpreted in the context

of the decline in overall alcohol consumption per capita in the U.S.

over the last 20 years. Over the same period, beer consumption has

grown, particularly including that of the heavily advertised " light

beers " , which contain ~25-35% fewer calories than regular beer per

serving because of reductions in carbohydrates. Beer has a high purine

content, predominantly as readily absorbable guanosine and beer intake

heightens urate production, compounding stimulatory effects of alcohol

metabolites on renal urate reabsorption. But there have been no adequate

direct comparisons of the effects of beer and wine on urate production,

serum urate levels, or on possible provocation of acute gouty arthritis.

Moreover, the observation of lack of an increased risk of incident gout

with moderate wine consumption (5) may reflect ascertainment bias from

as-yet unidentified factors. In essence, male " wine drinkers " may be

different from " beer drinkers. "

Practical Issues

The applicability to patients with established gout of conclusions from

the Health Professionals study of incident gout (4,5) is not yet clear.

This is the case not only for patients with disease that is

well-controlled on allopurinil or uricosuric therapy but also for more

complex cases in which multiple co-existing medical conditions and

medications are driving accelerated deposition of urate crystals in

tissues.

Recommendations for Patients

Consumption of meat, seafood, and alcoholic beverages in moderation and

attention to food portion size and content of non-complex carbohydrates

( " simple sugars " ) are cornerstones of healthy living and have salient

benefits for prevention and management of gout and hyperuricemia. There

are wide concerns about long-term health risks (not limited to

atherosclerosis) with currently popular " low carb " diets. There also are

specific and recent well-publicized concerns about the potential for

ketosis and other effects of popular " low carb " diets heightened in

animal protein and fat to exacerbate hyperuricemia and gout. Subjects

with gout already self-committed to such " low carb " diets should make

every effort to restrain fat content and meat or seafood portion sizes

of meals, to be careful to avoid " crash weight loss " , and to moderate

alcohol consumption. Consumption of vegetables with high purine content

or a diet high in protein by themselves do not appear to raise the risk

of developing gout.

At this point, it would be premature to conclude that dairy products

have direct protective effects for the development of gout or that

moderate wine consumption is preferential to moderate consumption of

other forms of alcohol for patients with established gout. But it is

possible that even moderate regular beer consumption factors into the

risk for developing gout in middle-aged men, possibly reflecting the

relatively high purine content of beer. " Light beers " would not be

expected to provide a significant advantage over " regular beers " with

respect to direct effects on serum uric acid, but longer-term effects on

weight management and glucose tolerance could be meaningful if " light

beer " consumption remains moderate.

Hotline Author: Terkeltaub, MD, VA Medical Center/University of

California San Diego , San Diego, CA

Disclosure: Dr. Terkeltaub currently serves as a paid consultant to

Novartis Pharmaceuticals and to TAP Pharmaceuticals.

Hotline Editors: L. Matteson, MD, MPH; Arthur Kavanaugh, MD.

References:

1. Terkeltaub RA. Clinical practice. Gout. N Engl J Med. 2003; 349:

1647-55.

2. Fam AG. Gout, diet, and the insulin resistance syndrome. J Rheumatol.

2002;29:1350-5.

3. Dessein PH, Shipton EA, Stanwix AE, Joffe BI, Ramokgadi J. Beneficial

effects of weight loss associated with moderate calorie/carbohydrate

restriction, and increased proportional intake of protein and

unsaturated fat on serum urate and lipoprotein levels in gout: a pilot

study. Ann Rheum Dis. 2000; 59: 539-43.

4. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich

foods, dairy and protein intake, and the risk of gout in men. N Engl J

Med. 2004;350:1093-103.

5. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol intake

and risk of incident gout in men: a prospective study. Lancet.

2004;363:1277-81.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org