Uric Acid: Step-by-Step Understanding

Uric acid is the root of all gout pain.

But how can a weak compound like uric acid cause so much pain and misery?

When you understand the answer to that question, you will be in a much better position to understand and manage your uric acid.

I know many people want simple answers and clear instructions to manage their gout. I provide help pages on all aspects of uric acid. So that you can find practical answers fast. However, I believe that you will get better treatment if you understand gout better.

To understand gout, you need to understand its root cause – uric acid.

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Hyperuricemia means uric acid levels that are too high. So, now we must ask: how high is too high?

In these hyperuricemia guidelines, I look at all aspects of excess uric acid, which should help you understand your gout, and make it easier for you to discuss high uric acid with your doctor. Note that hyperuricemia is a medical term for high uric acid. In these pages, I look at medical and other scientific literature to explain the nature of hyperuricemia, and it’s relationship to gouty arthritis.

These explanations help you understand gout better. However, if you are looking for practical help to manage gout, you will get that in other sections:

  1. To understand what high uric acid is, and how to manage it’s causes, see my Gout Symptoms guidelines
  2. To find remedies that will lower uric acid when it is too high, see my Gout Treatment guidelines
  3. For dietary changes that can help high uric acid, see my Gout Diet guidelines

Do you have Hyperuricemia chart
Do you have Hyperuricemia?

What Is Hyperuricemia

There is no “official” answer to What is Hyperuricemia?, though the most common definition is above 7mg/dL.

Hyperuricemia definitions vary, so here are a collection of articles that give you examples of how different levels apply in different situations.

Gout Without Hyperuricemia
The common message is: you can’t get gout if you don’t have hyperuricemia. This case study shows us that is not always true. Can you get gout when uric acid is normal? Certainly! Learn how gout happens despite normal urate. See how to recognize and control gout without hyperuricemia.

There is no need to be confused by conflicting views. All that really matters is that you know your own uric acid level, and have a good plan to control it

Hyperuricemia and Gout

These pages explain the relationship of hyperuricemia and gout.

Clinical Manifestations Of Hyperuricemia And Gout
Gout And Hyperuricemia

Hyperuricemia Symptoms& Causes

Symptoms and causes of hyperuricemia.

Drug Induced Hyperuricemia & Gout

Hyperuricemia and gout: Some medications can ‘precipitate’ gout.

Asymptomatic hyperuricemia

Hyperuricemia Treatment

Treating hyperuricemia is little different than treating gout. These studies include some specific references to hyperuricemia.

Treatment of hyperuricemia in patients with gout
Briefing document for febuxostat license application.

Hyperuricemia And Other Illnesses

Hyperuricemia and hypertension
Hyperuricemia and Stress
Psychosomatic Considerations in Hyperuricemia and Gout

Hyperuricemia: Next Steps

I am working on my layman’s summaries of these reports. Please subscribe to my free update service if you want to know when I publish them. There is a subscription form below on the right.

If you have any current issues understanding hyperuricemia, or any interesting experiences or opinions to share, please join the gout forum.

Leave Hyperuricemia to browse all Uric Acid Facts

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Gout at 3.5?

Gout is usually a problem when uric acid is over 5mg/dL, so can we get gout at 3.5?

Gout is caused by excess uric acid. The medical term for this is hyperuricemia. As I explain in those guidelines, doctors usually regard 7 as the start of hyperuricemia. I believe 7 is too high, as I believe anything over 5 carries the risk of gout, but is 5 still too high?

A friend asked me about gout at 3.5:

I have a friend who is having severe gouty attacks… But he claims his uric acid is 3.5. I am dumbfounded. Has anyone heard of this sort of thing??

Here is an extended version of my reply.

Three Reasons for Low Uric Acid Gout

Differential Gout Diagnosis

1. It isn’t gout.

I know that septic arthritis and pseudogout (calcium crystals not uric acid crystals) have similar symptoms. There may be others. A rheumatologist could differentiate this with joint fluid analysis.

In Gout & Rheumatoid Arthritis, I listed several common diseases that might be confused with gout. As well as septic arthritis and pseudogout, that gout study identifies traumatic arthritis and rheumatoid arthritis as diseases that might be confused with gout. If you know of others, please let me know in the Gout at 3.5 discussion.

See 2 more reasons for Gout at 3.5?

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Gout Without Hyperuricemia

The Gout Without Hyperuricemia case study gives us insight about the true nature of uric acid in the real world.

Medical science is driven by statistical analysis, clinical trials, and case studies. Statistics identify potential relationships that can be tested in clinical trials. Real world case studies then identify exceptions, which may help us refine our understanding, or force us to rewrite the rule book.

This case study helps us understand hyperuricemia better, and underlines the need to diagnose gout on an individual basis.

Gout Without Hyperuricemia Case Study

This case study is part of my exploration of the nature of hyperuricemia. The definition of hyperuricemia is quite vague, namely:

An abnormally high level of uric acid in the blood.

The definition fails to be definitive, as it depends entirely on the establishment of a “normal uric acid level.”

Though it is perfectly feasible to calculate a statistical norm, the medical value of doing do is zero. For medical purposes, comparison to a norm might give a general indication where to start looking, but it should never be seen as a rule. Many factors affect the transition from hyperuricemia to gout.

This case study focuses on temperature as a major factor that influences that transition. This is my layman’s summary of the published case study:

Gout without hyperuricemia.
McCarty DJ.
JAMA 1994;271:302-3.

The study is published in JAMA without the usual Methods, Results, Conclusions format, and so I will retain the published layout.

It opens with a paragraph explaining that acute gouty arthritis is rare when uric acid levels are consistently normal. However, the case study that follows illustrates the dangers of ruling out gout when uric acid is not high. The case study will explain why the properties of uric acid account for this phenomenon of normal urate causing gout.

Gout Without Hyperuricemia Case Study Report

I have extracted the history of the case as a timeline, so that you can see the progression. It is the study of an 88-year-old man, who by July 15 1992 was wheelchair-bound. I have retained the same units of measure for uric acid, so if you are more familiar with mmol/L, simply add a decimal point. Thus 208 μmol/L becomes 0.208 mmol/L, though we would normally round this to 0.21 mmol/L.

July 15 1980
Gout presumed by an internist. Treated with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).
July 22 1980
Uric acid tested at 375 μmol/L (6.3 mg/dL). No test of joint fluid for uric acid crystals
July 3 1984
Uric acid tested at 345 μmol/L (5.8 mg/dL)
Uric acid tested at 291, 369, and 357 μmol/L (4.9, 6.2, and 6.0 mg/dL).
Uric acid tested at 387 μmol/L (6.5 mg/dL).
Uric acid tested at 351 μmol/L (5.2 mg/dL).
May 7-15 1991
Hospitalized for polyarthritis. Treated with steroid shot plus prednisone and naproxen pills.
January 11 1992
Uric acid tested at 351 μmol/L (5.9 mg/dL).
April 1992
Right foot painfully swollen and unable to support weight. Codeine for pain control. X-ray shows bone damage [see below].
May 1992
Hospitalized for 2 weeks. Various suggested diagnoses, but not gout. Uric acid tested at 291, 363, and 309 μmol/L (4.9, 6.1, 5.2 mg/dL). Treated with naproxen, but only modest improvement at time of discharge.
July 15 1992
Start of rheumatologist consultancy. Test of joint fluid reveals uric acid crystals, Patient’s hands and feet cold to touch. Treated with colchicine, naproxen, and ranitidine [presumably to limit side effects of naproxen]. Uric acid tested at 381 μmol/L (6.4 mg/dL).
July 22 1992
Foot could bear weight without pain. Uric acid tested at 399 μmol/L (6.7 mg/dL).

Within the case report, the author notes that laboratory test results include a “normal” range. In this case it is 208-506 μmol/L (3.8-8.5 mg/dL). There is also a definition based on the solubility of uric acid, which is explained below. However, the author notes that, whichever definition you choose, all the tests between 1980 and 1992 are considered normal.

Normal Urate Levels Destroy Bone X-ray Image
X-ray of right foot showing small defects in first and third toes. Extensive erosion to fifth toe (inset).

Gout Without Hyperuricemia Case Study Comment

The author starts his commentary with 2 important points about the definition of hyperuricemia:

What is hyperuricemia, statistically?
Higher than 2 standard deviations above the mean for a randomly chosen population. Most labs use samples from blood donors [which is almost certain to include some gout sufferers].
What is hyperuricemia, medically?
Above the point at which crystals form.

The first definition will vary according to the population sampled [search for Normal Uric Acid? No Thanks! for more information]. The second is generally recognized to class readings above 416 μmol/L (7.0 mg/dL) as hyperuricemia [1]. However that is measured at a temperature of 37 °C. At 30 °C, the crystallization point drops to 268 μmol/L (4.5 mg/dL)[2-3]. Tophi are much more common in colder parts of the body[4], and the author refers to unpublished data that records average temperature of the big toe joint to be 32.8 °C.

Due to this specific case, and the recognition that urate deposits will form more readily at lower temperatures, the author recommends joint fluid analysis (arthrocentesis) in all arthritic patients:

Clearly, arthrocentesis is not an optional procedure in the study of patients with arthritis.

The report concludes with a review of other studies that report gout without hyperuricemia,[5-8] noting that other factors besides temperature must also be considered in individual cases.[9]

Gout Without Hyperuricemia: Next Steps

Hyperuricemia is a strong indicator of gout. However, doctors have long known that high uric acid does not automatically lead to gout. I explain why in my asymptomatic hyperuricemia pages.

Now we can see that absence of hyperuricemia should not rule out gout. Elsewhere, I have explained lower uric acid test results during a gout flare. Here we see that, if gout is suspected but uric acid levels are not high, we must also check other factors. Temperature can have a major influence, and other factors may also affect an individual.

Are you in a situation where you suspect gout, but cannot get a clear diagnosis, because you do not have hyperuricemia? Shout out in the gout forum, and I’ll help you convince your doctors, as I had to convince mine. Lowering uric acid is only relevant on an individual case basis. Statistical, and even medical, generalizations can be a guide, but target uric acid levels must be tailored to the gout patient.

Leave Gout Without Hyperuricemia to browse the Hyperuricemia guidelines

Gout Without Hyperuricemia References

  1. Levinson DJ, Becker MA. Clinical gout and the pathogenesis of hyperuricemia. In: McCarty DJ, Koopman WJ, eds. Arthritis and Allied Conditions. 12th ed. Philadelphia, Pa: Lea & Febiger; 1993:1773-1805.
  2. Loeb JN. The influence of temperature on the solubility of monosodium urate. Arthritis Rheum. 1972;15:189-192.
  3. Seegmiller JE. The acute attack of gouty arthritis. Arthritis Rheum. 1965;8:714-723.
  4. Macfarlane DG, Dieppe PA. Diuretic-induced gout in elderly women. Br J Rheumatol. 1985;24: 155-157.
  5. Hadler NM, Franck WA, Bress NM, Robinson DR. Acute polyarticular gout. Am J Med. 1974;56: 715-719.
  6. Hall AP, Barry PE, Dawber TR, McNamara M. Epidemiology of gout and hyperuricemia: a longterm population study. Am J Med. 1967;42:27-37.
  7. Wyngaarden JB, Kelley WN. Gout. In: Stanbury JB, Fredrickson DS, Wyngaarden JB, Goldstein JL, Brown MS, eds. The Metabolic Basis of Inherited Disease. 5th ed. New York, NY: McGraw-Hill International Book Co; 1983:1043-1114.
  8. Rodnan GP. The pathogenesis of aldermanic gout: procatarctic role of fluctuations in serum urate concentrations provoked by feast or alcohol. Clin Res. 1980;28:359A.
  9. McCarty DJ. Precipitation and deposition of monosodium urate monohydrate crystals. In: Gresser U, Zollner N, eds. Urate Deposition in Man and Its Clinical Consequences. Berlin, Germany: Springer Verlag; 1991:12-23.
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Gout Causes: 3 Types Not 2

For a long time, 2 types of gout causes have been recognized: over-producers and under-excreters.

This is important as it is the foundation of all gout treatment. If you change that foundation, you create a new view of gout treatment, with new opportunities.

This is a layman’s summary of a report that changes the foundation of gout causes. It is a highly technical investigation, and I will omit much of the scientific detail from this review. The full review is widely available on the Internet, so simply search for the title using my full Internet search.

continue reading Types of Gout

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Do You Work For Gout?

It seems strange asking if you work for gout.

You might work at your gout treatment plan, or work at learning more about gout.

But, work for gout?

What on earth could I mean?

Working For Gout

Whilst researching heat and ice as gout relief therapy, I discovered the phrase “occupational gout.”

This is not some new form of our much-reviled ailment. It refers to the situation where someone gets gout, or their gout is worsened, simply because of the work they do.

Read more about working for gout

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Hyperuricemia – Excess Uric Acid

Hyperuricemia means elevated uric acid. Everyone knows that excess uric acid causes gout.

But is it that simple?
No, there are many issues.

Where does uric acid come from?

You can’t buy it. Your body produces it by breaking down proteins. If you have too much, you’ve got hyperuricemia. I’ve covered 4 main reasons for excess uric acid below.

How much is too much?

No fixed level is right or wrong. 3-7 mg/dl is average. Some people have higher levels and no gout. If you have gout, you need to keep the level below 6 mg/dl.

How can I control it?

Managing uric acid is never easy. But there are several treatments that help. Understanding why you have a problem is the first step to solving it. Follow the guidance here and throughout my website to find ways to control uric acid that suit you.

Continue reading Hyperuricemia – Excess Uric Acid

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