Wednesday, March 4, 2015

Gout - Prevention and Treatment Options

Gout is a form of inflammatory arthritis mostly affecting joints of the periphery (feet, knees, hands, and elbows).1 The big toe is the most common and notorious site of acute gout attacks, and these attacks are extremely painful. Some have said the pain is on the same level of order as childbirth. Needless to say, gout is no fun ordeal to deal with.

With that being said, my goal is to help you understand how gout develops, and show you what you can do about it in order to prevent or treat it.

The Development of Gout


Gout results from a multi-step process that ultimately ends in the formation of uric acid crystals that are deposited into the joint spaces. Joint inflammation and pain then ensues leading to what is commonly called a ‘gout attack’.

Where do these uric acid crystals come from? And how do they form in the first place?

These questions are the most crucial to understand if you wish to rid yourself of gout or prevent it from occurring in the first place.

Uric acid crystals result from excessive amounts of uric acid in the blood, a condition known as hyperuricemia.2 Hyperuricemia develops when the body reaches a tipping point, where blood uric acid levels rise above a certain level known as the ‘saturation point’ which is approximately 6-7 mg/dL.1-3 This excess in uric acid in the blood is almost always the result of either and/or both of two different scenarios:

  1. Increased production of uric acid due to purine metabolism (breakdown of DNA and RNA molecules in the body)
  2. Decreased urinary excretion of uric acid by the kidneys



Genetic factors can also play a role in the above processes, but account for only approximately 6% of variation in blood uric acid levels amongst individuals.4 For individuals that do have a genetic component to gout, 90% of them suffer from the latter of the above two processes—poor urinary clearance of uric acid leading to hyperuricemia.5


Diet and Lifestyle Components of Gout


Diet and lifestyle factors play a big role in the development of gout. This is actually good news because these factors are modifiable by the person affected by gout. In essence, you have partial control over this aspect of whether or not you get gout or the degree of severity of gout should you come down with it. In particular, the choices made on a daily basis with what you eat play a large role in whether or not you are susceptible to gout. The study below highlights this point.

In the 2011 study titled, Risk Factors for Gout and Prevention: A Systemic Review of the Literature, investigators found that alcohol consumption (especially beer and liquor) along with meat/seafood consumption posed a significant increase in risk for developing gout.6 In addition, the consumption of sugar sweetened beverages and foods high in fructose also increased gout risk.

The above review looked at a wide body of evidence that included a total of 53 separate studies on risk factors for gout. Clearly, it is wise to dramatically reduce or even eliminate the consumption of alcohol, meat and seafood, soda, and junk foods high in sugar given the evidence in this review study.

One other interesting point in this study was the increased risk of gout attacks for those taking thiazide (hydrochlorothiazide) and loop (Lasix, Bumex) diuretics. If you are on these medications and having trouble with gout attacks you should talk to your doctor about switching to an alternative medicine.

In addition to looking at medication and dietary factors related to gout risk, the review also looked at prevalence between various chronic diseases and gout. Not surprisingly, the following medical conditions were associated with a higher incidence of gout – heart disease, diabetes, hypertension, hyperuricemia, obesity, kidney disease, elevated triglycerides and cholesterol levels, menopause, and undergoing surgery. Most of these diseases are a direct cause of the high-fat Western diet. Being overweight or obese plays a significant role in many of these illnesses too, further driving home the importance of what you choose to put on your plate. Losing weight by adopting a healthy, plant-based diet will maximize your ability to stay healthy, maintain a healthy weight, and avoid gout attacks.

Why would losing weight have such a big impact on the development of gout? Isn’t gout due to uric acid crystals and not fat? How does fat play a part in all of this? These are good questions to ask and there seems to be a plausible explanation to them.

Keeping excess body fat off may be of benefit due to its role in the inflammatory process of gout. Recent research has shown that an increase in uric acid crystal deposits in the joint(s) may not be enough in and of itself to cause the excruciating pain that goes along with gout. Instead, it is believed that free fatty acids—like those obtained when eating high-fat meals—acts synergistically with uric acid crystals in the joints to promote the inflammatory process leading to the inevitable debilitating pain of gout attacks.1,7

To explain this in laymen’s terms… The fat and uric acid crystals behave like two troublemakers, both needing one another to start a riot inside the joints. What follows is chaos as various white blood cells and inflammatory markers are released inside the joint in an attempt to deal with these ‘rioters’. Eventually the joint swells, becomes red, and excruciatingly painful. The rioters of fat and uric acid crystals have won.

Purine-Rich Foods and Gout


Another popular discussion when it comes to food consumption and gout is regarding purine-rich food items. It has been shown that purine-rich foods can exacerbate recurrent episodes of gout.8 As mentioned earlier in this article, the metabolism of purines in the body leads to uric acid. Increased uric acid leads to higher levels of uric acid in the blood. Anything that increases the amount of purines in the blood would cause hyperuricemia and eventually a greater risk of gout.

A 2012 study looked at this very topic.8 In this study, researchers analyzed the diets of over 600 individuals with previous gout attacks and assessed what they ate. Purine-rich food intake was separated out by animal versus plant sources. Researchers found that gout attacks increased with higher levels of purine consumption in the diet. There was up to five times as much gout in the group with the highest consumption of purine-rich animal foods compared to the lowest intake of purine-rich animal foods. Purine-rich plant foods also showed increases in gout, but on a much smaller scale. These increases were miniscule compared to the increases purine-rich animal food groups caused. The researchers’ conclusions from this study are found below:

In conclusion, our study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost five times among patients with gout. The impact from animal purine sources was substantially greater than that from plant purine sources. Avoiding or reducing purine-rich foods intake, especially of animal origin, may help reduce the risk of recurrent gout attacks.

Once again, it appears that adopting a whole foods, plant-based diet is beneficial in preventing recurrent gout attacks. It is naturally lower in fat, as well as being less problematic when it comes to the purine content.

For a list of purine content in various foods please refer to this chart from Brenda Davis, RD. Please note that even though dairy products are lower in purines, there are several other reasons from a health perspective to avoid this food group. To learn more on the health risks of dairy see my article – Milk – It Does a Body Bad, Really Bad.

Medical Treatment Options For Gout


Despite some people’s best efforts to evade gout, it still may rear its ugly head. In cases like these there are medications that can be used to treat the attack and to prevent recurrent attacks.

Short-term Drug Treatment Options


First, I’ll talk about drug therapy aimed at reducing the immediate pain and inflammation during an acute attack:1,3

- NSAIDs (Indomethacin, Ibuprofen, Naproxen, etc.) – Non-steroidal anti-inflammatory drugs are often first used to reduce both pain and inflammation in gout. The maximum dose of these medications is typically used providing some relief, but this also leads to an increase in side effects for these drugs. Some of these side effects are serious and include gastrointestinal ulceration/bleeding as well as worsening of heart and kidney disease.

- Colchicine – Colchicine is a first-line treatment option for acute gout attacks. It provides a 50% or greater reduction in pain for approximately 17%-23% of patients who take it. Diarrhea is the most bothersome side effect with colchicine, especially at higher doses. This is often the limiting factor in using colchicine as many people cannot tolerate the loose stools.

- Corticosteroids (Prednisone, methylprednisolone, etc.) – Both oral and injectable corticosteroids are used to help reduce inflammation associated with acute gout attacks. These agents are usually reserved for patients with a contraindication to taking both NSAIDs and colchicine. Their effectiveness is not yet backed by substantial clinical trials, but they may provide some relief given their anti-inflammatory mechanism of action. Injectable steroid shots directly into the joint may be attempted in a hospital setting. Oral steroids are utilized both inpatient and outpatient. Corticosteroids have numerous side effects including sleep disturbances, GI side effects, weight gain, and restlessness amongst other adverse effects.

Long-Term Drug Treatment Options


Long-term medication treatment options used to reduce future gout attacks work by attempting to keep blood uric acid levels below the saturation point of 6 mg/dL. This would help prevent hyperuricemia, but should only be implemented if diet and lifestyle changes are not enough to warrant the same results. The medications used in these cases consist of the following:1,3

- Allopurinol – Allopurinol is the preferred and first-choice urate-lowering therapy (ULT) drug to be used on patients. It has a better safety profile and lower cost than the newer agent febuxostat. Many physicians will prescribe 300mg or less per day of Allopurinol. However, according to clinical studies a dose of 400mg per day is needed in 90% of the population to reduce the blood uric acid level below 6 mg/dl. Possible side effects include diarrhea, nausea, headache, and rash. Patients with kidney disease have to be monitored closely with possible reduced doses used in gout prevention.

- Febuxostat (Uloric) – Febuxostat is a newer, more expensive agent used in the prevention of gout attacks. It costs 10-20 times more than allopurinol. The only advantage is there is no dose adjustment needed in patients with kidney disease like there is with allopurinol. Patients are prescribed 80mg, 120mg, or 240mg of febuxostat daily. Possible side effects include increased liver function tests, hypertension, dizziness, and nausea. There are also concerns that febuxostat can increase cardiac events (strokes, heart attack, and death) in those taking it. Higher doses of febuxostat exhibit a higher likelihood of causing side effects.

There are a other medications that may be used for gout on a more infrequent basis, but I will not cover them here. If you wish to learn more about these information is available in the studies referenced at the end of this article.

Conclusion


Although not fatal, gout is a painful condition that provides for a lot of grief and discomfort for those afflicted by it. This medical condition can likely be prevented if the proper steps are taken with diet and lifestyle modifications. This includes a switch to a whole foods, plant-based diet, the avoidance of meat/seafood and alcohol, and the avoidance of loop and thiazide diuretic drugs. In the rare case that gout still surfaces given these changes, medications are available to treat the pain and inflammation associated with acute attacks.

You have a lot of control over this painful disease. The keys to success lie in the form of a new grocery list and a colorful plate of delicious plant foods. Best of luck to you in your journey to live a healthy life and become gout-free!




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by Dustin Rudolph, PharmD
Clinical Pharmacist

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References:
1 Rees F, Hui M, Doherty M. Optimizing current treatment of gout. Nat Rev Rheumatol. 2014 May;10(5):271-83.
2 Barr WG. Uric Acid. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 165. Available from: http://www.ncbi.nlm.nih.gov/books/NBK273/.
3 Gonzalez EB. An update on the pathology and clinical management of gouty arthritis. Clin Rheumatol. 2012 Jan;31(1):13-21.
4 Reginato AM, Mount DB, Yang I, Choi HK. The genetics of hyperuricaemia and gout. Nat Rev Rheumatol. 2012 Oct;8(10):610-21.
5 Riches PL, Wright AF, Ralston SH. Recent insights into the pathogenesis of hyperuricaemia and gout. Hum Mol Genet. 2009 Oct 15;18(R2):R177-84.
6 Singh JA, Reddy SG, Kundukulam J. Risk factors for gout and prevention: a systematic review of the literature. Curr Opin Rheumatol. 2011 Mar;23(2):192-202.
7 Cronstein BN, Sunkureddi P. Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29.

8 Zhang Y, Chen C, Choi H, et al. Purine-rich foods intake and recurrent gout attacks. Ann Rheum Dis. 2012 Sep;71(9):1448-53.

Photo credit: HD Walls

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