Gout May Protect Against Alzheimer’s Disease


There may be a bright side to the excruciating pain of gout.

New research suggests that patients diagnosed with this acute inflammatory arthritis face a lower risk of developing Alzheimer’s disease (AD) compared with people without gout.

“Our findings provide the first population-based evidence for the potential protective effect of gout on the risk of AD, and support the neuroprotective role of uric acid,” saidHyon Choi, MD, DrPH, the study’s senior investigator, and director of epidemiology at Massachusetts General Hospital here.

Using data from The Health Improvement Network (THIN), an electronic medical records database representative of the U.K. general population, Choi and his colleagues identified 59,224 individuals with gout (70.8% male, mean age 65.3 years) and matched them to 238,805 controls without gout (71.1% male, mean age 65.3 years) based on age, sex, body mass index, date of study entry, and year of enrollment.

Gout diagnoses, outcomes, and dementia risk factors were identified from electronic medical records.

Over a median follow-up time of 5.1 years the study identified 309 new cases of AD in the gout group and 1,942 cases in the control group, showing an incidence rate of AD in the gout group of 1.0 per 1,000 person-years compared to 1.5 per 1,000 person-years in the comparison cohort, said Choi, who presented the results at the annual meeting of the American College of Rheumatology.

After adjusting for BMI, smoking, alcohol use, prior comorbid conditions, and cardiovascular drugs, the multivariate hazard ratio of AD among those with gout was 0.76 (95% CI 0.66 to 0.87), translating to a 24% lower risk of AD among people with a history of gout compared to those without.

No previous studies have examined the association of gout and AD risk, but Choi pointed out that data from the Rotterdam Elderly Study, published in Brain in 2009, showed an inverse association between serum uric acid levels and the risk of any dementia.

Specifically, the Brain study reported an 11% lower risk of any type of dementia per standard deviation increase in serum uric acid levels (odds ratio 0.89, 95% CI 0.80-0.99) over an 11-year follow-up period.

Furthermore, higher serum uric acid levels at baseline were associated with better cognitive function later in life, he explained.

While the potential biological mechanisms behind this association of uric acid and cognitive health are still speculative, uric acid has proven antioxidative properties and has been shown in animal models to protect against oxidative stress-induced dopaminergic neuron death, he said.

“There are several ongoing studies to prevent progression of Parkinson’s disease using uric acid-raising drugs. If confirmed by future studies, similar investigations may be warranted for AD,” he said.

Association of plasma uric acid with ischaemic heart disease and blood pressure: mendelian randomisation analysis of two large cohorts.


Abstract

Objectives To assess the associations between both uric acid levels and hyperuricaemia, with ischaemic heart disease and blood pressure, and to explore the potentially confounding role of body mass index.

Design Mendelian randomisation analysis, using variation at specific genes (SLC2A9(rs7442295) as an instrument for uric acid; and FTO (rs9939609), MC4R(rs17782313), and TMEM18 (rs6548238) for body mass index).

Setting Two large, prospective cohort studies in Denmark.

Participants We measured levels of uric acid and related covariables in 58 072 participants from the Copenhagen General Population Study and 10 602 from the Copenhagen City Heart Study, comprising 4890 and 2282 cases of ischaemic heart disease, respectively.

Main outcome Blood pressure and prospectively assessed ischaemic heart disease.

Results Estimates confirmed known observational associations between plasma uric acid and hyperuricaemia with risk of ischaemic heart disease and diastolic and systolic blood pressure. However, when using genotypic instruments for uric acid and hyperuricaemia, we saw no evidence for causal associations between uric acid, ischaemic heart disease, and blood pressure. We used genetic instruments to investigate body mass index as a potentially confounding factor in observational associations, and saw a causal effect on uric acid levels. Every four unit increase of body mass index saw a rise in uric acid of 0.03 mmol/L (95% confidence interval 0.02 to 0.04), and an increase in risk of hyperuricaemia of 7.5% (3.9% to 11.1%).

Conclusion By contrast with observational findings, there is no strong evidence for causal associations between uric acid and ischaemic heart disease or blood pressure. However, evidence supports a causal effect between body mass index and uric acid level and hyperuricaemia. This finding strongly suggests body mass index as a confounder in observational associations, and suggests a role for elevated body mass index or obesity in the development of uric acid related conditions.

Source:BMJ

 

Uric Acid Found to Be a Confounder, Not a Risk Factor, in CHD Risk.


Hyperuricemia, although associated with higher risks for cardiovascular disease and hypertension, is likely not a causal factor, but a confounder associated with higher body mass index, according to aBMJ study.

Researchers examined uric acid levels and did genetic analyses in two large Danish cohorts. Subjects were assessed for hypertension at study entry and were followed for the development of ischemic heart disease.

Increases in uric acid were associated with increased risk for both coronary disease and hypertension, but the associations disappeared when taking into account the role of a common mutation in theSLC2A9 gene linked to high levels of uric acid. The presence or absence of the mutation had no association with coronary risk. In fact, higher BMI levels were independently associated with increased uric acid.

The authors write that their findings “suggest that uric acid is of limited clinical interest” in coronary disease or blood pressure.

Source: BMJ 

 

7 Foods That Prevent Grout.


Gout is a disease that is caused by uric acid build-up in the body. Uric acid is formed when the digestive system breaks down purines in our food. A diet low in purines helps by allowing excess uric acid to be flushed out in the urine. 

gout

Some foods that prevent gout:

PINEAPPLE
Pineapple contains an enzyme called bromelain that is an anti-inflammatory. Research has found that supplementing with bromelain may relieve the pain associated with gout.

Ginger
Ginger is a powerful anti-inflammatory that has been found reapeatedly in clinical studies to reduce chronic inflammation. One study in mice found that a compound in ginger may help to reduce the inflammation associated with uric acid buildup.

Turmeric
Turmeric has long been recognized as an anti-inflammatory by many cultures and has been proven in several studies. Some experts recommend a daily dose of turmeric to reduce the inflammation associated with gout.

Cherry Juice
Cherry juice has been used to alleiviate gout symptoms for decades. Small studies in Italy and the United States have reported sucess with cherry juice as a gout treatment, though scientists are not certain what mechanism is active in producing this result. Cherry juice does not appear to lower uric acid levels directly but research suggests that its antiinflammatory properties may play a role in reducing gout attack occurrence from 3-4 times per year to about once a year.

Hot Peppers
Hot peppers are rich in vitamin C which has been shown to reduce uric acid levels.

Watercress
Watercress contains moderate levels of vitamins and minerals and is reputed to be very beneficial to the kidneys. It may help to rid the body of excess uric acid.

Lemons
Studies have found that the higher a person’s vitamin C intake, the lower the incidence of gout. Try adding lemon to your water every day to alleviate gout symptoms.

Source: http://www.naturalcuresnotmedicine.com

Gout Guidelines From ACR Include New Drugs, Diet.


New gout guidelines from the American College of Rheumatology are meant to improve gout management by providing clinicians with clear, readily implemented guidance on urate-lowering therapy (including diet and lifestyle changes), chronic tophaceous gouty arthropathy (CTGA), analgesic and antiinflammatory management of acute gouty arthritis, and drug prophylaxis of acute attacks.

The guidelines, reported in the October issue of Arthritis Care & Research in two parts, and include guidance on the new drugs febuxostat and pegloticase, recently approved for gout management and not yet addressed in the European League Against Rheumatism or British Society for Rheumatology gout guidelines.

Senior author Robert Terkeltaub, MD, told Medscape Medical News,”This is the first time in the 78-year history of ACR that there have been guidelines for the management of gout. This indicates how seriously people in rheumatology take this and how common the problem has become, with more than 8 million cases in the US, affecting 3.9% of adults. What we have here is a disease that is very well understood but ridiculously poorly managed.” Dr. Terkeltaub is chief of rheumatology at the Veterans Affairs Medical Center in San Diego, California, and professor of medicine and associate division director at the University of California in San Diego.

Old Disease, New Management

Part 1 of the guidelines focuses on hyperuricemia and CTGA. The top recommendation is for more intensive education of patients on diet, lifestyle choices, treatment objectives, and management of concomitant diseases; this includes recommendations on specific dietary items to encourage, limit, and avoid.

“We provide a comorbidity check-list for the clinician that I expect will be very useful in day-to-day practice,” Dr. Terkeltaub said. “We have also provided a cohesive set of diet and lifestyle recommendations. This has been a problem because of the fact and fiction mixed in to diet and lifestyle approaches to gout. The guideline is an advance because it provides a more actionable set of recommendations for physicians to talk about with their patients.”

Table. Comorbidity Checklist for Patients with Gout

Obesity, dietary factors
Excessive alcohol intake
History of urolithiasis
Chronic kidney disease
Potential genetic or acquired causes of uric acid overproduction (inborn error of purine metabolism, psoriasis, myeloproliferative or lymphoproliferative disease)
Lead intoxication

 

Dr. Terkeltaub added, “Many patients feel that diet and moderation alone should be sufficient to manage their gout. Diet is important, but what is really important is getting the serum urate to a target appropriate for that patient. At a bare minimum it should be < 6 mg/dL. In clinical practice the serum uric acid level is no longer part of the routine metabolic panel, but it is inexpensive and should be monitored regularly in gout patients.”

Dr. Terkeltaub noted that dietary or alcohol excess can increase uric acid and trigger acute gout attacks in susceptible individuals, but he said that dietary restrictions alone may not reduce serum urate levels enough to prevent joint damage in gout patients.

“The average age gout patient in our clinical trials has a serum uric acid level between 9.5 and 10 mg/dL. Even ideal diet and alcohol intake will likely lower that by only 10% to 15%, which will not bring the typical gout patient to a serum uric acid of 6 mg/dL. Often people need urate-lowering drugs to get them to the target level and keep them there. People feel that if they have fewer gout attacks, they are better, but the disease will progress unless serum uric acid is reduced to a level where deposits of urate crystals in the joint tissues will disappear,” Dr. Terkeltaub said.

Start Low, Go Slow With Allopurinol

The ACR guidelines recommend treating patients with a xanthine oxidase inhibitor, such as allopurinol, as the first-line pharmacologic urate-lowering therapy approach. The recommended goal is to reduce serum urate to less than 6 mg/dL, and the initial allopurinol dosage should be no greater than 100 mg/d, the guidelines say. This should be followed by gradual increase of the maintenance dose, which can safely exceed 300 mg even in patients with chronic kidney disease.

“Clinicians often start allopurinol at doses that are too high but maintain allopurinol at doses that are too low,” Dr. Terkeltaub said. “We give specific guidance on start low, go slow dose escalation.”

To avoid allopurinol toxicity, the guidelines recommend considering HLA-B*5801 prescreening of patients at particularly high risk for severe adverse reaction to allopurinol (eg, Koreans with stage 3 or worse kidney disease and all patients of Han Chinese and Thai descent).

For CTGA, the guidelines recommend combination therapy, with 1 xanthine oxidase inhibitor (allopurinol or febuxostat) and 1 uricosuric agent, when target urate levels are not achieved. They advise using probenecid as an alternative first-line urate-lowering drug in the setting of contraindication or intolerance to at least 1 xanthine oxidase inhibitor (except in patients with creatinine clearance below 50 mL/min). They also recommend pegloticase in patients with severe gout disease who do not respond to standard, appropriately dosed urate-lowering therapy.

“We provide guidance for dose-escalation of urate-lowering therapy for specific case scenarios of mild, moderate, and severe disease including for patients with destructive joint disease that is chronic to their gout. These provide ways to assess the patient in an office setting on clinical findings alone, with serum uric acid. Pictorial representation of most severe patients should help identify who needs more intensive uric acid-lowering therapy,” Dr. Terkeltaub said.

Acute Gout Requires Prompt Treatment

Part 2 of the guidelines covers therapy and prophylactic antiinflammatory treatment for acute gouty arthritis. These guidelines recommend initiating pharmacologic therapy within 24 hours of onset of acute gouty arthritis attack while continuing urate-lower therapy without interruption.

Nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, or oral colchicine are the recommended first-line treatment for acute gout, and combinations of these medications can be used for severe or unresponsive cases.

To prevent the acute gout flares that may accompany the early stages of urate-lowering therapy, the guidelines recommend oral colchicine or low-dose NSAIDs as long as there is no medical contraindication or lack of tolerance.

Dr. Terkeltaub advised caution with colchicine dosing. “One of the major problems in quality of care is that people were getting drowned in colchicine for acute gout. We assessed the evidence and decided to go with the FDA [Food and Drug Administration]-approved regimen of low-dose colchicine for early acute gout flare. That is a major recommendation. When people get drowned in high doses of colchicine for a long time for acute gout, the rate of adverse events is quite high.”

The recommendations were prepared during a 2-year project by an ACR task force panel that included 7 rheumatologists, 2 primary care physicians, a nephrologist, and a patient representative. The draft guidelines then went through 3 rounds of peer review, Dr. Terkeltaub said.

“I’d like to see better education of physicians and other primary caregivers, including nurse practitioners and physician assistants, and then better education of gout patients. If we only accomplish that, we’ll have accomplished a lot. There has been a systematic failure of both quality of care and patient education in gout,” Dr. Terkeltaub said.

Doug Campos-Outcalt, MD, scientific analyst for the American Academy of Family Physicians, reviewed the new guidelines for Medscape Medical News. Dr. Capos-Outcalt is chair of the Department of Family Medicine at the University of Arizona College of Medicine in Phoenix.

Dr. Campos-Outcalt said, “This is a reasonable, limited number of guidelines that are implementable. You don’t like to see guidelines that have 50 recommendations. The ACR guidelines also present, from a family physician perspective, no major changes in standard-of-care.” However, Dr. Campos-Outcalt suggested that a broader effort to disseminate the guidelines to primary care physicians will be needed because few of them regularly read the journal in which the guidelines appear.

Dr. Campos-Outcalt told Medscape Medical News that the guidelines seem reasonable but that before being influenced by them, he would like to take a closer look at the level of evidence each recommendation is based on. “We don’t like to see recommendations based on low-level evidence,” he said. Only about 20% of the ACR recommendations were based on top-quality “level A” evidence (supported by more than 1 randomized clinical trial or meta-analysis). About half of the recommendations were based on level C evidence (consensus opinion of experts, case studies, or standard of care).

Source: Mescape.com