Low Levels of Uric Acid and Diseases Associated with It
Blood uric acid levels are considered low (hypouricemia) at 2 mg/dl or less [1].
It is not considered to be a medical condition but may signal certain health problems.
Multiple Sclerosis, Parkinson’s Disease, and Motor Neuron Disease
The link between uric acid levels and neurological and nerve diseases is still unclear.
Some small studies have suggested a link between low uric acid and certain brain diseases, but large-scale studies haven’t confirmed this connection.
For example, lower blood values have been associated with the following disorders in limited studies:
- Multiple sclerosis (MS) [2]
- Alzheimer’s disease (AD) [3]
- Huntington’s disease (HD) [4]
- Parkinson’s disease (PD) [4]
However, these studies dealt with associations only, which means that a cause-and-effect relationship hasn’t been established.
Nonetheless, it has been proposed that higher blood uric acid levels may be neuroprotective.
In a large population-based cohort study, a negative relationship was observed between gout and Parkinson’s disease in patients aged 65 and above. A similar trend has been shown between uric levels and Huntington’s disease, suggesting that uric acid may play a role in preventing neurodegeneration [5, 6].
Additional research is needed to determine if uric acid levels within a certain range support brain health.
Optic Neuritis
In one study, uric acid levels were lower in patients with optic neuritis, an inflammatory demyelinating disease of the optic nerve that is often the first symptom of Multiple Sclerosis. These findings have not been replicated [7].
What Causes Low Uric Acid Levels?
Causes shown here are commonly associated with this low blood uric acid levels. Work with your doctor or other health care professional for an accurate diagnosis.
Wilson’s Disease
Wilson’s disease is a disease in which copper accumulates in tissues of vital organs like the brain and liver. It can lead to decreased blood uric acid levels because of associated kidney problems (i.e., Fanconi syndrome) that increase urinary uric acid excretion [8].
Medication/Treatments
Hypouricemia can be found in 1% of hospitalized patients. In most cases, the cause is related to drugs like salicylates, allopurinol, x-ray contrast agents, and glyceryl guaiacolate [1].
In addition, drugs like losartan (an angiotensin II receptor antagonist drug), fenofibrate (a drug of the fibrate class, mainly used to reduce cholesterol levels) and some non-steroidal anti-inflammatory drugs (NSAIDs) reduce the serum uric acid (SUA) levels [9].
Also, forced diuresis (increased in urination) used mainly in the treatment of renal colics (abdominal pain from kidney stones) in suicide-attempt patients may result in hypouricemia [1].
Chemotherapy and Cancer
IV (parenteral) nutrition and chemotherapy can lower uric acid levels. Levels are often monitored in cancer patients receiving chemotherapy. Several malignant diseases including Hodgkin’s disease, sarcoma, and glioblastoma have been associated with hypouricemia [1].
Scientists hypothesize that cancer tissue-specific metabolism and abnormal antidiuretic hormone production may lower uric acid in cancer patients, but the cause still remains unknown [1].
Minerals
Inadequate dietary zinc intake may lower uric acid levels, according to an old study on women [10].
Patients with Wilson disease, an inherited disorder that causes high copper/Fe levels, often experience hypouricemia [11].
Other Genetic Influences
The human urate transporter 1 (URAT 1) and human glucose transporter-like protein 9 (GLUT 9) are two kidney urate transporters.
According to a recent Korean study, genetic mutations in these two transporters can be responsible for idiopathic hypouricemia, which is when there is no other cause of low uric acid levels [12].
The gene SLC2A9 encodes a protein that helps transport uric acid in the kidney. Variants of this gene have associations with blood uric acid [13].
Therefore, uric acid levels may be influenced by genes. If you’ve gotten your genes sequenced, SelfDecode can help you determine how your genes have been linked with uric acid levels.
Hormones
Animal studies suggest that estrogen suppresses the production of the protein that eliminates urate in the kidney (proximal tubule epithelial cell organic anion transporter), while androgens stimulate it. Scientists hypothesize that this may explain lower serum urate levels in postmenopausal women as opposed to men, but larger studies are needed [14].
Factors that May Increase Uric Acid Levels
When to See a Doctor
It’s important to speak with your doctor if your uric acid levels are low. Your doctor should diagnose and treat any underlying conditions causing your abnormal levels.
Also, raising uric acid levels is usually detrimental. High uric acid levels signal gout, kidney problems, and other health issues. For example, a meat-heavy diet–high in purines–increases uric acid levels and causes flare-ups in people with gout [15].
On the other hand, people with low uric acid levels due to Wilson’s disease should follow a special low-copper diet [16].
Therefore, all dietary and lifestyle interventions should be based on the cause of your abnormal uric acid levels and your overall health.
With this in mind, you may try the complementary approaches listed below if you and your doctor determine that they could be appropriate. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.
1) Zinc
Zinc may normalize uric acid levels in people with Wilson’s disease who are deficient [17].
2) Animal Products
As mentioned, animal products like meat increase levels in general. This is usually considered detrimental, since a diet high in animal products (and purines) has only been studied in people with gout who have high uric acid levels. It’s unknown how a diet high in meat and animal products impacts low uric acid levels, but this will always depend on the underlying cause [18].
3) Inosine
Inosine, a uric acid precursor and nucleoside, increases uric acid levels in animals. Inosine is found in brewer’s yeast, fish, and organ meats. It’s also available as a supplement [19, 20].
However, inosine supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.
4) Avoiding Alcohol
On the one hand, alcoholic drinks (especially beer) increase uric acid levels and worsen symptoms in people with gout. But since alcohol can have wide-ranking harmful health consequences, doctors will recommend restricting or completely avoiding alcohol in the case of many diseases, including those linked with low uric acid levels [21].
For example, people with Wilson’s disease who have high copper and low uric acid levels are advised to avoid alcohol. This is because alcohol can damage the liver, which is already vulnerable due to excess copper in the body [22].
5) Exercise
Uric acid levels rise after strenuous exercise, potentially a result of purine nucleotide degradation during conditions of high energy usage. Intense exercise is not recommended to most people, since it puts too much stress on the body. Regular, moderate exercise supports overall health [23].
Uric Acid’s Proposed Antioxidant & Prooxidant Mechanisms
Source: [24]
No clinical evidence supports the antioxidant effects of uric acid. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
Scientists believe that uric acid can be both pro- and antioxidant, depending on the circumstances.
They are researching if uric acid affects the following antioxidant pathways in cells and animals:
- Scavenging reactive oxygen species and chelating transition metals [25, 26].
- Preventing peroxynitrite-induced protein nitrosation, fat and protein peroxidation, and the inactivation of tetrahydrobiopterin BH4, a cofactor necessary for NOS [27, 28, 29].
- Reducing copper-mediated LDL oxidation (but uric acid increases the oxidation of already oxidized LDL) [30].
- Increasing arginase activity, which diverts l-arginine from nitric oxide (NO) generation to urea production. Uric acid may also directly react with nitric oxide (NO) to produce nitrosated uric acid [30].
However, the following pathways point to uric acid’s oxidant (inflammatory) potential:
- Activating NADPH oxidase when taken up into fat cells. It stimulates the production of reactive oxygen species, which can initiate an inflammatory reaction [30].
- Uric acid can activate the NF-κB and MAPK pathway in vascular smooth muscle cells and increase the production of cyclooxygenase and monocyte chemoattractant protein-1 (MCP-1) [30].
None of these mechanisms have been explored in humans.
Learn More
- Uric Acid and Inosine May Increase IQ, Productivity, and Lifespan
- Causes of High Uric Acid, Associated Diseases, and Fixes
