The Quest for Happiness

Uric Acid

Dr Thanh-Tam Pham - 20/10/2022

Uric Acid

Dr Perlmutter in his book “Drop Acid” explore how elevated uric acid is connected to metabolic syndrome. 

It has now been established through large studies that elevated uric acid in childhood can be a predictor the development of high blood pressure, kidney disease and metabolic syndrome. 

Metabolic syndrome refers to a cluster of conditions that increase the risk of heart disease, stroke, diabetes, sleep apnoea, liver and kidney disease, cancer, and Alzheimer’s disease. The 5 key characteristics of metabolic syndrome are:

. high blood pressure

. elevated blood glucose

. excess body fat around the waist (greater than 102cm in men or 89cm in women)

. Elevated triglycerides

. abnormal cholesterol levels (low HDL or low “good” cholesterol}

The Uric acid- Nitric Oxide Connection.

. Fructose, Purines and alcohol increase Uric acid and Uric acid reduces Nitric Oxide production and damages NO functionality and thus causes Insulin resistance, diabetes, erectile dysfunction and reduce blood flow to organs. 

Uric acid is a powerful generator of oxidative stress which damages tissues and DNA and reduces NO function and further incite inflammation.

. Erectile dysfunction (ED) is associated with blood vessel problems and cardiovascular disease. Uric acid damages the inside lining of blood vessels via inflammation and oxidative stress. This reduces the activity of NO which is necessary for erectile dysfunction. The over consumption of soft drinks has been implicated in the slow and asymptomatic progression of ED which eventually results in full manifestation of ED.

. Uric acid suppresses autophagy (removes or recycles damaged cells) and diminishes the anti-inflammatory capacity of cells. 

Fructose is often touted as the “safer “sugar as it has a low glycaemic index as it does not trigger a rise in blood sugar with reflexive release of insulin from the pancreas. Unlike other types of sugar which immediately raises blood sugar level, fructose is handled exclusively by the liver.

Uric acid and gut health:

Gut bacteria are key to our survival. The gut microbiome plays a role in many physiological functions: manufacture neurotransmitters and vitamins that we could not produce, promote normal gastrointestinal function, protection from infection, regulate metabolism and help control blood sugar. The microbiome influences our immune system and inflammation levels therefore factor into our risk for illnesses such as depression, obesity, bowel disorder, diabetes, multiple sclerosis, diabetes, asthma, autism, Alzheimer’s disease, Parkinson’s and even cancer. Leaky gut allows food toxins and pathogens to pass into the blood triggering an aggressive and often prolonged immune response. Uric acid in the body is excreted to a significant degree by the intestines. Elevations in the acid change the composition of gut bacteria, favouring pro-inflammatory strains. Elevation of uric acid also promotes the decay of the intestinal lining paving the path to systemic inflammation. There is now a strong association between high uric acid, intestinal barrier dysfunction, and immune disorders. Researchers found that the bacteria in guts of gout patients were quite like those of people with type 2 diabetes and other features of metabolic syndrome. 

Fructose:

Fructose is found in fruit and honey but consuming these foods doesn’t increase uric acid levels. Drinking liquid fructose in fruit juice or other fructose-sweetened beverages is not the same as eating fibre-rich fruits and vegetables. Eating fructose triggers changes in the body that favour the storage of energy in the form of fat and activate the starvation pathway resulting in a vicious cycle of excessive eating. 

When fructose is consumed, it is quickly absorbed in the bloodstream and go to the liver to be metabolize by the enzyme fructokinase. This process uses ATP, so fructose metabolism depletes energy resources causing mitochondrial dysfunction and rapid rise of uric acid level. Fructose drains on energy in cells provokes a signal We’re running out of energy!  This makes the body to switch gears into energy preservation mode, metabolism slows down and increase storage in the form of fat. In fructose metabolism, ATP is converted to AMP and ultimately generates uric acid. A high level of uric acid further stimulates fructokinase. 

High uric acid exacerbates energy depletion and mitochondrial dysfunction, favours inflammation and oxidative stress, raise blood pressure, insulin resistance and trigger production of body fat, a useful state in a time of food scarcity if you are a hunter-gatherer. 

Fructose is metabolised in the liver and triggers lipogenesis, increase triglycerides, that is the formation of fat in the liver. Fat in the liver cells directly compromises the ability of insulin to store glucose and the generation of uric acid causes oxidative stress to islands of cells in the pancreas that produce insulin. So, fructose and elevated of uric acid are linked to development of diabetes and other metabolic disorders.

Fructose reduces leptin (induces a sense of fullness) and blunts the suppression of ghrelin (trigger hunger) resulting in greater appetite, more eating and increased leptin resistance.

Elevated uric acid is also found among people with high impulsivity, mild form of ADHD and bipolar disorder.

Role of Uric acid in Brain Decline:

Certain conditions like increased blood glucose, insulin resistance, obesity, diabetes, hypertension, and inflammation have been strongly correlated with risk of cognitive decline and brain shrinkage.

A high level of Uric acid was associated with a fourfold increased risk of dementia. And uric acid is associated with metabolic syndrome. Insulin resistance may spark the formation of the plaques in Alzheimer’s disease.

Greater consumption of sugary beverages was associated with lower total brain volume, lower hippocampal volume, and memory recall. 

As fructose raises uric acid and compromises insulin signalling, brain cells lose their ability to properly use glucose. The ketogenic diet has proved effective as an intervention for Alzheimer’s patients as it provides an alternative fuel -ketones. 

Drugs to lower uric acid like Allopurinol at high dose >200mg/day and febuxostat 40mg/day lower the risk of dementia by more than 20%. 

Sleep as medicine

Chronic sleep deprivation can cause confusion, memory loss, brain fog, low immunity and chronic infections, cravings for carbs, weight gain and obesity, cardiovascular disease, diabetes, and chronic anxiety and depression. Excessive sleep is now considered a potential early marker for cognitive decline. Adequate sleep means seven to eight hours of solid sleep.

There is a strong inverse association between the duration of sleep and uric acid level, sufficient quality sleep equates with low uric acid and short duration sleep correlates with uric acid level.

Salt

A high salt diet induces metabolic syndrome in mice. However, mice that are deficient in fructokinase to metabolize fructose and generates uric acid, do not develop metabolic syndrome. A high salt diet is associated with leptin resistance, excessive eating that leads to obesity insulin resistance, and fatty liver. 

Drugs that raise uric acid

Food that raises uric acid

Alcohol and xylitol

Xylitol is a natural sugar (technically a sugar alcohol). It was known to provoke and increase in uric acid by stimulating the breakdown of purines in the body. 

Some types of alcohol raise uric acid more than others such as beer more than liquor whereas moderate wine does not. 

Purine rich foods

Researchers found the risk of gout increased with seafood, red meat, alcohol, and fructose whereas coffee, dairy products and soy proteins reduced the risk. 

There are 5 basic tastes [ sweet, salty, sour, bitter, and savory (umami). Umami in Japanese is pleasant savory taste and owes it mostly to glutamate found in MSG (Monosodium glutamate). MSG is found in foods high in purines. MSG triggers the release of inflammatory chemicals, increase insulin resistance, obesity, hypertension, and high uric acid levels. 

Health conditions linked to elevated uric acid:

Psoriasis: The connection between psoriasis, psoriatic arthritis and gout has been documented for decades. Psoriasis is an immune-related chronic inflammatory skin disorder.

Renal insufficiency and chronic kidney disease: uric acid builds up as kidneys are not able to filter waste. 

Hypothyroidism and hyperthyroidism: low level of thyroid hormones will compromise uric acid secretion and elevated thyroid function leads to breakdown of tissues and hence the release of purines and cause elevation of uric acid.

Lead poisoning: lead essentially prevents uric acid from being excreted by the kidneys. 

Tumour lysis syndrome: anything that causes tissue (cellular) breakdown will raise uric acid such as chemotherapy, physical trauma, excessive exercise, and even fasting.

Lack of regular movements:sedentary behaviour was linked to premature death from all causes, as well as increased risk of cardiovascular disease, diabetes, and cancer. If you get up from the sitting position every hour for2 minutes of light activity, you can reduce the risk of dying prematurely by 33 percent!

Five acid – lowering supplements:

 

Reference:   “Drop Acid” - The Surprising Science of Uric Acid by Dr David Perlmutter.