Gabor Szendi:
Uric Acid: our old Friend
Western medicine considers high uric acid level an enemy, because several studies have been published on how uric acid forecasts insulin resistance,1 diabetes,1,2 high inflammation level,3 and blood pressure,4 fatty liver disease,5 obesity,1 and metabolic syndrome, moreover it causes gout. And what causes, according to general belief and modern medicine, high uric acid levels? - Purine containing foods, in other words, meat and plant foods with a purine content.6
The subject of uric acid and gout is only one example of how modern medicine turns connections upside down, how it treats consequences as a cause, and how it ignores facts in order to maintain myths. It was already proved in a study in the 1970s that in healthy subjects who consumed 6-7 times more protein than usual for 9 weeks, uric acid levels did not go up, only the uric acid secretion increased.7 As a result of a high protein diet the number of gout attacks dramatically decreased.8 According to the relevant studies, 90% of times, high uric acid level is caused by impaired kidney function.9
The myth that gout is caused by high meat consumption originates from the observation that, since ancient times, gout has been an illness of the rich. However, we now know that the common occurrence of gout in ancient Rome was caused by impaired kidney function following lead poisoning. Wine produced in those times had lead levels 1,000 times higher than the established safe limit today.10 Another much quoted example is the gout epidemics in 18th-19th century England that mainly hit the upper class ten percent of the population. One of the reasons for this was also lead poisoning from the much loved Porto wine produced in those times that proved to contain 300-1900 micrograms of lead per litre,10 and other types of wine was also often sweetened with "lead sugar", i.e. lead acetate. Kidney function impairment caused by lead is still common today and a close connection between uric acid levels and the level of lead in the blood has been established.11,12 Gout is 3.6 times more common among people with high lead levels.13 Another suspect cause of high uric acid level is fructose. Sugar consumption and the number of gout patients with in England and Holland continuously grew from the 17th century.14 (In the process of digestion sugar is broken down into one fructose and one glucose molecule.) In a 12-year monitoring study two glasses of sugary soft drinks daily doubled the risk of developing gout.15 Fructose both directly and indirectly increases uric acid levels through impaired kidney secretion caused by insulin resistance.16 Insulin resistance leads to obesity, and the risk of gout grows proportionately with the increased body mass index.17 Consuming alcohol also doubles the risk of gout.18
Uric acid and evolution
While in other mammals the uric acid level moves between 0.5-2.0 mg/dl, with humans it is typically on average between 4.0 and 6.0 mg/dl. High uric acid level can be observed in higher apes, so it is reasonable to assume that high uric acid level represents definite advantages. To connect gout with meat consumption is a nonsensical idea anyway because meat consumption played a central role in human evolution. During our evolutionary history high uric acid levels typical of humans had developed in gradual steps through the uricase enzyme (responsible for metabolising uric acid) becoming dysfunctional.19 The important function of high uric acid level is also suggested by the fact that the kidney re-absorbs 90% of uric acid thereby increasing its level.20 The evolutionary benefit of high uric acid level is most likely to be its antioxidant properties, and it developed when we lost our ability to synthesise vitamin C.21 Uric acid is quite a strong antioxidant, and it constitutes 50% of antioxidants circulating in our blood. As we will see later, the antioxidant function of uric acid may have played a very important role in the enlargement of our brain. Gout is very rare or unknown amongst natural people in spite of them having high uric acid levels.22-25 In South Asian populations belonging to the Aboriginal language family, uric acid levels are typically high, between 6-7.5 mg/dl. According to archaeological records the Maori people used to be very healthy and free of gout.26 On the basis of archaeological finds this is questioned today,27 but it is undoubted that amongst the Maoris and people of other Pacific ocean islands a dramatic rise in gout cases occurred when they embarked on a western lifestyle.25, 28, 29
It is obvious that high uric acid level originally representing an evolutionary benefit has turned into a disadvantage as a result of the effects of modern civilisation.
Uric acid and neurodegenerative illnesses
Geophysicist engineer, Egon Orowan came up with a surprising theory in 1955. He suggested that both in higher apes and humans it was elevated uric acid levels that allowed the brain to grow in size, in other words, we can thank it for our intelligence. 30 A lot of free radicals formulate in our brains that damage the function of neurons. As the speed of processors was increased by the development of the cooling of processors, the enlargement of the brain was made possible by the appropriate antioxidant protection. High uric acid levels did not only raise the human race above animals in terms of intelligence but it is also true amongst people that the higher uric acid level someone has, the higher their IQ is.31 Uric acid has a neuroprotective effect against oxidation,32 and in case of a brain injury every 1 mg/dl increase means a 12% increase for the chance of a good prognosis.33 (The upper limit of uric acid measured in the blood is 6.8 mg/dl, but even with people having 9 mg/dl or higher levels only 22% developed gout.34 The connection is true the other way around as well, after a stroke the more uric acid levels decrease the worse the prognosis and risk of death.35
In the various neurodegenerative diseases, such as Alzheimer's, Parkinson's, sclerosis multiplex, and amyotrophic lateral sclerosis, the various degenerative oxidative effects are considered to play a critical role.36
Alzheimer's disease
In a study of 29,000 gout patients it was proved that high uric acid levels offer a 22-25% protection against all sorts of dementia.37 In another study the data of 59,000 patients was analysed and it was found that gout represented a 24% protection against Alzheimer's disease.38
A meta-analysis of 11 Alzheimer's studies concluded that the participants had low uric acid levels.39 Others antioxidants as well as uric acid levels are all low both in mild cognitive impairments and in Alzheimer's disease.40 Low uric acid levels in middle aged people forecast cognitive impairment later,41 while high levels represent protection against dementia.42
Parkinson's disease
In Parkinson's disease it is the destruction of the diencephalic dopaminergic neurons that causes the various symptoms, with among others, movement abnormalities. When the brains of deceased Parkinson's patients were examined it was found that they had 54% lower levels of uric acid than the control group.43 An 8-year monitoring study of 56,000 people proved that gout represents a 34% protection against Parkinson's disease.44 According to another monitoring study of 18,000 people, the individuals with highest levels of uric acid enjoyed a 60% protection against Parkinson's disease compared with those with the lowest levels of uric acid.45 In the case of an already developed disease, high uric acid levels slow down the disease progression.46 The lower the uric acid level, the more severe Parkinson's disease is, and (tremor free) patients with a worse prognosis had a lower uric acid level than the ones with a better prognosis who showed tremor.47
For evolutionary reasons, milk and dairy products are not a part of the paleo diet, and the research into Parkinson' disease provides new reasons to avoid these foods. A number of studies have proved that the consumption of milk and dairy products significantly increases the risk of Parkinson' disease. In a 30-year monitoring study it was found that people who often eat dairy products have a 2.3 times higher risk of Parkinson' disease,48 while another study showed a 1.6 times higher risk.49 An autopsy study found 41% less dopaminergic neurons in the midbrain of people who used to consume a lot of milk.50 This kind of effect of milk and dairy products is not surprising because these foods significantly decrease uric acid levels,51 but it is also assumed that the chemical contaminations found in milk can also be responsible for this effect.50 According to the analysis, a daily 200 ml of milk increased the risk of Parkinson' disease by 17% and a daily 10 g of cheese by 13%.52
Parkinson's disease is forecast by the decreasing number of spontaneous blinks per minute53, as well as so-called REM sleep behaviour disorder, when the sufferer acts out their dreams.54
The risk of Parkinson's disease is significantly decreased by coffee in a dose dependent manner. Every three cups of coffee consumed daily decreases the risk of the disease by 25-32%. Smoking also results in a significantly decreased risk, with previous smokers showing 40% less and active smokers 60%.55 Both recreational drugs stimulate dopaminergic activity in the brain.
A study tried to slow down the progression of Parkinson's disease by giving a daily dose of 15 g of inosine.56 This amount inosine is capable of increasing the uric acid level of the blood by 2-3 mg/dl. In a secondary analysis the researchers noted modest trends towards slower Parkinson's disease progression rates with increasing urate. (Although sportsmen often take inosine for years, they do not experience side effects. However, it is not advisable to try this without medical control or at least the monitoring of uric acid levels).
Multiplex sclerosis (MS)
Analysing 20 million MS patients' case history it was found that in spite of the statistically expected 64 both gout and MS sufferers, only in 4 cases the two conditions existed at the same time, which means that MS and gout practically exclude each other.57 Examining twins where only one of them was an MS sufferer, the sibling with the lower uric acid level was the ill one.58 This result means that MS decreases uric acid levels. This is supported by the fact that, according to several studies, uric acid levels drop when MS flares up, and rises again in remission.59 Of course, the results are not always so orderly: many studies found low uric acid levels in both the active and passive phases of MS.60, 61 On the whole it seems that in the active, inflammatory phase of MS uric acid gets "used up", and that is why its level drops.62
In several studies with MS patients uric acid levels were raised by administering inosine, and by following the changes with MRI it was found that in some patients, as a result of the treatment, the number of relapses and the extent of tissue damage decreased.63, 64, 65
It is important to note that in the case of MS, high levels of vitamin D also protects against relapses,66 because vitamin D has a neuroprotective effect.
Amyotrophic lateral sclerosis
In amyotrophic lateral sclerosis which is accompanied by muscle dystrophy, low uric acid levels are also typical.67 In this often fast progressing illness, which often results in the death of the patient, according to one study every 1 mg/dl rise in uric acid level decreases the risk of death by 39%. In other words, uric acid can significantly lengthen the patient's life.68
Summary
High levels of uric acid, together with other antioxidants have made it possible for our brain to reach its contemporary big size, and also enable it to smoothly maintain its incredibly complex functioning until the end of our lives. The changes in our diet and lifestyle in the last 100-200 years have turned previously unknown neurodegenerative diseases into a common occurrence. Understanding the role of uric acid in the treatment and prevention of these and in other illnesses affecting the brain may open a new chapter in medicine.
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