Uric acid as biomarker and methyl-sister caffeine as preventive for Parkinson’s?

Parkinson disease (PD) is a slowly progressive disorder that affects movement, muscle control and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age. Parkinson’s disease attacks cells in the brain that regulate movement by releasing a chemical called dopamine. The loss of those cells leads to progressively disabling symptoms, including involuntary shaking, slow movement, stiffened muscle tone, and impaired balance. Levodopa, a precursor of dopamine, provides some relief from those symptoms but does not alter the disease course. Oxidative stress may contribute to the loss of brain cells that produce dopamine, leading to Parkinson’s disease and other neurodegenerative disorders. Urate (or uric acid) is a product of the body’s metabolism. Diets high in liver, seafood, and dried beans and peas tend to cause higher levels of urate in the blood, and are also associated with gout – a painful buildup of urate crystals in the joints. However, urate is a natural antioxidant, and it has been shown to quench several kinds of ROS, as shown in the picture below.

In 2008 investigators already demonstrated the link with urate by mining a repository of clinical data and tissue samples collected from Parkinson’s patients 40 years ago as part of a pioneering study called DATATOP, funded by NIH’s National Institute of Neurological Disorders and Stroke (NINDS). Individuals with Parkinson’s disease who had higher levels of a metabolite called urate in their blood and in cerebrospinal fluid (CSF) had a slower rate of disease progression. It may serve as one of the body’s major defenses against oxidative stress, or damage to cells caused by nitrogen and oxygen radicals. Experts emphasize there is no proof that elevating urate levels will help against Parkinson’s disease, and that it should not be attempted outside of a clinical trial. By analyzing the repository of clinical data and stored samples from the two-decade old DATATOP trial, scientists identified urate as a biomarker for the progression of the disease and suggested a potential new pathway for targeted therapy development. Also, prior epidemiology research in 2010 has shown that people who have gout or who consume foods associated with high urate have a lower incidence of Parkinson’s disease.

Now, scientists reported that analysis of participants in the Harvard Biomarkers Study (HBS) highlights the inverse association between low caffeine consumption and blood urate levels and PD. Beside urate, caffeine has been as well associated with a reduced risk of PD in multiple study groups and populations. Researchers therefore investigated whether these reduced risk factors are associated with PD in participants in the HBS, which is a longitudinal study designed to accelerate the discovery and validation of molecular diagnostic and progression markers of early-stage PD. Investigators conducted a cross-sectional, case-control study of 369 individuals with idiopathic PD and 197 healthy controls from the full HBS cohort. Urate was measured in plasma samples collected at each participant’s initial HBS visit. Caffeine intake was also assessed at each participant’s initial HBS visit using a semi-quantitative questionnaire. The questionnaire queried participants’ usual consumption of regular and decaf coffee, tea, and soft drinks during the previous 12 months in standard volumes (cups for coffee and tea and cans for soft drinks) with nine possible frequencies ranging from never to six or more per day.

Caffeine intake was lower in idiopathic PD patients compared to healthy controls. The odds of having PD decreased significantly with increasing caffeine consumption in a concentration-dependent manner across quintiles of caffeine consumption, adjusting for age, sex, BMI, and plasma urate. Compared with the lowest caffeine consumption quintile, the prevalence of PD was over 70 percent lower in the highest quintile. A strong inverse association was also observed with plasma urate levels both in males and females. An equally large association between urate and PD risk was observed among women, in contrasts with most prior studies of the association between urate and idiopathic PD stratified by sex. These findings support the generalizability of discoveries made with this cohort, which is well suited for deep analysis of relationships between dietary factors, genes, established and novel biomarkers, and clinical phenotypes of PD. The investigators caution that a recent large clinical trial of a urate-elevating treatment failed to demonstrate a benefit for people with PD over months to years. Thus, even though the current study strengthens the link between PD and lower urate levels, strategies to raise them cannot be recommended.

Rachit Bakshi, PhD, Lead Investigator, Department of Neurology, Massachusetts General Hospital, and Harvard Medical School, explained: “Both caffeine and urate possess neuroprotective properties via adenosine receptor antagonist and antioxidant actions, respectively. They both have protective properties in animal models of PD, raising the possibility of their disease-slowing potential. The strength of this new study relates to the robust approach, including the large and carefully followed cohort of people living with PD and the comprehensive set of outcome measures. It is an important basis to further develop future disease-modifying approaches to slow down the decline of this otherwise relentlessly progressive condition. However, caffeine has yet to be rigorously studied in a long-term PD trial, therefore increasing one’s caffeine intake cannot be recommended. Nevertheless, people who currently enjoy caffeine in coffee or tea may take additional pleasure in knowing of its therapeutic even if unproven potential. Identifying factors that are linked to lower likelihood of PD, offer a unique opportunity to understand the disease, and if the link were causal, then possibly to slow the disease”.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Bakshi R et al. J Parkinsons Dis. 2020; 10(2):505-510. 

Sleeman I et al. J Parkinsons Dis. 2019; 9(2):351-359. 

Kobylecki CJ et al. Ann Neurol. 2018; 84(2):178-190. 

Cortese M et al. Parkinsonism Relat Disord. 2018; 52:76-82.

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Informazioni su Dott. Gianfrancesco Cormaci 2449 Articoli
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry specialty in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it
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