Do Caffeine And More Selective Adenosine A2a Receptor Antagonists Protect Against Dopaminergic Neurodegeneration In Parkinson’s Disease
People who consume more caffeine are less likely to develop PD.
Caffeine blocks adenosine A2A receptors, accounting for some of its CNS actions.
Caffeine and more selective A2A antagonists like istradefylline are protective in PD models.
Neuronal and immune A2A receptors may mediate these neuroprotective effects.
Following The Progression Of Parkinson’s
Researchers studied the progression of Parkinson’s symptoms over 4 years in 79 people who had been newly diagnosed with the condition.
They found that higher caffeine consumption, from drinks like tea and coffee, was linked to the development of fewer motor and non-motor symptoms, and lower symptom severity.
The study also found that people who drank more caffeine started Parkinson’s medication, such as levodopa, later compared to those with lower caffeine consumption.
Caffeine Did Not Improve Movement
The new research included 121 adults aged 62 years, on average. All patients had been diagnosed with Parkinsons disease at least 4 years prior, and they were followed-up for between 6 and 18 months.
Half of the subjects were given 200 milligrams of caffeine twice daily which is the equivalent to around three cups of coffee each day while the remaining participants were given a placebo.
The researchers note that the caffeine-consuming participants began with a placebo and gradually increased their caffeine dose over the first 9 weeks, reaching 200 milligrams twice daily at week 9. This was to help them adjust to the caffeine.
Upon assessing the movement symptoms and quality of life of the participants, the researchers were unable to identify any differences between subjects who took caffeine and those who took the placebo.
While our previous study showed possible improvement in symptoms, that study was shorter, so its possible that caffeine may have a short-term benefit that quickly dissipates, notes Dr. Postuma.
Regardless, our core finding is that caffeine cannot be recommended as therapy for movement symptoms of Parkinsons disease.
Dr. Ronald B. Postuma
The team notes that the current study has some limitations. For example, they say that it is possible that some subjects did not meet the study requirements, and they did not measure blood caffeine levels to help account for this fact.
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Astrocytes And Their Role In Pd
Aside from being an A2A antagonist, caffeine may help stabilise the blood-brain barrier by regulating astrocytes and inflammatory processes in animal models . Astrocytes are glial cells found in the mammalian brain that play a pivotal role in maintaining various neuronal functions by transporting nutrients and metabolites to neurons through a number of transporters such as the malate-aspartate shuttle. There are two types of astrocytes found in substantia nigra: .
Research on astrocytes in mice has suggested that -synuclein affects only protoplasmic astrocytes but not fibrous astrocytes .
Astrocytes are significant players in the central nervous system as they develop and maintain the BBB and promote neurovascular coupling. One extreme of astrocytes faces endothelial cells to maintain BBB and control cerebral blood flow while the other extreme is in communication with numerous neurons . Moreover, astrocytes can release chemokines, gliotransmitters and help in the uptake of glutamate and GABA from the synaptic cleft. Other functions of astrocytes include pH regulation, K+ buffering, metabolising dopamine, and producing antioxidants such as gluthathione and superoxide dismutases .
3.2.1. Caffeine Inhibits Astrocyte-induced Inflammation in PD
Caffeine Has Been Found To Have Neuroprotective Effects In Patients With Parkinsons Disease
Study findings published in Neurology suggest that absolute lower levels of caffeine and caffeine metabolite profiles are promising diagnostic biomarkers for early Parkinsons Disease. This is consistent with the neuroprotective effect of caffeine previously revealed by epidemiologic and experimental studies.
A study of serum levels of caffeine in patients with Parkinsons Disease, published online in Neurology, found that serum levels of caffeine and 9 related metabolites were uniformly and significantly decreased in patients with Parkinsons Disease, despite an equivalent caffeine intake to controls. More importantly, serum levels of caffeine in patients with Parkinsons Disease related to caffeine intake significantly, but those in controls did more significantly, indicative of less caffeine absorption in patients with Parkinsons Disease.
There have been several reports suggesting an inverse association between daily caffeine consumption and a reduced risk of developing Parkinsons Disease in men, and in women not taking hormone replacement therapy, according to information cited in Neurology. Fujimaki M, Saiki S, Li Y, et al. Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease. Neurology. 2018 Jan 3.
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Drinking More Caffeine Can Help Reduce Your Risk Of Developing Parkinson’s Disease
It may be the morning wake-up ritual for most, but it turns out your cup of coffee or tea might be boosting more than just your energy levels. In a study published in the September 2020 online issue of the medical journal Neurology, tests found that patients with a genetic mutation that predisposes them to Parkinson’s disease were less likely to show signs of the disease’s onset if they drank more caffeine.
Foods High In Saturated Fat
Although the specific role of saturated fat in Parkinsons is still being studied, research suggests that a high dietary fat intake may increase your risk of this disease .
Generally speaking, diets high in saturated fat have been linked to chronic conditions like heart disease. As such, you may wish to keep these foods in moderation (
- palm oil
- some baked and fried foods
Conversely, a very small study notes that the keto diet which is high in fat is beneficial for some people with Parkinsons. However, a low fat diet also showed benefits. Overall, more research is needed .
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Why Should Coffee Reduce The Risk Of Parkinson’sdisease
Although the new research is suggestive of a linkbetween caffeine and Parkinson’s disease, it is too early to saythat caffeine will prevent Parkinson’s disease. Perhaps the brains ofpeople who like and dislike coffee are different. It may be that thisdifference results in the different incidence of Parkinson’s disease andin the consumption of coffee. Also, the study included older,Japanese-American men. It is unknown if the caffeine/Parkinson diseaserelationship holds for other ethnic groups, women and younger people. Aswith many preliminary studies, this research requires further experimentsto establish a causal link between caffeine and reduced incidence ofParkinson’s disease.
How much caffeine do you consume each day? Use this worksheetto keep track of the products with caffeine that you consume. Write downthe name of the product, the amount you consume of each product , the amount ofcaffeine in each product and the time that you consumed the product. Useseparate worksheets if you want to track your caffeine consumption ondifferent days.
Coffee May Help Some Parkinson’s Disease Movement Symptoms Research Suggests
- American Academy of Neurology
- While drinking caffeine each day does not appear to help improve sleepiness among people with Parkinsons disease, it may have a benefit in controlling movement, according to new research.
While drinking coffee with caffeine each day does not appear to reduce sleepiness among people with Parkinson’s disease, it may have a benefit in controlling movement, according to new research published in the August 1, 2012, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“Studies have shown that people who use caffeine are less likely to develop Parkinson’s disease, but this is one of the first studies in humans to show that caffeine can help with movement symptoms for people who already have the disease,” said study author Ronald Postuma, MD, MSc, with McGill University in Montreal and the Research Institute of the McGill University Health Center. Postuma is also a member of the American Academy of Neurology.
For the study, 61 people with Parkinson’s disease who showed symptoms of daytime sleepiness and some motor symptoms were given either a placebo pill or a pill with 100 milligrams of caffeine two times a day for three weeks, then 200 milligrams twice a day for three weeks, which was the equivalent of between two and four cups of coffee per day.
The study authors noted that the length of the study was short and that the effects of caffeine may lessen over time.
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Two Bifunctional Dimers Stopped A
According to Lee, the majority of drug compounds in development for Parkinsons have focused on increasing dopamine production of surviving nerve cells, but this is effective only as long as there are still enough cells to do the job, he notes.
- Around 60,000 Americans are diagnosed with Parkinsons each year
- Men are 1 ½ times more likely to develop Parkinsons than women
- More than 10 million people across the globe are living with Parkinsons.
For their study published in the journal ACS Chemical Neuroscience Lee and team took a different approach they set out to identify ways to protect dopamine-producing cells by halting the misfolding of a-synuclein.
With this in mind, the team used a caffeine scaffold to create eight new compounds called bifunctional dimers, which are molecules that connect two different substances that affect dopamine-producing cells.
Alongside caffeine, other compounds tested included nicotine, metformin , and aminoindan .
The team applied the dimers to a yeast model of Parkinsons disease, which is a yeast cell line that expresses a-synuclein-green fluorescent protein .
Our results suggest these novel bifunctional dimers show promise in preventing the progression of Parkinsons disease.
Parkinson’s Patients Had Less Caffeine In Their System Than Those Without Iteven When Susceptible
Researchers compared 188 people who had been diagnosed with Parkinson’s disease with 180 people without it. In each group, some members had the LRRK2 gene mutation that puts someone at higher risk of developing the disease but doesn’t guarantee that symptoms will develop. This set researchers out to test whether or not other factors affected the onset of Parkinson’s.
The team measured the caffeine levels in each person’s blood, with 212 participants from across both groups also providing information on their daily caffeine intake habits. Results found that those carrying the LRRK2 mutation that had been diagnosed with Parkinson’s had 76 percent less caffeine in their systems than people without the diseaseand also were found to drink 41 percent less caffeine per day than participants who were not diagnosed with the disorder. In addition, those with Parkinson’s but who were not carriers of the mutation had 31 percent lower levels of concentration in their bloodstream.
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Caffeine From Two To Four Daily Cups Of Coffee May Reduce Parkinson’s Disease Symptoms
Should doctors start prescribing coffee?
In the latest study to tie coffee to health benefits, new research finds a daily caffeine boost may ease symptoms of Parkinson’s disease in sufferers.
Parkinson’s is a degenerative brain disease that causes tremors, difficulty with walking, movement and coordination. The condition most commonly develops in adults over 50, and occurs when nerve cells in the brain that make the muscle-controlling neurotransmitter dopamine are slowly destroyed, leading to loss in muscle function. The cause of the disease remains unknown.
The study, published August 1 in the online issue of Neurology, tracked 61 people with Parkinson’s who were exhibiting symptoms of daytime sleepiness. Participants were assigned to receive either a placebo pill twice per day or a 100 milligram-caffeine pill twice per day for three weeks. After three weeks, those in the caffeine group were given a 200 milligram caffeine pill twice per day, about the caffeine equivalent found in two to four cups of coffee.
Six weeks into the study, people taking the caffeine pills averaged a five-point improvement on a ratings scale of Parkinson’s symptom severity compared to those who took placebos. Researchers called this a modest improvement, but one that might provide benefits to people with the disease.
Oddly enough, caffeine did not appear to help improve the patients’ daytime sleepiness problems.
Motor Benefit Of Caffeine In Pd Patients And Pd Models
The symptomatic effect of caffeine in PD was first tested in 1970s , but has been revisited by several clinical studies recently. The motor benefit of caffeine were documented in a pilot open-label, 6-week dose-escalation study and a 6-week randomized controlled trial of caffeine involving 61 PD patients . These clinical studies suggest that caffeine improved objective motor deficits in PD with the reduced total Unified PD Rating Scale score and the objective motor component. Furthermore, coffee consumption is associated with the reduced hazard ratio for the development of dyskinesia compared with subjects who consumed < 112 mg/day in the Comparison of the Agonist Pramipexole with Levodopa on Motor Complications of Parkinsons Disease and CALM Cohort extension studies . Based on these positive findings, caffeine was recently investigated for motor and disease-modification involving 121 PD patients PD in a phase 3, 5-years , two-arm, double-blind RCT, with a primary outcome focused on motor symptoms and disease-modification as a secondary outcome1. Unfortunately, with the primary outcome analysis after 6 months demonstrating no significant symptomatic benefit of caffeine , the study was terminated earlier than the planned.
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As Much As Four Cups Of Coffee
For the new study, Postuma and his colleagues randomly assigned 61 people with Parkinsons and in their mid-60s, on average, to six weeks of caffeine pills or identical drug-free placebo pills.
Participants in the caffeine group took 100 milligrams when they woke up and again after lunch for the first three weeks, then were bumped up to 200 milligrams twice a day for the rest of the study.
In comparison, a cup of brewed coffee typically has about 100 milligrams of caffeine and a 12-ounce soda has between 30 and 50 milligrams.
After the study period, people taking caffeine didnt report a clear improvement in sleepiness. But that group did improve on an overall scale of Parkinsons symptoms, including on measures of muscle rigidity and other movement problems.
The average benefit was a decrease of about five points on the disease rating scale, according to findings published Wednesday in Neurology. Postuma said a typical patient whos had Parkinsons for a few years would have a score of 30 to 40.
Five points on the scale is enough to say on average, Yeah, I feel a bit better, things are a little bit easier, he told Reuters Health.
Its not a massive difference, he added – but even a small change can have a real effect on peoples lives.
Postuma said the main drug prescribed for Parkinsons, levodopa, has a benefit three to four times greater than what his team found for caffeine pills.
In the meantime, a little extra caffeine probably wont hurt, researchers said.
Comparison Between Coffee And Non
Of the 284 de novo PD patients enrolled , a total of 204 patients and 80 patients were categorized as coffee drinkers and non-coffee drinkers , respectively. The coffee drinker group comprised current coffee drinkers and those who have had coffee in the past but have now stopped. Most of the patients who quit drinking coffee had a history of coffee drinking for more than 10years. As shown in Table , intergroup comparisons revealed that coffee drinkers were younger, included more men, younger in age at cardinal motor symptom onset, and reported more years in formal education than the non-coffee drinkers. When comparing motor- and ADL-related scores, coffee drinkers had significantly lower UPDRS motor scores as well as tremor , bradykinesia , and gait and posture scores than non-coffee drinkers. When the tremor was divided into rest and action tremors, only rest tremor showed a significant difference. Furthermore, the univariate analysis revealed that coffee drinkers had significantly lower tremor scores than non-coffee drinkers. However, PIGD and AR scores were not significantly different between the two groups. When comparing non-motor scores, we found that coffee drinkers had higher MMSE , but lower BDI and total NMSS scores than non-coffee drinkers.
Table 1 Demographics and clinical characteristics of patients with Parkinsons disease
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Caffeine May Influence Pd Pathology By Modulating Gut Microbiota
The gut microbiota in the human gastrointestinal tract is estimated to contain 10 times more microbial cells than human cells, and approximately 100200-times more protein coding genes than the human genome . The gut microbiota critically influence various aspects of human biology, including the absorption and metabolism of nutrients, vitamins, medications, and toxic compounds the development and differentiation of the intestinal epithelium and immune system, the maintenance of tissue homeostasis, and the prevention of pathogens invasion . The gut microbiota also plays an important role in gut-brain communication, and the neuroimmune system to maintain brain homeostasis, thus influencing brain function and behavior . In healthy subjects, the intestinal microbiota is generally stable over time, but compositional changes might occur following antibiotic usage or dietary modifications .
Coffee Consumption Linked To Less Severe Tremors In Men With Parkinson
A new study has found a dose-dependent relationship between coffee consumption and reduced severity of tremors in men with Parkinson disease.
A new study has found a dose-dependent relationship between coffee consumption and reduced severity of tremors in men with Parkinson disease .
Previous research has established that coffee is a negative risk factor for PD, a neurodegenerative disorder that produces motor symptoms, including tremor, as well as nonmotor symptoms. Based on mouse models, investigators have hypothesized that the caffeine in coffee offsets the loss of striatal dopamine and dopamine transporter binding sites seen in PD. There have been few studies that assessed how coffee consumption may be linked with the motor symptoms of PD, and they have suggested that coffee consumption has a positive effect.
The current study, published in BMC Neurology, aimed to determine the association between coffee drinking and motor symptoms in patients with newly diagnosed PD based on their gender. From 2011 to 2016, the researchers enrolled patients at the Chonnam National University Hospital outpatient clinic in China whose PD had been diagnosed by an expert in movement disorders but not yet treated. They had access to patients clinical history and neurological examination results, and they asked participants about their past and present coffee drinking habits in semistructured interviews.
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