From a study on Pubmed - Uric Acid (UA), historically considered as a waste of cellular metabolism, has now received increasing attention because it was found to directly participate in the pathogenesis of many human diseases including neurological disorders. On one hand, low levels of UA are detrimental to the neurons because of its induction it impairs antioxidant capacity in the cell. High levels of UA, on the other hand, lead to an inflammatory response contributing to gout or neuroprotection. In this review, we summarize this biphasic function of uric acid and highlight potential therapeutic targets to treat UA-related neurological diseases. - ncbi.nlm.nih.gov/pmc/articl...
Uric Acid: A Double Edged Sword - Cure Parkinson's
You have already been thoroughly refuted here:
No need to repeat.
The study you mentioned only looked at inosine. From the study author: No matter the results of SURE-PD3, urate remains a clue in Parkinson's. Laboratory and population studies show that urate is linked to Parkinson's. The results from SURE-PD3 may still help us learn more about the role of urate in Parkinson's and new ways to target the disease. And if inosine isn't the way to slow disease progression, that's beneficial too. It helps us close one door so we can now walk through another, and each door we try gets us closer to our goal. - michaeljfox.org/news/parkin...
Researchers are not ending their uric acid studies because of the results of the inosine trial.
From the same study author - "Parkinson's disease occurs and progresses because the cells in the brain that make dopamine and are essential for voluntary movements are damaged and lost. In laboratory studies, urate protects these brain cells. In epidemiological, or population, studies, researchers have found an association between higher levels of urate and a lower risk of Parkinson's as well as slower disease progression in people with Parkinson's.
Already discussed at the prior post
You posted many times that the inosine trial proved uric acid had no role in helping PD and that it was the definitive study ending the discussion. The study author said pretty much the opposite of that and most of what you've been posting.
I'm going to give more credibility to the conclusions of the researchers doing the published studies, like the inosine trial.
In your mind only. Try reading these things that you quoted more carefully:
"urate remains a clue in Parkinson's. Laboratory and population studies show that urate is linked to Parkinson's"
Note that they do not state causation.
"In laboratory studies, urate protects these brain cells" All kinds of things help in laboratory studies that prove to be ineffective or dangerous in the clinic.
"In epidemiological, or population, studies, researchers have found an association between higher levels of urate and a lower risk of Parkinson's as well as slower disease progression in people with Parkinson's." Right.
It is great these researchers want to get down to the bottom of what is causing this association. It is a safe bet they are not going to repeat the failed experiment of raising uric acid levels - they would not be permitted to do so even if they wanted to.
That trial ended in 2018, and uric acid and Parkinson's studies continue. It was not a safe bet that studies would not continue because they have. Who would not permit researcher's to not do studies? What governing body even exists that monitors all PD researchers worldwide? Do a date search on Pubmed. Your claims are not really study backed, so I'm not going to bother refuting them any more. I'll post what is working for us, the supporting studies and people can do what they want with the info.
Your ignorance is showing - according to federal regulations all human studies must be approved by an Institutional Review Board at the researchers' institution.
You also mischaracterized what I said which is right there in black and white. I never said researchers cannot study uric acid and Parkinson's. I said that no new studies of raising uric acid for Parkinson's would be permitted.
You have yet to actually refute anything so it is just as well you will no longer try.
Pubmed has wordwide studies, there is no governing worldwide body for PD studies, and uric acid / PD studies in the U.S. and worldwide, remain ongoing.
Every single one of these was an observational study - they merely measured existing uric acid levels and made no attempt to raise or tamper with these levels in any way.
Human studies outside the US are also regulated per United Nations guidelines.
That is because those are cheap to do. If researcher's didn't think UA was important for brain health they wouldn't keep studying it. Check these studies out from a search for uric acid + neuroprotective -
And - Altered serum uric acid concentrations, both above and below normal levels, have been linked to a number of disease states. An abnormally high uric acid level has been correlated with gout, hypertension, cardiovascular disease, and renal disease, whereas a reduced uric acid concentration has been linked to multiple sclerosis, Parkinson's disease, Alzheimer's disease, and optic neuritis. Historically, uric acid has been considered a marker of these disease states. Recent studies, however, have provided evidence that uric acid may actually play a role in the development or progression of such diseases. As a result, the manipulation of uric acid concentrations is now either included in, or being investigated for, the treatment of a variety of disease states. pubmed.ncbi.nlm.nih.gov/178...
This exchange is turning ugly and it shouldn't be. If uric acid is out of normal range, then it's a canary in the mine and appropriates an intervention to identify the cause of the abnormal hypouricemia. It may mean that your renal functions are compromised heading towards chronic kidney disease or you may be imbalanced nutritionally such as copper/iron toxic, zinc-deficient or experiencing oxidative stress and endothelial dysfunction, etc. An intervention to improve the detox and eating better/broader healthy diet, lower inflammation/stress, increasing exercise all should help towards raising a lower value (associated with PD, Alzheimer's, Huntington's, MS, CKD, etc) toward a more normal range for a better outlook while using serum UA levels as a potential biomarker as part of a strategy for managing PD as in the below study.
That is pretty much our strategy. We are looking at all those areas.
My uric acid value is 4 at the limit of the minimum which is 3.5; how much should it be in your opinion to be optimal (in the range of minimum 3.5, maximum 7) for a PWPs if I may ask?
I can't give you any specific advice but I will look up the tables in a meta-analysis paper on UA levels in PD patients vs. healthy controls, and post that here when I find it. To complicate things a bit, optimal UA ranges may also vary by race and gender.
There is also a graph in a study on all cause mortality that shows lower mortality from mid-range UA levels. That is shown in the nutritionfacts video on Parkinson's and the Uric Acid Sweetspot - nutritionfacts.org/video/pa...
ETA - Here are the tables from a meta-analysis of studies comparing the mean uric acid of PD patients versus healthy controls. You can click on the different figures to see the various tables - pubmed.ncbi.nlm.nih.gov/283....
The nutritionfacts site recommends 5 - 7. Current gout avoidance recommendations are generally below 6. Most of the healthy control means in the PD studies seem to be between 5 & 7 for men, though lower for women.
ok I will study them. Thank you.
This person has neglected to inform you that uric acid levels in excess of 5 mg/dl quadruple the risk of gout for men. See attached table. She has no excuse for this omission because she has already been informed of this fact.
The nutrition facts video that she touts is invalid because it relies upon observational studies that were incorrectly interpreted. I explain this in detail here: Association ≠ Causation. Do Not Be Led Astray By This Popular Health Guru
Hi PB, thanks for the table. IMHO a correlation is not a causation , but it is like a "loose thread" that, pulling it, can lead to new discoveries. (As you can see, I'm learning to use idioms but I'm not as good as my friend WTP 😁. Ironic).My UA is 4, would it probably be low if I didn't use niacin and dairy? I do not know. But is a low UA as much of a problem as a high value?
Low UA is not a problem. Over five is not good, 4 is an excellent value. Regarding much lower, abnormally low values, per book on clinical methods:
" Hypouricemia [low uric acid] produces no symptoms or known morbidity. Its fortuitous discovery on automated chemistry screening requires no therapy but should alert the physician to search for an underlying cause."
GioCas - Here is another study you might find of interest - "We further found a nonlinear and U-shaped association between SUA [serum uric acid] and mortality. The inflection point for the curve was found at a SUA level of 5.7 mg/dL. The hazard ratios (95% confidence intervals) for all-cause mortality were 0.80 (0.65-0.97) and 1.24 (1.10-1.40) to the left and right of the inflection point, respectively. This U-shaped association was observed in both sexes; the inflection point for SUA was 6 mg/dL in males and 4 mg/dL in females.
Conclusion - Both low and high SUA levels were associated with increased all-cause and cause-specific mortality, supporting a U-shaped association between SUA and mortality."
"Both low and high SUA levels were associated with increased all-cause and cause-specific mortality, "
An association without an understanding of the causation behind it is worthless as a cause for action. Many disease states cause low uric acid level which is an effect rather than a cause of the disease. Parkinson's is a case in point - people who have to consume a lot of levodopa end up low in protein and uric acid because protein interferes with levodopa absorption.
GioCas - Another interesting paper from 2017 on gout that corresponds well to the UA levels reported in the all cause papers:
"In in vitro studies, uric acid has shown an antioxidant and therefore protective effect. ......Chronic gout treatment....International guidelines recommend that uric acid levels be adjusted to well below the solubility limit of 6.8 mg/dL in order to prevent deposits. There are currently no available studies that have investigated the optimum target uric acid levels. The German College of General Practitioners and Family Physicians ...recommends that uric acid levels should be maintained below 6.5 mg (27). The EULAR advises uric acid levels of less than 6 mg/dL, and even as low as <5 mg/dL in patients with severe gout (B). "
In their table 1, they show the incidence of gout at UA levels under 7 at .1%
Ty Brenda, I will study also this.
Greeting from Italy
GioCas - You may find it helpful to check the dates on the studies you look at. In the old days doctors thought uric acid was bad and lower was healthier. Now they know it is more about balance, and that uric acid is brain protective at the right levels, only toxic if it gets too high or too low. This is reflected in the more recent studies. Higher cholesterol levels are actually associated with less PD risk as well, though obviously too high is associated with disorders like heart disease.
I followed your recommendation and only looked at recent studies. The result:
U‐Shaped Association Between Serum Uric Acid Levels With Cardiovascular and All‐Cause Mortality in the Elderly: The Role of Malnourishment
" Remarkably, among the low SUA (<4 mg/dL) strata, only malnourished participants had greater all‐cause and CVD‐related mortality. This modifying effect of malnourishment remained consistent across subgroups."
Low Serum Uric Acid Levels are a symptom not a cause. This explains why the interventional trial of raising uric acid levels for Parkinson's failed.
I was wondering if I weren't on Niacin B3 how much lower my UA would be. However it is an interesting topic, I will study it. TY
My husband hasn't been tested for B3 yet but we plan to do that. He feels better after having cereal that has a high niacin fortification so that may be a clue for him. I just started digging into the niacin aspect after finding this forum so I'm hoping more B3 is something that will help him. I noticed that nightshade foods, which are high in B3, are on the diet survey studies as being protective of PD, so we've just started eating more of those.
I read this morning that royal jelly is very high in B3. Then I looked it up in Pubmed and there actually was a study showing royal jelly improved PD symptoms in a rat model of PD.
IMHO forget the nightshade, dangerous stuff, in every sense. The b3 niacin would seem to raise UA.
Actually studies show nightshade vegetables have a protective association with PD, as does smoking. Researchers have speculated it is because vegetables like peppers and potatoes are nightshades like tobacco. The nutritionfacts site has a video on this - Parkinson's: The Benefits of Smoking Without the Risks - nutritionfacts.org/video/pe...
nightshades , nicotine, no thank! Pure poison.
Perhaps in very small doses they can be neuroprotective, but they are not elements to play with.
Many years ago at my old school of agriculture and plant research center we had both pure nicotine, once used as an insecticide, and the cultivation of various Solanaceae such as nightshades , the lethal dose of these substances is very high and I would not recommend an herbal tea of nightshades .
I have direct experience, no thanks.!
The video is just talking about eating common foods like peppers, eggplant, tomatoes and potatoes, which are in the nightshade family. Those foods have been linked to lower incidences of PD. (There is also a transcript option on the same page as the video if you don't want to watch the video, but it is pretty short - under 5 minutes.)
Yes that's all good stuff! mmmhh! If you like the genre here is a study on vitamins that however associates a diet with zero red meat, with good results and as a friend of mine suggested one of the areas with the highest incidence of PD is the metropolitan area of Buenos Aires, an area very high consumption of red meat.
Another UA & PD paper I found in my web surfing today with some more tables and mean UA levels between patients and controls. This one is from India:
Uric acid a neuroprotective biomarker of Parkinson's Disease
....Low serum uric acid level may cause Parkinson's disease. So larger studies are required to ﬁnd out optimum level of uric acid level to prevent both events . This study provides an association between uric acid levels and reduced occurrence of PD and its inversely relation to staging and duration of illness. Hyperuricemia acts as a neuroprotective marker from PD. Reduction in uric acid level is associated with increased risk of Parkinson's disease[PD]. Diet modiﬁcation, iron, zinc supplements increase uric acid; their role in preventing and reducing the morbidity of PD to be conﬁrmed with larger studies." researchgate.net/publicatio...
Yet another study that finds an association:
"Reduction in uric acid level is associated with increased risk of Parkinson's disease"
The reason for this association is uric acid is reduced in advanced Parkinson's patients taking levodopa because they have less opportunity to eat protein.
This poster persists in ignoring the fact that causation has been refuted by the failed interventional study: pubmed.ncbi.nlm.nih.gov/345...
Based on the mistaken idea that high uric acid levels are good for Parkinson's, this gold standard double-blind randomized controlled phase 3 study that raised uric acid levels was undertaken. This study was halted early for futility. Raising uric acid levels made Parkinson's patients worse - the patients with elevated uric acid progressed more quickly than those on placebo:
"participants randomized to inosine [progressed] (MDS-UPDRS score, 11.1 ...points per year) and placebo (MDS-UPDRS score, 9.9 ... points per year;"
They tried to excuse it because the worsening was not statistically significant. In any case this failure trumps observational studies.
High uric acid has been proven to cause kidney disease, and gout, and is strongly associated with stroke and heart attack. Hopefully at this point no one at this website will be deceived by this poster's propaganda.
park_bear & Brenda,
Given the apparent downside to elevated Uric Acid (UA) levels in diabetes, stroke, dementia, heart disease and gout, to name just a few, compared to a minimal upside if any in PD, it seems hard to justify the idea of elevating UA levels as a treatment option in PD considering the potential risks.
The study that park-bear posted is an actual large human study (RCT) where they raised UA levels, with Inosine . Any healthful effects were negligible in the PD participants.
The main apparent benefit that UA seems to offer is its antioxidant effects. If that is the case, there are other antioxidants that are at least as potent or more so than UA, which are more likely to confer heart health benefits, dementia benefit, stroke benefit, diabetes benefit, PD benefit and gout benefit. That seems like it may be a more viable option than UA, in my opinion based on potential risk / reward benefit.
Art - I hope you don't mind me posting links and snippets from recent, published papers in peer reviewed medical journals by actual Parkinson's researchers on the subject or current studies funded by grants on the Michael J. Fox Parkinson's Foundation site. You and other posters can read the information and decide if you find it applicable or not to your situation.
Here is a current study highlighted on the Michael J. Fox site - Uric Acid as an Antioxidant Treatment for LRRK2-associated Inherited Parkinson's Disease - Given the antioxidant property of uric acid and its involvement in the Nrf2 antioxidant pathway, it is likely to be therapeutic in LRRK2-associated inherited PD. michaeljfox.org/grant/uric-....
Can higher levels of caffeine and uric acid prevent Parkinson’s? - parkinsonslife.eu/parkinson... (2020 article)
Contrary to what other forum member's have posted, UA research did not stop with the inosine study. UA research remains a hot topic for PD, MS and Alzheimer's researchers. These are people with PhDs performing these studies who do nothing but research Parkinson's and related brain disorders, not random people making forum or blog posts.
The report on the failure of the interventional study was just published in September 2021
The grant for the study funded by the Michael J Fox foundation that you linked to was awarded in 2018. It is unlikely any more grants of this type will be awarded now. This idea is dead. The other link that you posted was of yet another observational study finding an association. Association is not causation. Persistence in error is not a virtue.
Hopefully at this point no one at this website will be foolish enough to attempt to raise their uric acid level.
I understand what you are saying about the potential that these studies may or may not show. I think I am looking at this from a different perspective than you.
I look at PD as a disease where time is of the essence for people who have it. These studies that are showing future potential, in reality are easily a decade or more away from possibly coming up with a treatment after completing all of the required studies and FDA requirements and many simply never even make it to phase three or die for lack of funding. To some PwP, that means that even if it works, it is beyond their lifespan. This forum has close to 20,000 members, some of whom are already in stage 4 or 5 of PD. For them this has little to no value.
There is no reason why the research can't be continued in the area of UA and I'm sure it will, but I do not see it as a reason to get excited at this time. Many things are discussed on this forum that show great potential, but again they could be one to two decades away if all goes well. I am more interested when something shows nearer term potential to slow or reverse the disease process or significantly improve quality of life. Things like B1, wriga's Broccoli seed experiment, high dose melatonin, mannitol, microbiome manipulation, Photobiomodulation, Citicoline, Ambroxol, Vinpocetine, Very Low Dose Lithium Orotate and FMT to name only a few. All have good safety profiles and some are already available. In the case of B1, MJFF refused to fund any studies for it because they said that since it is just a vitamin and if you want to know if it will help, then just try it. That's what forum members were already doing after a year of waiting for MJFF to decide that they would not fund B1.
It is your right to be excited about research into UA, but we just view that research differently and there is nothing wrong with that, as we all have opinions on this forum.
Well said Art and speaking of opinions I find UA an interesting topic for the PD to be put to a "hard test" to see how far it can lead us. The presumption of already knowing everything, in one way or another, is the first barrier to learning. Here we have evidence for, but also evidence against, which is why it is an interesting topic for one who seeks.
Art - I am unclear why you think vitamin B1 can be tested and corrected by just trying it by individuals but not uric acid. Both can be tested with simple blood tests. My husband had his uric acid tested at a Quest lab for $13, and it was out of range low. Now he has test strips from Amazon to use in between blood tests. I bought a UA meter for myself, also from Amazon, like a glucose meter. UA can be raised by common foods like tea and coffee and avoiding dairy. There are many diets on the Internet on what foods lower and raise UA levels if you look for gout diets.
Related links: "....some evidence exists regarding a potential protective effect of uric acid, poly-unsaturated fatty acids, coffee, and tea but mainly in men, whereas dairy products, particularly milk, might increase PD risk through contaminant mediated effect." ncbi.nlm.nih.gov/pmc/articl...
"These data support urate as a potentially protective factor in PD and suggest that dietary changes expected to increase plasma urate level may contribute to lower risk of PD." - academic.oup.com/aje/articl...
Report Highlights Potential Benefits of Drinking Coffee in Neurodegenerative Diseases, Including Parkinson’s - parkinsonsnewstoday.com/201...
He has done other things like correcting vitamin D and B12 deficiencies and Qi Gong, but the UA changes (per the test strips) seem to correlate the most with his tremor quieting and the rigidity lessening. This is, of course, anecdotal on our part, but we got the idea to test UA to begin with and adjust his diet from the Parkinson's research. That is what people with gout have to do. I don't see a lot of downside of getting UA levels into the healthy control group ranges from the PD studies. It can't hurt and might help.
He is in the process of testing everything mentioned in the PD studies - every vitamin, every mineral, metabolites, pesticides, leaky gut, Celiac, microbiome and more, plus all the regular lab tests the doctors run, and correcting what he can. So far it has worked out really well and I'm trying to share what has helped him. He did have his vitamin B1 levels tested and those were in range.
That was not my opinion about B1, that was MJFF's opinion.
As far as B1 testing, Dr. Costantini's experience was that almost all of his patients showed B1 levels that were in range prior to B1 treatment and then off the chart once B1 therapy was implemented. A B1 blood test does not show tissue levels, which he felt was what mattered, thiamine in the brain.
Regarding UA, the new RCT is very clear and based on their results in PwP, not of enough benefit to do further studies, after elevating UA to levels that have shown problems for the health issues I mentioned above. It will be interesting to see what the researchers that MJFF is funding turn up, though I am doubtful it is an RCT.
Please keep us updated on your husbands testing.
You are mischaracterising MJFF's response regarding B1 funding.
If the response that Roy has posted here (purporting to be a forward from M Colangeli) is correct, then:
- the b1 funding proposal made it through to round 2 of the review process. If they wanted to dismiss it out of hand on the basis that it is "just a vitamin", they would have done so at round 1.
- the stated reasons for rejection included:
1. That the stated goals were not realistic
2. That the requested funding would not be adequate
3. That the proposed team lacked the requisite trial experience.
They have said that PWP are welcome to self trial b1 as it is readily available, but that was not the primary, or a primary reason for the rejection of the funding request. It most certainly was not "MJFF refused to fund any studies for it because they said that since it is just a vitamin"
Art - Can you please explain what you mean by "the new RCT is very clear and based on their results in PwP, not of enough benefit to do further studies". Can you provide a supporting link? If you mean no more uric acid studies in PD patients, studies those are in progress with grants from the MJFF per the link above, plus there are more study grants on their I didn't post the links to. You can find them on the MJFF web site using their search feature for "uric acid".
There is Parkinson's and uric acid research going on all over the world right now in many countries including the U.S., India and China. It is a hot topic of interest among researchers, far from a dead end based on a single U.S. study on inosine supplements.
PwP = people with Parkinson's. An RCT is a Randomized Controlled Trial which is what the study was that park_bear linked to. It was a good sized study (298 participants) and the PwP participants did not show significant improvement after their uric acid levels were elevated via the use of Inosine and it was posted last month, so it is new. So this is considered more important than in vitro and animal studies.
Here is a link to that new abstract :
Here is the abstract quoted conclusion to the study:
>>> ' Conclusions and relevance: Among patients recently diagnosed as having PD, treatment with inosine, compared with placebo, did not result in a significant difference in the rate of clinical disease progression. The findings do not support the use of inosine as a treatment for early PD. ' <<<
One problem is that elevating the UA, even if it had a little benefit in the participants, that level significantly increases the risk for the other named health issues that I mentioned above.
Here is another quote from the abstract :
>>> ' Based on a prespecified interim futility analysis, the study closed early, with 273 (92%) of the randomized participants (49% women; mean age, 63 years) completing the study. Clinical progression rates were not significantly different between participants randomized to inosine (MDS-UPDRS score, 11.1 [95% CI, 9.7-12.6] points per year) and placebo (MDS-UPDRS score, 9.9 [95% CI, 8.4-11.3] points per year; difference, 1.26 [95% CI, -0.59 to 3.11] points per year; P = .18). Sustained elevation of serum urate by 2.03 mg/dL (from a baseline level of 4.6 mg/dL; 44% increase) occurred in the inosine group vs a 0.01-mg/dL change in serum urate in the placebo group (difference, 2.02 mg/dL [95% CI, 1.85-2.19 mg/dL]; P<.001). There were no significant differences for secondary efficacy outcomes including dopamine transporter binding loss. Participants randomized to inosine, compared with placebo, experienced fewer serious adverse events (7.4 vs 13.1 per 100 patient-years) but more kidney stones (7.0 vs 1.4 stones per 100 patient-years). ' <<<
So they closed this study early based on the poor results. That's why I said the results were pretty compelling. Since this study ended the way it did, it will likely significantly lessen the chances for future RCTs utilizing UA in PwP, imo.
I've posted links to some of the current worldwide studies on PD and UA in this and my other UA thread. The inosine study ended years ago, only addressed inosine as a supplement and did not prevent further PD-UA research.
There are many studies where a supplement is found detrimental, like vitamin E, but whole foods containing the supplement ingredient and many others, are beneficial. PD starts in the microbiome. A single supplement may not make significant microbome changes like whole food diet improvements can.
The topic is UA, not diet or microbiome, those are two completely different areas of research.
Randomized, double blind, placebo controlled trials are considered to be a gold standard in studies and carry considerable weight over lab studies, animal studies and this study was a good sized study. Given the bad results that this study showed, it is likely to have a negative impact on funding for future studies testing UA in PwP. They stopped this study early and that is a really hard barrier to overcome for future studies in terms of people willing to fund another RCT of this size. I'm not saying it can't happen, but I would not hold my breath waiting for another RCT like this one. That is my opinion Brenda and I think I understand your opinion, so I think we have communicated our thoughts with each other regarding UA to completion.
Uric acid and PD studies are currently ongoing with grants from the MJFF in the U.S. and there are numerous studies in other countries. That isn't my opinion, it is a fact.
The only evidence I saw from you on this matter was a grant awarded in 2018 and current status unknown. In any case this is irrelevant. Anyone can claim "ongoing studies" as an excuse for treatment failure so that excuse is no excuse at all. In this case it fails badly because the only kind of study that could overturn the existing record of a failed interventional study would be a successful interventional study of raising uric acid to treat Parkinson's, and that kind of study is not happening.
Reference - clinical trials in Parkinson's and uric acid:
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