36 replies to this topic

[geo12the]

My partner and I did 23&me and it turns out he has a really nasty SNP that greatly predisposes him to Parkinson’s (62% chance he will get it). No one in his family has it that he is aware of (they are all on Statin's which are known to decrease the risk).

We already take:

Fish oil (daily)

Resveratrol (daily)

Curcumin (daily)

MCT oil (daily)

Coenzyme Q- (every other day)

Vitamin D (every other day)

Multivitamin (couple of times a week)

Primrose oil (couple of times a week)

He is on statins for cholesterol (statin’s are associated with lower risk of developing Parkinson’s)

Any other supplements that would be good to help prevent the Parkinson’s in someone who is predisposed? Any that are bad? We may start c60/olive oil. By weird coincidence I bought a bunch of trehalose before we got the results because I wanted a healthy substitute for sucrose and I was intrigued by the reports that it stimulates autophagy and may have health benefits. It turns out trahalose may be promising for Parkinson’s and Alzheimer’s (I am at lightly elevated risk for) so we are using it as a substitute for sucrose.

[niner]

I would start with c60-oo. I'd also make sure that the multi didn't contain any iron or copper. Copper deficiency is quite rare, but its association with Alzheimers and MCI are too compelling to ignore. We have a couple recently active threads to this effect. I don't know what the exact association is between Cu and Parkinsons, but it's probably not good. A 62% chance of getting Parksinsons is a huge number. Is it by any chance a 62% increase in the odds of getting it? (that would be MUCH better) Do you happen to know what the rs code for the SNP is? (or the name of the gene?)

[Blankspace]

It's worth noting that: (23andme quote) "The heritability of Parkinson's is relatively low but a recent study estimated it to be about 27% in European populations. This means that environment generally plays a larger role than genetics in determining a person's risk for the disease." I'd not ignore this genetic predisposition, but I'd certainly not be overly concerned about the risk at this point. 1.6% is typical risk, +62% increased chance = 2.6% chance of disease.

Look into supplementing magnesium.
http://www.longecity...ease-functions/

[Darryl]

Nicotine is worth a 60% risk reduction and caffeine 30%. Oral tobacco works just as well.

The likely mechanism of risk reduction by caffeine.

> 3 cups of black tea daily delayed Parkinson's symptoms by 7.7 years.

High black tea consumption, but not green tea consumption, reduced Parkinson's risk by 71%

The hot topic in reducing Parkinson's risk 5 years ago appeared to be the Nrf2 endogenous antioxidant response pathway. Inducers include sulforaphane, curcumin, carnosic acid and other, less potent polyphenols from foods; a couple of orders more potent are the synthetic triterpenoids of the CDDO/bardoxolone family currently in clinical trials.

More recently, interest has focused on autophagy inducers. While there are a number of autophagy inducers from food, including spermidine, there are also a number of drugs, and more found every year, that are the subject of investigation. David Rubinsztein is perhaps the leading expert on autophagy inducers in the prevention of neurodegenerative diseases, his 2011 SENS lecture is worth viewing.

Edited by Darryl, 16 September 2013 - 11:57 PM.

[maxwatt]

Nicotine use protects against Parkinsons. Not that I recommend it, as there are enough negatives even if it is not smoked to outweigh that benefit for most people. But the mechanism - nicotine stimulates release of dopamine in the substantia nigra, apparently increasing the life of these brain cells, delaying or preventing PD. All known addictive drugs also stimulate dopamine release. I wouldn't recommend opiates, but marijuana is a fairly benign substance when used in moderation, and it is known to relieve Parkinson's symptoms. I suspect that regular use of marijuana in moderation would delay or prevent the onset of Parkinson's, though I do not know of studies to that effect - they haven't been done, and until recently would not have gotten funded. If you are fortunate enough to live in a medical marijuana state, and have a sympathetic doctor, go for it.

Most people with the gene do NOT develop PD; your partner does not have a 62% chance of getting PD, they mean his chances of getting the disease are 62% greater than an average person. Say average is 1% chance, then your partner's chance is 1.62 percent.

By the way, I also have the 23andme PD notice, enough so my immediate blood relatives were offered free tests so they could study it. None of my family have or have ever had PD.

[geo12the]

I would start with c60-oo.

How often? I am thinking about once a week?

A 62% chance of getting Parksinsons is a huge number. Is it by any chance a 62% increase in the odds of getting it? (that would be MUCH better) Do you happen to know what the rs code for the SNP is? (or the name of the gene?)

It's 61.2% chance of getting it during your lifetime. Increase in the odds of getting it is 86.38x! The gene is LRRK2. Rs code rs34637584. The SNP is a dominant mutation that changes the protein sequence. No one in his family has Parkinson’s that we are aware of but they are all on Statins which are thought to cut the risk in half. No family history of Parkinson’s so I thought perhaps it was a mistake or spontaneous mutation, however the SNP is common in people of Ashkenazi ancestry which he is.

Edited by geo12the, 17 September 2013 - 12:22 AM.

[geo12the]

Thanks for the information everyone.

Nicotine is worth a 60% risk reduction and caffeine 30%. Oral tobacco works just as well.

Nicotine use protects against Parkinsons.

http://www.ncbi.nlm....pubmed/23661325
I was just reading this interesting abstract about consumption of nicotine rich foods and PD.

marijuana is a fairly benign substance when used in moderation, and it

He used to indulge occasionally but no longer enjoys the effects (sais it makes him feel grouchy the next day) and has not partaken in many years.

From what I have read curcumin is promising for preventing PD and also resveratrol both of which we have been taking for a while. The most interesting compound to me is trehalose. This is a sugar, a disaccharide of glucose. It is about half as sweet as sucrose and somewhat less soluble. It’s broken down to glucose in your digestive tract but apparently about 1 or two percent of it is absorbed into your bloodstream. It seems to somehow act on the TOR pathway which stimulates autophagy, so it could potentially be reversing the root problems that lead the damage that manifests itself as PD.

[niner]

From SNPedia:

One copy of a rs34637584(A) allele is sufficient to greatly increase one's risk for Parkinson's disease. It is considered a disease causing mutation because it is rarely found in healthy, elderly people without Parkinson's disease, and it has been found in both familial and sporadic types of the disease. While there are many different SNPs that can influence one's risk for Parkinson's disease, rs34637584 is an especially common cause of the disease in Berber Arabs and Ashkenazi Jews. Overall, the risk of Parkinson's disease for a person who inherits a rs34637584(A) allele is 28% at age 59, 51% at 69, and 74% at 79, according to the International LRRK2 Consortium.[PMID 18539534]

So that's a pretty ugly gene, I'm afraid. I'd break out every gun in the arsenal. Would a nicotine patch do any good?

[geo12the]

So that's a pretty ugly gene, I'm afraid. I'd break out every gun in the arsenal. Would a nicotine patch do any good?

Nicotine has been shown to prevent the formation of the missfolded protein aggregates that cause PD.
I was thinking nicotine gum. But he had a very negative response when I mentioned it. He used to be a smoker and he said quitting was the hardest thing he ever had to do.
The instructions on the gum say that to quit smoking gradually decrease use of the gum to one or two pieces a day. I figure if he were to only do one piece of the lower dose (2mg) a day he would not get addicted but that the nicotine may help prevent the toxic protein missfolding and aggregation that gunks up the brain in PD.

[Darryl]

If you're curious about what level of nicotine use conferred PD protection, I think table 2 from this paper is informative:

Chen, H., et al. "Smoking duration, intensity, and risk of Parkinson disease."Neurology 74.11 (2010): 878-884

1-10 cigarettes/day in current smokers conferred a 42% risk reduction (while the heaviest current smoker cohort got 60%). Would have been nice if they had broken that down still further - ie, would the equivalent of 1 cigarette help much?

I suspect if I had that SNP (and a history of smoking addiction), I'd stick with a heavy coffee addiction, regular black tea, exercise, avoiding pesticide exposure & dairy products (risk factors), etc until PD symptoms showed up, and then see if I wanted to unlock the arsenal.

...

Addendum: The rs34637584 allele is in the gene for LRRK2, which regulates autophagic activity, and this more recent paper details effects from geo's partner's SNP G2019S. Some of the neuron's recycling bins aren't being picked up. Some lysosomes (the bins) were less acidic than normal, which perhaps effects their ability to breakdown unneeded, misfolded & aggregated proteins. While G2019S cells appeared to have more lysosomes (and hence may already have constituitively upregulated autophagy), autophagy inducer rapamycin seemed to reduce cytotoxicity when subject to a stressor.

Edited by Darryl, 17 September 2013 - 08:53 AM.

[rashlan]

Ibuprofen?

http://www.ncbi.nlm....ubmed/21368281/

[rikelme]

Methylene blue

 

Alternative Mitochondrial Electron Transfer as a Novel Strategy for Neuroprotection

Abstract

Neuroprotective strategies, including free radical scavengers, ion channel modulators, and anti-inflammatory agents, have been extensively explored in the last 2 decades for the treatment of neurological diseases. Unfortunately, none of the neuroprotectants has been proved effective in clinical trails. In the current study, we demonstrated that methylene blue (MB) functions as an alternative electron carrier, which accepts electrons from NADH and transfers them to cytochrome c and bypasses complex I/III blockage. A de novo synthesized MB derivative, with the redox center disabled by N-acetylation, had no effect on mitochondrial complex activities. MB increases cellular oxygen consumption rates and reduces anaerobic glycolysis in cultured neuronal cells. MB is protective against various insults in vitro at low nanomolar concentrations. Our data indicate that MB has a unique mechanism and is fundamentally different from traditional antioxidants. We examined the effects of MB in two animal models of neurological diseases. MB dramatically attenuates behavioral, neurochemical, and neuropathological impairment in a Parkinson disease model. Rotenone caused severe dopamine depletion in the striatum, which was almost completely rescued by MB. MB rescued the effects of rotenone on mitochondrial complex I-III inhibition and free radical overproduction. Rotenone induced a severe loss of nigral dopaminergic neurons, which was dramatically attenuated by MB. In addition, MB significantly reduced cerebral ischemia reperfusion damage in a transient focal cerebral ischemia model. The present study indicates that rerouting mitochondrial electron transfer by MB or similar molecules provides a novel strategy for neuroprotection against both chronic and acute neurological diseases involving mitochondrial dysfunction.

 

 

[celebes]

- Ubiquinol, PQQ, Tocotrienols

 

- Threonate, ALCAR, Uridine

 

- Ginseng, Jiaogulan, Curcumin, Pycnogenol, Black Tea

 

- Thiamine, B6, B12, C

 

- Magnesium, Zinc, Selenium, Iodine

 

- Cardio

 

 

 

With those odds, perhaps better to not skimp on the doses. Also consider eliminating Omega-6 from diet and adding virgin Coconut oil. Research stimulated by being vulnerable myself.

 

Edited by celebes, 06 May 2014 - 07:39 AM.

[rikelme]

Noopept

 

http://www.ncbi.nlm....pubmed/21986202

 

Neuroprotective and nootropic drug noopept rescues α-synuclein amyloid cytotoxicity.

Jia X¹, Gharibyan AL, Öhman A, Liu Y, Olofsson A, Morozova-Roche LA.

Author information

Abstract

Parkinson's disease is a common neurodegenerative disorder characterized by α-synuclein (α-Syn)-containing Lewy body formation and selective loss of dopaminergic neurons in the substantia nigra. We have demonstrated the modulating effect of noopept, a novel proline-containing dipeptide drug with nootropic and neuroprotective properties, on α-Syn oligomerization and fibrillation by using thioflavin T fluorescence, far-UV CD, and atomic force microscopy techniques. Noopept does not bind to a sterically specific site in the α-Syn molecule as revealed by heteronuclear two-dimensional NMR analysis, but due to hydrophobic interactions with toxic amyloid oligomers, it prompts their rapid sequestration into larger fibrillar amyloid aggregates. Consequently, this process rescues the cytotoxic effect of amyloid oligomers on neuroblastoma SH-SY5Y cells as demonstrated by using cell viability assays and fluorescent staining of apoptotic and necrotic cells and by assessing the level of intracellular oxidative stress. The mitigating effect of noopept against amyloid oligomeric cytotoxicity may offer additional benefits to the already well-established therapeutic functions of this new pharmaceutical.

Copyright © 2011 Elsevier Ltd. All rights reserved.

 

 

 

 

[rikelme]

Cinnamon

 

Cinnamon Treatment Upregulates Neuroprotective Proteins Parkin and DJ-1 and Protects Dopaminergic Neurons in a Mouse Model of Parkinson’s Disease

 

Abstract

Upregulation and/or maintenance of Parkinson’s disease (PD)-related beneficial proteins such as Parkin and DJ-1 in astrocytes during neurodegenerative insults may have therapeutic efficacy in PD. Cinnamon is a commonly used natural spice and flavoring material throughout the world. Here we have explored a novel use of cinnamon in upregulating Parkin and DJ-1 and protecting dopaminergic neurons in MPTP mouse model of PD. Recently we have delineated that oral feeding of cinnamon (Cinnamonum verum) powder produces sodium benzoate (NaB) in blood and brain of mice. Proinflammatory cytokine IL-1β decreased the level of Parkin/DJ-1 in mouse astrocytes. However, cinnamon metabolite NaB abrogated IL-1β-induced loss of these proteins. Inability of TNF-α to produce nitric oxide (NO) and decrease the level of Parkin/DJ-1 in wild type (WT) astrocytes, failure of IL-1β to reduce Parkin/DJ-1 in astrocytes isolated from iNOS (−/−) mice, and decrease in Parkin/DJ-1 in WT astrocytes by NO donor DETA-NONOate suggest that NO is a negative regulator of Parkin/DJ-1. Furthermore, suppression of IL-1β-induced expression of iNOS in astrocytes by NaB and reversal of NaB-mediated protection of Parkin/DJ-1 by DETA-NONOate in astrocytes indicate that NaB protects Parkin/DJ-1 in activated astrocytes via suppressing iNOS. Similarly MPTP intoxication also increased the level of iNOS and decreased the level of Parkin/DJ-1 in vivo in the nigra. However, oral treatment of MPTP-intoxicated mice with cinnamon powder and NaB reduced the expression of iNOS and protected Parkin/DJ-1 in the nigra. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions by cinnamon in MPTP-intoxicated mice. These results suggest that cinnamon may be beneficial for PD patients.

 

Full article link:

http://libgen.org/scimag/get.php?doi=10.1007%2Fs11481-014-9552-2

[ironfistx]

Peppers fight

 

http://www.huffingto..._n_3246499.html

[blood]

Nicotine In Peppers, Other Plants Linked With Lower Parkinson's Risk: Study
 
http://www.huffingto..._n_3246499.html

Researchers didn't find any link between overall vegetable consumption and Parkinson's risk, but they did find an association between increased peppers and Solanaceae consumption and decreased Parkinson's risk, among people who had no or minimal tobacco use history...

Interesting.

Unfortunately I often feel slightly ill after consuming raw Peppers.

The picture gallery accompanying that article presents some interesting factoids:

- A 1993 study found 3.8 ng/g of nicotine in a cauliflower, which means that a person would have to eat 263.4 grams of it to equal the effects of being in a room with a smoker for three hours...

- Perhaps the most interesting information, found in a previous study, is that eating 10 grams of eggplant results in the effects of passive smoking. An eggplant was found to contain 100 ng/g of nicotine. Don't worry just yet, though: You'd have to eat 20 pounds of eggplant before you experience the same effects as smoking one cigarette. That's a lot of eggplant!

- Green tomatoes had a higher level of nicotine in a previous study-- 42.8 ng/g. Eating 23.4 grams equaled the effect of passive smoking.

- The 1993 study found 4.1 ng/g of nicotine in ripe tomatoes. Eating 244 grams equals the effects of passive smoking.

- Pureed tomatoes were much higher. A previous study found 52 ng/gram of nicotine. Eating 19.2 grams equals the effects of passive smoking.

[niner]

Why not just slap on a very small nicotine patch?  If nicotine is anti-Parkinson.  Has that been shown?

[Freebytes]

I must agree with Rikelme on this one.  Methylene Blue has been shown to prevent tau protein formation that causes the symptoms of Alzheimer's and has been shown to have positive benefits against Parkinson's.  A good question is: Where can pure Methylene Blue be purchased without worry about toxins.  I think I may have heard of people taking it, but I do not know where they get it from.

 

 

[blood]

If nicotine is anti-Parkinson.  Has that been shown?

 
I think there are just the epidemiological/observational studies pointing to decreased risk of Parkinson's for smokers/ people who eat peppers.
 
Not sure if there have been any RCTs for prevention or treatment.
 
This study finds that people with mild cognitive impairment do benefit from a nicotine patch (15 mg/day for 6 months):
 

Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial.

Newhouse P1, Kellar K, Aisen P, White H, Wesnes K, Coderre E, Pfaff A, Wilkins H, Howard D, Levin ED.

Abstract

OBJECTIVE:
To preliminarily assess the safety and efficacy of transdermal nicotine therapy on cognitive performance and clinical status in subjects with mild cognitive impairment (MCI).

METHODS:
Nonsmoking subjects with amnestic MCI were randomized to transdermal nicotine (15 mg per day or placebo) for 6 months. Primary outcome variables were attentional improvement assessed with Connors Continuous Performance Test (CPT), clinical improvement as measured by clinical global impression, and safety measures. Secondary measures included computerized cognitive testing and patient and observer ratings.

RESULTS:
Of 74 subjects enrolled, 39 were randomized to nicotine and 35 to placebo. 67 subjects completed (34 nicotine, 33 placebo). The primary cognitive outcome measure (CPT) showed a significant nicotine-induced improvement. There was no statistically significant effect on clinician-rated global improvement. The secondary outcome measures showed significant nicotine-associated improvements in attention, memory, and psychomotor speed, and improvements were seen in patient/informant ratings of cognitive impairment. Safety and tolerability for transdermal nicotine were excellent.

CONCLUSION:
This study demonstrated that transdermal nicotine can be safely administered to nonsmoking subjects with MCI over 6 months with improvement in primary and secondary cognitive measures of attention, memory, and mental processing, but not in ratings of clinician-rated global impression. We conclude that this initial study provides evidence for nicotine-induced cognitive improvement in subjects with MCI; however, whether these effects are clinically important will require larger studies.

CLASSIFICATION OF EVIDENCE:
This study provides Class I evidence that 6 months of transdermal nicotine (15 mg/day) improves cognitive test performance, but not clinical global impression of change, in nonsmoking subjects with amnestic MCI.

Edited by blood, 23 December 2014 - 11:57 AM.

[blood]

Not sure if there have been any RCTs for prevention or treatment.

There have been some small clinical trials of nicotine as treatment for Parkinson's:
 

Can Nicotine be Used Medicinally in Parkinson's Disease?

... Clinical trials have yielded inconclusive results thus far and are hampered by different designs and small cohorts. Ongoing studies address either symptomatic motor or nonmotor symptoms, or neuroprotection. There is still no agreement on the daily dosage of nicotine or the method of administration. Together, these data suggest that nicotine or nicotinic receptor drugs have therapeutic potential for Parkinson's disease, although the specific treatment regimens remain to be determined...

In this study no treatment benefit was found:
 

Prog Neuropsychopharmacol Biol Psychiatry. 2004 Jan;28(1):31-9.

Lack of efficacy of a nicotine transdermal treatment on motor and cognitive deficits in Parkinson's disease.

Abstract
Studies assessing the efficacy of nicotine in Parkinson's disease (PD) have generated contradictory results. The controversy seems to stem from uncontrolled factors including the lack of objective measures, the practice effect in a test-retest design, and the absence of plasmatic dosage. This study aimed at further controlling these factors using transdermal nicotine in PD.

METHODS:
Twenty-two nonsmoking PD patients received a transdermal nicotine treatment over 25 days in increasing titrated doses. Motor and cognitive assessments were carried out on days 11 and 25 (low-dose and high-dose assessments, respectively) and after a 14-day washout period.

RESULTS:
Patients tolerated nicotine poorly. Thirteen (59%) withdrew, mostly because of acute side effects. In the remaining nine patients, nicotine neither improved nor worsened motor or cognitive functioning in comparison with 10 age, gender and education matched controls.

CONCLUSIONS:
Transdermal nicotine is not effective in treating motor and cognitive deficits in PD. The results obtained with our objective measures confirm a recent double-blind, placebo-controlled study that used clinical measures. It is possible that nicotine lacks specificity in targeting critical nicotinic receptors that might be involved in PD pathophysiology. The low tolerability may be related to such a lack of specificity of nicotine, which would directly stimulate the autonomic nervous system.

PMID: 14687854 [PubMed - indexed for MEDLINE]

[mike_nyc]

I like fisetin, found naturally in strawberries.

 

The neuroprotective effect of fisetin in the MPTP model of Parkinson's disease.

http://www.ncbi.nlm....pubmed/23938259

 

Natural plant compound prevents Alzheimer's disease in mice

http://www.salk.edu/...hp?press_id=655

 

A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease.

http://www.ncbi.nlm....pubmed/22846082

 

Mechanisms underlying the neuroprotective effects of fisetin and ibuprofen in the MPTP model of Parkinson’s disease

http://www.fasebj.or...bstracts/1004.7

[OneScrewLoose]

1mg of selegiline per day is probably the best thing you can do. At that dose he won't notice he's taking it. It's an MAO-B inhibitor. Tobacco has a natural MAO-B inhibitor that contributes to it's Parkinson's risk reduction.

If you want nicotine without the tobacco. Look into vaping. I vape on a regular basis. It does not produce smoke, so there's no tar or anything like that. Nicotine itself has shown potential to be neuroprotective, and nicotine outside of tobacco is less addictive than nicotine in tobacco.

[amark]

Google: U of Toronto /trehalose/parkinsons. 

[bocor]

I would recommend turmeric force 6 caps per day and algal dha 8 caps per day both increase neural stem cell proliferation and I was having problems with shakes nervous tension for months and this has helped extremely well I originally took for my herniated disc problems as the studies indicated this combo helped restore walking ability to people with spinal cord damage
The turneric force contains the turmerone which is the compound that grows new nerve cells plain curcumin doesn't have this
Dha is extremely important for healthy nervous system and communication

[geo12the]

Thanks for the suggestions!

 

He has been popping two 2 mg nicotine lozenges a day and takes one turmeric force cap in the morning and one tumeric BCM-95 cap in the late afternoon.  We use trehalose as a sweetener. Works well in many things but crystallizes easier than table sugar. Works great in cocktails we have on weekends. We also take fish oil, Res, vitamin D, Lithium orate. And take ibuprofen and cinnamon every other day. I am on the same regimen except for the nicotine pills. He is also on statins which have shown strong protective effects for PD.

 

About the contradictory results of nicotine in clinical trials-one possibility is that by the time someone starts showing symptoms of PD its too late to reverse the damage. it's possible nicotine might  help prevent PD, as suggested by association/epidemiological studies, but may have no benefit once you get it. That is a problem with clinical trials and lots of the neuroprotective  compounds, most trials are done with people already showing symptoms.

[geo12the]

Also my partner is Ashkenazi. Turns out that the PD susceptibility mutation he carries has somewhat lower penetrance in this population according to a recent study (Askanazi with this mutation are not as susceptible to PD as non-Askanazi)

Edited by geo12the, 21 January 2015 - 12:08 AM.

[rikelme]

Jaiogulan (a Chinese plant)! Looks very promising. You can start further search from this very informative Longecity thread:

17 Random Dopaminergic Supplements

[APBT]

From LEF:  http://www.lef.org/P...Disease/Page-01

 

[niner]

The LEF writeup on Parkinson's is pretty good.  Considering the role of mitochondrial dysfunction in Parkinson's, I would consider a mitochondrial antioxidant like c60 olive oil, MitoQ, or SkQ1.