#43

Thank you, Antoine, you are doing the Lord’s work here. I saw Viktor’s post and was going to respond, but didn’t have the energy, there are so many of such, and responding to each is like fighting weeds, soon there’s a new one. Life is too short to have to repeat the same things over and over again. I posted a study in another thread showing that NSAIDs were helpful in dementia, so whatever impact on leaky gut, it’s net positive - and this is a brand new one from this month:

Long-Term Exposure to Non-Steroidal Anti-Inflammatory Medication in Relation to Dementia Risk

https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.19411

And Viktor recommended a book by S. Gundry. That’s a red flag. Gundry is a notorious money spinner peddling discredited conspiracy theories to generate cash. He’s all over yt and in ads all over the net, the guy is a misinformation industry. Anyone who thinks that guy has any credibility really has done no research. The moment I saw that name, I could’ve stopped reading. It’s like you want to discuss astronomy and somebody starts the discussion by recommending a flat earth book - this is not going to go anywhere.

I was wondering if perhaps we could have a pinned post or FAQ where the most common talking points surrounding useless recommendations for conditions like PD and cholesterol denialism are dealt with citing studies, and whenever a poster comes along repeating one of those, one could send them to the FAQ/pin, instead of trying to deal with the same points over and over again. If we could do some kind of wiki here we could cut down on noise quite a bit?

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#44

It’s not my theory, but I fully support it. Since I don’t see a clear explanation for many diseases.
The gist of it: damage to the intestine (leaky gut) and subsequent inflammation, with increased levels of calprotectin in the feces and this is a marker of inflammation.
There is a lot of work supporting this theory:
https://www.nature.com/articles/s41598-023-45929-z

Exploratory analyses indicated that calprotectin levels were also associated with cerebrospinal fluid markers of AD, and with lower verbal memory function even among cognitively unimpaired participants. Taken together, these findings suggest that intestinal inflammation is linked with brain pathology even in the earliest disease stages. Moreover, intestinal inflammation may exacerbate the progression toward AD.

https://www.sciencedirect.com/science/article/abs/pii/S1568163723003021?via%3Dihub

Benefit of this review was to elucidate that high fecal calprotectin level in PD patients indicated gut dysbiosis and intestinal inflammation. Early increment of fecal calprotectin indicates the development of gut dysbiosis and/or gut-barrier injury which may precede motor symptoms by decades. Thus, fecal calprotectin could be a diagnostic and prognostic biomarker in PD. preclinical and clinical studies are warranted in this regard to emphasize the potential role of fecal calprotectin in PD neuropathology.

I can’t agree, but here’s another book that completely confirms the information in the first one:
David Perlmutter BRAIN MAKER
Or is Perlmutter also a red flag?

#45

Correlation is not causation.

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#46

Good to admit that you neither know nor understand anything. Ciao goodbye.

#48

You say that A causes Parkinson’s and dementia. We show you many high quality papers showing that A is protective against Parkinson’s in animal models and that the more you use A the less likely you are to develop these conditions. When asked to explain the discrepancy your only answer is “It’s not my theory, but I fully support it.” and you send some YouTube videos.

It’s OK but it’s just that here we’re trying to be a bit smarter when it comes to health. You better go to Reddit r/Supplements where you will find your crowd.

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#49

I don’t say there is no clear solution. I say that I have a hypothesis here

Which explains the cause of the various sorts of Parkinsons and gives an opportunity to manage the consequences and to some extent reverse it (although reversing is really hard and there a limits on regrowing neurons).

#50

Thank you, John_Hemming

Read a lot of interesting stuff, I honestly didn’t know that.
At the same time, not quite understanding the nature of the processes looked up on request: leaky gut and melatonin
The result pleased me, it turns out melatonin reduces inflammation in the small intestine. I knew many other ways to reduce inflammation, I didn’t know about this one.
You can read about it here:
https://www.sciencedirect.com/science/article/pii/S0753332224003718

Melatonin acts as an immune buffer that stimulates the immune response during immunosuppression and downregulates it during inflammation. These findings suggest that melatonin may have therapeutic potential in treating neurodegenerative diseases. The available melatonin levels appear to be significantly influenced by the intestinal environment. Therefore, under situations linked with dysbiosis, melatonin and the gut microbiota seem to coordinate and intensify one another. Thus, maintaining a healthy gut microbiome, reducing inflammation, optimizing melatonin levels, and supporting mitochondrial function may help prevent or slow the progression of MS, PD, and AD.

#51

I love this. I have 5 bikes (2 road, 1 gravel, 1 mountain, 2 track).

I also have a terrible urge to try new supplements. No matter how many I have tried and failed to get a benefit, the next one will be the end-all-be-all. I fight this urge every day by reminding myself that I’ve been down that road before.

It also works that way with romantic relationships. The next one will be perfect…

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#52

Hi Joseph yeah that was funny (given his education he must have known what n was, just wanted to make a joke.) :slight_smile: That’s a lot of bikes you have too! Totally relate to trying to find the end all be all supplement but think your chance of finding that is at least slightly better than finding the perfect relationship. :slight_smile:

Antoine on Dr, Ronald Hoffman’s radio show the other day he spoke of deep brain stimulation for Parkinson’s and how it is being improved to be more specific to the patient.

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#53

In the case of Semax the nasal spray is intended to help bypass the BBB and more rapid absorption (may be helpful following a stroke, etc). Subcutaneous use of Semax is also possible

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#54

Thanks for this I’ve revisited this thread - so much info. My brother is still doing fairly well - has added a 4th day at the gym but can only walk a mile tops and that’s difficult. He’s 80 now and folks say for that age a mile is great, but if not for the disease he’d still be walking 5 or so. He’ll be visiting me next week for 10 days from Austin to 6,700 feet - wondering if he’ll show any improvement with the higher altitude, there is some anecdotal evidence for that.

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#55

Hi. Good to hear about your brother’s progress at the gym.

Please tell us how your brother is doing there. Especially if there are changes over time (day 1 at altitude vs day 10 vs a few days later back to sea level). There’s indeed evidence (not only anecdotal, also animal models and clinical trials) about improvement with lower oxygen: Oxygen, hypoxia and hyperoxia - #203 by adssx

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#56

Thanks Antoine, I’ll do that and report back - certainly hope you are doing well.

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#57

Hi Antoine,

My brother has come and gone and unfortunately there was no improvement for him at the 6700 ft altitude. He’s trying so hard but struggles to walk even to the park with his poles, about one quarter mile from me. Even though he goes to the gym 4 times a week, his legs are significantly weaker than a year ago. The confusion is worse too but the physical symptoms are definitely worsening more rapidly than cognitive. I told him about lithium but he pays no attention to anything I suggest and can’t blame him as I’m always trying things for my fatigue that do nothing, but after he got home he saw a program re lithium so now will ask his doc about it. (I tried 5 mg orotate to see if it would help fatigue but did nothing.) His A1C has always been a bit high, I think 5.8 or 9, and on this site I’ve seen some threads re that and dementia so maybe he should ask his neurologist about a glucose lowering drug. Honestly with his Lewy Body Dementia diagnosis and being 80, I really doubt anything is going to help slow the progression but might as well try. Some folks will say most 80 years olds can’t walk that far but without this disease he’d be able to walk 5 or 6 miles, he loved to hike and travel. My 78 year old brother is currently on a month long trip to New Zealand and Australia. I hope you’re doing well - I’m so impressed with all your research and ability to understand it.

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#58

I think you should push the lithium orotate… cheap… easy… no side effects.

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#59

I’m sorry to hear that. It’s a very difficult situation. @DrFraser: do you have experience with LBD/DLB?

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#60

Currently this is a sad diagnosis with no disease modifying treatments and very similar treatment and drugs that are used for AD (for symptom relief) – e.g. Aricept, antipsychotics for behavior, cognitive stimulation, and exercise.

As with most neurodegeneration - the key issue is to not get it in the first place or take on some aggressive general measures very early in disease (preferably in the prodrome).

I don’t currently have any patients with LBD or AD - I have a whole lot that are at significant risk of getting these, but I hope that the metabolic optimization and other measures I take with such patients modify their progression to any symptomatic disease. Give me a decade and I’ll let everyone know.

The other issue is that my patients who are at high risk genetically are often doing a bunch of things in their lifestyle that already risk reduces 50% and we know in PD and I suspect in AD and LBD not being poor and being well educated also is protective.

I wish I had some magic here, but once you have significant neurodegeneration, currently I have no magic treatment or insights.

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#61

Thanks Antoine and Dr. Frazier,

From what I understand LBD is not genetic but AD is? He is well educated (Yale, international tax attorney all that…) and our family realizes we’re very fortunate to have finances and are close/support one another. I’m sure there are those navigating these horrible diseases with neither.

Antoine have you said what symptom lead you to a Parkinson’s diagnosis? If not maybe you’d rather not say. Damn I hope research comes up with a cure or at least significant treatment in the next decade.

#62

Major Genetic Risk Factors for Lewy Body Dementia

Gene / Locus Effect on LBD risk Clinical Evidence
APOE ε4 Strongest common genetic risk factor (OR ≈ 2.4, 95% CI 2.1–2.7) for pathologically confirmed LBD; shared with Alzheimer’s disease Two‑stage GWAS, 1,743 cases / 4,454 controls (Lancet Neurol 2018, Guerreiro et al.) 1 [Level I evidence]; confirmed in Chinese cohort (NPJ Parkinson’s Dis 2025, Hao et al.) 2 [Level II evidence]
GBA (glucocerebrosidase) Carriers have ~8‑fold higher LBD risk and earlier onset (63 y vs 69 y, p < 0.001); associated with more severe cognitive and motor impairment Multicenter case‑control, 721 DLB vs 1,962 controls (JAMA Neurol 2013, Nalls et al.) 3 [Level I evidence]; replicated in Ashkenazi Jewish cohort (JAMA Neurol 2016, Shiner et al.) 4 [Level II evidence]; neuropathology correlation (Acta Neuropathol 2024, Walton et al.) 5 [Level II evidence]
SNCA (α‑synuclein) Common and rare variants, duplications, and triplications increase risk; central to α‑synuclein aggregation GWAS and familial sequencing studies (Lancet Neurol 2018, Guerreiro et al.) [Level I evidence]; functional organoid confirmation (Ann Neurol 2021, Jo et al.) 6 [Level II evidence]
LRP10 Rare variants cause autosomal‑dominant PD/PDD/LBD spectrum; associated with α‑synuclein accumulation Multicenter linkage/exome study (Mov Disord 2018, Morgante et al.) 7 [Level II evidence]
MAPT (microtubule‑associated protein τ) Modest risk modulation; interacts with APOE and SNCA; less consistent across cohorts GWAS meta‑analysis (BMC Med 2022, Guo et al.) 8 [Level II evidence]
MAP3K15 (X‑linked locus) Newly identified female‑specific risk locus (OR ≈ 2.4) X‑chromosome GWAS 2,591 cases / 4,391 controls (NPJ Parkinson’s Dis 2024, Bayram et al.) 9 [Level II evidence]
Polygenic lysosomal/autophagy risk Cumulative risk from lysosomal pathway variants correlates with severity of Lewy pathology Polygenic risk analysis (Brain 2023, Tunold et a
#63

Wow this is a surprise to me. My other brother knows someone who developed drugs at BIOGEN and he knew little about LBD but sent some info he came across saying there was no genetic component so I just went with that. I can’t begin to understand these studies but did know about the APOE4 gene for AD but never heard that it also applied to LBD. None of us knows our status re that. I have read that alcohol plays no part in LBD but I’m not convinced. He drank a lot and that just can’t be good for one’s brain. Luckily it gives me a terrible headache as it’s “in the blood” as my mom used to say.

Thanks Dr. Fraser.

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