90 replies to this topic

[MIKE82]

here is a very good article about oral vs intravenous intake of trehalose

 

https://journals.lww...xADx20100319xMP

 

@2Sunny what exact trehalose product/company do you take?

[2Sunny]

Hi Mike,

 

So glad you found my discussion and decided to join in!!  I'm working at the moment and a little busy, but I will try to respond at length in time.  For now a couple very quick answers

 

1) I have examined Acetyl-DL-leucine at length before, and I feel that what it does in the body is covered by some of what I take now but more importantly there was a moderately large double blind placebo trial that showed no benefit hence I am not taking it at the moment, but you have inspired me to re-examine my thought.

2) I would like nothing more than to take trehalose intravenously, but sadly I am unaware of any way to do that at the moment.  I am also keenly aware that the Israeli company that first pioneered the idea and went bankrupt was planning on charging over $250000 per  year for treatment that would have required weekly injections for life.  So I'm happy that I think I am someone who probably passes a tiny amount into my blood stream.  I realize this is probably not true of everyone.  Also there is a company close to bring IV trehalose to market, but at the moment I don't remember the name.

3) I buy trehalose from a U.S. firm bulksupplements.com

 

Again so happy you found me, and can't wait to hear more about what you have learned!!

Joe in NY

 

P.S. On a totally separate  note I recently had the pleasure of visiting Poznan briefly.  The video below is me as captain of the flight landing in Poland. I've never seen a video of me actually landing before, but I guess a 777 coming to Poznan was a big deal and attracted a "plane spotter" who took the video of me landing and taxiing in.  I flew U.S. Army troops from Topeka Kansas to Poland on a charter.  My experience there was that Polish people are really really friendly.  Makes me want to visit on holiday!

 

 

Hello @2Sunny,

 

First I will introduce myself. I'm Mike from Poland, 41yrs, genetic Ataxia SCA 1. I have, so far, very little symptoms, slightly worse balance, not so smooth movements and little tremors when performing specific exercises. But my general condition is pretty good. I ride the bike every day, go windsurfing, snowboarding and staying active in general. I'm runing an IT business. I have been following this thread from the begining and I agree 100% with what you wrote here in all your posts. Big THANK YOU for that! Your story truly gives hope!

 

OK. And now some of my latest thoughts.

 

I have been taking trehalose orally for around 6 moths now but I'm also concerned about it's oral use effect once it digested as there is very little studies about oral route proved to be stopping the progression of SCA1. Did you at any point consider taking it intravenously and if yes, are you familiar with any brand or trehalose product that could be taken intravenously?

 

Atother topic: - did you hear about Intrabio company working on IB1000 N-acetyl-DL-leucine https://intrabio.com...s-publications/ which they already confirmed had a substential positive effect on Ataxia -Telangiectasia (about 11.0 points improvement (48.88%) in SARA score). Here is their latest study:

 

https://pubmed.ncbi....h.gov/35128617/

 

I know Ataxia -Telangiectasia is not the same as SCA 1 but if this IB1000 N-acetyl-DL-leucine works on several neuro degenerative inherited deaseases (like GM2 Gangliosidosis, Tay-Sachs and Sandhoff) maybe there is a chance it would work with SCA1 too. But I'm not sure if the N-acetyl-DL-leucine used by Intrabio is the same drug (amino acid) that can be found avaible to buy online. As they use their own names like IB1000, IB1001 or NALL.

 

 

What I found is this:

 

2013 trial with acetyl-dl-leucine

https://www.ncbi.nlm...les/PMC3824630/

 

but they used acetyl-dl-leucine not the N-acetyl-DL-leucine. yet, there was a noticable improvement in SARA score in this study.

 

My only concern is that the product made by Intrabio (IB1000 N-acetyl-DL-leucine) is a different drug than acetyl-dl-leucine.

 

 

this is acetyl-dl-leucine (avaible to buy )

https://www.mon-phar...30-tablets.html

 

and this seems to be N-acetyl-DL-leucine, but I'm not sure if it's avaible and safe to buy and intake as a regular drug:

https://www.sigmaald...uct/sigma/a1001

 

 

I wonder what are your thoughts on these topics.

 

Have a good day!

 

Mike

 

 

 

 

 

 

 

 

 

 

 

 

Edited by 2Sunny, 08 February 2023 - 08:44 PM.

[2Sunny]

Just thought it was time for an update.

 

Previously I had been a big believer in exercise as a crucial element to my routine.  However, I have a truth to admit.  In August of 2022 I contracted COVID and was laid up with a high fever and a terrible sore throat for about a week.  Obviously during that period exercising was out of the question.  Even after I recovered I felt weak for months and so did not resume my exercise routine.  I did continue to walk almost daily for about 30 minutes in the forest behind my house with my dogs.  Since August last year I have not resumed my exercise routine.  Now I have a double inguinal hernia that is scheduled to be repaired in August, but at the moment the hernias have become quite noticeable and I'm concerned that hard exercise would make them worse meaning I expect to continue not exercising until after the surgery and after I have fully recovered.  When will that be?  I really don't know.

 

Brief side note totally unrelated.  I had had dual inguinal hernias for decades, and they had remained very minor.  Once I stopped exercising and working my core they got worse quickly.  Did lack of exercise contribute to their worsening?  I have no idea, but there it is.

 

What's the point of that information?  Over the last  year I remain unchanged in symptoms related to ataxia.  In fact, I would go so far as to say I have had a tiny, tiny improvement. Last year my legs always felt "heavy" when I would do the daily dog walk in the woods.  At some point in the past year I upped my daily creatine intake, and since that change the feeling of heaviness in my legs is completely gone.

 

Here's my current list of supplement intake as well.  The changes are that I now split the B1 (thiamine) intake into two, morning and night.  I had been taking it all in the morning as some people reported excess B! would make them restless.  I have not found that to be a problem now that I split the intake.  Also, I upped my daily creatine from 6 g daily to 7.5 g daily.  I take creatine in pill form and this represents 5 pills in the AM and 5 in the PM where I had been taking 4 and 4.  Lastly, I read more research on vitamin D which did not find benefit for neurological disorders so I have reduced to a general low dose recommended by Harvard Med for general health.

 

So, that's it for this update.

 

Latest supplements list update:

  -AM&PM-

4 mg B-12 (methylcobalamin) (4 x 500 mcg pills AM/PM)  I found a study that showed chewing increased absorption

40 mg     PQQ (1 x 20 mg AM/PM)

100 mcg vitamin D (1 x 50 mcg  AM/PM)

140 mg   PURE Green Tea extract (1 x 70 mg AM/PM) 

180 mg   Theracurmin HP (1 x 90 mg AM/PM)

300 mg   Pterostilbene (2 x 75 mg AM/PM)

475 mg   Avmacol (1 pill AM/PM)

800 mg   Ubiquinol (2 x 200 mg AM/PM)

1333 mg NeuroMag ( 1 pill AM/PM) 

1500 mg vitamin B3 - Niagen (5 x 150 mg AM/PM) - the form of B3 is crucial NOT niacin but NIAGEN.

2000 mg taurine (1 x 1000 mg AM/PM)

2000 mg vitamin C (1 x 1000 mg AM/PM)

2000 mg vitamin B1 (2 x 500 mg AM/PM)

7500 mg creatine (5 x 750 mg  AM/PM) 

 

-AM-

70 g trehalose AM in coffee (3 heaping Tbs)

 

-PM-

5 mg lithium orotate

 

Edited by 2Sunny, 18 June 2023 - 12:18 PM.

[ambivalent]

If the researhc below applies to SCA1, then perhaps Biotin could be added to the thiamine within the protocol. There will be a small clinical trial with HD:

 

https://dnascience.p...ngtons-disease/

 

 

“When the researchers looked at the genes whose mRNAs the CPEB mRNAs control, they found three with elongated polyA tails – and the expression of this gene trio is also altered in Alzheimer’s disease and Parkinson’s disease. But it was a gene whose mRNA has a shorter polyA tail that brought vitamins unexpectedly into the picture: SLC19A3.

 

Mutations in SLC19A3 were already known to cause a brain disease that is treatable with biotin and thiamine! Biotin-thiamine-responsive basal ganglia disease (BTBGD) alters the protein that transports thiamine into cells. The condition causes lethargy, irritability, tremors, and spastic and uncontrollable movements, similar to HD. BTBGD arises from direct mutations in the thiamine transporter, whereas HD alters expression of the gene encoding the transporter (how rapidly it is transcribed into mRNA).

 

Adding high doses of biotin to the diet of people with BTBGD speeds transcription of SLC19A3, and that increases the levels of the protein that escorts thiamine into cells. But the thiamine deficiency is in the cerebrospinal fluid, not in the blood – perhaps explaining why thiamine levels are ok in the bloodwork of HD patients.

 

The vitamin connection inspired further experiments. Slices of striatum and cortex from the brains of deceased HD patients showed lower levels of the thiamine transporter. And thiamine was lowered in the cerebrospinal fluid but not in the blood, consistent with BTBGD.

 

More telling was that HD mice given high doses of biotin and thiamine in their water, starting at 3 weeks of age, no longer fell off the rotarod. And the brains of the pre-manifest mice given the vitamins were okay.”

 

On another forum, a woman whose husband was recently diagnosed with HD, was recommended to take thiamine by his neurologist, showing them a paper. He has been taking 1300 mgs of thiamine (B1) and 300mg of biotin (B7) daily for 5 months with no worsening of symptoms.

 

Edited by ambivalent, 14 July 2023 - 04:19 PM.

[ambivalent]

Here is a link to the clinical trial: 

 

https://classic.clin...how/NCT04478734

 

Two groups are high and low 1200mg thiamine/ 600mg biotin - 600mg thiamine/ 300 mg of biotin.

 

In addition it looks as though adding pantoethenic acid (VItamin B5) could be beneficial.

 

Vitamin B5 (d-pantothenic acid) localizes in myelinated structures of the rat brain: Potential role for cerebral vitamin B5 stores in local myelin homeostasis

 

"We recently found that cerebral pantothenate is markedly lowered, averaging ∼55% of control values in cases of Huntington’s disease (HD) including those who are pre-symptomatic, and that regions where pantothenate is lowered correspond to those which are more severely damaged"

 

"Remarkably, cerebral pantothenate was almost entirely localized to myelin-containing structures in both experimental groups"

 

"Furthermore, there is growing evidence that HD is characterized by myelin breakdown, providing a further potential link between its pathogenesis and cerebral pantothenate deficiency."

 

Full abstact:

 

"Vitamin B5 (d-pantothenic acid; pantothenate) is an essential trace nutrient that functions as the obligate precursor of coenzyme A (CoA), through which it plays key roles in myriad biological processes, including many that regulate carbohydrate, lipid, protein, and nucleic acid metabolism. In the brain, acetyl-CoA is necessary for synthesis of the complex fatty-acyl chains of myelin, and of the neurotransmitter acetylcholine. We recently found that cerebral pantothenate is markedly lowered, averaging ∼55% of control values in cases of Huntington’s disease (HD) including those who are pre-symptomatic, and that regions where pantothenate is lowered correspond to those which are more severely damaged. Here we sought to determine the previously unknown distribution of pantothenate in the normal-rat brain, and whether the diabetic rat might be useful as a model for altered cerebral pantothenate metabolism. We employed histological staining (Nissl) to identify brain structures; immunohistochemistry with anti-pantothenate antibodies to determine the distribution of pantothenate in caudate putamen and cerebellum; and gas-chromatography/mass-spectrometry to quantitate levels of pantothenate and other metabolites in normal- and diabetic-rat brain. Remarkably, cerebral pantothenate was almost entirely localized to myelin-containing structures in both experimental groups. Diabetes did not modify levels or disposition of cerebral pantothenate. These findings are consistent with physiological localization of pantothenate in myelinated white-matter structures, where it could serve to support myelin synthesis. Further investigation of cerebral pantothenate is warranted in neurodegenerative diseases such as HD and Alzheimer’s disease, where myelin loss is a known characteristic of pathogenesis."

Edited by ambivalent, 17 July 2023 - 02:25 PM.

[ambivalent]

Time-Restricted Ketogenic Diet in Huntington's Disease: A Case Study

 

 

"We report the case of a 41-year-old man with progressive, deteriorating HD who pursued a time-restricted ketogenic diet (TRKD) for 48 weeks. Improvements were measured in his motor symptoms (52% improvement from baseline), activities of daily living (28% improvement), composite Unified HD Rating Scale (cUHDRS) score (20% improvement), HD-related behavior problems (apathy, disorientation, anger, and irritability improved by 50–100%), and mood-related quality of life (25% improvement). Cognition did not improve. Weight remained stable and there were no significant adverse effects. This case study is unique in that a patient with progressive, deteriorating HD was managed with a TRKD, with subsequent improvements in his motor symptoms, activities of daily living, cUHDRS score, most major HD-related behavior problems, and quality of life. Our patient remains dedicated to his TRKD, which continues to provide benefit for him and his family."

[2Sunny]

 

Time-Restricted Ketogenic Diet in Huntington's Disease: A Case Study

 

 

"We report the case of a 41-year-old man with progressive, deteriorating HD who pursued a time-restricted ketogenic diet (TRKD) for 48 weeks. Improvements were measured in his motor symptoms (52% improvement from baseline), activities of daily living (28% improvement), composite Unified HD Rating Scale (cUHDRS) score (20% improvement), HD-related behavior problems (apathy, disorientation, anger, and irritability improved by 50–100%), and mood-related quality of life (25% improvement). Cognition did not improve. Weight remained stable and there were no significant adverse effects. This case study is unique in that a patient with progressive, deteriorating HD was managed with a TRKD, with subsequent improvements in his motor symptoms, activities of daily living, cUHDRS score, most major HD-related behavior problems, and quality of life. Our patient remains dedicated to his TRKD, which continues to provide benefit for him and his family."

 

 

Thanks ever so much for the update and links.  I've added biotin to my daily routine now.  As always it's absolutely impossible to say if any single element in my routine is more or less effective as my routine has so many parts, but the simple fact is I continue to feel great as time marches on.  When that will change - who knows.  I hope not for a LONG time

 

I did investigate KETO diets and fasting at one point many years ago and even tried KETO and fasting (at different times) for about 6 months myself.  I wish I had kept links to the research, but ultimately I was convinced that the benefits being seen by people on KETO or those fasting were actually the result of the body's increased production of NAD+ ergo I stopped and focused on what I consider to be a "healthy" diet.  What is a "healthy" diet?  That is the million dollar question, but currently my thought is a healthy diet includes very little processed food, large amounts of plants both cooked and raw, and small amounts of fish or poultry, rarely a burger or a steak when out with friends at a restaurant.

 

Thanks again for the links.  They are very much of great interest to me!!

Edited by 2Sunny, 22 August 2023 - 12:52 PM.

[ambivalent]

It's great to hear you are doing so well 2Sunny and I am relieved you don't mind the posts, I was concerned they were something of an imposition on your thread. I have a number of more posts to add  - I am sure there will be some overlap given your extensive research. 

 

I always though fasting would be beneficial to HD given its autophagic expression but there is considerable resistance in the UK, that any kind of reduction in calories is harmful. That paper addresses this point of the need of HD to consume high calories - I would have thought there has to be a conversation about this, this research albeit with one person shouldn't be ignored, it needs to be understood and could be a very powerful intervention. 

 

There was an HD phase 2 trial  with a "ketone oil", Triheptanoin, which was completed three years ago with over 100 HD people enrolled, but I have yet to find any results. 

 

https://classic.clin...=1&view=results

 

The phase 1 seemed impressive:

 

https://en.hdbuzz.net/185

 

But MCT oil might be quite effective:

 

https://foodforthebr...-REPORTdocx.pdf

 

"A study gave 52 people with pre-dementia either two tablespoons (30g) of C8 oil or a placebo and measured changes in their cognitive function. There were also able to measure how well neurons were functioning and determined that the participants brain cells were not fully firing, in other words they would be experiencing effectively a lack of brain energy which would be experienced as poor concentration, memory and ability to process information.

 

When they were given two tablespoons of C8 oil the half-firing neurons came back to life. Brain ketone metabolism increased by 230% indicating that their brain cells were switching to using ketones as fuel, and the more this was happening the more cognitive improvements occurred. The authors suggested than three tablespoons (45g) of C8 oil might be better."

 

There is more information here: 

 

https://coconutketones.com/

 

An interview from Dr Newport, mentioned anecdotal evidence of improved symptoms with HD (@26.30) and apparent case of stalling ALS progression.

 

https://daveasprey.c...-oil-ketones/  

[2Sunny]

I feel you pain as regards your PM about posts being taken down.  What an incredible shame moderators online have such incredible power to stifle freedom of speech.

 

As to the link you asked for it is now gone.  Dr. LaVonne Goodman maintained a website called Huntington's Disease Drug Works in which she gave her view on supplements and alternative therapies, but sadly she has taken the website down now.

 

Please keep adding links and posts here on research you find.  I love it, and it's definitely inspiring me to restart my own regular search for new info!

 

 

 

 

It's great to hear you are doing so well 2Sunny and I am relieved you don't mind the posts, I was concerned they were something of an imposition on your thread. I have a number of more posts to add  - I am sure there will be some overlap given your extensive research. 

 

I always though fasting would be beneficial to HD given its autophagic expression but there is considerable resistance in the UK, that any kind of reduction in calories is harmful. That paper addresses this point of the need of HD to consume high calories - I would have thought there has to be a conversation about this, this research albeit with one person shouldn't be ignored, it needs to be understood and could be a very powerful intervention. 

 

There was an HD phase 2 trial  with a "ketone oil", Triheptanoin, which was completed three years ago with over 100 HD people enrolled, but I have yet to find any results. 

 

https://classic.clin...=1&view=results

 

The phase 1 seemed impressive:

 

https://en.hdbuzz.net/185

 

But MCT oil might be quite effective:

 

https://foodforthebr...-REPORTdocx.pdf

 

"A study gave 52 people with pre-dementia either two tablespoons (30g) of C8 oil or a placebo and measured changes in their cognitive function. There were also able to measure how well neurons were functioning and determined that the participants brain cells were not fully firing, in other words they would be experiencing effectively a lack of brain energy which would be experienced as poor concentration, memory and ability to process information.

 

When they were given two tablespoons of C8 oil the half-firing neurons came back to life. Brain ketone metabolism increased by 230% indicating that their brain cells were switching to using ketones as fuel, and the more this was happening the more cognitive improvements occurred. The authors suggested than three tablespoons (45g) of C8 oil might be better."

 

There is more information here: 

 

https://coconutketones.com/

 

An interview from Dr Newport, mentioned anecdotal evidence of improved symptoms with HD (@26.30) and apparent case of stalling ALS progression.

 

https://daveasprey.c...-oil-ketones/  

 

[ambivalent]

Thanks 2Sunny, I should point out that I was not referring to posts taken down on this site but elsewhere. And that's nice to hear and kind of you to say so. Looking at the amount of research you had undertaken, I wasn't sure how much benefit I could add. 

 

I found is very disappointing though from a human effort perspective, to witness Roche scouring the data to find something in the failed data that might have been beneficial to one demographic, when there are so many impressive pre-clinical trials which have not been touched because it isn't profitable, and I sense the majority of the HD community aren't aware of this. It then becomes easy to believe that BP is the only solution and if they can't solve it then the problem is impenetrable. But they are trying to solve it in a specific way to design a molecule and make profits over a lifetime. TUDCA is a good example, and will put up a post about this. It looks very promising for HD (I assume with it SCA1, but you'd need to comment on that). Anyway, the first of a few posts.

A few weeks ago I looked at a paper targeting the choline system to treat HD: choline deficiency is thought to be a driver of HD symptoms. A study in the 70's had given HD patients high doses of choline but with only transient symptom reversal. I had also looked around to see whether Abram Hoffer / Orthomolecular had any cases dating back on treating HD, with say niacin/nicotinic acid perhaps reminded by the phase 1 biotin/thiamine trial for HD. I had incidentally found accounts of successful treatments of MS with nicotinic acid and thiamine in the 40s.

Well, I stumbled across a curious article by Hoffer around 40 years ago, concerning a woman in her 40s with probable HD, whose husband’s schizophrenia had been successfully with vitamin C and nicotinic acid, work ridiculed by then conventional medicine, though vindicated by recent research. His wife at risk of HD, unable to work for years, seemed to be symptomatic - gene testing was not possible then, naturally - decided to adopt her husband's protocol of vitamin C, E and nicotinic acid. She reversed symptoms and her husband noted in a letter to Hoffer that choline supplementation was especially beneficial. I assume this was a supplement she added (it still isn't recommended on orthomolecular for treating HD, they also have an additional brief case study). She of course may not have had the disease, the nocebo effect cannot be discounted, but nevertheless it is quite likely she had onset, and Hoffer was compelled to submit her case study. There was also a brief account of follow up one year later.

This seemed particularly interesting and I had wondered if perhaps this was caused by raised NAD levels. So I decided to investigate if increasing NAD levels could restore the choline system. The first paper that popped up, was a 30 year old paper, with no reference to NAD, which made sense of everything and was, I thought, one of the most remarkable and elegant results I had come across. I was and may still plan to start a thread, to receive wider comment on its implications - if a drug had been designed to do this, to create this effect, it would win a Nobel Prize. Or so I believed.

The paper was looking at raising choline levels in healthy rats. First out they gave the rats choline via i.p.. The result was a large but short lived spike in brain levels of choline. This tied in with the brief symptom-improvement of HD patients given choline supplementation in the 1970s: a surge of choline passes through the brain, providing symptom respite.

Then separately they decided to administer the rats with nicotinamide, without choline. And incredibly choline levels increased dramatically, like the choline administration, but unlike the choline, it lasted for hours.

How could this happen? One of nicotinamide's metabolites (shared with nicotinic acid) blocks choline from leaving the CSF, therefore presumably, enabling more reuptake of choline and so generates additional acetylcholine, a deficiency in which can cause symptoms experienced with HD and other neurodegenerative disorders .

Moreover, combining both nicotinamide and choline increases choline levels even further. Both of those results would seem to explain the woman with probable HD experiences with both nicotinic acid from her husband’s treatment, and then additionally with choline taken with nicotinic acid present.

As an analogy, perhaps the levels of brain-choline - and possibly thiamine and pantothenic acid - could be compared to a bath or reservoir where there is in flow - a tap - and an outflow - a plug hole say. 

 

For any inflow rate an equilibrium is achieved at a specific volume (I know this is obvious to an engineer!) - if we run the taps full on then eventually a certain volume is maintained at a pressure which creates an outflow rate equal to the inflow. If we turn the taps up, then inflow is greater than outflow, water rises til equilibrium is found once again, turn them down and the reverse happens.

 

HD appears to disrupt the production of transport proteins so there is less inflow. The current HD phase 1 trial is seemingly trying to increase thiamine levels through supplying more thiamine but also through biotin increasing the production of transport proteins.

 

Nicotinamide seems as though it might address the problem from the other side. If, back to the analogy, for good health a volume of water X needs to be maintained, and requires an inflow rate of Y, for say an outflow area of Z (plughole size). In HD patients that Y inflow rate may not be possible, and so the steady state / equilibrium volume much less than X results - but by decreasing Z, blocking up part of the plughole, an equilibrium of X can be achieved for an inflow rate much less than Y, for a tap say half turned on, because a greater volume is required to create an outflow rate equal to a fixed inflow rate, with a reduced size for the water to escape. We could in theory, say, maintain any volume in equilibrium for any given inflow rate, by adjusting the cross-sectional area of the outflow pipe or plug. 

 

Of course it is an analogy - biology is fixed like taps and plug holes - but if it is meaningful enough to be applicable, then it is quite a remarkable result and a great feature of nicotinamide. 

 

One question, does the metabolite block anything else - could this apply to thiamine or pantothenic acid? And of course does it apply to humans as well as rats and in models of HD.

 

The last quote of the paper is an all too typical appeal:

 

“The combined administration of choline and of a choline transport blocker analogous to nicotinamide may be of potential use in central cholinergic dysfunction.”

 

Edited by ambivalent, 23 August 2023 - 04:19 PM.

[2Sunny]

Ambivalent,

 

Again thank you for the post and fascinating links.  I couldn't agree more as regards Roche!  The laser focus on profit and the never ending search for a benefit after failure is all too familiar - BioHaven and Riluzole anyone . . . makes me sick just thinking about it.

 

I do, however, want to add my thoughts about some of what you post above.  Please, please do not interpret this as a personal remark.  I am writing to the handful of people who actually might read this thread in it's entirety.

 

  No doubt increasing choline can help some aspects of HD, BUT . . . the crux of my very first post on this thread and the entire point of my "alternative therapy" is to fight against the root cause of SCA1 and other polyglutamine disorders of which HD is one (arguably HD and SCA1 are the most similar to each other in this group).  That root cause in both SCA1 and HD is misfolded protein accumulation in the brain.  Those misfolded proteins have a cascade of impacts in the body, and molecules such as choline can improve damaged cell actvity, BUT improving choline levels does NOT act on the root cause.  Trehalose is proven in humans to improve autophagy (the clearing out of misfolded proteins) and NAD+ is needed by cells to take on the work of autophagy.  Niagen is unlike niacin and other forms of vitamin b3 in that not only does it boost NAD+ tremendously but it also enhances Sirtuin activity (which aids autophagy as well).  Niacin actually inhibits Sirtuin activity thereby working against the process of autophagy and many people can not take high doses of niacin without harm.  My point here is just to say I am not only looking for vitamins, foods, exercises, or supplements that reduce symptoms, but rather ways to hit at the root cause of the symptoms to stop them before they begin, and that is what my list of supplements is hopefully doing, plus . . . and this is important to me . . . each vitamin/supplement I list is backed by numerous papers explaining WHY it helps even if that research is in mice (although sometimes there is actual human research as well).  I am laser focused on finding and sharing research papers that explain in detail what benefit a particular molecule may have hence all the links.

 

Here is an example of what I am trying to say:

 

Degradation of misfolded proteins in neurodegenerative diseases; therapeutic targets and strategies

 

 

 

Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease.

 

Again please do not in any way take this as a reflection on you or your post.  It is my attempt to be clear about my own personal thoughts and how it relates to my ideas expressed here.

 

So again thanks for posting!   Joe

[Kentavr]

Hi!

 

Skin and autophagy:

 

https://www.cosmetic...lberry-exctract

 

Are you taking sublingual trehalose? After all, with sublingual administration, it is better absorbed into the blood and trehalose is more in the blood?

 

I have experience taking tregazola sublingually. I take 0.3 - 0.5 teaspoon under the tongue, and wait a few minutes. After that, almost no trehalose remains under the tongue - it is almost completely absorbed!

 

So I do 3-4 times, after which the absorption slows down dramatically. In this case, I take boiled water and wash it under my tongue, and then I keep plain water under my tongue for 2-3 minutes. After this, trehalose can again be well absorbed.

 

Thus I do 4 procedures. This takes approximately 40-45 minutes, resulting in about 8 teaspoons of trehalose being absorbed under the tongue.

 

Of the amazing side effects: mood improves significantly! There is a feeling of happiness! A few years ago, I read about an experiment where mice were driven into a depressive state, and then they were given trehalose, after which the mice returned to normal!

 

As far as I understand, neurodegeneration is also associated with a change in the functioning of the brain and its hormonal work. By improving our mood, we will not only allow better absorption of trehalose into the blood, but also affect our mood!

 

Thank you!

[ambivalent]

Joe, 

 

I completely agree and am not at all offended, your contributions and work have been incredible, and I agree the objective should be to treat the problem at source, so that an polyQ person's cellular biology is almost indistinguishable from that of a non-polQ person. A strategy to Increase autophagy and before that even preventing/reducing protein folding via ER stress suppression would hopefully be the ounce of prevention that would remove the need for a cure. 

 

I feel it certainly is potentially something in the armoury to reverse symptoms - if this is what happened - and perhaps dramatically change the mindset of sufferers to know there is something on the high street that could do far more and quickly, that any of the drugs that have been developed. Once people can see improvements are possible, then hopefully in will trigger an attitude shift. I have seen people openly ask for almost anything - and this could be a good and quick responsive intervention, if it works. I don't know if other typically preventative therapies could address symptoms as rapidly as is suggested here - but you would better know than I, but if not then it certainly has a place in the recovery of the disease, but I completely agree it should not end there - and to borrow from the analogy, we want the tap turned on full and this should be possible if stopping the unfolded protein build up. If we did have a standard of care treatment like this that worked as surmised, then we would experience much relief, but the job obviously would not at all be completed.

 

I am really on a mining exercise, trying to understand as I read, and put out there what I find - you're the quality control and refinery :o)

 

I haven't read or written anything on trehalose yet, I have a backlog! 

 

I really value your engagement, Joe, and am not at all in disagreement with you or in anyway offended. We want the best solutions :o)

 

Thanks for the links, I will have a read.  

[ambivalent]

In a previous post I mentioned there was an anecdote to add. On an HD forum recently I stumbled across a 6 year old post, where an individual claimed more or less to have delayed onset with lutein (he had "neurotoxicity for 26 years, which turned out to be Huntington's

 

The person seemed to imply having taken it for a couple of decades, and then started losing weight and developed symptoms of chorea - he switched brands to Doctors Best and, asserts, within half an hour those symptoms disappeared. He went on to suggest his neurologist would try this on other HD patients.

 

Several posts were deleted, likely the poster handled things insensitively, and it was broadly dismissed and taken as an example of what the community needed to be protected against.

 

That is of course a perfectly understandable mindset, but it results in trust only being placed in clinical trials and so a strict scientific method, which plays in the hands of BP - only they can create informed knowledge of the disease. With hope there is always the risk of disappointment - with people feeling worse than had they never been given it, but without it there is certainty.

 

I thought at least the guy’s story should have been checked out, and it took only a few minutes to see there is some credibility underpinning those claims - even if the account is fatuous, lutein as a potential intervention in HD clearly has merit. 

 

Incidentally, the half an hour symptom recovery claim seemed to have been dismissed too, though I don’t believe that to be entirely without some measure of feasibility either (Joe would be better informed). 

 

The 70s choline study on HD patients, seemed to suggest a rapid albeit brief improvement, I read too, though cannot find, of a physician in the 40s reporting intraspinal injections of thiamine, enabling advanced patients MS to walk - for a couple of hours. So there is the suggestion of a latent functional capacity, which may be reversed for as long as deficiencies in say, thiamine, or choline are redressed - so it would seem that a sustainable intervention could be rapid. 

 

On to Lutein: 

 

Soon discovered was a study of lutein on an HD model in rats with the following conclusion:

 

“Histopathological examination further affirmed the neuroprotective effect of lutein on 3-NP induced pathological lesions. The present study indicates that lutein is a promising candidate for the management of HD and related conditions.”

 

The link mentions clinical trials supporting the beneficial effect of lutein in Alzheimers, though not citing those trials. 

 

ER stress suppression maybe the mechanism:

 

Impact of ER Stress and ER-Mitochondrial Crosstalk in Huntington's Disease

 

“Accumulation of misfolded proteins in the ER or disruption of ER homeostasis causes ER stress and activates an evolutionarily conserved pathway called Unfolded protein response (UPR). Protein homeostasis disruption at organelle level involving UPR or ER stress response pathways are found to be linked to HD. Due to dynamic intricate connections between ER and mitochondria, proteins at ER-mitochondria contact sites (mitochondria associated ER membranes or MAMs) play a significant role in HD development. The current review aims at highlighting the most updated information about different UPR pathways and their involvement in HD disease progression.”  

 

Lutein, UPR and ER stress:

 

“Thus, lutein may have the pharmacological potential for protection against widespread disease conditions of ER stress.”

 

Lutein has been shown to be effective against AMD, while AMD progression is linked to ER stress. 

 

Also, there appears to be plenty of evidence of the cognitive benefits of lutein (Zeaxanthin)

 

Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223987/

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891800/

 

TUDCA, too, looks to be a promising candidate, through the same mechanism of controlling ER stress - there will be a post.

 

[ambivalent]

Vitamin D intervention on a mouse model of HD (2022). 

 

Restorative Action of Vitamin D3 on Motor Dysfunction Through Enhancement of Neurotrophins and Antioxidant Expression in the Striatum

 

Abstract:

 

"A number of studies has explored a positive correlation between low levels of serum Vitamin D3 (VD; cholecalciferol) and development of neurodegenerative diseases including Huntington’s disease (HD). In the present study, the prophylactic effect of VD on motor dysfunction was studied in an experimental model of HD. An HD-like syndrome was induced in male C57BL/6 mice through an intraperitoneal injection (i.p) of 3-NP for 3 consecutive doses at 12 h interval of time as described previously (Amende et al. 2005). This study investigated the in-vivo therapeutic potential of VD (500 IU/kg/day) supplementation on movement, motor coordination, motor activity and biochemical changes in this HD model. Mice were divided into four groups: Group I: Control (saline); Group II: 3-NP induced HD (HD); Group III: Vitamin D3 (VD) and Group IV: 3-NP induced + post Vitamin D3 injection (HD + VD). All groups of mice were tested for locomotion, gait analysis and rotarod performances over a span of 30-days. VD administration rescued locomotor dysfunction and neuromuscular impairment in HD mice with no change in gait dynamics. In addition, administration of VD to 3-NP treated mice led to a significant enhancement in the expression of key neurotrophic factors including brain-derived neurotrophic factor (BDNF) and nerve-growth factor (NGF), the Vitamin D receptor (VDR), and antioxidant markers (catalases [Cat] and glutathione peroxidase [GpX4]) in the striatum, suggesting a detoxification effect of VD. Altogether, our results show that VD supplementation induces survival signals, diminishes oxidative stress, and reduces movement and motor dysfunction in HD."

 

The rest of the paper is behind a paywall, which I somehow managed to see once, and copied the text, but only retrieved one of the charts which showed the remarkable impact vitamin D had on locomotion after 30 days with the HD model, compared to the model without the Vitamin D. It illustrates the intervention was very close the control and vitamin D groups, at a time when the model group locomotion measure had dropped off significantly:

 

https://ars.els-cdn....701-gr2_lrg.jpg

 

Discussion:

 

"....It is likely that in our study, the rescue effect of VD observed in behavior tasks involves the VD-VDR signal transduction pathway, potentiating survival signals via neurotrophins and decreasing oxidative stress, which in turn downregulates antioxidant stress markers (Fig. 8). It is known that VDR signaling is vital for mitochondrial integrity, combats ER stress and strengthens skeletal muscle activity at neuromuscular junction (Baydyuk and Baoji, 2014, Sakai et al., 2015, Bakhtiari-Dovvombaygi et al., 2021, Xu and Liang, 2021, Maity et al., 2022). In summary, our data suggests that Vitamin D3 mediates a neuroprotective effect in the striatum via enhancement in the expression of Vitamin D receptor (VDR) and vital neurotrophins, like BDNF and NGF, crucial for survival signals in HD."

 

A text dump of the paper save the references, which pastebin didn't seem to like:

 

https://pastebin.com/YVnMaAVj

[ambivalent]

Last time I checked curcumin was in your stack, Joe. An impressive paper on curcumin, and another flavanoids, in HD

 

 

Therapeutic and Mechanistic Effects of Curcumin in Huntington’s Disease 2021

 

https://www.ncbi.nlm...les/PMC8686321/

 

Conclusion

 

“Neurodegenerative disorders such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis could not be cured completely with the available therapies, rather this latter can only decrease the severity of disease symptoms and are associated with a number of undesirable side effects. Curcumin is a polyphenolic compound isolated from the rhizome of turmeric. It has a wide range of pharmacological properties and multiple therapeutic uses of curcumin have been reported so far. The role of curcumin in preventing and treating neurological disorders has also been investigated and numerous studies support the successful use of curcumin in neurodegenerative disorders including HD. Curcumin possesses the potential to halt the progression of neurodegeneration in HD by targeting multiple mechanisms including reducing oxidative and inflammatory stresses, metal ion chelation, transcriptional alterations and disaggregation of aggregated proteins by increasing the activity of HSPs. Having a favorable safety profile, curcumin could be an alternative to conventional therapies in treating and preventing HD. However, data from human studies are lacking and clinical trials should be highly encouraged in this regard.”

 

 

 

Dietary Flavonoids in the Management of Huntington’s Disease: Mechanism and Clinical Perspective (2020)

 

https://onlinelibrar...od.k.200203.001

 

Conclusions and future directions

 

"Current available therapies for the treatment of neurodegenerative disorders including AD, PD, HD, and ALS could not offer complete cure of diseases and are associated with a range of undesirable side effects. Flavonoids are natural polyphenols widely distributed in the plant kingdom and are present in most consumable dietary sources. Having a favorable side effects profile, they can offer an alternative therapeutic choice to conventional therapies in the prevention and treatment of neurodegenerative disorders including HD. In vitro and in vivo studies support the neuroprotective effects of flavonoids (hesperidin, naringin, quercetin, rutin, fisetin, myricetin, luteolin, and EGCG) in different models of neurodegeneration in HD. Flavonoids can modulate multiple mechanisms in neuroprotection by decreasing oxidative stress and inflammatory mediators, altering intracellular pathways, modulating gene expression, and chelating metal ions that are involved in neurodegeneration such as Fe and Cu. Thus, they can be a promising therapeutic choice for the treatment and prevention of HD; however, data from human studies are lacking and clinical trials should be highly encouraged in this regard."

 

[ambivalent]

Sunny, I know you weren;t too interested in addressing choline as it was too downstream but I thought you should take a look at this study given you're taking NR which iirc breaks down into N+R. There is a problem of increased hepatic poly(ADP-ribose) when nicotinamide is administerd to choline deficient rats. It appears to relate to decreased donor methylation status:

 

https://www.scienced...022316623035277

 

If choline deficinecy a symptom of SCA1 too, then maybe supplementing TMG or choline these guys recommended phosphatidylcholine. I see you have B12.

 

 

 

[Mind]

I recently interviewed Professor Clifford Steer and he talks a lot about UDCA benefitting ALS patients. Start early to combat the disease - is his advice. ALS and Huntington's Disease are mentioned in the second half of the podcast.

 

Clifford Steer Podcast.

Edited by Mind, 16 January 2024 - 09:44 PM.

[2Sunny]

Update:

 

I have Stage IV colorectal cancer.  Did Niagen cause this?  Maybe.

 

Targeting the NAD⁺ salvage pathway suppresses APC mutation-driven colorectal cancer growth and Wnt/β-catenin signaling via increasing Axin level

 

Edited by 2Sunny, 25 January 2024 - 01:58 PM.

[ambivalent]

 Hello Joe, 

 

I am so deeply sorry to learn of this - I wish you all the best.

 

I hope the longecity community can contribute ideas to help. If you're having chemotherapy, you could take some advice over combining Fasting-Mimic-Diet with treatment, as per researched by Longo. Obviously this may depend on cancer-type and stage of development but it could be worth a consideration.

 

UDCA, (as per discussed for neurodegnerative diseases) may have some cancer figting properties:

 

https://www.ncbi.nlm...les/PMC5510851/

 

I note too tudca increased in colon cancer, here:

 

https://www.ncbi.nlm...les/PMC5510851/

 

I wonder what the latter represents, whether it is causative or responsive. In the talk by Prof Steer he mentions udca increases many multiples during hibernation in black bears - it is speculative, but I wonder if that is a response to the cancer, rather than a driver.

 

I believe there is more out there on udca and cancer. If you are looking to the the community for possible options for cancer interventions, perhaps it could be worth considering a fresh thread?

 

.... wishing you the very best, Joe. 

 

 

 

 

 

 

Edited by Mind, 28 January 2024 - 05:45 PM.

[2Sunny]

 Hello Joe, 

 

I am so deeply sorry to learn of this - I wish you all the best.

 

I hope the longecity community can contribute ideas to help. If you're having chemotherapy, you could take some advice over combining Fasting-Mimic-Diet with treatment, as per researched by Longo. Obviously this may depend on cancer-type and stage of development but it could be worth a consideration.

 

UDCA, (as per discussed for neurodegnerative diseases) may have some cancer figting properties:

 

https://www.ncbi.nlm...les/PMC5510851/

 

I note too tudca increased in colon cancer, here:

 

https://www.ncbi.nlm...les/PMC5510851/

 

I wonder what the latter represents, whether it is causative or responsive. In the talk by Prof Steer he mentions udca increases many multiples during hibernation in black bears - it is speculative, but I wonder if that is a response to the cancer, rather than a driver.

 

I believe there is more out there on udca and cancer. If you are looking to the the community for possible options for cancer interventions, perhaps it could be worth considering a fresh thread?

 

.... wishing you the very best, Joe. 

 

 

 

 

 

 

I noted too, 

 

Joe, you have been a true inspiration in your approach to delay and reverse onset SCA-1, I hope that

 

Thanks very very much for the kind words and great links.  You are, as always, well read on topics that are spot on for me.

 

I am keeping a positive mental attitude whilst exercising regularly, eliminating all alcohol, meat, dairy, and even gluten this time, AND am doing variations of fast mimicing dieting.  I completed 5 weeks of radiation + chemo already which was round one and am starting round two of more intense chemo tomorrow Jan 29th, 2023.  On a more positive note my radiation oncologist brought in two CT Scans on the final day of treatment one from before treatment and one from that last day.   The scans showed that the two metastisized left side Common Iliac lymph nodes had reduced in size and didn't show any cancerous activity.  Those two lymph nodes were the only organs that were considered to be metastatic and which made me Stage IV and not Stage III.  It's a tiny piece of good news in a situation that I know still has bad odds, but I am grateful that things seem to be at least moving in the right direction initially. 

 

Anyways, thanks again for the kind words and helpful links!

 

Joe
 

Edited by 2Sunny, 28 January 2024 - 05:40 PM.

[ambivalent]

You're very welcome Joe. From the description you've provided, that does sound quite promising progress in obviously very challenging circumstances - the FMD from my understanding should certainly improve the efficacy of chemo and reduce side-effects. 

 

I had the briefest of correspondence with Prof Longo ten years ago - this was the address:

 

vlongo@usc.edu

 

Good luck with the chemo tomorrow, Joe.

 

 

[ambivalent]

Hello Joe, 

 

I hope the chemo is going as well as can be expected.

 

In this earlier post there was a reference to Dr Mathew Phillip's work, which has included more substantial studies of TRKD in other neurlogical diseases (a recent talk). However, he hasn't just applied TRKD to neurlogical diseases, but to cancer too, though not colon cancer. Mid-trial on brain cancer (Gliobastamo) as an adjunct therapy ~@41 on below link, though he appears to confer things to be going well at this stage, but also a very postive metastatic thymoma (~46.30) case study with extensive fasts (keto + 7 day fast per month, not clear the what of this fast, FMD?). But Dr Phillips is on twitter.

 

https://podcasts.app...i=1000643936494

 

Obviously, this is limited data and its early stages of the research, but impressive it seems so far, like the neurlogical disorders. @ 51.30 he said he believes the long fast was the fulcrum of her (metastatic thymoma case study) improvement (I believe too, adjunct therapy to chemo). 

 

 

 

Edited by ambivalent, 10 February 2024 - 06:19 PM.

[ambivalent]

I decided to look up a couple of personal-interest supplements in relation to colon cancer: fisetin and lutein.

 

Fisetin and cancer (3.4 on colon)

 

https://www.ncbi.nlm...les/PMC9782831/

 

I had an issue around blood clotting many years ago once possibly twice, though it has not been commonly reported. This may have been as a result of clearing senescent cells; cells which thought to play a role in wound healing. 

 

Another on lutein - deficiency correlates with colon cancer. Naturally, the research suggests diets rich in lutein could be preventative, especially in younger diagnosis, where the relationship appears stronger: 

 

https://www.scienced...002916523070247

 

A quick search:

 

lutein inhibits mammary tumor development in mice:

 

https://www.scienced...2231662301845X#

 

chemo protective effect of lutein in colon-cancer induced rats:

 

https://www.tandfonl...581.2010.516477

[ambivalent]

Hello Joe, 

 

I am hope the chemo is / has been going well. The following book popped up on amazon - perhaps further evidence supporting the use of fisetin.

 

 

[2Sunny]

Last infusion yesterday.  So far so good as in my side effects were minimal so life was mostly normal for me during this round of chemo.  Next is scans on the 24th of April to see what has changed if anything then surgery after which will result in a temporary colostomy.  Oh joy . . .  Ah well at least it should be reversible

 

[ambivalent]

Apologies for the delayed response Joe. I hope you are doing well - how did the scans go?

[2Sunny]

Apologies for the delayed response Joe. I hope you are doing well - how did the scans go?

 

Thanks for asking

 

Doesn't say anything about future recurrence, but after 5 weeks of radiation and 3 months of chemo my MRI showed tumor gone and lymph nodes normal.  Still scheduled for radical surgery to remove the area that had the tumor and will end up with a temporary stoma as a result, but for a Stage IV rectal cancer patient I couldn't ask for anything better at this point. I don't know how much of an impact this had, but I've been 95% vegan with small amounts of fish to supplement my protein intake, 100% alcohol free, 95% gluten free, and have been targeting 300 minutes per week minimum of exercise although usually I'm well over that.  My exercise is a far cry from what it once was though.  I just walk fast, do squats and planks, and high rep light weights for chest, back, and arms.  Plus I do walk the dogs in the woods for 30 minutes a day.

 

As far as supplements my daily list now is vastly reduced.  300 mg of Niagen, 150 mg of Pterostilbene, 1 g of Taurine, and 2000 IUs of vitamin D plus 50 g of trehalose in my morning coffee.  That's all my oncologist okay'd.

 

God willing if all is well next year post reversal of my stoma surgery I'll need to decide what supplements to resume.

Edited by 2Sunny, 22 May 2024 - 03:49 PM.

[ambivalent]

That is such teriffic news Joe, I am so very pleased to hear it. Some tough challenges ahead but welcome ones to have -  you certainly seem to have a resilient nature.  

 

Do keep the thread updated on all fronts. 

 

I wonder if TRKD would be ok with your oncologist - if you're interested here is Dr Phillips email address:

 

Matthew.Phillips@waikatodhb.health.nz

 

Once again congratulations Joe, and good luck with the upcoming op!

[ambivalent]

Hello Joe, 

 

I hope the treatment has continued to be a success and you are recovering well. 

 

Have you within your SCA-1 stack looked to managing C-Reactive Protein (CRP) levels? 

 

I noted from the following paper that in HD CRP spikes significantly in pre-manifest to then drop off in manifest-HD.

 

https://www.ncbi.nlm...6441/figure/F4/

 

from

 

https://www.ncbi.nlm...les/PMC4066441/

 

"It is therefore likely that these two factors, amylin and CRP, could interact to disrupt both metabolic and cardiovascular function in HD. Therefore, pharmacotherapeutic targeting of both or either of these circulating hormone systems in patients could present an important new avenue for remedial research."

CRP can be tested for regularly through blood tests, as many here do.

I created another thread a recent UDCA diabetes study  with impressive CRP lowering results:

https://www.ncbi.nlm...es/PMC10919985/

There maybe evidence the closely related taurine conjugated form of UDCA, TUDCA, could impact on amylin levels too. 

 

This mouse-study shows TUDCA increasing an enzyme known as the "insulin-degrading-enzyme" (IDE):

https://www.nature.c...598-017-13974-0

A study demonstrating the amylin clearing properties of IDE :

"The data strongly suggest that IDE is an amylin-degrading enzyme and plays an important role in the clearance of amylin and the prevention of islet amyloid formation."

https://www.jbc.org/...8558-5/fulltext

Once again I hope you are doing well Joe, and if the operation has happened that it proved to be a success.