The HDDW supplement trial was the best we thought we could do -- with the best (mouse) knowledge then available 6 years ago. And we followed several of the participants 5 years during which tapping and cognitive tests (which have since been shown to be some of the more sensitive measures) remained stable. It could very well be a long term placebo effect in those with healthy lifestyles and the energy to hope . . We never suggested this study was anything more than observational. And very important, my sister sent trehalose cookies and candies to participants every Christmas.

And it is time to change the HDDW "favorites" list. Would I recommend the same supplements now? Probably not -- based on new knowledge. At present, the negative CHDI mouse studies for creatine and CoQ-10 -- and the low levels that actually get into brain -- and a new study that suggests autophagy is down regulated by large doses of antioxidants: [www.ncbi.nlm.nih.gov] limits my enthusiasm for these supplements -- at least in high doses. I will keep trehalose, with positive results in academic labs and CHDI. It's cheap and safe, and may be protective at several different points -- autophogy and anti-inflammatory. And I'll keep the SSRI's too

And the likely best advice: exercise and more exercise.

Would I love to know whether CoQ-10 and creatine are helpful? Yes, but if I had the choice of a shorter trial with a promising new drug that gets into brain, has decent results in phase 2 -- I'd probably do that one.

Time to get off and update the HDDW pages . .

What about tumeric lavonne? I think it's a strong antioxidant too? I read awhile ago, that things that get rid of the protein clumps, are now finding the clumps are protective i think i read. Do you think you'll be taking it off your favourite list too? Interesting, any time i've tried tumeric, my hd gets worse, just food for thought.



Edited 1 time(s). Last edit at 06/30/2010 11:55PM by Barb.

I don't think there is enough information to recommend it. I don't think antioxidants are bad -- just that we should be careful about using huge doses of any of them. Medical studies so far have found no benefit -- and some harm by using large doses: I reviewed this a while back at HDDW [hddrugworks.org]

And published after that review, we can add the negative DHA omega 3 study done in Alzheimer's -- which showed no benefit.

Can you recommend a dosage of Treholose? I thought the dosage was like 75 grams which is so much. If that is the dosage what is the best way to take it?

My husband is also taking the equivalent of 1cup of blueberry/day - are you saying that this may not be good for him?

Thanks very much.



Edited 1 time(s). Last edit at 07/01/2010 01:43PM by Hope2.

I'm going to keep creatine at 20g a day on my list. My brother was in an open label trial at Mass General at that level and his symptoms improved. He has a higher CAG than I (43).

All the other stuff I take falls into the "can't hurt, might help" category. There was an HD mouse study done with blueberries at the mouse equivalent of a cup per day. That prevented symptoms.

Will

Hi Will,


I don't disagree with you, but have been thinking more about the "can't hurt" idea. The divide between "supplement" and "drug" is basically a legal distinction, not a chemical/biological one.

For a long time, people have been taking vitamins (including A&E) and other supplements because they were antioxidants and therefore "couldn't hurt". However, some analyses have shown that taking Vitamin A and E can actually *increase* risk of death in the general population:

"Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention; Systematic Review and Meta-analysis." JAMA 2007;297:842-857.

The study highlighted by Lavonne above gives a potential mechanism for how antioxidants might be a mixed bag, therapeutically.

So I think we have to be very careful with the concept that things can't hurt, is all I'm suggesting. It's for this reason that I personally don't take any supplements, despite thinking about it a lot. Lots of exercise and a good diet are the only things I can think of that really couldn't hurt.





jeff

I remember the blueberry study Will

I?m confused by the sudden need by some to scare people away from supplements - especially since supplements are essentially all we have (beyond excercise).

First, I'm really hopeful that the creatine study by Steven Hersch will deliver positive results. I sat in on his presentation and he's looking for participants in this three year trial. This is an opportunity to be one of our "HD Heroes" who bring a treatment to the HD community.

Info on CREST-E Creatine Trials

Secondly, the study cited by Jeff seems to have some challengers. Various critics cite valid reasons for the report to be questioned. One of the more thoughtful commentaries is found at:

http://weightoftheevidence.blogspot.com/2007/03/antioxidant-supplements-dangerous.html

I don?t want to start a prolonged argument here regarding the pros and cons of supplements. There are enough ?researchers? who?ve been fighting this battle for years and I suppose it can be reasonably argued either way. If you?re so inclined you can read the counter argument and decide for yourself.

What I will argue about is that I know enough people feel that they are benefited by their supplement program that arguments to the contrary, or attempts to instill fear of supplements, certainly seems counter-productive for the HD community.

Steve



Edited 1 time(s). Last edit at 07/02/2010 06:19AM by SteveI.

You're right steve.(sorry i didnt read your links steve, but i agree with what youre saying) You know, when i first read these posts i was like, oh they must be right, and of course i had to throw in that im sensitive to some supplements, but then i'm sensitive to everything lol. But then after thinking for awhile, i was thinking, why did lavonne and jeff do this? Everything that we have fought for to be pro-active, suddenly, oh don't bother? It was like, later in the day, these posts hit me really strange, and i would like to know why these things are being posted, what's the sudden beef with supplements? And why on another thread when i said high dose memantine is too high, and i take low dose memantine, was i told that by taking memantine i am taking a risk? No i am not. I'm not going to mexicano and getting some funky dunky treatment. I am using a med that works very good for alzheimers, is a completely approved drug, and i am just using it off label for hd. There are no hd drugs, all hd drugs are off label drugs. I don't like it when there appears to be a sudden anti-supplemenat agenda? Or anti try anything, except what some people want to push you to try if it's on their agenda. I may have hd, but i'm not stupid. What's the hidden agenda lavonne? Acr16?



Edited 2 time(s). Last edit at 07/01/2010 11:32PM by Barb.

Lavonne, i hadnt even noticed this ricidulous statement, that supplements maybe caused a long term placebo effect! geez! Well uhmmm, if a long term placebo effect is able to fool the doctors and the patients, them uhmmm lol, i'd say it's working

i think a point that is being missed is that even though creatine and coq 10 may be effective, it is not a cure. i read an article on this website saying that the clinical trials for those supplements are getting 200 million dollars in government grants. thats quite a bit of money when trials for adult stem cell research at the end of the year will get a hundreth of that... and really who knows if the government is going to be so ready to produce that kind of money again when a cure comes along because so much has already been spent in hungtingtons research.



Edited 1 time(s). Last edit at 07/02/2010 02:30AM by queencity04.

Queencity, creatine and CoQ are not getting 200 million. Nothing close to that. Any government grants are beyond our control. Now that creatine and Co-Q is in the last stage of trials, they should be finished up.

Lavonne, I see no need to discourage people from these trials. For one there aren't that many alternatives, and if they are going to be set up to exclude people on maintenance meds who can't just stop them for a trial, these people might as well do the trials they can do. Give people trials they can do of something more promising, they will probably opt for those trials. And don't try make it dumb things like 1970's Russian antihistamines based on untrustworthy Soviet data. It's not like the medical trials to date have been that great compared to the creatine or Co-Q trials.

Also general population studies of anti-oxidants might actually not be too very relevant. You have not made a case for quality of life issues which may be improved. What was the particular projected length of of time lost from the general population? Were peoples lives shortened by months from 73 years and 6 monthes to 73 and 3 months? Does that really bother a person who is midstage at 40 years old? Quality of life is much more important than quantity in the case of HD and especially if one is tacking life on to the the end stage of HD. I will always keep these things in the "can't hurt" category.. because we are comparing hurt of creatine to hurt of HD and not some average person.

I feel a weird agenda at play that is not honest. Say what you mean and mean what you say. Lavonne it's your work that has been encouraging in the first place.. and other work. One mouse study which I have never heard of to the contrary compared to all the rest which are at the very least not negative about creatine shouldn't change much. Especially when we can shortly have hard data compared guesses which seem to go this way and that. And there is no trial I am aware of that is an alternative to these trials ... so how long is a person to wait for the ghost trial?

I'm not sure the point is being missed, but it's certainly worth revisiting. Researchers want to avoid the use of the word cure because they really aren't shooting for a cure ... that bar is WAY too high. Since we have researchers on the board at HDSA we have had a few discussions about whether or not we should use the word "cure" in the mission statement. I usually argue that the HD community doesn't care whether we call it a cure or a treatment - as long as long as it delays the progression of the disease to an acceptable point.

HD is a genetic disease. It's part of our DNA and can't be "cured" in the classical sense. At least not with the technology we have today.

Even cell therapy isn't as much a cure as it is a treatment that targets the more serious damage caused by HD.

When we use the word "cure" we are referring to a treatment or combination of treatments that will delay the progression of the disease to be more closely in line with our normal physical and mental deterioration so that those who are afflicted with the disease can experience a normal life.

I'm hoping for two treatments. The first is one which significantly slows cell death. The other is a treatment that will safely encourage the replacement of those cells that have died.

Although treatment of the manifest symptoms of HD is a great thing, "the cure" in my opinion will come in the form of treatments that will seriously retard the degeneration of the brain that starts around 13 years before observable symptoms.

On a global scale, the only effective "cure" for an inherited disease is to not pass it on. If they can figure out a way to reduce the costs associated with pre-implantation genetic diagnosis so that nearly everyone could afford it "out of pocket" then we would could make a serious dent in the percent of the population that will develop HD.

Steve

Hi all-

First of all, I am very glad this discussion is taking place. The more open discussion the better. And even better than that is when people bring experiments and evidence to the debate.

Second, I don't what "supplements" means, used by itself. Jeff made a good point that there appears to some evidence that a couple of specific things - "supplements" previously thought to be completely safe (Vitamins A & E to be precise) - may not be completely safe at high doses in the general population. Let the debate about that continue.

Third, LaVonne was referring to data from a new paper by David Rubinsztein, a long-standing HD investigator at Cambridge University that was just published on-line June 28 - at the very least we owe a big "Thank You" to LaVonne for staying right on top of things.

Since LaVonne was kind enough to post a link to the paper I assume that the people who have already posted here have read it. For those just joining the debate, this is probably the excerpt that makes the point she was trying to make (LaVonne, correct me if I am wrong):

"We do not suggest that treatments aimed at ameliorating oxidative stress may not have their place as therapy, but rather that better understanding of their interaction with other cellular processes may allow for more appropriately designed (and therefore more effective) treatment. For example, since the effects of antioxidants on autophagy appear dose-dependent, it is possible that dose may be crucial in balancing the effects of these drugs, and that higher doses may not necessarily mean greater efficacy. This may be of particular relevance as higher doses of some antioxidants have been proposed for use in HD (3)."

This is the abstract referred to in footnote 3:

"Evidence of oxidant damage in Huntington's disease: translational strategies using antioxidants.

Stack EC, Matson WR, Ferrante RJ.

Abstract

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder characterized by progressive motor dysfunction, emotional disturbances, dementia, and weight loss. It is caused by an expanded trinucleotide CAG repeat in the gene coding for the protein, huntingtin. Although no one specific interaction of mutant huntingtin has been suggested to be the pathologic trigger, a large body of evidence suggests that, in both the human condition and in HD mice, oxidative stress may play a role in the pathogenesis of HD. Increased levels of oxidative damage products, including protein nitration, lipid peroxidation, DNA oxidation, and exacerbated lipofuscin accumulation, occur in HD. Strong evidence exists for early oxidative stress in HD, coupled with mitochondrial dysfunction, each exacerbating the other and leading to an energy deficit. If oxidative damage plays a role in HD, then therapeutic strategies that reduce reactive oxygen species may ameliorate the neurodegenerative process. Two such strategies, using coenzyme Q(10) and creatine, have been proposed. Although each agent has had limited efficacy in HD patients, the optimal therapeutic dose may have been underestimated. High-dose coenzyme Q(10) and creatine are safe and tolerable in HD patients and are currently under investigation. In addition, there are parallels in reducing markers of oxidative stress in both HD mice and HD patients after treatment. It is likely that high-dose coenzyme Q(10), creatine, or both agents, will represent a cornerstone defense in ameliorating the progression of HD.

My point is - we can't wish evidence away when our investigators produce it. Instead we should evaluate it in a critical way, try to replicate important experiments and, when appropriate ask ourselves how we should be adapting our strategy to find treatments. The last thing we should do is ignore it.

Shame on us if we don't at least try to follow-up on Dr Rubinsztein's work to at least make sure this effect does not confound possibly beneficial results in the CoQ or creatine trials.

Robi

Robi Blumenstein
CHDI Management/CHDI Foundation
robi.blumenstein@chdifoundation.org
www.chdifoundation.org

I sense a divide here between technical and non-technical folks. Jeff has a foot in both camps as a gene carrier and a researcher. One large reason for taking supplements is to give us the feeling that we're doing something besides waiting for treatments and a cure. If that results in a placebo effect, that's fine with me.

I stopped taking A/Beta Carotene a number of years ago due to possible harmful effects. The evidence on anti-oxidants sounds convincing, so I'll stop E also. I don't take C in large doses (1000mg/day), so I'll continue with that.

When I started supplements in 2003 after testing positive, I did notice an effect. My mind seemed sharper, my memory seemed better (I didn't need to write down a grocery list of 4 items), and I seemed calmer about life's little irritations. I also noticed that my driving seemed better. I felt more confident driving right next to concrete barriers. It was almost like my eyesight had improved, but that wasn't the case. My contacts prescription is the same as it's always been.

I still think my lifelong running has been the major factor in keeping me symptom free by generating more new cells than the gene is killing. But, I'm convinced supplements are helping.

Will

Thanks Will, for leading me to clarify:

I don't mean to suggest that pHDs should not take ANY supplements - only that EACH specific "supplement" (or each specific combination of supplements) should be considered for dose, effect, side effects, interactions with other treatments, etc. based on all the available evidence. Unfortunately it's not subject that lends itself to generalities.

And your point about exercise is a good one, too.

Cheers,

Robi

Robi Blumenstein
CHDI Management/CHDI Foundation
robi.blumenstein@chdifoundation.org
www.chdifoundation.org

Is 400IU/day of E high?

Reminds me of the book that I got when I was pregnant - it was 3 inches thick and proceeded to scare the crap out of me. You must have exactly x amount of magnesium - too much will cause this in the baby and too little will cause that, same with A, D, zinc and on and on and on... Eventually I had to toss the book and go by my gut.

What Will said is so true - part of the benefit of supplements is being proactive... that feeling (for caretakers too) is worth so much.

When my husband was diagnosed all the doc said in terms of what we should be doing was "lots of fruits and vegetables and take a multi-vitamin" which I translated to mean "you are screwed!". we were given a little hope online learning about the blueberry, creatine, treholose etc. Having conflicting reports on these "couldn't hurt, may help" items is very discouraging...

I too "feel" that the supplement cocktail, where low dose creatine and CoQ, blueberries, trehalose and omega 3 was used was helpful to the small subgroup of HDDW participants with moderately early disease who took them. I'd like to hope that this was an added effect of combining agents -- or whether these people were proactive in exercise and diet too -- or whether hopeful expectation and frequent caring interaction from HDDW folks changed levels of protective brain chemicals, I don't (and can't) know. I do know I was glad to see they remained stable.

So I was surely sad (even initially felt betrayed) to hear that CHDI had not confirmed the earlier mouse studies. So now we have both positive and negative studies. What are we to do when we don't have a clue which one is more predictive in people.

We all have different opinions -- and I greatly respect Jeff and Will and those of all who have posted here. I think the best we can do is to have a healthy lifestyle, keep an open mind, stay informed and listen to both sides of the argument -- and (like Will and Jeff) get involved with clinical research. And now that COHORT will be coming to Washington State -- I'll finally get to DO what I preach -- join a clinical study.
Happy July 4th to everyone!

Will - I understand what you're saying about self-directed supplements providing a feeling of engagement. I guess I derive this mostly from my day to day work, so supplements end up being one more thing to worry about, rather than a help.

Also, I think you're correct that only you can judge your anecdotal experience with supplements. I find that, as North Americans, we have this tendency to want to live in statistics - but we're all an "N" of 1, and if things are working, they're working.

Good luck,


jeff

Hi everyone. This is my first time writing here. I read this daily for hope and inspiration. My husband died in 2001 with hd. We had three children, two boys and a daughter. In 2006 my son was diagnosed with hd and is now in mid stages. In 2009 my other son was diagnosed with hd and is also in mid stages. I pray daily for strength, I used to pray that my children would never have to go thru what their dad did. But I realize that hd is their future. I am confused on what everyone is saying about supplements. Can anyone tell me what my sons should be taking. They take 1200 CoQ10, folic acid, one is on aricept and the other is on aminda (not sure of spelling) and both are on antidepressants and sleeping medication. My son that was diagnosed in 2009 his attitude is very good. Is happy each day he is here. My other son has 2 to 3 blow ups a day and is very angry. To watch your children, even though they are 37 and 36, it hurts and I want to help and I don't know what to do.
Thank you, Lynne