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NAD+ Precursors, Glaucoma, and Wallerian Degeneration

nmn nad+ nmnat

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#31 warner

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Posted 27 March 2018 - 02:24 AM

I went back and re-read post #17. Can you describe the software you are using for visual field testing and the computer monitor you use? Do you do your testing at the same time of the day? If it is daytime, how do you control ambient light?

 

I think most of your questions are addressed in previous posts, but I'll try to expand on those a bit.  For tonight, I only have time to address the above point properly, so I'll stick to that...

 

In post #17 I presented a partial list of the many things that can affect visual field testing.  At home, there are a couple of disadvantages, like lighting and head position, that add some imprecision, but most other factors are better controlled than when doing a standard HFA, plus I can do much more testing.  This is exemplified by the fact that my occasional HFA tests over the years are so noisy, when compared over time, that they are virtually useless for tracking progression details.  I'm not surprised by that (and experts generally agree that you need a very large number of HFA tests to say anything certain about progression), given how sensitive visual field results are to mundane factors like mood, attention, hunger, etc.

 

I do my best to control lighting, computer screen, etc., plus many other factors that are poorly controlled in standard HFA testing (time of day, hunger, mood, etc.).  To improve reproducibility, one also needs a system to stay focused during the multi-minute test.  Also, if you change your approach to the testing in some significant way, then you'll need to account for that by determining its effect on the visual field count and take that into consideration going forward (i.e., for proper comparison to past data).  So, in general, I'd say that my own testing is much more precise and reproducible than standard HFA testing.  (In fact, I only do HFA testing because the eye docs are required to do that for insurance purposes.)

 

An interesting example of another advantage I have over standard testing is that I can make use of an important piece of information that the standard test makes no effort to measure:  by mentally counting the seen stimuli during testing, I can eliminate all "false positives" where I know that I've pressed the mouse button accidentally (an over-eager response).  On average, of 224 stimuli, this accounts for about 2 of the false positives, but varies from test to test, adding significant variability, and over-estimating visual field response.  So, between improvements like that, being able to better control many other factors, and being able to repeat testing often enough to overcome any remaining imprecision, I'm confident that the past 10 years of VFC results are reliable enough to tell us something about B3 supplementation and glaucoma progression.


Edited by warner, 27 March 2018 - 02:30 AM.

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#32 warner

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Posted 27 March 2018 - 04:40 AM

Oops, minor mistake - should read:  On average, of 224 stimuli, this accounts for about 2 of the positives reported by the program, but varies from test to test, adding significant variability, and over-estimating visual field response.  (i.e., the program, like the standard test, sees only mouse clicks, and doesn't take advantage of the times when I know that I accidentally clicked w/o a stimulus)

 

btw, this doesn't eliminate the cases where you're not sure whether you saw a stimulus or not, but all VF testing is subject to that uncertainty.  And given enough cases like that (barely perceptible stimuli), it's easy to see why mood, attention, etc., can significantly affect results if such factors are not controlled adequately, or if testing is not repeated often enough to average out such noise.



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#33 warner

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Posted 27 March 2018 - 10:05 AM

In regard to your post #19, do you have any data regarding RNFL loss in months ~100 to 120? If you are experiencing RNFL loss on NR, I do not think VFC would rebound the way your results show. So one tentative conclusion would be that NR reduces VF response in a manner similar to NA, and that this is independent of RNFL loss (exactly as it was around month 30-35 when you were on NA). Have you considered that possibility? Do you have RNFL results to confirm or refute this hypothesis?

 

It's possible to interpret your VFC data as indicating that none of NA, NR or NAM are helpful to your vision as measured by this test. I could further read this data as saying that both NR and NA suppress your VFC count in a dose-dependent manner while NAM appears to cause somewhat less suppression.

 

In addition to the RNFL data, you need a period with "no B3" again to paint a better picture of the treatment effect. A "no B3" period of 6-12 months would seem appropriate. After that, maybe you could do two trials with B3. One would involve B3 only and the second would incorporate the suggestion from post #24 to use methyl donors along with B3. The idea behind adding methyl donors is that insufficient methylation capacity in the RGC's might explain your reduced VFC during each B3 trial.

No further RNFL loss in months 100 to 120.  However, its typical that vision loss follows RNFL loss by months to years, so those 3 declining NR points may still be due to past RNFL loss.  Also, the remaining nerve fiber may be stressed in a way that results in vision decline that is recoverable.  So its misleading to suggest OCT-measured RNFL loss = vision loss = complete nerve death.

 

As you imply, (daytime) 250 mg NR did not appear to be helpful in any way (wrt glaucoma progression), and may even be harmful, at least with respect to reducing VFC.  It didn't stop vision loss tied to RNFL loss, and, for all we know, makes progression worse.  At best, it only depresses VFC in a reversible manner, like NA did.  But, as with NA, we don't know that such suppression would be completely reversible over the long haul.  (These points were made in previous posts.)

 

The big question is whether NAM stops progression (pushing the lemmings back from the edge of the cliff)?  The mice studies say yes, which does not conflict with my data (so far).  In this interpretation, 250 mg daytime NR probably does nothing helpful (for glaucoma), while the 1000 mg nighttime NAM (8.4x the molar amount of NR) probably helps stabilize the remaining nerve fiber (time will tell).  Whether the improved VFCs with NAM are due to reversing an NR effect, vs. stabilizing stressed nerve fiber, is open to question.

 

On the other hand, I think its highly unlikely that going with "no B3" will increase VFCs further, given (1) the loss of RNFL corresponding exactly to the areas of vision loss, (2) the fact that the NAM improved VFCs while still taking 250 mg NR (i.e., I was not substituting one for the other), and (3) there is no evidence that NAM causes the retinal edema that NA does, which appears to be related to NA's VFC-lowering.  I guess I'm making a small bet here that the NR is not harmful (and may be helpful in other areas), or that whatever eye harm NR does is offset by the NAM.  But the NAM itself seems like a good bet, especially given the mice studies.

 

wrt future experimentation, I'd like to see first what the NAM does wrt stabilizing RNFL and VFCs.  I mentioned in an earlier post being willing to sacrifice a bit of vision to learn things that would save future vision, but I'm still generally doing those experiments in the context of attempts to improve health (taking NR alone was such an attempt), and won't choose experiments that I think will cause harm.  In that context, at this point, choosing to use NA, or NR without NAM, or no B3 at all, would likely be eye-harmful, so I'll probably avoid those experiments.

 

---------------

ugh, let's try this again... from previous post:  (i.e., the program, like the standard test, sees only mouse clicks, and doesn't take advantage of the times when I know that I accidentally clicked w/o seeing the stimulus)


Edited by warner, 27 March 2018 - 10:09 AM.


#34 HempOil

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Posted 27 March 2018 - 01:39 PM

wrt future experimentation, I'd like to see first what the NAM does wrt stabilizing RNFL and VFCs.  I mentioned in an earlier post being willing to sacrifice a bit of vision to learn things that would save future vision, but I'm still generally doing those experiments in the context of attempts to improve health (taking NR alone was such an attempt), and won't choose experiments that I think will cause harm.  In that context, at this point, choosing to use NA, or NR without NAM, or no B3 at all, would likely be eye-harmful, so I'll probably avoid those experiments.

 

Hi warner,

 

In light of your harm avoidance preference, does the advice on anti-agingfirewalls.com against supplementing with nicotinamide concern you? Here is the link, where section 5 discusses it and comes to the conclusion that:

 

It is now clear that high concentrations nicotinamide are harmful to health.  HIgh doses of dietary niacin probably produce the same effects, despite the many benefits of high dose niacin.  With aging, nicotinamide levels already go up.  Adding more nicotinamide is probably not going to “cure” aging.  Adding a methyl donor to eliminate nicotinamide (such as betaine) may be a good thing.



#35 warner

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Posted 27 March 2018 - 03:26 PM

In light of your harm avoidance preference, does the advice on anti-agingfirewalls.com against supplementing with nicotinamide concern you? Here is the link, where section 5 discusses it and comes to the conclusion that:  It is now clear that high concentrations nicotinamide are harmful to health.  HIgh doses of dietary niacin probably produce the same effects, despite the many benefits of high dose niacin.  With aging, nicotinamide levels already go up.  Adding more nicotinamide is probably not going to “cure” aging.  Adding a methyl donor to eliminate nicotinamide (such as betaine) may be a good thing.

Yup, I'm not expecting NAM to extend my lifespan... except that by saving my eyesight it would allow me to continue to do the research that may result in such extension. :)  That's also why I tried the NR first, w/o NAM.  But then the mice (glaucoma) and human (skin cancer) studies appeared, along with my disappointing NR results, and at some point you simply have to face reality.  Also, I've minimized the NAM dose (night only), and its a dose that is known to be well below the level of methyl donor depletion that extends NAM's blood half-life.  Plus there is a simple way of explaining NAM's effectiveness:  it may simply be providing NAD precursor to local tissue where such precursors are in short supply, such as nerve fiber at night, or previously sun-exposed skin.  (So it may be better used as a local eye drop, or in direct application to the skin.)

 

I have betaine on my list to look at (again).  And there is probably a more clever, effective way of addressing whatever NAD-related issue there is with both skin cancer and glaucoma that we haven't yet discovered/proved.  But in the meantime, given my personal results, the mouse studies, the lack of any good evidence that 1000 mg of NAM has ever done anyone any harm, and lots of evidence of beneficial skin effects, it seems prudent for someone with glaucoma to try taking NAM in a manner similar to what I've been doing.  (btw, I'm not up here trying to convince anyone of anything.  Posting just helps organize thoughts, exposes what I'm doing to healthy criticism, and may be of help to others in a similar situation.)


Edited by warner, 27 March 2018 - 03:28 PM.

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#36 jimsmith

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Posted 27 March 2018 - 06:24 PM

Hi Warner,

 

I have not been able to find in this thread any information on the specific software you use for your VFC testing or any information about your computer monitor and testing details. I apologize if I keep missing it.

 

I am seeking specific materials & methodology information. For example, what is the name of the software? What brand and size computer monitor do you use? Is the screen matte or glossy? How far do you sit from the monitor? Are you testing only central vision (say 10 degrees) or do you have some system (such as multiple monitors or a huge monitor) that allows you to test peripheral vision out to, say, 30 degrees?

 

You also don't say what you do to control lighting, for example. Do you only test after dark and use room lighting? You mention that you control for these things, but you don't give any details we could use to begin to replicate your investigation. Presumably some (not all) of the treatment effects you have seen would be seen by anyone, glaucoma patient or not.

 

Jim



#37 warner

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Posted 27 March 2018 - 07:55 PM

I have not been able to find in this thread any information on the specific software you use for your VFC testing or any information about your computer monitor and testing details. I apologize if I keep missing it.

I mentioned that the software was "VisionField", which you may have mistaken as merely descriptive.  I'll come back tonight and address all of these (good) questions when I have time.  VisionField is no longer being sold (recall I've been at this for about 10 years!), but there are other apps available, one of which I'll point out later.  In general, there is a big difference between setting up a system that is useful for tracking one's own progression, versus using a standard system where results can be compared across subjects, and where the latter is often promoted by the medical profession to the detriment of the former. imho



#38 warner

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Posted 28 March 2018 - 07:40 PM

Probably best to do this VFT (visual field testing) app review from perspective of someone looking to set up a home VFT system (or, in my case, replace an existing one no longer being distributed).  This will highlight what I’ve found important/useful, but is unlikely to match the reader’s needs and preferences exactly.

 
- app should be simple to use, reliable, store complete test results, etc.  [In a search I did last year, MRF = Melbourne Rapid Fields looked like one of the better choices, from https://glance-optical.com/, although when I last checked it required an iPad to run it, with there being a free Melbourne Rapid Fields version downloadable from App Store for US customers.  In general, the US eye profession and FDA seems to be discouraging development and use of such at-home apps, which is a shame.]
 
- app should display stimuli (light dots) of varying size/intensity in a random manner over an area large enough to cover the retinal surface of interest (and I don’t want an app that gets too clever about what stimuli it bothers to display – just give me a fixed number of stimuli each time so I can count them)
 
- in the past, I’ve been testing 24 degrees, covered by 54 locations, 4 stimuli each location (like Humphrey’s 24-2 standard testing), so it would make the transition to a new app simpler if it supported a similar approach
 
- it would be nice to be able to test a wider area, or narrower area more densely, if desired, but not a deal breaker since the 24 degrees adequately covers my glaucomatous vision loss (and the corresponding number of locations and stimuli take a few minutes to cover, which is probably the limit on one’s attention span per test, especially if you want to do the tests fairly often)
 
- I’m not at all concerned that the app numerically match standard results (or even generate similar types of numbers), since that is likely a fool’s errand given the complexities involved, and will just distract you from focusing on what you need to do to reliably monitor your personal visual field response
 
- the app should (at least) report the total number of positives (clicks when stimulus was present), as well as false positives (clicks when stimulus not present, a measure of trigger-happiness)  [I would then compare the positives reported to the count I did in my head of stimuli seen, choosing the lower of the two counts as the best estimate of the positive count for that test because (1) when my count < positives, then positives contain cases where stimulus was shown but I didn’t actually see it, and (2) less commonly, when my count > positives, then I must have seen stimuli that were not there (i.e., just noise in visual field)]
 
- results by location should be displayed in a grid similar to the standard output so that one can quickly see the variation in visual field sensitivity by retinal location, although this is not as reliable as the total positives count, since the grid location results are more subject to small variations in head location [OCT RNFL measurements are a more precise way of monitoring glaucomatous damage location]
 
- the app will inevitably attempt to cleverly do and calculate more stuff, which I’ll likely ignore [and if I can’t find an app that meets the above (simple) requirements, then I’ll probably just create one :)]
 
- follow the app’s instructions for head positioning (typically using blind spot location), plus any lighting or computer display tips
 
- choose a testing location where you can control ambient light, computer brightness, etc. [I do this in an office with shades closed, and a desk lamp on each side of the screen, which just happens to be my original setup from 10 years ago (i.e., probably not the best setup)]
 
- if testing both eyes, switch which eye is first tested each time to eliminate bias related to first vs. second testing (such as due to differences in fatigue, attentiveness, etc.);  also avoid doing too many tests at one sitting, since this will introduce eye fatigue with lower visual field response
 
- limit distractions, and develop a routine that keeps you focused during testing;  the simple counting I do of stimuli seen helps a lot, and gives you a sense of how far the test has progressed;  if asked to focus on one location during the testing, try shifting focus slightly left or right after each stimulus to keep your eye from wandering (i.e., give it something to do -- some apps deal with this by having you move fixation from stimulus to stimulus, keeping the eye busy)
 
- choose testing times when you’re not emotional, tired, hungry, etc.  [the exception to these tips being, of course, when you’re actually testing the effect of something you would normally control]
 
- block the non-tested eye in a way that is not stressful (use an eye occluder of some sort)
 
- develop a testing routine that maximizes test result (positive count) reproducibility/precision;  on a positive count basis, it should be possible to routinely reproduce test results within a few counts of one another (out of 200+ stimuli), with a block of about 6 tests producing a well-distributed set of results about the mean
 
- if a set of associated test results are not well-disributed about their mean, then do more testing;  don’t eliminate apparent outliers without doing sufficient retesting, and without a plausible reason for the outlier
 
- the reproducibility of your test results indicates what degree of visual field change is possible for you to determine with such testing [as illustrated by my comparison of B3 effects on VFCs, where significance required a difference in means beyond the imprecision of each block of tests – you can do a T-test, etc., to make it more complicated, but it should be obvious when plotted that result sets differ, or not]
 
- if making a significant change to your testing routine, do enough testing immediately before and after the change to measure the effect the change had on results
 
This approach will give you a good measure of your overall visual field response in each eye.  And although the results will not be directly (numerically) comparable to others, or to results from standard testing, they need not be any less reliable, benefiting from the control of many factors ignored in standard testing, as well as the ability to do more testing as needed to overcome imprecision (averaging out sources of noise).  Allowing you to answer lots of interesting questions about how lifestyle changes affect your vision.


#39 stefan_001

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Posted 18 June 2018 - 07:34 AM

https://www.scienced...350946217301258

"Here, we discuss a new area of research examining the role of NAD+ and sirtuins in regulating retinal metabolism and in the pathogenesis of retinal degenerative diseases. Indeed, the results of numerous studies suggest that NAD+ intermediates or small molecules that modulate sirtuin function could enhance retinal metabolism, reduce photoreceptor death, and improve vision."

 


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#40 warner

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Posted 28 June 2018 - 02:27 AM

update...  I recently replaced my computer and was able to purchase a new VisionField license from this site:

https://bersoft.com/...field/order.htm

Although I've kept the same monitor, etc., the new computer has a different graphics card, and comparison of results between the computers showed that the new system produces, on average, a visual field count that is 1 less than the old computer, so I'm using that value to adjust the new results for comparison with old results (as discussed in a previous post).

 

I've remained on the 1000 mg/d NAM (taken at night, as described previously), with no significant change in visual field counts since last posting 3 months ago.


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#41 HempOil

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Posted 28 June 2018 - 12:21 PM

Thank you for the update warner. Please continue to post your observations.



#42 johnross47

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Posted 22 July 2018 - 07:37 PM

Very interesting read. I was referred to a hospital.- based specialist because of pressure anomalies in an eye test. I'm fortunate to live much of the time in Scotland where we get free eye tests, and at my age, 71, we get a very complete set, including photographs, field tests, pressure tests etc. I have the early stages of cataracts and AMD in addition to the pressure issues; the full set, so as you can imagine, this is an issue to which I am paying a great deal of attention.

 

I'm currently taking 250mg/day of NR with 3-4 day rests every four weeks. My diet looks like the one recommended by research, high in lutein and zeaxanthin. It's what I've eaten for years. I also wear sunglasses a lot more than I used to and I've bought a hat.

 

Has there been any response from the research group to your input on night-time NAM?



#43 warner

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Posted 23 July 2018 - 12:53 AM

Has there been any response from the research group to your input on night-time NAM?

Never got a response from that research group.  I haven't seen any further loss of visual field response while being on the nightly 1000 mg NAM (split into 2 x 500 mg doses, about 3.5 hours apart, as described above).  As I recall, there's also some interest in, and limited evidence for, using NAM to slow AMD progression.

 

wrt NR, I'm about 2 weeks into use of 375 mg/d sublingual NMN in place of the 250 mg/d NR I had been taking for the past couple of years.  I'll post the results of visual field testing (as done above) for this experiment, but, so far, I'm not seeing any significant change associated with switch to NMN.  I'm also watching several other factors that my wife and I test daily, and will report on those too (weight, body fat, blood pressure, etc.).  Since we're both pretty healthy, however, it may be that we won't see the types of changes reported by Lawrence and others, or at least not at 375 mg/d, even if sublingual.  We'll see!

 

btw, I think ABN will ship overseas if you want to try sublingual NMN...

https://alivebynatur...5-mg-each-copy/

 

and, imho, they make a pretty good case for switching from NR to sublingual NMN...

https://alivebynatur...d-boosters/nmn/

 

also, their facebook page has a new note about improving(?) their sublingual formulation with next batch in mid-August...

Alive By Nature Really good points - glad to see such understanding. We added stevia both for sweetener and to aid absorption. The slow dissolve helps absorption also, and makes it a bit of a time-release into the bloodstream. But many people find the slow dissolve and size to be inconvenient, so the next batch due mid August is about 1/2 the size, less sweet, better flavor, and faster dissolve time.


Edited by warner, 23 July 2018 - 12:58 AM.

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#44 markymark

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Posted 24 July 2018 - 09:53 AM

@warner and the other contributors,

I thank you very much for sharing your experiences and insight about "B3" and glaucoma. I am trying to provide my mom (87 yrs and healthy otherwise) with best possible treatment for her PEX-glaucoma. After two trabeculotomies the IOP is nor longer a problem for 4-5 years, but visual field still got worse. But this is not new to you, I guess. I is all about stopping RGC decay.

 

My question is, were your positive results with NAM and NR achieved against a background brought about by other retinoprotectants, which are used for glaucoma, such as citocoline https://www.ncbi.nlm...pubmed/29450391, Palmitoylethanolamide (PEA) https://www.ncbi.nlm...ubmed/26664738, Q10, B12, vinpocetine? I even ordered SKQ1 drops from russia, which arrived two weeks ago.

 

I do not want to distract the thread from its origin "NAD+ and glaucoma", but I feel that the other retinoprotectants I mentioned above should be part of the equation.

https://www.ncbi.nlm...pubmed/29472700

Eye (Lond). 2018 May;32(5):938-945. doi: 10.1038/s41433-018-0050-2. Epub 2018 Feb 23. Neuroprotective agents in the management of glaucoma.
 

 

best MM



#45 warner

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Posted 24 July 2018 - 02:24 PM

My question is, were your positive results with NAM and NR achieved against a background brought about by other retinoprotectants, which are used for glaucoma, such as citocoline https://www.ncbi.nlm...pubmed/29450391, Palmitoylethanolamide (PEA) https://www.ncbi.nlm...ubmed/26664738, Q10, B12, vinpocetine? I even ordered SKQ1 drops from russia, which arrived two weeks ago.

Thanks for the links.  With PEX-glaucoma, at least you have a handle on the immediate cause.  And yes, I'm skeptical of the emphasis glaucoma specialists put on IOP lowering vs. other forms of retinal protection, including overall health, adequate sleep, exercise, etc.  Q10 and B12 are included in my supplement regime, as well as Melatonin, Lutein/Zeaxanthin, and DHA (as Carlson's Concentrated Super DHA 500 mg, with minimal excess fish oil/calories).

 

I guess one issue with the other proposed protectants is that their effectiveness appears to be marginal compared to the dramatic effects that inexpensive NAM had in the mice studies.  Also, we have the skin cancer reduction, acne reduction, and other positive effects at the relatively low and safe 1000 mg/d dosage.

 

wrt IOP reduction to below-normal levels (i.e., significantly less than about 15 mm Hg), I've been doing research during the past 6 months that shows that such reduction can create conditions that promote glaucoma progression by an unexpected route.  I'll return later today when I have more time to present these findings, the relevance being that they may help explain why, at least in some cases, IOP reduction does not always halt glaucoma progression.


Edited by warner, 24 July 2018 - 02:25 PM.


#46 warner

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Posted 25 July 2018 - 02:02 PM

I got caught up yesterday analyzing the latest OCT results.  I also realized that I should probably limit what I post hear since it may become the subject of a published case study, and that we haven't yet completed the study.  So I'll stick to highlighting the most important results, which should be enough for others to at least check, via ONH (optic nerve head) OCTs, whether this problem is of relevance to their glaucoma treatment.

 

The fluid mechanics of the eye rely on small pressure differences near venous pressure levels (8-15 mm Hg).  Small changes to such pressures can wreak havoc on the eye, as exemplified by glaucoma, wherein a rise in IOP (normally about 15), can both reduce perfusion and increase the translaminar pressure gradient (the pressure across the lamina cribrosa), resulting in nerve fiber damage and corresponding vision loss.  In most cases, IOP above normal can be effectively lowered with glaucoma drops, surgery, etc., effectively eliminating the problem and halting glaucoma progression.  However, when glaucomatous damage appears to be present under conditions of normal IOP (NTG = normal tension glaucoma), then IOP lowering would reduce IOP to sub-normal levels, and one might hypothesize that there could be some negative consequences to that, given the effort the eye makes to keep IOP near 15.

 

Having been diagnosed with NTG back in 2011, the strategy has been to lower IOPs below normal (to 12-15 range), and verify that glaucoma progression has been stopped.  Since that time, however, I've had a few instances over the years of fluid accumulation in the middle layers of my retina ("retinoschisis", not retina detachment), typically occurring after bouts of extreme exertion.  In recent years, this phenomenon has been documented as being more likely to occur in glaucoma patients, along with damage to the border of the lamina cribrosa at the optic disk rim.  (I can provide some links to such research for those interested.)

 

The following image shows one of the more extreme examples of this retinoschisis, as well as the apparent source of fluid at a defect in the LC,

 

Attached File  before IOP increase.jpg   50.69KB   1 downloads

 

In the literature, this phenomenon has remained mysterious, and solutions can become quite drastic (various surgical procedures) if the fluid grows to the extent that it threatens the macula (central vision).  However, after a lot of research and some failed experimentation, it finally occurred to me that I should simply try raising IOP modestly to stop fluid influx from the LC defect.  That's because, at normal IOPs, there should be no fluid movement into the retina, since both choroidal fluid and cerebrospinal fluid (CSF) pressures are less than normal IOP.  However, if IOP is reduced below normal, then that may be inviting fluid into the retina from the choroid or CSF.  So here's what happened when IOP was raised from 12-15 to 15-17:

 

Attached File  after IOP increase.jpg   46.2KB   1 downloads

 

That quickly shut down the fluid influx from the defect, as well as leakage of fluid under pressure through the retina at a separate location (not shown) where RNFL loss had been occurring.  In other words, it appears that glaucoma treatment to lower IOPs was making possible the influx of fluid that damaged the RNFL, resulting in additional vision loss.  In next post, I'll discuss some of the implications of this, and how you'd check for this using OCTs.


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#47 warner

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Posted 25 July 2018 - 03:11 PM

- First, this experience provides another reason to look for means other than IOP reduction to slow glaucoma progression, especially if starting with normalish IOPs (thus its relevance to this NAD thread).

 

- It also illustrates the complex etiologies that may be involved with "glaucoma".  In fact, in this case, my vision losses may have more to do with my moderate myopia (also known to contribute to LC and other defects), and/or with past pre-2011 highish IOPs when not as healthy, and nothing at all to do with current normalish IOPs (i.e., I may have been misdiagnosed with NTG back in 2011, although that depends on what one includes in the "NTG" umbrella).

 

What to look for (with OCT scans):

 

- The LC defect often occurs near the inferotemporal region of the ONH disk rim.  And since the defect occurs along the circular disk rim, it is best visualized with an ONH radial (star) scan (i.e., a series of scans done at different angles, all centered over the ONH).

 

- The defect, if leaking fluid, may or may not create significant fluid accumulation (retinoschisis), depending on whether the fluid can find an escape route to the vitreous through the retina and RNFL.  In either case, the release of fluid through the RNFL presumably can damage the RNFL at that location, resulting in corresponding vision loss.  Also, if that's the primary source of RNFL damage, then vision loss might be limited to that single location.  (In fact, one can imagine that such patients, treated with glaucoma drops, resulting in destruction of localized RNFL, would later be declared as "stable" due to the IOP-lowering glaucoma drop treatment!)

 

- A typical RNFL circle scan used to monitor glaucoma will not see the LC defect or fluid accumulation unless the latter is quite large.  Similary, you won't see the fluid accumulation in your visual field (as a faint border near your blind spot when blinking) unless the accumulation is quite extensive.

 

Finally, it's hard to say how common this type of "glaucoma" etiology may be.  Not only have others not been looking for it, but it is relatively difficult to see, especially if it occurs as a smallish leak of fluid to the vitreous, without major accumulation.  Also, it appears that the tissue above the LC defect can block (or at least slow) most fluid influx even when P > IOP, and that some event (such as extreme exertion in my case) is necessary to create the path for more extensive fluid influx to occur, presumably then held open by P > IOP.  But I'd nonetheless suggest, for those with glaucoma, getting an ONH radial scan done, and taking a close look at the optic disk rim for possible fluid entry points, esp. in the inferotemporal region of each eye (or whatever region corresponds to where you've had vision loss.)


Edited by warner, 25 July 2018 - 03:21 PM.

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#48 warner

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Posted 26 July 2018 - 01:54 AM

For those not familiar with OCT radial scans, they are now part of advanced glaucoma tracking systems, such as Heidelberg's Glaucoma Module Premium Edition,

https://business-lou...laucoma-module/

where they're used to measure RNFL thickness changes closer to the disk rim, rather than the more arbitrary location used with RNFL circle scans.  And here's a good video describing the many issues that they are attempting to address,

with the caveat that not many have switched to this new system, probably because its benefits relative to simple RNFL circle scans haven't been shown yet to justify the added complexity and expense.  Anyway, the system does, however, make use of ONH radial scans, as shown in the links, and you can ask your eye specialist to have OCT ONH radial scans done independently of the advanced glaucoma packages, to check for lamina cribrosa defects and fluid influx.


Edited by warner, 26 July 2018 - 01:58 AM.

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#49 smithx

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Posted 20 October 2018 - 07:07 AM

The abstract says:

 

... Collectively, our data indicate that maintaining NAD+ is not sufficient to protect DRG neurons from vincristine- induced axon degeneration, and elevating NMN, by itself, is not sufficient to cause degeneration. Nonetheless, the combination of FK866 and NAR, which bypasses NMN formation, may provide a therapeutic strategy for neuroprotection.

 

 

They are talking about a specific syndrome which occurs during vincristine chemotherapy where NMN goes too high and causes neuronal damage.

In the paper they state:

 

After 16 h of vincristine treatment, NMN levels increased from undetectable to 14.5 ± 6.8 pmol/10**6 cells and NAD+ fell to about 40% of control levels

Perhaps someone else knows how to calculate this. I'm not sure what the "/10**6 cells" portion means in terms of calculations.

 

But 14.5 - 6.8 pmol is 11.7 pmol and if it were 11.7 pmol/ul then that would (unless I'm calculating wrong) be only 3mg/L !

The number of liters of water in a 70Kg adult human is estimated here (http://www.physiolog..._adult_man.html) as 42.

 

If this were correct (and I'm pretty sure it isn't), then this potentially neurotoxic level of NMN would be achieved at 3*42 or only 126mg of NMN!

 

The authors of the paper state that the problem is seen with vincristine, but they do call out NMN as a potential neurotoxin.

 

Could someone else go through this and come up with how many mg of NMN is equivalent to this pathological level (albiet measured in vitro) mentioned in this study?

 

 


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#50 able

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Posted 20 October 2018 - 01:05 PM

The abstract says:

 

 

They are talking about a specific syndrome which occurs during vincristine chemotherapy where NMN goes too high and causes neuronal damage.

In the paper they state:

 

 

This is talking about an excessive buildup of NMN INSIDE THE CELLS, due to the chemotherapy damage that prevents some cells from processing NMN on to NAD. Not from supplementation with NMN.  It is confusing.  

 

What I found disturbing is Dr Brenner trying to confuse this issue even further, while implying NR supplementation would somehow magically have the opposite effect. 

 

He tweeted:

 

Intracellular NMN causes degeneration of damaged neurons. While NR is neuroprotective

 

He implies that somehow NMN supplements will contribute to a buildup of NMN inside cells, while NR supplements would not.

 

Inside the cell, NR-> NMN -> NAD. It is the last step that is faulty in this disease/injured state, so IF NMN supplements made the situation worse, NR supplements would do the same.

 

To me, it looks like a dishonest and opportunistic attempt to confuse people on the science to boost the sagging Chromadex stock price.


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#51 Phoebus

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Posted 20 October 2018 - 02:29 PM

This is a very interesting article. The bottom line is that the nad+ precursor nicotinic acid riboside (NAR) may be safer to use than  NR or NMN.

 

 

yeah, thats the take away. NAR may be the safest most effective NAD precursor yet. But everyone is all in on NMN/NR so maybe too late for NAR? 

 

really interesting 


 

 

To me, it looks like a dishonest and opportunistic attempt to confuse people on the science to boost the sagging Chromadex stock price.

 

Chormadex is a shady company, that does shady things and is ran by shady people. 

 

Thats all I gotta say there 


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#52 Harkijn

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Posted 20 October 2018 - 03:26 PM

I inadvertently derailed the NMN Personal Experience thread by posting about this particular study in which preventing accumulation of NMN is found helpful in preventing  Chemotherapy Induced Peripheral Neuropathy. In fibroblasts. So my main object is here to lighten the moods on the NMN forum and I hope all who want to scrutinize this difficult subject will post here and not on the personal experiences forum.

I attach the full study so everyone can judge for himself.

Attached Files


Edited by Harkijn, 20 October 2018 - 03:28 PM.

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#53 Hebbeh

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Posted 20 October 2018 - 04:43 PM

However, elevating NMN was not sufficient to cause axon degeneration, as neurons treated with NAR and NMNsyn displayed an elevation in NMN but did not degenerate.

 

 



#54 smithx

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Posted 20 October 2018 - 10:41 PM

This is talking about an excessive buildup of NMN INSIDE THE CELLS, due to the chemotherapy damage that prevents some cells from processing NMN on to NAD.

 

Sure, but if NMN at that level can cause neurotoxicity, are we certain that:

 

- 250mg sublingual doesn't translate to at least 140mg in the blood

- That 140mg in the blood doesn't, by diffusion or active transport, translate to at least 11.7 pmol in neurons?

 

If both things may be true, and even though elevated NMN by itself was not enough to immediately cause neurological damage, it would still suggest lower doses more frequently (if supplementing) rather than higher doses at any time.


Edited by smithx, 20 October 2018 - 10:59 PM.

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#55 MikeDC

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Posted 21 October 2018 - 03:21 AM

https://www.ncbi.nlm...mn accumulation

An earlier article on the same issue. Both NMN and NR supplement is bad for injured axons.
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#56 smithx

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Posted 22 October 2018 - 02:42 AM

Wallerian degeneration has been implicated in multiple sclerosis.

 

So this *may* mean that people with MS and perhaps other neuropathies should consider not taking or taking  very small quantities of NMN and NR.

 

https://mssociety.ca...tiple-sclerosis







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