34 replies to this topic

[xks201]

Not too worried about something being off topi. To an idiot it's all off topic.

[Flex]

Thx

[Phoenicis]

This is an excellent review of what Nicotinamide has been used for so far and even covers possible doses in humans:

 

Haar et al., The Use of Nicotinamide as a Treatment for Experimental Traumatic Brain Injuryand Stroke: A Review and Evaluation.Clinic Pharmacol Biopharmaceut S1: 005.doi:10.4172/2167-065X.S1-005

 

That review cites a study showing that in mice doses of 500 mg/kg have been shown to "increase levels of ATP and NAD+as well as reduce PARP activation and DNA fragmentation". According to the review, a human dose of 3,000mg translates into about 35-50 mg/kg in a mouse (depending on weight). So that means your dose is about 10 times less than the dose used for rodents in the study.

 

I don't think that means much though, because this study on AD model mice showed that 40 microgram/g/day (40mg/kg/day) doses in mice maintained SIRT1 proteins at a higher level, elevated NAD+ and improved brain bioenergetics by improving mitochondrial dynamics, autophagy-lysosome procession, CREB, synaptic plasticity, learning and memory. That dose seems to translate almost exactly into a human dose of 3g/day.

 

Nam is a weak inhibitor of PARP1, Nam is an end-product of NAD+ metabolism by PARP1 and that is why it can act as an inhibitor. [1] NAD+ repletion rescues neurons from death induced by PARP1, but does not inhibit the enzyme. [1]

 

The review does also mention that old mice showed low responses to Nam compared to young mice in some studies.

 

 

 

"Evidence from animal models suggests that NAM treatment may be an interesting avenue to explore in clinical populations of TBI and stroke. It is naturally occurring and inexpensive. It has shown considerable improvements of deficits in rodent models on multiple types of injury. It even has a reasonable time-window for administration (up to 4-8 hours in the rodent). With regards to dosing in rodent models of TBI, it was shown that the 50 mg/kg dose showed considerable behavioral effects [47,49] and that to exhibit maximal recovery, a dose closer to 150 mg/kg per day may be necessary [50]. In rodent models of stroke, it was shown that doses as low as 125-250 mg/kg could have some effect [52,56], but that maximal recovery would be exhibited at 500 mg/kg [53].

 

However, it remains to be seen whether a dose of 150 mg/kg or more would be necessary to see improvement in humans and whether it would be tolerated with minimal side-effects.In humans, doses as high as 80 mg/kg have been shown to be tolerated reasonably well [78,79] and one study showed no detrimental effects of long-term NAM dosing at 50 mg/kg [80]. Even considering potential toxicity issues, NAM may exert reasonable protective effects following human TBI. It may be a particularly interesting target to be used in combination therapies as it is a relatively easily administered drug and is likely to have very few negative interactions with other drugs.However, its use may be limited to younger populations due to the negative effects seen in aged populations.

 

[...]

 

One is the question of the upper limits for human toxicity of NAM. Very high doses are tolerated in rats, but can have undesirable side-effects in humans, with nausea being the primary complaint [79]. Many studies looking at disorders such as diabetes and skin conditions have had an upper limit of 3000 mg/day for humans, translating into roughly a 35-50 mg/kg dose (depending on weight) [81]. However,side-effects such as nausea may be tolerable when considering the damage associated with TBI, particularly if looking at a short-term treatment. Another question requiring investigation is the long-term efficacy of NAM. A large portion of the studies discussed above were conducted in the acute period (24 hours to 7 days) following the injury event and the ones that assessed function in the chronic period were rarely longer than 30 days. While strong effects were seen in the early post-injury period, it remains to be seen whether or not there are improvements in long-term functional recovery. However,even if NAM is found only to accelerate recovery, it still may be a good candidate for investigation in clinical trials. One final question requiring investigation is the efficacy of NAM in older populations.This is of particular interest since the risk for stroke increases with age and aged populations are one of the larger at-risk groups for TBI. The single study that evaluated aged populations in rats showed severely reduced effects of NAM treatment [64]. However, this finding needs to be further investigated to determine whether or not NAM is only effective in certain populations"

→ source (external link)

 

[1] Alano et al., NAD+ Depletion is Necessary and Sufficient for PARP-1-Mediated Neuron Death, 2010 J Neurosci. 30(8).

Edited by Phoenicis, 05 August 2014 - 02:14 AM.

[Phoenicis]

Looks like the first link to the review isn't working, you can click on the link at the bottom of the yellow box instead.

 

Also I think I may have confused the 3000mg dose as translating into 35-50mg/kg in mice. It looks like they were obviously converting between two human dosing measurements. I'm not sure but I think converting from those mouses doses into human doses could result in extremely large doses ranging from 10-90g/day and I obviously am not suggesting that anyone take such a large dose. 

 

It looks like a human dose of 80mg/kg/day is highest that's been tested and found to be clinically tolerated. That's about 5.5g/day for a 70kg person.

Edited by Phoenicis, 05 August 2014 - 03:10 AM.

[Phoenicis]

This study had poor result for 14month old mice (middle aged?) and seemed to attribute this to their age. Conversely in the Alzheimers model mice study, they were 13 months old and showed great results. NAMPT and the circadian cycle need fixing, that's for sure.

 

NR could be added to given extra reassurance, it's a shame that the company that makes it raised their prices dramatically. They also bought up process patents from unis, so I'm not sure we'll be seeing much competition.