5 replies to this topic

[resveratrol_guy]

Can anyone cite literature which provides even an order-of-magnitude answer to this question? I don't care if you're a Nobel laureate or an amateur. All I'm looking for here is a citation. The answer would be expressed in units of NGF mass per brain mass or volume.

 

Why we should we care?

 

Well, it seems that we've identified 2 practical ways of increasing intracranial NGF: (1) intranasal insufflation of (beta)NGF saline solution and (2) consumption of xanthohumol, generally as one component of ashitaba and its extracts. The problem is that #1 is very expensive, degrades rapidly, and is mostly wasted; while #2 can increase brain NGF density by 20% in a matter of days in rodents, but we don't know if this is actually superior to #1. In other words, despite being an inefficient route of administration, #1 might be doubling or tripling the amount of free NGF in the CSF. Without having any idea of the amount of NGF to begin with, all we can say is that so-many nanograms probably penetrate the olfactory nerve in a given insufflation session. But we can't compare the two in a quantitative manner.

 

Personally, I've started drinking ashitaba chalcones (read: xanthohumol) in the past week and noticed significant neurological benefits, but I'm stuck wondering whether this is simply a latent benefit of my betaNGF insufflation experience, which might be expected to occur based on typical neuroregeneration timelines in the literature. Or maybe it's all down to something else. The quantification of gross NGF influx in both cases would go a long way toward answering this question.

 

[resveratrol_guy]

I found this paper in which a Korean team carried out measurements of NGF in human saliva. While it doesn't directly answer this question, it does presumably provide a mechanism by which to answer the following question: To what extent is substance X raising my NGF secretion? Granted, the degree of secretion in the salivary glands would probably be much more than in the brain, as any substance which increases such secretion would naturally exert most of its influence in the mouth, where it would presumably be ingested. Still, I think it's a reasonable hypothesis that larger changes in salivary NGF correlate with larger changes in brain NGF; the relationship is likely monotonic, assuming that the substance is known to cross the BBB.

 

If you think about it, this sort of saliva test is of great utility to us as nootropic analysts: in theory, given enough measurements, we should be able to determine how much substance X raises brain NGF per dollar spent. Granted, there are plenty of other targets such as BDNF, AMPK, etc. that we care about, which might not be amenable to this method, but this is much better than trying to guess via brain games how strong a signal we've actually sent. I doubt whether the Koreans actually realized the economic value of their approach!

 

[gamesguru]

Looks like slightly less than 5μg/kg NGF.  Column #1 is untreated/control(table 5):

 

 

Obviously rats/mice, not humans:

 

 

And as for BDNF, strongly region-dependent, reportedly ~60x NGF, or around 300μg/kg BDNF:

 

 

Using the ELISA kit from Millipore (USA) (rats and pigs) and Promega (rats, pigs, mice), BDNF levels could be measured in whole-blood samples from rats, but not in whole blood from mice and pigs (Fig. 2 a). In plasma, we were able to measure BDNF in rats and pigs, but not in mice (Fig. 2b). In the hippocampus, a high-expression region for BDNF, BDNF was measurable in all three species when using the Millipore ELISA kit for rat and pig samples and the Promega ELISA kit for mouse samples. The hippocampal BDNF levels in rats and mice were comparable, while hippocampal BDNF levels in pigs were 5-fold higher (636.1±158, 559.9±171.2 and 3415±1228 pg BDNF/mg total protein for rats, mice and pigs, respectively) (Fig. 2 c).

(there is no larger figure, sorry)

Fig. 2

Brain-derived neurotrophic factor (BDNF) levels in (a) blood, (b) plasma and (c) hippocampus in rats, pigs and mice. (a) BDNF levels in whole blood could be measured in rats, but were undetectable in mice and pigs. (b) In plasma, we were able to measure BDNF in rats and pigs, but not in mice. (c) In hippocampus, pigs showed 4- to 5-fold higher BDNF concentrations than rats and mice [let's hope humans show even more!]. n.d., Non-detectable. Error bars indicate s.e.m.

[chrisp2]

What Ashitaba product are you taking?  (And how much?)

 

I'm upping my dose of Lion's Mane, but am intrigued about Ashitaba.

 

Swanson (as I'm sure you know) has a standardized Xanthohumol product available...

[resveratrol_guy]

Looks like slightly less than 5μg/kg NGF.  Column #1 is untreated/control(table 5):

 

Congratulations! You have just passed an extremely challenging Turing test.

 

So yes, if we say that the human brain weighs roughly a kg, then NGF densities on the order of 5 pg/mg would expand to 5 ug. Furthermore, even accounting for metabolic differences (which I don't think apply, in this case) -- and a factor of 2 for possible NGF-vs-betaNGF confusion -- would suggest at least 1 ug betaNGF equivalent brain content. This data point is gold because it's informative as to dose-vs-background information -- in other words, how big a splash should we attempt to make?

 

As it happens, the human intracranial NGF injection trial circa 2000 involved anywhere from 0.5 to 6 milligrams to the hippocampus. Your data point only increases my confidence that this was vastly superfluous (and largely wasted) on the one hand, but suffered from lack of frequency (a maximum of 3 injections) on the other. Rita-Levi Montalcini's NGF eye drops probably delivered more useful NGF over her many years of use, than those injections. And yet, as discussed in the NGF spray thread, we have a 2015 paper showing conclusively that the patients who received the injections had more neurons in the affected area, than those who did not, relative to baseline. Which is all to say that chronic low dose betaNGF should be seriously considered as an Alzheimer's prophylactic (except that it won't be, because it's not patentable, which relegates it to the realm of DIY).

Edited by resveratrol_guy, 11 October 2015 - 02:25 PM.

[resveratrol_guy]

What Ashitaba product are you taking?  (And how much?)

 

I'm upping my dose of Lion's Mane, but am intrigued about Ashitaba.

 

Swanson (as I'm sure you know) has a standardized Xanthohumol product available...

 

I'm drinking liquid ashitaba chalconoid sap (read: xanthoangelol), 20 mL a day. I also take a heaping teaspoon of lion's mane. I would say, thus far, that betaNGF generated more pronounced short term effects than either of them, insofar as cognition is concerned. The most obvious effect from the ashitaba has been hunger control, although in my case I'm calorically restricted and really don't fancy losing any more weight.

 

I discussed the chemistry details on 10/8/2015 over here. Above all, see the note about 8-prenylnaringenin contamination of xanthohumol supplements.
 

Edited by resveratrol_guy, 11 October 2015 - 02:46 PM.