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Offline Delomelanican

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Re: Natural supplements
« Reply #10 on: January 30, 2014, 12:14:43 AM »
Does it surprise you there are no placebo trials, where would this non patentable funding come from, hmmm? Either way, nicotinamide is an endogenous ligand for GABA receptor /benzodiazepine complex which anxiolytic sedative effects are similar to a benzodiazepine. The molecular biology has been presented, just because there are no placebo trials doesn't mean it's ineffective for anxiety. If you'd like, you can go wade through the hundreds of anecdotes on numerous forums. Its also interesting that you promote benzodiazepine usage whilst backing a neurogenesis themed treatment. Benzodiazepines impair neurogenesis.



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Offline insights

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Re: Natural supplements
« Reply #11 on: January 30, 2014, 02:29:22 AM »
Does it surprise you there are no placebo trials, where would this non patentable funding come from, hmmm?

Fishoil and exercise aren't patentable either, yet there are lots of studies showing they work and how they work.

Quote
Either way, nicotinamide is an endogenous ligand for GABA receptor /benzodiazepine complex which anxiolytic sedative effects are similar to a benzodiazepine.


But does it work that way in practice?  Some of the people promoting nicotinamide are also promoting another Russian idea, Picamilon (nicotinoyl-GABA), supposedly GABA in a form which crosses the blood-brain-barrier (BBB), with studies of similar quality supporting it. The only problem is that the whole rationale for it is deeply flawed. It isn't necessary and can't work as advertised.

Firstly, not only does no functioning brain lack GABA, which is a byproduct of the Krebs/citric acid cycle that fuels the brain and is so abundant that the blood-brain-barrier has billions of tiny pumps to remove the excess. The problem isn't a lack of GABA, but a lack of benzo-GABA binding sites and those that exist are less sensitive than normal. Throwing more GABA at them is akin to filling a gas tank to overflowing because the sparkplugs don't work.

Secondly, GABA analogue pharmaceuticals such a gabapentin and pregabalin which do the same thing have almost no impact on GABA, affecting the glutamate system instead. Some people do achieve worthwhile results when taking them, but most don't IME.  The odds of GABA molecules from outside a synapse having any impact on neuro transmission across that synapse is vanishingly small even if it was released by an adjacent synapse.

Quote
If you'd like, you can go wade through the hundreds of anecdotes on numerous forums.

Just as I can find thousands of anecdotes supporting homeopathy preparations, including from the Queen of Britain who is a great believer. They prove nothing. The placebo effect sees many feeling an improvement even when taking homeopathy's distilled water and alcohol. More than enough to have a very profitable business.

Quote
Its also interesting that you promote benzodiazepine usage whilst backing a neurogenesis themed treatment. Benzodiazepines impair neurogenesis.

Yes, they do impair neurogenesis. And I do suggest benzodiazepines despite this. Because they are the lesser of two evils. I'd much rather see someone take benzodiazepines to help them cope with the heightened anxiety produced when antidepressants initially enhance serotonin activity even if it slows the onset of the therapeutic response a little than see them stop taking the med. It is an unfortunate fact of life that most of those prescribed antidepressants stop taking them before they begin to work because of the side-effects, especially the anxiety.

Secondly, while I discourage using benzodiazepines as first line daily anti anxiety meds, some people simply cannot tolerate antidepressants for a variety of reasons, and for them benzodiazepines are better than having nothing.

Then there is the third category of people who only need help with occasional anxiety. For them benzodiazepines are a better bet than taking antidepressants daily. In that role they work well and have few side-effects.

Ian
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NOTE: I'm not a doctor, and particularly not yours, so there may be factors I'm unaware of. Therefore all advice is of a general nature and you should consult your doctor before following any of it, especially before changing med doses.

Offline Delomelanican

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Re: Natural supplements
« Reply #12 on: January 30, 2014, 09:28:30 PM »
Lol... As I said before, the physiological functions of niacinamide have been studied . It is an anti anxiolytic. This isn't some random snake oil bullshit that Has no research backing it as you seem to be suggesting. Please pay attention to the research cited , because you continually fail to acknowledge this.

Everything you are saying is purely subjective . I have posted research backing my claims, where are yours? That's right , you don't have any. You have absolutely no basis to deny any of nicotinamides function in the brain because you have no studies suggesting this. Find me studies that suggest niacinamide doesn't have any anxiolytic effects. If you cannot supply any , then there really is point in continuing to post your own untested and unscientific beliefs.On the contrary the opposite is shown.

http://orthomolecular.org/library/jom/2005/pdf/2005-v20n03-p167.pdf

Research presented has shown that niacinamide does have anxiolytic effects and does impact GABA and serotonin levels in the brain. Niacinamide has a similar action as benzodiazepines, but do not produce dependence or have the negative long term effects associated with benzodiazepine usage.
You want to discredit niacinamide, have research to back up your claims otherwise don't post trying to discredit it when you lack sources.
I'll just wait while you find the research to support your beliefs that niacinamide doesn't have anxiolytic or therapeutic properties.
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Offline insights

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Re: Natural supplements
« Reply #13 on: January 30, 2014, 10:45:19 PM »
Please pay attention to the research cited , because you continually fail to acknowledge this.

I have read it, and I'm not persuaded that it is that robust. About the only research that shows it might have significant affect on benzodiazepine-GABA complex binding sites has been on seizures and then only when administered in large doses by injection.

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Research presented has shown that niacinamide does have anxiolytic effects

The Russian research makes assertions without any robust, i.e. randomized, double blind, placebo control data supporting it.  If you have some, please post it.

Quote
and does impact GABA and serotonin levels in the brain.

Which indicates nothing. Again, no brain lacks GABA. It isn't the problem, the number and sensitivity of BZD-GABA binding sites is [1]. If I remove half the spark plugs in your car will filling the gas tank to overflowing get the engine to run smoothly?

As for serotonin, increasing serotonin increases anxiety, as the millions that have experienced it when first taking serotonergic antidepressants will testify. Serotonergic antidepressants decrease serotonin. Antidepressants such as tianeptine which enhance the removal of serotonin from synapses work at least as well as those that inhibit its removal. The therapeutic effects of antidepressants do not rely on their affect on serotonin levels.

Ian


References:

[1]
Hasler G, Nugent AC, Carlson PJ, et al. (2008)
Altered cerebral gamma-aminobutyric acid type A-benzodiazepine receptor binding in panic disorder determined by [11C]flumazenil positron emission tomography.
Arch Gen Psychiatry. Oct;65(10):1166-75 (Abstract)

Geuze E, van Berckel BN, Lammertsma AA, et al. (2007)
Reduced GABAA benzodiazepine receptor binding in veterans with post-traumatic stress disorder.
Mol Psychiatry. 2008 Jan;13(1):74-83 (Abstract)

Cameron OG, Huang GC, Nichols T, et al. (2007)
Reduced gamma-aminobutyric acid(A)-benzodiazepine binding sites in insular cortex of individuals with panic disorder.
Arch Gen Psychiatry. Jul;64(7):793-800. (Abstract)

Bremner JD, Innis RB, Southwick SM, et al. (2000)
"Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder."
Am J Psychiatry Jul; vol 157(7):1120-6 (Abstract)

Bremner JD, Innis RB, White T, et al (2000)
"SPECT [I-123]iomazenil measurement of the benzodiazepine receptor in panic disorder."
Biol Psychiatry  Jan 15; vol 47(2):96-106 (Abstract)

Malizia AL.  (1999)
"What do brain imaging studies tell us about anxiety disorders? "
J Psychopharmacol Dec; vol 13(4):372-8 (Abstract)

Morimoto K. 1999
Benzodiazepine receptor imaging in the brain: recent developments and clinical validity
Kaku Igaku. May;36(4):307-13. (Abstract)

Malizia AL, Cunningham VJ, Bell CJ, et al. (1998)
"Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET study."
Arch Gen Psychiatry Aug; vol 55(8):715-20 (Abstract)

Tokunaga M, Ida I, Higuchi T, Mikuni M. (1997)
"Alterations of benzodiazepine receptor binding potential in anxiety and somatoform disorders measured by 123I-iomazenil SPECT."
Radiat Med May-Jun; vol 15(3):163-9 (Abstract)

Uchiyama M, Sue H, Fukumitsu N, et al. (1997)
"Assessment of cerebral benzodiazepine receptor distribution in anxiety disorders by 123I-iomazenil-SPECT: comparison to cerebral perfusion scintigraphy by 123I-IMP."
Nippon Igaku Hoshasen Gakkai Zasshi Jan; vol 57(1):41-6 (Abstract)




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NOTE: I'm not a doctor, and particularly not yours, so there may be factors I'm unaware of. Therefore all advice is of a general nature and you should consult your doctor before following any of it, especially before changing med doses.

Offline Delomelanican

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Re: Natural supplements
« Reply #14 on: January 30, 2014, 11:05:04 PM »
Since you didn't read the last study I posted I will summarize a few abstracts. Still waiting on your sources which discredit niacinamide.

"patientwith anorexia nervosa an insufficient sup-ply of vitamin B3 or protein resulted in re-duced urinary levels of the serotonin break-down product, 5-hydroxy-indolacetic acid(5-HIAA).32 The authors of this report pos-tulated that a deficiency of vitamin B3 re-duced the feedback inhibition upon thekynurenine pathway, resulting in more tryp-tophan being diverted to the kynureninepathway, making less substrate available forthe synthesis of serotonin. By contrast, theuse of pharmacological doses of vitamin B3can increase the production of serotonin.33In a rat study, the administration of 20 mgof niacin resulted in increased levels of 5-HIAA and decreased levels of xanthurenicacid via the kynurenine pathway.34 Taki ngpharmacological doses of niacinamide (orany other form of vitamin B3) would increasethe production of serotonin, by divertingmore tryptophan to become substrate forserotonin synthesis"2. Judd LE, Poskitt BL: Pellagra in a patient with aneating disorder. Br J Dermatol, 1991;125:71-72.
33. Gedye A: Hypothesized treatment for migraineusing low doses of tryptophan, niacin, calcium,caffeine, and acetylsalicylic acid. Med Hypoth-eses, 2001;56:91-94.
34. Shibata Y, Nishimoto Y, Takeuchi F, Tatsuma Y:Tryptophan metabolism in various nutritive con-ditions. Acta Vitamin Enzymol, 1973; 29: 190

"Niacinamide modulated spinal cord activity, and had anticonflict, an-ticonvulsant, muscle relaxing and hypnotic effects. The potency of ni-acinamide was found to be equivalent to a highly potent benzodiazepine.Niacinamide had a low affinity to the benzodiazepine-binding site inthe mammalian brain. This low affinity may have been the result of thebinding assay used, or it may have been a reflection that more than onebinding-site existed by which niacinamide exerted its benzodiazepine-like properties."
. Möhler H, Polc C, Cumin R, Pieri L, Kettler R:Nicotinamide is a brain constituent withbenzodiazepine-like actions. Nature, 1979; 278:563-565.

"Niacinamide antagonized the effects of diazepam, therefore interactingwith the benzodiazepine receptor in vivo. However, niacinamide did notmimic the benzodiazepine properties of diazepam when tested withthe rat head-turning model. Niacinamide probably does havebenzodiazepine-like properties at different benzodiazepine receptor sitesin the CNS, but its effects are unrelated to the actions of gamma-aminobutyric acid (GABA)."Slater P,  Longman DA:  Effects of diazepam andmuscimol on GABA-mediated neurotrans-mission: interactions with inosine and nicoti-namide. Life Sci, 1979; 25: 1963-1967.


"Niacinamide had a qualitatively similar effect to that of diazepam. It wasconcluded that niacinamide exerted its effects by influencing the turnoverof serotonin, noradrenaline (norepinephrine), dopamine and GABA in thoseareas of the brain thought to be unbalanced in anxiety." Kennedy B, Leonard BE: Similarity between theaction of nicotinamide and diazepam on neu-rotransmitter metabolism in the rat. BiochemSoc Trans, 1980; 8: 59-60.



"Niacinamide could possibly be a competitive antagonist for thebenzodiazepine receptor since it prevented the binding of kynurenineto the benzodiazepine receptor. It was further postulated that this ac-tion was more likely of central origin than peripheral origin. It couldnot be determined if niacinamide’s action was indeed related to itsoccupation of the benzodiazepine receptor."
28. Lapin IP: Nicotinamide, inosine and hypoxan-thine, putative endogenous ligands of thebenzodiazepine receptor, opposite to diazepamare much more effective against kynurenine-induced seizures than against pentylenetetra-zol-induced seizures. Pharmacol BiochemBehav, 1981; 14: 589-593.


"Niacinamide was structurally dissimilar to the benzodiazepine receptors.Niacinamide did not act as a specific ligand for the benzodiazepinereceptor, but instead had a weak binding affinity for the receptor."

Markin RS, Murray WJ: Searching for the en-dogenous benzodiazepine using the graph theo-retical approach. Pharm Res, 1988;5:408-412.

"
Niacinamide and its analogs possessed properties similar tobenzodiazepines at various zones of the cerebral cortex by influencingthe GABA-ergic system."
"30. Akhundov RA, Dzhafarova SA, Aliev AN: Thesearch for new anticonvulsant agents based onnicotinamide. Eksp Klin Farmakol, 1992;55:27-29.



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Offline insights

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Re: Natural supplements
« Reply #15 on: January 30, 2014, 11:21:47 PM »
Since you didn't read the last study I posted I will summarize a few abstracts. Still waiting on your sources which discredit niacinamide.

My problem is that there aren't any supporting its credibility with the degree of rigour there is for the other supplements. Until you produce them, I'm not about to recommend niacinamide. I'm not into zealotry, just cold hard facts and these studies don't have enough facts. You want to shout about it from the rooftops, that's fine, but don't demand I do.

Ian

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NOTE: I'm not a doctor, and particularly not yours, so there may be factors I'm unaware of. Therefore all advice is of a general nature and you should consult your doctor before following any of it, especially before changing med doses.

Offline Delomelanican

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Re: Natural supplements
« Reply #16 on: January 30, 2014, 11:24:23 PM »
Really, increasing serotonin increases anxiety?

Increased blood serotonin concentrations are correlated with reduced tension/anxiety in healthy postpartum lactating women.

http://www.ncbi.nlm.nih.gov/pubmed/23541877

Associations between whole-blood serotonin and subjective mood in healthy male volunteers.
http://www.ncbi.nlm.nih.gov/pubmed/15927346/


Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin 1A receptors.
http://www.ncbi.nlm.nih.gov/pubmed/15469887

The role of cortical serotonin in anxiety and locomotor activity in Wistar rat
http://www.ncbi.nlm.nih.gov/pubmed/19331468

How to increase serotonin in the human brain without drug
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077351/

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Offline Delomelanican

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Re: Natural supplements
« Reply #17 on: January 30, 2014, 11:30:41 PM »
Since you didn't read the last study I posted I will summarize a few abstracts. Still waiting on your sources which discredit niacinamide.

My problem is that there aren't any supporting its credibility with the degree of rigour there is for the other supplements. Until you produce them, I'm not about to recommend niacinamide. I'm not into zealotry, just cold hard facts and these studies don't have enough facts. You want to shout about it from the rooftops, that's fine, but don't demand I do.

Ian

The problem is you have provided no sources, or references which disagree with niacinamide's biochemical and therapeutical effects. I rely on scientific research as opposed to conjecture and opinions backed by an unqualified individual. You are not a neuroscientist , and you have not provided sources to discredit niacinamide's actions.

Case studies were linked , along with the outlined biochemical and postulated mechanism of actions. Numerous different studies/ researchers are cited .
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Offline anxious J

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Re: Natural supplements
« Reply #18 on: February 03, 2014, 08:02:25 PM »
Really, increasing serotonin increases anxiety?

Increased blood serotonin concentrations are correlated with reduced tension/anxiety in healthy postpartum lactating women.

http://www.ncbi.nlm.nih.gov/pubmed/23541877

Associations between whole-blood serotonin and subjective mood in healthy male volunteers.
http://www.ncbi.nlm.nih.gov/pubmed/15927346/


Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin 1A receptors.
http://www.ncbi.nlm.nih.gov/pubmed/15469887

The role of cortical serotonin in anxiety and locomotor activity in Wistar rat
http://www.ncbi.nlm.nih.gov/pubmed/19331468

How to increase serotonin in the human brain without drug
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077351/

Do you take this yourself then ? And what Dosage Do u Recomand for Anxiety Control ??
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Offline johnathonm

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Re: Natural supplements
« Reply #19 on: February 05, 2014, 02:10:35 PM »
Does it surprise you there are no placebo trials, where would this non patentable funding come from, hmmm?

Fishoil and exercise aren't patentable either, yet there are lots of studies showing they work and how they work.

Quote
Either way, nicotinamide is an endogenous ligand for GABA receptor /benzodiazepine complex which anxiolytic sedative effects are similar to a benzodiazepine.


But does it work that way in practice?  Some of the people promoting nicotinamide are also promoting another Russian idea, Picamilon (nicotinoyl-GABA), supposedly GABA in a form which crosses the blood-brain-barrier (BBB), with studies of similar quality supporting it. The only problem is that the whole rationale for it is deeply flawed. It isn't necessary and can't work as advertised.

Firstly, not only does no functioning brain lack GABA, which is a byproduct of the Krebs/citric acid cycle that fuels the brain and is so abundant that the blood-brain-barrier has billions of tiny pumps to remove the excess. The problem isn't a lack of GABA, but a lack of benzo-GABA binding sites and those that exist are less sensitive than normal. Throwing more GABA at them is akin to filling a gas tank to overflowing because the sparkplugs don't work.

Secondly, GABA analogue pharmaceuticals such a gabapentin and pregabalin which do the same thing have almost no impact on GABA, affecting the glutamate system instead. Some people do achieve worthwhile results when taking them, but most don't IME.  The odds of GABA molecules from outside a synapse having any impact on neuro transmission across that synapse is vanishingly small even if it was released by an adjacent synapse.

Quote
If you'd like, you can go wade through the hundreds of anecdotes on numerous forums.

Just as I can find thousands of anecdotes supporting homeopathy preparations, including from the Queen of Britain who is a great believer. They prove nothing. The placebo effect sees many feeling an improvement even when taking homeopathy's distilled water and alcohol. More than enough to have a very profitable business.

Quote
Its also interesting that you promote benzodiazepine usage whilst backing a neurogenesis themed treatment. Benzodiazepines impair neurogenesis.

Yes, they do impair neurogenesis. And I do suggest benzodiazepines despite this. Because they are the lesser of two evils. I'd much rather see someone take benzodiazepines to help them cope with the heightened anxiety produced when antidepressants initially enhance serotonin activity even if it slows the onset of the therapeutic response a little than see them stop taking the med. It is an unfortunate fact of life that most of those prescribed antidepressants stop taking them before they begin to work because of the side-effects, especially the anxiety.

Secondly, while I discourage using benzodiazepines as first line daily anti anxiety meds, some people simply cannot tolerate antidepressants for a variety of reasons, and for them benzodiazepines are better than having nothing.

Then there is the third category of people who only need help with occasional anxiety. For them benzodiazepines are a better bet than taking antidepressants daily. In that role they work well and have few side-effects.

Ian

In the states there is always Lovaza... :p
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