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Supplements for Neuropathy
Re: Supplements for Neuropathy
In article <7o-dnaTvdI6VKdnVnZ2dnUVZ_sTinZ2d@earthlink,com >,
Marshall Price <d021317c@yahoo,com > wrote:
> Bob Arnold wrote:
> > In article <-5mdnfjWNLwkbbLVnZ2dnUVZ_tHinZ2d@earthlink,com >,
> > Marshall Price <d021317c@yahoo,com > wrote:
> >
> >> jay wrote:
> >>>>> What supplements provide relief from polyneuropathy?
> >>>> Nobody seems to have mentioned the most obvious one, thiamine!
> >>> My multi-vitamin says one tablet has 75mg of Thiamine HCl (5000%). Is
> >>> this too much?
> >> It sounds like too much to me, but many people take that much, or
> >> more. The multi-vitamin-mineral tablets I take afford about one DV
> >> (that is, 100%) for each vitamin and mineral, except for the major
> >> minerals. (For thiamine, that means 1.5mg.)
> >>
> >> But I also take a few vitamins "on the side" for specific purposes,
> >> and I expect to get most of my nutrients from food, not to mention the
> >> zillions of honored guest symbiotes in my digestive tract. I'd be lost
> >> without them. ;-)
> >
> >
> > It's not too much. I take 540mg Thiamine per day.
>
> The general consensus suggests that taking that much thiamine may
> lead to relative deficiencies of the other water-soluble vitamins. Do
> you take any of them, and if not, are you looking out for deficiency
> symptoms?
Yes, I take fairly high doses of the rest of the b-complex.
> (Personally, I take lots of niacin [B3] and pyridoxine [B6], mainly
> to keep my blood lipid profile healthy, along with riboflavin [B2] to
> balance the pyridoxine, and a Centrum-like tablet for general
> "insurance" purposes. But I do experiment, too.)
In article <7o-dnaTvdI6VKdnVnZ2dnUVZ_sTinZ2d@earthlink,com >,
Marshall Price <d021317c@yahoo,com > wrote:
> Bob Arnold wrote:
> > In article <-5mdnfjWNLwkbbLVnZ2dnUVZ_tHinZ2d@earthlink,com >,
> > Marshall Price <d021317c@yahoo,com > wrote:
> >
> >> jay wrote:
> >>>>> What supplements provide relief from polyneuropathy?
> >>>> Nobody seems to have mentioned the most obvious one, thiamine!
> >>> My multi-vitamin says one tablet has 75mg of Thiamine HCl (5000%). Is
> >>> this too much?
> >> It sounds like too much to me, but many people take that much, or
> >> more. The multi-vitamin-mineral tablets I take afford about one DV
> >> (that is, 100%) for each vitamin and mineral, except for the major
> >> minerals. (For thiamine, that means 1.5mg.)
> >>
> >> But I also take a few vitamins "on the side" for specific purposes,
> >> and I expect to get most of my nutrients from food, not to mention the
> >> zillions of honored guest symbiotes in my digestive tract. I'd be lost
> >> without them. ;-)
> >
> >
> > It's not too much. I take 540mg Thiamine per day.
>
> The general consensus suggests that taking that much thiamine may
> lead to relative deficiencies of the other water-soluble vitamins. Do
> you take any of them, and if not, are you looking out for deficiency
> symptoms?
Yes, I take fairly high doses of the rest of the b-complex.
> (Personally, I take lots of niacin [B3] and pyridoxine [B6], mainly
> to keep my blood lipid profile healthy, along with riboflavin [B2] to
> balance the pyridoxine, and a Centrum-like tablet for general
> "insurance" purposes. But I do experiment, too.)
Re: Supplements for Neuropathy
In article
<739091c9-61a5-4257-844a-cbc2e72bd0e6@r66g2000hsg.googlegroups,com >,
jay <jaym1212@hotmail,com > wrote:
> What supplements provide relief from polyneuropathy? Would the
> following be the most important? Already doing paleo-type diet,
> moderate exercise and multi-vitamins.
>
> Benfotiamine
> Vitamin B6 (P-5-P)
> R-Lipoic Acid
> NAC
> Acetyl-L-Carnitine
I've had neuropathy too.
A couple of points:
+ Stoke the GABA channel. Homocysteine blocks it, so anything that
lowers homocysteine should work - methyl-B12, folic acid, betaine, SAMe,
creatine, choline. (Insulin resistance interferes with GABA receptor
function, by the way.) You can boost GABA production per se with
magnesium, taurine and a few of the previously mentioned items.
Magnesium also antagonizes the actions of Substance P.
+ Check for molybdenum deficiency, which is common in diabetes and
depresses metallothionein synthesis. Also check for metals poisoning
and other toxicities.
+ Intermittent fasting - eat as much as you want the first day, then
fast the second day and repeat. Much easier than calorie restriction
and doesn't require expert nutritional supervision.
+ Acetyl-l-carnitine upregulates the low affinity nerve growth factor
receptor (p75NGFR) - thus its limited ability to regrow peripheral
nerves. p75 accelerates growth in some cancers (e.g. gliomas) and
shrinks other cancers. Make sure you understand what ALCAR is doing to
your cancer risk. (A high enough dose should also send your hair
follicles into catagen.)
+ Butyrate (~3g daily). It's an HDAC inhibitor produced in the gut
from fiber. It requires carnitine for absorption and metabolization.
Butyrate directly induces autophagy.
+ If you're taking lipoic acid, take plenty of biotin.
+ For pain relief, low-dose naltrexone blocks dependency, increases
analgesia and reduces tolerance/addiction when used in conjunction with
standard opioids.
+ Green tea extract (analgesia via PPARalpha agonism, maybe PKC
inhibition).
+ Atrial natriuretic factor (produced via certain types of heat stress).
+ gluatmine (HO-1)
+ Vitamin D3 (via HIF-1?).
+ DHEA (like carnitine, it's a PKC inhibitor and thus raises the pain
threshold).
+ Death of gut bacteria can lower the pain threshold [PMID 17159985].
+ Cox-2 inhibitors can actually induce autoimmunity and sometimes
sensitize nerves to pain.
In article
<739091c9-61a5-4257-844a-cbc2e72bd0e6@r66g2000hsg.googlegroups,com >,
jay <jaym1212@hotmail,com > wrote:
> What supplements provide relief from polyneuropathy? Would the
> following be the most important? Already doing paleo-type diet,
> moderate exercise and multi-vitamins.
>
> Benfotiamine
> Vitamin B6 (P-5-P)
> R-Lipoic Acid
> NAC
> Acetyl-L-Carnitine
I've had neuropathy too.
A couple of points:
+ Stoke the GABA channel. Homocysteine blocks it, so anything that
lowers homocysteine should work - methyl-B12, folic acid, betaine, SAMe,
creatine, choline. (Insulin resistance interferes with GABA receptor
function, by the way.) You can boost GABA production per se with
magnesium, taurine and a few of the previously mentioned items.
Magnesium also antagonizes the actions of Substance P.
+ Check for molybdenum deficiency, which is common in diabetes and
depresses metallothionein synthesis. Also check for metals poisoning
and other toxicities.
+ Intermittent fasting - eat as much as you want the first day, then
fast the second day and repeat. Much easier than calorie restriction
and doesn't require expert nutritional supervision.
+ Acetyl-l-carnitine upregulates the low affinity nerve growth factor
receptor (p75NGFR) - thus its limited ability to regrow peripheral
nerves. p75 accelerates growth in some cancers (e.g. gliomas) and
shrinks other cancers. Make sure you understand what ALCAR is doing to
your cancer risk. (A high enough dose should also send your hair
follicles into catagen.)
+ Butyrate (~3g daily). It's an HDAC inhibitor produced in the gut
from fiber. It requires carnitine for absorption and metabolization.
Butyrate directly induces autophagy.
+ If you're taking lipoic acid, take plenty of biotin.
+ For pain relief, low-dose naltrexone blocks dependency, increases
analgesia and reduces tolerance/addiction when used in conjunction with
standard opioids.
+ Green tea extract (analgesia via PPARalpha agonism, maybe PKC
inhibition).
+ Atrial natriuretic factor (produced via certain types of heat stress).
+ gluatmine (HO-1)
+ Vitamin D3 (via HIF-1?).
+ DHEA (like carnitine, it's a PKC inhibitor and thus raises the pain
threshold).
+ Death of gut bacteria can lower the pain threshold [PMID 17159985].
+ Cox-2 inhibitors can actually induce autoimmunity and sometimes
sensitize nerves to pain.
Re: Supplements for Neuropathy
Forgot two strategic approaches specific to diabetes:
1) Raise the NAD+/NADH ratio. Niacinamide or niacin. This ratio
governs blood flow and directly affects neuropathy.
2) Inhibit GSK-3b. This should help alleviate insulin resistance.
Also, citrulline supplementation might be a better idea than arginine
for increasing nitric oxide. BH4 might also be helpful if you have high
homocysteine/OOHO- levels - although the increased catecholamine
synthesis by BH4 might actually enhance your sensitivity to pain even as
it improves your oxidative status.
Forgot two strategic approaches specific to diabetes:
1) Raise the NAD+/NADH ratio. Niacinamide or niacin. This ratio
governs blood flow and directly affects neuropathy.
2) Inhibit GSK-3b. This should help alleviate insulin resistance.
Also, citrulline supplementation might be a better idea than arginine
for increasing nitric oxide. BH4 might also be helpful if you have high
homocysteine/OOHO- levels - although the increased catecholamine
synthesis by BH4 might actually enhance your sensitivity to pain even as
it improves your oxidative status.
Re: Supplements for Neuropathy
Kofi wrote:
> Forgot two strategic approaches specific to diabetes:
>
> 1) Raise the NAD+/NADH ratio. Niacinamide or niacin. This ratio
> governs blood flow and directly affects neuropathy.
>
> 2) Inhibit GSK-3b. This should help alleviate insulin resistance.
>
> Also, citrulline supplementation might be a better idea than arginine
> for increasing nitric oxide. BH4 might also be helpful if you have high
> homocysteine/OOHO- levels - although the increased catecholamine
> synthesis by BH4 might actually enhance your sensitivity to pain even as
> it improves your oxidative status.
There's a bit of controversy over whether niacinamide and "non-flush"
or time-release forms of vitamin B-3 are as effective as plain niacin
(nicotinic acid) for lowering blood triglycerides, total cholesterol,
and LDL cholesterol, and raising HDL cholesterol. But there's no
question that niacin is quite effective, and the only complaint against
it is that it causes the famous niacin flush. But if you're familiar
with it and prepared for it, it's not only "no problem," but it can be
quite pleasant.
It makes me feel contented, healthy, and invigorated. It makes me
want to get moving, yawn, stretch, wash my face, take a shower, brush my
teeth, scrub my back, touch my toes, and so on.
Thiamine is a well-known tonic, but for me, at least, niacin acts as
a tonic, too.
About insulin resistance. In my reading about fasting, it seems that
almost everybody who advocates fasting (in any form) brings up insulin
resistance sooner or later, claiming that fasting cures it.
Since I personally fasted and lost a lot of weight at the same time,
without the benefit of a doctor's supervision, I don't know whether I
had insulin resistance, or if so, whether fasting or weight loss cured
it. But I can say it was the fear of metabolic syndrome which prompted
me, and with my waist down to thirty inches (max), I doubt I've got it,
but still suspect I'm prone to it.
All right. Enough anecdotal nonsense for now! :-)
--
Marshall Price of Miami
Known to Yahoo as d021317c
Kofi wrote:
> Forgot two strategic approaches specific to diabetes:
>
> 1) Raise the NAD+/NADH ratio. Niacinamide or niacin. This ratio
> governs blood flow and directly affects neuropathy.
>
> 2) Inhibit GSK-3b. This should help alleviate insulin resistance.
>
> Also, citrulline supplementation might be a better idea than arginine
> for increasing nitric oxide. BH4 might also be helpful if you have high
> homocysteine/OOHO- levels - although the increased catecholamine
> synthesis by BH4 might actually enhance your sensitivity to pain even as
> it improves your oxidative status.
There's a bit of controversy over whether niacinamide and "non-flush"
or time-release forms of vitamin B-3 are as effective as plain niacin
(nicotinic acid) for lowering blood triglycerides, total cholesterol,
and LDL cholesterol, and raising HDL cholesterol. But there's no
question that niacin is quite effective, and the only complaint against
it is that it causes the famous niacin flush. But if you're familiar
with it and prepared for it, it's not only "no problem," but it can be
quite pleasant.
It makes me feel contented, healthy, and invigorated. It makes me
want to get moving, yawn, stretch, wash my face, take a shower, brush my
teeth, scrub my back, touch my toes, and so on.
Thiamine is a well-known tonic, but for me, at least, niacin acts as
a tonic, too.
About insulin resistance. In my reading about fasting, it seems that
almost everybody who advocates fasting (in any form) brings up insulin
resistance sooner or later, claiming that fasting cures it.
Since I personally fasted and lost a lot of weight at the same time,
without the benefit of a doctor's supervision, I don't know whether I
had insulin resistance, or if so, whether fasting or weight loss cured
it. But I can say it was the fear of metabolic syndrome which prompted
me, and with my waist down to thirty inches (max), I doubt I've got it,
but still suspect I'm prone to it.
All right. Enough anecdotal nonsense for now! :-)
--
Marshall Price of Miami
Known to Yahoo as d021317c
Re: Supplements for Neuropathy; counteracting niacin flush
> Kofi wrote:
> > Forgot two strategic approaches specific to diabetes:
> >
> > 1) Raise the NAD+/NADH ratio. Niacinamide or niacin. This ratio
> > governs blood flow and directly affects neuropathy.
...
> There's a bit of controversy over whether niacinamide and "non-flush"
> or time-release forms of vitamin B-3 are as effective as plain niacin
> (nicotinic acid) for lowering blood triglycerides, total cholesterol,
> and LDL cholesterol, and raising HDL cholesterol. But there's no
> question that niacin is quite effective, and the only complaint against
> it is that it causes the famous niacin flush. But if you're familiar
> with it and prepared for it, it's not only "no problem," but it can be
> quite pleasant.
I didn't suggest niacinamide for any of these reasons. It directly
produces NAD+ and thus raises the NAD+/NADH ratio. This has a
beneficial effect on local blood flow, reducing pressure on nerves.
The authors below seem oblivious to the beneficial role that PGD2 plays
in the effects of niacin [PMID 15037193]. FYI, niacin raises PGD2,
raises 15d-PGJ2 which activates PPARgamma. PPARgamma agonists raise
trans-glutaminase levels - and Celiacs make antibodies to
trans-glutaminase.
: Br J Pharmacol. 2008 Apr;153(7):1382-7. Epub 2008 Jan 28.
The flavonoid luteolin inhibits niacin-induced flush.
Papaliodis D, Boucher W, Kempuraj D, Theoharides TC.
Laboratory for Molecular Immunopharmacology and Drug Discovery,
Department of Pharmacology and Experimental Therapeutics, Tufts
University School of Medicine, Tufts-New England Medical Center, Boston,
MA, USA.
BACKGROUND AND PURPOSE: Sustained release niacin effectively lowers
serum cholesterol, LDL and triglycerides, while raising HDL. However,
75% of patients experience cutaneous warmth and itching known as flush,
leading to discontinuation. Acetylsalicylic acid (aspirin) reduces this
flush only by about 30%, presumably through decreasing prostaglandin D2
(PGD2). We investigated whether niacin-induced flush in a rat model
involves PGD2 and 5-HT, and the effect of certain flavonoids.
EXPERIMENTAL APPROACH: Three skin temperature measurements from each ear
were recorded with an infrared pyrometer for each time point immediately
before i.p. injection with either niacin or a flavonoid. The temperature
was then measured every 10 min for 60 min. KEY RESULTS: Niacin (7.5 mg
per rat, equivalent to a human dose of 1750 mg per 80 kg) maximally
increased ear temperature to 1.9+/-0.2 degrees C at 45 min. Quercetin
and luteolin (4.3 mg per rat; 1000 mg per human), administered i.p. 45
min prior to niacin, inhibited the niacin effect by 96 and 88%,
respectively. Aspirin (1.22 mg per rat; 325 mg per human) inhibited the
niacin effect by only 30%. Niacin almost doubled plasma PGD2 and 5-HT,
but aspirin reduced only PGD2 by 86%. In contrast, luteolin inhibited
both plasma PGD2 and 5-HT levels by 100 and 67%, respectively.
CONCLUSIONS AND IMPLICATIONS. Niacin-induced skin temperature increase
is associated with PGD2 and 5-HT elevations in rats; luteolin may be a
better inhibitor of niacin-induced flush because it blocks the rise in
both mediators.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 18223672
> Kofi wrote:
> > Forgot two strategic approaches specific to diabetes:
> >
> > 1) Raise the NAD+/NADH ratio. Niacinamide or niacin. This ratio
> > governs blood flow and directly affects neuropathy.
...
> There's a bit of controversy over whether niacinamide and "non-flush"
> or time-release forms of vitamin B-3 are as effective as plain niacin
> (nicotinic acid) for lowering blood triglycerides, total cholesterol,
> and LDL cholesterol, and raising HDL cholesterol. But there's no
> question that niacin is quite effective, and the only complaint against
> it is that it causes the famous niacin flush. But if you're familiar
> with it and prepared for it, it's not only "no problem," but it can be
> quite pleasant.
I didn't suggest niacinamide for any of these reasons. It directly
produces NAD+ and thus raises the NAD+/NADH ratio. This has a
beneficial effect on local blood flow, reducing pressure on nerves.
The authors below seem oblivious to the beneficial role that PGD2 plays
in the effects of niacin [PMID 15037193]. FYI, niacin raises PGD2,
raises 15d-PGJ2 which activates PPARgamma. PPARgamma agonists raise
trans-glutaminase levels - and Celiacs make antibodies to
trans-glutaminase.
: Br J Pharmacol. 2008 Apr;153(7):1382-7. Epub 2008 Jan 28.
The flavonoid luteolin inhibits niacin-induced flush.
Papaliodis D, Boucher W, Kempuraj D, Theoharides TC.
Laboratory for Molecular Immunopharmacology and Drug Discovery,
Department of Pharmacology and Experimental Therapeutics, Tufts
University School of Medicine, Tufts-New England Medical Center, Boston,
MA, USA.
BACKGROUND AND PURPOSE: Sustained release niacin effectively lowers
serum cholesterol, LDL and triglycerides, while raising HDL. However,
75% of patients experience cutaneous warmth and itching known as flush,
leading to discontinuation. Acetylsalicylic acid (aspirin) reduces this
flush only by about 30%, presumably through decreasing prostaglandin D2
(PGD2). We investigated whether niacin-induced flush in a rat model
involves PGD2 and 5-HT, and the effect of certain flavonoids.
EXPERIMENTAL APPROACH: Three skin temperature measurements from each ear
were recorded with an infrared pyrometer for each time point immediately
before i.p. injection with either niacin or a flavonoid. The temperature
was then measured every 10 min for 60 min. KEY RESULTS: Niacin (7.5 mg
per rat, equivalent to a human dose of 1750 mg per 80 kg) maximally
increased ear temperature to 1.9+/-0.2 degrees C at 45 min. Quercetin
and luteolin (4.3 mg per rat; 1000 mg per human), administered i.p. 45
min prior to niacin, inhibited the niacin effect by 96 and 88%,
respectively. Aspirin (1.22 mg per rat; 325 mg per human) inhibited the
niacin effect by only 30%. Niacin almost doubled plasma PGD2 and 5-HT,
but aspirin reduced only PGD2 by 86%. In contrast, luteolin inhibited
both plasma PGD2 and 5-HT levels by 100 and 67%, respectively.
CONCLUSIONS AND IMPLICATIONS. Niacin-induced skin temperature increase
is associated with PGD2 and 5-HT elevations in rats; luteolin may be a
better inhibitor of niacin-induced flush because it blocks the rise in
both mediators.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 18223672
Re: Supplements for Neuropathy; counteracting niacin flush PGD2
It is nice to know that the niacin flushing is mediated by the
arachidonic acid metabolites PGD2 and PGJ2 and that some antioxidants
naturally inhibit it. Do you know which particular cyclooxygenase
(COX) enzyme makes the PGD2 eicosanoid? Perhaps luteolin targets it
specifically.
Taka
Kofi wrote:
> > Kofi wrote:
> > > Forgot two strategic approaches specific to diabetes:
> > >
> > > 1) Raise the NAD+/NADH ratio. Niacinamide or niacin. This ratio
> > > governs blood flow and directly affects neuropathy.
>
> ...
>
> > There's a bit of controversy over whether niacinamide and "non-flush"
> > or time-release forms of vitamin B-3 are as effective as plain niacin
> > (nicotinic acid) for lowering blood triglycerides, total cholesterol,
> > and LDL cholesterol, and raising HDL cholesterol. But there's no
> > question that niacin is quite effective, and the only complaint against
> > it is that it causes the famous niacin flush. But if you're familiar
> > with it and prepared for it, it's not only "no problem," but it can be
> > quite pleasant.
>
> I didn't suggest niacinamide for any of these reasons. It directly
> produces NAD+ and thus raises the NAD+/NADH ratio. This has a
> beneficial effect on local blood flow, reducing pressure on nerves.
>
> The authors below seem oblivious to the beneficial role that PGD2 plays
> in the effects of niacin [PMID 15037193]. FYI, niacin raises PGD2,
> raises 15d-PGJ2 which activates PPARgamma. PPARgamma agonists raise
> trans-glutaminase levels - and Celiacs make antibodies to
> trans-glutaminase.
>
>
> : Br J Pharmacol. 2008 Apr;153(7):1382-7. Epub 2008 Jan 28.
>
> The flavonoid luteolin inhibits niacin-induced flush.
>
> Papaliodis D, Boucher W, Kempuraj D, Theoharides TC.
> Laboratory for Molecular Immunopharmacology and Drug Discovery,
> Department of Pharmacology and Experimental Therapeutics, Tufts
> University School of Medicine, Tufts-New England Medical Center, Boston,
> MA, USA.
>
> BACKGROUND AND PURPOSE: Sustained release niacin effectively lowers
> serum cholesterol, LDL and triglycerides, while raising HDL. However,
> 75% of patients experience cutaneous warmth and itching known as flush,
> leading to discontinuation. Acetylsalicylic acid (aspirin) reduces this
> flush only by about 30%, presumably through decreasing prostaglandin D2
> (PGD2). We investigated whether niacin-induced flush in a rat model
> involves PGD2 and 5-HT, and the effect of certain flavonoids.
> EXPERIMENTAL APPROACH: Three skin temperature measurements from each ear
> were recorded with an infrared pyrometer for each time point immediately
> before i.p. injection with either niacin or a flavonoid. The temperature
> was then measured every 10 min for 60 min. KEY RESULTS: Niacin (7.5 mg
> per rat, equivalent to a human dose of 1750 mg per 80 kg) maximally
> increased ear temperature to 1.9+/-0.2 degrees C at 45 min. Quercetin
> and luteolin (4.3 mg per rat; 1000 mg per human), administered i.p. 45
> min prior to niacin, inhibited the niacin effect by 96 and 88%,
> respectively. Aspirin (1.22 mg per rat; 325 mg per human) inhibited the
> niacin effect by only 30%. Niacin almost doubled plasma PGD2 and 5-HT,
> but aspirin reduced only PGD2 by 86%. In contrast, luteolin inhibited
> both plasma PGD2 and 5-HT levels by 100 and 67%, respectively.
> CONCLUSIONS AND IMPLICATIONS. Niacin-induced skin temperature increase
> is associated with PGD2 and 5-HT elevations in rats; luteolin may be a
> better inhibitor of niacin-induced flush because it blocks the rise in
> both mediators.
>
> Publication Types:
> * Research Support, Non-U.S. Gov't
>
> PMID: 18223672
It is nice to know that the niacin flushing is mediated by the
arachidonic acid metabolites PGD2 and PGJ2 and that some antioxidants
naturally inhibit it. Do you know which particular cyclooxygenase
(COX) enzyme makes the PGD2 eicosanoid? Perhaps luteolin targets it
specifically.
Taka
Kofi wrote:
> > Kofi wrote:
> > > Forgot two strategic approaches specific to diabetes:
> > >
> > > 1) Raise the NAD+/NADH ratio. Niacinamide or niacin. This ratio
> > > governs blood flow and directly affects neuropathy.
>
> ...
>
> > There's a bit of controversy over whether niacinamide and "non-flush"
> > or time-release forms of vitamin B-3 are as effective as plain niacin
> > (nicotinic acid) for lowering blood triglycerides, total cholesterol,
> > and LDL cholesterol, and raising HDL cholesterol. But there's no
> > question that niacin is quite effective, and the only complaint against
> > it is that it causes the famous niacin flush. But if you're familiar
> > with it and prepared for it, it's not only "no problem," but it can be
> > quite pleasant.
>
> I didn't suggest niacinamide for any of these reasons. It directly
> produces NAD+ and thus raises the NAD+/NADH ratio. This has a
> beneficial effect on local blood flow, reducing pressure on nerves.
>
> The authors below seem oblivious to the beneficial role that PGD2 plays
> in the effects of niacin [PMID 15037193]. FYI, niacin raises PGD2,
> raises 15d-PGJ2 which activates PPARgamma. PPARgamma agonists raise
> trans-glutaminase levels - and Celiacs make antibodies to
> trans-glutaminase.
>
>
> : Br J Pharmacol. 2008 Apr;153(7):1382-7. Epub 2008 Jan 28.
>
> The flavonoid luteolin inhibits niacin-induced flush.
>
> Papaliodis D, Boucher W, Kempuraj D, Theoharides TC.
> Laboratory for Molecular Immunopharmacology and Drug Discovery,
> Department of Pharmacology and Experimental Therapeutics, Tufts
> University School of Medicine, Tufts-New England Medical Center, Boston,
> MA, USA.
>
> BACKGROUND AND PURPOSE: Sustained release niacin effectively lowers
> serum cholesterol, LDL and triglycerides, while raising HDL. However,
> 75% of patients experience cutaneous warmth and itching known as flush,
> leading to discontinuation. Acetylsalicylic acid (aspirin) reduces this
> flush only by about 30%, presumably through decreasing prostaglandin D2
> (PGD2). We investigated whether niacin-induced flush in a rat model
> involves PGD2 and 5-HT, and the effect of certain flavonoids.
> EXPERIMENTAL APPROACH: Three skin temperature measurements from each ear
> were recorded with an infrared pyrometer for each time point immediately
> before i.p. injection with either niacin or a flavonoid. The temperature
> was then measured every 10 min for 60 min. KEY RESULTS: Niacin (7.5 mg
> per rat, equivalent to a human dose of 1750 mg per 80 kg) maximally
> increased ear temperature to 1.9+/-0.2 degrees C at 45 min. Quercetin
> and luteolin (4.3 mg per rat; 1000 mg per human), administered i.p. 45
> min prior to niacin, inhibited the niacin effect by 96 and 88%,
> respectively. Aspirin (1.22 mg per rat; 325 mg per human) inhibited the
> niacin effect by only 30%. Niacin almost doubled plasma PGD2 and 5-HT,
> but aspirin reduced only PGD2 by 86%. In contrast, luteolin inhibited
> both plasma PGD2 and 5-HT levels by 100 and 67%, respectively.
> CONCLUSIONS AND IMPLICATIONS. Niacin-induced skin temperature increase
> is associated with PGD2 and 5-HT elevations in rats; luteolin may be a
> better inhibitor of niacin-induced flush because it blocks the rise in
> both mediators.
>
> Publication Types:
> * Research Support, Non-U.S. Gov't
>
> PMID: 18223672
Reply from: -- messaggio eliminato --
Date: 06 Jun 2008, 19:35
-- deleted messages --
Reply from: -- messaggio eliminato --
Date: 07 Jun 2008, 12:19
-- deleted messages --
Re: Supplements for Neuropathy; counteracting niacin flush PGD2
> That was very educational, thanks much Kofi. Seems the prostaglandins
> are deeply involved in almost everything. Because we can influence
> their levels via diet (reducing or increasing arachidonic acid - AA -
> from which they are made) there should be more studies focused on
> returning the Omega-6 amounts consumed to what we had been evolving on
> rather than trying to overcome the "soy and corn oils" by further
> increasing the consumption of Omega-3 which basically act like the
> NSAIDs. Also I think the "destructive" 5-LOX cascade may predominate
> at higher AA levels compared to the sometimes useful COX-1/2
> cascades.
Interesting you bring this up. Omega-3s are competing substrates for
ALOX5/leukotrienes as well.
> And high carbohydrate/sugar diet may be doing the same. Do
> we need PLA-2 for making AA available to the COXs (this may be the
> key)??
Don't know, but butyrate has an interesting connection, as do
viagra-type compounds:
portal venous blood transfusions in organ transplantation is
immunosuppressive and may be mediated by increased Kupffer cell
production of the immunosuppressive arachidonic acid metabolite
prostaglandin E2 (PGE2); butyrate is known to enhance gene transcription
and enhances Kupffer cell PGE2 production by altering cyclooxygenase and
phospholipase A2 (PLA2) activity and augmenting the immunosuppressive
effect of portal venous transfusion in Lewis rats; Kupffer cells from
portally transfused animals produced significantly more PGE2 than
saline-transfused controls; adding butyrate to the culture medium
further increased PGE2 production as much as sevenfold in Kupffer cells
of portally transfused animals; short-chain fatty acids propionate and
hexanoate did not increase PGE2 production; butyrate added to Kupffer
cells from transfused animals slightly upregulated inducible
cyclooxygenase (COX-2) mRNA levels and increased PLA2 activity fivefold;
Kupffer cell immune function was affected by in vitro butyrate treatment
causing a significant drop in production of TNFalpha; butyrate may be a
useful immunoregulatory agent in organ transplantation protocols which
seek to enhance transcription of immunosuppressive molecules [PMID
9733608] (if butyrate more generally increases PGE2 in other cell types,
this would indicate that the anticancer effects of butyrate could be
boosted with specific COX-2 inhibition - which is exactly what an
earlier paper concluded [PMID 15378772])
phospholipids like arachidonic acid and phosphatidic acid are potent
activators of PLCepsilon, increasing the rate of PI hydrolysis by 8- and
50-fold; the mechanism appears to be a reduction of K(m); adding cPLA2
or PLD with PLCepsilon leads to activation of PDE activity
(phosphodiesterase) [PMID 16953585] (AT1R is coupled to PLC, activates
it and increases cytosolic Ca2+; other AT1 receptor effects include
vasoconstriction, aldosterone synthesis and secretion, increased
vasopressin secretion, cardiac hypertrophy, augmentation of peripheral
noradrenergic activity, vascular smooth muscle cells proliferation,
decreased renal blood flow, renal renin inhibition, renal tubular sodium
reuptake, modulation of central sympathetic nervous system activity,
cardiac contractility, central osmocontrol and extracellular matrix
formation; angiotensin II also increases thirst and the need for salt
and the secretion of ACTH in the anterior pituitary)
> That was very educational, thanks much Kofi. Seems the prostaglandins
> are deeply involved in almost everything. Because we can influence
> their levels via diet (reducing or increasing arachidonic acid - AA -
> from which they are made) there should be more studies focused on
> returning the Omega-6 amounts consumed to what we had been evolving on
> rather than trying to overcome the "soy and corn oils" by further
> increasing the consumption of Omega-3 which basically act like the
> NSAIDs. Also I think the "destructive" 5-LOX cascade may predominate
> at higher AA levels compared to the sometimes useful COX-1/2
> cascades.
Interesting you bring this up. Omega-3s are competing substrates for
ALOX5/leukotrienes as well.
> And high carbohydrate/sugar diet may be doing the same. Do
> we need PLA-2 for making AA available to the COXs (this may be the
> key)??
Don't know, but butyrate has an interesting connection, as do
viagra-type compounds:
portal venous blood transfusions in organ transplantation is
immunosuppressive and may be mediated by increased Kupffer cell
production of the immunosuppressive arachidonic acid metabolite
prostaglandin E2 (PGE2); butyrate is known to enhance gene transcription
and enhances Kupffer cell PGE2 production by altering cyclooxygenase and
phospholipase A2 (PLA2) activity and augmenting the immunosuppressive
effect of portal venous transfusion in Lewis rats; Kupffer cells from
portally transfused animals produced significantly more PGE2 than
saline-transfused controls; adding butyrate to the culture medium
further increased PGE2 production as much as sevenfold in Kupffer cells
of portally transfused animals; short-chain fatty acids propionate and
hexanoate did not increase PGE2 production; butyrate added to Kupffer
cells from transfused animals slightly upregulated inducible
cyclooxygenase (COX-2) mRNA levels and increased PLA2 activity fivefold;
Kupffer cell immune function was affected by in vitro butyrate treatment
causing a significant drop in production of TNFalpha; butyrate may be a
useful immunoregulatory agent in organ transplantation protocols which
seek to enhance transcription of immunosuppressive molecules [PMID
9733608] (if butyrate more generally increases PGE2 in other cell types,
this would indicate that the anticancer effects of butyrate could be
boosted with specific COX-2 inhibition - which is exactly what an
earlier paper concluded [PMID 15378772])
phospholipids like arachidonic acid and phosphatidic acid are potent
activators of PLCepsilon, increasing the rate of PI hydrolysis by 8- and
50-fold; the mechanism appears to be a reduction of K(m); adding cPLA2
or PLD with PLCepsilon leads to activation of PDE activity
(phosphodiesterase) [PMID 16953585] (AT1R is coupled to PLC, activates
it and increases cytosolic Ca2+; other AT1 receptor effects include
vasoconstriction, aldosterone synthesis and secretion, increased
vasopressin secretion, cardiac hypertrophy, augmentation of peripheral
noradrenergic activity, vascular smooth muscle cells proliferation,
decreased renal blood flow, renal renin inhibition, renal tubular sodium
reuptake, modulation of central sympathetic nervous system activity,
cardiac contractility, central osmocontrol and extracellular matrix
formation; angiotensin II also increases thirst and the need for salt
and the secretion of ACTH in the anterior pituitary)
Re: Supplements for Neuropathy; counteracting niacin flush PGD2
On Jun 11, 10:58 am, Kofi <k...@anon.un> wrote:
> butyrate added to Kupffer
> cells from transfused animals slightly upregulated inducible
> cyclooxygenase (COX-2) mRNA levels and increased PLA2 activity fivefold;
Saturated fatty acids are also known to stimulate AA release likely
via PLA2 activity. AFAIK sugar does the same and additionally
inhibits AA synthesis. What we need would be a nutrient/supplement
which downregulates 5-LOX while upregulating COX and leaves PLA2
alone. I can think of only AKBA which comes close to this at the
moment.
Taka
On Jun 11, 10:58 am, Kofi <k...@anon.un> wrote:
> butyrate added to Kupffer
> cells from transfused animals slightly upregulated inducible
> cyclooxygenase (COX-2) mRNA levels and increased PLA2 activity fivefold;
Saturated fatty acids are also known to stimulate AA release likely
via PLA2 activity. AFAIK sugar does the same and additionally
inhibits AA synthesis. What we need would be a nutrient/supplement
which downregulates 5-LOX while upregulating COX and leaves PLA2
alone. I can think of only AKBA which comes close to this at the
moment.
Taka
Re: Supplements for Neuropathy; counteracting niacin flush PGD2
In article <kofi-837123.12350806062008@news.east.earthlink,net >,
Kofi <kofi@anon.un> wrote:
> I keep trying to tell people *not* to inhibit the COX enzymes unless
> they've got a life-threatening condition like cancer.
Really? So you tell people not to take curcumin or turmeric, green
tea, resveratrol, fish oil, Rosemary, or low-dose aspirin?
In article <kofi-837123.12350806062008@news.east.earthlink,net >,
Kofi <kofi@anon.un> wrote:
> I keep trying to tell people *not* to inhibit the COX enzymes unless
> they've got a life-threatening condition like cancer.
Really? So you tell people not to take curcumin or turmeric, green
tea, resveratrol, fish oil, Rosemary, or low-dose aspirin?
Re: Supplements for Neuropathy; counteracting niacin flush PGD2
In article <nospam-9BE4F2.06453308062008@newsclstr03.news.prodigy,net >,
Bob Arnold <nospam@aol,com > wrote:
> In article <kofi-837123.12350806062008@news.east.earthlink,net >,
> Kofi <kofi@anon.un> wrote:
>
> > I keep trying to tell people *not* to inhibit the COX enzymes unless
> > they've got a life-threatening condition like cancer.
>
> Really? So you tell people not to take curcumin or turmeric, green
> tea, resveratrol, fish oil, Rosemary, or low-dose aspirin?
Yeah. They *can* cause unexpected long-term problems in people with odd
forms of autoimmunity because of their actions on PGE2. It depends on
what else they're doing to balance it out. These substances are all
quite complicated and they may inhibit one type of enzyme in one cell
and do something completely different in another.
Most people taking curcumin or green tea aren't really getting
pharmacological levels of the substances for sustained periods of time.
EGCG requires citric acid or lemon juice to protect it through the
stomach and curcumin requires CYP inhibition. I've actually tried the
later and it severely exacerbated my autoimmune problems and difficulty
fighting infections. TGF-B1 inhibition/PPARgamma agonism might have
played a significant role. In particular, PPARgamma increases
transglutaminases which Celiacs target with autoantibodies. TGF-B1
activates Tregs.
In article <nospam-9BE4F2.06453308062008@newsclstr03.news.prodigy,net >,
Bob Arnold <nospam@aol,com > wrote:
> In article <kofi-837123.12350806062008@news.east.earthlink,net >,
> Kofi <kofi@anon.un> wrote:
>
> > I keep trying to tell people *not* to inhibit the COX enzymes unless
> > they've got a life-threatening condition like cancer.
>
> Really? So you tell people not to take curcumin or turmeric, green
> tea, resveratrol, fish oil, Rosemary, or low-dose aspirin?
Yeah. They *can* cause unexpected long-term problems in people with odd
forms of autoimmunity because of their actions on PGE2. It depends on
what else they're doing to balance it out. These substances are all
quite complicated and they may inhibit one type of enzyme in one cell
and do something completely different in another.
Most people taking curcumin or green tea aren't really getting
pharmacological levels of the substances for sustained periods of time.
EGCG requires citric acid or lemon juice to protect it through the
stomach and curcumin requires CYP inhibition. I've actually tried the
later and it severely exacerbated my autoimmune problems and difficulty
fighting infections. TGF-B1 inhibition/PPARgamma agonism might have
played a significant role. In particular, PPARgamma increases
transglutaminases which Celiacs target with autoantibodies. TGF-B1
activates Tregs.
Re: Supplements for Neuropathy; counteracting niacin flush PGD2
Kofi wrote:
> In article <nospam-9BE4F2.06453308062008@newsclstr03.news.prodigy,net >,
> Bob Arnold <nospam@aol,com > wrote:
>
>
>>In article <kofi-837123.12350806062008@news.east.earthlink,net >,
>> Kofi <kofi@anon.un> wrote:
>>
>>
>>>I keep trying to tell people *not* to inhibit the COX enzymes unless
>>>they've got a life-threatening condition like cancer.
>>
>>Really? So you tell people not to take curcumin or turmeric, green
>>tea, resveratrol, fish oil, Rosemary, or low-dose aspirin?
>
>
> Yeah. They *can* cause unexpected long-term problems in people with odd
> forms of autoimmunity because of their actions on PGE2. It depends on
> what else they're doing to balance it out. These substances are all
> quite complicated and they may inhibit one type of enzyme in one cell
> and do something completely different in another.
>
> Most people taking curcumin or green tea aren't really getting
> pharmacological levels of the substances for sustained periods of time.
> EGCG requires citric acid or lemon juice to protect it through the
> stomach and curcumin requires CYP inhibition. I've actually tried the
> later and it severely exacerbated my autoimmune problems and difficulty
> fighting infections. TGF-B1 inhibition/PPARgamma agonism might have
> played a significant role. In particular, PPARgamma increases
> transglutaminases which Celiacs target with autoantibodies. TGF-B1
> activates Tregs.
EGCG has different effects on the pancreas than it has on the liver.
EGCG can reduce some natural endogenous antioxidant enzymes at high
enough doses. "The effect of NAC and SOD on PEPCK and G6Pase gene
expression was also examined. As expected, NAC and SOD completely
reversed EGCG-mediated PEPCK and G6Pase gene repression. NAC partially
inhibited the effect on insulin-mediated repression of the PEPCK gene,
but not the G6Pase gene (Fig. 6, panels B and C). These results show
that EGCG regulates tyrosine phosphorylation and gene expression by a
redox-dependent mechanism and provides additional evidence that the
PEPCK and G6Pase genes are regulated by multiple signaling pathways.
[...] The effects of EGCG are reversed by NAC and SOD, whereas those of
insulin are mostly unaffected, suggesting that the former acts by a
different mechanism. In most cell types, EGCG is an antioxidant.
However, in hepatoma cells, EGCG is a pro-oxidant. This is not
completely unexpected because other compounds, such as ascorbate, can
act either as an antioxidant or pro-oxidant, depending on the cellular
environment (47). Curcumin, a phytochemical responsible for the color of
turmeric, has antioxidant activity in many different cell types but
displays pro-oxidant qualities in the presence of transition metals,
such as copper, which exist in the kidney and liver at relatively high
concentrations (48).
The data presented here suggest that EGCG regulates protein-tyrosine
phosphorylation by modulating the redox state of the cell. One possible
mechanism for the observed actions of EGCG in hepatoma cells is the
inhibition of PTPs, which contain an oxidizable cysteine in their active
site (39, 49). It is possible that EGCG causes oxidation of this
cysteine residue in redox-sensitive phosphatases, and NAC and SOD
reverse this effect. Several PTPs, including PTP-1B and leukocyte
antigen-related phosphatase, dephosphorylate the insulin receptor and
IRS-1, making these phosphatases candidates for modification by ROS
produced in response to EGCG (50-52)." Source: Epigallocatechin
Gallate, a Constituent of Green Tea, Represses Hepatic Glucose
Production - http :// www .jbc.org/cgi/content/full/277/38/34933
Frank
Kofi wrote:
> In article <nospam-9BE4F2.06453308062008@newsclstr03.news.prodigy,net >,
> Bob Arnold <nospam@aol,com > wrote:
>
>
>>In article <kofi-837123.12350806062008@news.east.earthlink,net >,
>> Kofi <kofi@anon.un> wrote:
>>
>>
>>>I keep trying to tell people *not* to inhibit the COX enzymes unless
>>>they've got a life-threatening condition like cancer.
>>
>>Really? So you tell people not to take curcumin or turmeric, green
>>tea, resveratrol, fish oil, Rosemary, or low-dose aspirin?
>
>
> Yeah. They *can* cause unexpected long-term problems in people with odd
> forms of autoimmunity because of their actions on PGE2. It depends on
> what else they're doing to balance it out. These substances are all
> quite complicated and they may inhibit one type of enzyme in one cell
> and do something completely different in another.
>
> Most people taking curcumin or green tea aren't really getting
> pharmacological levels of the substances for sustained periods of time.
> EGCG requires citric acid or lemon juice to protect it through the
> stomach and curcumin requires CYP inhibition. I've actually tried the
> later and it severely exacerbated my autoimmune problems and difficulty
> fighting infections. TGF-B1 inhibition/PPARgamma agonism might have
> played a significant role. In particular, PPARgamma increases
> transglutaminases which Celiacs target with autoantibodies. TGF-B1
> activates Tregs.
EGCG has different effects on the pancreas than it has on the liver.
EGCG can reduce some natural endogenous antioxidant enzymes at high
enough doses. "The effect of NAC and SOD on PEPCK and G6Pase gene
expression was also examined. As expected, NAC and SOD completely
reversed EGCG-mediated PEPCK and G6Pase gene repression. NAC partially
inhibited the effect on insulin-mediated repression of the PEPCK gene,
but not the G6Pase gene (Fig. 6, panels B and C). These results show
that EGCG regulates tyrosine phosphorylation and gene expression by a
redox-dependent mechanism and provides additional evidence that the
PEPCK and G6Pase genes are regulated by multiple signaling pathways.
[...] The effects of EGCG are reversed by NAC and SOD, whereas those of
insulin are mostly unaffected, suggesting that the former acts by a
different mechanism. In most cell types, EGCG is an antioxidant.
However, in hepatoma cells, EGCG is a pro-oxidant. This is not
completely unexpected because other compounds, such as ascorbate, can
act either as an antioxidant or pro-oxidant, depending on the cellular
environment (47). Curcumin, a phytochemical responsible for the color of
turmeric, has antioxidant activity in many different cell types but
displays pro-oxidant qualities in the presence of transition metals,
such as copper, which exist in the kidney and liver at relatively high
concentrations (48).
The data presented here suggest that EGCG regulates protein-tyrosine
phosphorylation by modulating the redox state of the cell. One possible
mechanism for the observed actions of EGCG in hepatoma cells is the
inhibition of PTPs, which contain an oxidizable cysteine in their active
site (39, 49). It is possible that EGCG causes oxidation of this
cysteine residue in redox-sensitive phosphatases, and NAC and SOD
reverse this effect. Several PTPs, including PTP-1B and leukocyte
antigen-related phosphatase, dephosphorylate the insulin receptor and
IRS-1, making these phosphatases candidates for modification by ROS
produced in response to EGCG (50-52)." Source: Epigallocatechin
Gallate, a Constituent of Green Tea, Represses Hepatic Glucose
Production - http :// www .jbc.org/cgi/content/full/277/38/34933
Frank
Re: Supplements for Neuropathy; counteracting niacin flush
Kofi wrote:
>> Kofi wrote:
>>> Forgot two strategic approaches specific to diabetes:
>>>
>>> 1) Raise the NAD+/NADH ratio. Niacinamide or niacin. This ratio
>>> governs blood flow and directly affects neuropathy.
>
> ....
>
>> There's a bit of controversy over whether niacinamide and "non-flush"
>> or time-release forms of vitamin B-3 are as effective as plain niacin
>> (nicotinic acid) for lowering blood triglycerides, total cholesterol,
>> and LDL cholesterol, and raising HDL cholesterol. But there's no
>> question that niacin is quite effective, and the only complaint against
>> it is that it causes the famous niacin flush. But if you're familiar
>> with it and prepared for it, it's not only "no problem," but it can be
>> quite pleasant.
>
> I didn't suggest niacinamide for any of these reasons. It directly
> produces NAD+ and thus raises the NAD+/NADH ratio. This has a
> beneficial effect on local blood flow, reducing pressure on nerves.
>
> The authors below seem oblivious to the beneficial role that PGD2 plays
> in the effects of niacin [PMID 15037193]. FYI, niacin raises PGD2,
> raises 15d-PGJ2 which activates PPARgamma. PPARgamma agonists raise
> trans-glutaminase levels - and Celiacs make antibodies to
> trans-glutaminase.
>
>
> : Br J Pharmacol. 2008 Apr;153(7):1382-7. Epub 2008 Jan 28.
>
> The flavonoid luteolin inhibits niacin-induced flush.
>
> Papaliodis D, Boucher W, Kempuraj D, Theoharides TC.
> Laboratory for Molecular Immunopharmacology and Drug Discovery,
> Department of Pharmacology and Experimental Therapeutics, Tufts
> University School of Medicine, Tufts-New England Medical Center, Boston,
> MA, USA.
>
> BACKGROUND AND PURPOSE: Sustained release niacin effectively lowers
> serum cholesterol, LDL and triglycerides, while raising HDL. However,
> 75% of patients experience cutaneous warmth and itching known as flush,
> leading to discontinuation. Acetylsalicylic acid (aspirin) reduces this
> flush only by about 30%, presumably through decreasing prostaglandin D2
> (PGD2). We investigated whether niacin-induced flush in a rat model
> involves PGD2 and 5-HT, and the effect of certain flavonoids.
> EXPERIMENTAL APPROACH: Three skin temperature measurements from each ear
> were recorded with an infrared pyrometer for each time point immediately
> before i.p. injection with either niacin or a flavonoid. The temperature
> was then measured every 10 min for 60 min. KEY RESULTS: Niacin (7.5 mg
> per rat, equivalent to a human dose of 1750 mg per 80 kg) maximally
> increased ear temperature to 1.9+/-0.2 degrees C at 45 min. Quercetin
> and luteolin (4.3 mg per rat; 1000 mg per human), administered i.p. 45
> min prior to niacin, inhibited the niacin effect by 96 and 88%,
> respectively. Aspirin (1.22 mg per rat; 325 mg per human) inhibited the
> niacin effect by only 30%. Niacin almost doubled plasma PGD2 and 5-HT,
> but aspirin reduced only PGD2 by 86%. In contrast, luteolin inhibited
> both plasma PGD2 and 5-HT levels by 100 and 67%, respectively.
> CONCLUSIONS AND IMPLICATIONS. Niacin-induced skin temperature increase
> is associated with PGD2 and 5-HT elevations in rats; luteolin may be a
> better inhibitor of niacin-induced flush because it blocks the rise in
> both mediators.
>
> Publication Types:
> * Research Support, Non-U.S. Gov't
>
> PMID: 18223672
I have a suspicion the flush does me good somehow.
--
Marshall Price of Miami
Known to Yahoo as d021317c
Kofi wrote:
>> Kofi wrote:
>>> Forgot two strategic approaches specific to diabetes:
>>>
>>> 1) Raise the NAD+/NADH ratio. Niacinamide or niacin. This ratio
>>> governs blood flow and directly affects neuropathy.
>
> ....
>
>> There's a bit of controversy over whether niacinamide and "non-flush"
>> or time-release forms of vitamin B-3 are as effective as plain niacin
>> (nicotinic acid) for lowering blood triglycerides, total cholesterol,
>> and LDL cholesterol, and raising HDL cholesterol. But there's no
>> question that niacin is quite effective, and the only complaint against
>> it is that it causes the famous niacin flush. But if you're familiar
>> with it and prepared for it, it's not only "no problem," but it can be
>> quite pleasant.
>
> I didn't suggest niacinamide for any of these reasons. It directly
> produces NAD+ and thus raises the NAD+/NADH ratio. This has a
> beneficial effect on local blood flow, reducing pressure on nerves.
>
> The authors below seem oblivious to the beneficial role that PGD2 plays
> in the effects of niacin [PMID 15037193]. FYI, niacin raises PGD2,
> raises 15d-PGJ2 which activates PPARgamma. PPARgamma agonists raise
> trans-glutaminase levels - and Celiacs make antibodies to
> trans-glutaminase.
>
>
> : Br J Pharmacol. 2008 Apr;153(7):1382-7. Epub 2008 Jan 28.
>
> The flavonoid luteolin inhibits niacin-induced flush.
>
> Papaliodis D, Boucher W, Kempuraj D, Theoharides TC.
> Laboratory for Molecular Immunopharmacology and Drug Discovery,
> Department of Pharmacology and Experimental Therapeutics, Tufts
> University School of Medicine, Tufts-New England Medical Center, Boston,
> MA, USA.
>
> BACKGROUND AND PURPOSE: Sustained release niacin effectively lowers
> serum cholesterol, LDL and triglycerides, while raising HDL. However,
> 75% of patients experience cutaneous warmth and itching known as flush,
> leading to discontinuation. Acetylsalicylic acid (aspirin) reduces this
> flush only by about 30%, presumably through decreasing prostaglandin D2
> (PGD2). We investigated whether niacin-induced flush in a rat model
> involves PGD2 and 5-HT, and the effect of certain flavonoids.
> EXPERIMENTAL APPROACH: Three skin temperature measurements from each ear
> were recorded with an infrared pyrometer for each time point immediately
> before i.p. injection with either niacin or a flavonoid. The temperature
> was then measured every 10 min for 60 min. KEY RESULTS: Niacin (7.5 mg
> per rat, equivalent to a human dose of 1750 mg per 80 kg) maximally
> increased ear temperature to 1.9+/-0.2 degrees C at 45 min. Quercetin
> and luteolin (4.3 mg per rat; 1000 mg per human), administered i.p. 45
> min prior to niacin, inhibited the niacin effect by 96 and 88%,
> respectively. Aspirin (1.22 mg per rat; 325 mg per human) inhibited the
> niacin effect by only 30%. Niacin almost doubled plasma PGD2 and 5-HT,
> but aspirin reduced only PGD2 by 86%. In contrast, luteolin inhibited
> both plasma PGD2 and 5-HT levels by 100 and 67%, respectively.
> CONCLUSIONS AND IMPLICATIONS. Niacin-induced skin temperature increase
> is associated with PGD2 and 5-HT elevations in rats; luteolin may be a
> better inhibitor of niacin-induced flush because it blocks the rise in
> both mediators.
>
> Publication Types:
> * Research Support, Non-U.S. Gov't
>
> PMID: 18223672
I have a suspicion the flush does me good somehow.
--
Marshall Price of Miami
Known to Yahoo as d021317c
Re: Supplements for Neuropathy
Kofi wrote:
> In article
> <739091c9-61a5-4257-844a-cbc2e72bd0e6@r66g2000hsg.googlegroups,com >,
> jay <jaym1212@hotmail,com > wrote:
>
>> What supplements provide relief from polyneuropathy? Would the
>> following be the most important? Already doing paleo-type diet,
>> moderate exercise and multi-vitamins.
>>
>> Benfotiamine
>> Vitamin B6 (P-5-P)
>> R-Lipoic Acid
>> NAC
>> Acetyl-L-Carnitine
>
> I've had neuropathy too.
>
> A couple of points:
>
> + Stoke the GABA channel. Homocysteine blocks it, so anything that
> lowers homocysteine should work - methyl-B12, folic acid, betaine, SAMe,
> creatine, choline. (Insulin resistance interferes with GABA receptor
> function, by the way.) You can boost GABA production per se with
> magnesium, taurine and a few of the previously mentioned items.
> Magnesium also antagonizes the actions of Substance P.
>
> + Check for molybdenum deficiency, which is common in diabetes and
> depresses metallothionein synthesis. Also check for metals poisoning
> and other toxicities.
>
> + Intermittent fasting - eat as much as you want the first day, then
> fast the second day and repeat. Much easier than calorie restriction
> and doesn't require expert nutritional supervision.
>
> + Acetyl-l-carnitine upregulates the low affinity nerve growth factor
> receptor (p75NGFR) - thus its limited ability to regrow peripheral
> nerves. p75 accelerates growth in some cancers (e.g. gliomas) and
> shrinks other cancers. Make sure you understand what ALCAR is doing to
> your cancer risk. (A high enough dose should also send your hair
> follicles into catagen.)
>
> + Butyrate (~3g daily). It's an HDAC inhibitor produced in the gut
> from fiber. It requires carnitine for absorption and metabolization.
> Butyrate directly induces autophagy.
>
> + If you're taking lipoic acid, take plenty of biotin.
>
> + For pain relief, low-dose naltrexone blocks dependency, increases
> analgesia and reduces tolerance/addiction when used in conjunction with
> standard opioids.
>
> + Green tea extract (analgesia via PPARalpha agonism, maybe PKC
> inhibition).
>
> + Atrial natriuretic factor (produced via certain types of heat stress).
>
> + gluatmine (HO-1)
>
> + Vitamin D3 (via HIF-1?).
>
> + DHEA (like carnitine, it's a PKC inhibitor and thus raises the pain
> threshold).
>
> + Death of gut bacteria can lower the pain threshold [PMID 17159985].
>
> + Cox-2 inhibitors can actually induce autoimmunity and sometimes
> sensitize nerves to pain.
Whew! That's a lot to absorb at one sitting.
About acetyl-L-carnitine, you said:
> A high enough dose should also send your hair
> follicles into catagen.
What does that mean? (I'm not familiar with the word "catagen.")
--
Marshall Price of Miami
Known to Yahoo as d021317c
Kofi wrote:
> In article
> <739091c9-61a5-4257-844a-cbc2e72bd0e6@r66g2000hsg.googlegroups,com >,
> jay <jaym1212@hotmail,com > wrote:
>
>> What supplements provide relief from polyneuropathy? Would the
>> following be the most important? Already doing paleo-type diet,
>> moderate exercise and multi-vitamins.
>>
>> Benfotiamine
>> Vitamin B6 (P-5-P)
>> R-Lipoic Acid
>> NAC
>> Acetyl-L-Carnitine
>
> I've had neuropathy too.
>
> A couple of points:
>
> + Stoke the GABA channel. Homocysteine blocks it, so anything that
> lowers homocysteine should work - methyl-B12, folic acid, betaine, SAMe,
> creatine, choline. (Insulin resistance interferes with GABA receptor
> function, by the way.) You can boost GABA production per se with
> magnesium, taurine and a few of the previously mentioned items.
> Magnesium also antagonizes the actions of Substance P.
>
> + Check for molybdenum deficiency, which is common in diabetes and
> depresses metallothionein synthesis. Also check for metals poisoning
> and other toxicities.
>
> + Intermittent fasting - eat as much as you want the first day, then
> fast the second day and repeat. Much easier than calorie restriction
> and doesn't require expert nutritional supervision.
>
> + Acetyl-l-carnitine upregulates the low affinity nerve growth factor
> receptor (p75NGFR) - thus its limited ability to regrow peripheral
> nerves. p75 accelerates growth in some cancers (e.g. gliomas) and
> shrinks other cancers. Make sure you understand what ALCAR is doing to
> your cancer risk. (A high enough dose should also send your hair
> follicles into catagen.)
>
> + Butyrate (~3g daily). It's an HDAC inhibitor produced in the gut
> from fiber. It requires carnitine for absorption and metabolization.
> Butyrate directly induces autophagy.
>
> + If you're taking lipoic acid, take plenty of biotin.
>
> + For pain relief, low-dose naltrexone blocks dependency, increases
> analgesia and reduces tolerance/addiction when used in conjunction with
> standard opioids.
>
> + Green tea extract (analgesia via PPARalpha agonism, maybe PKC
> inhibition).
>
> + Atrial natriuretic factor (produced via certain types of heat stress).
>
> + gluatmine (HO-1)
>
> + Vitamin D3 (via HIF-1?).
>
> + DHEA (like carnitine, it's a PKC inhibitor and thus raises the pain
> threshold).
>
> + Death of gut bacteria can lower the pain threshold [PMID 17159985].
>
> + Cox-2 inhibitors can actually induce autoimmunity and sometimes
> sensitize nerves to pain.
Whew! That's a lot to absorb at one sitting.
About acetyl-L-carnitine, you said:
> A high enough dose should also send your hair
> follicles into catagen.
What does that mean? (I'm not familiar with the word "catagen.")
--
Marshall Price of Miami
Known to Yahoo as d021317c
