Supplements for Neuropathy

> And I ate two to six cups of cooked oat bran every day, which also
> has been proven to work.

Make sure you rule out Celiac disease first. It's associated with
neuropathies.

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.

http://groups.google.com/group/sci.m...882fac4251f24?

<><

http://groups.google.com/group/sci.m...245343707310e?

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.

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?

(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.)

--
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

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

On Jun 2, 8:07*pm, Marshall Price <d0213...@yahoo.com> wrote:
> Kofi wrote:
> > In article
> > <739091c9-61a5-4257-844a-cbc2e72bd...@r66g2000hsg.googlegroups.com>,
> > jay <jaym1...@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

Catagen:the involutional phase of hair growth.
Compare meanings of the words anagen
and telogen.

Involutional: a normal process characterized by a decrease
in the size of an organ caused by a decrease in the size
of cells. The word has another use as well.

In short: the categen phase comes just before the rest phase and
then shedding.

jay 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


Here's my list links to info on polyneuropathy treatment employing
supplements and blood sugar control: All have been very helpful.

http://www.medscape.com/viewarticle/565795_1

http://www.ncbi.nlm.nih.gov/pubmed/8...?dopt=Abstract

http://www.diabetesincontrol.com/res...ryarticle=5702

http://www.tga.gov.au/adr/aadrb/aadr0504.htm

http://www.ncbi.nlm.nih.gov/pubmed/16609090

http://www.diabeteshealth.com/read/2008/04/23/5161.html

http://www.diabetic-talk.org/dpn.htm

http://diabetesmonitor.com/m57.htm

http://www.benfotiamine.org/FAQ.htm#faq10

http://dcf.evms.edu/research/nutrinerve.html

http://www.neuroeffex.com/

http://www.dlife.com/dLife/do/ShowCo...s_oct2006.html

http://www.dlife.com/dLife/do/ShowCo...us_012808.html

trigonometry1972@gmail.com | wrote:
> On Jun 2, 8:07 pm, Marshall Price <d0213...@yahoo.com> wrote:
>> Kofi wrote:
>>> In article
>>> <739091c9-61a5-4257-844a-cbc2e72bd...@r66g2000hsg.googlegroups.com>,
>>> jay <jaym1...@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.")
>
> Catagen:the involutional phase of hair growth.
> Compare meanings of the words anagen
> and telogen.
>
> Involutional: a normal process characterized by a decrease
> in the size of an organ caused by a decrease in the size
> of cells. The word has another use as well.
>
> In short: the categen phase comes just before the rest phase and
> then shedding.

Darn! It's in my medical dictionary. I *still* don't have the thing
memorized. ;-)

So why will acetyl-L-carnitine do that?

(I like it because it hides the brain damage. But hair hides the
skull damage, so it's hardly an easy decision to make!)

--
Marshall Price of Miami
Known to Yahoo as d021317c

> > And I ate two to six cups of cooked oat bran every day,
> > which also has been proven to work.
>
> Make sure you rule out Celiac disease first. *It's associated with
> neuropathies.

I think unadulterated oats are now considered safe; however, oats can
be contaminated by equipment/facilities that also process wheat,
barley or rye.

In the past, after eating Cinnamon Toast Crunch cereal (wheat, sugar,
rice flour, canola, fructose, maltodextrin, dextrose) for two weeks,
any meal with usual amount of hot chilies would cause both of my hands/
wrist to feel as if capsaicin was applied there direclty. Other corn/
oat based cereals didn't have this effect.

> I've had neuropathy too.

Kofi, thanks for the exhaustive list.

> ....check for metals poisoning and other toxicities.

I had my mercury amalgams removed now almost 20 years ago. Not sure if
that was a factor.

> + *Intermittent fasting

During short 12-hour fasts, I notice nerve pain/numbness subsides
considerably.

> + *Butyrate (~3g daily).

Would eating psyllium produce similar results?

> + *Green tea extract

Not sure, but tea seems to reduce my sciatica.

> + *Atrial natriuretic factor (produced via certain types of heat stress)..

Would hot showers work?

On Tue, 3 Jun 2008 14:00:38 -0700 (PDT), jay <jaym1212@hotmail.com>
wrote:

>> > And I ate two to six cups of cooked oat bran every day,
>> > which also has been proven to work.
>>
>> Make sure you rule out Celiac disease first. *It's associated with
>> neuropathies.
>
>I think unadulterated oats are now considered safe; however, oats can
>be contaminated by equipment/facilities that also process wheat,
>barley or rye.
>
>In the past, after eating Cinnamon Toast Crunch cereal (wheat, sugar,
>rice flour, canola, fructose, maltodextrin, dextrose) for two weeks,
>any meal with usual amount of hot chilies would cause both of my hands/
>wrist to feel as if capsaicin was applied there direclty. Other corn/
>oat based cereals didn't have this effect.

Did it also affect your feet?

Was it symmetrical?

Did you check your blood glucose?

I can't speak for anyone else but that many fast carbs would spike my
BG and cause the onset of peripheral neuropathy

The chillies might just amplify the pain

>> In the past, after eating Cinnamon Toast Crunch cereal fo two weeks,
>> any meal with usual amount of hot chilies would cause both of my hands/
>> wrist to feel as if capsaicin was applied there direclty.
>
> Did it also affect your feet?

No, and I haven't had any numbness/tingling in my feet. But they do
get sore from walking, possibly more so when consuming beef and
chicken.

> Was it symmetrical?

Yes, the icy/hot feeling in hands and wrists was symmetrical.

> Did you check your blood glucose?

No, but based on past measurements, it probably went in to the mid
100's.

> I can't speak for anyone else but that many fast carbs would spike my
> BG and cause the onset of peripheral neuropathy

Me too, and that was one of the reasons for shifting more to meats.

> The chillies might just amplify the pain

Actually, the icy/hot feeling generated by chillies feels good in a
weird way and drowns out the more aggravating pain/numbness.

jay wrote:


>>+ Butyrate (~3g daily).

> Would eating psyllium produce similar results?

Psyllium can act as a prebiotic. Probiotics that increase the bacteria
that ferment fibers to produce short chain fatty acids including
butyrate might get this effect, but it depends on how bioavailable ~3
grams of butyrate is versus that produced in the lower digestive tract,
i.e., the distal ileum and proximal colon. Some yogurts include active
bacteria for this purpose.

A Scholar.Google search for the terms
butyrate+diabetic+neuropathy+human+clinical+trials -
http://tinyurl.com/45a9bt.

Modulatory effect of butyric acid - a product of dietary fiber
fermentation in experimentally induced diabetic rats.PMID: 12231422

Frank

> >
> > It's not too much. I take 540mg Thiamine per day.

Taking this much won't actually enhance uptake. There's only so much
you can push into your system at once. You might want to consider
benfotiamine as a substitute.

>
> 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?
>
> (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.)

Keep in mind that too much B6 can cause symptoms resembling 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.

....

> 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

> 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.")

It's the rest phase for hair follicles. They fall out and go dormant.

> > ....check for metals poisoning and other toxicities.
>
> I had my mercury amalgams removed now almost 20 years ago. Not sure if
> that was a factor.

It can stay in bones and fat a long time. Since diabetics also have low
molybdenum levels, this affects metallothionein synthesis and this could
lead you to move mercury out more slowly. In fact, mercury tends to
accumulate in diabetic cardiomyopathy because of loss of HDAC
inhibition. I posted on this in sci.life-extension if you're interested.

> > + *Butyrate (~3g daily).
>
> Would eating psyllium produce similar results?

Only if you have adequate gut bacteria levels. If you have a history of
antibiotic use, this could be a problem. Gut flora also decline with
age.

>
> > + *Green tea extract
>
> Not sure, but tea seems to reduce my sciatica.

GTE is also raises the pain threshold via PPARalpha agonism.

> > + *Atrial natriuretic factor (produced via certain types of heat
> > stress).
>
> Would hot showers work?

No. But it would probably induce other heat shock protective factors.

> Darn! It's in my medical dictionary. I *still* don't have the thing
> memorized. ;-)
>
> So why will acetyl-L-carnitine do that?
>
> (I like it because it hides the brain damage. But hair hides the
> skull damage, so it's hardly an easy decision to make!)

Hair and nerves share some contradictory signals. I think this may have
to do with the fact that keratinocytes actually play a role at the very
edge of the nervous system, relaying temperature sensations through
various vannilloid receptors. In any event, ALCAR regenerates nerves by
slowly upregulating p75NGFR. Signaling through this receptor also sends
follicles into catagen. Carnitines in general also raise tolerance to
pain via PKC inhibition and carnitines are important in the
metabolization of butyrate, an HDAC inhibitor - and this activates FOXP3
and switches on regulatory T-cells (Tregs), which then guard against
autoimmunity. Since testosterone is a carnitine transporter, men have
greater natural levels of carnitine and this may be why we have a higher
pain threshold and are at less risk for upper body pain and autoimmune
disorders (except in redheads who have an MC-1 receptor mutation; they
have a higher tolerance of pain - esp. redheaded women - because opiates
stay around in their bloodstream longer; they also have greater skin
cancer risk and, perhaps not so coincidentally, they report enjoying sex
more). Hitting p75 also alters your cancer risk; some go up (like CNS
cancer); some go down.

These differential effects on hair and nerves also occur with other
neurogenic signals like BDNF, NGF, NT-3 and various other tyrosine
kinase ligands (which soy components like genistein also effect, by the
way). They're great for growing new neurons and preventing nerve cell
death but they're hell on hair follicles. Probably not so great if
you've got a brain tumor either. I explained the effects on hair at
alt.baldspot years ago.

Forgot one other approach to pain - fry the receptors.

resiniferatoxin is a tolerable analogue of capsaicin appropriate for in
vivo use; it is a vanilloid receptor agonist (TRPV1) which desensitizes
C-fibers that transmit pain; sensory nerve inactivation by
resiniferatoxin improves insulin sensitivity; desensitization improves
oral glucose tolerance, insulin secretion and whole body insulin
sensitivity in diabetic fatty Zucker rats; insulin secretion was lowered
and glucose uptake improved [PMID 15883192]

P.S. Did I mention mixing opiates with low-dose naltrexone to prevent
dependence and tolerance?

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 <kofi-7F3861.00004005062008@news.east.earthlink.net>,
Kofi <kofi@anon.un> wrote:

> > >
> > > It's not too much. I take 540mg Thiamine per day.
>
> Taking this much won't actually enhance uptake. There's only so much
> you can push into your system at once. You might want to consider
> benfotiamine as a substitute.

I take benfotiamine too. And, everything is divided into 4 doses
spread throughout the day, and taken with meals when possible. But, I
wasn't aware that uptake was an issue with any B vitamins.

> >
> > 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?
> >
> > (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.)
>
> Keep in mind that too much B6 can cause symptoms resembling neuropathy.

I take pyrodoxamine. Last I've seen, it's questionable whether it can
cause neuropathy like pyridoxine.

On Wed, 4 Jun 2008 11:18:04 -0700 (PDT), jay <jaym1212@hotmail.com>
wrote:

>>> In the past, after eating Cinnamon Toast Crunch cereal fo two weeks,
>>> any meal with usual amount of hot chilies would cause both of my hands/
>>> wrist to feel as if capsaicin was applied there direclty.
>>
>> Did it also affect your feet?
>
>No, and I haven't had any numbness/tingling in my feet. But they do
>get sore from walking, possibly more so when consuming beef and
>chicken.

Circulation?

>> Was it symmetrical?
>
>Yes, the icy/hot feeling in hands and wrists was symmetrical.
>
>> Did you check your blood glucose?
>
>No, but based on past measurements, it probably went in to the mid
>100's.

Mine doesn't start unless I go over 140 - 150 (this number seems to be
the common point of onset for several of us) the bugger is a single
brief spike seems to have effects that last several hours even after
the BG has dropped back to normal, I take extra care what I eat when
I'm out for that very reason.

>> I can't speak for anyone else but that many fast carbs would spike my
>> BG and cause the onset of peripheral neuropathy
>
>Me too, and that was one of the reasons for shifting more to meats.
>
>> The chillies might just amplify the pain
>
>Actually, the icy/hot feeling generated by chillies feels good in a
>weird way and drowns out the more aggravating pain/numbness.

Yes that'd work.

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

In article
<a25fb8a8-6eb4-4bc0-baa8-daf40acf58c1@s50g2000hsb.googlegroups.com>,
Taka <taka0038@gmail.com> wrote:

> 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.

If it's got a "2" in its name, it's straight out of COX-2.

I keep trying to tell people *not* to inhibit the COX enzymes unless
they've got a life-threatening condition like cancer.

Here's a small list of what PGD2 and PGJ2 do:

sleep disturbances in depressed patients correlate with serum fatty acid
concentrations (myristic, palmitic, palmitoleic, oleic, linoleic,
eicosadienoic and docosahexaenoic acid/DHA), especially palmitoleic and
eicosadienoic acids; palmitoleic and oleic acids seem to be particularly
important given their role as precursors to the sleep-inducing oleamide;
linoleic and eicosadienoic acid could be important as precursors the the
sleep mediator PGD2 [PMID 17123808]

PGD2 can be harmful or helpful to neuron survival depending on which
receptor it docks to; high levels are protective against stroke damage
and its beneficial effects generally outweight its negative effects;
it¹s particularly good at protecting against glutamate excitotoxicity;
other products of COX-2 like PGE2 are also protective
<http://www.sciencedaily.com/releases/2005/02/050217224933.htm>

atherosclerotic plaques rupture when they contain more prostaglandin E2
than PGD2 (which would associate more with NFKB and MMP-9
downregulation); COX-2 inhibition is only protective when the pathway
tilts more toward PGD2 [PMID 15155382]

niacin interferes with the cAMP/PKA pathway and massively stimulates
PGD2 formation (perhaps accounting for its benefit in atherosclerosis);
the major metabolite of PGD2, 15d-PGJ2, is the body¹s most potent
PPARgamma activator [PMID 15037193]

topical application of methylnicotinate can greatly increase PGD2 levels
without going through the mast cells [PMID 1373750]

PPARgamma is expressed in vascular cells and has antiinflammatory
actions on them; atherosclerotic lesion development is promoted by the
presence of inflammatory cells like monocytes and T-cells which release
IL-6, TNF-a and the activation of vascular smooth muscle cells (VSMCs);
in monocyte/macrophages, PPARgamma turns down the inflammatory regulator
CCAAT/enhancer-binding protein-delta (C/EBP-delta) which controls TNF-a,
IL-1b, IL-6; PPARgamma has been found to inhibit NFKB, AP-1 and STAT
too; 15d-PGJ2 is a natural PPARgamma ligand and also inhibits
C/EBP-delta in VSMCs; oxidized linoleic acid, a component of oxidized
LDL, is also a natural PPARgamma ligand but may be proatherogenic by
promoting foam cells from monocytes
<http://circres.ahajournals.org/cgi/content/full/91/5/373>

PGE2 is essential to male sexual identity as pregnant female rats given
NSAIDs which inhibit PGE2 had male pups who were less interested in sex
whereas female pups exposed to PGE2 were masculinized; PGE2 increased
connections of the preoptic area to other neurons in the brain; this
indicates some deep connection between testosterone and inflammation
<http://www.newscientist.com/news/news.jsp?id=ns99995026>

PGE2 via EP2/EP4 receptor signaling has antiinflammatory effects on the
expression of inducible genes; in synovial fibroblasts, PGE2 inhibits
MCP-1 (monocyte chemoattractant protein-1) production by IL-1beta;
NSAIDs may intercept a natural regulatory circuit that limits the
magnitude of inflammation [PMID 15361371]

in lung cancer, COX-2 and PGE2 underlie an immunosuppressive network
that is important in the formation of non-small cell lung cancer; CD4+
CD25+ regulatory T-cells (Tregs) block antitumor immune responses when
tumors secrete PGE2 and activate Foxp3 in the Tregs which increases Treg
activity; this effect was significantly reduced without an EP4
(E-prostanoid) receptor and totally absent without an EP2 receptor;
COX-2 inhibitors (Vioxx, Celebrex) reduced Treg activity, blocked FoxP3
and decreased tumor growth (this provides a pathway whereby COX-2
inhibitors can exaggerate allergies) [PMID 15958566]

On Jun 7, 2:35 am, Kofi <k...@anon.un> wrote:
> In article
> <a25fb8a8-6eb4-4bc0-baa8-daf40acf5...@s50g2000hsb.googlegroups.com>,
>
> Taka <taka0...@gmail.com> wrote:
> > 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.
>
> If it's got a "2" in its name, it's straight out of COX-2.
>
> I keep trying to tell people *not* to inhibit the COX enzymes unless
> they've got a life-threatening condition like cancer.
>
> Here's a small list of what PGD2 and PGJ2 do:
>
> sleep disturbances in depressed patients correlate with serum fatty acid
> concentrations (myristic, palmitic, palmitoleic, oleic, linoleic,
> eicosadienoic and docosahexaenoic acid/DHA), especially palmitoleic and
> eicosadienoic acids; palmitoleic and oleic acids seem to be particularly
> important given their role as precursors to the sleep-inducing oleamide;
> linoleic and eicosadienoic acid could be important as precursors the the
> sleep mediator PGD2 [PMID 17123808]
>
> PGD2 can be harmful or helpful to neuron survival depending on which
> receptor it docks to; high levels are protective against stroke damage
> and its beneficial effects generally outweight its negative effects;
> it¹s particularly good at protecting against glutamate excitotoxicity;
> other products of COX-2 like PGE2 are also protective
> <http://www.sciencedaily.com/releases/2005/02/050217224933.htm>
>
> atherosclerotic plaques rupture when they contain more prostaglandin E2
> than PGD2 (which would associate more with NFKB and MMP-9
> downregulation); COX-2 inhibition is only protective when the pathway
> tilts more toward PGD2 [PMID 15155382]
>
> niacin interferes with the cAMP/PKA pathway and massively stimulates
> PGD2 formation (perhaps accounting for its benefit in atherosclerosis);
> the major metabolite of PGD2, 15d-PGJ2, is the body¹s most potent
> PPARgamma activator [PMID 15037193]
>
> topical application of methylnicotinate can greatly increase PGD2 levels
> without going through the mast cells [PMID 1373750]
>
> PPARgamma is expressed in vascular cells and has antiinflammatory
> actions on them; atherosclerotic lesion development is promoted by the
> presence of inflammatory cells like monocytes and T-cells which release
> IL-6, TNF-a and the activation of vascular smooth muscle cells (VSMCs);
> in monocyte/macrophages, PPARgamma turns down the inflammatory regulator
> CCAAT/enhancer-binding protein-delta (C/EBP-delta) which controls TNF-a,
> IL-1b, IL-6; PPARgamma has been found to inhibit NFKB, AP-1 and STAT
> too; 15d-PGJ2 is a natural PPARgamma ligand and also inhibits
> C/EBP-delta in VSMCs; oxidized linoleic acid, a component of oxidized
> LDL, is also a natural PPARgamma ligand but may be proatherogenic by
> promoting foam cells from monocytes
> <http://circres.ahajournals.org/cgi/content/full/91/5/373>
>
> PGE2 is essential to male sexual identity as pregnant female rats given
> NSAIDs which inhibit PGE2 had male pups who were less interested in sex
> whereas female pups exposed to PGE2 were masculinized; PGE2 increased
> connections of the preoptic area to other neurons in the brain; this
> indicates some deep connection between testosterone and inflammation
> <http://www.newscientist.com/news/news.jsp?id=ns99995026>
>
> PGE2 via EP2/EP4 receptor signaling has antiinflammatory effects on the
> expression of inducible genes; in synovial fibroblasts, PGE2 inhibits
> MCP-1 (monocyte chemoattractant protein-1) production by IL-1beta;
> NSAIDs may intercept a natural regulatory circuit that limits the
> magnitude of inflammation [PMID 15361371]
>
> in lung cancer, COX-2 and PGE2 underlie an immunosuppressive network
> that is important in the formation of non-small cell lung cancer; CD4+
> CD25+ regulatory T-cells (Tregs) block antitumor immune responses when
> tumors secrete PGE2 and activate Foxp3 in the Tregs which increases Treg
> activity; this effect was significantly reduced without an EP4
> (E-prostanoid) receptor and totally absent without an EP2 receptor;
> COX-2 inhibitors (Vioxx, Celebrex) reduced Treg activity, blocked FoxP3
> and decreased tumor growth (this provides a pathway whereby COX-2
> inhibitors can exaggerate allergies) [PMID 15958566]

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. 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)??

BTW it's known fact that aspirin induces asthma in susceptible
subjects ...

Taka

(LOX = lipoxygenase; PLA-2 phospholipase A2)

Kofi wrote:
>>> It's not too much. I take 540mg Thiamine per day.
>
> Taking this much won't actually enhance uptake. There's only so much
> you can push into your system at once. You might want to consider
> benfotiamine as a substitute.
>
>> 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?
>>
>> (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.)
>
> Keep in mind that too much B6 can cause symptoms resembling neuropathy.

I haven't had any such symptoms since my fast.

--
Marshall Price of Miami
Known to Yahoo as d021317c