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.

+ Butyrate (~3g daily).

Would eating psyllium produce similar results?

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.)

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.

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.

In article
a25fb8a8-6eb4-4bc0-baa8-daf40acf5... at (no spam) s50g2000hsb.googlegroups.com>,

Taka <taka0... at (no spam) 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]

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.

In article <kofi-7F3861.00004005062008 at (no spam) news.east.earthlink.net>,
Kofi <kofi at (no spam) 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.

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

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?

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

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)??

In article <kofi-837123.12350806062008 at (no spam) news.east.earthlink.net>,
Kofi <kofi at (no spam) 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?

butyrate added to Kupffer
cells from transfused animals slightly upregulated inducible
cyclooxygenase (COX-2) mRNA levels and increased PLA2 activity fivefold;