Question:
Someone else brought this to my attention. Several months ago we noted
that increasing Bcl-2 expression was likely to inhibit hair growth.
It's known that lithium has a neuroprotective effect via increasing
Bcl-2 and also causes hair loss. It's plausible to think the two might
be related and it's plausible to wonder if curcumin and grape seed
extract are inappropriate topicals for similar reasons. (For those of
you who don't know, Bcl-2 is a gene which blocks apoptotic cell death.)
It appears - if I read this finding correctly - that frontal hairs from
the balding scalp are struggling for their lives and have upregulated
Bcl-2 about 50% in an attempt to do so. This upregulation might account
for some or all of the lower growth cycles we see in these follicles.
It also means that pathways to keep them alive via Bcl-2 are likely to
keep more follicles alive but dormant - or at the very least limit the
effectiveness of antiinflammatory treatments which happen to have this
effect on Bcl-2.
I would note that this is not the only substance good for nerve growth
but bad for hair growth: NT-4, BDNF and proteasome activity in general.
Answer:
No. Lithium inhibits PGE1 (see my paper: Backon J. Lithium-induced
improvement of myotonia: relevance of prostagandin E1 blockade by
lithium. J Neurology Neurosurgery and Psychiatry 1985;48:606-607).
Curcumin, a lipoxygenase inhibitor, involves a different pathway.
About 10 (??) years ago there was a paper in the journal Molecular
Endocrinology on androgen inhibiting effects of lipoxygenase inhibitors.
So topical application of the orange spice turmeric on the scalp
(which also inhibits NFKappaB) would be perfect if it weren't for the
fact that turmeric would STAIN your scalp orange. There is white
curcumin but it costs $500 per pound and is prohibitive in price.
I looked into the curcumin angle sometime back chasing down some
studies. What I find is typical of many other natural remedies. That
is you will find 3 papers that indirectly support the hypothesis that
its good and 1 paper which does just the opposite.
Since no standardized extract of cucumin exist and there are probably
many other molecules mixed in there, there is no way to know whether
it hurts or helps mpb and to what extent.
I cannot quite recall what paper it was that made me say 'ah forget
it' but it was something negative about curcumin promoting
inflammation or something.
If they could have a study to test curcumin or any natural remedy
directly against mpb, that would really make a case.
I went back and rechecked my information on curcumin. It does a lot of
things including blocking the AP-1 pathway and, in cancer cells at
least, downregulating bcl-2 activity although I couldn't find anything
definitive about its effects in skin cells. While it has a number of
valuable anti-inflammatory effects, it's been shown to inhibit VEGF and
fibroblast proliferation. Do you have any evidence besides its NFKB/Bcl
activites? My research indicates it works on prostate cancer cells via
pathways other than those involving androgens.
There is evidence of PGE1 being used to treat chemotherapy induced
alopecia. Are you saying that the hair loss caused by lithium occurs
via its actions on bcl-2 or PGE1?
Yes.
Let's start from scratch:
1. angiogenesis (creation of new blood vessels) is of major importance
in hair growth in male pattern baldness.
2. The mechanism is due to VEGF
3. It's well known in the literature (dozens of studies) that prostaglandin E1
induces angiogenesis and increases VEGF levels and acts as a vasodilator.
4. [More recently, in 2003 a connection was made between eNOS and PGE1]
5. lithium which induces hair loss is a potent inhibitor of PGE1.
6. PGE1 has a bell-shaped curve with different responses to different levels.
7. A large number of factors inhibit the enzyme delta-6-desaturase preventing
the production of PGE1 from linolenic acid.
8. Another factor is thromboxane synthetase which can also inhibit PGE1
by another pathway.
9. About 20 years ago, I found (and published) that ginger, the common
spice, is a potent inhibitor of thromboxane synthetase without a
concomitant increase in PGF2alpha (which would inhibit PGE1 by raising
levels of PGE2. [see also the research on COX2 (cyclo-oxygenase).
10. inhibition of thromboxane synthetase engenders the elevation
of PGI2 (prostacyclin). [BTW Latanprost used in treating glaucoma
has the side effect of increasing hair growth of eyelashes]
11. My suggestion: ingest turmeric with piperine (1/4 tsp black pepper)
to increase its bioavailability. On the one hand, you'd have the powerful
anti-androgenic and anti-inflammatory effects of cucrumin. To increase
VEGF, one might want to topically apply to a wet scalp something like
evening primrose oil or borage oil (which contain gamma-linolenic acid
bypassing the problems of delta-6-desaturase) and this oil would be
pre-mixed with some powdered ginger (or perhaps a few drops of ginger oil
if such an item exists). The turmeric would also increase heat shock
protein 70 (HSP70).
12. If a penetration enhancer would be added (quite a trvial thing) you'd
have a nice way to treat MPB. [P.S. If someone out there gets a patent on
this, what I just wrote is "prior art" :-) ]
13. Last but not least: you'd want to also simultaneously inhibit all three
inflammatory cytokines (iNOS, TNFalphs and NFkppaB). This can be done
only via injection of the hormone atrial natriuretic factor (ANF) [or more
simply by sitting in a very hot Jacuzzi up to your neck for 20-30 minutes]
which also drastically increases levels of ANF.
