On Jun 17, 10:32 pm, MattLB <mat...[at]angelfire.com> wrote:
- quote -

Perhaps I can supply my answer to this question - when AA is released
by the PLA2 action it stimulates inflammation. Freed AA is just more
substrate for 5-LOX and later COX-1,2 to make the pro-inflammatory
eicosanoids. Inflammation is not targeted to any particular germ, it
just happens where AA is released and metabolized into the
eicosanoids. Anti-germ antibodies can stimulate AA release at the
places where germs are present at best. AA is also released by
mechanical tissue damage. Killing the germs also takes bite on the
own tissues which are repaired afterwards. VitC helps fighting the
cold because it stimulates the release of even more AA than the germs
could do on their own. This induces powerful inflammatory response
which kills the germs quicker but also substantially damages own
tissues such as the mucous membranes which take longer time to heal
afterwards (you know the long-lasting colds). Well, as Monty has been
pointing out, some common "germs" are better be treated as symbionts
without taking such powerful substances such as AA to start war with
them and turning them into ugly clingy attackers. I hope you got it
right, I am saying that VitC acts like a non-specific immunostimulant
by freeing more AA (something like the prolactin hormone in the end
effect) - this is backed by my original citation. And people are
doing crazy things like boosting the AA release by VitC and inhibiting
AA metabolisation by aspirin/tylenol at the same time - same as
consuming Omega-6 vegetable oils and then counteracting their negative
effects with Omega-3 oils.

Taka

Taka wrote:
- quote -

One PUFA radical can start a chain reaction affecting many others
(dependent on antioxidant status), regardless of oxygen levels. I'm
surprised you didn't know that.

- quote -

You can guess all you want, but that doesn't make your original
comments any more true.

- quote -

Any time insulin levels are low, hormone sensitive lipases in the
adipose tissue break down TGs into free fatty acids. These enter the
blood and are transported via albumin throughout the body. The reason
type I diabetics have acidosis is that the huge number of free fatty
acid molecules reaching the liver overwhelm its ability to burn them,
so lots of ketone bodies are produced as a side product.

- quote -

That's not what the thread's about so it would be veering off the
topic, even if I had a quick answer for you, which I don't.

MattLB

On Jun 16, 4:06 am, "DrollTroll" <fit...[at]optonline.net> wrote:
- quote -

Do you understand what catalysis is all about? O2 can oxidize PUFAs
directly but this takes very long time, like drying the oil painting.
The redox pair of unbound Fe and VitC greatly speeds up this reaction
by recycling each other and producing high levels of ROS which react
with PUFAs much faster that O2 alone. In this process the iron
continuously shifts between Fe3+ and Fe2+ so both are bad. I
recommend you read the previous thread about haptoglobin SNPs which
increase free iron (bound iron is not of much problem):

http://tinyurl.com/3gzfbd

Also see here:

http://pmid.us/17644791+16256097+15306193

http://pmid.us/15047650+18032779

Am J Clin Nutr. 2004 Nov;80(5):1194-200.

Does supplemental vitamin C increase cardiovascular disease risk in
women with diabetes?

Lee DH, Folsom AR, Harnack L, Halliwell B, Jacobs DR Jr.
Division of Epidemiology, School of Public Health, University of
Minnesota, Minneapolis 55454, USA.

BACKGROUND: Vitamin C acts as a potent antioxidant; however, it can
also be a prooxidant and glycate protein under certain circumstances
in vitro. These observations led us to hypothesize that a high intake
of vitamin C in diabetic persons might promote atherosclerosis.
OBJECTIVE: The objective was to examine the relation between vitamin C
intake and mortality from cardiovascular disease. DESIGN: We studied
the relation between vitamin C intake and mortality from total
cardiovascular disease (n = 281), coronary artery disease (n = 175),
and stroke (n = 57) in 1923 postmenopausal women who reported being
diabetic at baseline. Diet was assessed with a food-frequency
questionnaire at baseline, and subjects initially free of coronary
artery disease were prospectively followed for 15 y. RESULTS: After
adjustment for cardiovascular disease risk factors, type of diabetes
medication used, duration of diabetes, and intakes of folate, vitamin
E, and beta-carotene, the adjusted relative risks of total
cardiovascular disease mortality were 1.0, 0.97, 1.11, 1.47, and 1.84
(P for trend < 0.01) across quintiles of total vitamin C intake from
food and supplements. Adjusted relative risks of coronary artery
disease were 1.0, 0.81, 0.99, 1.26, and 1.91 (P for trend = 0.01) and
of stroke were 1.0, 0.52, 1.23, 2.22, and 2.57 (P for trend < 0.01).
When dietary and supplemental vitamin C were analyzed separately, only
supplemental vitamin C showed a positive association with mortality
endpoints. Vitamin C intake was unrelated to mortality from
cardiovascular disease in the nondiabetic subjects at baseline.
CONCLUSION: A high vitamin C intake from supplements is associated
with an increased risk of cardiovascular disease mortality in
postmenopausal women with diabetes.
PMID: 15531665


Am J Clin Nutr. 2003 Dec;78(6):1074-8.

Vitamin C and cancer chemoprevention: reappraisal.

Lee KW, Lee HJ, Surh YJ, Lee CY.
Department of Food Science and Technology, School of Agricultural
Biotechnology, Seoul National University, Seoul, South Korea.

Several studies have reported that even a moderate daily dose of
supplementary vitamin C (200 mg) induces the formation of genotoxins
from lipid hydroperoxides, thereby resulting in DNA damage and
initiation of carcinogenesis. However, other reports questioned the
experimental designs used and suggested that the chemopreventive
effects of vitamin C may be linked to the inhibition of tumor
promotion as well as to the blocking of tumor initiation. In this
article, we discuss issues of contention and some controversies
related to the potential chemopreventive effects of vitamin C in
carcinogenesis.
PMID: 14668266

Taka

On Jun 17, 12:16 am, MattLB <mat...[at]angelfire.com> wrote:
- quote -

Without oxygen, 1 molecule Fe can oxidize 1 molecule PUFA but if
oxygen is present 1 molecule of Fe can catalyze the oxidation of
thousands of PUFA molecules (of course if you have thousands of O2
molecules).

- quote -

Well I guess VitC can produce AGEs as well, but most of them are
derived from PUFAs anyway.

- quote -

Never heard of that, triglycerides yes but free FAs floating in the
blood? Perhaps you mean chylomicrons?

- quote -

Anyway MattLB, to contribute to this thread in a constructive way tell
us what is your idea of the molecular mechanism by which VitC enhances
immunity and fights infections in the body?

Taka

On Jun 13, 5:06 pm, Taka <taka0...[at]gmail.com> wrote:
- quote -

So are many other molecules that also don't have the metabolic
consequences of high sugar levels.

- quote -

All of which has nothing to do with what happens when they get inside
the cells.

- quote -

Not true. Iron can react with lipid hydroperoxides and others without
the presence of oxygen.

- quote -

Something sugars and vit C don't have in common you mean.

- quote -

Only when insulin levels are high. At other times, especially on low
carb diets, levels of free FA are high.

MattLB

"Taka" <taka0038[at]gmail.com> wrote in message
news:9b4f0d67-dc25-4f26-9a71-1f9b93edeed6[at]a1g2000hsb.googlegroups.com...
- quote -


Well, the first cite I found in my boy scout googling "shows" that alpha
tocopherol all by its lonesome forms lipid peroxides. They even show a
mechanism. Vit C stops this.
So your "if any" remark is immediately refuted--apparently you did not
bother to read my cite.
Do you think this is the *only* cite of its kind, regarding Vit E?? Did I
get lucky?
iirc, I think even some of *your cites* discussed Vit E in this regard.

And on what authority do you "trust" one study over another? Do you have
personal laboratory experience in the field, or have you compiled citations
of these articles, for putative credibility?

And, how does one selectively deliver Vit C "to the right places"??




- quote -

Boy-scout chemist or not, I know that acid lowers pH, hot water raises temp,
and reducing agents reduce, they don't oxidize.

"transition metal ion mediated pro-oxidant effect" is self-explanatory.
Since you seem to be the expert, why don't you discuss the *mechanisms* by
which these ions oxidize? Or peroxidize? I would be genuinely interested
in a coherent explanation.

For example, Fe3+ is more of an oxidant than Fe2+, by definition. Which
suggests, btw, that FeSO4 is a "safer" source of iron than FeCl3.
Vit C is famous for reducing Fe3+ to Fe2+. So how can this be *pro
oxidizing*?? Fe2+ may still be oxidizing, but markedly less than Fe3+

I can think of only one way Fe2+ could be made more oxidizing than Fe3+:

There may be an enzyme that has a greater binding constant for Fe2+ than for
Fe3+. If this Fe2+(enzyme) complex is in fact the culprit in an oxidizing
or peroxidizing (pro-inflammatory?) process, then indeed Vit C would be
increasing pro-oxidation in this specific context.

Which is not likely, because afaik, transition metals are buried inside
enzymes (metallo enzymes), and I don't recall ions often binding to enzymes
at active sites, for obvious reasons of poor regulatory control by
ubiquitously available ions.

Mg2+ stabilizing ATP is of course a different story.

And, you would be obligated to show that this transition metal ion-enzyme
complex exists. You, or one of those studies, referred to VitC-Fe complex;
I doubt if such a thing exists, just as intact FeCl3 in solution does not
exist.

Transition metal complexes *do* in fact exist, strictly in the form of
coordination compounds, such as Cr(nicotinate)3. But this has nothing to do
with oxidation or reduction, but rather simple transport of Cr3+.

Please cite mechanisms, if you are able to. These are much more informative
and convincing than dart-thrown abstracts.
--
DT




- quote -

"Taka" <taka0038[at]gmail.com> wrote in message
news:9b4f0d67-dc25-4f26-9a71-1f9b93edeed6[at]a1g2000hsb.googlegroups.com...
- quote -

That's right Taka, iv administration can kill cancer cells and given that
cancers have high expression of hsps, particularly if one of those is HO32,
which may increase the free mitochondrial iron pool, and that vitamin C
itself does this, perhaps via upregulated HO32(don't know), it is not that
surprising that iv administration can facilitate cancer cell death, though I
suspect by necrosis not apoptosis. Oral administration won't work because
once tissue saturation is reached the rest of the vit C is not absorbed. To
maximise the effect I wonder if iron administration would also be a good
idea.



- quote -

Small/appropriate VitC amount at the right place is good and essential
for e.g. collagen synthesis. Large amount at the wrong place may be
dangerous depending on the presence of Fe, PUFAs and the like. AFAIK
there are fewer studies, if any, showing a proinflammatory properties
of VitE. VitE protects from lipid peroxides while VitC may facilitate
their formation. Since lipid peroxides are proapoptotic and activate
p53 high doses of VitC are used intravenously to kill cancers. The
genotoxicity of VitC was refuted later by an artificial system in
vitro experiment which I wouldn't trust as much as the original
Science paper:

Science 15 June 2001:
Vol. 292. no. 5524, pp. 2083 - 2086
DOI: 10.1126/science.1059501

Vitamin C-Induced Decomposition of Lipid Hydroperoxides to Endogenous
Genotoxins

Seon Hwa Lee, Tomoyuki Oe, Ian A. Blair*

Epidemiological data suggest that dietary antioxidants play a
protective role against cancer. This has led to the proposal that
dietary supplementation with antioxidants such as vitamin C (vit C)
may be useful in disease prevention. However, vit C has proved to be
ineffective in cancer chemoprevention studies. In addition, concerns
have been raised over potentially deleterious transition metal ion-
mediated pro-oxidant effects. We have now determined that vit C
induces lipid hydroperoxide decomposition to the DNA-reactive
bifunctional electrophiles 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal,
and 4-hydroxy-2-nonenal. The compound 4,5-Epoxy-2(E)-decenal is a
precursor of etheno-2'-deoxyadenosine, a highly mutagenic lesion
found
in human DNA. Vitamin C-mediated formation of genotoxins from lipid
hydroperoxides in the absence of transition metal ions could help
explain its lack of efficacy as a cancer chemoprevention agent.

For you "Boy Scout chemists", do you have any idea what the transition
metal ion-
mediated pro-oxidant effects are? This is different from the PLA2
induction

Taka

"John Hasenkam" <johnh[at]goawayplease.com> wrote in message
news:7-idnaWzgq3MXs7VnZ2dnUVZ8vWdnZ2d[at]westnet.com.au...
- quote -

If Vit C *lowers* oxidation numbers (probably on all the transition metals,
Fe and Cu among them), why would that be pro-inflammatory?

And what is "pro-inflammatory" anyway? Pro-oxidative?
--
DT





- quote -

In the context of a large free iron pool(and possibly other metals) vitamin
C might be pro-inflammatory. Otherwise ... Don't sweat PLA2 so much, it is
even released via glutamate activity, as is AA. Both help. Balance,
concentrations, context, not presence or absence.


"Marshall Price" <d021317c[at]yahoo.com> wrote in message
news:raqdnWzghfEv6czVnZ2dnUVZ_oTinZ2d[at]earthlink.com...
- quote -

On Jun 14, 4:07 am, "DrollTroll" <fit...[at]optonline.net> wrote:
- quote -

So how would you explain the numerous studies using VitC to oxidize
PUFAs in vitro and its genotoxic effects in vivo? E.g.:

Mol-Cell-Biochem. 1997 Apr; 169(1-2): 171-6

In vitro influence of ascorbate on lipid peroxidation in rat testis
and heart microsomes.

Lipid peroxidation (LPO) in rat testis and heart microsomes was
compared using the ADP/Fe2+ as initiator with and without ascorbate at
different concentrations. The extent of LPO was estimated by the
levels of TBARS and PUFA. Without ascorbate, LPO was higher in heart
than in testis despite elevated levels of catalase in heart. With
increased ascorbate concentrations, a biphasic effect of LPO was
observed. For a concentration less than or = 0.2 mM, ascorbate acted
as pro-oxidant and increased TBARS correlated with decreased PUFA were
observed both in testis and heart. Above 0.2 mM, ascorbate acts as
antioxidant but differences in the rate of LPO were observed. In heart
decreased TBARS correlated with increased PUFA whereas in testis TBARS
only decreased, PUFA were not significantly modified. These results
suggest different mechanisms in LPO initiation in the two organs.
Increasing concentrations of H2O2 produced directly elevated TBARS
levels in testis while a lag phase was observed in heart before the
increase, suggesting that H2O2 was the essential ROS produced by
ascorbate-ADP/Fe2+. The effects of scavengers such as catalase and
ethanol showed an inhibitory effect on TBARS production only in
testis, suggesting the role of H2O2/OH. as an initiator of LPO. In
heart, catalase produced a slight increase in TBARS levels whereas no
modification was observed with ethanol, suggesting a possible direct
activation by ADP/Fe2+ through a metal-oxo intermediate.


http://dx.doi.org/10.1016/S0278-6915(03)00164-9
Induction of lipid peroxidation in biomembranes by dietary oil
components

Prooxidant formation and resulting lipid peroxidation are supposed to
be involved in the pathogenesis of various diseases including cancer.
Cancer risk is possibly influenced by the composition of diet with
high intake of fat and red meat being harmful and high consumption of
fruits and vegetables being protective. Since dietary oils may contain
potential prooxidants, the aim of the present study was to prove (i)
whether oxidative stress in biomembranes may be induced by dietary
oils and if, (ii) which impact it has on the viability and
proliferation of cultured colon (carcinoma) cells. Lipid hydroperoxide
content in dietary oils increased after heating. Linoleic acid
hydroperoxide (LOOH) and/or oils with different hydroperoxide contents
induced lipid peroxidation in liposomes, erythrocyte ghosts and colon
cells. Upon incubation with liposomes, both LOOH and heated oil
induced lipid peroxidation only in the presence of iron and ******
ascorbate *******. LOOH was sufficient to start lipid peroxidation of
erythrocyte ghosts. LOOH incorporates into the lipid bilayer
decreasing membrane fluidity and initiating lipid peroxidation in the
lipid phase. When cultured cells (IEC18 intestinal epithelial cells,
SW480 and HT29/HI1 colon carcinoma cells) were exposed to LOOH, they
responded by cell death both via apoptosis and necrosis. Cells with
higher degree of membrane unsaturation were more susceptible and
antioxidants (vitamin E and selenite) were protective indicating the
involvement of oxidative stress. Thus, peroxidation of biomembranes
can be initiated by lipid hydroperoxides from heated oils. Dietary
consumption of heated oils may lead to oxidative damage and to cell
death in the colon. This may contribute to the enhanced risk of colon
cancer due to regenerative cell proliferation.


http://dx.doi.org/10.1016/S0009-3084(97)00038-8
Mechanisms of lipid peroxidation in human blood plasma: a kinetic
approach

There is strong evidence that the oxidation of plasma lipoproteins
plays an important role in atherogenesis. The exact mechanisms by
which lipoprotein oxidation occurs in the presence of other plasma
constituents, however, remains unclear. To investigate the role of
different antioxidants for this process, we studied the oxidation of
human plasma supplemented in vitro with physiological amounts of major
plasma antioxidants -tocopherol, ubiquinol-10, ascorbate, urate,
bilirubin and albumin. The plasma was diluted 2-fold and oxidized by
3.75 mM Cu(II). The concentrations of the antioxidants, fatty acids,
linoleic acid hydroperoxides and oxycholesterols in oxidizing plasma
were measured. The oxidation was characterized by three consecutive
phases similar to the known lag, propagation, and decomposition phases
of low density lipoprotein oxidation. The rate of the initiation of
oxidation as calculated from antioxidant consumption rates was raised
by supplementation with -tocopherol or ascorbate. The oxidation rate
in the lag phase was lowered by supplementation with any of the
antioxidants, whereas in the propagation phase the oxidation rate was
slightly higher in supplemented than in unsupplemented plasma. The
kinetic chain length in the lag phase was less than one in
supplemented plasma and about one in unsupplemented plasma. The chain
length in the propagation phase was between three and six for all
plasma samples. A higher rate of urate consumption and a reduced rate
of -tocopherol consumption were found in plasma supplemented with
ascorbate in comparison with unsupplemented plasma. These data suggest
that: (i) the reduction of Cu(II) by -tocopherol and ascorbate is a
major initiating event in Cu(II)-catalyzed oxidation of human plasma;
(ii) the following lag phase is caused by radical-scavenging effects
of all antioxidants with -tocopherol as a major lipophilic and urate
as a major hydrophilic scavenger; (iii) interactions between
antioxidants, such as regeneration of ascorbate by urate and of -
tocopherol by ascorbate, take place during the lag phase; (iv) in the
absence of added antioxidants the oxidation in the lag phase can occur
via a chain reaction; and (v) in the propagation phase the oxidation
is not inhibited by antioxidants and occurs autocatalytically.


J Lab Clin Med. 1989 Sep;114(3):243-9.

Iron loading modifies the fatty acid composition of cultured rat
myocardial cells and liposomal vesicles: effect of ascorbate and alpha-
tocopherol on myocardial lipid peroxidation.

Link G, Pinson A, Kahane I, Hershko C.
Department of Nutrition, Hebrew University Hadassah Medical School,
Jerusalem, Israel.

Increased generation of free radicals and accelerated lipid
peroxidation are important manifestations of iron toxicity. We have
studied the effect of iron loading on lipid peroxidation in cultured
rat myocardial cells by direct measurement of the fatty acid
composition of cellular lipids. Iron loading produced by 24-hour
incubation of cultured cells with 0.36 mmol/L ferric ammonium citrate
resulted in a moderate reduction in polyunsaturated fatty acids
(PUFAs) such as 22:5 and 22:6. A more drastic reduction in PUFAs and
an apparent reciprocal increase in the proportion of saturated fatty
acids were both obtained after 24 hours of incubation of liposomal
vesicles prepared from whole cell lipid extracts with iron at between
pH 4.5 and pH 5.5. Reduction of 22:5 and 22:6 was first noticed at 3
hours, and undetectable levels were reached by 12 and 24 hours of
incubation. Ascorbate had a biphasic effect on liposomal PUFA levels:
at low concentrations (0.057 mmol/L) it enhanced the iron-induced
changes in liposomal fatty acid composition, but at higher
concentrations (0.57 and 5.7 mmol/L), it inhibited these changes.
Unlike ascorbate, alpha-tocopherol (0.023 to 2.3 mmol/L) inhibited the
iron-induced reduction in PUFAs in a dose-dependent manner, with
complete inhibition of the iron effect at 2.3 mmol/L. These
observations underline the particular sensitivity of PUFAs to iron-
induced lipid peroxidation. They also illustrate the ability of
ascorbate and alpha-tocopherol to modify iron-induced lipid
peroxidation. Further studies are required to explore the possible
therapeutic implications of these observations in clinical iron
overload.
PMID: 2769018


Int J Biochem Cell Biol. 1996 Feb;28(2):137-49.

A possible mechanism for initiation of lipid peroxidation by ascorbate
in rat liver microsomes.

Casalino E, Sblano C, Landriscina C.
Laboratory of Biochemistry, University of Bari, Italy.

The mechanism by which lipid peroxidation progresses has been known
for years, but there is disagreement regarding the mode of its
initiation. The aim of this study was to examine: (a) the role of
endogenous iron in the initiation of ascorbate-induced lipid
peroxidation in microsomal and liposomal membranes; (b) the role of
oxygen-free radicals in this process; and (c) the redox state of
ascorbate during the course of lipid peroxidation. Ascorbate-induced
lipid peroxidation was assessed by measuring hydroperoxide and
thiobarbituric acid reactive substances (TBARS) formation in membranes
after incubation in Tris-HCl buffer (pH 7.4) for 15 min. To confirm
the role of endogenous iron and oxygen-free radicals, the effect of
iron chelating agents (EDTA and thiourea) and radical scavengers
(benzoate, mannitol, catalase and SOD) on lipid peroxidation was
examined. Spectrophotometric measurements and ESR spectra have made it
possible to determine ascorbate concentration and its redox state.
Ascorbate promoted lipid peroxidation in both rat liver microsomes and
liposomes without addition of exogenous iron. Iron chelating agents
such as EDTA and thiourea inhibited lipid peroxidation, while SOD,
catalase, mannitol and benzoate had no effect. The addition of 5
microM Fe2+ (or Fe3+) to the incubation mixture did not significantly
alter hydroperoxide production, but that of TBARS was increased. Lipid
peroxidation significantly altered the fatty acid profile in
microsomes and liposomes, the most affected being the C20:4 and C22:6
species. Ascorbate in Tris-HCl buffer (pH 7.4) autoxidized very
slowly. Its oxidation was catalyzed by Fe3+ ions at a rate determined
by incubation time and iron concentration. In contrast, no ascorbate
oxidation occurred in the presence of microsomes when lipid
peroxidation was proceeding at a maximal rate. Under these conditions
a typical ascorbyl radical ESR spectrum signal greater than that
arising from ascorbate alone was obtained and the magnitude of this
signal was unchanged by variations of microsome or ascorbate
concentrations. A ferrous ion ascorbyl radical complex was responsible
for this signal. These results suggest that ************ an ascorbate-
microsomal iron complex is responsible for the initiation of lipid
peroxidation, **************and that during this process ascorbate
remains in its reduced form.
PMID: 8729001

Taka

"Taka" <taka0038[at]gmail.com> wrote in message
news:22d34952-4edc-48d1-a477-0ad7efc82b7c[at]x1g2000prh.googlegroups.com...
- quote -


Highly unlikely, as per my response to MattLB.
VitC (fresh Vit C, at any rate) is a reducing agent, likely rendering O2, Fe
etc. unable to oxidize pufa's. It is a kind of sacrificial molecule, as are
the conjugated systems of Vits A and E, beta carotene, CLA's, poss. some
amino acids, etc.

Altho structurally Vit C appears simple, it is actually subtlely
complicated, having both pH effects AND redox effects, both of which are
independent, iirc.

It is a well-studied molecule, and you would have to *chemically support*,
via a proposed mechanism, just how VitC would promote peroxide formation,
when its putative function is directly opposite to this.

re the VLCKD (kd = ketogenic diet?), seems to support atkins.

Except that if this really is ketogenic, long term it screws up the body so
badly that any specific lipid profiles are irrlevant. This has been proven
in the military, and pregnant women on ketogenic diets wind up with brain
damaged kids. Wonder why.....

Big diff. between low carb and ketogenic.
--
DT




- quote -

"MattLB" <mattlb[at]angelfire.com> wrote in message
news:d6828707-c6e6-41fe-9c2e-3ffcfc2a394d[at]k30g2000hse.googlegroups.com...
- quote -

Not a likely scenario.
Vit C is actually an equilibrium solution between oxy- and de-oxy ascorbic
acid, which are redox couples, whose specific purpose is "reducing"
oxidative compounds, among them Fe3+ to Fe2+, and Cu2+ to Cu1+, which
radically affects absorption rates of these minerals.
iirc, this occurs via a reactive double bond in VitC reversibly converting
to a single bond.

Unlikely for C itself to become a free radical.
--
DT




- quote -

On Jun 13, 9:33 pm, MattLB <mat...[at]angelfire.com> wrote:
- quote -

And as specific as the chronic inflammatory states are ...

- quote -

Yet VitC is made from sugar, enters cells via the same receptors as
sugar and its absorption is competitively inhibited by sugar ...

- quote -

Like our wonderful PUFAs. BTW you forgot oxygen without which iron is
powerless. The combination O2+Fe+VitC+PUFAs is the best setting for
getting full spectrum of lipid hydroperoxides and free radicals and
you can even get so called AGEs if you throw in sugars.

I have mentioned previously how sugar and saturated fatty acids (which
are rare in their free form in the body BTW) release AA:

http://tinyurl.com/52y4kk

http://tinyurl.com/4c6w9l

And a recent article has been posted showing how the carbohydrate
restriction has antiinflammatory effects even in people full of AA:

Lipids. 2008 Jan;43(1):65-77. Epub 2007 Nov 29.

Comparison of low fat and low carbohydrate diets on circulating fatty
acid composition and markers of inflammation.

Forsythe CE, Phinney SD, Fernandez ML, Quann EE, Wood RJ, Bibus DM,
Kraemer WJ, Feinman RD, Volek JS.
Department of Kinesiology, University of Connecticut, 2095 Hillside
Road, Unit 1110, Storrs, CT, 06269-1110, USA.

Abnormal distribution of plasma fatty acids and increased inflammation
are prominent features of metabolic syndrome. We tested whether these
components of metabolic syndrome, like dyslipidemia and glycemia, are
responsive to carbohydrate restriction. Overweight men and women with
atherogenic dyslipidemia consumed ad libitum diets very low in
carbohydrate (VLCKD) (1504 kcal:%CHO:fatrotein = 12:59:28) or low in
fat (LFD) (1478 kcal:%CHO:fatrotein = 56:24:20) for 12 weeks. In
comparison to the LFD, the VLCKD resulted in an increased proportion
of serum total n-6 PUFA, mainly attributed to a marked increase in
arachidonate (20:4n-6), while its biosynthetic metabolic intermediates
were decreased. The n-6/n-3 and arachidonic/eicosapentaenoic acid
ratio also increased sharply. Total saturated fatty acids and 16:1n-7
were consistently decreased following the VLCKD. Both diets
significantly decreased the concentration of several serum
inflammatory markers, but there was an overall greater anti-
inflammatory effect associated with the VLCKD, as evidenced by greater
decreases in TNF-alpha, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and
PAI-1. Increased 20:4n-6 and the ratios of 20:4n-6/20:5n-3 and n-6/n-3
are commonly viewed as pro-inflammatory, but unexpectedly were
consistently inversely associated with responses in inflammatory
proteins. In summary, a very low carbohydrate diet resulted in
profound alterations in fatty acid composition and reduced
inflammation compared to a low fat diet.
PMID: 18046594

Taka

On Jun 12, 8:10 pm, Marshall Price <d0213...[at]yahoo.com> wrote:
- quote -

Just another inflammatory (hoho) and disingenous headline from Taka,
I'm afraid.

Having looked briefly at the paper the whole thing is very non-
specific. Basically when you raise blood levels of vitamin C to
*pharmacological* levels by directly injecting Vit C into the
bloodstream (i.e. not by eating supplements) you see increased
activation of molecules involved in oxidative stress.

In the presence of iron, vitamin C can become a free radical that can
then damage other molecules and lead to activation of various enzymes.
One of these causes the release of arachidonic acid within the cell.
These is as specific as the connection is. Mentioning sugar is a
complete red herring. Any molecule that can become a free radical
through interaction with iron will have the same effect.

The experiments were also done using cells growing in flasks, with
vitamin C directly added to the cell medium, so have rather little
connection to the human body where the vitamin C is consumed along
with a host of other molecules.

MattLB

On Jun 13, 4:10 am, Marshall Price <d0213...[at]yahoo.com> wrote:
- quote -

To make long story short, AA needs to be converted to proinflammatory
metabolites called eicosanoids to exert its immunity boosting and
destructive effects. Before these metabolites can be created by the
action of the 5-LOX and COX-1,2 enzymes, AA has to be released/cleaved
off from the membrane phospholipids. This cleavage is done by the
PLA2 enzymes which turn to be quite important in the regulation and
localization of the inflammatory responses. You can read about them
e.g. in Wikipedia:

http://en.wikipedia.org/wiki/PLA2

Expressing PLA2 is like igniting your car engine, which can have
different types of fuel in it (e.g. the gasoline with added sugar as
Monty recently mentioned). Some pathogens explore this by expressing
and excreting their own PLA2 enzymes which ignite powerful
inflammatory responses in the affected tissues.

I have found some papers posted previously showing that sugar and
saturated fatty acids also upregulate PLA2. It's not as drastic as in
the case of the pathogens or reaction to infection and tissue damage
but enough to cause silent chronic inflammation. In the
abovementioned paper VitC also stimulates PLA2 what is understandable
given its immune-boosting effects. If you catch cold you drink VitC
drink with added sugar, right? It will inflame your body what helps
to kill the invading germs. Helps in the short term and if the germs
are really bad but also damages your own tissues which need to be
repaired afterwards. A better approach is to downregulate the
inflammatory mediators derived from AA by ingesting COX inhibitors
like ginger or EVO. Then there will be no tissue damage and the germs
start behaving more like symbionts and decrease in number if they are
not those nasty types which are better be killed with antibiotics
anyway.

The bottom line is VitC stimulates the release of AA at higher doses
so it's foolish taking it as supplementary antioxidant when you have
no need to boost your immunity. There are papers showing that VitC is
even genotoxic what is likely caused by its reactions with Fe and
PUFAs:

http://tinyurl.com/66w78p

Taka

Taka wrote:
- quote -

Come on, Taka. You chose the subject line, and you said "similar in
structure and effects to sugar," and this is a discussion group, so how
about some discussion?

Sugar has 12 carbons; ascorbic acid has six. Sugar provides quick
energy, ascorbic acid provides none. Most antioxidants are
anti-inflammatory; ascorbic acid is an antioxidant, but you say it's
"proinflammatory."

Surely you realize this stuff is hard reading or incomprehensible to
almost everybody in this newsgroup but you, so please help us understand
what it says and why you said what you did.

--
Marshall Price of Miami
Known to Yahoo as d021317c

"Taka" <taka0038[at]gmail.com> wrote in message
news:82cab1e3-cdd6-4b8f-8620-c809ddec531b[at]b1g2000hsg.googlegroups.com...
- quote -

Didn't understand a g-d thing in this abstract--or the point--but the reason
sugar and VitC are similar in structure is because Vit C is enzymatically
biosynthesized from sugar, in most mammals, in relatively few steps.

As is synthetic vitC, iirc. Not enyzymatically, as both r, s isomers are
produced equally, but the starting material is sugar, which is why it was
always pretty cheap.

It probably is *still* pretty cheap, but since every g-d thing is now
"branded" up the kazoo on the retail level, prices are probably artificially
10x higher than necessary. by the time it gets to our sorry retail asses.

Why we and a few other species lost the ability to synthesize vit C is
interesting evolutionary speculation.
--
DT


- quote -

Similar in structure and effects to sugar ...
Taka

Mol Cell Biochem. 2008 May 22.

Redox-active antioxidant modulation of lipid signaling in vascular
endothelial cells: vitamin C induces activation of phospholipase D
through phospholipase A(2), lipoxygenase, and cyclooxygenase.

Steinhour E, Sherwani SI, Mazerik JN, Ciapala V, O'Connor Butler E,
Cruff JP, Magalang U, Parthasarathy S, Sen CK, Marsh CB, Kuppusamy P,
Parinandi NL.
Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary,
Allergy, Critical Care, and Sleep Medicine, Department of Medicine,
College of Medicine, The Ohio State University, Columbus, OH, USA.

We have earlier reported that the redox-active antioxidant, vitamin C
(ascorbic acid), activates the lipid signaling enzyme, phospholipase D
(PLD), at pharmacological doses (mM) in the bovine lung microvascular
endothelial cells (BLMVECs). However, the activation of phospholipase
A(2) (PLA(2)), another signaling phospholipase, and the modulation of
PLD activation by PLA(2) in the ECs treated with vitamin C at
pharmacological doses have not been reported to date. Therefore, this
study aimed at the regulation of PLD activation by PLA(2) in the
cultured BLMVECs exposed to vitamin C at pharmacological
concentrations. The results revealed that vitamin C (3-10 mM)
significantly activated PLA(2) starting at 30 min; however, the
activation of PLD resulted only at 120 min of treatment of cells under
identical conditions. Further studies were conducted utilizing
specific pharmacological agents to understand the mechanism(s) of
activation of PLA(2) and PLD in BLMVECs treated with vitamin C (5 mM)
for 120 min. Antioxidants, calcium chelators, iron chelators, and
PLA(2) inhibitors offered attenuation of the vitamin C-induced
activation of both PLA(2) and PLD in the cells. Vitamin C was also
observed to significantly induce the formation and release of the
cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic
acid (AA) metabolites and to activate the AA LOX in BLMVECs. The
inhibitors of PLA(2), COX, and LOX were observed to effectively and
significantly attenuate the vitamin C-induced PLD activation in
BLMVECs. For the first time, the results of the present study revealed
that the vitamin C-induced activation of PLD in vascular ECs was
regulated by the upstream activation of PLA(2), COX, and LOX through
the formation of AA metabolites involving oxidative stress, calcium,
and iron.
PMID: 18496733