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