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Science Forum Index » Life Extension Forum » Vitamin C-mediated Maillard Reaction in the Lens...
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| Olafur Pall Olafsson... |
 Posted: Sat May 03, 2008 10:39 pm |
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Ann N Y Acad Sci. 2008 Apr;1126:194-200.
Related Articles, Links
Click here to read
Vitamin C-mediated Maillard Reaction in the Lens Probed in a
Transgenic-mouse Model.
Fan X, Monnier VM.
CWRU, 2103 Cornell Rd., Wolstein Research Building, Cleveland, OH
44106. vmm3 at (no spam) cwru.edu.
Aging human lens crystallins are progressively modified by yellow
glycation, oxidation, and cross-linked carbonyl compounds that have
deleterious properties on protein structure and stability. In order to
test the hypothesis that some of these compounds originate from
oxidized vitamin C, we have overexpressed the human vitamin C
transporter 2 (hSCVT2) in the mouse lens. We find that levels of
ascorbic and dehydroascorbic acid are highly elevated compared to the
wild type and that the lenses have accumulated yellow color and
advanced Maillard reaction products identical with those of the human
lens. Treatment of the mice with nucleophilic inhibitors can slow down
the process, opening new avenues for the pharmacological prevention of
senile cataractogenesis.
PMID: 18448816 [PubMed - in process]
Related Articles
* Vitamin C mediates chemical aging of lens crystallins by the
Maillard reaction in a humanized mouse model. [Proc Natl Acad Sci U S
A. 2006]
* The effect of UVA light on the anaerobic oxidation of
ascorbic acid and the glycation of lens proteins. [Invest Ophthalmol
Vis Sci. 2003]
* High galactose levels in vitro and in vivo impair ascorbate
regeneration and increase ascorbate-mediated glycation in cultured rat
lens. [Exp Eye Res. 1996]
* Structure and mechanism of formation of human lens
fluorophore LM-1. Relationship to vesperlysine A and the advanced
Maillard reaction in aging, diabetes, and cataractogenesis. [J Biol
Chem. 1999]
* Transition metal-catalyzed oxidation of ascorbate in human
cataract extracts: possible role of advanced glycation end products.
[Invest Ophthalmol Vis Sci. 2000]
* >> See all Related Articles...
Here are a few quotes from the full text article:
"Because of the high reactivity of ASA degradation products with
proteins and its presence in high concentrations in the human lens, we
and others have postulated that it is, in part, responsible for the
progressive damage to the aging human lens crystallins.8-10 However,
it has not been possible to unequivocally implicate vitamin C in this
aging process because the products formed are not specific for this
vitamin."
"To confirm the role of vitamin C in lens ag, we took advantage of the
fact that the mouse lens has very low levels of the vitamin and
engineered a mouse that selectively overexpresses the human vitamin C
transporter 2 (hSVCT2)11 in both the epithelium and fiber-like lens
cells. Consequently, lenticular levels of vitamin C and its oxidation
products dramatically increased, resulting in accelerated formation of
several advanced glycation end products (AGEs) identical with those of
the aging human lens. With the use of this humanized mouse model, we
conducted a first intervention study with potential inhibitors to test
the feasibility of preventing ascorbylation in aging lenses."
"Finally, lenticular levels of ASA and DHA measured by HPLC in
trichloroacetic acid extract were fivefold to 15-fold elevated. ASA
increased from approximately 0.2 mM to 0.5-2.5 mM, and DHA increased
from 10 ìM to 40-250 ìM in the transgenic lenses (Fig. 1B and C)."
"Finally, we noticed in the course of this work that the 12-month-old
transgenic lenses had acquired a yellow color similar to that observed
in older human lenses (Fig. 2)."
In the quote below AG is Aminoguanidine and PM is pyridoxamine while
NC-I and NC-II are nucleophilic compounds whose names were not given
in the full text.
"Toward this end, we have tested five candidate inhibitors in a 7-
month-long intervention study. NC-I was able to significantly decrease
the lysine-arginine cross-link pentosidine by more than 50% (Table 2)
(P < 0.04) and suppressed by 60% the increase in the lysine-modified
AGE product CML (Table 2) (P < 0.007). NC-II-treated mice showed
significantly decreased pentosidine level (Table 2) (P < 0.003) but no
change in CML. NC-I but not NC-II tended to decrease the lysine-linked
modification CEL. It should be noted that the latter was only mildly
elevated, as previously observed,15 suggesting that MGO formation is
not an important pathway in the oxidative degradation of ASA. Animals
treated with AG, PM, NC-I, and NC-II showed improvements of lysine-
lysine cross-link compound K2P. Because of large standard deviations,
none of them reached significance. Animals treated with AG, PM, and
pentosidine showed no significant improvement in any of the other
measured AGEs."
"The above data strongly implicate vitamin C in at least one form of
the chemical processes that affect the aging human lens crystallins.
Furthermore, the hSVCT2-äenáA mouse is an animal model capable of
reproducing, within a very short time, the yellow discoloration and
crystallin modifications that increase over several decades in the
human lens. These findings suggest that a substantial part of the
yellowing process to aging human lens crystallins likely arises from
vitamin C. These two statements and their significance for the aging
human lens and cataractogenesis need to be examined. At the outset, it
should be noted that cataracts, i.e., the formation of light-
scattering protein aggregates, can occur at any age as a result of
mutations in any of the lens proteins that are critically involved in
lens transparency. Thus, chemical modification of lens crystallins is
not needed for opacification to occur, and, in the absence of overt
cataractogenic conditions and risk factors, the healthy lens can
remain transparent for decades while being progressively discolored.
Concerning this latter process, however, several epidemiological and
clinical studies have revealed a strong association among lens color,
lens fluorescence, and the nuclear sclerosis that accompany age-onset
cataract formation.20,21 It is, therefore, reasonable to postulate
that the accumulation of protein modifications by vitamin C oxidation
and other Maillard reaction products may predispose lens crystallins
toward destabilization and aggregation, as supported by several in
vitro studies.22-24" |
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| Posted: Sun May 04, 2008 10:10 am |
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I don't have an access to the full paper of the abstract above (PMID:
18448816)but a study that preceded it is available free at:
http://www.pnas.org/cgi/content/full/103/45/16912
The Discussion section summarizes the take home message from their
work thus far:
"What are the implications of our findings concerning vitamin C
supplementation, lenticular aging, and cataractogenesis? On one hand,
the vanishing low vitamin C levels in the mouse lens imply that
millimolar concentrations of the vitamin are not necessary for
maintaining lens clarity. On the other hand, low serum levels of the
vitamin have been associated with increased risk of cataractogenesis
in the human (29), and various studies suggest that supplementation of
the vitamin is beneficial for decreasing the risk of cataractogenesis
(30), in particular under conditions that favor oxidant stress (31).
Proposed mechanisms include the scavenging of free radicals by the
vitamin itself or in conjunction with glutathione that is present in
millimolar concentrations in rodent lenses. Thus, vitamin C joins the
ranks of those metabolites that are essential for life, such as
glucose, fatty acids, and oxygen, but can inflict damage when the
cell's defenses are weakened by diabetes, end-stage renal disease,
poor nutrition, exposure to UV light, or old age itself.
The discovery that high cellular concentrations of vitamin C can
inflict damage in such a short time, as in the hSVCT2-äenáA mouse,
could be relevant to other tissues with high SVCT2 activity, such as
the hippocampus and the adrenal glands, in which ascorbate
concentrations reach up to 10 mM (32, 33). Both tissues can be
severely affected in their function during aging, and thus the
possibility emerges that excess vitamin C oxidation in hippocampal
neurons (34) may, for example, contribute to age-related
neurodegenerative diseases. Further work is required to understand how
vitamin C damages lens crystallins and other molecular structures
during aging. In that regard, the hSVCT2-äenáA mouse provides an
extraordinary tool for the development of drugs that can delay this
aspect of the lenticular aging process."
Arbor |
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| Olafur Pall Olafsson... |
| Posted: Sun May 04, 2008 10:24 am |
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On May 4, 8:10 pm, soowhatdouth... at (no spam) hotmail.com wrote:
Quote: I don't have an access to the full paper of the abstract above (PMID:
18448816)but a study that preceded it is available free at:http://www.pnas..org/cgi/content/full/103/45/16912
The Discussion section summarizes the take home message from their
work thus far:
Thanks for the additional information Arbor. BTW If you want to read
the full text article of the study I posted just contact me and I'll
send you a copy.
Olafur
Quote: "What are the implications of our findings concerning vitamin C
supplementation, lenticular aging, and cataractogenesis? On one hand,
the vanishing low vitamin C levels in the mouse lens imply that
millimolar concentrations of the vitamin are not necessary for
maintaining lens clarity. On the other hand, low serum levels of the
vitamin have been associated with increased risk of cataractogenesis
in the human (29), and various studies suggest that supplementation of
the vitamin is beneficial for decreasing the risk of cataractogenesis
(30), in particular under conditions that favor oxidant stress (31).
Proposed mechanisms include the scavenging of free radicals by the
vitamin itself or in conjunction with glutathione that is present in
millimolar concentrations in rodent lenses. Thus, vitamin C joins the
ranks of those metabolites that are essential for life, such as
glucose, fatty acids, and oxygen, but can inflict damage when the
cell's defenses are weakened by diabetes, end-stage renal disease,
poor nutrition, exposure to UV light, or old age itself.
The discovery that high cellular concentrations of vitamin C can
inflict damage in such a short time, as in the hSVCT2-äenáA mouse,
could be relevant to other tissues with high SVCT2 activity, such as
the hippocampus and the adrenal glands, in which ascorbate
concentrations reach up to 10 mM (32, 33). Both tissues can be
severely affected in their function during aging, and thus the
possibility emerges that excess vitamin C oxidation in hippocampal
neurons (34) may, for example, contribute to age-related
neurodegenerative diseases. Further work is required to understand how
vitamin C damages lens crystallins and other molecular structures
during aging. In that regard, the hSVCT2-äenáA mouse provides an
extraordinary tool for the development of drugs that can delay this
aspect of the lenticular aging process."
Arbor |
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| Thomas Carter... |
| Posted: Sun May 04, 2008 1:52 pm |
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Guest
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On May 4, 4:24 pm, Olafur Pall Olafsson <olafurp... at (no spam) yahoo.com> wrote:
Quote: On May 4, 8:10 pm, soowhatdouth... at (no spam) hotmail.com wrote:
I don't have an access to the full paper of the abstract above (PMID:
18448816)but a study that preceded it is available free at:http://www.pnas.org/cgi/content/full/103/45/16912
The Discussion section summarizes the take home message from their
work thus far:
Thanks for the additional information Arbor. BTW If you want to read
the full text article of the study I posted just contact me and I'll
send you a copy.
Olafur
"What are the implications of our findings concerning vitamin C
supplementation, lenticular aging, and cataractogenesis? On one hand,
the vanishing low vitamin C levels in the mouse lens imply that
millimolar concentrations of the vitamin are not necessary for
maintaining lens clarity. On the other hand, low serum levels of the
vitamin have been associated with increased risk of cataractogenesis
in the human (29), and various studies suggest that supplementation of
the vitamin is beneficial for decreasing the risk of cataractogenesis
(30), in particular under conditions that favor oxidant stress (31).
Proposed mechanisms include the scavenging of free radicals by the
vitamin itself or in conjunction with glutathione that is present in
millimolar concentrations in rodent lenses. Thus, vitamin C joins the
ranks of those metabolites that are essential for life, such as
glucose, fatty acids, and oxygen, but can inflict damage when the
cell's defenses are weakened by diabetes, end-stage renal disease,
poor nutrition, exposure to UV light, or old age itself.
The discovery that high cellular concentrations of vitamin C can
inflict damage in such a short time, as in the hSVCT2-äenáA mouse,
could be relevant to other tissues with high SVCT2 activity, such as
the hippocampus and the adrenal glands, in which ascorbate
concentrations reach up to 10 mM (32, 33). Both tissues can be
severely affected in their function during aging, and thus the
possibility emerges that excess vitamin C oxidation in hippocampal
neurons (34) may, for example, contribute to age-related
neurodegenerative diseases. Further work is required to understand how
vitamin C damages lens crystallins and other molecular structures
during aging. In that regard, the hSVCT2-äenáA mouse provides an
extraordinary tool for the development of drugs that can delay this
aspect of the lenticular aging process."
Arbor- Hide quoted text -
- Show quoted text -
Hi Olafur,
The best preventative action against cataracts is the wearing of sun
glasses. The second best is hi vitamin C supplementation. This appears
to be effective even in women. Here’s what I have on it. (carnosine
eye drops may be better, but this is less well documented.)
Thomas
J Nutr. 2002 Jun;132(6):1299-306.
Vitamin C is associated with reduced risk of cataract in a
Mediterranean
population.
Valero MP, Fletcher AE, De Stavola BL, Vioque J, Alepuz VC.
London School of Hygiene and Tropical Medicine, London, UK.
mpvalero at (no spam) usp.br
Cataract is an important visual problem of older people and a
substantial health
care cost in many countries. Most studies investigating risk factors
for
cataract have been conducted in the United States, and there is less
information
on the possible role of dietary factors in European populations. We
conducted a
case-control study to investigate the association of antioxidant
vitamins
(vitamin C, vitamin E, vitamin A, beta-carotene, alpha-carotene,
beta-cryptoxanthin, lycopene, zeaxanthin and lutein) and minerals
(zinc and
selenium) and risk of cataract in a Mediterranean population. Cases
with
cataract (343) and 334 age/sex frequency-matched controls aged 55 to
74 y were
selected from an ophthalmic outreach clinic in Valencia, Spain.
Participants
were interviewed about their diet using a Food Frequency
Questionnaire, and
other information on potential confounders, such as smoking, alcohol,
and
education. Blood samples were analyzed by a colorimetric method for
vitamin C
and by reversed-phase HLPC for other blood antioxidants. Blood levels
of vitamin
C above 49 micromol/L were associated with a 64% reduced odds for
cataract (P <
0.0001). Dietary intake of vitamins C, E and selenium were marginally
associated
with decreased odds (P = 0.09, P = 0.09, P = 0.07, respectively),
whereas
moderately high levels of blood lycopene (>0.30 micromol/L) were
associated with
a 46% increased odds of cataract (P = 0.04). Our results strengthen
the evidence
for a protective role for vitamin C on the aging lens as this effect
was seen in
a population characterized by high vitamin C intakes.PMID: 12042450
this paper is a horrible example of scientific integrity. The lycopene
association was very moderate and insignificant, around 15%. There was
a dose dependant effect of C 70% reduction in the 5th quintile and
there was very good, low OR for zinc as well as other good reductions
for other nutrients.
Cataracts vs zinc
cataracts vs vitamin C
cataracts vs carotenoids
cataracts vs lycopene……………………..
SUMMARY OF CLINICAL TRIALS OF CATARACTS VS
VITAMIN C
RESULT
DOSAGE TIME SPAN COHORT #
1 Same study as #3.
500 6.3 n/a
2 600% reduction of progression
750 3 300
3 No effect on cataracts 500
6.3 4500
.75 OR for loss of sight
4 36% reduction n/a
5.5 2100
44% reduction (in 2nd group) n/a
5.5 3200
Epidemiological studies show better results for a gram dose and a
ten year duration. 2/3 studies show some affect. #1 was poorly
reported on in an unkown , limited scope journal. #3 the cohort was
examined for cataracts by photo, not in person, so they may have
missed a lot. #4b the cohort was split five ways, so a good affect
might have been lost in the vitamin C group. #2, the only real
positive trial was sponsored by Roche, the world’s largest maker of
vitamin C.
These are the refs for the above trials
1: Sackett CS, Schenning S.
The age-related eye disease study: the results of the clinical trial.
Insight. 2002 Jan-Mar;27(1):5-7.
PMID: 11962062 [PubMed - indexed for MEDLINE]
2: Chylack LT Jr, Brown NP, Bron A, Hurst M, Kopcke W, Thien U,
Schalch W.
The Roche European American Cataract Trial (REACT): a randomized
clinical trial
to investigate the efficacy of an oral antioxidant micronutrient
mixture to slow
progression of age-related cataract.
Ophthalmic Epidemiol. 2002 Feb;9(1):49-80.
PMID: 11815895 [PubMed - indexed for MEDLINE]
3: Age-Related Eye Disease Study Research Group.
Arch Ophthalmol. 2001 Oct;119(10):1439-52. Related Articles, Links
A randomized, placebo-controlled, clinical trial of high-dose
supplementation with vitamins C and E and beta carotene for age-
related cataract and vision loss: AREDS report no. 9.
Age-Related Eye Disease Study Research Group.
BACKGROUND: Experimental and observational data suggest that
micronutrients with antioxidant capabilities may retard the
development of age-related cataract. OBJECTIVE: To evaluate the effect
of a high-dose antioxidant formulation on the development and
progression of age-related lens opacities and visual acuity loss.
DESIGN: The 11-center Age-Related Eye Disease Study (AREDS) was a
double-masked clinical trial. Participants were randomly assigned to
receive daily oral tablets containing either antioxidants (vitamin C,
500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) or no
antioxidants. Participants with more than a few small drusen were also
randomly assigned to receive tablets with or without zinc (80 mg of
zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as
part of the age-related macular degeneration trial. Baseline and
annual (starting at year 2) lens photographs were graded at a reading
center for the severity of lens opacities using the AREDS cataract
grading scale. MAIN OUTCOME MEASURES: Primary outcomes were (1) an
increase from baseline in nuclear, cortical, or posterior subcapsular
opacity grades or cataract surgery, and (2) at least moderate visual
acuity loss from baseline (>/=15 letters). Primary analyses used
repeated-measures logistic regression with a statistical significance
level of P =.01. Serum level measurements, medical histories, and
mortality rates were used for safety monitoring. RESULTS: Of 4757
participants enrolled, 4629 who were aged from 55 to 80 years had at
least 1 natural lens present and were followed up for an average of
6.3 years. No statistically significant effect of the antioxidant
formulation was seen on the development or progression of age-related
lens opacities (odds ratio = 0.97, P =.55). There was also no
statistically significant effect of treatment in reducing the risk of
progression for any of the 3 lens opacity types or for cataract
surgery. For the 1117 participants with no age-related macular
degeneration at baseline, no statistically significant difference was
noted between treatment groups for at least moderate visual acuity
loss. No statistically significant serious adverse effect was
associated with treatment. CONCLUSION: Use of a high-dose formulation
of vitamin C, vitamin E, and beta carotene in a relatively well-
nourished older adult cohort had no apparent effect on the 7-year risk
of development or progression of age-related lens opacities or visual
acuity loss.
PMID: 11594943 full text
Over half of the participants took antioxidants on their own. Blood
levels of C went up only 14%, down 10% in placebo. Pills were taken
once per day. 56% were female and 8% smokers.
4 1: Arch Ophthalmol. 1993 Sep;111(9):1246-53. Related Articles,
Links
The Linxian cataract studies. Two nutrition intervention trials.
Sperduto RD, Hu TS, Milton RC, Zhao JL, Everett DF, Cheng QF, Blot WJ,
Bing L, Taylor PR, Li JY, et al.
National Eye Institute, Bethesda, Md.
OBJECTIVE: To determine whether the vitamin/mineral
supplements used in two cancer intervention trials affected the risk
of developing age-related cataracts. DESIGN: Two randomized, double-
masked trials with a duration of 5 to 6 years and end-of-trial eye
examinations. SETTING: Rural communes in Linxian, China. PARTICIPANTS:
In trial 1, 2141 participants aged 45 to 74 years, and, in trial 2,
3249 participants aged 45 to 74 years. INTERVENTIONS: Multivitamin/
mineral supplement or matching placebo in trial 1; factorial design to
test the effect of four different vitamin/mineral combinations in
trial 2 (retinol/zinc, riboflavin/niacin, ascorbic acid/molybdenum,
and selenium/alpha-tocopherol/beta carotene). MAIN OUTCOME MEASURES:
Prevalence of nuclear, cortical, and posterior subcapsular cataracts
in treatment groups at end of trials. RESULTS: In the first trial,
there was a statistically significant 36% reduction in the prevalence
of nuclear cataract for persons aged 65 to 74 years who received the
supplements. In the second trial, the prevalence of nuclear cataract
was significantly lower in persons receiving riboflavin/niacin
compared with persons not receiving these vitamins. Again, persons in
the oldest group, 65 to 74 years, benefited the most (44% reduction in
prevalence). No treatment effect was noted for cortical cataract in
either trial. Although the number of posterior subcapsular cataracts
was very small, there was a statistically significant deleterious
effect of treatment with riboflavin/niacin. CONCLUSIONS: Findings from
the two trials suggest that vitamin/mineral supplements may decrease
the risk of nuclear cataract. Additional research is needed in less
nutritionally deprived populations before these findings can be
translated into general nutritional recommendations. PMID: 8363468 |
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| Taka... |
| Posted: Mon May 05, 2008 6:55 pm |
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With all these reports and personal experience I am wondering whether
the loss of the ability to synthesize VitC in human liver was not
intentional for achieving longevity in the evolving apes. Uric acid
which took over its function together with cholesterol/lipoproteins
may be a better antioxidant to be used in the unsaturated lipid
environment like the human brain and eyes.
Taka |
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| Thomas Carter... |
| Posted: Tue May 06, 2008 8:18 am |
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On May 6, 12:55�am, Taka <taka0... at (no spam) gmail.com> wrote:
Quote: With all these reports and personal experience I am wondering whether
the loss of the ability to synthesize VitC in human liver was not
intentional for achieving longevity in the evolving apes. �Uric acid
which took over its function together with cholesterol/lipoproteins
may be a better antioxidant to be used in the unsaturated lipid
environment like the human brain and eyes.
Taka
Hi Taka,
If you believe this be sure to take plenty of vit C. While its plasma
levels are only about 1/8 those of uric acid, there is a very
efficient mechanism for maintaining the ratio of reduced to oxidized
vit C at about 60% in the plasma and nearly 100% in the cells.
C is a much stronger reducing agent than uric acid and consequently is
the primary molecule than reduces it in the plasma, maintaining its
ability to act as a free radical scavenger rather than as an oxidizing
agent.
Numerous epidemiological papers report that cardiovascular and total
mortality is directly associated with uric acid levels, and inversely
with vit C levels even in women. There is some question in the
scientific community as to whether the association with uric acid is a
cause or a result of cardiovascular disease. (some hypothesize that it
may be due to an attempt by the body to counter oxidative damage.)
Apparently they have failed to notice that that the longer term
prospective studies such as the Framington and NHANES studies are
those that report the strongest associations. OTOH hi vit C levels
are convincingly related to lower cardiovascular and total mortality.
I know of no paper that has reported on combined hi levels of both,
but all the negative association of uric acid and mortality is seen in
the upper quartile. This hi level is generally due to hi meat
consumption, especially red meat, a cause of gout. Men eat more meat
than women, and are benefited much more by hi vit C consumption very
lightly suggesting a synergism for combined hi levels.
Thomas |
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| Taka... |
| Posted: Tue May 06, 2008 6:41 pm |
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Guest
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On May 7, 3:18 am, Thomas Carter <tomcarter... at (no spam) yahoo.com> wrote:
Quote: On May 6, 12:55�am, Taka <taka0... at (no spam) gmail.com> wrote:
With all these reports and personal experience I am wondering whether
the loss of the ability to synthesize VitC in human liver was not
intentional for achieving longevity in the evolving apes. �Uric acid
which took over its function together with cholesterol/lipoproteins
may be a better antioxidant to be used in the unsaturated lipid
environment like the human brain and eyes.
Taka
Hi Taka,
If you believe this be sure to take plenty of vit C. While its plasma
levels are only about 1/8 those of uric acid, there is a very
efficient mechanism for maintaining the ratio of reduced to oxidized
vit C at about 60% in the plasma and nearly 100% in the cells.
C is a much stronger reducing agent than uric acid and consequently is
the primary molecule than reduces it in the plasma, maintaining its
ability to act as a free radical scavenger rather than as an oxidizing
agent.
Numerous epidemiological papers report that cardiovascular and total
mortality is directly associated with uric acid levels, and inversely
with vit C levels even in women. There is some question in the
scientific community as to whether the association with uric acid is a
cause or a result of cardiovascular disease. (some hypothesize that it
may be due to an attempt by the body to counter oxidative damage.)
Apparently they have failed to notice that that the longer term
prospective studies such as the Framington and NHANES studies are
those that report the strongest associations. OTOH hi vit C levels
are convincingly related to lower cardiovascular and total mortality.
I know of no paper that has reported on combined hi levels of both,
but all the negative association of uric acid and mortality is seen in
the upper quartile. This hi level is generally due to hi meat
consumption, especially red meat, a cause of gout. Men eat more meat
than women, and are benefited much more by hi vit C consumption very
lightly suggesting a synergism for combined hi levels.
Thomas
AFAIK all the deleterious effects of uric acid have simple physical
basis - once it starts crystallizing it forms needles which are
tearing apart cells and irritating tissues provoking the inflammatory
response. If the uric acid level is kept just bellow the
crystallization point it has no adverse effects and functions as an
antioxidant (weaker than VitC on molar basis but stronger given its
concentration in blood I guess). pH is one factor affecting the
crystallization point/solubility of uric acid. Also fructose seems to
be contributing to elevated uric acid levels more than the meat. VitC
is essential for collagen synthesis in trace amounts but its effects
at higher concentration are dubious. The exception may be killing of
the cancer cells starved of sugar :-)
Taka |
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