High Dose Vit. C with Alpha-tocopherol Is Not Useful for Diminishing Oxidative Stress and DNA Damage in Healthy Elderly Adults.

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Author

Message

rs1000b@yahoo.com

Posted: Fri May 02, 2008 11:42 am

Guest

Anthropus

Posted: Sat May 03, 2008 10:57 am

Guest

<rs1000b@yahoo.com> wrote in message
news:bed2308e-06b8-4de8-951d-2ad584f3d193@f36g2000hsa.googlegroups.com...
Ann Nutr Metab. 2008 Apr 29;52(2):167-173 [Epub ahead of print]

High Dosage of Ascorbic Acid and Alpha-Tocopherol Is Not Useful for
Diminishing Oxidative Stress and DNA Damage in Healthy Elderly Adults.

[snip]

The usual questions:
i) what form of 'alpha-tocopherol' did they use, and why?
ii) why do we once again have people wasting time and money comparing 500mg
of C with 1000 mg --- when what we really want is to see 500 mg compared
with 5,000 or 10,000mg?

Another pathetic non-study, in other words: subtly designed to show nothing
significant while still looking like a serious piece of work...

M.

Thomas Carter...

Posted: Sun May 04, 2008 1:56 pm

Guest

On May 3, 11:57 am, "Anthropus" <Anthro... at (no spam) me.co.uk> wrote:

Quote:

rs10... at (no spam) yahoo.com> wrote in message

news:bed2308e-06b8-4de8-951d-2ad584f3d193 at (no spam) f36g2000hsa.googlegroups.com...
Ann Nutr Metab. 2008 Apr 29;52(2):167-173 [Epub ahead of print]

High Dosage of Ascorbic Acid and Alpha-Tocopherol Is Not Useful for
Diminishing Oxidative Stress and DNA Damage in Healthy Elderly Adults.

[snip]

The usual questions:
i) what form of 'alpha-tocopherol' did they use, and why?
ii) why do we once again have people wasting time and money comparing 500mg
of C with 1000 mg --- when what we really want is to see 500 mg compared
with 5,000 or 10,000mg?

Another pathetic non-study, in other words: subtly designed to show nothing
significant while still looking like a serious piece of work...

M.

Hi RS,

Addition of this latest report gives me seven abstracts
measuring antioxidative parameters vs vitamins C and E, usually
combined with other antioxidants. All seven report some sign of
efficacy. The post by RS reports an insignificant beneficial trend of
three parameters. Most of the papers measured multiple parameters and
reported significant trends, but this can be a chance occurance when
more than one effect is measured and the p values are not way below .
05. Also notable is that some of thsese positive results are in groups
with poor oxidative status. Never the less they represent positive
evidence of oxidative benefits, at least in men.
My studies convincingly show that vitamins C and E are
beneficial when given to men at a dose of at least 500 mg C bid, and
400 IU E. As I’ve previously reported, this protocol has been tested
only four times on primary endpoints or important secondary factors
such as atherosclerosis. It was significantly beneficial in all four.
Only one of these oxidative papers conform to the
minimum protocol I’ve established and it is unequivically positive.
(1 Cool

. The other six taken together are strongly suggestive of a
benefit. Had they been stratified for gender, I’m sure they would have
been more suggestive yet.
Vitamin C is likely to be detrimental for diabetic
women due to their inability to properly sequester iron. It is almost
surely detrimental to diabetic women with the haptoglobin 2-2 genetic
allele, and likely to be detrimental to non diabetic women with this
allelic morph. It may also be detrimental to hapto 2-2 men. Other
males should take at least 500 mg C tid and 800 IU of full spectrum
vitamin E in my opinion.
Women naturally have better oxidative status than men,
but don’t handle iron as well. This may be why they see little or no
benefit from C. Diabetics handle iron quite poorly, and this may be
why these women see a detriment with C. I’ve seen no evidence on the
benefits of C in diabetic men. There may be none, or even a detriment.
Haptoglobin is a protein involved in the process of sequestering iron
during the catabolism of red blood cells. The 2-2 allele is less
efficient in this process and allows oxidative stress due to the
Fentoin reaction which is a recycling of iron and C, generating free
radicals. These free radicals apparently can be used by the immune
system in fighting disease and/or cancer, and it may be for this
reason that hapto 2-2 allelic carriers have longer life span despite
more oxidative stress. Menadione (vitamin K3) is the deprenylated form
of K, and also forms a ROS generating recycling pair with C. An
ongoing clinical trial is testing this combination against cancer.
Menadione is a metabolite of vitamin K2 and may be some of the reason
that multiple trials have shown its efficacy against multiple cancer
types.
OTOH vitamin E appears to be quite beneficial for
diabetics with the 2-2 allele. Here’s a quote from PMID: 18032779
which is a report of a large clinical trial involving 1400 subjects,
it was terminated early due to the large benefit seen.

“CONCLUSIONS: Vitamin E supplementation appears to reduce
cardiovascular events in individuals with DM and the Hp 2-2
genotype” (ClinicalTrials.gov NCT00220831).

Thomas

( Cool

Ann Nutr Metab. 2008 Apr 29;52(2):167-173 [Epub ahead of print]
High Dosage of Ascorbic Acid and Alpha-Tocopherol Is Not Useful for
Diminishing Oxidative Stress and DNA Damage in Healthy Elderly
Adults.
Retana-Ugalde R, Casanueva E, Altamirano-Lozano M, González-Torres C,
Mendoza-Núñez VM.
Unidad de Investigación en Gerontología, Facultad de Estudios
Superiores Zaragoza, Universidad Nacional Autónoma de México, Mexico
City, Mexico.
Aim: To determine the useful dosage of ascorbic acid and alpha-
tocopherol against oxidative stress and DNA damage in the elderly.
Methods: A double-blind controlled clinical assay carried out in a
sample of 66 healthy subjects divided into three age-paired random
groups with 22 subjects in each group. Group A received placebo and
group B was administered 500 mg of ascorbic acid and 400 IU of alpha-
tocopherol, whereas group C received 1,000 mg of ascorbic acid and
400
IU of alpha-tocopherol for a 6-month period. The following
measurements were performed before and after the 6-month treatment
period: thiobarbituric acid reactive substances (TBARS); total
antioxidant status (TAS); superoxide dismutase (SOD), and glutation
peroxidase (GPx) and DNA damage by comet assay. Results: After 6
months, group B subjects exhibited an increase in SOD and GPx enzyme
levels; however, this was not statistically significant (p > 0.05).
Likewise, TBARS and TAS concentrations remained unchanged (p > 0.05).
In addition, in group C the decrease in TBARS and increase in SOD,
GPx, and TAS were not statistically significant (p > 0.05).
Similarly,
average DNA migration showed no significant differences with high-
dosage ascorbic acid and alpha-tocopherol. Conclusion: These findings
suggest that administration of 1,000 mg of ascorbic acid plus 400 IU
of alpha-tocopherol for 6 months is not useful for diminishing
oxidative stress and DNA damage in healthy elderly adults. Copyright
©
2008 S. Karger AG, Basel. PMID: 18446021

(10) J Rheumatol. 2005 Feb;32(2):275-82.Related Articles, Links
Effects of vitamins C and E on oxidative stress markers and
endothelial function in patients with systemic lupus erythematosus: a
double blind, placebo controlled pilot study.
Tam LS, Li EK, Leung VY, Griffith JF, Benzie IF, Lim PL, Whitney B,
Lee VW, Lee KK, Thomas GN, Tomlinson B.

Department of Medicine and Therapeutics, Department of Radiology, and
the Clinical Immunology Unit, Hong Kong Cancer Institute, Hong Kong.
tamls_813 at (no spam) yahoo.com

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) experience
excess morbidity and mortality due to coronary artery disease (CAD)
that cannot be fully explained by the classical CAD risk factors.
Among emerging CAD risk factors, oxidative stress is currently being
emphasized. We evaluated the effects of longterm antioxidant vitamins
on markers of oxidative stress and antioxidant defense and endothelial
function in 39 patients with SLE. METHODS: Patients were randomized to
receive either placebo or vitamins (500 mg vitamin C and 800 IU
vitamin E daily) for 12 weeks. Markers of oxidative stress included
malondialdehyde (MDA) and allantoin. Antioxidants measured included
erythrocyte superoxide dismutase and glutathione peroxidase, plasma
total antioxidant power (as FRAP value), and ascorbic acid and vitamin
E concentrations. Endothelial function was assessed by flow-mediated
dilatation (FMD) of the brachial artery and plasma concentration of
von Willebrand factor (vWF) and plasminogen activator inhibitor type 1
(PAI-1). Primary outcome of the study included the change in lipid
peroxidation as revealed by MDA levels. Secondary outcomes included
changes in allantoin and antioxidant levels and change in endothelial
function. RESULTS: After treatment, plasma ascorbic acid and alpha-
tocopherol concentrations were significantly (p < 0.05) increased only
in the vitamin-treated group, associated with a significant decrease
(p < 0.05) in plasma MDA. Other oxidative stress markers and
antioxidant levels remained unchanged in both groups. FMD and vWF and
PAI-1 levels remained unchanged in both groups. CONCLUSION: Combined
administration of vitamins C and E was associated with decreased lipid
peroxidation, but did not affect endothelial function in patients with
SLE after 3 months of therapy.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15693087 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

(12) Am J Clin Nutr. 2003 Jan;77(1):150-9.Related Articles, Links
Improved antioxidant and fatty acid status of patients with cystic
fibrosis after antioxidant supplementation is linked to improved lung
function.

Wood LG, Fitzgerald DA, Lee AK, Garg ML.

Discipline of Nutrition and Dietetics, Faculty of Health, University
of Newcastle, Callaghan, NSW, Australia.

BACKGROUND: Oxidative stress, as measured by 8-iso-prostaglandin F(2)
(alpha) (8-iso-PGF(2)(alpha)), and depleted antioxidant defenses were
shown in stable cystic fibrosis (CF) patients. The plasma fatty acid
status of CF patients was linked to oxidative stress after respiratory
exacerbations. OBJECTIVE: We examined changes in plasma 8-iso-PGF(2)
(alpha), antioxidant defenses, plasma fatty acid status, and clinical
markers resulting from short-term antioxidant supplementation. DESIGN:
Forty-six CF patients were randomly assigned to either group A [low
dose of supplement (10 mg vitamin E and 500 micro g vitamin A)] or
group B [high dose of supplement (200 mg vitamin E, 300 mg vitamin C,
25 mg beta-carotene, 90 micro g Se, and 500 micro g vitamin A)].
Plasma concentrations of 8-iso-PGF(2)(alpha), vitamins E and C, beta-
carotene, zinc, selenium, and copper; plasma fatty acid composition;
erythrocyte glutathione peroxidase (EC 1.11.1.9) and superoxide
dismutase (EC 1.15.1.1) activities; lung function; and dietary intake
were measured before and after 8 wk of supplementation. RESULTS:
Antioxidant defenses in group B improved, whereas those in group A did
not: in groups B and A, the mean (+/- SEM) changes (Delta) in vitamin
E were 10.6 +/- 1.5 and -1.9 +/- 0.9 micro mol/L, respectively (P <
0.001), (Delta)beta-carotene were 0.1 +/- 0.04 and -0.01 +/- 0.02
micro mol/L, respectively (P = 0.007), (Delta)selenium were 0.51 +/-
0.10 and -0.09 +/- 0.04 micro mol/L, respectively (P < 0.001), and
(Delta)glutathione peroxidase activity were 1.3 +/- 0.3 and -0.3 +/-
0.6 U/g hemoglobin, respectively (P = 0.016). There were no
significant differences between the groups in Delta8-iso-PGF(2)
(alpha), (Delta)vitamin C, (Delta)fatty acid composition,
(Delta)superoxide dismutase activity, (Delta)lung function, or
(Delta)white cell count. Within group B, (Delta)beta-carotene
correlated with (Delta)percentage of forced vital capacity (r = 0.586,
P = 0.005), (Delta)selenium correlated with (Delta)percentage of
forced expiratory volume in 1 s (r = 0.440, P = 0.046), and
(Delta)plasma fatty acid concentrations correlated with
(Delta)percentage of forced expiratory volume in 1 s (r = 0.583, P 0.006) and Delta8-iso-PGF(2)(alpha) (r = 0.538, P = 0.010).
CONCLUSIONS: Whereas increased beta-carotene, selenium, and fatty acid
concentrations are linked to improved lung function, increased plasma
fatty acid concentrations are linked to oxidative stress. If oxidative
stress is deemed to be important to the clinical outcome of CF
patients, means of reducing oxidative stress while maintaining a high-
fat, high-energy diet must be investigated.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

PMID: 12499335 [PubMed - indexed for MEDLINE]

(1 Cool

Eur J Nutr. 2001 Aug;40(4):178-84.Related Articles, Links
Effects of alpha-tocopherol, beta-carotene and ascorbic acid on
oxidative, hormonal and enzymatic exercise stress markers in habitual
training activity of professional basketball players.

Schröder H, Navarro E, Mora J, Galiano D, Tramullas A.

Sports Medicine Barcelona, Department of Nutrition, Spain.
helmuts at (no spam) teleline.es

BACKGROUND: Intense physical exercise has been associated with an
increase of free radical production. When the body's natural defense
systems against free radicals are overwhelmed, oxidative stress
increases. AIM OF THE STUDY: This study examined the effects of a
vitamin antioxidant supplement, (composed of 600 mg alpha-tocopherol,
1000 mg ascorbic acid and 32 mg beta-carotene) on oxidative, hormonal,
and enzymatic exercise stress markers during habitual training
activity over 35 days. METHODS: The plasma concentrations of ascorbic
acid, alpha-tocopherol, beta-carotene, testosterone, cortisol and
lipid peroxides and the serum activities of lactate dehydrogenase and
creatine kinase were measured at four time points: pre-supplementation
(PS), pre-training (PT), after training (AT) and 24 h after training
(24h-AT) in 13 professional basketball players of the first Spanish
Basketball League (ACB). RESULTS: Antioxidant supplementation led to a
significant increase of alpha-tocopherol and beta-carotene from PS to
PT. Plasma lipid peroxides decreased about 27.7% after 35 days of
antioxidant treatment. A significant decrease of lactate dehydrogenase
serum activity was observed during the 24 h recuperation time. During
this time the anabolic/catabolic balance increased about 29.8% in the
antioxidant supplemented group, although this increase did not reach
statistical significance. CONCLUSIONS: The results of the present
study suggest that supplementation with alpha-tocopherol, beta-
carotene and ascorbic acid might partially account for the hormonal
and enzymatic stress marker profile observed during habitual training
activity of professional basketball players.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

PMID: 11905959 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

(22) J Am Coll Nutr. 1997 Aug;16(4):357-65.Related Articles, Links
Effect of a two-year supplementation with low doses of antioxidant
vitamins and/or minerals in elderly subjects on levels of nutrients
and antioxidant defense parameters.

Girodon F, Blache D, Monget AL, Lombart M, Brunet-Lecompte P, Arnaud
J, Richard MJ, Galan P.

Laboratoire de Biochimie des Lipoprotéines, Université de Bourgogne,
Digon, France.

BACKGROUND: Eighty-one elderly hospitalized subjects (> 65 years) were
recruited for a double-blind placebo-controlled study to examine low
dose supplementation of antioxidant vitamins and minerals on
biological and functional parameters of free radical metabolism.
Subjects were randomly assigned to one of the four treatment groups,
daily receiving for 2 years: placebo group; mineral group: 20 mg zinc,
100 micrograms selenium; vitamin group: 120 mg vitamin C (Vit C), 6 mg
beta-carotene (beta CA), 15 mg vitamin E (Vit E); mineral and vitamin
group: Zn 20 mg, Se 100 micrograms, Vit C 120 mg, beta CA 6 mg, Vit E
15 mg. RESULTS: Fifty-seven subjects completed the study. A large
frequency of Vit C, Zn and Se deficiencies were observed at baseline.
As early as 6 months of treatment, a significant increase in vitamin
and mineral serum levels was observed in the corresponding groups. The
increases ranged from 1.1-4.0 fold depending on the nutrient.
Antioxidant defense, studied in vitro with a test using red blood
cells in presence of 2,2'-azo-bis (2-amidinopropane) by hydrochloride,
showed an increase of cell resistance in patients receiving vitamins
(p = 0.002); it was positively correlated with serum Vit C (p <
0.0001), alpha-tocopherol/cholesterol (p = 0.06), beta CA (p 0.0014), serum Cu and Se (p < 0.05). Moreover, red blood cell
antioxidant defense was reduced in elderly compared with young control
subjects (50% hemolysis time: 69 +/- 14 mn and 109 +/- 12 mn,
respectively). Erythrocyte glutathione peroxidase activity was
enhanced in groups receiving minerals, whereas no significant change
was observed for other indicators of oxidative stress (erythrocyte
superoxide dismutase activity, thiobarbituric acid-reactive
substances, total glutathione, reduced and oxidized forms).
DISCUSSION: Our results provide experimental evidence that a low dose
supplementation with vitamins and minerals was able to normalize
biological nutrient status as early as 6 months of treatment. In
addition, our data indicate that antioxidant defense in elderly
subjects was improved with low doses of vit C, vit E and beta CA as
studied by means of a functional test utilizing red blood cells
challenged in vitro with free radicals.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

PMID: 9263186 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

(26) Circulation. 1993 Dec;88(6):2780-6.Related Articles, Links
Comment in:
Circulation. 1994 Dec;90(6):3119-21.

Effect of combined supplementation with alpha-tocopherol, ascorbate,
and beta carotene on low-density lipoprotein oxidation.

Jialal I, Grundy SM.

Center for Human Nutrition, University of Texas Southwestern Medical
Center, Dallas 75235-9052.

BACKGROUND. Data continue to accumulate supporting a proatherogenic
role for oxidized low-density lipoprotein (Ox-LDL). Antioxidant
micronutrients such as ascorbate, alpha-tocopherol, and beta carotene,
levels of which can be favorably manipulated by dietary measures
without side effects, could be a safe approach in inhibiting LDL
oxidation. In fact, in vitro studies have shown that all three
antioxidants can inhibit LDL oxidation. The present study was
undertaken to ascertain both the safety and antioxidant effect of
combined supplementation with alpha-tocopherol, ascorbate, and beta
carotene on LDL oxidation. METHODS AND RESULTS. The effect of combined
supplementation with alpha-tocopherol (800 IU/d) plus ascorbate (1.0 g/
d) and beta carotene (30 mg/d) on copper-catalyzed LDL oxidation was
tested in a randomized, placebo-controlled study in two groups of 12
male subjects over a 3-month period. Blood samples for the lipoprotein
profile, antioxidant levels, and LDL isolation were obtained at
baseline and at 3 months. Neither placebo nor combined antioxidant
therapy resulted in any side effects or exerted an adverse effect on
the plasma lipoprotein profile. Compared with placebo, combined
antioxidant therapy resulted in a significant increase in plasma
ascorbate and lipid standardized alpha-tocopherol and beta carotene
levels (2.6-, 4.1-, and 16.3-fold, respectively). At baseline, there
were no significant differences in the time course curves and kinetics
of LDL oxidation as evidenced by the thiobarbituric acid reacting
substances (TBARS) assay and the formation of conjugated dienes.
However, at 3 months, combined supplementation resulted in a twofold
prolongation of the lag phase and a 40% decrease in the oxidation
rate. The combined antioxidant group was also compared with a group
that received 800 IU of alpha-tocopherol only. Although the combined
antioxidant group had significantly higher ascorbate and beta carotene
levels than the group supplemented with alpha-tocopherol alone, there
were no significant differences between the two groups with respect to
LDL oxidation kinetics. CONCLUSIONS. Combined supplementation with
ascorbate, beta carotene, and alpha-tocopherol is not superior to high-
dose alpha-tocopherol alone in inhibiting LDL oxidation. Hence, alpha-
tocopherol therapy should be favored in future coronary prevention
trials involving antioxidants.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 8252691 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

(33) Int J Vitam Nutr Res. 1993;63(1):27-30.Related Articles, Links
Total radical-trapping antioxidant potential (TRAP) of plasma: effects
of supplementation of young healthy volunteers with large doses of
alpha-tocopherol and ascorbic acid.

Mulholland CW, Strain JJ.

Human Nutrition Research Group, University of Ulster, Coleraine,
Northern Ireland.

A randomized, placebo-controlled double-blind supplementation trial
was conducted on 32 adults to assess the effect of dl-alpha-tocopherol
(1 g/day for 28 days) or ascorbic acid (AA) (1 g/day for 28 days)
separately or in combination on the total radical-trapping antioxidant
potential (TRAP) of plasma. Subjects were divided into 4 groups of 8
and received the following: Group 1, placebo; Group 2, ascorbic acid;
Group 3, alpha-tocopherol; Group 4, alpha-tocopherol and AA.
Antioxidant potential was assessed using the TRAP technique (a
specific measure of the capacity of the secondary antioxidants,
vitamins E, C, reduced thiol compounds and urate in plasma to resist
controlled in vitro peroxidation). TRAP values were estimated at
baseline and after treatment (day 29). Group means of the antioxidant
vitamins at baseline were within normal values for both ascorbic acid
(62-82 mumol/l) and alpha-tocopherol (24-29 mumol/l). Despite marked
increases post-supplementation in plasma alpha-tocopherol levels in
Groups 3 (94%) and 4 (91%) and in AA levels in Groups 2 (82%) and 4
(32%), there were no significant differences (analysis of variance)
between the 4 treatment groups for TRAP values on day 29. Paired-t-
testing revealed significant (P < 0.01) increases in post-
supplementation TRAP values in Groups 2 and 3.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 8320055

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