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Medical Forum / General / Nutrition / July 2008

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Dietary "antioxidants" ineffective in vivo

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Taka - 10 Jul 2008 07:31 GMT
Br J Nutr. 2002 Apr;87(4):343-55.

Green tea extract only affects markers of oxidative status
postprandially: lasting antioxidant effect of flavonoid-free diet.

Young JF, Dragstedt LO, Haraldsdóttir J, Daneshvar B, Kall MA, Loft S,
Nilsson L, Nielsen SE, Mayer B, Skibsted LH, Huynh-Ba T, Hermetter A,
Sandström B.
Research Department of Human Nutrition, Royal Veterinary and
Agricultural University, Frederiksberg, Denmark.

Epidemiological studies suggest that foods rich in flavonoids might
reduce the risk of cardiovascular disease and cancer. The objective of
the present study was to investigate the effect of green tea extract
(GTE) used as a food antioxidant on markers of oxidative status after
dietary depletion of flavonoids and catechins. The study was designed
as a 2 x 3 weeks blinded human cross-over intervention study (eight
smokers, eight non-smokers) with GTE corresponding to a daily intake
of 18.6 mg catechins/d. The GTE was incorporated into meat patties and
consumed with a strictly controlled diet otherwise low in flavonoids.
GTE intervention increased plasma antioxidant capacity from 1.35 to
1.56 (P<0.02) in postprandially collected plasma, most prominently in
smokers. The intervention did not significantly affect markers in
fasting blood samples, including plasma or haemoglobin protein
oxidation, plasma oxidation lagtime, or activities of the erythrocyte
superoxide dismutase, glutathione peroxidase, glutathione reductase
and catalase. Neither were fasting plasma triacylglycerol,
cholesterol, alpha-tocopherol, retinol, beta-carotene, or ascorbic
acid affected by intervention. Urinary 8-oxo-deoxyguanosine excretion
was also unaffected. Catechins from the extract were excreted into
urine with a half-life of less than 2 h in accordance with the short-
term effects on plasma antioxidant capacity. Since no long-term
effects of GTE were observed, the study essentially served as a fruit
and vegetables depletion study. The overall effect of the 10-week
period ********** without dietary fruits and vegetables was a decrease
in oxidative damage to DNA, blood proteins, and plasma lipids,
concomitantly with marked changes in antioxidative defence.
************
PMID: 12064344

Eur J Nutr. 1999 Jun;38(3):149-57.

Green tea extract decreases plasma malondialdehyde concentration but
does not affect other indicators of oxidative stress, nitric oxide
production, or hemostatic factors during a high-linoleic acid diet in
healthy females.

Freese R, Basu S, Hietanen E, Nair J, Nakachi K, Bartsch H, Mutanen M.
Division of Nutrition, University of Helsinki, Finland.

BACKGROUND: Green tea contains polyphenolic catechins which can act as
antioxidants and thus decrease the risk for cardiovascular diseases.
AIM OF THE STUDY: To investigate whether green tea extract differs
from placebo in its effects on markers of antioxidant status, lipid
peroxidation, nitric oxide production, thromboxane production, and
blood coagulation during a controlled high linoleic acid diet in
healthy subjects. METHODS: Twenty healthy non-smoking females (23-50
years) participated in a 4-week controlled intervention study. The
experimental diet was rich in linoleic acid (9 en%) and contained fat,
protein, and carbohydrates: 27, 14, and 59 en%, respectively. In
addition, the subjects ingested encapsulated green tea extract (3 g/d)
or placebo mixture in a double-blind manner. Fasting blood samples and
five 24-hour urines were collected before and at the end of the 4-week
experimental period. Same samples were received from 10 control
subjects. RESULTS: Green tea extract significantly decreased plasma
malondialdehyde (MDA) concentration in comparison with the placebo
treatment. The treatments did not differ in serum lipids, indicators
of antioxidant status, urinary 8-isoprostaglandin F2 alpha, 2,3-
dinorthromboxane B2, nitric oxide metabolites or coagulation
indicators. CONCLUSIONS: We conclude that an amount of green tea
extract which corresponds to 10 cups of tea per day for 4 weeks does
not have specific effects on several indicators related to risk of
cardiovascular diseases in comparison with placebo treatment. The
relatively small but significant decrease in lipid peroxidation
indicated by decreased plasma MDA was not associated with changes in
markers of oxidative stress (urinary 8-isoprostaglandin F2 alpha and
blood oxidized glutathione) or hemostasis.
PMID: 10443337

Eur J Nutr. 2006 Mar;45(2):113-22. Epub 2005 Jul 20.

The effects of cranberry juice consumption on antioxidant status and
biomarkers relating to heart disease and cancer in healthy human
volunteers.

Duthie SJ, Jenkinson AM, Crozier A, Mullen W, Pirie L, Kyle J, Yap LS,
Christen P, Duthie GG.
Phytochemicals and Genomic Stability Group, Rowett Research Institute,
Greenburn Road, Bucksburn, Aberdeen (Sco) AB21 9SB, UK.

BACKGROUND: Consumption of fruit and vegetables is associated with a
decreased risk of heart disease and cancer.This has been ascribed in
part to antioxidants in these foods inactivating reactive oxygen
species involved in initiation or progression of these diseases. Non-
nutritive anthocyanins are present in significant amounts in the human
diet. However, it is unclear whether they have health benefits in
humans. AIM: To determine whether daily consumption of anthocyanin-
rich cranberry juice could alter plasma antioxidant activity and
biomarkers of oxidative stress. METHODS: 20 healthy female volunteers
aged 18-40 y were recruited. Subjects consumed 750 ml/day of either
cranberry juice or a placebo drink for 2 weeks. Fasted blood and urine
samples were obtained over 4 weeks. The total phenol, anthocyanin and
catechin content of the supplements and plasma were measured.
Anthocyanin glycosides were identified by tandem mass spectrometry (MS-
MS). Vitamin C, homocysteine (tHcy) and reduced glutathione (GSH) were
measured by HPLC. Total antioxidant ability was determined using
electron spin resonance (ESR) spectrometry and by the FRAP assay.
Plasma total cholesterol, high density lipoprotein (HDL), and low
density lipoprotein (LDL) cholesterol and triglycerides (TG) were
measured. Glutathione peroxidase (GSH-Px), catalase (CAT) and
superoxide dismutase (SOD) activities were measured in erythrocytes.
Urine was collected for analysis of malondialdehyde (MDA) by HPLC and
8-oxo-deoxyguanosine (8-oxo-dG) by ELISA. Endogenous and induced DNA
damage were measured by single cell gel electrophoresis (SCGE) in
lymphocytes. RESULTS: Vitamin C, total phenol, anthocyanin and
catechin concentrations and FRAP and ESR values were significantly
higher in the cranberry juice compared with the placebo. Cyanidin and
peonidin glycosides comprised the major anthocyanin metabolites
[peonidin galactoside (29.2%) > cyanidin arabinoside (26.1%) >
cyanidin galactoside (21.7%) > peonidin arabinoside (17.5%) > peonidin
glucoside (4.1%) > cyanidin glucoside (1.4 %)]. Plasma vitamin C
increased significantly (P<0.01) in volunteers consuming cranberry
juice. No anthocyanins (plasma) or catechins (plasma or urine) were
detectable and plasma total phenols, tHcy,TC,TG,HDL and LDL were
unchanged. The antioxidant potential of the plasma, GSH-Px, CAT and
SOD activities, and MDA were similar for both groups. Supplementation
with cranberry juice did not affect 8-oxo-deoxyguanosine in urine or
endogenous or H(2)O(2)-induced DNA damage in lymphocytes. CONCLUSIONS:
Cranberry juice consumption did not alter blood or cellular
antioxidant status or several biomarkers of lipid status pertinent to
heart disease. Similarly, cranberry juice had no effect on basal or
induced oxidative DNA damage. These results show the importance of
distinguishing between the in vitro and in vivo antioxidant activities
of dietary anthocyanins in relation to human health.
PMID: 16032375
Kofi - 10 Jul 2008 10:44 GMT
According to recent research, you need to make sure the polyphenols are
shepherded through the digestion process with citric acid or lemon
juice.  I wouldn't really draw conclusions from any in vivo trials
unless they acknowledge that fact.
Taka - 11 Jul 2008 16:50 GMT
Even the own body natural antioxidants can be dangerous when out of
control:

Cancer Res. 1997 Apr 15;57(8):1468-74.

Enhanced skin carcinogenesis in transgenic mice with high expression
of glutathione peroxidase or both glutathione peroxidase and
superoxide dismutase.

Lu YP, Lou YR, Yen P, Newmark HL, Mirochnitchenko OI, Inouye M, Huang
MT.
Department of Chemical Biology, College of Pharmacy, Rutgers, The
State University of New Jersey, Piscataway 08855-0789, USA.

Female transgenic mice (C57BL/6 x CBA/J)F1 with a 1-fold increase in
expression of glutathione peroxidase (GP) or with a 1-fold increase in
the expression of GP and a 3-4-fold increase in the expression of
superoxide dismutase (SOD) had an enhanced carcinogenic response to
initiation by 7,12-dimethylbenz[a]anthracene (DMBA) followed by
promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). GP- or GP
+SOD-transgenic mice that were initiated by a single topical
application of 200 nmol of DMBA followed by promotion with 8 nmol of
TPA twice weekly for 30 weeks developed an average of 10.9 or 11.0
skin tumors per mouse and a 100% tumor incidence in comparison with
the corresponding nontransgenic mice, which had 3.9 tumors per mouse
and an 83% tumor incidence. After stopping TPA application, partial
skin tumor regression occurred more rapidly in nontransgenic mice than
in either type of transgenic mouse. At 10 weeks after termination of
TPA treatment, 9-11% of the tumor-bearing transgenic mice and 26% of
the tumor-bearing nontransgenic mice had complete regression of their
tumors. Histopathological examination of 96 skin papillomas revealed
that the area, location, degree of tumor dysplasia, bromodeoxyuridine
labeling index, and p53 protein levels were closely intercorrelated.
Further analysis indicated that papillomas with the same grade of
dysplasia had a higher bromodeoxyuridine labeling index and a greater
p53 protein level in GP- or GP+SOD-transgenic mice than those in
nontransgenic mice. The data indicated that overexpression of skin
antioxidant enzymes GP or GP+SOD, which are enzymes that are believed
to protect cells from oxidative damage by scavenging reactive oxygen
species, lead to the increased, rather than the decreased,
tumorigenesis in a DMBA/TPA two-stage skin carcinogenesis model.
PMID: 9108447
Bob Arnold - 11 Jul 2008 19:30 GMT
> According to recent research, you need to make sure the polyphenols are
> shepherded through the digestion process with citric acid or lemon
> juice.  I wouldn't really draw conclusions from any in vivo trials
> unless they acknowledge that fact.

Not citric acid. Ascorbic acid. Or, did you have another study in mind?

J Agric Food Chem. 2003 Jan 29;51(3):828-33.

Stabilizing effect of ascorbic acid on flavan-3-ols and dimeric
procyanidins from cocoa.

Zhu QY, Hammerstone JF, Lazarus SA, Schmitz HH, Keen CL.

Department of Nutrition, University of California, Davis, California
95616, USA.

Cocoa flavanols and procyanidins have numerous biological activities.
It is known that (-)-epicatechin, (+)-catechin,
epicatechin-(4beta-8)-epicatechin (dimer B2), and
epicatechin-(4beta-6)-epicatechin (dimer B5) are unstable at
physiologic pH, degrading almost completely within several hours,
whereas they are relatively stable at pH 5.0. The present study
investigated the effects of ascorbic and citric acid on the stability
of monomers and dimers in simulated intestinal juice (pH 8.5) and in
sodium phosphate buffer (pH 7.4). The addition of ascorbic acid to
the incubation mixture significantly increased the stability of the
monomers and dimers, whereas the addition of citric acid provided no
protective effects. LC-MS showed that with the degradation of dimer
B2 and dimer B5, doubly linked A-type dimers were formed. The present
results, although not directly transferable to in vivo conditions,
suggest that ascorbic acid may stabilize cocoa flavanols and
procyanidins in the intestine where the pH is neutral, or alkaline,
before absorption.

PMID: 12537465
Taka - 12 Jul 2008 02:11 GMT
> In article <kofi-694C23.04445910072...@news.west.earthlink.net>,
>
[quoted text clipped - 34 lines]
>
> PMID: 12537465

AFAIK this all applies only as far as to the portal vein.  From the
liver up, the antioxidants work by different mechanisms such as
stimulating the xenobiotic detox processes and affecting gene
transcription.

Taka
Kofi - 13 Jul 2008 04:48 GMT
> > According to recent research, you need to make sure the polyphenols are
> > shepherded through the digestion process with citric acid or lemon
> > juice.  I wouldn't really draw conclusions from any in vivo trials
> > unless they acknowledge that fact.
>
> Not citric acid. Ascorbic acid. Or, did you have another study in mind?

I had a study in mind from this year about green tea but I couldn't dig
it up.  My database of articles is getting too large.
François Rose - 13 Jul 2008 12:22 GMT
> In article <nospam-A00194.13301211072...@newsclstr02.news.prodigy.com>,
>
[quoted text clipped - 9 lines]
> I had a study in mind from this year about green tea but I couldn't dig
> it up.  My database of articles is getting too large.

pmid 18001060
discussed at sle here
http://tinyurl.com/ypcgkb

François Rose
François Rose - 14 Jul 2008 00:02 GMT
> > In article <nospam-A00194.13301211072...@newsclstr02.news.prodigy.com>,
>
[quoted text clipped - 14 lines]
>
> François Rose

I got muddled up above, about the study Kofi might think of:
In fact, I was thinking about  that one (that also appears here:
http://tinyurl.com/6pozpg

Common tea formulations modulate in vitro digestive recovery of green
tea catechins.Green RJ, Murphy AS, Schulz B, Watkins BA, Ferruzzi MG.
Department of Food Science, Purdue University, West Lafayette, IN
47907, USA.

Epidemiological evidence suggests a role for tea catechins in
reduction of chronic disease risk. However, stability of catechins
under digestive conditions is poorly understood. The objective of this
study was to characterize the effect of common food additives on
digestive recovery of tea catechins. Green tea water extracts were
formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL
epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate
(EGCG), and epicatechin-gallate (ECG), respectively. Common commercial
beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA),
milk (bovine, soy, and rice), and citrus juice (orange, grapefruit,
lemon, and lime) were formulated into finished tea beverages at
incremental dosages. Samples were then subjected to in vitro digestion
simulating gastric and small intestinal conditions with pre- and post-
digestion catechin profiles assessed by HPLC. Catechin stability in
green tea was poor with <20% total catechins remaining post-digestion.
EGC and EGCG were most sensitive with less, not double equals 10%
recovery. Teas formulated with 50% bovine, soy, and rice milk
increased total catechin recovery significantly to 52, 55, and 69%
respectively. Including 30 mg AA in 250 mL of tea beverage
significantly (p<0.05) increased catechin recovery of EGC, EGCG, EC,
and ECG to 74, 54, 82, and 45% respectively. Juice preparation
resulted in the highest recovery of any formulation for EGC (81-98%),
EGCG (56-76%), EC (86-95%), and ECG (30-55%). These data provide
evidence that tea consumption practices and formulation factors likely
impact catechin digestive recovery and may result in diverse
physiological profiles.

PMID: 17688297 [PubMed - indexed for MEDLINE]

François Rose
Kofi - 14 Jul 2008 11:25 GMT
In article
<82f4af7f-26bb-4110-a1aa-fd3e1383f2f0@34g2000hsf.googlegroups.com>,

> > In article <nospam-A00194.13301211072...@newsclstr02.news.prodigy.com>,
> >
[quoted text clipped - 13 lines]
>
> pmid 18001060

No, that's not the one.  This is.  I wonder if the juice improves uptake
via some sort of CYP inhibition.

Mol Nutr Food Res. 2007 Sep;51(9):1152-62. 

Common tea formulations modulate in vitro digestive recovery of green
tea catechins.
*  Green RJ,
*  Murphy AS,
*  Schulz B,
*  Watkins BA,
*  Ferruzzi MG.

Department of Food Science, Purdue University, West Lafayette, IN 47907,
USA.

Epidemiological evidence suggests a role for tea catechins in reduction
of chronic disease risk. However, stability of catechins under digestive
conditions is poorly understood. The objective of this study was to
characterize the effect of common food additives on digestive recovery
of tea catechins. Green tea water extracts were formulated in beverages
providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC),
epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and
epicatechin-gallate (ECG), respectively. Common commercial beverage
additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk
(bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon,
and lime) were formulated into finished tea beverages at incremental
dosages. Samples were then subjected to in vitro digestion simulating
gastric and small intestinal conditions with pre- and post-digestion
catechin profiles assessed by HPLC. Catechin stability in green tea was
poor with <20% total catechins remaining post-digestion. EGC and EGCG
were most sensitive with less, not double equals 10% recovery. Teas
formulated with 50% bovine, soy, and rice milk increased total catechin
recovery significantly to 52, 55, and 69% respectively. Including 30 mg
AA in 250 mL of tea beverage significantly (p<0.05) increased catechin
recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively.
Juice preparation resulted in the highest recovery of any formulation
for EGC (81-98%), EGCG (56-76%), EC (86-95%), and ECG (30-55%). These
data provide evidence that tea consumption practices and formulation
factors likely impact catechin digestive recovery and may result in
diverse physiological profiles.

PMID: 17688297
Taka - 15 Jul 2008 06:43 GMT
> In article
> <82f4af7f-26bb-4110-a1aa-fd3e1383f...@34g2000hsf.googlegroups.com>,
[quoted text clipped - 50 lines]
> were most sensitive with less, not double equals 10% recovery. Teas
> formulated with 50% bovine,

This reminds me the recent findings about milk in tea negating the tea
benefits discussed here extensively (poor British milk tea
drinkers!).  Could the "experts" get it right once for all please?
Looks like the neverending battle between Ornish and Atkins.

Taka

> soy, and rice milk increased total catechin
> recovery significantly to 52, 55, and 69% respectively. Including 30 mg
[quoted text clipped - 7 lines]
>
> PMID: 17688297
Kofi - 19 Jul 2008 19:07 GMT
> This reminds me the recent findings about milk in tea negating the tea
> benefits discussed here extensively (poor British milk tea
> drinkers!).  Could the "experts" get it right once for all please?
> Looks like the neverending battle between Ornish and Atkins.

These results aren't recent.  Several years back they looked at the
health benefits for people putting milk in their tea vs. those who
didn't and it was pretty clear back then.

Atkins looks like he's won.  Wow.  Carbs go straight into cholesterol.  
Whoda thunk it.

There do appear to be gender effects.  Women do slightly less better on
Atkins.  I wonder if it's their lower carnitine content and it this
affects their fat pathway (esp. via PPARalpha).
 
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