Antioxidant Clinical Summaries

 

Websites (for official abstracts and full text of articles) www.pubmed.org  and www.nutools.com

 

 

 

Alpha-Lipoic Acid: a metabolic antioxidant which regulates NF-kappa B signal transduction and protects against oxidative injury 

 

Alpha-Lipoic Acid influences a number of cell processes.  These include:

·         Direct radical scavenging

·         Recycling of other antioxidants

·         Accelerating GSH synthesis

·         Modulating transcription factor activity especially that of NF-kappa B

 

L. Packer  (May, 1998) Drug Metab Rev. 30(2):245-75  [Department of Molecular and Cell biology, University of California, Berkeley 94720-3200.]

 

 

 

The pharmacology of the antioxidant lipoic acid.

 

  1. Lipoic acid has a therapeutic effect related to antioxidant activity.
  2. Antioxidant activity depends upon the kind of oxidative stress and the kind of oxidizable substrate (e.g., DNA, lipid protein)
  3. Four antioxidant properties of lipoic acid have been studied:

4.       A reduction of lipoic acid produces dihydrolipoic acid (DHLA) which has even more antioxidant properties than does lipoic acid.  DHLA is also able to regenerate endogenous antioxidants and to repair oxidative damage

  1. Lipoic acid can chelate Fe2= and Cu2+ by chelating Cd2+
  2. Lipoic acid may act as an antioxidant against the pro-oxidant activity produced by DHLA
  3. DHLA is able to regenerate the endogenous antioxidants Vitamins E and C, and glutathione.
  4. Peptide methionine sulfoxide reductase provided by DHLA enhances the repair of oxidatively damaged proteins such as alpha-1 antiprotease.
  5. Through the reduction of lipoic acid the cell can draw on its NADH pool for antioxidant activity additionally to its NADPH pool.
  6. Within antioxidant pharmacology, lipoic acid is a model compound.

 

Biewenga, GP; Haenen, GR; Bast, A. (September, 1997)  Gen. Pharmacol. 29(3):315-31 [Leiden/Amsterdam Center for Drug Research, Vrie Universiteit, Department of Pharmacochemistry, The Netherlands]

 

 

 

Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress.

 

In vitro studies have shown that alpha-lipoic acid (LA) is an antioxidant.  LA oral supplementation decreases plasma-and LDL oxidation and urinary isoprostanes.   LA  also significantly increases the lag time of LDL lipid peroxide formation for both copper-catalyzed and AAPH-induced LDL oxidation.

 

Marangon, K; Devaraj, S; Tirosh, O; Packer, L; Jialal, I (November, 1999)  Free Radic boil Med. 27(9-10):1114-21 [Department of Pathology, University of Texas Southwester Medical Center at Dallas, 75235-9073]

 

 

 

Prevention of hypertension, insulin resistance, and oxidative stress by alpha-lipoic acid.

 

High-glucose feeding of laboratory rats rapidly induced hypertension and insulin resistance in association with the induction of a vascular oxidative stress.  A decrease in the activity of plasma glutathione peroxiadase observed in the glucose-fed rats was prevented by lipoic acid treatment. The antihypertensive action and the prevention of insulin resistance by lipoic acid appears to be associated to its antioxicative properties.

 

El Midaoui, A; de Champlain, J. (February, 2002) Hypertension 39(2):303-7   [Department of Physiology, Faculty of Medicine, University of Montreal, Quebec, Canada]

 

 

 

 

ANTIOXIDANTS

 

Vegetables, fruits, and phytoestrogens in the prevention of diseases.

 

The intake of 400-600 g/d of fruits and vegetables is associated with reduced incidence of many common forms of cancer.  Diets rich in plant foods are also associated with a reduced risk of heart disease and many chronic diseases of aging.  These foods contain phytochemicals that have anti-cancer and anti-inflammatory properties which confer many health benefits. 

 

Red foods contain lycopene, the pigment in tomatoes, which is localized in the prostate gland and may be involved in maintaining prostate health, and which has also been linked with a decreased risk of cardiovascular disease.

 

Green foods, including broccoli, Brussels sprouts and kale, contain glucosinolates which have also been associated with a decreased risk of cancer.  Other bioactive substances in green tea and soybeans have health benefits as well.

 

White-green foods like garlic and others in the onion family contain allyl sulphides which may inhibit cancer cell growth.

 

Consumers are advised to ingest one serving of each of the seven color groups daily. The recommendation of the National Cancer Institute and American Institute for Cancer Research provides guidelines of five to nine servings per day. 

 

Heber, D (April-June, 2004)  J Postgrad Med. 50(2):145-9.  [UCLA Center for Human Nutrition, Los Angeles, CA   dheber@mednet.ucla.edu]

 

 

 

Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not?
 
Foods and beverages rich in phenolic compounds, especially flavonoids, have often been associated with decreased risk of developing several diseases.   Alleged health-promoting effects of flavonoids are usually attributed to their powerful antioxidant activities.   Phenols might exert direct effects within the gastrointestinal tract, because of the high concentrations present. These effects could include:

 

binding of prooxidant iron,

scavenging of reactive nitrogen, chlorine, and oxygen species, and

perhaps inhibition of cyclooxygenases and lipoxygenases  

 

We argue that tocopherols and tocotrienols may also exert direct beneficial effects in the gastrointestinal tract and that their return to the gastrointestinal tract by the liver through the bile may be physiologically advantageous.

 

Halliwell, B; Rafter, J; Jenner, A (January, 2005) Am J Clin Nutr. 81(1 Suppl):268S-276S.  [Department of Biochemistry, Faculty of Medicine, Singapore. bchbh@nus.edu.sg]

 

 

Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study.
 
BACKGROUND: Antioxidants may protect the aging brain against oxidative damage associated with pathological changes of Alzheimer disease (AD).   Cross-sectional and prospective study of dementia. Elderly (65 years or older) county residents were assessed in 1995 to 1997 for prevalent dementia and AD, and again in 1998 to 2000 for incident illness. 

 

RESULTS:  Use of vitamin E and C (ascorbic acid) supplements in combination was associated with reduced AD prevalence   A trend toward lower AD risk was also evident in users of vitamin E and multivitamins containing vitamin C, but we saw no evidence of a protective effect with use of vitamin E or vitamin C supplements alone, with multivitamins alone, or with vitamin B-complex supplements. CONCLUSIONS: Use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD. Antioxidant supplements merit further study as agents for the primary prevention of AD.

 

Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC; Cache County Study Group. (January, 2004)  Arch Neurol. 61(1):82-8.  [Department of Mental Health, Bloomberg School of Public Health, The Johns Hopkins University, Hampton House Room 857, 624 N Broadway, Baltimore, MD 21205, USA. pzandi@jhsph.edu]

 

 

Effect of a multivitamin and mineral supplement on infection and quality of life. A randomized, double-blind, placebo-controlled trial.
 
BACKGROUND: Use of multivitamin and mineral supplements is common among U.S. adults, yet few well-designed trials have assessed the reputed benefits.  TEST GROUP: 130 community-dwelling adults stratified by age (45 to 64 years, or > or = 65 years) and presence of type 2 diabetes mellitus.  INTERVENTION: Multivitamin and mineral supplement or placebo taken daily for 1 year.    CONCLUSIONS: A multivitamin and mineral supplement reduced the incidence of participant-reported infection and related absenteeism in a sample of participants with type 2 diabetes mellitus and a high prevalence of subclinical micronutrient deficiency. 

 

Barringer TA, Kirk JK, Santaniello AC, Foley KL, Michielutte R.  (March 4, 2003) Ann Intern Med.138(5):365-71.  [University of North Carolina School of Medicine at Carolinas Medical Center, Charlotte, North Carolina, USA. tbarringer@carolinas.org]

 

 

Relationship of serum antioxidants to asthma prevalence in youth.
 
            The relationship of serum vitamin E, beta-carotene, vitamin C, and selenium to asthma was investigated among 7,505 youth (4-16 years old) in the Third

            National Health and Nutrition Examination Survey.   Serum vitamin E had little or no association with asthma.  In separate models, a SD increase in beta-

            carotene, vitamin C, and selenium  was associated with a 10-20% reduction in asthma prevalence.

 

Serum cotinine was used to identify youth with no cigarette smoke exposure and passive exposure (7%): Active smokers were too few to be studied further. The selenium-asthma association was stronger in youth who were smoke exposed (p = 0.075).  A SD increase in selenium was associated with a 50% reduction in asthma prevalence in youth with passive smoke exposure compared with a 10% reduction in youth with no smoke exposure. The findings support an association of antioxidants with prevalent asthma, which for some antioxidants is stronger among children exposed to cigarette smoke.

 

Rubin RN, Navon L, Cassano PA.  (February 1, 2004)    Am J Respir Crit Care Med.;169(3):393- 8.  (Epub 20 NOV2003) [Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.]
 

 

 

Effects of 6-month multivitamin supplementation on serum concentrations of alpha-tocopherol, beta-carotene, and vitamin C in healthy elderly women.
 

Two hundred twenty free-living, healthy women aged 60-91 years (median 63 years) were recruited by newspaper advertisement in Hanover, Germany and its environs.     Subjects were randomly assigned to receive either a multivitamin/mineral or placebo capsule with identical appearance for six months containing 36 mg 36mg vitamin E, 150 mg vitamin C, and 9 mg beta-carotene. Serum concentrations of vitamin C, alpha-tocopherol, and beta-carotene were measured initially and after six months of supplementation.  RESULTS: Median serum concentrations of alpha-carotene and vitamin E increased significantly in the supplemented group, whereas no significant modifications were observed in the placebo group.   After supplementation none of the members of the supplemented group had tocopherol concentrations below 30 micromol/L and only one woman of the supplemented group had a serum beta-carotene concentration below 0.4 micromol/L. The change in serum concentrations of vitamin C and E in the supplemented group depended on the status at baseline. CONCLUSION: A six-month supplementation with physiological doses of antioxidant vitamins improves the blood concentration of these nutrients even in relatively well-nourished elderly women or, as seen for vitamin C, prevents reduction of serum concentrations. Prevalence of suboptimal serum concentrations can be reduced.

 

Wolters M, Hermann S, Hahn A. (March, 2004) Int J Vitam Nutr Res. 74(2):161-8.  [Institute of Food Science, Department of Applied Chemistry, University of Hanover. maike.wolters@lw.uni-hannover.de]

 

 

 

Intakes of antioxidants in coffee, wine, and vegetables are correlated with plasma carotenoids in humans.

The consumption of fruits and vegetables reduces the risk of major chronic degenerative diseases. The active compounds and the mechanisms involved in this protective effect have not been well defined. We collected 7-d weighed dietary records in a group of 61 adults with corresponding plasma samples. The intake of total antioxidants was significantly correlated with plasma lutein, zeaxanthin, and lycopene. Among individual food groups, coffee, wine, and vegetables were significantly correlated with dietary zeaxanthin, beta-carotene, and alpha-carotene. These data agree with the hypothesis that dietary antioxidants other than the well-known antioxidants contribute to our antioxidant defense. Surprisingly, the single greatest contributor to the total antioxidant intake was coffee.

 

(The total intake of antioxidants was approximately 17 mmol/d with beta-carotene, alpha-tocopherol, and vitamin C contributing <10%. The intake of coffee contributed approximately 11.1 mmol, followed by fruits (1.8 mmol), tea (1.4 mmol), wine (0.8 mmol), cereals (i.e., all grain containing foods; 0.8 mmol), and vegetables (0.4 mmol).)

Svilaas A, Sakhi AK, Andersen LF, Svilaas T, Strom EC, Jacobs DR Jr, Ose L, Blomhoff R.
(March, 2004)  J Nutr. 134(3):562-7.  [Lipid Clinic, Medical Department, Rikshospitalet, University of Oslo, Oslo, Norway.]

 

 

 

 

Influence of combined antioxidant nutrient intakes on their plasma concentrations in an elderly population.

Data from a cross-sectional survey of 746 non-institutionalized, Boston-area elderly individuals (aged > or = 60 years old) were analyzed to assess the relation between antioxidant nutrient intake and plasma antioxidant status. Intakes of vitamin C and carotenoids and supplemental vitamin E were estimated by using 3-d diet records. 

·         Plasma alpha-tocopherol concentrations were 18% greater in individuals consuming > or = 220 mg vitamin C/d compared with those with intakes < 120 mg/d.

·         Plasma carotenoid concentrations were 13% higher across increasing categories of vitamin C intake).

An increasing intake of carotenoids was moderately associated with higher plasma alpha-tocopherol and unrelated to ascorbic acid status. An increasing intake of supplemental vitamin E was weakly correlated with plasma ascorbic acid   and unrelated to carotenoid status.

 

These results provide epidemiologic evidence that increasing intake of either vitamin C, vitamin E, or carotenoids is associated with greater plasma concentrations of one or both of the other antioxidant vitamins and not associated with any impairment in antioxidant status.

 

Jacques PF, Halpner AD, Blumberg JB.  (December, 1995)  Am J Clin Nutr.;62(6):1228-33.
[Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111]


 

beta-Carotene and alpha-tocopherol are synergistic antioxidants.
 
Cooperative interaction between fat-soluble antioxidants were examined in a membrane model.  It was revealed that a combination of beta-carotene and alpha-tocopherol results in an inhibition of lipid peroxidation significantly greater than the sum of the individual inhibitions.  The data provide evidence that beta-carotene can act synergistically with alpha-tocopherol as an effective radical-trapping antioxidant in membranes.

 

Palozza P, Krinsky NI.  (August 15, 1992) Arch Biochem Biophys.;297(1):184-7. Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111-1837.

 

 

 

Beta-carotene with vitamins E and C offers synergistic cell protection against NOx.

The peroxynitrite anion and the nitrogen dioxide (radical) are important toxic species which can arise in vivo from nitric oxide.

 

Both in vivo and in vitro cell protection is demonstrated for beta-carotene in the presence of vitamin E and vitamin C. 

 

A synergistic protection is observed (between Vitamins E and C)--compared either of these anti-oxidants, individually.  This may be explained in terms of an electron transfer reaction in which the beta-carotene radical is repaired by vitamin C.


Bohm F, Edge R, McGarvey DJ, Truscott TG.  (October, 1998)  FEBS Lett. 9; 436(3):387-9. [Department of Dermatology (Charite), Humboldt University, Berlin, Germany.]



Zeaxanthin in combination with ascorbic acid or alpha-tocopherol protects ARPE-19 cells against photosensitized peroxidation of lipids.

 
The antioxidant action of carotenoids is believed to involve quenching of singlet oxygen and scavenging of reactive oxygen radicals.   We found that zeaxanthin-supplemented cells, in the presence of either alpha-tocopherol or ascorbic acid, were significantly more resistant to photoinduced oxidative stress. Cells with added antioxidants exhibited increased viability and accumulated less lipid hydroperoxides than cells without the antioxidant supplementation. Such a synergistic action of zeaxanthin and vitamin E or C indicates the importance of the antioxidant interaction in efficient protection of cell membranes against oxidative damage induced by photosensitized reactions.

 

Wrona M, Rozanowska M, Sarna T.  (May, 2004) Free Radic Biol Med. 1;36(9):1094-101.   [Department of Biophysics, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland.]

 

 

 
CAROTENOIDS

 

Dietary supplementation with a natural carotenoid mixture decreases oxidative stress.

31 free-living healthy nonsmoking volunteers were recruited by posters and e-mails in The University of Reading.  The volunteers consumed a daily supplement (for 3 weeks in a randomized crossover design separated by a 12 week washout phase) comprising either capsules containing just fish oil (4 x 1 g) or fish oil (same dosage), but also containing a natural carotenoid mixture (4 x 7.6 mg) The carotenoid mixture provided a daily intake of beta-carotene (6.0 mg), alpha-carotene (1.4 mg), lycopene (4.5 mg), bixin (11.7 mg), lutein (4.4 mg) and paprika carotenoids (2.2 mg).

 

Blood and urine samples were collected on days 0 and 21 of each dietary period.

CONCLUSIONS:

·         Consumption of the natural carotenoid mixture lowered the increase in oxidative stress induced by the fish oil as assessed by ex vivo oxidative stability of LDL and DNA degradation product in urine.

·        The carotenoid mixture also enhanced the plasma triglyceride-lowering effect of the fish oil. 

 

Kiokias S, Gordon MH.  (September, 2003)  Eur J Clin Nutr. 57(9):1135-40.  Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The University of Reading, Whiteknights, Reading, UK.


 
Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts.
 

BACKGROUND: Carotenoids may reduce lung carcinogenesis because of their antioxidant properties   The relation between lung cancer risk and intakes of alpha-carotene, beta-carotene, lutein, lycopene, and beta-cryptoxanthin in 2 large cohorts was studied.  

·         275 new cases of lung cancer were diagnosed in 46,924 men; during a 12-y follow-up period,

·         519 new cases were diagnosed in 77,283 women.

Carotenoid intakes were derived from the reported consumption of fruit and vegetables on food-frequency questionnaires administered at baseline and during follow-up.   RESULTS: In the pooled analyses, alpha-carotene and lycopene intakes were significantly associated with a lower risk of lung cancer. Lung cancer risk was significantly lower in subjects who consumed a diet high in a variety of carotenoids     In subjects who never smoked, a 63% lower incidence of lung cancer was observed. CONCLUSION: Data from 2 cohort studies suggest that several carotenoids may reduce the risk of lung cancer.

 

Michaud DS, Feskanich D, Rimm EB, Colditz GA, Speizer FE, Willett WC, Giovannucci E.  (October, 2000)  Am J Clin Nutr.  72(4):990-7.   [Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA 02115]


 

Non-antioxidant properties of carotenoids.
 
Dietary antioxidants, such as:

Carotenoids

Tocopherols

vitamin C and

flavonoids

reveal additional biological effects which might be of importance in context with the prevention of degenerative diseases

 

Stahl W, Ale-Agha N, Polidori MC.  (March-April, 2002) Biol Chem.;383(3-4):553-8.  [Institut fur Physiologische Chemie I, Heinrich-Heine-Universitat Dusseldorf, Germany.]

 

 

Supplementation of a low-carotenoid diet with tomato or carrot juice modulates immune functions in healthy men.
 

Beta-carotene has been shown to enhance immune functions in humans.  The objective of this study was to investigate the effects of a low-carotenoid diet supplemented with either tomato (providing high amounts of lycopene) or carrot juice (providing high amounts of alpha- and beta-carotene) on immune functions in healthy men.

 

METHOD: In a blinded, randomized, cross-over study, male subjects on a low-carotenoid diet consumed 330 ml/day of either tomato juice (37.0 mg/day lycopene) or carrot juice (27.1 mg/day beta-carotene and 13.1 mg/day alpha-carotene) for 2 weeks with a 2-week depletion period after juice intervention

 

CONCLUSIONS:

·         Increased plasma carotenoid concentrations after vegetable juice consumption are accompanied by a time-delayed modulation of immune functions in healthy men consuming a low-carotenoid diet.

·         Juice consumption resulted in relatively fast responses in plasma carotenoid concentrations.

 

Watzl B, Bub A, Briviba K, Rechkemmer G. (2003)   Ann Nutr Metab. 47(6):255-61. Institute of Nutritional Physiology, Federal Research Centre for Nutrition, Haid-und-Neu-Strasse 9, DE-76131 Karlsruhe, Germany. bernhard.watzl@bfe.uni-karlsruhe.de


 


Coenzyme Q10 serum levels in Huntington's disease.
 

Mitochondrial dysfunction contributes to the neurodegenerative process in Huntington's disease (HD). Coenzyme Q10 (CoQ10) enhances mitochondrial complex I activity and may therefore provide a therapeutic benefit in HD.

 

We compared serum CoQ10 levels of previously untreated-and treated HD patients with those of healthy controls.   Our results support that CoQ10 supplementation in HD patients may reduce impaired mitochondrial function in HD.

 

Andrich J, Saft C, Gerlach M, Schneider B, Arz A, Kuhn W, Muller T.   (2004)  J Neural Transm Suppl. (68):111-6. Department of Neurology, St Josef Hospital, Ruhr University, Bochum, Germany.

 

 

 

Age-related changes in plasma coenzyme Q10 concentrations and redox state in apparently healthy children and adults.

 


Coenzyme Q10 (CoQ) is an endogenous enzyme cofactor, which may provide protective benefits as an antioxidant.  

 

The objectives of this study are to determine if age-related differences in reduced CoQ (ubiquinol), oxidized CoQ (ubiquinone), and CoQ redox state exist in childhood, and to establish reference intervals for these analytes in healthy children. Apparently healthy children (n=68) were selected from individuals with no history of current acute illness, medically diagnosed disease, or current medication treatment. Self-reported healthy adults (n=106) were selected in greater Cincinnati.


Mean total CoQ and ubiquinol concentrations are similar in younger children (0.2-7.6 years) and adults (29-78 years); however, lipid-adjusted total CoQ concentrations are significantly increased in younger children.   

 

Miles MV, Horn PS, Tang PH, Morrison JA, Miles L, DeGrauw T, Pesce AJ.  (September, 2004)  Clin Chim Acta;347(1-2):139-44.  [Divisions of Pathology and Laboratory Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA. michael.miles@cchmc.org]


 

 

Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson's disease.

Features of Parkinson's disease (PD) include:

oxidative stress,

nigral mitochondrial complex I deficiency

and visual dysfunction,

 

all of which are also associated with coenzyme Q(10) (CoQ(10)) deficiency  Our results indicate a moderate beneficial effect of oral CoQ(10) supplementation and a significantly better improvement of FMT performance compared with placebo in PD patients.

 

Muller T, Buttner T, Gholipour AF, Kuhn W.  (May, 2003) Neurosci Lett. 8;341 (3):201-4.
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, Germany. thomas.mueller@ruhr-uni-bochum.de

 

 

 

Biochemical, physiological, and medical aspects of ubiquinone function.

 

Ubiquinone (coenzyme Q) , in addition to its well-established function as a component of the mitochondrial respiratory chain, in recent years it has acquired increased attention as an antioxidant.

 

It:

·         Occurs in all cellular membranes as well as in blood serum and in serum lipoproteins

·         Protects membrane phospholipids and serum low-density lipoprotein from lipid preoxidation

·         Protects mitochondrial membrane proteins and DNA from free-radical induced oxidative damage

·         Acts independently of other antioxidants such as Vitamin E

 

Administration of ubiquinone as a dietary supplement seems to lead primarily to increase serum levels, which may account for most its reported beneficial effects.

 

Ermster  L, Dallner G  (May 24, 1995)  Biochim Biophys Acta 1271(1):195-204.  [Department of Biochemistry, Arrhenius Laboratories of Natural Sciences, Stockholm University, Sweden.]

 

 

 

 

 

Effects of coenzyme Q10 in early Parkinson disease; evidence of slowing on the functional decline.

  

Parkinson disease (PD) is a degenerative neurological disorder.  Coenzyme Q10 was tested (testing and evaluation occurred over a 16 month period followed by an 16 month follow-up period) and proved safe and well tolerated at dosages of up to 1200mg/d.  At this level it appeared to slow the progressive deterioration of function in PD…

 

Shults CW, Oakes D, Kieburtz K, Beal MF, et al. (October 2002)  Arch Neurol 59(10):1541-50.   [Department of Neurosciences, Mail code 0662, University of California-San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0662]

 

 

 

 

GREEN  TEA

 

Effect of increased tea consumption on oxidative DNA damage smokers: a randomized controlled study.

 

Tea drinking has been associated with decreased occurrence of cancer and heart disease.  One potential mechanism for these findings is the strong antioxidant effect of tea polyphenols.  A phase II randomized controlled tea intervention trial was designed  to study the effect of high consumption (4 cups/d) of decaffeinated green or black tea on oxidative DNA damage as measured by urinary 8-hydroxydeoxyguanosine (8-OhdG) among smokers over a 4 month period.  A total of 133 of 143 smokers completed the intervention.  Plasma and urinary levels of catechins rose significantly in the green tea group compared with drinkers of black tea or water, only.  This data suggests that regular green tea drinking might protect smokers from oxidative damages and could reduce cancer risk or other diseases caused by free radicals associated with smoking.

 

Hakim IA, Harris RB, et al.  (October, 2003) J Nutr. 133(10):3303S-3309S  [Mel and Enid Zuckerman Arizona College of Public Health, University of Arizona, Tucson AZ 85724.  ihakim@azcc.arizona.edu]

 

 

 

A new function of green tea: prevention of lifestyle-related diseases.

 

In the normal human life span, there occur lifestyle-related diseases that may be preventable with nontoxic agents…Green tea is one of the most practical cancer preventives as has been shown in various in vitro and in vivo experiments, along with epidemiological studies.    It was hypothesized that  green tea might be a preventive agent for chronic inflammatory diseases.  Testing was conducted on its inhibitory effect TNF-alpha gene expression in transgenetic mice as a model of human idiopathic pulmonary fibrosis which also fequently develop lung cancer.  Expressions of TNF-alpha and IL-6 were inhibited in the lungs of these mice after treatment with green tea in drinking water for four months.  In a separate study in Saitama Prefecture, Japan, people found consuming over 10 cups of green tea a day suffered almost no cardiovascular disease.  These data suggest that green tea has preventive effects on both chronic inflammatory diseasea and lifestyle-related diseases (including cardiovascular disease and cancer), resulting in prolongation of life span.

 

Sueoka N et al (April, 2001) Ann N Y Acad Sci 928:274-80  [Saitama Cancer Center Research Institute, Japan]

 

 

 

 

Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement.

 

Green and black tea polyphenols have been extensively studied as cancer chemopreventive agents.  Many in vitro experiments have supported their strong antioxidant activity.  Thirty healthy subjects were randomly assigned to three different sequences of green tea, black tea, or a green tea extract supplement in an experiment with a one-week washout period in between treatments.  Flavanol absorption was enhanced when tea polyphenols were administered as a green tea supplement in capsule form and led to a small , but significant increase in plasma antioxidant activity compared with just teas themselves.  These observations suggest that green tea extract supplements retain the beneficial effect of green tea…without the side effects of caffeine associated with the green and black tea beverages. 

 

Henning SM, Niu Y et al (December, 2004)  Am J clin Nutr.  80 (6):1558-64  [Center for Human Nutrition, David Geffen School of Medicini and the Department of Biostatistics, School of Public Health, University of California, Los Angeles 90095  shenning@mednet.ucla.edu

 

 

 

 

Green tea consumption enhances survival of epithelial ovarian cancer.

 

In Hangzhou, China 254 patients recruited during 1999-2000 with histopahtologically confirmed epithelial ovarian cancer  were followed up for a minimum of three years.  Close relatives were also traced.  The variables examined included their survival time and the frequency and quantity of tea consumed post-diagnosis.  The survival experience was different between tea drinkers and nondrinkers.  78 % of the tea-drinkers survived to the time of the interview compared to 48% of the non-tea-drinkers.  Tea-drinkers were defined as those who consumed more than 500g of dried tea leaves/year.  This equates to brewing one batch or more of green tea per day of approximately 2 g of dried tea leaves per batch.  The corresponding dose-response relationships were significant.  We conclude that increasing the consumption of green tea post-diagnosis may enhance epithelial ovarian cancer survival.

 

Zhang M, Lee AH et al (November, 2004)  Intl J Cancer  112 (3):465-9  [School of Public Health, Curtin University of Technology, Perth, WA, Australia]

 

 

 

 

 

Tea catechin synergies in inhibition of cancer cell proliferation and of a cancer specific cell surface oxidase (ECTO-NOX).

  

The anticancer properties of tea catechins are most frequently attributed to the principal catechin, (-) epigallocatechin-3-gallate (EGCg).  Efficacy was evaluated studying growth of cultured HeLa cells and inhibition of the enzymatic activity.  Various synthetic mixtures based on purified catechins and decaffeinated tea extracts treated enzymatically to reduce the ester bond-containing catechins varying in EGCg content were of comparable efficacy to decaffeinated green teas extracts .  Such mixtures appear to offer potential cancer protection and therapeutic advantages over those of EGCg alone.  The mixtures’ advantages stem appear to be lowered toxicity of the mixture to normal cells and a more efficient blood delivery of orally-administered catechins to a tumor sight.  

 

Morre DJ et al (May, 2003)  Pharmacol Toxicol 92 (5):234-41.  [Departments of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907  Morre@pharmacy.purdue.edu]

 

 

 

LYCOPENE

 

Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in women.

 

Growing evidence suggests that lycopene has significant in vitro antioxidant potential.  A study involving 39,876 middle-aged and elderly women initially free of cardiovascular disease and cancer was recently concluded.  Blood samples were volunteered and collected from about 71% of these.   Data such as smoking status, age and eventual discovery of cardio vascular disease were compiled.  Plasma lycopene,other carotenoids, retinal and total cholesterol were likewise measured.    Conclusions drawn from this study confirmed that higher plasma lycopene concentrations are associated with a lower risk of cardiovascular disease in women.  Neverthless, further studies are encouraged and particularly the determinants of plasma lycopene concentrations need to be better understood.

 

Sesso HD et al (January, 2004) Am J Clin Nutr 79 (1):47-53.  [Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School. Boston MA 02215  hsesso@hsph.harvard.edu]

 

 

 

 

Lycopene and vitamin C concentrations increase in plasma and lymphocytes after tomato intake.  Effects on cellular antioxidant protection.

 

Hypothesis:  That regular consumption of small amounts of tomato products can protect lymphocyte DNA and lipids from oxidative damage.  TEST:  12 healthy female subjects (mean age 25.2) were instructed to follow a standardized diet for one week, followed by three weeks consumption of the same diet, but enriched with small amounts of different tomato products.  (An average of 8mg lycopene, 0.5 mg beta-carotene and 11 mg of Vitamin C per day comprised the enrichment.)  Plasma and lymphocyte concentrations of carotenoids, Vitamin C and Vitamin E were analyzed.  RESULTS:  Dietary intervention with tomato products increased lycopene concentration both in plasma and lymphocytes.  Vitamin C increased approximately 35% in plasma and by approximately 230% in lymphocytes.  Vitamin E decreased significantly in plasma, but not in lymphocytes.  Finally, there was an improve protection from DNA oxidative damage with no significant effect on malondialdehye (MDA) levels.  CONCLUSIONS:  These results suggest that tomato products are not only good sources of lycopene, but also sources of bioavailable vitamin C.  A regular intake of small amounts of tomato products can increase cell protection from DNA damage induced by oxidant species.    Since there are different antioxidants present in tomatoes, this effect may originate from synergism of the same.

 

Riso P, et al.  (October, 2004)  Eur J Clin Nutr.  58 (10):1350-8.  [Department of Food Science and Technology, Division of Human Nutrition, University of Milan, Italy.  Patrizia.riso@unimi.it]

 

 

 

 

Lymphocyte lycopene conentration and DNA protection from oxidative damage is increased in women after a short period of tomato consumption.

 

Several epidemiologic studies have suggested a role of tomato products in protecting against cancer and chronic diseases.  In nine adult women an evaluation of whether the consumption of 25g of tomato puree for 14 consecutive days increased plasma and lymphocyte carotenoids concentration.   The paste contained 7mg lycopene and 0.3 mg beta-carotene.)    Levels were assessed both before and after the period of tomato intake.  The conclusion of this study is that small amounts of tomato puree added to the diet over even a short period can increase carotenoids concentrations and the resistance of lymphocytes to oxidative stress.

 

Porrini M, Riso P.  (February, 2000)  J Nutr.  130 (2):189-92.  [Department of Food Science and Technology, University of Milan, Italy]

 

 

 

 

 

Does tomato consumption effectively increase the resistance of lymphocyte DNA to oxidative damage?

 

Lycopene, the main carotenoid in tomato, has been shown to be a potent antioxidant in vitro.  Ten healthy women were divided into two groups of five subjects each to test tomato intake on plasma carotenoids concentrations and lymphocyte resistance of oxidative stress.  Before and after each diet period plasma carotenoid concentrations and primary lymphocyte resistance to oxidative stress were analyzed.  RESULTS:  Tomato consumption had a beneficial effect on cellular antioxidant capacity in vivo conferring a decrease of lymphocyte DNA damage of 33% when subjected to hydrogen peroxide.  Also total plasma lycopene concentrations increased by 0.5 micromol/L in the group that consumed the tomato diet while those who did not, experienced an actual decrease of .02 micromol/L.    Thus, tomato products may reduce the susceptibility of lymphocyte DNA to oxidative damage.

 

Riso P et al. (April, 1999) Am J Clin Nutr 69 (4):712-8.  [Department of food Science and Technology, University of Milan, Italy.  Nutr_lab@imiucca.csi.unimi.it]

 

 

 

VITAMIN   C

 

Vitamin C supplementation and respiratory infections: a systematic review

 

Military personnel and other subjects living under conditions comparable to military recruits were analyzed to find out whether Vitamin C supplementaion affects respiratory infections.  Seven trials were conducted with military personnel. Three trials with students in crowded lodgings, and two trial with marathon runners.  A statistically significant reduction in the incidence of both the common cold and pneumonia were noted in the bulk of the trials.

 

Hemila H (November, 2004) Mil Med 169 (11):920-5  [Department of Public health, University of Helsinki, Finland]

 

 

 

 

Vitamin C and risk of coronary heart disease in women

 

In 1980 an investigation of 85,118 female nurses who completed a detailed questionnaire commenced that assessed their consumption of Vitamin C and other nutrients and was followed up for 16 years.  After adjustment for age, smoking and a variety of other coronary risk factors we observed a modest, but significant inverse association between total intake of vitamin C and risk of coronary heart disease.  Among women who did not use Vitamin C supplements or multivitamins, the association between intake of Vitamin C from diet alone and incidence of coronary heart disease was weak and not significant.  In conclusion it appears that users of Vitamin C supplements are at lower risk for coronary heart disease.

 

Osganian SK et al (July, 2003)  J Am Coll Cardiol.  42 (2): 246-52 [Department of Medicine, Children’s Hospital, Boston, MA  stravroula.osganian@TCH.harvard.edu]

 

 

 

 

Vitamin C  supplementaion decreases oxidative DNA damage in mononuclear blood cells of smokers.

 

Antioxidants, in particular Vitamin C, have been suggested to decrease oxidative DNA damage.  Such effects have been shown in mononuclear blood cells in the first few hours after ingestion…In a recent study ingestion of slow release Vitamin C formulation was associated  protective effects to DNA.  Overall the slow release tablets of vitamin C formulation had a more pronounced and sustained protective effect on base damage compared with the plain release tablets.    Plasma vitamin E was unaltered in the first 12 hours after ingestion of a single tablet, suggesting that the antioxidant effect was mediated by Vitamin C.  In conclusion the study revealed that long-term vitamin C supplementation at a dosage of 500mg together with Vitamin E of 1182 mg, decreases the steady-state level of oxidative DNA damage in mononuclear blood cells of smokers.

 

Moller P (October, 2004)  Eur J Nutr  43 (5):267-74  [Institute of Public Health 9c/o Dept. of Pharmacology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark   fipm@farmakol.ku.dk]

 

 

 

 

Decreased levels of plasma vitamin C and increased concentrations of inflammatory and oxidative stress markers after stroke.

 

 

Inflammation is a critical component of the complex pathophysiological response to stroke.  Vitamin C has been shown to have important roles in cell performance and vascular function.  In a study of 15 stroke victims it was found that their systems had lower plasma levels of Vitamin C than did nonstroke patients. Additionally stroke patients had elevated serum levels of C-reactive protein and a host of other indicators of special concern.

 

Sanchez-Moreno C et al (January, 2004) Stroke 35 (1):163-8  [Nutrition and Neurocognition Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging, Boston, MA 02111]

 

 

 

 

 

Antioxidant vitamins and mortality in older persons:  finding from the nutrition add-on study to the Medical Research Council Trial of Assessment and Management of Older People in the community.

 

Older persons are at risk of both poor nutrition and increased oxidative stress.  Plasma ascorbate concentrations fall with increasing age, and concentrations of other antioxidants may also be reduced.  1214 randomly selected participants from lists compiled by 51 British family practitioners provided a blood sample and were interviewed about their usual diet with the use of a food-frequency questionnaire.  Statistical analyses were based on deaths after follow-up.  The test results indicated that low blood Vitamin C concentrations in the older British population are strongly predictive of mortality.  In other words, in general terms the higher the ascorbate concentrations the lower the cardiovascular disease mortality and all-cause mortality.

 

Fletcher AE et al (November, 2003)  Am J clin Nutr 78(5):999-1010  [Centre for Aging and Public Health. London School of Hygiene and Tropical Medicine, UK   astrid.fletcher@lshtm.ac.uk

 

 

 

 

VITAMIN  E

 

Gamma-tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting shingolipid synthesis.

 

Gamma-Tocopherol (gammaT), the predominant form of Vitamin E in diets, but not alpha-tocopherol, the major Vitamin E form in tissues and supplements, inhibits proliferation of prostate cancer cell, and lung cancer cells.  Combinations of some vitamin E forms, such as gammaT or its combination with delta-tocopherol, exhibit additive or synergistic inhibitory effects.  In conclusion, this study demonstrates that gammaT and mixed Vitamin E forms induce death of prostate cancer cells.  Thus certain Vitamin E forms may be valuable as anticancer agents.

 

Jiang Q et al (December, 2004)  Proc Natl Acad Sci USA  101 (51):17825-30  [Children’s Hospital Oakland Research institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609  qjiang@purdue.edu]

 

 

 

 

 

Association of vitamin E and C supplement use with cognitive function and dementia in elderly men

 

The Honolulu-Asia Aging Study is a longitudinal study of Japanese-American men living in Hawaii.  Data for this study came from a study of 3,385 men, age 71-93 years, whose use of Vitamin E and C supplements had been ascertained previously.  The subjects were stratified in four groups.  In a multivariate model controlling for other factors, a significant protective effect was found for vascular dementia in men who had reported taking both Vitamin E and C supplements in 1988.   They were also protected against mixed/other dementia.   No protective effect was found for Alzheimer’s dementia.  However, among those without dementia, use of either Vitamin E or C supplements alone in 1988 was associated significantly with better cognitive test performance at the 1991 to 1993 examination.  These results suggest that Vitamin E and C supplements may protect against vascular dementia and may improve cognitive function in late life.

 

Masaki KH (March, 2000)  Neurology 54 (6):1265-72  [Division of Geriatric Medicine, University of Hawaii, John A. Burns School of Medicine, Honolulu  kamal@hhp2.hawaii-health.com]

 

 

 

 

 

 

Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons:  the Established Populations for Epidemiologic Studies of the Elderly.

 

Whether Vitamin C enhanced the effects of Vitamin E in supplement form was studied and in relation to mortality risk in 11,178 persons aged 67-105.  All participated in the Established Populations for Epidemiologic Studies of the Elderly in 1984-1993.  Participants were asked to report all nonprescription drugs currently used, including vitamin supplements.  During the follow-up there were 3490 deaths.  Use of Vitamin E reduced the risk of all-cause mortality and the risk of coronary disease mortality.  Adjustment for alcohol use, smoking history, aspirin use, and medical conditions did not substantially alter these findings which are consistent with those for younger persons and suggest protective effects of Vitamin E supplements in the elderly. 

 

Losonczy KG et al (August, 1996)  Am J Clin Nutr  64 (2):190-6  [Epidemiology, Demography and biometry Program, National Institute on Aging, Bethesda, MD 20892-9205  klosoncz@gibbs.oit.unc.edu]

 

 

 

 

 

Vitamin E supplementation and in vivo immune response in healthy elderly subjects.  A randomized controlled trial.

 

A total of 88 free-living, healthy subjects at least 65 years of age were assigned to two groups.  One group consumed placebos and the other group was subdivided into those that consumed 60 mg  200 mg or 800 mg per day of Vitamin E for 235 days.  Supplementation with /vitamin E for four months improved certain clinically relevant indexes  of cell-mediated immunity in healthy elderly.   Subjects consuming 200 mg per day of Vitamin E had a 65% increase delayed-type hypersensitivity skin response (DTH) which is good, and a six-fold increase in antibody titer to hepatitis B compared with the placebo group.  These results indicated that a level of Vitamin E greater than currently recommended enhances certain clinically relevant in vivo indexes of T-cell-mediated function in healthy elderly persons.  No adverse effects were observed with Vitamin E supplementation. 

 

Meydani SN et al (May 1997)  JAMA 277(17):1380-6  [Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston MA 02111   SvMeydanivlM@HNRC. TUFTS.EDU]

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