Escolar Documentos
Profissional Documentos
Cultura Documentos
Academic Profiles:
Medical Doctor FMUI, 1986
Internist FMUI, 1996
Post Graduate Education in Geriatric Medicine Dept. of
Geriatric & Rehab Medicine Royal Adelaide Hosp.,
Australia, 1997
Consultant (Subspecialist) in Geriatric Medicine FMUI,
2000
Master of Clinical Epidemiology Universitas Indonesia,
2003
Doctor of Philosophy (PhD) Universitas Indonesia, 2006
Professor in Medicine - Universitas Indonesia, 2013
Current Position:
Chair Indonesian Internal Medicine College
Chair Indonesian Geriatric Medicine Society
Chair The Center for Clinical Epidemiology and
Evidence-Based Medicine (CEEBM) Cipto
Mangunkusumo Hosp.
Vice Chair The Indonesian Journal of Internal Medicine
Senior staff in Geriatric Medicine Div Internal Medicine
Dept, FMUI
The Role of
Antioxidant in
Elderly
SITI SETIATI
Free Radical Theory of Aging
A free radical is any chemical species (atom, ion or molecule)
that contains an unpaired or odd number of electrons and by
far the most common source of free radicals in biological
systems is oxygen.
Wickens AP. Ageing and the free radical theory. Respiration Physiology 2001;128:37991.
AFAR. Theories of Aging
Free Radical Theory of
Aging (2)
This produces a number of short-lived intermediates
including the formation of superoxide (O2 ),
hydrogen peroxide (H2O2) and the hydroxyl radical
(-OH). Both the superoxide and hydroxyl radicals
have a free electron in their outer orbit and are
highly reactive oxidants.
As they are highly reactive and unstable, they look
for other electron and react with other substances,
especially with protein and unsaturated fatty acid.
Wickens AP. Ageing and the free radical theory. Respiration Physiology 2001;128:37991.
Sing B. Seminar report on Free radical theory of Aging.
https://www.slideshare.net/sameersaharan1/presentation-on-34578313
Sing B. Seminar report on Free radical theory of Aging.
https://www.slideshare.net/sameersaharan1/presentation-on-34578313
OXIDATIVE STRESS LEADS TO CELL INJURY
IN MANY ORGANS
Reactive Oxidative Stress
Indeed, the ROS scavenge capacity depends on the number and position of the hydroxyl
group and substituent, as well as glycosylation of phytochemical molecules. Generally,
phytochemicals with more hydroxyl groups may have a stronger antioxidant capacity.
Si H, Liu D. Dietary antiaging phytochemicals and mechanisms associated with
prolonged survival. The Journal of nutritional biochemistry. 2014;25(6):581-591..
Activation of AMPK
At cellular level, activated AMPK inhibits hepatic
gluconeogenesis, promotes fatty acid oxidation and
insulin sensitivity and regulates mitochondrial
biogenesis.
Activating AMPK may help multiple longevity pathways to promote healthy aging.
AMPK activation gradually declines during aging. It is possible that the age-related
increase in chronic inflammation levels is responsible for the suppression in AMPK
activity.
AMPK increases longevity by reducing protein production and enhancing autophagy.
Quercetin, curcumin, and epicatechin were also associated with activation of the AMPK
pathway, suggesting that activation of AMPK may serve as a central mechanism for many
observed biological effects of phytochemicals
Si H, Liu D. Dietary antiaging phytochemicals and mechanisms associated with
prolonged survival. The Journal of nutritional biochemistry. 2014;25(6):581-591..
Sirt-1
pathway
The sirtuin pathway, most
notable for its association
with the anti-aging effects
of calorie restriction, has
received particular
attention.
Turmeric
Cardiovascular disease
Broccoli
Pomegranate
Green tea AND cardiovascular
CENTRAL
MEDLINE database (Cochrane Database)
Useful articles: 4
1. Gang Liu, Xue-Nan Mi, Xin-Xin Zheng, Yan-Lu Xu, Jie Lu, and Xiao-Hong Huang. Effects of tea intake on blood pressure: a meta-analysis of randomised controlled trials. British Journal of
Nutrition (2014), 112, 10431054
2. Khalesi S, Sun J, Buys N, Jamshidi A, Nikbakht-Nasrabadi E, Khosravi-Boroujeni H. Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials.
Eur J Nutr (2014) 53:12991311
3. Wang ZM, Zhou B, Wang YS, Wang QM, Yan JJ, Gao W, Wang LS. Black and green tea consumption and the risk of coronary artery disease: a meta-analysis. Am J Clin Nutr 2011;93:50615.
4. Hartley L, Flowers N, Holmes J, Clarke A, Stranges S, Hooper L, Rees K. Green and black tea for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews
2013, Issue 6. Art. No.: CD009934.
Green Tea and Cardiovascular
AUTHORS Liu, et. al (2014) Khalesi, et. al. (2014) Wang et. al (2011) Hartley et. al. (2013)
(Year)
AIM To asess the short effect To asess the effect of To asess the association To assess the effect of
and long effect of green green tea catechin to between green tea green tea (and black
tea (and black tea) in lower blood pressure consumption and risk of tea) prvent the
lowering blood CAD. cardiovascular disease.
pressure.
METHODS Systemmatic review, Systemmatic review, meta Meta analysis Systemmatic review,
meta analysis anatlysis meta analysis
STUDIES 6 RCTs for acute effect 13 RCTs (n=1040) 3 case control 2 RCTs measure blood
INCLUDED (n=203) 2 prospective cohort pressure. (n=167)
21 RCTs for long term N = 53,586 4 RCTs measure lipid
effect (n=1273) profile (n= 327)
STUDIES Acute: 1-35 h 3 weeks 3 months 7-13 years 1-3 months
DURATION Long: 1-24 minggu
CONCLU- The acute intake of Green tea and its There is an association Green tea lowers the
SION green tea had no effects catechins may improve between the highest blood pressure (sistolic
on systolic and diastolic blood pressure, total and green tea consumption and diastolic), lipid
BP. After long-term low-density lipoprotein and reduced profile, except HDL.
green tea significantly cholesterol. risk of CAD (RR: 0.72)
reduced systolic and
diastolic BP.
Aim: The present study systematically reviewed randomised controlled trials and
examined the effect of green tea consumption on blood pressure using meta-
analysis.
Methods: Search of ProQuest, PubMed, Scopus and Cochrane Library (CENTERAL)
was conducted, to identify eligible articles. Articles from 1995 to 2013 were
included. A random-effect model was chosen to calculate the effect of combined
trials.
Result: Thirteen studies were included in the meta-analysis. Green tea consumption
significantly changed systolic blood pressure, by -2.08 mm Hg (95 % CI -3.06, -1.05),
and diastolic blood pressure, by -1.71 mm Hg (95 % CI -2.86, -0.56), compared to the
control. Changes in lipid profile, blood glucose and body mass index were also
assessed in the meta-analysis. A significant reduction was found in total cholesterol
(-0.15 mmol/L [95 % CI -0.27, -0.02]) and low-density lipoprotein cholesterol (-0.16
mmol/L [95 % CI -0.22, -0.09]).
Conclusion The present meta-analysis suggests that green tea and its catechins
may improve blood pressure, and the effect may be greater in those with
systolic blood pressure >130 mm Hg.
Aim: We performed a meta-analysis of randomised controlled trials to
determine the changes in systolic and diastolic BP due to the intake of black
and green tea.
Method: A systematic search was conducted in MEDLINE, EMBASE and the
Cochrane Controlled Trials Register up to May 2014. The weighted mean
difference was calculated for net changes in systolic and diastolic BP using
fixed-effects or random-effects models. Previously defined subgroup analyses
were performed to explore the influence of study characteristics.
Result: . A total of twenty-five eligible studies with 1476 subjects were selected.
The acute intake of tea had no effects on systolic and diastolic BP. However,
after long-term tea intake, the pooled mean systolic and diastolic BP were
lower by -18 (95 % CI -24, -11) and -14 (95 % CI -22, -06) mmHg,
respectively When stratified by type of tea, green tea significantly reduced
systolic BP by 21 (95 % CI 229, 212) mmHg and decreased diastolic BP by 17
(95 % CI 229, 205) mmHg,
Conclusion: The present findings suggest that long-term (12 weeks)
ingestion of tea could result in a significant reduction in systolic and
diastolic BP
Gang Liu, Xue-Nan Mi, Xin-Xin Zheng, Yan-Lu Xu1, Jie Lu1 and Xiao-Hong Huang. Effects of tea intake on blood
pressure: a meta-analysis of randomised controlled trials. British Journal of Nutrition (2014), 112, 10431054
Green tea AND diabetes
MEDLINE database CENTRAL
(Cochrane Database)
868 39 Date: 2006-2017;
Study Type:
Only items with links clinical trial,
Humans, 10 years, systematic review;
English, Adult 18+ Speciality: all
years. Language: English
48 39
Filtering by title and abstract:
Diabetes mellitus type 2, fasting blood glucose, abnormalities glucose.
5 13
Full text availability and similarity with other
resources
5 3
Useful articles: 8
Green Tea and DIabetes
AUTHORS Jing, et. al. (2009) Hsu, et. al. (2011) MacKenzie, et. al. Liu,et. al. (2014)
(Year) (2007)
AIM To conduct a meta- To examine the effect of a To examine the effect of To examine the effects
analysis of studies that decaffeinated green tea a decaffeinated green of green tea extract in
assessed the extract (GTE) on obese tea extract (GTE) on type 2 diabetic patients.
association of tea individuals with type 2 obese individuals with
consumption and the diabete type 2 diabete
risk of type 2 diabetes
METHODS Systemmatic review, RCT (n =80) RCT (n=49) RCT (n=92)
meta analysis Placebo vs 856 mg extract (placebo vs 375 mg/d, or
9 cohort studiies, n= 750 mg/day)
324,111/11,400
STUDIES 5-18 years 16 weeks 3 months 16 weeks
DURATION
CONCLU- Tea consumption 4 There is no statistically The changes of HbA1C There is significant
SION significant difference were not significantly differences between
cups per day may
lower the risk of between the GTE group different between study two groups in
and placebo group in any arms. triacylglycerol level and
type 2 diabetes . of the anthropometric or ghrelin level, but not in
lab variables assessed. fasting blood glucose
However, there were and HbA1C level.
some statistically
significant within-group
GTE changes detected
Green Tea and DIabetes
AUTHORS Huang, et. al. (2013) Toolsee, et. al. (2013) Mousavi, et. al. (2013) Mozaffari-Khosravi, et.
(Year) al. (2014)
AIM To explore the To examine the effects of To examine the effects To compare the effect of
associations of green green tea extract in type 2 of green tea extract in sour and green
tea and rock tea diabetic patients type 2 diabetic patients tea consumption on
consumption with risk insulin resistance and
of impaired fasting oxidative stress in DM.
glucose (IFG) and
impaired glucose
tolerance (IGT)
METHODS Cross sectional RCT (n=155) RCT (n=63) RCT (n=100)
(n= 4808) Placebo vs green tes 4 cups GT/d vs 2 cups Sour tea VS green tea
< 1 cup/w vs 1-15cup/w extract Gt/day vs placebo
vs 16-30 cup/ w vs 30
cup/w
STUDIES - 14 weeks 8 weeks 4 weeks
DURATION
CONCLU- Consumption of green Green tea consumption There is no significantly Both tea didnt reduce
SION or rock tea may protect during the 14-week period differences in fasting significantly fasting
against the of study did not affect blood glucose, HbA!C, or blood glucose and lipid
development of type 2 fasting plasma glucose, lipid profile. profile.
diabetes mellitus, the level of the
particularly in those H1Ac, or lipid profile.
who drink 1630 cups
per week.
OBJECTIVE: To conduct a meta-analysis of studies that assessed the association of tea
consumption and the risk of type 2 diabetes.
RESEARCH DESIGN AND METHODS: We performed a systematic literature search through
November 2008 in PUBMED, MEDLINE, EMBASE, and Cochrane Database of Systematic
Reviews. The search was limited to English language studies. Studies were excluded if
they were type 1 diabetes, animal studies. Nine cohort studies were identified by two
authors, and summary relative risks (RRs) were calculated using a random-effects model.
RESULTS: We identified nine cohort studies, including 324,141 participants and 11,400
incident cases of type 2 diabetes with follow-up ranging from 5 to 18 years. The
summary adjusted RR did not show that tea consumption was associated with a reduced
type 2 diabetes risk (RR, 0.96; 95% confidence interval (CI), 0.921.01). Evidence from
the results of our stratified analyses revealed that tea consumption 4 cups per day (RR,
0.8; 95% CI, 0.70.93) might play a role in the prevention of type 2 diabetes.
CONCLUSIONS: This meta-analysis indicates that tea consumption 4 cups per day may
lower the risk of type 2 diabetes.
Broccoli OR sulforaphane AND cardiovascular OR diabetes
MEDLINE database CENTRAL
(Cochrane Database)
280
Date: 2006-2017;
Study Type: clinical
Only items with links trial, systematic
Humans, 10 years, English, review; Speciality: all
Adult 18+ years.
0
21
Filtering by title and abstract:
Hypertension, cardiovascular disease, coronary arthery disease, heart failure,
diabetes.
3 0
Useful articles: 3
1. Christiansen B, Bellostas Muguerza N, Petersen AM, Kveiborg B, Madsen CR, Thomas H, Ihlemann N, Srensen JC, Kber L, Srensen H, Torp-Pedersen
C, Domnguez H. Ingestion of broccoli sprouts does not improve endothelial function in humans with hypertension. PLoS One. 2010 Aug 27;5(8):e12461. doi:
10.1371/journal.pone.0012461.
2. Bahadoran Z, Mirmiran P, Hosseinpanah F, Rajab A, Asghari G, Azizi F. Broccoli sprouts powder could improve serum triglyceride and oxidized LDL/LDL-
cholesterol ratio in type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Diabetes Res Clin Pract. 2012 Jun;96(3):348-54. doi:
10.1016/j.diabres.2012.01.009. Epub 2012 Feb 9.
3. Bahadoran Z, Tohidi M, Nazeri P, Mehran M, et. al. Effect of broccoli sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind clinical
trial. Int J Food Sci Nutr, November 2012; 63(7): 767771
Broccoli and Cardiovascular or diabetes
AUTHORS Christiansen et. al. Bahadoran et. al. (2012) Bahadoran et. al. (2012)
(Year) (2010)
AIM To asess the effect of To asess the broccoli To asess the effect of
broccoli to blood sprout powder (BSP) to broccoli sprout powder
pressure and lower lipid profile in (BSP) in blood glucose,
endothelial function. type 2 diabetic patients insulin serum, and IR in
type 2 diabetic patients.
METHODS RCT (n-40) RCT (n =81) RCT (n-81)
16 95
Filtering by title and abstract:
Hypertension, cardiovascular disease, coronary arthery disease, heart
failure, diabetes
5 2
Full text availability
AUTHORS Tang, et. al (2008) Akazawa, et. al. (2012) Cheungsamarn, et.
(Year) al. (2014)
8 2
Full text availability
Useful articles: 9
Pomegranate and Cardiovascular
AUTHORS Asgary, et. al. (2013) Davidson, et. al. (2009) Lynn, et. al. (2012) Matthew et al (2012)
(Year)
AIM To asess the effect of To asess the effect of To examine the effect of investigated whether a
pomegrnate juice (150 pomegranate juice (240 pomegranate juice (330 test drink enriched in
ml/d) in cardiovascular ml/d) in carotid intima ml/day) on pulse wave pomegranate
risk. thickness in men and velocity (PWV), blood polyphenols, consumed
women with moderate pressure (BP) and with a high-fat meal, can
risk for CHD. plasma antioxidant reduce postprandial
status. lipaemia and improve
vascular function and
blood pressure
METHODS RCT (n=20) RCT (n=289) RCT (n=51) n=19
STUDIES 2 weeks 18 months 4 weeks 2 and 4 h
DURATION
CONCLU- Pomegranate juice have Pomegranate juice Pomegranate juice have Pomegranate juice will
SION beneficial effect in consumption had no beneficial effect in reduce the triasilgliserol
reducing systolic and significant effect on reducing systolic and (TAG) when drinks
diastolic blood overall CIMT progression diastolic blood pressure. during high fat meal.
pressure. rate.
Pomegranate and Cardiovascular
AUTHORS Soare, et. al. Shema-Didi, et.al. Wu, et. al. (2015) Rivara, et. al. (2014) Sahebkar et. al.
(Year) (2014) (2014) (2017)
AIM To asess the To investigate the To asess the effects To examine whether To investigate the
effect of popular effect of a year-long of pomegranate short-term effect of
dietary consumption of juice in supplementation with pomegranate juice in
supplements Pomegranate juice cardiovascular risk, pomegranate juice and reducing systolic and
(inc. (PJ), on two physical extract is safe and well diastolic blood
Pomegranate) in cardiovascular (CV) performance, and tolerated. pressure
cardiovascular some plasma
risk factors:
risk. variables.
hypertension and
lipid profile.
METHODS RCT (n=56) RCT (n=101) RCT (n=33) randomized, crossover, Systemmatic review,
pilot clinical trial (n=24) meta-analysis (8
RCTs, n= 595)
STUDIES 6 months 1 year 6 months 4 weeks 4 weeks-1 year
DURATION
CONCLU- There is no Regular PJ Pomegranate Both pomegranate juice Pomegranate juice
SION cardiovascular or consumption by HD supplementation and extract do not reduce systolic and
metabolic effects patients reduced significantly influence markers of diastolic blood
of dietary systolic blood reduced both SBP inflammation or pressure.
supplements pressure and and DBP, especially oxidative stress nor
(inc. improved lipid profile in HD patients. affect predialysis blood
Pomegranate) in (triacilglycerol) There is no effect pressure.
nonobese on any other
relatively healthy metrics of CV risk or
individuals physical function
Aims: To systematically review and meta-analyze available evidence from randomized
placebo-controlled trials (RCTs) investigating the effects of pomegranate juice
consumption and blood pressure(BP).
Method: A comprehensive literature search in Medline and Scopus was carried out to
identify eligible RCTs.A meta-analysis of eligible studies was performed using a random-
effects model. Quality assessment,sensitivity analysisand publication bias evaluations
were conducted using standard methods.
Results: Quantita-tive data synthesis from 8 RCTs showed significant reductions in both
systolic [weighed mean difference(WMD): 4.96 mmHg, 95% CI: 7.67 to 2.25, p <
0.001) and diastolic BP (WMD: 2.01 mmHg, 95% CI:3.71 to 0.31, p = 0.021) after
pomegranate juice consumption.
2 2
Full text availability
1 0
Useful articles: 1
Pomegranate and Diabetes
STUDIES 3h
DURATION
CONCLUSION The results demonstrated
decreased FBG, increased -
cell function among T2D
participants, 3 hours after PJ
administration
Polyphenol reduce PSA progression in men
with prostate cancer
This study found a significant short-term, favourable effect on the percentage rise
in PSA in men managed with AS and WW following ingestion of this well-tolerated,
specific blend of concentrated foods.
However, there are some weaknesses in this study:
1. This study selected subjects then randomized to divide them, either as placebo
group or food suplement group with ratio 2:1, which is uncommon in RCTs
research.
2. This study only measure PSA as an outcome. It should be supported with other
clinical measurement.
Take Home Message
Free radical theory is one of the oldest theory explaining
about ageing process.
Using antioxidant could delay the ageing process.
Further researches with large sample is needed to prove
the benefit effect of antioxidant either improving
elasticity of blood vessels or controlling blood glucose.
Aims: Investigate the effects of dietary supplementation with
antioxidant vitamins C or E on (1) plasma glucose and insulin
concentrations, as an indicator of the capacity for antioxidant to
interfere with disease process and (2) on glycated haemoglobin A1C
as a measure of antioxidant effects on posttranslational protein
modification implicated in disease complications.
Method: meta analysis (14 RCT)
Result: Dietary antioxidant supplementation did not affect plasma
glucose or insulin levels, suggesting that they could not interfere with
the pathogenesis of insulin resistance. However, HbA1C levels were
significantly reduced by antioxidant supplementation, suggesting that
antioxidants may have some benefit in protecting against the
complications of type 2 diabetes