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1
Food as Medicine
Using Foods to Treat Disease
and to Maximise Optimal
Wellness
By
Stephen Eddey M.H.Sc., B.Sc.(Comp.Med.),
Dip.App.Sc.(Nat.), Ass.Dip.App.Sc.(Chem.),
Cert.IV(Workplace & Training),N.D.
1
Food as Medicine
Finding the right nutrition for:
 Obesity
 Anti-aging/Wellness
 Diseases





Heart Disease
Detoxification
Cancer
Inflammation
Functional foods
1
2
Food as Medicine –
Evolution of the Human Diet
taken from work done by:
Prof. Neil Mann, Australia
2
Basic Questions
•
Who were our ancestors ?
•
What did our ancestors eat ?
•
How do we know?
•
What dietary changes have occurred ?
•
What impact have dietary changes had ?
2
Evolution and Diet
Evolution in a geological context
Mammalian
insectivores
Or
G
Ch
Primates
H. erectus
Apes Ramapithecus “Lucy” H. habilis H. sapiens
(hominid)
Oldest stone tools
Oligocene
Miocene
25 mya
Pliocene
10 mya
Pleistocene
2 mya
Major climatic change
10,000
ya
Australopithecus
aferensis
Approximately
4 million
years ago
3
Evolution and Diet
Dietary changes
•Miocene apes: Specialised, leaf /fruit eaters >15 mya
•Ramapithecus: First hominoid, ~ 10 mya
leaves /fruit /roots /meat scavenger (5-10% energy)
•Lucy: First hominid, small, upright stance, ~ 4.5 mya,
fruits /roots /nuts /meat (>10% energy), probably hunted !
•Homo habilis: First tool maker, hunter, ~ 3 mya,
fruits /meat /roots /nuts (meat > 20% energy)
•Homo erectus: Tall, large brain, big game hunter, ~ 1.5 mya
meat /fruits /roots /nuts (meat 20-50% energy)
•Homo sapiens: Organised big game hunters, ~ 400,000 ya
energy intake from meat estimated > 60%
roots, fruits, vegetation, nuts, seeds
3
Optimal Foraging Theory

Pre-agriculture we were hunter-gatherers

Day-to-day survival depended on daily energy intake
being adequate

Body energy use = Basal metabolism + activity

Best choices were foods with the greatest energy
return (ie energy content - energy expenditure for collection and
preparation)

High energy dense foods became critical
(evident in brain gut trade off in our species)
4
Human Brain Size
Brain 1800
size
(cc) 1400
Homo sapiens

1000
600

Homo erectus
(Aiello
&
Wheeler
1995)
Homo habilis
Australopithecines
200
0
1
2
3
Age in millions of years
4
4
Gut morphology and diet
Chimpanzee
Insectivores
Humans
Horse
Rabbit
Cat
Gorilla
Dog
Frugivores
Folivores (mid-gut)
Faunivores
Folivores (fore-gut)
Cow
Martin, 1994.
The life of primates.
In: The Cambridge
Encylopedia of
Human Evolution
5
Hunter-Gatherers in Recent Time

Dietary data on 181 HG societies recorded in:
“Ethnographic Atlas” (Murdoch 1967)

Animal:Plant subsistence ratio: 65:35
(Cordain, Brand-Miller, Mann, Eaton & Speth, Am J Clin Nutr, 2000)

Broad characteristic dietary macro-nutrient
composition
Hunter-gatherers
USA
Australia
Protein
19 - 35%
(15.5%)
(17.0%)
Carbohydrate
Fat
22 - 40%
28 - 47%
(49.0%)
(34.0%)
(45.1%)
(32.4%)
Atherosclerosis
32
PPHT induces Vascular
Disease
“Recent research shows close association of
postprandial
hyperlipidaemia
(PPHL)
with
atherosclerosis. PPHL is closely correlated with
carotid intima-media thickness in normolipidaemic
and hyperlipidaemic individuals independent of other
risk factors.”
Misra A, Wasir JS, Vikram NK. Carbohydrate diets, postprandial hyperlipidaemia,
abdominal obesity & Asian Indians: A recipe for atherogenic disaster. Indian J Med Res.
2005 Jan;121(1):5-8.
32
Food as Medicine – PPHT
induced Vascular Disease
“Higher daytime triglyceridaemia with similar fasting
triglyceride levels was observed in subjects with
premature coronary artery disease (CAD) as
compared to their first-degree relatives without CAD.
Indeed some evidence suggests that postprandial
plasma triglyceride levels (3-4 h postmeal) predict
future myocardial infarction better than fasting
triglyceride levels.”
Misra A, Wasir JS, Vikram NK. Carbohydrate diets, postprandial hyperlipidaemia,
abdominal obesity & Asian Indians: A recipe for atherogenic disaster. Indian J Med Res.
2005 Jan;121(1):5-8.
32
PPHT induced Vascular
Disease - Mechanisms
“It is associated with alterations in several
atherogenic factors; increase in intestinally-derived
chylomicrons and their remnants, increase in VLDL
and remnants secreted by liver, decrease in HDL,
and increase in small dense LDL particles which are
more susceptible to oxidation.”
Misra A, Wasir JS, Vikram NK. Carbohydrate diets, postprandial hyperlipidaemia,
abdominal obesity & Asian Indians: A recipe for atherogenic disaster. Indian J Med Res.
2005 Jan;121(1):5-8.
44
Antiaging Nutrition
Calorie Restriction
45
Anti Aging Nutrition – Calorie
Restriction
“Calorie Restriction (CR), the selective reduction of
energy intake without compromising other essential
nutrients, is the most powerful intervention known to
retard biological aging in mammals, as assessed by
extension of mean and maximum lifespan, reduced
incidence or progression of age-associated
diseases, and preserved physiological function and
molecular fidelity with age.”
Michael Rae. It's Never Too Late: Calorie Restriction is Effective in Older Mammals
Rejuvenation Research. Volume 7, Page 3-8, May 2004
45
Anti Aging Nutrition – Calorie
Restriction
46
Anti Aging Nutrition – Calorie
Restriction
“Although attenuation of age-related deficits has
been reported for different interventions, such as
exercise and hormone replacement, calorie
restriction (CR) is the only one reproducibly shown to
slow aging and reduce age-related diseases in
controlled studies.”
Julie A. Mattison, George S. Roth, Donald K. Ingram, Mark A. Lane
Endocrine Effects of Dietary Restriction and Aging: The National Institute on Aging Study
Journal of Anti-aging Medicine. Volume 4, Page 215-223, September 2001
46
Anti Aging Nutrition – Calorie
Restriction
“It has become apparent that many of the beneficial
effects of CR reported in rodents are also evident in
monkeys. These include reductions in body weight,
fat mass, plasma insulin and glucose, increased
insulin sensitivity, delayed maturation, and lower
blood lipids with increased HDL.”
Julie A. Mattison, George S. Roth, Donald K. Ingram, Mark A. Lane
Endocrine Effects of Dietary Restriction and Aging: The National Institute on Aging Study
Journal of Anti-aging Medicine. Volume 4, Page 215-223, September 2001
46
Calorie Restriction: Mechanism of Action
47
The Thyroid and Calorie
Restriction
“Calorie restriction has been shown to have
immediate effects on thyroid hormones in SpragueDawley rats. T3 decreased by 60% within 3–4 days
of restricted feeding and T4 levels were significantly
lower within 7 days of diet change. These changes
persisted for over a year but returned to normal with
7 days of re-feeding.”
Julie A. Mattison, George S. Roth, Donald K. Ingram, Mark A. Lane
Endocrine Effects of Dietary Restriction and Aging: The National Institute on Aging Study
Journal of Anti-aging Medicine. Volume 4, Page 215-223, September 2001
47
Resveratrol; a calorie
restriction mimetic
“Resveratrol, a small molecule found in red wine,
is reported to slow aging in simple eukaryotes
and has been suggested as a potential calorie
restriction mimetic.”
Matt Kaeberlein et al. Substrate specific activation of sirtuins by resveratrol. J Biol
Chem. 2005
47
Resveratrol; a calorie
restriction mimetic
“Resveratrol has also been reported to act as a
Sirtuin activator, and this property has been
proposed to account for its anti-aging effects.
We show here that resveratrol is a substratespecific activator of yeast Sir2 and human SirT1.”
Matt Kaeberlein et al. Substrate specific activation of sirtuins by resveratrol. J Biol
Chem. 2005
48
What are Sirtuins?
“Sirtuins have been implicated in several
important cellular processes, including genomic
stability, DNA repair, transcriptional silencing,
p53-mediated apoptosis, and adipogenesis.”
Matt Kaeberlein et al. Substrate specific activation of sirtuins by resveratrol. J Biol
Chem. 2005
48
What are Sirtuins?
“In addition, Sir2- orthologs have been shown to
promote longevity in yeast, worms, and flies,
supporting the hypothesis that Sirtuins may act as
evolutionarily conserved regulators of aging. Deletion
of Sir2 increases rDNA recombination and shortens
life span, while over-expression has the opposite
effect.”
Matt Kaeberlein et al. Substrate specific activation of sirtuins by resveratrol. J Biol
Chem. 2005
48
Resveratrol: Mechanism of
Action
“Calorie restriction is the only intervention known to
increase life span in yeast, worms, flies, and
mammals, and resveratrol has been proposed to be
a potential CR mimetic. The mechanism by which
CR increases replicative life span in yeast had been
thought to require activation of Sir2.”
Matt Kaeberlein et al. Substrate specific activation of sirtuins by resveratrol. J Biol
Chem. 2005
49
Insulin and Aging
49
Anti Aging Nutrition –
Carbohydrate Restriction
“It is generally accepted that caloric restriction
retards ageing in laboratory rodents. Interestingly,
Research has shown that total calories must be
restricted to increase lifespan. Restriction of dietary
protein or fat calories did not extend lifespan.”
Richardson A, Liu F, Adamo ML, Van Remmen H, Nelson JF. The role of insulin and
insulin-like growth factor-I in mammalian ageing. Best Pract Res Clin Endocrinol Metab.
2004 Sep;18(3):393-406.
49
Anti Aging Nutrition – Insulin
Restriction
“It is noteworthy that low plasma insulin
concentrations in humans have been shown to be
correlated with reduced mortality risk and that low
insulin resistance, usually associated with reduced
plasma insulin, has been found in one centenarian
population.”
Richardson A, Liu F, Adamo ML, Van Remmen H, Nelson JF. The role of insulin and
insulin-like growth factor-I in mammalian ageing. Best Pract Res Clin Endocrinol Metab.
2004 Sep;18(3):393-406.
52
Low Fat Diets
Their effects on the biomarkers of aging
52
Low Fat Diets
“To validate our hypothesis that reduction in dietary
fat may result in changes in androgen metabolism,
39 middle-aged white, healthy men (50 to 60 years)
were studied while they were consuming their usual
high fat, low fiber diet and after 8 weeks modulation
to an isocaloric low fat, high fiber diet.”
Wang C, Catlin DH, Starcevic B, Heber D, Ambler C, Berman N, Lucas G, Leung A,
Schramm K, Lee PW, Hull L, Swerdloff RS. Low Fat High Fiber Diet Decreased Serum
and Urine Androgens in Men J Clin Endocrinol Metab. 2005 Mar 1
52
Low Fat Diets Reduce
Androgens in Men
“After diet modulation, mean serum testosterone (T)
concentration fell (p<0.0001) accompanied by small
but significant decreases in serum free testosterone
(p=0.0045), 5 alpha dihydrotestosterone (DHT,
p=0.0053), and adrenal androgens (Androstendione,
p=0.0135; DHEA-S, p=0.0011).”
Wang C, Catlin DH, Starcevic B, Heber D, Ambler C, Berman N, Lucas G, Leung A,
Schramm K, Lee PW, Hull L, Swerdloff RS. Low Fat High Fiber Diet Decreased Serum
and Urine Androgens in Men J Clin Endocrinol Metab. 2005 Mar 1
53
Low Fat Diets Reduce
Androgens in Men
“Metabolic clearance rates of T were not changed
and production rates of T showed a downward trend
while on low fat diet modulation. We conclude that
reduction in dietary fat intake (and increase in fiber)
results in 12% consistent lowering of circulating
androgens levels without changing the clearance.”
Wang C, Catlin DH, Starcevic B, Heber D, Ambler C, Berman N, Lucas G, Leung A,
Schramm K, Lee PW, Hull L, Swerdloff RS. Low Fat High Fiber Diet Decreased Serum
and Urine Androgens in Men J Clin Endocrinol Metab. 2005 Mar 1
53
53
Inflammation and Heart Disease
54
hs-C Reactive Protein (hs-CRP)
Hs-CRP is the single biggest risk factor for
atherosclerosis. It is the new ‘LDL’ for heart
disease and predicts vascular events better
than any other single parameter.
The more carbohydrate consumed in the diet,
the higher the levels of hs-CRP are.
54
Osiecki, H. (2004) Alternative Medicine Review, 9, 32-53.
54
CRP Promotes Cardiovascular
Disease
“CRP
was shown to possess proatherogenic
properties. For example, CRP activates endothelial
cells to express adhesion molecules, ICAM-1,
vascular cell adhesion molecule 1, selectins, and
the chemokines, monocyte chemotactic protein 1.”
V. Pasceri, J.T. Willerson and E.T. Yeh, Direct proinflammatory effect of C-reactive
protein on human endothelial cells. Circulation 102 (2000), pp. 2165–2168.
55
CRP Promotes Cardiovascular
Disease
“CRP also induces the secretion of interleukin 6
and endothelin 1 and decreases the expression
and bioavailability of endothelial nitric oxide
synthase in human endothelial cells.”
S. Verma, C.H. Wang, S.H. Li et al., A self-fulfilling prophecy: C reactive protein
attenuates nitric oxide production and inhibits angiogenesis. Circulation 106 (2002),
pp. 913–919.
55
High Carb Eating Promotes hs-CRP
“Dietary glycemic load is significantly and positively
associated with plasma hs-CRP in healthy middleaged women, independent of conventional risk
factors for ischemic heart disease.”
Simin Liu, JoAnn E Manson, Julie E Buring, Meir J Stampfer, Walter C Willett and Paul
M Ridker. Relation between a diet with a high glycemic load and plasma
concentrations of high-sensitivity C-reactive protein in middle-aged women.
American Journal of Clinical Nutrition, Vol. 75, No. 3, 492-498, March 2002
55
High Carb Eating Promotes hs-CRP
“Exacerbation of the proinflammatory process may
be a mechanism whereby a high intake of rapidly
digested and absorbed carbohydrates increases
the risk of ischemic heart disease, especially in
overweight women prone to insulin resistance.”
Simin Liu, JoAnn E Manson, Julie E Buring, Meir J Stampfer, Walter C Willett and Paul
M Ridker. Relation between a diet with a high glycemic load and plasma
concentrations of high-sensitivity C-reactive protein in middle-aged women.
American Journal of Clinical Nutrition, Vol. 75, No. 3, 492-498, March 2002
56
Simin Liu, JoAnn E Manson, Julie E Buring, Meir J Stampfer, Walter C Willett and Paul
M Ridker. Relation between a diet with a high glycemic load and plasma concentrations
of high-sensitivity C-reactive protein in middle-aged women. American Journal of Clinical
Nutrition, Vol. 75, No. 3, 492-498, March 2002
56
DHEA Declines with Metabolic
Syndrome
Testosterone Declines with
Metabolic Syndrome
57
“Super Diets”
Which Diet for Which Person?
57
Super Diets – Zone Diet
The Zone Diet is based on work done by Barry
Sears. It states that a macronutrient ratio of 30
protein: 40 carbs and 30 fats (30:40:30) is the best
ratio for health. This ratio should be maintained at
each meal. The Zone Diet also restricts calories
and has some scientific backing.
57
Super Diets – Zone Diet
Pros:
 Some scientific backing
 Restricts calories (mainly refined carbs)
 Balances sugars
Cons:
 Difficult to administer
 Have to ratio each meal
 Restricts calories
58
Super Diets – Atkins
The Atkins diet is based on the ‘hunter and gatherer’
style diet. It severely restricts refined cabs, while
allows liberal meats, vegies, salads, cheese, fish,
eggs, nuts and seeds. Of all the diet, this has the
most scientific backing (41 clinical trials as of Mar.
2005) and the most critics. The consumer starts on
a severe carb restriction, then a gradual increase
in ‘good’ carbs until the weight loss normalises.
58
Super Diets – Atkins
Pros:
 Most scientifically backed
 Effective for fat loss, CVD, diabetes and Syndrome X
 Been around for over 30 years
Cons:
 Difficult initially to administer
 A lot of critics of the diet
 Shunned by medical experts
59
Super Diets – Ornish
Dean Ornish is an extremely low fat, low calorie diet.
The theory is that fats are the cause of
atherosclerosis and the only way to rid this build up
is to severely restrict fats. Recently he has
conceded that some oils may be beneficial (fish
oils etc.). Limited scientific support of his
principles.
59
Super Diets – Ornish
Pros:
 Effective for weight loss in the short term
 Some, not all risk factors for atherosclerosis reduce (some
increase)
 Bases the diet on whole foods
Cons:
 Low in fat
 Hard to adhere to
 Not much scientific support
59
Super foods
59
Broccoli is Anti-carcinogenic
“Although many epidemiological studies have
indicated that vegetables reduce the risk of chronic
diseases, it remains unclear whether single
extracted chemicals or whole vegetables are
effective. Cruciferous vegetables are rich in
isothiocyanates which protect the human body
against carcinogenesis.”
Murashima M, Watanabe S, Zhuo XG, Uehara M, Kurashige A. Phase 1 study of
multiple biomarkers for metabolism and oxidative stress after one-week intake of
broccoli sprouts. Biofactors. 2004;22(1-4):271-5.
60
Broccoli is Anti-carcinogenic
“In 1992, sulforaphane, an isothiocyanate, was
isolated from broccoli and showed phase 2
enzyme inducer activity [3]. Extracts of broccoli
sprouts have 10–100 fold inducer activity of phase
2 enzymes compared to mature broccoli [4].
Mature broccoli also contains indole compounds
that induce not only phase 2 enzymes but also
phase 1 enzymes.”
Murashima M, Watanabe S, Zhuo XG, Uehara M, Kurashige A. Phase 1 study of
multiple biomarkers for metabolism and oxidative stress after one-week intake of
broccoli sprouts. Biofactors. 2004;22(1-4):271-5.
60
Broccoli is Anti-carcinogenic
“The anticarcinogenic effects of cruciferous
vegetables may derive from the glucosinolates
they contain; these are degraded into indoles and
isothiocyanates. Indoles were studied in relation to
breast cancer partly because of their effects on
estrogen metabolism, and isothiocyanates (ITCs)
are chemopreventive agents in animal models,
perhaps due in part to their potent effects on
inhibition of phase 1 and induction of phase II
enzymes.”
Breast cancer risk in premenopausal women is inversely associated with consumption of
broccoli, a source of isothiocyanates, but is not modified by GST genotype. J Nutr.
2004 May;134(5):1134-8.
60
Broccoli is Anti-carcinogenic
“In this case-control study specifically designed to
examine associations between diet and breast
cancer, we found that consumption of cruciferous
vegetables, particularly broccoli intake, was
associated with a reduced risk of premenopausal
breast cancer. Significant risk reduction was not
noted for postmenopausal women.”
Breast cancer risk in premenopausal women is inversely associated with consumption of
broccoli, a source of isothiocyanates, but is not modified by GST genotype. J Nutr.
2004 May;134(5):1134-8.
61
Broccoli is Anti-atherogenic
“One week intake of broccoli sprouts significantly
reduced total cholesterol and LDL cholesterol.
Females had no significant reduction in total
cholesterol but showed increased HDL cholesterol.
Triacylglycerol levels were abnormal in six subjects
at baseline. After treatment, three of them moved
into normal range.”
Murashima M, Watanabe S, Zhuo XG, Uehara M, Kurashige A. Phase 1 study of
multiple biomarkers for metabolism and oxidative stress after one-week intake of
broccoli sprouts. Biofactors. 2004;22(1-4):271-5.
61
Broccoli: Anticancer King
“The consumption of cruciferous vegetables has
been associated with a reduced risk of cancer of
the lung, stomach, colon and rectum. The health
benefits of cruciferous vegetables such as
broccoli, Brussels sprouts, cabbage, and bok
choy have been attributed to their high
concentration
of
glucosinolates.
The
chemoprotective effect of indole-3-carbinol, a
constituent of these vegetables, has been shown
to have chemopreventive effects.”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases.J
Postgrad Med 2004;50:145-149
61
Broccoli: Anticancer King
“Isothiocyanates (found in Broccoli) act as anticarcinogens by inducing Phase II conjugating
enzymes, in particular Glutathione S-tranferases.”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases.J
Postgrad Med 2004;50:145-149
62
Sulforaphane from Broccoli
Causes G2/M Cell Arrest
“Previously, we showed that sulforaphane (SFN), a
naturally occurring cancer chemopreventive
agent, effectively inhibits proliferation of PC-3
human prostate cancer cells by causing caspase9- and caspase-8-mediated apoptosis. Here, we
demonstrate that SFN treatment causes an
irreversible arrest in the G(2)/M phase of the cell
cycle.”
Singh SV, Herman-Antosiewicz A, Singh AV, Lew KL, Srivastava SK, Kamath R,
Brown KD, Zhang L, Baskaran R. Sulforaphane-induced G2/M phase cell cycle
arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle
25C. J Biol Chem. 2004 Jun 11;279(24):25813-22. Epub 2004 Apr 08.
62
Sulforaphane from Broccoli
Causes G1 Cell Arrest
“We demonstrated that sulforaphane arrested cellcycle progression in G1 phase by a significant
down-modulation of cyclin D3. Moreover,
sulforaphane induced apoptosis (and also
necrosis), mediated by an increase in the
expression of p53, whereas it exerted little effect
on bcl-2 and bax levels. These findings indicate
that sulforaphane can exert protective effects
inhibiting leukemic cell growth.”
Fimognari C, Nusse M, Berti F, Iori R, Cantelli-Forti G, Hrelia P.
Sulforaphane modulates cell cycle and apoptosis in transformed and nontransformed human T lymphocytes. Ann N Y Acad Sci. 2003 Dec;1010:393-8.
62
Isothiocyanates from Broccoli
Promote Detoxification
“Plants of the family Brassicaceae contain high
levels of glucosinolates. The latter compounds
are degraded to isothiocyanates, some of which
have been shown to be potent inducers of phase
II detoxification enzymes in vitro.”
Munday R, Munday CM. Induction of phase II detoxification enzymes in rats by plantderived isothiocyanates: comparison of allyl isothiocyanate with sulforaphane and
related compounds. J Agric Food Chem. 2004 Apr 7;52(7):1867-71.
63
Isothiocyanates from Broccoli
Cause Decreased Cancer Growth
“Taken together, our findings suggest that selected
ITCs can rapidly initiate growth inhibition of
cancer cells by simultaneously modulating
multiple cellular targets, and their antiproliferative
activity may be largely unaffected by their
metabolism and disposition in vivo.”
Zhang Y, Tang L, Gonzalez V. Selected isothiocyanates rapidly induce growth
inhibition of cancer cells. Mol Cancer Ther. 2003 Oct;2(10):1045-52.
63
Broccoli Eradicates H. pylori
“Consumption of oral broccoli sprouts was temporally
associated with eradication of H. pylori infection in
three of nine patients. Most patients found broccoli
sprouts palatable. Further studies are needed to
determine the optimal dose of broccoli sprouts and
whether concomitant proton pump inhibitors or
antibiotics might augment the effectiveness.”
Galan MV, Kishan AA, Silverman AL. Dig Dis Sci. 2004 Aug;49(7-8):1088-90. Oral
broccoli sprouts for the treatment of Helicobacter pylori infection: a preliminary report.
63
Evolution and Nutrition
“Humans and a few primate species have
trichromatic colour vision so that they are able to
distinguish red from green. All other mammals
have dichromatic vision and cannot distinguish
between the two colours. One hypothesis for the
evolution of this visual ability was that it conferred
an advantage by enabling primates to distinguish
red fruits from the green background of forest
leaves.”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases. J
Postgrad Med [serial online] 2004 [cited 2005 Mar 9];50:145-149.
64
Tomatoes
64
Lycopene in Tomatoes
“Several studies have linked the consumption of
tomatoes and tomato products with a decreased
risk of cancer and cardiovascular disease. The
health benefits of lycopene have been attributed to
its antioxidant properties, although other
mechanisms of lycopene action are possible,
including
the
modulation
of
intercellular
communication, hormonal and immune system
changes, and enhancement of gap junctional
communication.”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases. J
Postgrad Med 2004;50:145-149.
64
Lycopene Reduces Cancers
“In breast cancer cells, lycopene can interfere with
insulin-like growth factor 1-stimulated tumour cell
proliferation. The relationship between lycopene
intake and prostate cancer risk has been reported
and supported by studies linking low plasma levels
of lycopene with an increased risk.”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases. J
Postgrad Med 2004;50:145-149.
65
Lycopene Reduces Cancers
“Lycopene administration may reduce proliferation
and increase apoptosis in human prostate tissue
where lycopene is the predominant carotenoid.
The anti-proliferative properties may extend to
other types of cancer, including that of the
colorectum. Lycopene may also inhibit cholesterol
synthesis and enhance LDL degradation.”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases. J
Postgrad Med 2004;50:145-149.
65
Green Tea
The Great Anti-cancer
Drink
65
Green Tea: Anticancer Drink
“Tea is one of the most popular beverages in the
world and the consumption of tea has been
associated with a decreased risk of developing
cancer of the ovary, oral cavity, colon, stomach,
and prostate. This beneficial health effect has
been attributed to the epigallocatechin gallate
(EGCG).”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases.J
Postgrad Med 2004;50:145-149
66
Green Tea inhibits Cancer
Growth
“In
recent
years,
epigallocatechin-3-gallate
(EGCG), the major polyphenolic constituent
present in green tea, has shown remarkable
effects in inhibiting cancer cell growth both in cell
culture system and in in vivo tumour models.”
Gupta S, Hussain T, Mukhtar H. Molecular pathway for (-)-epigallocatechin-3-gallateinduced cell cycle arrest and apoptosis of human prostate carcinoma cells.
Arch Biochem Biophys. 2003 Feb 1;410(1):177-85.
66
Green Tea Upregulates p21, an
anti cancer gene
“Earlier studies in our laboratory have shown that
treatment of androgen-sensitive and androgeninsensitive human prostate carcinoma cells with
EGCG resulted in G0/G1 phase cell cycle arrest
and apoptosis, irrespective of the p53 status of
these cells. This effect was mediated by
upregulation in the protein expression of
WAF1/p21.”
Gupta S, Hussain T, Mukhtar H. Molecular pathway for (-)-epigallocatechin-3-gallateinduced cell cycle arrest and apoptosis of human prostate carcinoma cells.
Arch Biochem Biophys. 2003 Feb 1;410(1):177-85.
66
Green Tea Normalises the
Cyclins that Drive Cancer Cells
“In the present study, we demonstrate that EGCG,
via modulation in the cki–cyclin–cdk machinery,
results in a G1 phase arrest of the cell cycle
followed by apoptosis of human prostate
carcinoma cells.”
Gupta S, Hussain T, Mukhtar H. Molecular pathway for (-)-epigallocatechin-3-gallateinduced cell cycle arrest and apoptosis of human prostate carcinoma cells.
Arch Biochem Biophys. 2003 Feb 1;410(1):177-85.
67
67
Green Tea Inhibits Cancer
“Epidermal growth factor receptor (EGFR) activation
is absolutely required for cervical cell proliferation.
This suggests that EGFR-inhibitory agents may be
of therapeutic value. In the present study, we
investigated the effects of epigallocatechin-3gallate (EGCG), a bioactive green tea polyphenol,
on EGFR signalling in cervical cells.”
Sah JF, Balasubramanian S, Eckert RL, Rorke EA. Epigallocatechin-3-gallate inhibits
epidermal growth factor receptor signaling pathway. Evidence for direct inhibition of
ERK1/2 and AKT kinases. J Biol Chem. 2004 Mar 26;279(13):12755-62. Epub 2003
Dec 29.
67
Green Tea Inhibits Cancer
“EGCG inhibits epidermal growth factor-dependent
activation of EGFR, and EGFR-dependent
activation of the mitogen-activated protein kinases
ERK1/2. EGCG also inhibits EGFR-dependent
AKT activity.”
Sah JF, Balasubramanian S, Eckert RL, Rorke EA. Epigallocatechin-3-gallate inhibits
epidermal growth factor receptor signaling pathway. Evidence for direct inhibition of
ERK1/2 and AKT kinases. J Biol Chem. 2004 Mar 26;279(13):12755-62. Epub 2003
Dec 29.
68
Green Tea Inhibits Cancer:
Mechanisms
EGCG increased p53, p21(WAF-1), and p27(KIP-1)
levels, reduced cyclin E level, and reduced CDK2
kinase activity. EGCG also caused a G(1) arrest.
Moreover, sustained EGCG treatment caused
apoptotic cell death.
“These results suggest that EGCG acts to selectively
inhibit multiple EGF-dependent kinases to inhibit
cell proliferation.”
Sah JF, Balasubramanian S, Eckert RL, Rorke EA. Epigallocatechin-3-gallate inhibits
epidermal growth factor receptor signaling pathway. Evidence for direct inhibition of
ERK1/2 and AKT kinases. J Biol Chem. 2004 Mar 26;279(13):12755-62. Epub 2003
Dec 29.
68
Green Tea Inhibits Cancer:
Actives
“Many cell culture and animal studies have shown
that catechins, the main compounds of the green
tea leaves, are potent natural inhibitors of several
RTKs.”
Gouni-Berthold I, Sachinidis A. Molecular mechanisms explaining the preventive effects
of catechins on the development of proliferative diseases. Curr Pharm Des.
2004;10(11):1261-71.
68
Green Tea Protects Against
LDL Oxidation
69
Teas Protects Against LDL
Oxidation
69
Teas Benefit Atherosclerosis
69
Soy
Soy Prevents and
Treats Cancer, while
also preventing Heart
Disease
70
Soy Normalises Oestrogen
Activity
“Soy protein naturally contains isoflavones, primarily
genistein and daidzein, phytoestrogens which act
like very weak oestrogens or anti-oestrogens
similar to raloxifene, and selective oestrogen
response modifiers. In some tissues, soy acts as a
mild pro-oestrogen (bone and brain) while in others
it acts as an anti-oestrogen (breast and uterus).”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases Postgrad
Med 2004;50:145-149
70
Soy Normalises Oestrogen
Activity
“Soy isoflavones bind with very low affinity (1/50,000
to 1/100,000 the affinity of estradiol) to the alphaestradiol receptor, which mediates pro-oestrogen
effects in the breast and uterus, but isoflavones
and estradiol bind equally well to the beta-estradiol
receptor, which mediates the effects of oestrogen
on lipids, bones and brain.”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases Postgrad
Med 2004;50:145-149
70
Soy Normalises Oestrogen
Activity
“Soy protein isoflavones have been shown to
influence not only sex hormone metabolism and
biological activity but also intracellular enzymes,
protein synthesis, growth factor action, malignant
cell proliferation, differentiation and angiogenesis,
providing strong evidence that these substances
may have a protective role in cancer.”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases Postgrad
Med 2004;50:145-149
71
Soy is Anticarcinogenic
“Differences in dietary patterns in these Asian
countries possibly contribute to lower risk of
developing
colon
cancer,
and
frequent
consumption of soybeans and soy-based products
is known as a possible determinant. Potential
anticarcinogenic compounds found in soybeans
include isoflavones, protease inhibitors and
saponins.”
Antiproliferative crude soy saponin extract modulates the expression of IkappaBalpha,
protein kinase C, and cyclooxygenase-2 in human colon cancer cells.
Kim HY, Yu R, Kim JS, Kim YK, Sung MK. Cancer Lett. 2004 Jul 8;210(1):1-6.
71
Soy Reduces Cancer in Asians
and Japanese
“The incidences of breast and prostate cancers are
much higher in the United States and European
countries compared with Asian countries such as
Japan and China. One of the major differences in
diet between these populations is that the
Japanese and the Chinese consume a traditional
diet high in soy products.”
Sarkar FH, Li Y. Soy isoflavones and cancer prevention. Cancer Invest. 2003;21(5):74457.
71
Forms of Soy Consumed by
the Japanese
“In Japan, soy is consumed in various forms,
including dried or green soybeans, tofu (soybean
curd),
natto
(fermented
soybeans),
miso
(fermented soybean paste), okara (tofu lees),
soybean sprouts, soymilk, yuba (soy milk skin),
kinako (soy flour), and soy sauce.”
Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S Soy, isoflavones, and breast
cancer risk in Japan. J Natl Cancer Inst. 2003 Jun 18;95(12):906-13.
72
Soy: Mechanisms of Actions
“Several experimental studies have shown that soy
or isoflavones have anticarcinogenic effects on
hormone-related cancers and that these effects
may be related to their estrogenic, antiestrogenic,
or other activities.”
Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S Soy, isoflavones, and breast
cancer risk in Japan. J Natl Cancer Inst. 2003 Jun 18;95(12):906-13.
72
Soy: Mechanisms of Actions
“Other possible anticarcinogenic mechanisms
associated with soy or isoflavones include
inhibiting protein tyrosine kinases or other
enzymes that interfere with cell growth and
survival; stimulating sex hormone-binding globulin
production, thereby decreasing the amount of free
and active hormone in the blood; protecting DNA
from damage via antioxidant effects; and inhibiting
angiogenesis.”
Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S Soy, isoflavones, and breast
cancer risk in Japan. J Natl Cancer Inst. 2003 Jun 18;95(12):906-13.
72
Isoflavones Reduce Breast
Cancer in the Japanese
“Because Japanese women have a low incidence of
breast cancer and a high intake of isoflavones,
approximately 700 times that of U.S. Caucasians,
the Japanese population is an ideal setting for
determining whether an association exists.”
Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S Soy, isoflavones, and breast
cancer risk in Japan. J Natl Cancer Inst. 2003 Jun 18;95(12):906-13.
73
Isoflavones and Miso Reduce
Breast Cancer in the Japanese
“Our cohort study found a statistically significant
inverse association between miso soup or
isoflavone intake and risk of breast cancer in
Japanese women.”
Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S Soy, isoflavones, and breast
cancer risk in Japan. J Natl Cancer Inst. 2003 Jun 18;95(12):906-13.
73
Isoflavones and Miso Reduce
Breast Cancer in the Japanese
“Women with the highest intake of isoflavone (as
genistein, 25.3 mg/day) or those with the highest
consumption of miso soup (three or more
bowls/day) had approximately half the risk of
breast cancer as women with the lowest intake of
isoflavone (as genistein, 6.9 mg/day) or those with
the least consumption of miso soup (less than
once a day), respectively.”
Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S Soy, isoflavones, and breast
cancer risk in Japan. J Natl Cancer Inst. 2003 Jun 18;95(12):906-13.
73
Genistein is Anticarcinogenic
“Soy isoflavones have been identified as dietary
components having an important role in reducing
the incidence of breast and prostate cancers.
Genistein, the predominant isoflavones found in
soy, has been shown to inhibit the carcinogenesis
in animal models.”
Sarkar FH, Li Y. Soy isoflavones and cancer prevention. Cancer Invest. 2003;21(5):74457.
74
Genistein Treats Various
Cancers
“Genistein, a naturally occurring isoflavone, displays
antitumour, antimetastatic and antiangiogenic
properties, described in various experimental in
vitro and in vivo models. The results of several
epidemiological studies suggest that soybean
consumption may contribute to lower incidence of
breast, colon, prostate, thyroid, and head and neck
cancers.”
Radzikowski C, Wietrzyk J, Grynkiewicz G, Opolski A. Genistein: a soy isoflavone
revealing a pleiotropic mechanism of action - clinical implications in the treatment
and prevention of cancer. Postepy Hig Med Dosw (Online). 2004 Feb 27;58:128-39.
74
Genistein (Soy) Potentates
Chemotherapy Drugs
“These results clearly suggest that genistein pre-
treatment, which inactivates NF-kappaB activity,
together with other cellular effects of genistein,
may contribute to increased cell growth inhibition
and apoptosis inducing effects of nontoxic doses of
docetaxel and cisplatin, which could be a novel
strategy for the treatment of pancreatic cancer.”
Li Y, Ellis KL, Ali S, El-Rayes BF, Nedeljkovic-Kurepa A, Kucuk O, Philip PA, Sarkar FH.
Apoptosis-inducing effect of chemotherapeutic agents is potentiated by soy
isoflavone genistein, a natural inhibitor of NF-kappaB in BxPC-3 pancreatic cancer
cell line. Pancreas. 2004 May;28(4):e90-5.
74
The Saponins in Soy are
Anticarcinogenic
“Soybean contains 0.5–2% saponin, and is a
significant source of saponins in human diets.
Previous reports indicated that soybean saponins
suppress the growth of colon tumour cells in vitro,
and a 2% crude soybean saponin diet inhibited a
carcinogen-induced colonic aberrant formation in
rats.”
Antiproliferative crude soy saponin extract modulates the expression of IkappaBalpha,
protein kinase C, and cyclooxygenase-2 in human colon cancer cells.
Kim HY, Yu R, Kim JS, Kim YK, Sung MK. Cancer Lett. 2004 Jul 8;210(1):1-6.
75
The Saponins in Soy are
Anticarcinogenic
“PKC is a well-known mediator for cell proliferation.
Treatment of colon adenocarcinoma cells with
crude soy saponin extract caused decreases in
PMA-induced PKC expression, and the expression
was significantly lower in cells treated with 600
ppm of saponin.”
Antiproliferative crude soy saponin extract modulates the expression of IkappaBalpha,
protein kinase C, and cyclooxygenase-2 in human colon cancer cells.
Kim HY, Yu R, Kim JS, Kim YK, Sung MK. Cancer Lett. 2004 Jul 8;210(1):1-6.
75
The Saponins in Soy are
Anticarcinogenic – COX 2
“Our findings indicate that crude soy saponin extract
significantly reduce colon adenocarcinoma cell growth
with down-regulations of COX-2 and PKC expression.
Also, decreases in COX-2 and PKC expression was
inversely related to IkB
degradation indicating
soybean saponin possibly interfere the NFkBdependent signalling pathway by suppressing IkB
degradation. The NFkB pathway is an extensively
studied signal transduction cascade involved in
inflammatory responses during carcinogenesis .”
Antiproliferative crude soy saponin extract modulates the expression of IkappaBalpha,
protein kinase C, and cyclooxygenase-2 in human colon cancer cells.
Kim HY, Yu R, Kim JS, Kim YK, Sung MK. Cancer Lett. 2004 Jul 8;210(1):1-6.
75
Soy Treats Androgen Dependent
and Independent Prostate Cancer
“Epidemiological
studies suggest an inverse
association between soy intake and prostate
cancer (Pca) risk. We have previously observed
that soy isoflavone genistein induces apoptosis
and inhibits growth of both androgen-sensitive and
androgen-independent Pca cells in vitro.”
Hussain M, Banerjee M, Sarkar FH, Djuric Z, Pollak MN, Doerge D, Fontana J, Chinni S,
Davis J, Forman J, Wood DP, Kucuk O. Soy isoflavones in the treatment of prostate
cancer. Nutr Cancer. 2003;47(2):111-7.
76
Isoflavones Benefit 2-OH:16-OH
Oestrogen Ratios
“The finding that equol excretion, but not total
isoflavone excretion, correlated positively with the
2-OH E(1):16alpha-OH E(1) ratio suggests that
the colonic bacterial profile associated with equol
production may be involved in oestrogen
metabolism, and may therefore possibly influence
breast cancer risk.”
Atkinson C, Skor HE, Dawn Fitzgibbons E, Scholes D, Chen C, Wahala K, Schwartz SM,
Lampe JW. Urinary equol excretion in relation to 2-hydroxyestrone and 16alphahydroxyestrone concentrations: an observational study of young to middle-aged women.
J Steroid Biochem Mol Biol. 2003 Jul;86(1):71-7.
76
Soy Reduces Heart Disease
“The Shanghai Women's Health Study, a
population-based prospective cohort study of
approximately
75,000
Chinese
women,
documented a dose-response relationship
between soy food intake and risk of coronary
heart disease, providing direct evidence that soy
food consumption may reduce the risk of
coronary heart disease in women.”
Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases. J
Postgrad Med 2004;50:145-149.
76
Olive Oil
77
Olive Oil Prevents Oxidation
“On the one hand, virgin olive oil, with its very high
content of MUFA (mainly oleic acid), greatly
enriches all biological membranes so that it
partially and gradually substitutes the other fatty
acids, mainly polyunsaturated fatty acids (PUFA).
This process produces membranes that are less
susceptible to oxidative injury.”
Battino M, Ferreiro MS. Ageing and the Mediterranean diet: a review of the role of
dietary fats. Public Health Nutr. 2004 Oct;7(7):953-8.
77
Olive Oil Prevents Oxidation
“Because of the increased concentration of oleic
acid, which – while maintaining an optimal fluidity
for membrane functionality – at the same time
slows down the propagation of lipid peroxidation
phenomena that usually require the fatty acids to
possess two or more double bonds.”
Battino M, Ferreiro MS. Ageing and the Mediterranean diet: a review of the role of
dietary fats. Public Health Nutr. 2004 Oct;7(7):953-8.
77
Olive Oil Prevents Oxidation
“On the other hand, virgin olive oil also contains a
large amount of antioxidant molecules (like atocopherol, several different phenolic compounds
and even coenzyme Q). These molecules are wellknown free-radical scavengers that neutralise the
toxic species and sometimes even prevent the
early steps of their formation, in this way protecting
biological structures from oxidative insult.”
Battino M, Ferreiro MS. Ageing and the Mediterranean diet: a review of the role of
dietary fats. Public Health Nutr. 2004 Oct;7(7):953-8.
78
Olive Oil Prevents Oxidation
“The actual efficacy of dietary interventions based on
virgin olive oil, as a unique source of fat for
modifying the fatty acid pattern of biological
membranes making them less prone to suffer
oxidative modifications, has been widely
demonstrated.”
Battino M, Ferreiro MS. Ageing and the Mediterranean diet: a review of the role of
dietary fats. Public Health Nutr. 2004 Oct;7(7):953-8.
78
Olive Oil and Atherosclerosis
“Diets rich in olive oil have been shown to be more
effective in lowering total cholesterol and low
density lipoprotein (LDL) cholesterol than
conventional dietary treatments not containing high
levels of MUFA.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
78
Olive Oil and Atherosclerosis
“Oxidation of lipoproteins, in particular LDL, plays a
fundamental role in the pathogenesis of
arteriosclerosis.
Olive
oil
(50
g/day)
supplementation to the diet of healthy males
significantly reduced LDL susceptibility to in vitro
oxidation in periods as short as 1 week.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
79
Olive Oil Doesn’t Help if
Replacing Other Fats
“However, in a meta-analysis of 14 studies carried
out in the years 1983 to 1994, replacement of
saturated fatty acids with either MUFA or
polyunsaturated fatty acids (PUFA) led to similar
decreases in total and LDL cholesterol relative to
the high-saturated fat diets.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
79
Olive Oil and Atherogenesis
“Despite the ability of diets enriched with PUFA to
reduce plasma cholesterol level, the degree of
unsaturation in these fatty acids influences the
susceptibility of LDL to undergo oxidative
modifications, making these particles more prone
to peroxidation and in principle more atherogenic.
In addition, MUFA lead to favourable changes in
the lipid profile of lipoproteins, generating LDL
particles more resistant to oxidative modifications”
Battino M, Ferreiro MS. Ageing and the Mediterranean diet: a review of the role of
dietary fats. Public Health Nutr. 2004 Oct;7(7):953-8.
79
Olive Oil and Hypertension
“Following 4 weeks of olive oil consumption, there
was an increase in n-3 fatty acids and a decrease
in the n-6:n-3 fatty acid ratio in the erythrocyte
membranes. Furthermore, both the systolic and
diastolic pressures fell by approximately 8 mm Hg
during the olive oil diet, whereas blood pressure
was not significantly affected by the sunflower oil
diet.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
80
Olive Oil and Hypertension
“In a double-blind randomized crossover study,
hypertensive patients incorporated olive oil
(MUFA) or sunflower oil (PUFA) into a nutritionally
balanced diet for a 6-month period. Blood pressure
was significantly lower at the end of the MUFA diet
compared with the PUFA diet.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
80
Olive Oil, Protein and
Cognitive Decline
“Results showed an inverse relationship between
energy intake from monounsaturated fatty acids
(MUFA) and cognitive decline. In a recent
longitudinal study of a well-nourished and
cognitively
unimpaired
sample
of
elderly
community residents, a significant association
between
protein
intakes
and
cognitive
performances was found.”
F Panza1, V Solfrizzi1, AM Colacicco1, A D’Introno1, C Capurso1, F Torres1, A Del
Parigi1,2, S Capurso1 and A Capurso Mediterranean diet and cognitive decline.
Public Health Nutrition: 7(7), 959–963.
80
Olive Oil and Cognitive Decline
“High MUFA intake per se appears to be associated
with the preservation of cognitive functions in
healthy elderly people. This effect could be related
to the role of fatty acids in maintaining the
structural integrity of neuronal membranes.”
F Panza1, V Solfrizzi1, AM Colacicco1, A D’Introno1, C Capurso1, F Torres1, A Del
Parigi1,2, S Capurso1 and A Capurso Mediterranean diet and cognitive decline.
Public Health Nutrition: 7(7), 959–963.
81
Olive Oil Prevents Cancers
“Overall, the evidence to support increased olive oil
consumption as a means to prevent several
varieties of cancer is convincing, but it is unclear
which component of the oil is responsible for the
chemoprotective effect. In the past, the high-oleic
acid content of the oil was thought to be the
important anticancer factor in olive oil. New
evidence suggests that oleic acid may not be as
important as other components.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
81
Olive Oil Prevents Cancers
“Reactive oxygen and nitrogen species, implicated in
several human pathologies including cancer, are
scavanged by the phenolics found in virgin olive
oil. Furthermore, hypotheses regarding squalene
as a potent inhibitor of carcinogenesis have
emerged.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
81
Olive Oil Prevents Breast
Cancer
“In case-control studies, consumption of olive oil has
been shown to reduce the estimated relative risk of
breast cancer in Spain and in Greece. Diets rich in
olive oil have been shown to have an antitumor
effect in rat models.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
82
Olive Oil Polyphenols Prevent
Breast Cancer
“Results of a meta-analysis of 97 reports of
experiments in rodents indicates that MUFA alone
do not have a significant effect on tumour
incidence. Thus, the strong protective associations
reported for olive oil intake may not be exclusively
related to its fatty acid composition but rather
attributed to its high levels of antioxidants and
other constituents.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
82
Olive Oil Prevents Colon
Cancer
“Olive oil consumption was negatively associated
with colorectal cancer incidence. Possible
mechanisms include the hypothesis that olive oil
may influence secondary bile acid patterns in the
colon that, in turn influence polyamine metabolism
in colonic enterocytes in ways that reduce
progression from normal mucosa to adenoma and
carcinoma.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
82
Olive Oil is Anti-inflammatory
“In macrophages collected from animals fed olive oil,
tumour necrosis factor (TNF) production was
somewhat
reduced
in
response
to
a
lipopolysaccharide (LPS) stimulus. After 4 weeks
on experimental diets olive oil significantly reduced
interleukin-1 production.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
83
Oils and Cancers
“Dietary fat intake was not associated with breast
cancer risk when data were pooled for eight
prospective studies; however, the populations
included in the analysis did not habitually consume
olive oil. Consumption of MUFA in these studies
was predominately from meat and dairy sources. A
recent Swedish study reported that a high intake of
omega-6 PUFA was associated with increased
breast cancer risk, whereas MUFA consumption
led to reduced risk.”
Stark AH, Madar Z. Olive oil as a functional food: epidemiology and nutritional
approaches. Nutr Rev. 2002 Jun;60(6):170-6.
83
Garlic
The Prevention of Atherosclerosis and Cancer
83
Garlic Prevents Diseases
“Recent studies have demonstrated that allium
vegetables, especially garlic, have very high
antioxidant activity among vegetables examined.
Garlic is a popular spice added to several edible
preparations all over the world and is a remedy for
a variety of ailments. It has been reported to
possess antifungal, antibacterial, hypoglycaemic,
hyperglycemie, hypolipidaemic, antiatherosclerotic
properties, and has been claimed to be effective
against a number of diseases.”
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
84
Garlic Prevents Cancers
“Epidemiological studies have shown an inverse
correlation between the consumption of garlic (and
other allium vegetables) and gastric cancer in
certain areas. Several animal experiments have
shown that garlic treatment and aged garlic, in
particular, counteracts formation and the
development of various forms of experimentally
induced tumours.”
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
84
Garlic Prevents Cancers
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
84
Garlic Prevents Cancers
“The preventive effects of garlic on human cancer
have been reported, for example, in China
Gangshan county, where residents consume a
large amount of garlic (on average 20 g garlic
daily), this county had the lowest gastric cancer
death rates (3.45/100000) and, in contrast, Quixia
county, where little garlic is eaten, had the highest
(40/100000).”
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
85
Garlic Prevents Cancers Better
than Chemotherapy
“A number of researchers have shown the inhibitory
effect of garlic on tumour growth using various
cancer cell lines. The Chinese researchers using
gastric cancer cell lines have shown that fresh
garlic extract and diallyl trisulfide were more potent
than 5-fluorouracil or mitomycin C in killing these
cancer cells.”
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
85
Garlic Prevents Cancers:
Mechanisms
The hypothesis underlying how garlic works is that
garlic might raise the activity of enzyme systems
that detoxify carcinogens. Several enzyme
systems are known to oxidize, reduce, or
hydrolyze (phase I reaction) and then conjugate or
otherwise effect (phase 2 reaction) drugs,
metabolites, carcinogens, and other toxic
chemicals, thereby increasing their polarity and
excretability.
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
85
Garlic Prevents Cancers:
Mechanisms
“They also have demonstrated an increase in the
GSH levels in rats fed alcohol and garlic protein
along with a near normal activity of Superoxide
dismutase, glutathione peroxidase, glutathioneStransferase (GST), and catalase.”
“Glutathione S-transferase is an important enzyme
that conjugates electrophiles and assists in the
detoxification of many carcinogens and other
xenobiotics.”
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
86
Garlic Prevents Cancers:
Reducing Phase I Detoxification
“Yang and collegues have postulated that diallyl
sulphide (DAS) and its metabolites, diallyl
sulphoxide and diallyl sulphone (scheme 4), inhibit
cytochrome P450 2El.”
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
86
Garlic Prevents Cancers:
Reducing Phase I Detoxification
“Since P450 2El is vital in catalyzing the activation of
N-nitrosodimethyl amine (NOMA), 1,2-dimethyl
hydrazine (DMH), benzene, alkanes, halogenated
hydrocarbons, and many other low molecular
weight environmental chemicals, inhibition of this
enzyme is expected to block toxicity and
carcinogenecity of these compounds.”
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
86
Garlic Prevents Cancers:
Antioxidant Effects
“The effects of garlic on the activities of a number of
antioxidant enzymes have been studied. The
enzymes include glutathione peroxidase, GST,
catalase, Superoxide dismutase. In these studies,
it has been shown that garlic can scavenge free
radicals and is a successful antioxidant, wherein
garlic has the potency to induce activity of the
antioxidant enzymes.”
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
87
Garlic Prevents Cancers:
Summary
“Cancer prevention through dietary modification
appears to be a practical and cost effective
possibility. Our survey of the literature suggests
that garlic may be classified as a dietary
anticarcinogen on the basis of epidemiological and
experimental investigation. Its anticarcinogenic role
is particularly appealing in terms of preventing
gastrointestinal cancer.”
Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a
review. Crit Rev Food Sci Nutr. 2004;44(6):479-88.
93
Detoxification
Foods that enhance detoxification
94
Phase I Detox Alone Causes
Cancers
“Most carcinogen share quite unreactive and
innocuous
procarcinogens,
which
require
conversion by cellular (Phase 1) enzymes to highly
reactive, electrophilic, ultimate carcinogens that
react directly with nucleophilic centers of
macromolecules such as DNA, to produce a series
of damaging events that can evolve into cancer.”
Paul Talalay Chemoprotection against cancer by induction of Phase2 enzymes.
BioFactors 12 (2000) 5–11
94
Phase I : 2 Balance is Critical
“Consequently the outcome of carcinogen exposure
is controlled in large part by the balance between
Phase 1 enzymes that can generate ultimate
carcinogens and Phase 2 enzymes that detoxify
these products.”
Paul Talalay Chemoprotection against cancer by induction of Phase2 enzymes.
BioFactors 12 (2000) 5–11
94
Phase I : 2 Balance is Critical
“Although these families of enzymes are under
genetic and hormonal control, they are also
regulated by inducers, and the shifting of this
balance by induction toward the dominance of
Phase 2 enzymes has emerged as an important
strategy for achieving chemoprotection against
toxicity and malignancy.”
Paul Talalay Chemoprotection against cancer by induction of Phase 2 enzymes.
BioFactors 12 (2000) 5–11
95
Brassica Foods Boost Phase 2
“Allyl isothiocyanate (AITC) is formed from sinigrin, a
glucosinolate that is present in many Brassica
vegetables. In the present study, the effect of
various dose levels of AITC on the activities of the
phase 2 detoxification enzymes quinone reductase
(QR) and glutathione S-transferase (GST) in rat
tissues has been examined.”
Munday R, Munday CM. Selective induction of phase II enzymes in the urinary bladder
of rats by allyl isothiocyanate, a compound derived from Brassica vegetables. Nutr
Cancer. 2002;44(1):52-9.
95
Brassica Foods Boost Phase 2
“High dose levels of AITC, given daily for 5 days,
increased the activity of QR and/or GST in the
liver, kidneys, lungs, spleen, urinary bladder,
glandular and nonglandular stomach, duodenum,
jejunum, ileum, cecum, and colon plus rectum of
the animals.”
Munday R, Munday CM. Selective induction of phase II enzymes in the urinary bladder
of rats by allyl isothiocyanate, a compound derived from Brassica vegetables. Nutr
Cancer. 2002;44(1):52-9.
95
Brassica Foods Boost Phase 2
“The dose level of AITC found to be effective in rats
approaches the level that could be achieved
through human consumption of Brassica
vegetables, suggesting that induction of phase 2
enzymes by food-derived isothiocyanates could
contribute to the lower incidence of bladder cancer
observed in individuals who regularly consume
such vegetables.”
Munday R, Munday CM. Selective induction of phase II enzymes in the urinary bladder
of rats by allyl isothiocyanate, a compound derived from Brassica vegetables. Nutr
Cancer. 2002;44(1):52-9.
96
Herbal Teas and Liver
Detoxification
“After four weeks of pretreatment, different
cytochrome P450 (CYP) isoforms and phase 2
enzyme activities were determined by incubation of
liver microsomes or cytosol with appropriate
substrates. Activity of CYP1A2 in the liver
microsomes
of
rats
receiving
dandelion,
peppermint or chamomile tea was significantly
decreased (P < 0.05) to 15%, 24% and 39% of the
control value, respectively.”
Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing
enzymes in rats. J Pharm Pharmacol. 2001 Oct;53(10):1323-9.
96
Herbal Teas and Liver
Detoxification
“CYP1A2 activity was significantly increased by
pretreatment with caffeine solution. No alterations
were observed in the activities of CYP2D and
CYP3A in any group of the pretreated rats. Activity
of CYP2E in rats receiving dandelion or
peppermint tea was significantly lower than in the
control group, 48% and 60% of the control,
respectively.”
Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing
enzymes in rats. J Pharm Pharmacol. 2001 Oct;53(10):1323-9.
96
Herbal Teas and Liver
Detoxification
“There was a dramatic increase (244% of control) in
the activity of phase 2 detoxifying enzyme UDPglucuronosyl transferase in the dandelion teapretreated group. There was no change in the
activity of glutathione-S-transferase. The results
suggested that, like green and black teas, certain
herbal teas can cause modulation of phase 1 and
phase 2 drug metabolizing enzymes.”
Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing
enzymes in rats. J Pharm Pharmacol. 2001 Oct;53(10):1323-9.
97
Detoxification: Role of the
Liver
“The liver plays an important role in protecting the
organism from potentially toxic chemical insults
through its capacity to convert lipophiles into more
water-soluble metabolites which can be efficiently
eliminated from the body via the urine.”
Grant DM. Detoxification pathways in the liver. J Inherit Metab Dis. 1991;14(4):421-30.
97
Detoxification: Role of the
Liver
“This protective ability of the liver stems from the
expression of a wide variety of xenobiotic
biotransforming
enzymes
whose
common
underlying feature is their ability to catalyse the
oxidation, reduction and hydrolysis (Phase 1)
and/or conjugation (Phase 2) of functional groups
on drug and chemical molecules.”
Grant DM. Detoxification pathways in the liver. J Inherit Metab Dis. 1991;14(4):421-30.
97
Detoxification: Role of the
Liver
“The broad substrate specificity, isoenzyme
multiplicity and inducibility of many of these
enzyme systems make them particularly well
adapted to handling the vast array of different
chemical structures in the environment to which we
are exposed daily. However, some chemicals may
also be converted to more toxic metabolites by
certain of these enzymes, implying that variations
in the latter may be important predisposing factors
for toxicity.”
Grant DM. Detoxification pathways in the liver. J Inherit Metab Dis. 1991;14(4):421-30.
98
Detoxification: Role of the
Liver
There are 4 major phase II liver detoxification
pathways:




Methylation
Glycination
Glucuronidation
Glycination
98
Detoxification: Role of Garlic
Diallyl sulfide (DAS), diallyl disulfide (DADS), and
diallyl trisulfide (DATS) are major components of
garlic oil. Among these components, DADS has
been well documented as the most potent in antitumour action against human tumour cell lines
from colon, lung, and skin. We now report that
DATS is the most potent inducer of phase 2
enzymes among allyl sulfides in rat liver.
Fukao T, Hosono T, Misawa S, Seki T, Ariga T. The effects of allyl sulfides on the
induction of phase II detoxification enzymes and liver injury by carbon tetrachloride.
Food Chem Toxicol. 2004 May;42(5):743-9.
98
Fukao T, Hosono T, Misawa S, Seki T, Ariga T. The effects of allyl sulfides on the
induction of phase II detoxification enzymes and liver injury by carbon tetrachloride.
Food Chem Toxicol. 2004 May;42(5):743-9.
99
Soy Increases Phase 2 Liver
Enzymes
“The data indicate that dietary soy enhances phase 2
enzyme activity, especially quinone reductase and
uridine 5'-diphosphate-glucuronosyl transferase,
which could lead to protection from potentially
harmful xenobiotics.”
Appelt LC, Reicks MM. Soy feeding induces phase II enzymes in rat tissues. Nutr
Cancer. 1997;28(3):270-5.
99
Turmeric Increases Phase II
Liver Enzymes
“Curcumin, a yellow pigment from Curcuma longa, is
a major component of turmeric and is commonly
used as a spice and food colouring material and
exhibits
antiinflammatory
antitumour,
and
antioxidant properties. In this study we therefore
investigated the effect of dietary supplementation
of curcumin on the activities of antioxidant and
phase II-metabolizing enzymes involved in
detoxification.”
Iqbal M, Sharma SD, Okazaki Y, Fujisawa M, Okada S. Dietary supplementation of
curcumin enhances antioxidant and phase II metabolizing enzymes in ddY male
mice: possible role in protection against chemical carcinogenesis and toxicity.
Pharmacol Toxicol. 2003 Jan;92(1):33-8.
99
Turmeric Increases Phase 2
Liver Enzymes
“Dietary supplementation of curcumin (2%, w/v) to
male ddY mice for 30 days significantly increased
the activities of glutathione peroxidase, glutathione
reductase, glucose-6-phosphate dehydrogenase
and catalase to 189%, 179%, 189%, and 181% in
liver and 143%, 134%, 167% and 115% in kidney
respectively as compared with corresponding
normal diet fed control (P<0.05-0.001).”
Iqbal M, Sharma SD, Okazaki Y, Fujisawa M, Okada S. Dietary supplementation of
curcumin enhances antioxidant and phase II metabolizing enzymes in ddY male
mice: possible role in protection against chemical carcinogenesis and toxicity.
Pharmacol Toxicol. 2003 Jan;92(1):33-8.
100
Turmeric Increases Phase 2
Liver Enzymes
“Parallel to these changes, curcumin feeding to mice
also resulted in a considerable enhancement in the
activity of phase 2-metabolizing enzymes viz.
glutathione S-transferase and quinone reductase
to 1.7 and 1.8 times in liver and 1.1 and 1.3 times
in kidney respectively as compared with
corresponding normal diet fed control (P<0.050.01).”
Iqbal M, Sharma SD, Okazaki Y, Fujisawa M, Okada S. Dietary supplementation of
curcumin enhances antioxidant and phase II metabolizing enzymes in ddY male
mice: possible role in protection against chemical carcinogenesis and toxicity.
Pharmacol Toxicol. 2003 Jan;92(1):33-8.
100
Turmeric Increases Phase 2
Liver Enzymes
“In general, the increase in activities of antioxidant
and phase 2-metabolizing enzymes was more
pronounced in liver as compared to kidney. The
induction of such detoxifying enzymes by curcumin
suggest the potential value of this compound as
protective agent against chemical carcinogenesis
and other forms of electrophilic toxicity.”
Iqbal M, Sharma SD, Okazaki Y, Fujisawa M, Okada S. Dietary supplementation of
curcumin enhances antioxidant and phase II metabolizing enzymes in ddY male
mice: possible role in protection against chemical carcinogenesis and toxicity.
Pharmacol Toxicol. 2003 Jan;92(1):33-8.
101
The “Polypill” – The New
Preventative Medicine
101
The “Polypill”
“In 2003 Wald and Law introduced the concept of the
Polypill. The advocates of the Polypill selected six
pharmacological components that by modifying
different risk factors of cardiovascular disease
multiplicatively might reduce the levels of
cardiovascular disease in the population by more
than 80%.”
Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP. The
Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to
reduce cardiovascular disease by more than 75%. BMJ. 2004 Dec
18;329(7480):1447-50.
101
The “Polypill”
N J Wald, M R Law. A strategy to reduce cardiovascular disease by more than 80%.
BMJ. 2003 June 28; 326(7404): 1419.
102
Who Should Take the “Polypill”?
“Among people without existing disease, the most
discriminatory screening factor is age. As 96% of
deaths from ischaemic heart disease or stroke
occur in people aged 55 and over, treating
everyone in this group would prevent nearly all
such deaths.”
N J Wald, M R Law. A strategy to reduce cardiovascular disease by more than 80%.
BMJ. 2003 June 28; 326(7404): 1419.
102
The “Polypill”
N J Wald, M R Law. A strategy to reduce cardiovascular disease by more than 80%.
BMJ. 2003 June 28; 326(7404): 1419.
102
The “Polypill” Theoretical
Benefits
N J Wald, M R Law. A strategy to reduce cardiovascular disease by more than 80%.
BMJ. 2003 June 28; 326(7404): 1419.
103
The “Polypill” Conclusion
“It is time to discard the view that risk factors need to
be measured and treated individually if found to be
“abnormal.” Instead it should be recognised that in
Western society the risk factors are high in us all,
so everyone is at risk; that the diseases they cause
are common and often fatal; and that there is much
to gain and little to lose by the widespread use of
these drugs. No other preventive method would
have so great an impact on public health in the
Western world.”
N J Wald, M R Law. A strategy to reduce cardiovascular disease by more than 80%.
BMJ. 2003 June 28; 326(7404): 1419.
103
The “Polymeal”
Tastier and Healthier?
103
The “Polymeal” Effects
“Combining all the ingredients of the Polymeal
resulted in cardiovascular disease being reduced
by 76% (95% confidence interval 63% to 84%).
Whether increasing the amount of each ingredient
would increase the effect of the Polymeal is
uncertain. On the other hand, decreasing the
quantities could be expected to reduce the effects
of the Polymeal.”
Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP. The
Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to
reduce cardiovascular disease by more than 75%. BMJ. 2004 Dec
18;329(7480):1447-50.
The “Polymeal”
Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP. The
Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to
reduce cardiovascular disease by more than 75%. BMJ. 2004 Dec
18;329(7480):1447-50.
104
The “Polymeal” Increases Life
Expectancy
“The effect of the Polymeal represented a large
increase in total life expectancy and life
expectancy free from cardiovascular disease and a
decrease in life expectancy with cardiovascular
disease for both men and women. For men, taking
the Polymeal would result in increases of 6.6 years
in total life expectancy and 9.0 years in life
expectancy free from cardiovascular disease.”
Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP. The
Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to
reduce cardiovascular disease by more than 75%. BMJ. 2004 Dec
18;329(7480):1447-50.
The “Polymeal” Increases Life
Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP. The
Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to
reduce cardiovascular disease by more than 75%. BMJ. 2004 Dec
18;329(7480):1447-50.
105
The “Polymeal” Increases Life
Expectancy
“The Polymeal is an effective, natural, probably
safer, and tastier alternative to the Polypill to
reduce cardiovascular disease and increase life
expectancy in the general population. The effect
was consistent in both men and women at age 50.”
Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP. The
Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to
reduce cardiovascular disease by more than 75%. BMJ. 2004 Dec
18;329(7480):1447-50.
105
The “Polymeal” Increases Life
Expectancy: Side Effects
“Adverse effects reported for garlic include
malodorous breath and body odour. As garlic is
destined for mass treatment, few people will still
notice this after a while. No additional adverse
effects should be expected from the other
ingredients of the Polymeal.”
Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP. The
Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to
reduce cardiovascular disease by more than 75%. BMJ. 2004 Dec
18;329(7480):1447-50.
105
The “Polymeal” Increases Life
Expectancy: Side Effects
“Driving motor vehicles or performing activities that
require high levels of attention shortly after the
consumption of the Polymeal should be avoided.
Moreover, considering the disturbing adverse
effects of garlic, we do not recommend taking the
Polymeal before a romantic rendezvous, unless
the partner also complies with the Polymeal.”
Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP. The
Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to
reduce cardiovascular disease by more than 75%. BMJ. 2004 Dec
18;329(7480):1447-50.