food as medicine using foods to treat disease and to maximise optimal wellness by stephen eddey...

Food as Medicine

Using Foods to Treat Disease and to Maximise Optimal

WellnessBy

Stephen Eddey M.H.Sc., B.Sc.(Comp.Med.), Dip.App.Sc.(Nat.), Ass.Dip.App.Sc.(Chem.),

Cert.IV(Workplace & Training),N.D.

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Food as Medicine

Finding the right nutrition for: Obesity Anti-aging/Wellness Diseases

Heart Disease Detoxification Cancer Inflammation Functional foods

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Food as Medicine – Evolution of the Human Diet

taken from work done by:

Prof. Neil Mann, Australia

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• Who were our ancestors ?

• What did our ancestors eat ?

• How do we know?

• What dietary changes have occurred ?

• What impact have dietary changes had ?

Basic Questions

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Evolution and DietEvolution in a geological context

Oligocene Miocene Pliocene Pleistocene

25 mya 10 mya 2 mya 10,000ya

Mammalianinsectivores

Primates Apes Ramapithecus “Lucy”(hominid)

H. habilis

H. erectus

H. sapiens

Or

GCh

Oldest stone tools

Major climatic change

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Australopithecusaferensis

Approximately4 million

years ago

Evolution and DietDietary 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

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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)

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Human Brain Size

Brainsize(cc)

0 1 2 3 4Age in millions of years

200

1800

1000

600

1400

Homo sapiens

Homo erectus

Homo habilis

Australopithecines

(Aiello&

Wheeler1995)

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Gut morphology and diet

Insectivores

Horse

Rabbit

Chimpanzee Humans

Frugivores

GorillaDog

Cat

Cow

Folivores (mid-gut)

Faunivores

Folivores (fore-gut)

Martin, 1994.The life of primates.In: The CambridgeEncylopedia ofHuman Evolution

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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 22 - 40% (49.0%) (45.1%)

Fat 28 - 47% (34.0%) (32.4%)

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Atherosclerosis

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.

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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.”


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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.”


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Antiaging Nutrition

Calorie Restriction

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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 MammalsRejuvenation Research. Volume 7, Page 3-8, May 2004

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“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. LaneEndocrine Effects of Dietary Restriction and Aging: The National Institute on Aging Study Journal of Anti-aging Medicine. Volume 4, Page 215-223, September 2001

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“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. LaneEndocrine Effects of Dietary Restriction and Aging: The National Institute on Aging Study Journal of Anti-aging Medicine. Volume 4, 5-223, September 2001

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Calorie Restriction: Mechanism of Action46

The Thyroid and Calorie Restriction

“Calorie restriction has been shown to have immediate effects on thyroid hormones in Sprague-Dawley 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. LaneEndocrine Effects of Dietary Restriction and Aging: The National Institute on Aging Study Journal of Anti-aging Medicine. Volume 4, Page 215-223, September 2001

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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

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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 substrate-specific activator of yeast Sir2 and human SirT1.”


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What are Sirtuins?

“Sirtuins have been implicated in several important cellular processes, including genomic stability, DNA repair, transcriptional silencing, p53-mediated apoptosis, and adipogenesis.”


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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.”


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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.”


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Insulin and Aging

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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.

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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.

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Low Fat Diets

Their effects on the biomarkers of aging

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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

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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).”


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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.”


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Inflammation and Heart Disease

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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.

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Osiecki, H. (2004) Alternative Medicine Review, 9, 32-53.

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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.

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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.

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High Carb Eating Promotes hs-CRP

“Dietary glycemic load is significantly and positively associated with plasma hs-CRP in healthy middle-aged 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

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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.”


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http://www.ajcn.org/content/vol75/issue3/images/large/015888A.jpeg

DHEA Declines with Metabolic Syndrome

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Testosterone Declines with Metabolic Syndrome

“Super Diets”

Which Diet for Which Person?

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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.

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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

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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.

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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

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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.

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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

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Super foods

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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.

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“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.”


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“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.

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“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.

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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.”


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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

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Broccoli: Anticancer King

“Isothiocyanates (found in Broccoli) act as anti-carcinogens by inducing Phase II conjugating enzymes, in particular Glutathione S-tranferases.”


Postgrad Med 2004;50:145-149

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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 caspase-9- 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.

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Sulforaphane from Broccoli Causes G1 Cell Arrest

“We demonstrated that sulforaphane arrested cell-cycle 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 non-transformed human T lymphocytes. Ann N Y Acad Sci. 2003 Dec;1010:393-8.

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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 plant-derived isothiocyanates: comparison of allyl isothiocyanate with sulforaphane and related compounds. J Agric Food Chem. 2004 Apr 7;52(7):1867-71.

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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.

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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.

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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.

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Tomatoes

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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.

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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.”


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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.”


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Green Tea

The Great Anti-cancer Drink

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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).”


Postgrad Med 2004;50:145-149

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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-gallate-

induced cell cycle arrest and apoptosis of human prostate carcinoma cells.

Arch Biochem Biophys. 2003 Feb 1;410(1):177-85.

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Green Tea Upregulates p21, an anti cancer gene

“Earlier studies in our laboratory have shown that treatment of androgen-sensitive and androgen-insensitive 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-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells.


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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-gallate-

induced cell cycle arrest and apoptosis of human prostate carcinoma cells.


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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-3-gallate (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.

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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.”


Dec 29.

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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.”


Dec 29.

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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.

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Green Tea Protects Against LDL Oxidation

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Teas Protects Against LDL Oxidation

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Teas Benefit Atherosclerosis69

Soy

Soy Prevents and Treats Cancer, while also preventing Heart Disease

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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

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“Soy isoflavones bind with very low affinity (1/50,000 to 1/100,000 the affinity of estradiol) to the alpha-estradiol 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.”


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“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.”


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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.

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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):744-57.

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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.

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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.”


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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.”


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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.”


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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.”


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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.”


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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):744-57.

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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.

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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.

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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.”



74

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.”



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 NFkB-dependent signalling pathway by suppressing IkB degradation. The NFkB pathway is an extensively studied signal transduction cascade involved in inflammatory responses during carcinogenesis .”



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.

75

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 16alpha-hydroxyestrone 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.”


76

Olive Oil

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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.”


77

Olive Oil Prevents Oxidation“On the other hand, virgin olive oil also contains a

large amount of antioxidant molecules (like a-tocopherol, several different phenolic compounds and even coenzyme Q). These molecules are well-known 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.”


77

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.”


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.”


78

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.”


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”


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.”


79

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.”


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.

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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.”


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.”


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.”


81

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.”


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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.”


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.”


82

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.”


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.

83

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.”


84

Garlic Prevents Cancers


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).”


84

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.”


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.


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, glutathioneS-transferase (GST), and catalase.”

“Glutathione S-transferase is an important enzyme that conjugates electrophiles and assists in the detoxification of many carcinogens and other xenobiotics.”


85

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.”


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.”


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.”


86

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.”


87

Detoxification

Foods that enhance detoxification

93

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

94

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


“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.”


95


“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.”


95

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


“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.”


96


“There was a dramatic increase (244% of control) in the activity of phase 2 detoxifying enzyme UDP-glucuronosyl transferase in the dandelion tea-pretreated 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.”


96

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


“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.”


97


“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.”


97


There are 4 major phase II liver detoxification pathways:

Methylation Glycination Glucuronidation Glycination

98

Detoxification: Role of GarlicDiallyl 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 anti-tumour 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.

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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.

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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).”


99


“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<0.05-0.01).”


100


“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.”


100

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.

101

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.”


102

The “Polypill”


102

The “Polypill” Theoretical Benefits


102

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.”


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.”


103

The “Polymeal”


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.”


104

The “Polymeal” Increases Life


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.”


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.”


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.”


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food as medicine using foods to treat disease and to maximise optimal wellness by stephen eddey...

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