9/12/18 Supported by Dietary Characteristics of the Traditional - PDF document

9/12/18 Supported by Dietary Characteristics of the Traditional Mediterranean Diet • A variety of minimally processed wholegrains and legumes as the staple food • Plenty of - and a huge diversity of - fresh vegetables consumed daily • Fresh fruits as the typical daily dessert; sweets based on nuts, extra virgin olive oil and honey consumed only during celebratory occasions • Extra virgin olive oil, nuts and seeds the principal source of fat • Moderate consumption of fish • Dairy products (mainly local cheese and yoghurt) consumed in low amounts; butter, cream and milk never used, except for milk in coffee and for infants • Red and processed meat consumed only once every week or two • Wine consumed in low to moderate amounts with meals Tosti et al 2018 In 1993 Oldways created the Mediterranean Diet Pyramid – in partnership with the Harvard School of Public Health and the WHO – as a healthier alternative to the USDA’s original food pyramid. 1

9/12/18 The Hypothesised effectors of the Mediterranean Diet Tosti et al 2018 Intake of saturated fat is ~8% energy due to low intake of milk, meat & Lipid butter Lowering Total fat 25-35% energy from evoo, nuts, seeds & germ of wholegrains Effect Nuts also provide plant sterols High intake of soluble fibres from wholegrains, beans and fruit Fermentation by microbiota - increased short chain fatty acids – inhibits cholesterol synthesis Extremely low in trans fats Rich in beta-carotene, vit C, vit E, folate, polyphenols & selenium Reduced Reduction in oxidised LDL & inflammatory markers Reduced Inflammation Inflammation & Phytoprotectants in the aleurone layer of wheat bran – ferulic acid is & the major polyphenol & has antioxidant + anti-inflammatory effects Oxidative Oxidative Stress Germ of wholegrains contains spermidine – cardioprotective, neuroprotective & anti-inflammatory effects (Madeo et al 2018) Stress EVOO contains several potent antioxidants & oleocanthal which acts via the same anti-inflammatory pathway as ibuprofen – although the dose matters to have an effect 2

9/12/18 • Energy restricted but nutrient dense diets shown to be effective in reducing cancer in animal models – traditional Med diet achieves this being low GI, whole food & high fibre Modification • Short chain fatty acids produced induce satiety by inhibiting gastric emptying & increasing gut hormones of hormones • In women Med diet shown to decrease the activity of hormones that stimulate cancer cell growth such as IGF-1, & growth testosterone & oestrogen (Kaaks et al 2003) • Low GI, high omega-3 & mono fats, lower branched chain factors amino acids – reduce insulin resistance & hyperinsulinaemia • High fibre – increases excretion of carcinogenic substances • High in phytoestrogens & wealth of anti-cancer phytochemicals EVOO Phenolic Subclasses Oleocanthal • First documented in literature in early 90’s • Around 2000 ws identified as the phytochemical responsible for the distinct peppery taste and pungency in evoo ( oleo for olive, canth for sting, and al for aldehyde) • Levels vary in evoo – more robust oils have higher levels • Mimics ibuprofen – inhibits COX1 and COX2 enzymes = anti-inflammatory action • 50ml evoo a day corresponds to ~10% ibuprofen pain relieving dose Parkinson & Keast 2014 3

9/12/18 • Lower incidence of many cancers in Med populations including breast, prostate, lung & GI cancers Oleocanthal & • COX2 enzyme implicated in pathogenesis of many cancers – oleocanthal of interest being a COX2 inhibitor Cancer • Also been shown to encourage cell apoptosis, anti- proliferative effects on cancer cell lines & prevents tumour growth • Anti-inflammatory effect beneficial in joint-degenerative disease – decreases markers of arthritis (Parkinson & Keast 2014) • Ibuprofen known to have beneficial effects on neuro- degenerative disease therefore much interest in Other Potential oleocanthal (Giusti et al 2018) Benefits • In elderly Australian cohort those with Alzheimer’s disease & mild cognitive impairment had a lower adherence to a Med diet than healthy controls (Gardener et al 2012) (The Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) study) Not Just Oleocanthal • Great review: Bioactivity of Olive Oil Phenols in Neuroprotection (Angeloni et al 2017) • Brain tissue is very prone to oxidative stress – high energy requirements, high oxygen consumption, high PUFA content, low antioxidant defences • “Oleuropein and hydroxytyrosol act as direct free radical scavengers, hydroxytyrosol and oleocanthal are strong cyclooxygenases (COX) inhibitors and oleuropein counteracts low density lipoprotein (LDL) oxidations” • Describes potential benefits in spinal cord injury, stroke, Alzheimer’s, Parkinson’s, MS & ALS – most studies only in animal or in vitro studies to date, but show promise 4

9/12/18 Mechanisms of action of evoo phenols in preventing / counteracting AD Black = Animal studies Red = In vitro studies Angeloni et al 2017 Lower Intake of Protein & Specific Amino Acids • Total protein 20% lower than typical Western diet • Mostly plant protein – from legumes & whole grains • Protein >20% energy associated with increased cancer (4- fold) & mortality (75%) in those aged <=65 – eliminated if plant protein (Levine et al 2014) • Ratio of animal to plant protein results in 40% lower methionine – in animal models methionine restriction extends lifespan & reduces cancer (Brown-Borg & Buffenstein 2017) • Branched chain amino acids play key role in modulating insulin sensitivity – circulating levels higher in insulin- resistance – associated with an 11-13% increase increased risk of type 2 diabetes (Lynch & Adams 2014) • Choline & L-carnitine (rich in meat, cheese & eggs) 50% lower – gut microbiota produces tri-methylamine N-oxide (TMAO) & this increases CVD risk Microbiota • High fibre increases the levels of specific bacterial groups that produce short chain fatty Mediated acids, particularly butyrate • Long term adherence to plant-rich Med Diet Effects shown to increase microbiota diversity – essential for healthy immune function, gut health & potential knock-on effect on longevity & healthy ageing 5

9/12/18 “In the past, the surplus of energy required to perform the high levels of physical labour (approximately 70–80 h of work per week) was provided by the consumption of energy-dense A Qualifier… food, such as extra-virgin olive oil, wine, and dried fruits” Tosti et al 2018 Retraction of the PREDIMED Trial • In June the NEJM retracted the 2013 study “Primary prevention of cardiovascular disease with a Mediterranean diet” (Estruch et al 2013) • Published corrected version (Estruch et al 2018) • Problems identified: household members not randomised, some participants at 1 site (out of 11) not randomised & apparent inconsistent use of randomisation tables at 1 other site PREDIMED Study • Men (age 55-80) women (aged 60-80) with no CVD but type 2 diabetes or at least 3 major risk factors • 3 dietary intervention groups: a Mediterranean diet supplemented with extra virgin olive oil, a Mediterranean diet supplemented with nuts, or a control low fat diet • 7447 recruited – 1588 participants known or suspected to deviate from proper randomisation protocol • Authors re-ran analysis without these participants 6

9/12/18 Summary of Dietary Recommendations Med diet + olive oil group – given a polyphenol-rich extra virgin olive oil Med diet + nuts – 30g serve daily (walnuts, almonds & hazelnuts given) What Changed? • Not much! • In both the original and republished study, the incidence of CVD in the Med diet groups was lowered by ~30% cf low fat control group • Conclusion: “In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet.” Estruch et al 2018 7

9/12/18 Estruch et al 2018 New Research from Modern Olives 2 Te s t s o n 9 c o m m o n c o o k i n g o i l s • Effect of heating to 240°C for 15 minutes • Effect of heating to 180°C for 6 hours % o f P o l a r C o m p o u n d s i n O i l • Most common chemical parameter used in industrial kitchens to determine the moment that the oil is no longer safe to be used P o l a r C o m p o u n d s L i n k s • Polar compounds include aldehydes, alkyl benzenes and other aromatic hydrocarbons • Linked to cancer and neurodegenerative diseases such as Alzheimer's and Parkinson's • Typically, different country standards place the level between 24 and 27% Test 1: Effect of Heat Preliminary results from the Evaluation of chemical and physical changes in different commercial oils during heating; Authors: De Alzaa, F.; Guillaume, C.; and Ravetti, L.; Modern Olives 8