Overview: Obesity Energy – what can go wrong Inflammation- what does it mean Other factors Current trends- do diets work? Looking to the future...
Obesity Implicated as a risk factor for many different disorders including: CVD Diabetes type II Some Cancers BPH Female infertility & uterine fibroids Gallstones Pregnancy disorders such as pre-eclampsia
Relieving the economic burden ofdisease “coronary heart disease, prostate and breast cancer, diabetes and obesity account for 75% of health-care costs, yet the progression of these diseases can be stopped or even reversed with intensive lifestyle changes.” Ornish D. Lancet Oncol. 2009 Jul;10(7):638-9
Current trends: Nutrition and Lifestyle Intervention.
Functional Medicine: Functional medicine involves understanding the origins, prevention, and treatment of complex, chronic disease.
Clinical psychoneuroimmunology andnutritional medicine (CPNI) Interactions between the nervous system and the immune system, and the mutual relationship between behaviour and health. The main disciplines that are brought together are psychology, neurology, immunology, endocrinology, evolutionary biology and epigenetics. Research has revealed that human physiology and the external environment interact dynamically.
Considerations: Epigenetics: concerned with how our environment changes gene expression Proteomics: concerned with proteins expressed by a genome. Nutrigenomics: the science of how food substances alter gene expression within human cells.
Food is information for ourepigenome (gene expression) Food provides signals for cellular function to programme for health and disease.
An environmental mismatch:“through nearly all human evolution genetic adaptation was closely coupled with environmental alterations. Now, however, cultural change comes too rapidly for genetic accommodation to keep pace.”Prev Med. 2002 Feb; 34(2): 109-18
Our environment is changing the wayour genes are expressed “ ...recent studies indicate that environmental factors & diet can perturb the way genes are controlled by DNA methylation & covalent histone modifications. Unexpectedly, and not unlike genetic mutations, aberrant epigenetic alterations and their phenotypic effects can sometimes be passed on to the next generation.” Mutat. Res. 2006 Aug 30;6001-2):46-57
Factors influencing glycaemic control Traditional model: Regulation of blood sugar- insulin and glucagon Functional model: Metabolic Intelligence: Balancing act, the adrenals, pituitary gland, intestines and pancreas work in synchrony to achieve blood glucose balance.
Losing equilibrium: T3 & T4 Sex hormones Corticosteroids Growth hormones Normal Normal insulin catabolism CATABOLISM ANABOLISM
How do we confuse the metabolic system? Erratic eating patterns and fad diets may confuse the metabolic system Poor blood sugar regulation will lead to reduced response to insulin Breakdowns occur in signalling Hypothalamus develops a resistance to leptin signals (Halle & Persson, 2003) Primary role is to coordinate metabolic, endocrineand behvioural responses to starvation.
How do we confuse the metabolic system? Chronic stress and adrenal function-- stress elevated cortisol induces insulin resistance and inflammation Symptoms of high cortisol: intermittent fatigue, irritability, dysglycaemia, sleep disturbances, central obesity
The motion picture of Diabetes Central cortisol resistance precedes peripheral insulin resistance. Garcia-Prieto et al.; Cortisol secretary pattern and glucocorticoid feedback sensitivity in women from a Mediterranean area: relationship with anthropometric characteristics, dietary intake and plasma fatty acid profile. Clin Endocrinol (Oxf)). 2007 Feb;66(2):185-91. Higher expression of glucocorticoid receptors on the liver precede insulin resistance.
Clinical PNI – Metamodel 1 Causes (nutrition, inactivity, lack of sunshine, tabaco) Cortisol Resistance Insulin resistance LGI Proximate medicine The symptom
The result: T3 & T4 Sex hormones Abnormal insulin Corticosteroids Growth hormones Normal catabolism CATABOLISM ANABOLISM
Other factors: Thyroid function- sets metabolic rate and responsible for energy release Psychological factors- serotonin, dopamine Immune Dysfunction- it is now widely accepted that obesity is associated with a level of chronic inflammation in the body.
Toxicity and its impact on mitochondrial function Chemical known as obesogens are known to induce obesity Loss of circadian rhythm- studies have demonstrated that melatonin can reduce diet-induced obesity in rats (Prunet- Marcassus, 2003) Imbalance of gut flora- function of ghrelin and leptin; Experiments performed on mice colonized with human gut microbes showed that changes in diet that resulted in the mice becoming obese (high carb to Western diet) allowed a rapid switch in microbial community.... when this modified gut flora was transferred to germ free mice, the obese phenotype was also passed on. (Turnbaugh P J et al, 2009)
Current trends: do DIEts work? Insulin resistance is affected by the factors mentioned earlier, what‟s also interesting is that erratic eating patterns and fad diets may confuse the metabolic system, a breakdown occurs in the signalling, the hypothalamus develops a resistance to leptin signals (Halle and Persson, 2003) Evidence now clearly demonstrates that the body gets “stingier” in its use of calories after each diet (Muls E et al, 1995)
What is our aim:Control dysglycaemia:Minimise the effect of the inflammation responseImprove anti-oxidant status
MEDITERRANEAN diet:Neopolitan researchers found that participantsassigned to a Mediterranean diet: • Lost more weight • Experienced greater improvements in glycaemic control • Showed improvements in coronary risk measures (Esposito K, 2009)
Med-style diet for type 2 diabetes (Eposito et al 2009): “compared with a low-fat diet, a low carbohydrate, Mediterranean-style diet led to more favourable changes in glycaemic control and coronary risk factors and delayed the need for anti-hyperglycaemic drug therapy in overweight patients with newly diagnosed type 2 diabetes.” Ann Intern med. 2009 sep 1; 151(5): 306-14
REVIEW OF 35 STUDIES ON THEMED DIET “The MED diet showed favourable effects on lipoprotein levels, endothelium vasodilation, insulin resistance metabolic syndrome, antioxidant capacity, myocardial and cardiovascular mortality, and cancer incidence in obese patients and those with previous myocardial infarction.” Serra-Majem et al.; Nutrition Reviews 64(2): S27-S47
MED diet reduces inflammation “compared with patients consuming the control diet, patients consuming the intervention diet had significantly reduced serum concentrations of hs-CRP, IL-6, IL-7 & IL- 18, as well as decreased insulin resistance.” Eposito et al., JAMA 2004;292:1440-1446
Mediterranean Diet: • Rich in cereals, fruit, nuts, legumes, whole grains, fish, olive oil • Low in dairy, meat, junk food, fat • High in beta-carotene, vitamin C, tocopherols, polyphenols, minerals, soluble fibre.
What about fat??“Consumption of mono-unsaturated fatty acids isthought to increase insulin sensitivity, and thiscomponent of the diet may explain the favourableeffect of the MED diet.” Esposito K, 2009
Good fat is better than low fat: The Medl-RIVAGE study: reduction of CVR disease risk factors after a 3-mo intervention with a MED-type diet or a low fat diet. “our data predicted a 9%reduction in cardiovascular disease risk with the low-fat diet and 15% reduction with this particular MED diet”Vincent-Baudry et al.; Am J Clin Nutrition 2005; 82:964-71
Inflammation: immune dysfunction Morbid obesity is now known to be associated with low- grade systemic inflammation & immune activation Pro-inflammatory cytokines are synthesized and released in human adipose tissue : TNF-alpha, IL-1, IL-6, IFN-gamma
The anti-inflammatory diet “the MED diet ensures adequate intake of whole grains, fruits, vegetables, nuts, fish, cereals, legumes and olive oil; all this together with moderate consumption of alcohol, predominantly wine, leads to high ingestion of dietary fibre, antioxidants, magnesium and unsaturated fatty acids. Therefore, the MED diet could serve as an anti-inflammatory dietary pattern, which could protect from or even treat diseases that are related to chronic inflammation, including visceral obesity, type 2 diabetes and the metabolic syndrome.” Giugliano D, Esposito K. MED diet & Metabolic diseases. Curr Opin Lipidol. 2008 Feb; 19(1):63-8
Benefits of the MED diet Improved glycaemic control Reduction in Cardiovascular risk Reduction in inflammation
Micronutrients for genomic stability....A new paradigm for RDAs “current recommended dietary allowances for vitamins & minerals are based largely on the prevention of disease of deficiency, eg scurvy in the case of vitamin C. Because diseases of development, degenerative disease and aging itself are partly caused by damage to DNA it seems logical that we should focus better our attention on defining optimal requirements of key minerals and vitamins for preventing damage to both nuclear and mitochondrial DNA.” Food and Chemical Toxicology 40(2002)1113-1117
Nutrients & compounds researched Chromium Gymnema Sylvestre Magnesium Bitter Melon Alpha Lipoic Acid Fenugreek Omega 3 EFAs Bilberry Manganese Gingko Biloba Zinc Ginseng, Vitamin D Garlic Vitamin E Cinammon B vitamins Results, are mixed and vary according to the aims of the Vitamin C trial
Metabolic Foods Medical foods: “super-nutrition” containing nutrients needed for specific clinical conditions. Trial using these with MED diet, vs MED diet alone Low GI (doesn‟t cause insulin spike) Soy protein (for body composition & lipids) 2 g plant sterols(healthy cholesterol levels) Targetted phytonutrients (cellular signal improvement)
Lifestyle Intervention:And not to forget activity levels:
To move or not to move?? That is thequestion. • More frequent television viewing in adolescence and early adulthood is associated with greater BMI gains through to mid-adulthood and with central adiposity in mid-life. (Ashcroft, J 2008)
Activity „Our results strongly suggest that the increased risk of obesity owing to genetic susceptibility can be blunted through physical activity. These findings suggest the important role of physical activity in public health efforts to combat obesity, particularly in genetically susceptible individuals.‟ Rampersaud E et al. Physical activity may help offset genetic risk for obesity” Archives of Internal Medicine, 2008; 168:1791-1797
Nutrition is/as Medicine Nutritional intervention is the upstream intervention in people with metabolic disorders in Diabetes .... In contrast medical intervention is approximate downstream intervention for people suffering with metabolic disorders. The proximate intervention should be used to gain time for repairing the motion picture.