This document provides an overview of obesity, energy balance, inflammation, and other factors related to metabolic health. It discusses how factors like stress, poor diet, lack of activity, and environmental toxins can disrupt metabolic processes and gene expression, leading to issues like insulin resistance, obesity, and disease. The document recommends addressing the root causes of metabolic imbalance through a Mediterranean-style diet high in nutrients and low in inflammation-promoting foods. Regular physical activity and lifestyle factors are also important to maintain metabolic health and gene expression. The goal is to take an integrative, upstream approach to metabolic disorders through nutrition and lifestyle interventions before relying on downstream medical treatments.

1. Ms. Bavinder Heer MRPharmS, Dip CNM
Integrative Health Practitioner
(Pharmacist & Nutritional Therapist)

3. Overview:
 Obesity
 Energy – what can go wrong
 Inflammation- what does it mean
 Other factors
 Current trends- do diets work?
 Looking to the future...

4. 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

5. Relieving the economic burden of
disease
 “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

6. Current trends:
Nutrition and Lifestyle
Intervention.

7. Functional Medicine:
Functional medicine involves understanding
the origins, prevention, and treatment of
complex, chronic disease.

9. Clinical psychoneuroimmunology and
nutritional 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.

10. 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.

11. Food is information for our
epigenome (gene expression)
Food provides signals for cellular
function to programme for health and
disease.

12. What can go wrong?

13. 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

14. Our environment is changing the way
our 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

15. Traditional model

16. 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.

17. The effects of food

18. Losing equilibrium:
T3 & T4 Sex hormones
Corticosteroids Growth
hormones
Normal Normal insulin
catabolism
CATABOLISM ANABOLISM

19. 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, endocrine
and behvioural responses to starvation.

20. Reactive Hypoglycaemia.

21. Symptoms of Reactive Hypoglycaemia
 Irritability • Insomnia
 Anxiety • Cravings
 Depression • Excessive thirst
 Mood swings • Addictions
 Poor concentration • Drowsiness
 Fat storage (midriff) • Excessive sweating
 Brain fog

22. 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

23. 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.

24. Clinical PNI – Metamodel 1
Causes
(nutrition, inactivity, lack of sunshine,
tabaco)
Cortisol
Resistance
Insulin
resistance
LGI
Proximate
medicine
The symptom

25. The result:
T3 & T4
Sex hormones
Abnormal
insulin
Corticosteroids
Growth
hormones
Normal
catabolism
CATABOLISM ANABOLISM

26. 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.

27.  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)

28. The new shape:

29. 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)

30. What is our aim:
Control dysglycaemia:
Minimise the effect of the
inflammation response
Improve anti-oxidant status

31. MEDITERRANEAN diet:
Neopolitan researchers found that participants
assigned to a Mediterranean diet:
• Lost more weight
• Experienced greater improvements in glycaemic
control
• Showed improvements in coronary risk measures
(Esposito K, 2009)

32. 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

33. REVIEW OF 35 STUDIES ON THE
MED 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

34. 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

35. 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.

36. What about fat??
“Consumption of mono-unsaturated fatty acids is
thought to increase insulin sensitivity, and this
component of the diet may explain the favourable
effect of the MED diet.”
Esposito K, 2009

37. 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

38. 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

39. 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

40. Benefits of the MED diet
 Improved glycaemic control
 Reduction in Cardiovascular risk
 Reduction in inflammation

41. 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

42. 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

43. 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)

45. Lifestyle Intervention:
And not to forget activity levels:

46. To move or not to move?? That is the
question.
• 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)

47. 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

48. We are designed to move!

50. 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.

51. Shokran