Rhona CreeganMSc Clinical Biochemistry, Dip ACN

Master of Nutrition Medicine

PhD (cand), ECU

Associate of the Australasian College of Nutritional and Environmental Medicine (ACNEM)

“Optimising Health with Nutrition and Lifestyle”

rhona@omeganutrition.com.au www.omeganutrition.com.au

Neurodegeneration: unravelling the puzzle

A Nutrition Medicine Perspective

Beta amyloidNFT

NutrientsΩ3

OxidationInflammation

APOE cholesterol

HormonesNTs

Toxins

The Alzheimer’s Puzzle

Insulin Resistance

What is insulin resistance?

• Elevated cholesterol• Elevated triglycerides• Low HDL• High blood pressure• Increased waist to hip ratio

AD and Atherosclerosis- Siblings in a Dysfunctional Family?

• Amyloid plaque and atherosclerotic plaque have so much in common

• Both are damage control responses to high cholesterol in a pro-inflammatory environment, usually associated with Insulin Resistance

Alzheimer’s Disease is a Neuroendocrine Disorder resembling a

form of Diabetes.

Individuals with Type 2 diabetes have a higher risk of learning and memory

problems and cognitive decline.

Starr VL, Convil A. Curr Opin Pharmacol 2007;7:638-42

The Emergence of Type 3 Diabetes: The Dementia of the 21st Century“The co-existence of brain insulin deficiency and resistance suggests that AD may represent a brain-

specific form of diabetes, i.e type 3 diabetes”

de la Monte et al. J Alz Dis 2006; 10: 89-109

• AD – low CSF insulin levels, higher plasma insulin levels, and reduced glucose disposal compared to healthy controls.

Watson and Craft, CNS Drugs 2003: 17(1):27-45

Insulin – So much more than glucose regulation!

• Brain’s consumption of glucose critical to fuel high energy machinery. 18-30% glucose consumed but only 2% of body weight.

• Master hormone regulating other hormones (sex steroids, thyroid, adrenal)

• Growth factors such as IGF-1, cell signalling

• Influences plasticity - ability to form new connections

Insulin and β-amyloid

• Insulin increases Aβ trafficking from inside to outside the cell. β-amyloid needs to be outside the cells to be degraded.

• The enzyme that degrades insulin (IDE) also degrades β-amyloid. Insulin competes for enzyme.

• β-amyloid affects function of insulin by moving receptor from cell surface to inside cell causing IR.

Insulin and Acetylcholine

The Importance of Insulin in Memory Formation

Inflammation

Chronic low grade inflammation causes cellular damage, reduced energy production

and increased oxidative stress.

Elevated cytokines disrupt BBB

LIFE IS INFLAMMATORY

Unrelenting stress, modern diet, excess body fat, metabolic syndrome, chronic illness

Oxidation

CNS vulnerable to free radical damage:

•High metabolic rate

•High lipid content

•Relatively low antioxidant enzymes compared to other tissues

Hormonal Balance

• Insulin affects other hormones such as testosterone and oestrogen

• High and low oestrogen can impact memory. Oestrogen receptors found in cholinergic neurones

• IR reduces SHBG. Insulin affects adrenal steroid synthesis

Insulin Resistance

Insulin Resistanc

e

Fatty liver ↓ detox

↓ SHBG and hormonal imbalance

Increased body fat

Elevated cytokines and inflammation

hypertension

Elevated fatty acids

Elevated cholesterol and dyslipidaemia

Nutrition Medicine Approach to Healthy Brain Ageing

Environmental Inputs – Diet &

Exercise

Hormonal and Neurotransmitter

Balance

Detoxification and Biotransformation

Energy Production

and Oxidative Stress

Immune and Inflammatory

Balance

Gastrointestinal Balance

Diet (Eating plan)

Optimised to correct for insulin resistance and dyslipidaemia

(insulin – fat storing)

Protein, carb and fats in right ratio

don’t be SAD, tour the Mediterranean

Remove reactive foods

Maximise antioxidant intake

Dietary Carbohydrate

Low GI/GL complex carbohydrates (vegetables, fruits, legumes, whole grains)

Limit simple sugars and fructose <10% daily energy intake – depend on how much

metabolic rehab required

High carbohydrate diets can cause insulin resistance, dyslipidaemia, high blood

pressure and fatty liver

Dietary Fat

Required for energy, cell membrane structure, immune function, hormone synthesis, bile acid production and

cell signalling

Type of fat is important and contributes to disease risk

Monounsaturated fats – olive oil, vegetable oils, avocado, nuts

Helps to lower cholesterol levels by binding esters within the cell

Unsaturated : saturated fat ratio should be approx 2:1

Polyunsaturated fatsHigh InsulinTrans fats, ageing, alcohol, nutrient deficiencies, high cholesterol

Fatty Acid Balance

• DHA most abundant PUFA in brain- major structural and functional role

• Forms neuroprotectin D1 – anti-inflammatory and prevents programmed cell death

• Binds to nuclear receptors which activate genes involved with anti-inflammatory processes and lipid metabolism – FAT BURNING!

Antioxidant status

• High levels to prevent lipid peroxidation and mitochondrial damage

• Vit C , mixed tocopherols, tocotrienols, flavonoids, carotenoids, selenium, resveratrol, alpha lipoic acid, green tea, turmeric

• N-acetylcysteine increases glutathione levels

Specific Nutrients

Insulin Sensitivity:

DHA, alpha lipoic acid, Cr, Hops, proanthocyandins, cinnamon, acetyl carnitine, vitamin D

Mitochondrial energetics:

CoQ10, ALA, B complex, Mg

Alzheimer’s Disease

ginkgo, turmeric, acetyl carnitine, green tea, phosphatidylserine, vitamin D

Preventing “D”ecline

• VDR present in neurons and glial cells

• Supports immune function in brain

• Reduction in VDR expression in hippocampal cells in AD

• Helps rebuild brain connections

• Role in insulin signalling

Recipe for HealthEat fresh whole foods, high in

protein and limit processed foods that are high GI and contain

sugar, synthetic fats and preservatives

Exercise regularly to increase metabolic rate, reduce body fat,

improve CV function and stimulate lymphatic removal of toxins

Drink plenty of purified water

Recipe for HealthExercise – every opportunity

Healthy Body

Composition

↓Inflammation

↓Oxidation

↓Toxin load

↓Cellular

Degeneration

Healthy Brain Ageing

Supplement the diet with a broad range of nutrients which will address the key

contributors to chronic neurodegenerative disease and ageing