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”
[email protected] 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