Transcript Nutrition and Depression Deborah Colson DipION MBANT CNHC

DEMENTIA PREVENTION
DEBORAH COLSON MSC DIPION
Guildford GP Education – Update Week
Royal Surrey County Hospital, 6 November 2014
BACKGROUND
Deborah Colson MSc DipION MBANT CNHC
Nutritional Therapist
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Specialist in nutrition / lifestyle for disorders of nervous system
Institute for Optimum Nutrition (DipION, 2002)
MSc Nutritional Therapy (University of Westminster, 2014)
Author of Optimum Nutrition for Your Child and Optimum
Nutrition for your Child's Mind, Alzheimer's Prevention Plan
• Professional Association: British
Association for Applied Nutrition
and Nutritional Therapy (BANT)
• Regulator: Complementary and
Natural Healthcare Council (CNHC)
Professional Standards Authority
Accredited Voluntary Register (AVR)
Clinical Practice
• Brain Bio Centre
• Clinic for nutritional treatment of mental health
and neurological disorders (since 2003)
• Wholly owned by charity Food for the Brain
whose aim is to raise awareness of the link
between nutrition and mental health
• Re:Cognition Health
• Multi-disciplinary cognitive health clinic
• The Insight Network
• Network of therapists and psychiatrists
What is Nutritional Therapy?
• The application of nutrition and health
science to enable individuals to maximise
their health potential
• Holistic therapy, complementary to medicine
• Manages biochemical / nutritional
imbalances which impact health
• Genetic, environmental and psychosocial
factors considered
How does Nutritional Therapy work?
• Full case history
• Biochemical / nutritional tests recommended
• Practical dietary, lifestyle and supplement
advice given, tailored to the individual
• Optimise biochemistry
• Address risk factors
• Manage drug-nutrient interactions
• Informed by evidence base
• Favourable risk:benefit ratio
• ‘Wholistic’ – benefits are broad
Nutrition and lifestyle-related factors
• blood glucose control
• essential fatty acids
• minerals
• Mg, Se, Zn, Cr, Mn, I, Cu, Ca
• vitamins
• D, Bs, C, E, A, K
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amino acids
phytonutrients
Mediterranean diet
microbiome
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homocysteine
drug-nutrient interactions
food intolerances
oxidative stress
environmental toxins
stress
sleep
exercise
social activity
Well-established dementia risk factors
Risk Factor
Age
Type II Diabetes
Overweight
Hypertension (mid-life)
Dyslipidaemia (mid-life)
Smoking, ↓physical activity
↓Education, mental/social stimulation
Genetics – ApoE et al
Modifiable?
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Other nutrition & lifestyle risk factors
Risk Factor
↑ HbA1c (w/out diabetes)
↓ Adherence to Mediterranean diet
↓Omega-3 / fish consumption
↑Homocysteine / ↓B vitamins
↓Vitamin D
↑Oxidative stress / ↓antioxidant nutrients
↑Alcohol
↓Polyphenols (curcumin et al)
↑Stress
Modifiable?
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Reversal of cognitive decline:
A novel therapeutic program
• Personalised intensive diet, lifestyle, supplement
programme
• 10 pts (Alzheimer's, amnestic mild cognitive impairment
(aMCI), or subjective cognitive impairment (SCI))
• 9/10 showed subjective or objective improvement in cognition
from 3-6 months (1/10 = very late stage AD).
• 6/10 had had to discontinue working or were struggling with
their jobs at the time of presentation, and all were able to
return to work or continue working with improved performance.
• Improvements sustained. Longest follow-up is 2.5 years from
initial treatment, with sustained and marked improvement.
Bredesen DE (2104) Reversal of cognitive decline: A novel therapeutic
program. Aging (Albany NY) 6(9):707-17.
Evidence base
• Limited due to:
• Lack of pharmaceutical interest and
non-pharmaceutical funding
• Challenge of studying nutrients/diet
in RCT setting
• Synergy of nutrients often ignored
Evidence-based practice
“the conscientious, explicit and judicious use of
current best evidence in making decisions
about the care of the individual patient. It
means integrating individual clinical expertise
with the best available external clinical
evidence from systematic research.”
Sackett D, 1996
Evidence-based practice
EBP: Hierarchy of evidence
BMJ Clinical Evidence
DEMENTIA
Blood glucose
• Diabetes is a known risk factor
• n = 2 067, mean age 76 yrs
• In subjects without diabetes, higher glucose levels
(6.4 vs 5.5 mmol/l) in preceding 5 years associated with
increased risk of dementia HR 1.18 (95% CI 1.04 - 1.33)
p=0.01
• In subjects with diabetes, higher glucose levels were also
related to an increased risk of dementia (p=0.002)
• glucose level 10.5 mmol/l vs 8.9 mmol/l, HR 1.40 (95% CI, 1.12 1.76)
Crane et al (2013) Higher glucose levels may be risk factor for dementia
(even in absence of diabetes). NEJM 369(6):540-8
2008, 5:51
Genetic factors
ApoE ε4 PSEN-1, -2,
others
Biological factors
HTN, CVD, DM
hypoperfusion
Environmental factors
Trauma, toxins, diet
Vascular compromise
Oxidative stress
Neuroinflammation
Tau (hyperphosphorylation
βAmyloid
Carbs vs protein
• n = 24, obese, premenopausal women (20-50yrs)
no diabetes or prediabetes randomised to:
• 6 months, 500 kcal/day
• HP (30% protein, 40% carbohydrates, 30% fat), or
• HC (15% protein, 55% carbohydrates, 30% fat)
Kitabchi AE et al, (2013 ) Effects of high-protein versus high-carbohydrate
diets on markers of β-cell function, oxidative stress, lipid peroxidation,
proinflammatory cytokines, and adipokines in obese, premenopausal
women without diabetes: a randomized controlled trial. Diabetes Care
36(7):1919-25
High protein (HP) vs high carbohydrate (HC)
CRP ( -2.1 vs. -0.8 mg/L, P = 0.0003)
inflammation
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TNFα (-1.8 vs. -0.9 pg/mL, P < 0.0001)
inflammation
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IL-6 (-1.3 vs. -0.4 pg/mL, P < 0.0001)
inflammation
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E-selectin (-8.6 vs. -3.7 ng/mL, P = 0.0007)
inflammation
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β-cell function (7.4 vs. 2.1, P < 0.0001)
metabolic/obesity/DM
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insulin sensitivity (4 vs. 0.9, P < 0.0001)
metabolic/obesity/DM
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adiponectin (1,284 vs. 504 ng/mL, P = 0.0011)
metabolic/obesity/DM
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free fatty acid (-0.12 vs. 0.16 mmol/L, P = 0.0002)
dyslipideamia
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REE (259 vs. 26 kcal, P < 0.0001)
metabolism
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dichlorofluorescein (-0.8 vs. -0.3 µmol/L, P < 0.0001)
cellular oxidative stress
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malondialdehyde (-0.4 vs. -0.2 μmol/L, P = 0.0004)
lipid peroxidation
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Kitabchi AE et al (2013 ) Diabetes Care 36(7):1919-25
Omega-3
linseeds,
walnuts
and their
oils,
green veg
ALA
18:3 ω−3
Omega-6
∆6 desaturase
Mg, Zn, B3, B6, C
trans fats, alcohol,
stress, sat fats
∆5 desaturase
Mg, Biotin
trans fats, alcohol,
stress, sat fats
EPA
20:5 ω-3
oily fish
meat
dairy
eicosanoids, resolvins
(anti-inflammatory)
DHA
22:6 ω-3
resolvins, protectins
(anti-inflammatory)
LA
18:2 ω−6
GLA
18:3 ω−6
nuts, seeds
seed oil
Evening Primrose Oil /
borage oil
DGLA
20:3 ω−6
AA
20:4 ω-6
eicosanoids
(anti-inflammatory)
eicosanoids
(pro-inflammatory)
RBC omega-3 and brain ageing
Lower RBC DHA levels are associated with
smaller brain volumes and a “vascular”
pattern of cognitive impairment even in
persons free of clinical dementia
Tan Z.S. et al., 2012 Red blood cell omega-3 fatty acid levels and markers
of accelerated brain aging. Neurology, 78(9):658-664
Omega-3 and fish
• Prospective study, Chicago Health and Aging Project
(CHAP), 1993-2000, followed up 3.9 years for development
of AD
• n = 815 community-dwelling, 65-94 years, free from AD
• 131 developed AD
• Fish ≥ 1/week: 60% less risk of AD vs non-consumers (RR,
0.4; 95% CI, 0.2-0.9)
• Total intake of omega-3, and DHA intake associated with
reduced risk of AD. EPA not associated with AD
• Conclusion: Dietary intake of n-3 fatty acids and weekly
consumption of fish may reduce risk of incident Alzheimer
disease.
M. Morris, et al.. (2003) Consumption of fish and n-3 fatty acids and risk of
incident Alzheimer disease. Arch Neurol, 60:940-946
Omega-3 and fish
• Prospective cohort, 210 elderly
• Fish consumers had significantly less 5-y subsequent
cognitive decline than nonconsumers (p = 0.01)
• Linear trend for relation between the intake of EPA+DHA
and cognitive decline (p = 0.01)
• An average difference of 380 mg/d in EPA+DHA intake
was associated with a 1.1-point difference in cognitive
decline (p = 0.01).
van Gelder et al., (2007) Fish consumption, n-3 fatty acids, and subsequent 5-y
cognitive decline in elderly men: the Zutphen Elderly Study, Am J Clin Nutr.
85(4):1142-7
Cochrane Review: Omega-3
“Direct evidence on the effect of omega-3
PUFA on incident dementia is lacking”
Sydenham E et al., (2012) Cochrane Database Syst Rev. Omega 3 fatty acid
for the prevention of cognitive decline and dementia. 13;6:CD005379.
BDNF
• Brain-derived neurotrophic factors
• Neurogenesis occurs throughout life
• New neurons are fragile and survival is uncertain
• BDNF supports survival of these neurons and
synaptic connections
• Exercise, vitamin D, omega-3 promote BDNF
Vitamin D
• Higher serum vitamin D3 levels are associated with
better cognitive test performance in patients with
Alzheimer's disease
Oudshoorn et al, Dement Geriatr Cogn Disord. (2008)
• Vitamin D deficiency is associated with low mood and
worse cognitive performance in older adults
Wilkins et al, Am J Geriatr Psychiatry (2006)
• Vitamin D inversely associated with increased odds of
cognitive impairment (p for linear trend = .001)
Llewellyn et al, (2009) Serum 25-Hydroxyvitamin D Concentration and Cognitive
Impairment. J Geriatr Psychiatry Neurol.
Vitamin D
• Hypovitaminosis D is prevalent among older
adults
• Stimulates neurotrophin release (BDNF)
• Protects the brain by buffering antioxidant
and anti-inflammatory defences against
vascular injury and improving metabolic and
cardiovascular function
Cherniack EP et al., (2009) Some new food for thought: the role of vitamin
D in the mental health of older adults. Curr Psychiatry Rep. 11:12-9
Sources of vitamin D
Full-body exposure to UVB
(15 to 20 minutes at midday
in summer, fair skin, no sun-block)
10,000 iu D3
Cooked tuna sardines, mackerel
or salmon (3-3.5 oz)
200 – 360 iu D3
Shitake mushrooms
(fresh 3.5 oz)
100 iu D2
Egg yolk
20 iu D2 or D3
Cod liver oil (1 tbspn)
1,360 iu D3
200 iu = 5µg 10,000 iu = 250µg
Vitamin D – how much?
• 5000 iu/day vitamin D3 for 12 months
increased serum D to > 74 nmol/l for 92% of
45 nursing home residents.
• Average level 125 nmol/l.
• No adverse effects seen
Mocanu V et al., (2009) Long-term effects of giving nursing home residents
bread fortified with 125 µg(5000 IU) vitamin D(3) per daily serving. Am J
Clin Nutr. 89(4):1132-7
Homocysteine
“77 cross-sectional studies on >34,000
subjects and 33 prospective studies on
>12,000 subjects have shown associations
between cognitive deficit or dementia and
homocysteine and/or B vitamins”
Smith AD (2008) The worldwide challenge of the dementias: a role for B
vitamins and homocysteine? Food Nutr Bull. 29(2 Suppl):S143-72
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Homocysteine
• Treatment with B vitamins (FA, B6, B12) for 24
months significantly slowed the rate of brain
atrophy in elderly subjects with MCI
• Rate of atrophy per year (p =0.001)
• B vitamins = 0.76% [95% CI, 0.63–0.90]
• placebo = 1.08% [0.94–1.22]
• Greater rate of atrophy was associated with
lower final cognitive test scores
Smith AD et al. (2010) Homocysteine-Lowering by B Vitamins Slows the Rate of
Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized
Controlled Trial. PLoS ONE
Homocysteine-lowering nutrients
• Folic acid
• Vitamin B12
400µg
100µg
• Vitamin B6
20mg
• Vitamin B2
10mg
• Zinc
5 mg
Green, leafy veg, pulses
Animal products (eggs, meat,
dairy etc)
Eggs, cheese, fish, mushrooms,
broccoli, lentils, yoghurt, nuts
Wholemeal bread, oily fish,
walnuts, lentils, bananas, chicken
Sardines, eggs, tofu, oysters,
lamb, seeds, nuts
• These levels may be found in a good multi or B-complex
How much B12?
• 50µg/day effective in restoring normal B12
status in people over the age of 50
• 10µg/day no more effective than placebo
• UK RDA = 1.5µg/day
Seal et al., (2002) A Randomized, Double-Blind, Placebo-Controlled
study of Oral Vitamin B12 Supplementation in Older Patients with
Subnormal or Borderline Serum Vitamin B12 Concentrations Journal
of the American Geriatric Society, vol 50, pp. 146-151
How much B12 ?
• Dose-finding RCT to determine lowest oral dose of cyanocobalamin to
normalize biochemical markers of vitamin B12 deficiency in older people
with mild vitamin B12 deficiency
• defined as a serum vitamin B12 level of 100 to 300 pmol/L (135-406 pg/mL)
and a methylmalonic acid (MMA) level of 0.26 µmol/L or greater.
• n = 120, 16 weeks, daily oral doses used: 2.5, 100, 250, 500, and 1000 µg
• Mean reductions in MMA: 16%, 16%, 23%, 33%, and 33%, respectively
• 647 - 1032 µg/d cyanocobalamin associated with 80% - 90% of
estimated maximum reduction in MMA
• Conclusion: Lowest dose of oral cyanocobalamin required to normalize
mild vitamin B12 deficiency is more than 200 times greater than the
Dutch RDA, which is approximately 3 µg daily.
Eussen et al., (2005) Oral cyanocobalamin supplementation in older people
with vitamin B12 deficiency: a dose-finding trial, Arch Intern Med
Mediterranean diet
Published studies suggest that greater
adherence to Mediterranean diet is associated
with slower cognitive decline and lower risk of
developing Alzheimer disease.
Lourida et al, (2013) Mediterranean diet, cognitive function, and
dementia: a systematic review. Epidemiology
Vitamin E
• n = 5395, 55+ years, free of dementia, provided dietary
information at baseline
• mean follow-up period of 9.6 years
• higher intake of vitamin E at study baseline was associated
with lower long-term risk of dementia (P = .02 for trend).
• Lowest tertile of vitamin E intake vs highest tertile were 25%
less likely to develop dementia (HR 0.75; 95% CI 0.59-0.95)
• Dietary intake of vitamin C, beta carotene, and flavonoids were
not associated with dementia risk (P > .99 for trend for vitamin
C and beta carotene and P = .60 for trend for flavonoids)
Devore EE et al, (2010) Dietary antioxidants and long-term risk of
dementia. Arch Neurol. 67:819-25.
Superfoods??
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Turmeric (curcumin)
Berries (flavonoids, anthocyanidins)
Brassicas (sulphoraphane)
Green tea (catechins, L-theanine)
Grapes / wine (resveratrol)
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Polyphenols
• Produced by plant as defence mechanism
• UV radiation, browsing animals, infection
• Hormetic response to stress
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Not part of our biochemistry
Not used for structure or to activate enzymes
Affect quality of our biochemistry
Regulators of our microbiome
Polyphenols
• Potential role as neuroprotective agents.
• Curcumin, catechins, and resveratrol (beyond
their antioxidant activity) are involved in antiamyloidogenic and anti-inflammatory
mechanisms.
• Correlations between neuroprotective functions
and potential therapeutic value in AD.
Davinelli S et al., (2012) Pleiotropic Protective Effects of Phytochemicals in
Alzheimer's Disease Oxid Med Cell Longev. doi: 10.1155/2012/386527
Polyphenols
• Food sources:
• Colourful
fruits, vegetables, herbs,
spices, seeds, nuts
Cochrane: Exercise and dementia
...promising evidence that exercise programs
can have a significant impact in improving
ability to perform activities of daily living and
possibly in improving cognition in people with
dementia
Forbes D et al, (2013) Exercise programs for people with dementia.
Cochrane Database Syst Rev 12:CD006489.
Alcohol
• A J-shaped relationship may exist between alcohol consumption
and cognitive decline in MCI patients
Xu G et al., (2009) Alcohol consumption and transition of mild cognitive
impairment to dementia. Psychiatry Clin Neurosci. 63:43-9
• In MCI pts, up to 1 drink/day of alcohol or wine may decrease
the rate of progression to dementia.
Solfrizzi V et al., (2007) Alcohol consumption, mild cognitive impairment,
and progression to dementia.; Italian Longitudinal Study on Aging Working
Group. Neurology 68:1790-1799
• Some evidence to suggest that limited alcohol intake in earlier
adult life may be protective against incident dementia later
Peters R et al., (2008) Alcohol, dementia and cognitive decline in the
elderly: a systematic review. Age and Ageing 37:505-512
Drug-nutrient interactions
Drug
Effect
PPI
H-2 receptor antagonists
↓ B12, minerals
Metformin
↓ B12
Statins
↓ Co-enzyme Q10
Advice for the patient
Do:
• Eat low-carb Mediterranean
style
• ↑ vegetables, fresh fruit, seeds,
nuts, legumes, cereals, oils, fish,
eggs
• X trans fats, refined carbs, sugar
• Engage in physical, mental and
social activity
• Consider supplementing fish oil,
multi / B-complex, vitamin D
• Drink water
Don’t:
• Eat BAD
• British Average Diet
• Eat sugar or refined
carbohydrates
• Drink juice
• Smoke
• Over consume alcohol or
caffeine
• Be chronically stressed
What can you do?
• Test homocysteine
• B vitamin supplementation to bring down to 8µmol/l
• Test B12
• B12 supplementation (100µg/day) to maintain in top
half of range
• Test red cell folate
• Folate supplementation to maintain in range
• Test vitamin D3
• D3 supplementation to maintain above 125 nmol/l
Deborah Colson MSc DipION
e [email protected]
w www.thinkingnutrition.co.uk
@thinkinutrition
 07957 277 811