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The Brain and Nutrition: why we y
should be interested?
AT t S i
A Taster Session
Ri i H
Rini Hoogkamer
k
Child & Adolescent Psychiatrist
Norwich, Norfolk
rini hoogkamer@nsft nhs uk / [email protected]
[email protected]
/ rhoogkamer@doctors org uk
Th B i
The Brain and Nutrition: why we should be interested?
d N t iti
h
h ld b i t
t d?
Introduction
& Aims
Ai
“We might be Turkeys, but this can g
y,
help save your bacon"
Th B i
The Brain and Nutrition: why we should be interested?
d N t iti
h
h ld b i t
t d?
Topics for this session:
1.Brain and Evolution
2F d
2.Food
3.Inflammation
4.Specifics:
1.Vitamin D
2.Fatty acids (“fish oil”)
y
(
)
3.Vitamins & minerals
5 P ti t
5.Patients and us, dietary advice
d
di t
d i
The Brain and Nutrition: why we should be interested?
The Brain and Nutrition: why we should be interested?
Aims, restated:
,
•
•
•
•
Framework to think about food and the brain Framework
to think about food and the brain
Pointers to further information
Some specifics
Application:
– Self and Family
Self and Family
– Patients
– (Research)
‘Q i ’
‘Quiz’
1. Where do monkeys live?
1
Where do monkeys live?
2. What does Zinc taste like?
3 Name 6 Vitamins?
3.
N
6 Vit i ?
4. What is the difference between food allergy and food i l
intolerance?
?
5. Name 4 minerals important to brain function?
6. What came first, the omega‐3 or the omega‐6?
7. What is dementia?
8. What unit do you measure vitamin D in?
Th B i
The Brain and Nutrition: why we should be interested?
d N t iti
h
h ld b i t
t d?
Topics for this session:
1.Brain and Evolution
2 Food
2.Food
3.Inflammation
4.Specifics:
1.Vitamin D
1
Vit i D
2.Fatty acids (“fish oil”)
3.Vitamins & minerals
5 Patients and us dietary advice
5.Patients and us, dietary advice
T
Top of the Food Chain: implications
f th F d Ch i i li ti
• Think (we) can eat anything, regardless
• Lazy
Lazy biochemistry –
biochemistry assumes that somebody assumes that somebody
else has done the work
• Mutations may go unnoticed –
d change in h
p
y
behavioural pattern may unmask this
– E.g. food or religious rules
Brain and Evolution
Brain and Evolution
Wh t i th b i ’ f ti ?
What is the brain’s function?
• Homeostatic Servo Mechanism
Homeostatic Servo Mechanism
• Input Æ Black Box Æ Output
• Manage organisms requirement
• Manage organisms environment
• Manages ‘the future’
M
‘th f t ’
And if things are well, little or no action is required
Brain and Evolution
Brain and Evolution
• A brain is expensive
• 2‐3% weight, 20+% energy use
% i h
%
needs constant supply – sensitive
• needs constant supply • It is well protected, but we still need to look after it
ft it
Brain and Evolution
Brain and Evolution
Energy: Energy:
It is important, also for the brain
B ki (
Breaking (research) news –
h)
early September 2012:
• Dietary Supplement Speeds Up Clinical Efficacy of SSRIs
y pp
p
p
y
– Creatine, well known as a sports supplement, seems to have a clinically significant beneficial effect when used together with SSRI
– Does this mean that (re‐)energising the depressed brain is the way ahead?
(
(or is it synergy, and does it make SSRI work better)
dd
k
kb
)
In Kyoon Lyoo et al, A J Psych Sept 2012
Percentage Change in Hamilton Depression Rating Scale (HAM‐D)
D) Score for Women Score for Women
• Percentage Change in Hamilton Depression Rating Scale (HAM
With Major Depressive Disorder Assigned to Creatine Monohydrate (5g/day) or Placebo Augmentation of SSRI (escitalopram 20mg)
Mean changes in total score with 95% confidence intervals are shown. Changes in depression score were analysed by using mixed‐effects model repeated‐measures analysis. Main effects for treatment group, visit, and their interaction were included in the model. Age and baseline HAM‐D score were also included as covariates in the model.
•b Significant difference between groups in intent‐to‐treat analysis (p<0.001).
Significant difference between groups in intent to treat analysis (p<0 001)
•Study in Korean women – so possible special case and not directly transferrable to UK teenagers. But there is other work on Creatine and it could be interesting
•
Also in the News this Week
Risk for ADHD With Outcomes of Interest
Characteristic/Exposure
aOR (95% CI)
Maternal GDM
1.91 (1.21 - 3.01)
Low SES
2.04 (1.56 - 2.68)
g
Smoking
1.48 ((1.19 - 1.84))
Perinatal health problems
1.69 (1.40 - 2.03)
Atopic eczema
1 62 (1
1.62
(1.30
30 - 2.02)
2 02)
Breastfeeding
0.83 (0.69 - 0.996)
aOR = adjusted
j
odds ratio;; CI = confidence interval
•
•
•
Arch Pediatr Adolesc Med. Published online September 10, 2012. doi:10.1001/archpediatrics.2012.1078 (Hypothesis: Could all/most of these ‘correlations’ be mediated through disturbed brain‐body homeostasis, and activation of chronic inflammatory processes
What would the role be of changes in nutrition/lifestyle as we have seen in our society in last 2 generations (e.g. omega‐3 contend of breast milk has steeply declined’ which might well be important – see further on in presentation)
In the News this Week too:
Premature death after self‐harm: a multicentre cohort study
•
•
•
•
•
•
•
•
•
•
•
•
Helen Bergen PhD a, Prof Keith Hawton DSc a , Keith Waters RMN b, Jennifer Ness MSc b, Jayne Cooper PhD c, Sarah Steeg BA c, Prof Navneet Kapur
FRCPsych c
Background
People who self‐harm have an increased risk of premature death. The aim of this study was to investigate cause‐specific premature death in individuals who self‐harm, including associations with socioeconomic deprivation.
Methods
h d
We undertook a cohort study of patients of all ages presenting to emergency departments in Oxford, Manchester, and Derby, UK, after self‐poisoning or self‐injury between Jan 1, 2000, and Dec 31, 2007. Postcodes of individuals' place of residence were linked to the Index of Multiple Deprivation 2007 in England. Mortality information was supplied by the Medical Research Information Service of the National Health Service. Patients were followed up to t e e d o 009 e ca cu ated age sta da d sed o ta ty at os (S s) a d yea s o e ost ( ), a d e tested o assoc at o s t soc oeco o c
the end of 2009. We calculated age‐standardised mortality ratios (SMRs) and years of life lost (YLL), and we tested for associations with socioeconomic deprivation.
Findings
30 950 individuals presented with self‐harm and were followed up for a median of 6∙0 years (IQR 3∙9—7∙9). 1832 (6∙1%) patients died before the end of follow‐up. Death was more likely in patients than in the general population (SMR 3∙6, 95% CI 3∙5—3∙8), and occurred more in males (4∙1, 3∙8—4∙3) than females (3∙2, 2∙9—3∙4). Deaths due to natural causes were 2—7∙5 times more frequent than was expected. For individuals who died of any cause, mean YLL was 31∙4 years (95% CI 30∙5—32∙2) for male patients and 30∙7 years (29∙5—31∙9) for female patients. Mean YLL for natural‐cause deaths was 25∙9 years (25∙7—26∙0) for male patients and 25∙5 years (25∙2—25∙8) for female patients, and for external‐cause deaths was 40∙2 years (40∙0—40∙3) and 40∙0 years (39∙7—40∙5), respectively. Disease of the circulatory (13∙1% in males; 13∙0% in females) and digestive (11∙7% in males; 17∙8% in females) systems j
y
q
p
p
(χ
were major contributors to YLL from natural causes. All‐cause mortality increased with each quartile of socioeconomic deprivation in male patients (χ2 trend 39∙6; p<0∙0001), female patients (13∙9; p=0∙0002), and both sexes combined (55∙4; p<0∙0001). Socioeconomic deprivation was related to mortality in both sexes combined from natural causes (51∙0; p<0∙0001) but not from external causes (0∙30; p=0∙58). Alcohol problems were associated with death from digestive‐system disease, drug misuse with mental and behavioural disorders, and physical health problems with circulatory‐system disease.
Interpretation
Ph i l h l h d lif
Physical health and life expectancy are severely compromised in individuals who self‐harm compared with the general population. In the management l
i d i i di id l h
lf h
d ih h
l
l i
I h
of self‐harm, clinicians assessing patients' psychosocial problems should also consider their physical needs.
Funding Department of Health Policy Research Programme.
http://www.thelancet.com/journals/lancet/article/PIIS0140‐6736(12)61141‐6/fulltext#
((Alternative interpretation: DSH/suicidality
/
is indicating body‐mind dysfunction (disturbed (
homeostasis); chronic inflammatory processes might be link – see rest of this presentation)
Further in the News this Month
Eat your way to dementia
Cover Story NewScientist Volume 215, Issue 2880 (1 September 2012)
By Bijal Trivedi
http://dx.doi.org/10.1016/S0262‐4079(12)62276‐3
(see further on in presentation: (see
further on in presentation:
work done on dementia models suggesting it could be
a brain specific form of Diabetes Mellitus (‘type 3 DM))
B i
Brain and Evolution
d E l ti
WE ALL EAT
BUT IS IT THE SAME
BUT IS IT THE SAME
•
•
•
•
•
As each other?
A th i th f il ?
As others in the family?
As our grandparents?
g
p
As people a few centuries ago?
A i P l li hi times?
As in Paleolithic
i
?
B i
Brain and Evolution
d E l ti
Exercise:
• 3‐5 Minutes 3‐5 Minutes ‘chat
chat with neighbour
with neighbour’::
• what did you ate on ‘Monday’ (as the presentation was part of a conference, given on Thursday, Monday was most likely the last time the audience had reliably conference
given on Thursday Monday was most likely the last time the audience had reliably
eaten in a ‘standard working day’ pattern)
• would your great–grandparents have recognised it
Our Food In Context
Our Food In Context
•
•
•
•
Multimillion of years of evolution
Agriculture: ‐10.000 years ago
I d ti l
Industrial revolution
l ti
20th Century Food Science
Century Food Science
• Genetic
Genetic adaptation has been unable to keep up adaptation has been unable to keep up
with cultural progress
• Natural selection: only minor alterations in past 10 000 years
10.000 years
•
Eaton, Eaton & Konner http://www.direct‐ms.org/pdf/EvolutionPaleolithic/Eaton%20Paleo%20Nutri%20Review%20EJCN.pdf
The Paleo Diet The Paleo
Diet
(what our ancestors 10.000 ‐50.000 years ago would have eaten, and what we are therefore more likely to be genetically adapted too)
Nobody knows for sure, of course, but:
• Carbs: much higher glycaemic index, no sugar
• Fats: less, different composition, Fats: less different composition
– NO trans fatty acids
– Omega‐3 to 6 balance 1:1, not 1:20
O
3 6b l
11
1 20
•
•
•
•
Proteins: higher (? But from plants?)
Fibres: much higher
Electrolytes: much more Potassium then Sodium
Electrolytes: much more Potassium then Sodium
Micronutrients: more (x2‐5)
•
•
Eaton, Eaton & Konner
aton, aton & Konner 1997,
997,
Work by Prof Loren Cordain, Colorado
Th B i
The Brain and Nutrition: why we should be interested?
d N t iti
h
h ld b i t
t d?
Topics for this session:
1.Brain and Evolution
2 Food
2.Food
3.Inflammation
4.Specifics:
1.Vitamin D
1
Vit i D
2.Fatty acids (“fish oil”)
3.Vitamins & minerals
5 Patients and us dietary advice
5.Patients and us, dietary advice
Nature does not want to be eaten!
Nature does not want to be eaten!
Defensive mechanism
Defensive mechanism
– Chemical Warfare
• Nicotine
• Caffeine
• Spices
– Phytate
ytate
• Chelates
• Needs breaking down
Needs breaking down
– Gluten
– Lectins
L i
• E.g. Soybean agglutinin Our sense of taste and smell
Our sense of taste and smell
• Function
Function of Nose and Taste buds;
of Nose and Taste buds;
• Guardians of our nervous system
y
• Remember, things do not want to be eaten, they will try to defend themselves
– Caffeine
– Nicotine
• Medication tastes (unpleasantly, to warn CNS that something is trying t
to enter that will change it’s functioning –
t th t ill h
it’ f ti i
choice: accept or accept or
reject?)
• Zinc Test (try it out later)
(Lamberts Zincatest taster)
Food
This is a vast topic, often skated over, and certainly not taught about much in most medical schools.
But is should deserve more, as it is important to us, our health and our brains.
‘Let food be thy medicine & let thy medicine be food’
Quote from Hippocrates, ‘father of Western Medicine, 460 BC to 377 BC
(I am pretty sure similar quotes can be found in most if not all other traditional cultures/civilisations)
Some aspects I will only briefly mention, but there is an whole world of knowledge about them available in books etc:
• Allergy
Allergy and Intolerances
and Intolerances
• Traditional Food Processingg
And some aspects I will spend a bit more time on:
• Inflammation
• ‘ We are overfed, but undernourished’
•
Cases that can be made for supplementation, with specifics, or with ‘general insurance policy’ of the multi‐
vitamin/mineral type
All
Allergy and Intolerances
dI t l
• Vast area, complex and somewhat controversial
• Allergy: measurable, IgE, mast cells and histamine
•
up to 5% USA children have (food) allergy
p
(
)
gy
•
encouraging work with micro exposures to encouraging
work with micro exposures to
retrain the immune system
F dI t l
Food Intolerance 1
1
•
•
•
•
•
Food Immune Reactivity:
Delayed reaction to eating ingredients
Delayed reaction to eating ingredients
Hours, days
No IgE or histamine
Slow insidious; damage!
Slow, insidious; damage!
•Common Baddies:
•gluten dairy nightshades (potato tomato) egg
•gluten, dairy, nightshades (potato, tomato), egg, oranges, soy
F dI t l
Food Intolerance 2
2
• Leads to vast array of chronic ‘maladies’
• Immune
Immune system always on the go, with no system always on the go, with no
proper switch off
• ?Over‐reactivity spreads through body
y p
g
y
• But general response weakens over time
•
(think ‘the Black Knight from Monty Python and the Holy Grail)
F dI t l
Food Intolerances 3
3
• Elimination Diets:
• They work, but are ever so hard to implement They work but are ever so hard to implement
and maintain ‘in real life’
– Feingold in California: lamb, rice, pear
– Egger in UK Europe
gg
p
– Dutch group 2011
Should we take more note of traditional food production? Or go to even more rigorous food
production? Or go to even more rigorous food processing (with supplementation)
Th B i
The Brain and Nutrition: why we should be interested?
d N t iti
h
h ld b i t
t d?
Topics for this session:
1.Brain and Evolution
2 Food
2.Food
3.Inflammation
f
4.Specifics:
1.Vitamin D
1
Vit i D
2.Fatty acids (“fish oil”)
3.Vitamins & minerals
5 Patients and us dietary advice
5.Patients and us, dietary advice
Inflammation
Chronic
Chronic Low level
Low‐level Inflammation
I fl
Inflammation
ti
Brain and Inflammation:
• From inflammation to sickness and depression: when the immune system
depression: when the immune system subjugates the brain
• Robert Dantzer et al. Nat Rev Neurosci. 2008 January; 9(1): 46–56
January; 9(1): 46
56. • doi: 10.1038/nrn2297
‘Auto –Immune Mind’
•
Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain Nat Rev Neurosci 9(1) 46–56
when the immune system subjugates the brain. Nat. Rev. Neurosci. 9(1),46
56 (2008). (2008)
Shabbir Amanullah (Royal College of Psychiatrists 201: 174 doi: 10.1192/bjp.bp.111.106229) From a therapeutic point of view psychiatry as a specialty is in an unenviable position If despite extensive
From a therapeutic point of view, psychiatry as a specialty is in an unenviable position. If, despite extensive •
interventions, a patient takes his or her own life, the physician is often perceived as having failed that person. Rarely is a consultant oncologist challenged about a non‐responsive patient: ‘surely, there must be something you could have done differently?’ Despite rapid advances across medicine, psychiatrists frequently wonder why placebos work ‘just as well’ in some disorders. •
Rethinking how the mind, in all its complexity and might, is deeply fallible may help us. In depression, negative automatic thoughts prevent people from functioning normally; in post‐traumatic stress disorder, a distressing memory can almost take on a ‘life
memory can almost take on a life of its own
of its own’. In obsessive–compulsive disorder, one is confronted with a In obsessive–compulsive disorder one is confronted with a
persistence of such thoughts despite insight that they are ‘silly’. As phenomena, the thoughts appear to be ‘against the mind’ •
That the mind chooses to attack itself is in itself analogous to the body’s autoimmune reaction. We assume g
y
that childhood events shape our subsequent reactions to events. Why then do apparently well‐adapted individuals struggle or indeed develop depression in later life? From a non‐biological perspective, how do some of the most accomplished people have low self‐esteem? Evidence and clinical experience support a combination of different interventions for psychiatric disorders One target is the immediate ‘inflammatory’
combination of different interventions for psychiatric disorders. One target is the immediate inflammatory response, and perhaps psychoactive medications for agitation/anxiety do that, but parallel to this, antidepressants and antipsychotics may act like immune suppressants – as thought suppressants. We know that psychotherapeutic approaches help, but we may need to add meditation to our interventions in an effort to suppress extraneous unwanted thoughts, as alternatives to the conventional combination of psychotherapy and psychopharmacology. Sugar does not exist in Nature as a g
food source for human beings
• We are geared to find the right input in difficult circumstances (ultimate survival
difficult circumstances (ultimate survival machines)
• Scarce things get priority, but also have cut‐
out procedures
out procedures
– Energy
– Salt
S l
– Protein
• But we do not adapt quickly at genetic level
– Sugar was never abundant, so slow ‘stop’ to input
S gar as ne er ab ndant so slo ‘stop’ to inp t
A Different View on AGE‐ingg
• Advanced Glycation
y
Endproducts
p
((AGE))
•
Think of the look between raw beef and cooked beef, then young skin vs. old skin:
•
IIn both of these cases the more cooked beef, and the older skin are more b th f th
th
k d b f d th ld ki
damaged then their previous state. A d h
And where America goes, we follow
A
i
f ll
• 35.7% of people in the US are obese, • (putting them at greater risk of Alzheimer
(putting them at greater risk of Alzheimer's)
s)
•
And now evidence suggest that it either starts young, or a new phenomenon is developing:
• Obesity and Metabolic Syndrome and Functional and Structural Brain Impairments in Adolescence, Pediatrics Sept 3rd 2012
•
Po Lai Yau, PhDa, Mary Grace Castro, BSa, Adrian Tagania, Wai Hon Tsui, MSa, and Antonio Convit, MD
M t b li S d
Metabolic Syndrome (Pediatrics Sept 3
rd
2012)
Definition used in study:
• Waist Circumference (>90th centile)
• Raised Triglycerides (>hundred and 10 mg/dL)
Raised Triglycerides (>hundred and 10 mg/dL)
• Reduced HDL Cholesterol (<40/50 mg/dL)
(
/
g/ )
• Raised Blood Pressure (>90th centile)
• Insulin Resistance (QUICKI <350)
doi: 10.1542/peds.2012‐0324
Metabolic Syndrome (Pediatrics
Metabolic Syndrome (P di t i Sept 3
S t3
rd
2012)
49 adolescence with metabolic syndrome, 62 controls
• Lower cognitive performance
Lower cognitive performance
– Arithmetic, spelling, attention, mental flexibility
– Trend to lower IQ
• Reduction embrace structural integrity
– Smaller hippocampus increased CSF, Smaller hippocampus increased CSF
– Reduction microstructural integrity major white matter tracts
doi: 10.1542/peds.2012‐0324
3 (!) T
3 (!) Types of Diabetes Mellitus
f Di b t M llit
• Type 1: results from autoimmune destruction of insulin‐producing beta cells of the pancreas
• Type
Type 2: a metabolic disorder that is characterized by 2: a metabolic disorder that is characterized by
high blood glucose in the context of insulin resistance and relative insulin deficiency
resistance and relative insulin deficiency
• TType 3!: Alzheimer Disease (may) represent a form of 3! Al h i
Di
(
)
f
f
diabetes mellitus that selectively afflicts the brain –
more on this in next few slides
•
(Suzanne de la Monte Brown University)
(Suzanne de la Monte, Brown University)
I li
Insulin and the brain
d th b i
• Encourages plasticity
g p
y
• Regulates neurotransmitters e.g. Acetylcholine
• Growth & regulation of blood vessels in the brain brain
p
g
p
pp
p
• Improves glucose uptake hippocampus and frontal lobe
– Spatial memory: 'crystallises where food is’
S ti l
'
t lli
h
f di ’
Our Brain and Nutrition:
Our
Brain and Nutrition:
why should we care
why should we care
Al h i
Alzheimer as form of DM
f
f DM
• “data provide strong evidence that AD is i t i i ll
intrinsically a neuroendocrine disease caused d i di
d
y
p
by selective impairments in insulin and IGF signalling mechanisms, including deficiencies in local insulin and IGF production”
in local insulin and IGF production
(Alzheimer's Disease Is Type 3 Diabetes–Evidence Reviewed, S de la Monte et al., Diabetes Sci Technol. 2008 November; 2(6): 1101–1113)
Th B i
The Brain and Nutrition: why we should be interested?
d N t iti
h
h ld b i t
t d?
Topics for this session:
1.Brain and Evolution
2 Food
2.Food
3.Inflammation
4.Specifics:
1.Vitamin D
1
Vit i D
2.Fatty acids (“fish oil”)
3.Vitamins & minerals
5 Patients and us dietary advice
5.Patients and us, dietary advice
Vitamin D
Vitamin D
• Vitamin D information sources:
Vitamin D information sources:
• See handout ‘Barts’ guidelines on Vitamin D
• My trust’s (NSFT Norfolk & Suffolk) Protocol
• Pearce and Cheetham ,BMJ Jan 2010: Diagnosis and Management of Vitamin D deficiency
and Management of Vitamin D deficiency, Clinical review
• ‘The vitamin D Solution, by Michael Holick, ISBN 978‐0‐452‐29688‐6
• Internet e.g. Vitamin D Council
Vitamin D In the News
Vitamin D In the News
Vitamin D supplementation:
Vitamin
D supplementation:
Does not work in depression?
• Vitamin D Supplementation and Depression in the Women’s Health Initiative Calcium and Vitamin D Trial (Bertone‐Johnson et al. Am J Ep 2012) ‐ but low dose (400iu) supplementation!! This is a dose that would be 1/10th of the physiological dose from UVB sunlight in subtropics
•
•
•
Vitamin D Supplementation and Depression in the Women
Vitamin
D Supplementation and Depression in the Women’ss Health Initiative
Health Initiative
Calcium and Vitamin D Trial,Bertone‐Johnson et al. Am J Ep 2012
http://aje.oxfordjournals.org/content/176/1/1.full.pdf Does help during pregnancy?
•
Wagner, Taylor &Hollis: 4000iu safe and fewer complications, W
T l &H lli 4000i
f
df
li ti
supplementation in this study is more in line with ‘evolutionary reality’ – Study well worth looking into
reality
St d
ll
th l ki i t
Vitamin D: 'The Sunshine Vitamin'
Vitamin D: 'The Sunshine Vitamin'
So what is Vitamin D?
So what is Vitamin D?
Vitamin D is a group of fat
fat-soluble
soluble
secosteroids. In humans, vitamin D is
unique
q both because it functions as a
prohormone and because the body
can synthesize it (as vitamin D3) when
sun exposure is adequate (hence its
nickname, the "sunshine vitamin").
Wikipedia
p
Vitamin D ‘Classical’ Metabolism
Margarine
Eggs
Salmon
John Cannell and Bruce Hollis, Alternative Medicine Review Volume 13, Number 1 March 2008
Wh t d
What does Vitamin D do? 1/3
Vit i D d ? 1/3
1 Rickets
1.Rickets
• And it is back in UK (epilepsy, child protection)!
Ri k t (1/3 continued)
Rickets ( /
d)
Clinical
•
Clinical (continued)
Progressive softening and widening of bone structure
•
Greenstick fractures
•
Delayed closure/wide fontanel
l d l
/ id f
l
•
Delayed teeth eruption
•
Caput Quadratum (Frontal bossing)
•
Craniotabes
•
Rachitic Rosary
•
Prominence of Costochondral Junctions
•
Biochemical
•
Ca2+ low or normal (if presentation is seizure: low)
Harrison’s grove
•
Phosphate low
•
Kyphoscoliosis
•
Alk Phos high (?2‐3x)
•
Wid
Wide wrist (c knob)
i t ( k b)
•
Parathyroid hormone high
h id h
hi h
•
Double malleolus
•
Vit D 25‐OH low
•
Genovarus (bow leg)
(bow leg)
•
Vit D 1 25‐OH
Vit D 1,25
OH usually low
usually low
•
Genovalvus (knock knee)
Wh t d
What does Vitamin D do? Vit i D d ? (2/3)
( / )
2
2.
Osteomalacia
Wh t d
What does Vitamin D do? Vit i D d ? (3/3)
3 Osteoporosis
3.Osteoporosis
Vitamin D ‘Non‐Classical’
Vitamin D Non‐Classical Metabolism
Metabolism
Margarine
Eggs
Salmon
John Cannell and Bruce Hollis, Alternative Medicine Review Volume 13, Number 1 March 2008
Latitudes: you might not be where you think
Latitudes: you might not be where you think
• Point of this ‘map of the world’ exercise is to think about where in the world our genetic adaptation thinks we should be; if we life at higher latitude then our ancestors, we are at increased risk of not being able to make enough vitamin D when we have an outdoor lifestyle. Vitamin D: 'The Sunshine Vitamin'
Vitamin D: 'The Sunshine Vitamin'
• Vitamin D is best thought of not as a vitamin but as a (seco)‐steroid pro‐hormone
(seco)‐steroid pro‐hormone
• Production starts in the skin out of 7‐dehydrocholesterol under influence of UVB light
• It
It’ss levels are highly regulated and it is very difficult to go levels are highly regulated and it is very difficult to go
‘toxic’
• It is involved in the regulation of many biological functions It i i l d i th
l ti
f
bi l i l f ti
and organ systems
• You and your patients need more then you were taught: supplement, sunbathe or ‘tan’
supplement, sunbathe or tan
Vit i D d F d
Vitamin D and Food
Vitamin D plays an important role in the setting up (in utero and early life) of the i
(i
d
l lif ) f h
y
innate immune system
• It helps set up your bodies basic ‘outlook on life, food and feeding
Present in seafood, added to our food quite a ,
q
lot, but at present no standard fortification in UK as done in USA
in UK, as done in USA
Vitamin D: How to Read Research
Vitamin D: How to Read Research
• Unit used
i
d
– ng/ml = 2.5 nmol/l
g/
/
– 1 IU = 1/40 mcg; 200IU = 5 mcg
•
•
•
•
•
Chemical Used:
Cholecalciferol (D3) or Ergocalciferol (D2)
Oral or i m
Oral or i.m.
Daily or bolus ?interval
?Do we need 1‐2 mcg/kg /day for optimal health?
Vit i D li i l i li ti
Vitamin D: clinical implications
• Check out yourself and family – see wall chart
• In‐patients etc. do not see the sun when it shines; glass blocks all –
hi
l bl k ll see UV meter
UV
t
DV17306
• Anxiety aches and pains could be vitamin D deficiency – osteomalacia
deficiency • As can be weird and wonderful presentations
• Supplement and enjoy the sun!!
Th B i
The Brain and Nutrition: why we should be interested?
d N t iti
h
h ld b i t
t d?
Topics for this session:
1.Brain and Evolution
2 Food
2.Food
3.Inflammation
4.Specifics:
1.Vitamin D
1
Vit i D
2.Fatty acids (“fish oil”)
3.Vitamins & minerals
5 Patients and us dietary advice
5.Patients and us, dietary advice
Essential Fatty Acids
Essential Fatty Acids
Background:
•
There are some truly ‘essential’ fatty acids, y
y
,
and then some more for some
• We all need C18 fatty acids of Ω‐3 (marine) and Ω‐6 (seeds) variety
• But some can’t make the C20 and higher ones
• And others ‘just use a lot’ (alcoholism?)
F tt A id
Fatty Acids
• Brian is mostly water (80%)
• Remainder is mostly Fat (60%)
• 20% of which are highly unsaturated long chain 20% of which are highly unsaturated long chain
fatty acids:
– Omega‐3
– Omega‐6
Omega 6
Structural
Functional
• Rhino as the ultimate vegetarian ‘machine’:
– Lots of omega‐6, hardly any omega‐3
– And has very little brain –see next slide
– (This idea/pictures stolen form Prof Crawford, see literature list)
Not Much Omega‐3
Omega‐3
Omega
3 Long Chain Fatty Acids
Long Chain Fatty Acids
Omega‐3
Omega
3 Long Chain Fatty Acids
Long Chain Fatty Acids
L
Long Chain Poly‐Unsaturated Fatty Acids
Ch i P l U t t d F tt A id
• Structural
– Cell wall
C ll ll
– Membrane Fluidity
• Functional
– Eicosanoid precursors
• Signalling molecules
• From C20 essential fatty acids
y
• Oxidised easily
¾Prostaglandines, Tromboxanes, Leucotrienes
¾Prostaglandines, Tromboxanes, Leucotrienes
F tt A id S th i
Fatty Acid Synthesis
Body can, in theory, elongate
But it can’tt ‘start’
But it can
start desaturation
desaturation from saturated
from saturated
Can’t ‘convert ‐3 into ‐6 or vice versa
Traditional diet had ‐3 and ‐6 in roughly equal di i
l di h d
d i
hl
l
amounts
• Western diet overabundance of omega‐6
•
•
•
•
–
–
–
–
Seeds Cheap
More stable
Mostly Inflammatory/catabolic
E
Essential Fatty Acids
ti l F tt A id
• Follicular Keratosis (a sign of possible long chain fatty acid problems)
fatty acid problems)
Essential Fatty Acids
Essential Fatty Acids
• Physical
Physical signs & symptoms associated with signs & symptoms associated with
essential fatty acid deficiencies (FADS):
• Thirst
• Frequent Urination
• Dry Hair
Dry Hair
• Dandruff
• Follicular Keratosis
• Brittle Nails
•Of
Of course everything can be caused by something else too, which course everything can be caused by something else too which
should be ‘excluded’/considered
?Oxford Theory of Magno‐Cellular y
g
Processing Deficits
Prof John Stein
• Yes, the older brother of Rick (fishy connections)
Yes the older brother of Rick (fishy connections)
‘The CNS Information Super Highway’
1. If you want it processed fast,
2 You use fast molecules
2.
You use fast molecules
3. Omega‐3 and derivatives are you best friends
•Auditory, visual, motor co‐ordination; y
cerebellar clock function
The Brain and Nutrition: why we should be interested?
y
Omega 3: some research
Omega‐3: some research
Neurodevelopmental Problems:
• Oxford‐Durham Study 2005
• The DOLAB Study
Th DOLAB St d 2012
Depression:
• Nemets et al. Am J Psych 2006
• Psychosis:
• Amminger et al. Arch Gen Psych 2010
The Brain and Nutrition: why we should be interested?
y
Omega 3 (EPA DHA or fish or what):
Omega‐3 (EPA, DHA or fish, or what):
• ALSPAC Study (Hibbeln et al. Lancet 2007) – more fish during pregnancy ‘better’
• DOMI
DOMInO
O study: DHA supplementation does not d DHA
l
i d
p ((Makrides et al. JAMA 2010))
help • DOLAB Study: Docosahexaenoic Acid for Reading, Cognition and Behavior
d h i in Children Aged 7–9 Years: A Randomized, i Child
d 9
d i d
Controlled Trial (Richardson et al.)
Essential Fatty Acids
y
• Borderline, Mood and Anxiety
Reviews:
• Fish Oils is Not Snake Oils; editorial L. Eugene Arnold, JAACAP Oct 2011
•
Omega‐3 Fatty Acid Supplementation for the Treatment of Children with ADHD Symptomatology: Systematic Review and Meta‐analysis: M Bloch, A Q
Qawasmi, JAACAP Oct 2011:
i JAACAP O t 2011
•
•
•
Moderate effect size (.31), but there is one
B tt f EPA th DHA
Better for EPA than DHA contend
t d
Place in context of alternatives
•
PS: Earlier in the day at the Manchester Conference, Edmund Sonuga‐Barke presented data on a meta‐analysis he was doing for European Journal, which showed lower overall effect‐size of about .20, but it ‘held’ under stricter conditions, unlike the ‘psychological therapies’.
b t 20 b t it ‘h ld’ d t i t
diti
lik th ‘
h l i l th
i ’
Essential Fatty Acids
Essential Fatty Acids
Summary:
• Probably works, effect size 0.30+
y
,
• For individuals can be spectacular!
• Psychosis NNT 4.5 h
(Rx daily capsule for 3/12 in high risk group)
EPA or DHA? •
Emphasis for (really) young and old on DHA (building) rest on EPA (functional) at least in short
(building) , rest on EPA (functional) at least in short term; also anti‐inflammatory potential
• Omacor/MaxEpa +/_ Forceval +/ Forceval (multivitamin/mineral supplement)
(
/
)
Th B i
The Brain and Nutrition: why we should be interested?
d N t iti
h
h ld b i t
t d?
Topics for this session:
1.Brain and Evolution
2 Food
2.Food
3.Inflammation
4.Specifics:
1.Vitamin D
1
Vit i D
2.Fatty acids (“fish oil”)
3.Vitamins & minerals
5 Patients and us dietary advice
5.Patients and us, dietary advice
N
Neuro transmitters
t
itt
Made out of food pre‐cursers
– Amino acids
– Co
Co‐factors
factors (vitamins and minerals)
(vitamins and minerals)
– Enzyme systems, with rate limiting factors
But if machinery not maintained, working But
if machinery not maintained working
optimally, or not enough raw materials: • tension in supply and demand chain
Vitamins & Minerals
Vitamins & Minerals
Vitamins:
•
“Vital Amines (Funk 1912)”
(
)
• Organic compound required by an organism as a vital nutrient in limited amounts
• Water‐soluble : B‐complex (precursors enzyme p (p
y
co‐factors) and C
• Fat‐soluble: A D, E, K
l bl
Vitamins & Minerals
Vitamins & Minerals
Dietary Minerals:
Dietary
Minerals:
•
the chemical elements required by living q
y
g
organisms
• Major: calcium, phosphorus, potassium, sulphur, sodium, chlorine, and magnesium
• Minor (Trace): iron, cobalt, copper, zinc, molybdenum iodine and selenium
molybdenum, iodine, and selenium
• Ultra Trace: boron,
Ul T
b
chromium
h
i
Chromium?
Chromium:
• Need 100‐600 microgram/day
Need 100 600 microgram/day
• Chromium Picolinate 600 microgram/day for Chromium Picolinate 600 microgram/day for
atypical depression http://www.ncbi.nlm.nih.gov/pubmed/16184071
• Enhances
Enhances efficacy of insulin: improved glucose efficacy of insulin: improved glucose
absorption
Selenium?
Selenium:
• Need 50‐200 microgram
g
• More clear headed, energetic and composed
• Delays cognitive decline
• Post partum mental Health: <EPDS
P t
t
t l H lth EPDS
•
•
(p
(p<.05; 100mcg/day J Matern
;
g/ y
Fetal Neonatal Med. 2011 Jan;24(1):104‐8. Epub
; ( )
p 2010 Jun 8.
Effect of supplementation with selenium on postpartum depression: a randomized double‐
blind placebo‐controlled trial. Mokhber N et al., Iran
• Involved in thyroid hormone production/regulation
Zinc?
Zinc: • need 2‐12 mg per day (when healthy)
• Involved in many enzymatic reactions, both y
y
,
body and brain: immune system, healing growth BDNF agonist NMDA receptor
growth, BDNF, agonist NMDA receptor
• Depression:
– Levels low
– Add on in antidepressant therapy Add on in antidepressant therapy (Siwek et al.2009 Affect Disord.
et al 2009 Affect Disord
2009 Nov;118(1‐3):187‐95. Epub 2009 Mar 10)
ZincaTest: have a go!
Iron?
Iron:
• Check for celiac disease, heavy periods, diet ,
yp
,
(‘vegetarian’)
• Involved in:
• Neurotransmitter production esp. dopamine
Neurotransmitter production esp dopamine
• Sleep wake transition problems
p
p
• ADHD
• Mild supplementation (too much is toxic too)
Magnesium?
Magnesium:
• Need 400 mg/day (or more)
• Centre of chlorophyll (green leafy vegetables!) and nuts
• Difficult to measure functional levels, as large amount in Bones
• SE: speeds up bowels Æ
Æ Diarrhoea (easily reversed)
Magnesium
• ADHD: Improvement of neurobehavioral disorders in children : Improvement of neurobehavioral disorders in children
supplemented with magnesium‐vitamin B6 (Mousain‐Bosc et al Magnes Res. 2006 Mar;19(1):46‐52)
al., Magnes
Res 2006 Mar;19(1):46 52)
• 6 mg/kg Mg and .6 mg/kg B6, 8 weeks+
• 40 ADHD children
• Less HA, aggression, emotionally labile, better school concentration
• Depression: treatment resistant see Eby, Med Hypothesis : treatment resistant see Eby, Med Hypothesis
2010
•
Involved in N‐methyl‐D‐aspartate
Involved in N
methyl D aspartate (NMDA) coupled calcium (NMDA) coupled calcium
channels : helps ’relaxation’
?3 5MG/KG AT NIGHT for Tics/sleep
?3‐5MG/KG AT NIGHT for Tics/sleep
M lti it i
Multivitamins and Minerals?
d Mi
l?
Complex interactions, so why not ‘mix them all together –
h
insurance policy
l
• Gesch study: BJPsych 2001, prisoners
– Forceval and Fish oil
F
l d Fi h il
• Bonnie Kaplan’s work
– EmpowerPlus
• From BNF: one Forceval, one Omacor (or 3 MaxEpa) per day gives you a good start
MaxEpa) per day gives you a good start
The Brain and Nutrition: why we should be interested?
The Brain and Nutrition: why we should be interested?
Topics for this session:
1.
2.
3.
4.
Brain and Evolution
Food
Inflammation
Specifics:
1. Vitamin D
2 Fatty acids (
2.
Fatty acids (“fish
fish oil
oil”))
3. Vitamins & minerals
5. Patients and us, dietary advice
What can we do with all this information?
In a perfect world, we would maybe change the way we live and eat, for our selves, our families, AND our patients.
However reality is that this is not easy at all
However, reality is that this is not easy at all.
Starting with self is probably the first realistic step, although clinicians who work in in‐patient settings have some chance of applying this knowledge to current patients (I have experienced that occasionally committed families can make adjustments to their life‐style and dietary patterns, leading to clinically meaningful improvements but it really needs commitment (and the world is against them)
meaningful improvements, but it really needs commitment (and the world is against them)
So here is my ‘shot’ at trying to change you:
1. Get your vitamin D levels checked, and supplement to level of at least 100nmol/L
2. Think about omega‐3 supplementation
g
pp
3. Think about your nutrition and eating patterns
official advice:
‘THE MANTRA’
mixed and varied
5 portions of ‘fruit and veg’ a day
Better Advice
Evidence based follow up studies show that Evidence
based follow up studies show that
different advice would work much better:
• Stampfler & Willett et al. @ Harvard have published extensively see below
published extensively ‐
see below
• Michael Pollan (non‐academic ‘food writer’)
(
)
Do not eat anything that your (great‐) grandmother would not recognise as food
would not recognise as food
• tailored to individual – nutritional genomics
g
Stampfler & Willet ‐
p
Harvard
BE LIKE A SUPPLEMENT EATER:
1.
2.
3.
4.
From the Nurses Health Study:
Don’t smoke
BMI < 25
30 minutes exercise a day
Diet:
1. Low in trans fat
1
i
f
2. High poly/saturated fatty acid ratio
3. Whole grain
Whole grain
4. Fish meal twice a week
5. RDA folic acid
6 More then half a unit alcohol/day
6.
h h lf
i l h l/d
Rewards: 80%CVD; <90%Type2DM; <70% colon cancer
Food: the alternative
‘Q i ’
‘Quiz’ revisited
i it d
1. Where do monkeys live?
2 What does Zinc taste like?
2.
What does Zinc taste like?
3. Name 6 Vitamins?
4 What is the difference between food allergy and food 4.
Wh t i th diff
b t
f d ll
df d
intolerance?
5 Name 4 minerals important to brain function?
5.
N
4 i
l i
b i f
i ?
6. What came first, the omega‐3 or the omega‐6?
7. What is dementia?
y
8. What unit do you measure vitamin D in?
9. What will you eat and drink tonight?
W bR
Web Resources
•
•
•
•
www.fabresearch.orgg
www.vitamindcouncil.org
http://www.grassrootshealth.net/
Vit i D P
Vitamin D: Pregnancy and Lactation ‐
d L t ti
P
Preventing ti
p
,
g
y
Complications, Growing Healthy Babies (http://www.ucsd.tv/search‐
details aspx?showID 18716)
details.aspx?showID=18716)
Books to Read
Books to Read
• Michael
Michael Crawford & David Marsh: The Driving Crawford & David Marsh: The Driving
Force
• David Horrobin: The Madness of Adam and Eve
• Michael F. Holick: The Vitamin D Solution
• Carole Wagner, Sarah Taylor & Bruce Hollis: New Carole Wagner Sarah Taylor & Bruce Hollis: New
Insights Into Vitamin D
• Richardson: They are what you feed them
• Michael Pollen: In defence of real food
h l ll
d f
f
lf d
A ti l t R d
Articles to Read
• Pearce & Cheatham BMJ 2010: Vit D
• Bloch & Qawasmi CAAP Oct 2011: Omega‐3
•
•
•
•
•
Please do not hesitate to contact me if you have nay questions, remarks, suggestions Please
do not hesitate to contact me if you have nay questions, remarks, suggestions
etc
Brain/body/environment interaction is an area I am obviously interested in, know a li l b
little about, but am not an expert in.
b
i
Therefore I am happily corrected/updated etc.
I have tried to have my ‘fact’
I have tried to have my fact as accurate as I could, but might not have succeeded as accurate as I could but might not have succeeded
everywhere. I have also tried to get as many references as I could.
Hope you have enjoyed some new and interesting thought.