2b. Detoxification Flashcards
What is detoxification?
Process of transforming fat-soluble toxins into water-soluble compounds that can be eliminated via urine or bile
In which cells does detoxification primarily take place?
Hepatocytes
How can detoxification be supported in clinic?
Minimise toxic load
Support detoxification pathways
Support elimination pathways
What are xenobiotic toxins?
Foreign substances found in the body that are not derived from a normal diet or produced endogenously e.g. pesticides, food additives, heavy metals, medications, industrial chemicals
Examples of endogenous toxins
GI microbes/dysbiotic bacteria
Waste products from normal metabolic processes e.g. urea from ammonia
Poorly detoxified/eliminated hormones e.g. chronic constipation = reduced oestrogen elimination
Examples of exogenous chemical toxins
BPA
Pesticides
Phthalates
PBDEs
PAHs
Solvents
Sources of BPA
Food tins
Plastic packaging
What conditions can poor BPA detoxification/elimination be associated with?
T2D
Infertility
Oestrogen disruption
Source of pesticides
Crops
Water contamination
What conditions can poor pesticide detoxification/elimination be associated with?
AZD
Infertility/erectile dysfunction
RA
SLE
Cancer
Sources of phthalates
Plastics
Beauty products
What conditions can poor phthalate detoxification/elimination be associated with?
T2D
Infertility
Allergies
Sources of PBDEs
Flame retardants
Farmed fish
What conditions can poor PBDE detoxification/elimination be associated with?
Insulin resistance
Child behavioural problems
Sources of PAHs
Air pollution/vehicle exhausts
What conditions can poor PAH detoxification/elimination be associated with?
COPD
T2D
ADHD
AZD
Atopic conditions
Sources of solvents
Vehicle exhausts
Smoking
Foods
What conditions can poor solvent detoxification/elimination be associated with?
AZD
Infertility
MS
RA
Autism
Examples of exogenous metal toxins
Aluminium
Mercury
Arsenic
Sources of aluminium
Foil
Anti-perspirants
Vaccines
What conditions can poor aluminium detoxification/elimination be associated with?
AZD
Mitochondrial damage
Sources of mercury
Amalgams
Fish (esp larger)
Water
Vaccines
Air pollution
What conditions can poor mercury detoxification/elimination be associated with?
Chronic fatigue
Neurological damage
Hashimoto’s
ADHD
Infertility
SLE
Sources of arsenic
Water
Rice
Chicken
What conditions can poor arsenic detoxification/elimination be associated with?
T2D
Gout
Cancer
Peripheral neuropathy
Methods for reducing toxins in life
Eat organic
Avoid farmed/large fish
Avoid plastic packaging
Avoid non-stick pans
Air purifier
Water filter
Non-chemical ridden beauty, cleaning products
Avoid alcohol, smoking, drugs
Signs/symptoms of sluggish/sad liver
Poor appetite
Fatigue
Nausea esp in morning
Difficulty digesting fatty foods
Alcohol intolerance
Dry skin/itching
Waking between 1am and 3am
Headaches
Dark circles under eyes
Yellowing of whites of eyes
Yellow coating on tongue
Methods of testing for toxins
Hair analysis - toxins
Urine - heavy metals
Blood - heavy metals
Stool analysis
Genetic profiling
Why are AOs crucial following P1 detoxification?
P1 generates free radicals
AOs help to avoid tissue damage by converting free radicals to non-toxic molecules
What are the 3 main groups of AOs?
AO enzymes
Chain breaking AOs (enhances stability of oxidation)
Transition metal-binding proteins
Examples of AO enzymes
Superoxide dismutase (SOD)
Catalase
Glutathione peroxidase
Glutathione reductase
What do superoxide dismutase enzymes do?
Convert superoxide to hydrogen peroxide
(hydrogen peroxide is then detoxified by catalase or glutathione peroxidase)
Nutrients needed for superoxide dismutase enzymes to work
Zn
Cu
Mn
What do catalase enzymes and glutathione peroxidase do?
Convert hydrogen peroxide to H2O and O2
Nutrient needed for catalase enzymes to work
Fe
Nutrient needed for glutathione peroxidase enzymes to work
Se
What do glutathione reductase enzymes do?
Regenerates glutathione that has been oxidised
Nutrient needed for glutathione reductase enzymes to work
B3
Examples of chain-breaking AOs
C
E
Flavonoids
Carotenoids
Food sources of vit E
Sunflower seeds
Almonds
OO
Avocado
Sweet potato
Food sources of flavonoids
Quercetin - red apples, red onion
Anthocyanins - red grapes
Catechins - green tea
Kaempferol - kale, spinach
Food sources of carotenoids
Yellow, orange, red fruits and veg
Green veg
Example of transition metal AOs
Metallothionein (MT)
What do metallothioneins do?
Bind to essential and toxic heavy metals
Reduce oxidative stress
Nutrients needed for metallothionein AOs
Cysteine (legumes, sunflower seeds, eggs, chicken)
Zn
Cu
Se
What is P0 of detoxification?
Entry of the toxin into the cell
Exit of the unmetabolised toxin from storage inside cells e.g. adipocytes
How do fat soluble toxins leave the cell?
Via diffusion
How do water soluble toxins leave the cell?
Via a transporter
Examples of water soluble toxin transporters
Solute carriers
ATP binding cassette carriers
What happens during P1 detoxification?
Transformation enzymes (CYP450) and a toxin/hormone reaction creates an active binding site on the toxin
This makes the toxin more water soluble but also more reactive
How many CYP450 enzymes are there?
50 - 100
Does each CYP450 enzyme detoxify a specific compound or are they broad?
Specifity
How does increased exposure to one toxin affect the CYP450 enzymes?
Each enzyme is produced in response to exposure to a certain toxin
Increased exposure to a toxin increases the amount of that enzyme to degrade it
This can happen at the expense of other enzymes and toxin biotransformation/ degradation
What can increase P1 activity?
Toxic load through:
Smoking
Alcohol
Caffeine
Chargrilled food
Why must the progression of P1 to P2 happen quickly?
To minimise the damaging effects of intermediary products
What can affect an individual’s ability to metabolise toxins in P1?
SNPs
Diet
Availability of nutrient co-factors
Why will P2 be slowed down if P1 is upregulated?
Due to overwhelm
Lack of dietary co-factors