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Nutrition 2 (Semester I) > 2b. Detoxification > Flashcards

2b. Detoxification Flashcards

1
Q

What is detoxification?

A

Process of transforming fat-soluble toxins into water-soluble compounds that can be eliminated via urine or bile

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2
Q

In which cells does detoxification primarily take place?

A

Hepatocytes

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3
Q

How can detoxification be supported in clinic?

A

Minimise toxic load
Support detoxification pathways
Support elimination pathways

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4
Q

What are xenobiotic toxins?

A

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

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5
Q

Examples of endogenous toxins

A

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

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6
Q

Examples of exogenous chemical toxins

A

BPA
Pesticides
Phthalates
PBDEs
PAHs
Solvents

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7
Q

Sources of BPA

A

Food tins
Plastic packaging

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8
Q

What conditions can poor BPA detoxification/elimination be associated with?

A

T2D
Infertility
Oestrogen disruption

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9
Q

Source of pesticides

A

Crops
Water contamination

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10
Q

What conditions can poor pesticide detoxification/elimination be associated with?

A

AZD
Infertility/erectile dysfunction
RA
SLE
Cancer

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11
Q

Sources of phthalates

A

Plastics
Beauty products

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12
Q

What conditions can poor phthalate detoxification/elimination be associated with?

A

T2D
Infertility
Allergies

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13
Q

Sources of PBDEs

A

Flame retardants
Farmed fish

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14
Q

What conditions can poor PBDE detoxification/elimination be associated with?

A

Insulin resistance
Child behavioural problems

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15
Q

Sources of PAHs

A

Air pollution/vehicle exhausts

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16
Q

What conditions can poor PAH detoxification/elimination be associated with?

A

COPD
T2D
ADHD
AZD
Atopic conditions

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17
Q

Sources of solvents

A

Vehicle exhausts
Smoking
Foods

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18
Q

What conditions can poor solvent detoxification/elimination be associated with?

A

AZD
Infertility
MS
RA
Autism

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19
Q

Examples of exogenous metal toxins

A

Aluminium
Mercury
Arsenic

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20
Q

Sources of aluminium

A

Foil
Anti-perspirants
Vaccines

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21
Q

What conditions can poor aluminium detoxification/elimination be associated with?

A

AZD
Mitochondrial damage

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22
Q

Sources of mercury

A

Amalgams
Fish (esp larger)
Water
Vaccines
Air pollution

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23
Q

What conditions can poor mercury detoxification/elimination be associated with?

A

Chronic fatigue
Neurological damage
Hashimoto’s
ADHD
Infertility
SLE

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24
Q

Sources of arsenic

A

Water
Rice
Chicken

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25
Q

What conditions can poor arsenic detoxification/elimination be associated with?

A

T2D
Gout
Cancer
Peripheral neuropathy

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26
Q

Methods for reducing toxins in life

A

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

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27
Q

Signs/symptoms of sluggish/sad liver

A

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

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28
Q

Methods of testing for toxins

A

Hair analysis - toxins
Urine - heavy metals
Blood - heavy metals
Stool analysis
Genetic profiling

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29
Q

Why are AOs crucial following P1 detoxification?

A

P1 generates free radicals
AOs help to avoid tissue damage by converting free radicals to non-toxic molecules

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30
Q

What are the 3 main groups of AOs?

A

AO enzymes
Chain breaking AOs (enhances stability of oxidation)
Transition metal-binding proteins

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31
Q

Examples of AO enzymes

A

Superoxide dismutase (SOD)
Catalase
Glutathione peroxidase
Glutathione reductase

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32
Q

What do superoxide dismutase enzymes do?

A

Convert superoxide to hydrogen peroxide
(hydrogen peroxide is then detoxified by catalase or glutathione peroxidase)

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33
Q

Nutrients needed for superoxide dismutase enzymes to work

A

Zn
Cu
Mn

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34
Q

What do catalase enzymes and glutathione peroxidase do?

A

Convert hydrogen peroxide to H2O and O2

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35
Q

Nutrient needed for catalase enzymes to work

A

Fe

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36
Q

Nutrient needed for glutathione peroxidase enzymes to work

A

Se

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37
Q

What do glutathione reductase enzymes do?

A

Regenerates glutathione that has been oxidised

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38
Q

Nutrient needed for glutathione reductase enzymes to work

A

B3

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39
Q

Examples of chain-breaking AOs

A

C
E
Flavonoids
Carotenoids

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40
Q

Food sources of vit E

A

Sunflower seeds
Almonds
OO
Avocado
Sweet potato

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41
Q

Food sources of flavonoids

A

Quercetin - red apples, red onion
Anthocyanins - red grapes
Catechins - green tea
Kaempferol - kale, spinach

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42
Q

Food sources of carotenoids

A

Yellow, orange, red fruits and veg
Green veg

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43
Q

Example of transition metal AOs

A

Metallothionein (MT)

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44
Q

What do metallothioneins do?

A

Bind to essential and toxic heavy metals
Reduce oxidative stress

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45
Q

Nutrients needed for metallothionein AOs

A

Cysteine (legumes, sunflower seeds, eggs, chicken)
Zn
Cu
Se

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46
Q

What is P0 of detoxification?

A

Entry of the toxin into the cell
Exit of the unmetabolised toxin from storage inside cells e.g. adipocytes

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47
Q

How do fat soluble toxins leave the cell?

A

Via diffusion

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48
Q

How do water soluble toxins leave the cell?

A

Via a transporter

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49
Q

Examples of water soluble toxin transporters

A

Solute carriers
ATP binding cassette carriers

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50
Q

What happens during P1 detoxification?

A

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

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51
Q

How many CYP450 enzymes are there?

A

50 - 100

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52
Q

Does each CYP450 enzyme detoxify a specific compound or are they broad?

A

Specifity

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53
Q

How does increased exposure to one toxin affect the CYP450 enzymes?

A

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

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54
Q

What can increase P1 activity?

A

Toxic load through:
Smoking
Alcohol
Caffeine
Chargrilled food

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55
Q

Why must the progression of P1 to P2 happen quickly?

A

To minimise the damaging effects of intermediary products

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56
Q

What can affect an individual’s ability to metabolise toxins in P1?

A

SNPs
Diet
Availability of nutrient co-factors

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57
Q

Why will P2 be slowed down if P1 is upregulated?

A

Due to overwhelm
Lack of dietary co-factors

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58
Q

How to support P1 detoxification

A

Go organic to minimise exposure to pesticides
Minimise exposure to xenobiotics in toiletries and household products
Stop smoking
Avoid caffeine
Avoid chargrilled/smoked foods
Reduce or ideally eliminate alcohol
Avoid unnecessary medications
Avoid use of plastics in contact with food

59
Q

Dietary co-factors to support P1 detoxification

A

B vits (action of CYP450 enzymes
BCAAs - leucine, isoleucine, valine

60
Q

Food sources of B vits

A

Whole grains
Legumes
Mushrooms
Sunflower seeds
Eggs
Fish

61
Q

Food sources of leucine, isoleucine and valine

A

Quinoa
Fish
Eggs
Meat

62
Q

What do SNPs on genes have the potential to do during detoxification?

A

Increase toxicity by speeding up conversion of compounds to reactive intermediary products
Cause an accumulation of unmetabolised toxins

63
Q

What do CYP1A2 enzymes metabolise?

64
Q

What impact does a SNP on CYP1A2 have on caffeine metabolism?

A

Slows it down

65
Q

What do CYP1A1 enzymes do?

A

Deactivate oestrogen
Detoxifies PAHs and solvents

66
Q

What impact does a SNP on CYP1A1 have?

A

Increases risk of oestrogen dominance
PAHs damage DNA - increasing cancer risk

67
Q

How can a SNP on CYP1A1 be supported?

A

Avoid chargrilled meat/smoked food
Avoid smoking
Avoid exposure to industrial pollutants and synthetic oestrogens
Focus on plant foods - rainbow, green tea, apples, berries
Su rich foods - cruciferous, broccoli sprouts (I3C) and alliums

68
Q

What happens during P2 detoxification?

A

A variety of chemical reactions occur to the reactive toxins to make them safe to be released into the blood or bile for excretion via kidneys or bowel

69
Q

What are the 6 pathways of P2 detoxification?

A

Glucuronidation
Sulphation
Glutathione conjugation
Amino acid conjugation
Acethylation
Methylation

70
Q

What enzyme is involved in glucuronidation?

A

UDP-glucuronosyltransferases

71
Q

What happens during glucuronidation?

A

Glucuronic acid is added to the P1 metabolite

72
Q

Food sources of glucuronic acid

A

Apples
Broccoli
Alfalfa

73
Q

What are detoxified during glucuronidation?

A

Oestrogens
NSAIDs
Morphine

74
Q

What is glucuronidation inhibited by?

A

Aspirin
Smoking
OCP
Fluoride

75
Q

Foods to support glucuronidation

A

Citrus peel
Brassica veg
Turmeric

76
Q

What enzyme is involved in sulphation?

77
Q

What happens during sulphation?

A

Sulphate is added to the P1 metabolite

78
Q

Food sources of sulphur

A

Brassicas
Onion
Garlic
Cruciferous

79
Q

What are detoxified during sulphation?

A

Steroid hormones
Food additives
Industrial chemicals

80
Q

What is sulphation inhibited by?

A

NSAIDs
Tartrazine

81
Q

What enzyme is involved in acetylation?

82
Q

What happens during acetylation?

A

An acetyl group is added to the P1 metabolite

83
Q

What are detoxified during acetylation?

A

Smoke
Histamine

84
Q

What is acetylation inhibited by?

A

B and C deficiency

85
Q

What is acetylation enhanced by?

A

B1, 5
C
Butyric acid

86
Q

What enzymes are involved in methylation?

A

COMT
PEMT
(ones ending in MT)

87
Q

What happens during methylation?

A

A methyl group is added to the P1 metabolite

88
Q

What are detoxified during methylation?

A

Steroid hormones
Dopamine
Adrenaline
Arsenic

89
Q

What inhibits methylation?

A

B12 deficiency
B9 (folate) deficiency
High sucrose diet

90
Q

Which nutrients enhance methylation?

A

Methionine
Betaine
Choline
B2, 6, 9, 12
Folate
Mg

91
Q

What enzyme is involved in glutathione conjugation?

92
Q

What happens during glutathione conjugation?

A

Reactive P1 metabolises are reacted with glutathione

93
Q

What is detoxified during glutathione conjugation?

A

Xenobiotics
Paracetamol
Heavy metals

94
Q

What is glutathione conjugation inhibited by?

A

Deficiencies in:
Se
B6
Zn
Glutathione

95
Q

What enhances glutathione conjugation?

A

Brassicas
Turmeric
Citrus peel
Alpha lipoic acid

96
Q

What enzyme is involved in amino acid conjugation?

A

Amino acid transferases

97
Q

What happens during amino acid conjugation?

A

An amino acid (mostly glycine) is added to the P1 metabolite

98
Q

What is detoxified during amino acid conjugation?

A

Xenobiotics
Drugs

99
Q

What is amino acid conjugation inhibited by?

A

Low protein diet

100
Q

What is amino acid conjugation enhanced by?

A

Glycine - legumes, seaweed, cauliflower, meat, fish, eggs
Taurine
Glutamine
Arginine

101
Q

What is Nrf2?

A

A transcription factor key to regulating the body’s detoxification and AO system

102
Q

What does Nrf2 do?

A

Increases endogenous AOs to protect against reactive intermediates
Promotes P2 pathways

103
Q

Which conditions is Nrf2 considered protective against?

A

Cancer
Kidney dysfunction
CV disease
Neurological disease

104
Q

Which foods regulate Nrf2 activity?

A

Phytonutrients - curcumin, broccoli, garlic, epicatechins, lycopene, resveratrol, isoflavones, rosemary, pomegranate, naringenin

105
Q

What is glutathione’s role in P1 and P2?

A

P1 - protects against reactive metabolites
P2 - essential compound for glutathione conjugation

106
Q

What are glutathione’s other roles apart from P1 and P2?

A

Mitochondrial protection
Bind and transports mercury out of cells and the brain across the BBB

107
Q

Which amino acid is essential for glutathione synthesis?

108
Q

Food sources of cysteine

A

Legumes
Eggs
Sunflower seeds

109
Q

Which conditions have low levels of glutathione be associated with?

A

AI
CV disease
Liver diseases
Pulmonary diseases
Neurodegenerative disease

110
Q

How can glutathione levels be increased?

A

Decrease depletion (by reducing oxidative stress)
Decrease toxic load
Optimise melatonin
Alpha lipoic acid
Milk thistle
NAC
Resveratrol
Cruciferous veg
Cordyceps

111
Q

What role does the GSTM1 gene have?

A

Responsible for the removal of xenobiotics, carcinogens and products of oxidative stress

112
Q

What can a SNP on the GSTM1 gene lead to?

A

Reduced capacity for liver detoxification (esp P2)

113
Q

How can a SNP on the GSTM1 gene be supported?

A

Minimise toxic load
Increase AOs (eat the rainbow)
Increase cruciferous veg (for the sulforaphane) and alliums
Milk thistle
NAC
Alpha lipoic acid
Se

114
Q

What happens during P3 detoxification?

A

Removal and excretion
Detoxified products are pumped into blood or bile for elimination

115
Q

What sort of proteins are involved in P3?

A

Antiporter

116
Q

How can P3 be induced?

A

Fasting
Good hydration

117
Q

How can fasting induce P3

A

Being in a lipolytic state allows toxins stored in fat cells to be mobilised and eliminated

118
Q

What can inhibit P3?

A

High doses of isolated phytonutrients
Curcumin
Epicatechins

119
Q

Which herbs can support bile production and flow?

A

Dandelion root
Globe artichoke
Burdock root (flow only)

120
Q

What 2 factors can influence the efficiency of excretion?

A

Diet
Microflora

121
Q

How can diet influence excretion?

A

Fibre binds conjugated xenobiotics
Decreases stool transit time
Reduces amount of deconjugating enzymes in the stool

122
Q

How can microflora influence excretion?

A

Dysbiosis can produce enzymes such as beta-glucuronidase that deconjugate P2 compounds and reduce elimination
Deconjugated xenobiotics re-enter the blood and are sent back to the liver for processing

123
Q

How does milk thistle protect the liver?

A

Strong AO properties
Protects liver from P1 metabolites

124
Q

Examples of conditions where milk thistle could be useful

A

High alcohol intake
Medications
Hepatitis

125
Q

Which medicinal mushrooms are hepatoprotective?

A

Shiitake
Maitake
Cordyceps

126
Q

What are the key genes for metabolising oestrogen?

A

CYP1A1
CYP1B1
COMT

127
Q

Why is the CYP1A1 gene important in oestrogen metabolism?

A

Converts oestrogen into 2OH oestrogens which are neutral or beneficial to the body

128
Q

Why is the CYP1B1 gene important in oestrogen metabolism?

A

Converts oestrogen into 4OH oestrogens
Can promote the synthesis of harmful molecules (quinones) which damage DNA and potentially initiate cancer

129
Q

Why is the COMT gene important in oestrogen metabolism?

A

Methylation of 2OH and 4OH before detoxification of these oestrogens occur

130
Q

Which detoxification pathways are involved in the elimination of oestrogen?

A

Sulphation
Glucuronidation

131
Q

SNPs on which genes increase the risk of hormone-related cancers?

132
Q

What happens when oestrogen enters the bowel?

A

Certain gut bacteria deconjugate it, allowing for recirculation via beta-glucuronidase enzymes

133
Q

What can raised beta-glucuronidase be due to?

A

Overgrowth of bacteria e.g. E. coli, Clostridium perfringens

134
Q

How can raised beta-glucuronidase due to bacterial overgrowth be supported?

A

Mung bean sprouts
Orange peel (infused tea)
Apples
Broccoli
Calcium D-glucarate

135
Q

Food sources to optimise oestrogen metabolism

A

Cruciferous veg
Broccoli sprouts (I3C content)
Fibre
Fruit/veg
Water

136
Q

What should be avoided to optimise oestrogen metabolism?

A

Dairy
Excess alcohol/caffeine
Water from plastic bottles
Anti-perspirants
Hormonal contraceptives
Non-organic meat/eggs

137
Q

In what ways can bowel elimination be supported?

A

Hydration
Fibre
Mucilaginous foods
Eradicate pathogens
Repopulate microflora
Support intestinal mucosa

138
Q

How do the kidneys play a role in elimination?

A

Filters undesirable products such as:
Uric acid
Creatinine
Hormone metabolites
P2 metabolites

139
Q

In what ways can kidney elimination be supported?

A

Stop drugs that damage the kidneys e.g. NSAIDs, paracetamol
Avoid table salt
Avoid high animal protein intake
Increase water intake
Address GI dysbiosis

140
Q

Which herbs can be used to support kidney elimination?

A

Celery seed
Dandelion root
Nettle

141
Q

How can beetroot juice support kidney elimination?

A

Vasodilation
Improved microcirculation

142
Q

How can blueberries support kidney elimination?

A

Protects kidneys from gut-derived endotoxins

143
Q

How can skin elimination be supported?

A

Avoid toxins on the skins
Saunas - vasodilation/increased perspiration
Epsom salt baths - to open pores and draw out wastes
Burdock root - reconditions the skin

144
Q

How can lymphatic elimination be supported?

A

Exercise/movement
Dry skin brushing
Massage
Abdominal breathing

Nutrition 2 (Semester I) (15 decks)

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