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

2b. Detoxification Flashcards

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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
What conditions can poor arsenic detoxification/elimination be associated with?
T2D Gout Cancer Peripheral neuropathy
26
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
27
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
28
Methods of testing for toxins
Hair analysis - toxins Urine - heavy metals Blood - heavy metals Stool analysis Genetic profiling
29
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
30
What are the 3 main groups of AOs?
AO enzymes Chain breaking AOs (enhances stability of oxidation) Transition metal-binding proteins
31
Examples of AO enzymes
Superoxide dismutase (SOD) Catalase Glutathione peroxidase Glutathione reductase
32
What do superoxide dismutase enzymes do?
Convert superoxide to hydrogen peroxide (hydrogen peroxide is then detoxified by catalase or glutathione peroxidase)
33
Nutrients needed for superoxide dismutase enzymes to work
Zn Cu Mn
34
What do catalase enzymes and glutathione peroxidase do?
Convert hydrogen peroxide to H2O and O2
35
Nutrient needed for catalase enzymes to work
Fe
36
Nutrient needed for glutathione peroxidase enzymes to work
Se
37
What do glutathione reductase enzymes do?
Regenerates glutathione that has been oxidised
38
Nutrient needed for glutathione reductase enzymes to work
B3
39
Examples of chain-breaking AOs
C E Flavonoids Carotenoids
40
Food sources of vit E
Sunflower seeds Almonds OO Avocado Sweet potato
41
Food sources of flavonoids
Quercetin - red apples, red onion Anthocyanins - red grapes Catechins - green tea Kaempferol - kale, spinach
42
Food sources of carotenoids
Yellow, orange, red fruits and veg Green veg
43
Example of transition metal AOs
Metallothionein (MT)
44
What do metallothioneins do?
Bind to essential and toxic heavy metals Reduce oxidative stress
45
Nutrients needed for metallothionein AOs
Cysteine (legumes, sunflower seeds, eggs, chicken) Zn Cu Se
46
What is P0 of detoxification?
Entry of the toxin into the cell Exit of the unmetabolised toxin from storage inside cells e.g. adipocytes
47
How do fat soluble toxins leave the cell?
Via diffusion
48
How do water soluble toxins leave the cell?
Via a transporter
49
Examples of water soluble toxin transporters
Solute carriers ATP binding cassette carriers
50
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
51
How many CYP450 enzymes are there?
50 - 100
52
Does each CYP450 enzyme detoxify a specific compound or are they broad?
Specifity
53
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
54
What can increase P1 activity?
Toxic load through: Smoking Alcohol Caffeine Chargrilled food
55
Why must the progression of P1 to P2 happen quickly?
To minimise the damaging effects of intermediary products
56
What can affect an individual's ability to metabolise toxins in P1?
SNPs Diet Availability of nutrient co-factors
57
Why will P2 be slowed down if P1 is upregulated?
Due to overwhelm Lack of dietary co-factors
58
How to support P1 detoxification
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
Dietary co-factors to support P1 detoxification
B vits (action of CYP450 enzymes BCAAs - leucine, isoleucine, valine
60
Food sources of B vits
Whole grains Legumes Mushrooms Sunflower seeds Eggs Fish
61
Food sources of leucine, isoleucine and valine
Quinoa Fish Eggs Meat
62
What do SNPs on genes have the potential to do during detoxification?
Increase toxicity by speeding up conversion of compounds to reactive intermediary products Cause an accumulation of unmetabolised toxins
63
What do CYP1A2 enzymes metabolise?
Caffeine
64
What impact does a SNP on CYP1A2 have on caffeine metabolism?
Slows it down
65
What do CYP1A1 enzymes do?
Deactivate oestrogen Detoxifies PAHs and solvents
66
What impact does a SNP on CYP1A1 have?
Increases risk of oestrogen dominance PAHs damage DNA - increasing cancer risk
67
How can a SNP on CYP1A1 be supported?
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
What happens during P2 detoxification?
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
What are the 6 pathways of P2 detoxification?
Glucuronidation Sulphation Glutathione conjugation Amino acid conjugation Acethylation Methylation
70
What enzyme is involved in glucuronidation?
UDP-glucuronosyltransferases
71
What happens during glucuronidation?
Glucuronic acid is added to the P1 metabolite
72
Food sources of glucuronic acid
Apples Broccoli Alfalfa
73
What are detoxified during glucuronidation?
Oestrogens NSAIDs Morphine
74
What is glucuronidation inhibited by?
Aspirin Smoking OCP Fluoride
75
Foods to support glucuronidation
Citrus peel Brassica veg Turmeric
76
What enzyme is involved in sulphation?
SULT
77
What happens during sulphation?
Sulphate is added to the P1 metabolite
78
Food sources of sulphur
Brassicas Onion Garlic Cruciferous
79
What are detoxified during sulphation?
Steroid hormones Food additives Industrial chemicals
80
What is sulphation inhibited by?
NSAIDs Tartrazine
81
What enzyme is involved in acetylation?
NAT
82
What happens during acetylation?
An acetyl group is added to the P1 metabolite
83
What are detoxified during acetylation?
Smoke Histamine
84
What is acetylation inhibited by?
B and C deficiency
85
What is acetylation enhanced by?
B1, 5 C Butyric acid
86
What enzymes are involved in methylation?
COMT PEMT (ones ending in MT)
87
What happens during methylation?
A methyl group is added to the P1 metabolite
88
What are detoxified during methylation?
Steroid hormones Dopamine Adrenaline Arsenic
89
What inhibits methylation?
B12 deficiency B9 (folate) deficiency High sucrose diet
90
Which nutrients enhance methylation?
Methionine Betaine Choline B2, 6, 9, 12 Folate Mg
91
What enzyme is involved in glutathione conjugation?
GST
92
What happens during glutathione conjugation?
Reactive P1 metabolises are reacted with glutathione
93
What is detoxified during glutathione conjugation?
Xenobiotics Paracetamol Heavy metals
94
What is glutathione conjugation inhibited by?
Deficiencies in: Se B6 Zn Glutathione
95
What enhances glutathione conjugation?
Brassicas Turmeric Citrus peel Alpha lipoic acid
96
What enzyme is involved in amino acid conjugation?
Amino acid transferases
97
What happens during amino acid conjugation?
An amino acid (mostly glycine) is added to the P1 metabolite
98
What is detoxified during amino acid conjugation?
Xenobiotics Drugs
99
What is amino acid conjugation inhibited by?
Low protein diet
100
What is amino acid conjugation enhanced by?
Glycine - legumes, seaweed, cauliflower, meat, fish, eggs Taurine Glutamine Arginine
101
What is Nrf2?
A transcription factor key to regulating the body's detoxification and AO system
102
What does Nrf2 do?
Increases endogenous AOs to protect against reactive intermediates Promotes P2 pathways
103
Which conditions is Nrf2 considered protective against?
Cancer Kidney dysfunction CV disease Neurological disease
104
Which foods regulate Nrf2 activity?
Phytonutrients - curcumin, broccoli, garlic, epicatechins, lycopene, resveratrol, isoflavones, rosemary, pomegranate, naringenin
105
What is glutathione's role in P1 and P2?
P1 - protects against reactive metabolites P2 - essential compound for glutathione conjugation
106
What are glutathione's other roles apart from P1 and P2?
Mitochondrial protection Bind and transports mercury out of cells and the brain across the BBB
107
Which amino acid is essential for glutathione synthesis?
Cysteine
108
Food sources of cysteine
Legumes Eggs Sunflower seeds
109
Which conditions have low levels of glutathione be associated with?
AI CV disease Liver diseases Pulmonary diseases Neurodegenerative disease
110
How can glutathione levels be increased?
Decrease depletion (by reducing oxidative stress) Decrease toxic load Optimise melatonin Alpha lipoic acid Milk thistle NAC Resveratrol Cruciferous veg Cordyceps
111
What role does the GSTM1 gene have?
Responsible for the removal of xenobiotics, carcinogens and products of oxidative stress
112
What can a SNP on the GSTM1 gene lead to?
Reduced capacity for liver detoxification (esp P2)
113
How can a SNP on the GSTM1 gene be supported?
Minimise toxic load Increase AOs (eat the rainbow) Increase cruciferous veg (for the sulforaphane) and alliums Milk thistle NAC Alpha lipoic acid Se
114
What happens during P3 detoxification?
Removal and excretion Detoxified products are pumped into blood or bile for elimination
115
What sort of proteins are involved in P3?
Antiporter
116
How can P3 be induced?
Fasting Good hydration
117
How can fasting induce P3
Being in a lipolytic state allows toxins stored in fat cells to be mobilised and eliminated
118
What can inhibit P3?
High doses of isolated phytonutrients Curcumin Epicatechins
119
Which herbs can support bile production and flow?
Dandelion root Globe artichoke Burdock root (flow only)
120
What 2 factors can influence the efficiency of excretion?
Diet Microflora
121
How can diet influence excretion?
Fibre binds conjugated xenobiotics Decreases stool transit time Reduces amount of deconjugating enzymes in the stool
122
How can microflora influence excretion?
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
How does milk thistle protect the liver?
Strong AO properties Protects liver from P1 metabolites
124
Examples of conditions where milk thistle could be useful
High alcohol intake Medications Hepatitis
125
Which medicinal mushrooms are hepatoprotective?
Shiitake Maitake Cordyceps
126
What are the key genes for metabolising oestrogen?
CYP1A1 CYP1B1 COMT
127
Why is the CYP1A1 gene important in oestrogen metabolism?
Converts oestrogen into 2OH oestrogens which are neutral or beneficial to the body
128
Why is the CYP1B1 gene important in oestrogen metabolism?
Converts oestrogen into 4OH oestrogens Can promote the synthesis of harmful molecules (quinones) which damage DNA and potentially initiate cancer
129
Why is the COMT gene important in oestrogen metabolism?
Methylation of 2OH and 4OH before detoxification of these oestrogens occur
130
Which detoxification pathways are involved in the elimination of oestrogen?
Sulphation Glucuronidation
131
SNPs on which genes increase the risk of hormone-related cancers?
SULT UGT
132
What happens when oestrogen enters the bowel?
Certain gut bacteria deconjugate it, allowing for recirculation via beta-glucuronidase enzymes
133
What can raised beta-glucuronidase be due to?
Overgrowth of bacteria e.g. E. coli, Clostridium perfringens
134
How can raised beta-glucuronidase due to bacterial overgrowth be supported?
Mung bean sprouts Orange peel (infused tea) Apples Broccoli Calcium D-glucarate
135
Food sources to optimise oestrogen metabolism
Cruciferous veg Broccoli sprouts (I3C content) Fibre Fruit/veg Water
136
What should be avoided to optimise oestrogen metabolism?
Dairy Excess alcohol/caffeine Water from plastic bottles Anti-perspirants Hormonal contraceptives Non-organic meat/eggs
137
In what ways can bowel elimination be supported?
Hydration Fibre Mucilaginous foods Eradicate pathogens Repopulate microflora Support intestinal mucosa
138
How do the kidneys play a role in elimination?
Filters undesirable products such as: Uric acid Creatinine Hormone metabolites P2 metabolites
139
In what ways can kidney elimination be supported?
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
Which herbs can be used to support kidney elimination?
Celery seed Dandelion root Nettle
141
How can beetroot juice support kidney elimination?
Vasodilation Improved microcirculation
142
How can blueberries support kidney elimination?
Protects kidneys from gut-derived endotoxins
143
How can skin elimination be supported?
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
How can lymphatic elimination be supported?
Exercise/movement Dry skin brushing Massage Abdominal breathing

Nutrition 2 (Semester I) (15 decks)

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