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nut 2 sem 1 > Detoxification and Nutrigenomics > Flashcards

Detoxification and Nutrigenomics Flashcards

1
Q

What is the study of the interaction between nutrition and genes in the prevention of treatment of disease

A

Nutrigenomics

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2
Q

What is made up of DNA and a physical unit?

A

A gene

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3
Q

What is an inherited characteristic such as shyness?

A

A trait

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4
Q

What is a variant form of a gene (e.g. eye colour)?

A

Allele

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5
Q

What is a Phenotype?

A

How genetic and environmental influences come together to create physical appearance and behaviour.

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6
Q

What is the study of genes?

A

Geonomics

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7
Q

What are the four nucleotide bases?

A

Adenine, Cytosine, Thymine, Guanine

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8
Q

What is methionine required for?

A

Methylation, which is needed to switch genes on and off.

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9
Q

What do ‘codons’ make up?

A

Genes, relating to specific functions

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10
Q

SNPs with 1 variant, meaning ‘some changes’ are called?

A

Heterozygous

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11
Q

SNPs with variants in both chromosomes, meaning there is a increase in function are called?

A

Homozygous

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12
Q

What is Gene BC01?

A

Codes for enzyme that converts beta-carotene to retinol.
Increase liver and fish oil supplements

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13
Q

What is Gene VDR?

A

Codes for Vit D receptor.
Optimal Vit D, sun exposure, mushrooms, oily fish, eggs

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14
Q

What is Gene TNF?

A

Codes for prod. of pro-inflammatory cytokines (protein)
Decrease pro-inflam foods and increase anti-inflam (green tea, SMASH, flax, avo, berries)

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15
Q

What is genetic information useful for?

A

Methylation (prod. of glutathione/homocysteine regulation)
Detoxification (the phases 0-3)
Neurotransmitters (Hormone synthesis / Metabolism)
Vit conversion/receptor function

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16
Q

What is methylation?

A

Process of adding a methyl group (CH3) to a substrate.
Involved in almost every metabolic process in the body.

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17
Q

What does methylation contribute to?

A
  1. Gene regulation (turning genes on and off)
  2. RNA/DNA synthesis (growth/repair)
  3. Detoxification (hormones such as oestrogen)
  4. Energy prod. (CoQ10/ATP)
  5. Myelination and neurotransmitter prod. (dopa/sero to melatonin)
  6. Immune function (immune cell synthesis)
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18
Q

What are the dietary co-factors for methylation?

A

Folate
B12
B6
B2
Choline
Betaine (TMG)
Zinc

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19
Q

How is SAMe formed?

A

Form the AA Methionine

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20
Q

What is the system that produces SAMe reliant on?

A

The active form of folate - methylfolate.

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21
Q

What disrupts methylation?

A
  1. Insufficient substrates (folate and methionine)
  2. Lack of essential cofactors (B12, B2, B6, Zinc)
  3. SNPs affecting enzyme activity
  4. Drugs (OCP/Metformin decrease B-vits)
  5. Toxin Exposure
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22
Q

What does impaired methylation cause?

A

CVD
Cancer
Infertility
CFS
Neurological diseases

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23
Q

How do you assess for poor methylation?

A

Genetics testing (Methylation SNP)
Homocysteine testing (If methylation is poor, homocysteine levels will be high.

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24
Q

Which cycle is MTHFR part of?

A

Folate Cycle

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25
Q

What does MTHFR code for?

A

Codes the enzyme converting folate into a methylated form

Dietary recommendations for this SNP:
- Optimise dietary folate
- Consider methylated folate supp
- Optimise B2

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26
Q

Which cycle is MTR / MTRR part of?

A

Methionine Cycle

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27
Q

What does MTR / MTRR code for?

A

Codes for the enzyme methionine synthesis which increases the conversion of homocysteine to methionine.

Dietary recommendations for this SNP:
Vitamin B12 and folate foods (co-factors in the conversion of homo to methionine.

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28
Q

What is transsulphuration?

A

Another output route for homocysteine that provides a substrate for glutathione synthesis and the key phase 2 detoxification processes of sulphation and glutathione conjugation.

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29
Q

Which cycle is CBS part of?

A

Transsulfuration Cycle

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30
Q

What does CBS code for?

A

It converts homocysteine to cystathionine which means less homo converted and potential decrease in SAMe. With faster conversion to ammonia putting pressure on urea cycle and increasing the need for more glutathione.

Dietary recommendations for this SNP:
Zinc, choline, TMG (beetroot), decrease animal protein).

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31
Q

Which cycle is eNOS part of?

A

The urea cycle

32
Q

What does eNOS code for?

A

It is responsible for generating nitric oxide from arginine, playing a role in vasodilation.

Dietary recommendations for this SNP:
Increase antioxidants
Moderate intake of animal protein (ammonia gathering)
Support NO prod. with L-arginine and beetroot juice.

33
Q

What is the process of transforming fat soluble toxins and xenobiotics into water-soluble compounds that can be eliminated via urine or bile?

A

Detoxification

34
Q

Where does detoxification take place?

A

Hepatocytes

35
Q

How can we support detoxification

A

Minimise toxic load
Support elimination pathways
Support detox pathways

36
Q

What is a toxin?

A

A poison produced in organisms that is active at low concentrations
An agent that disturbs the physiology and can be harmful to the body
Foreign substances found in the body that are not derived from diet or produced endogenously.

37
Q

What are endogenous toxins?

A
  1. GI Microbes
    Toxic compounds (alcohol) released from undesirable bacteria/fungi
    Fragments of dysbiotic bacteria (LPS), entering bloodstream causing immune reactions
  2. Waste products from normal metabolic processes (e.g. urea not properly metabolised in liver)
  3. Poorly detoxed/eliminated hormones
38
Q

Name 6 endogenous chemical toxins

A

Bisphenols (BPA) linked to T2DB
Pesticides linked to Alzheimer’s
Phthalates (beauty) linked to T2DB
Aluminium linked to Alzheimer’s
Mercury linked to CFS
Arsenic linked to T2DB

39
Q

What are 10 symptoms of sluggish liver detoxification?

A
  1. Poor appetite and fatigue
  2. Nausea in AM
  3. Gallstones
  4. Difficulty digesting fatty foods
  5. Pale, fatty stools that float
  6. Intolerance to alcohol
  7. Waking between 1 - 3am
  8. Dark circles under eyes
  9. Thick yellow coating of tongue
  10. Body odour.
40
Q

How can you test for detoxification effectiveness?

A

Hair analysis (toxic elements)
Urine (heavy metals)
Blood (metals)
Stool
Genetics

41
Q

How to antioxidants support detoxification?

A

By converting free radicals / ROS to stable, non-toxic molecules

42
Q

What are the three groups of antioxidants?

A
  1. Antioxidant enzymes
  2. Chain-breaking antioxidants
  3. Transition metal-binding proteins
43
Q

Describe Group 1 - Antioxidant Enzymes

A

We produce these

a. SOD: Covers superoxide to hydrogen peroxide which is detoxed by catalase (NUTS: Z, Cp, Mang)

b. CATALASE: Converts hydrogen peroxide to H2O / O2 (NUTS: Fe)

c. GLUTATHIONE PEROXIDASE: Same as catalase (NUTS: Selenium)

d. GLUTATHIONE REDUCTASE: Regenerates glutathione (NUTS: B3)

44
Q

Describe Group 2 - Chain Breaking Antioxidants

A

a. Vit E (sunflower seeds, almonds, olive oil
b. Vit C (peppers, kiwi, berries, citrus)
c. Flavonoids (Quercetin - red onion, apples)
d. Carotenoids (yellow/orange fruit and veg.

45
Q

Describe Group 3 - Transition Metal Binding Proteins

A

MT - cysteine rich proteins that bind to heavy metals (eggs, chicken, legumes)

46
Q

What is Detoxification Phase Zero?

A

The entry of a toxin into a cell or exit of unmetabolized toxin from storage inside the cell (adipocyte)

  • Fat soluble toxins diffuse through the cell membrane
  • Water soluble toxins need to access or leave the cell through a transporter (SLC or ATP binding cassette carriers)
47
Q

What is Detoxification Phase 1?

A

Involves transformation enzymes known as CYP450 enzymes in the liver

Most toxins that arrive in the hepatocytes are lipophilic so have to go via PH1

The CYP450 + toxin/hormone reaction creates and active binding site on the toxin making them water soluble and more reactive in order to conjugate in P2

CYP450 involves 50-100 enzymes this means the liver can accommodate a wide range of chemical exposure.

Many enzymes are produced in response to increased exposure to a toxin by producing more of the enzyme that degrades it. This can happen at the expense of other toxin transformation biotransformation.

Induction of p1 enzymes without co-induction of p2 can increase reactive intermediaries = more oxidative stress.

Progression from P1 - 2 must happen quickly to minimise damaging effects of intermediary products.

SNPs, diet and nut co-factors can influence the ability to metabolise toxins

P2 enzymes are less flexible that P1

P1 will be upregulated due to toxic load, whilst P2 will be slow due to overwhelm from P1 or lack of cofactors.

48
Q

How can you support P1 Detoxification?

A

Reduce the toxic load to slow P1
Organic to minimize intake of pesticides
Minimise xenobiotics in toiletries
Stop smoking and avoid caffeine
Avoid chargrilled / smoked food
Reduce booze
Avoid unnecessary meds
Avoid plastics with food.

Up B-Complex vits (alcohol depleted Bs)
B-rich food: whole grains, legumes, mushrooms, sunflower seeds, wild fish, eggs

Up BCAAs: quinoa, fish and eggs

49
Q

Name 5 P1 SNPS

A
  1. CYP2E1: Alcohol
  2. CYP1A2: Caffeine (slow caffeine metabolizer)
  3. CYP2C9: Warfarin
  4. CYP19A1: Testosterone
  5. CYP 1A1: Oestrogen deactivation (Increases risk of oest.dominance. Avoid chargrilled, go plant-based (green teas/berries) and sulphur rich foods
50
Q

What is Phase 2 Detoxification?

A

A variety of chemical reactions which add functional groups to reactive toxins to make them safe to be released into the blood or bile for excretion via kidneys or bowel.

There are 6 pathways all dependant on substrates to carry out their function. AAs are important.

51
Q

Name the 6 pathways

A
  1. Glucuronidation
  2. Sulphation
  3. Glutathione Conjugation
  4. Amino Acid Conjugation
  5. Acetylation
  6. Methylation
52
Q

Describe Glucuronidation

A
  • Glucuronic acid is added to the P1 metabolite
  • It detoxifies osetrogen, NSAIDS
  • It is inhibited by aspirin, smoking, OCP
  • Required Glucuronic acid (apples/broccoli)
  • Enhanced by citrus peel, brassica veg
53
Q

Describe Sulphation

A
  • Sulphate is added to P1 metabolite
  • It detoxifies steroid hormones (oestrogen)/food additives
  • Inhibited by NSAIDS
  • Requires sulphur containing AAs (cysteine and methionine) (Brassica veg: onion, garlic)
54
Q

Describe Acetylation

A
  • An acetyl group is added to P1 metabolite
  • It detoxifies smoke
  • Inhibited by Vit B & C Deficiency
  • Enhanced by B1, 5, Vit C, Butyric acid (SCFA)
55
Q

Describe Methylation

A
  • A methyl group is added to P1 metabolite
  • It detoxifies steroid hormones inc. oestrogen/dopa/adrenaline
  • Inhibited by B12, folate def.
  • Enhanced by methionine, betaine, choline, B2, 6, 12, folate & Mg
56
Q

Describe AA Conjugation

A
  • An AA is added to P1 metabolite
  • It detoxifies xenobiotics / drugs (Aspirin/statin)
  • Inhibited by low protein diet
  • Enhanced by Glycine (legumes), taurine, glutamine and arginine.
57
Q

Describe Glutathione Conjugation

A
  • Reactive P1 metabolites are reacted with glutathione
  • It detoxifies xenobiotics, paracetamol, heavy metals
    It requires glycine, glutamine and cysteine for formation of glutathione
    Inhibited by Sel, B6, Zinc, Glutathione deficincies
    Enhanced by brassica veg (broccoli sprouts), turmeric and citrus peel.
58
Q

What is Nrf2?

A

Increasing the gene expression Nrf2 supports P2

The transcription factor Nrf2 is key to regulating the body’s detoxification and antioxidant system

Nrf2 increased endogenous antioxidants to protect reactive intermediaries and promote P2 pathways

Nrf2 is protective against oxidative stress conditions (CVD/Cancer)

59
Q

How do phytonutrients support P2

A

They scavenge ROS and regulate Nrf2 activity

60
Q

Which foods can regulate Nrf2 activity?

A
  1. Curcumin
  2. Broccoli
  3. Garlic
  4. Green Tea
  5. Lycopenes - tomatoes
  6. Resveratrol - red grapes
61
Q

Describe Glutathione

A

It is a crucial antioxidant that protects against reactive metabolites from P1 and is essential for glutathione conjugation in P2

62
Q

Which AA is rate-limiting for glutathione sysnthese?

A

Cysteine (sources legumes, sunflower seeds, eggs)

63
Q

What is critical to mitochondria protection?

A

Glutathione

64
Q

What are low levels of glutathione linked to?

A

Neurodegenerative diseases
Autoimmunity
CVD
Liver diseases

65
Q

What binds and transports mercury out of cells and out of the brain across the BBB?

A

Glutathione!

66
Q

How can you increase glutathione levels?

A

Decrease depletion - decrease oxidative stress
Decrease toxic load
Optimise melatonin (i.e. sleep hygiene)
Increase B6
Milk Thistle
NAC
Resveratrol (red grapes)
Cruciferous Veg

67
Q

Name a P2 SNP

A

Glutathione GSTM1

68
Q

What does GSTM1 do?

A

Most active member of the GST family and is responsible for the removal of xenobiotics, carcinogens and products of oxidative stress.

An absent gene is common, resulting in reduced capacity for liver detox.

Dietary intake for the SNP
Reduce toxic load
Increase antioxidants
Increase cruciferous veg (for the sulphur) and alliums
Milk thistle, NAC, ALA, Selenium.

69
Q

What is P3 Detoxification?

A

The removal and excretion phase where detoxified products are pumped into blood or bile for elimination.

To induce P3 - fasting: being in a lipolytic state allows toxins stored in fat cells to be mobilized and eliminated.

70
Q

How do you support P3?

A

Turmeric and Green Tea, however curcumin and epicatechins inhibit P3!!!
Good hydration
Bile flow prod. support (globe artichoke/dandelion root)

71
Q

What is efficiency of excretion dependent on?

A

Diet - fibre binds conjugated xenobiotics, decreases stool transit time and reduces the amount of deconjugating enzymes in stools.
Microbiota - dysbiosis - undesirable bacteria can produce enzymes such as BETA GLUCURONIDASE that deconjugate P2 compounds, reducing elimination.
Deconjugated xenobiotics re-enter the blood and are sent back to the liver for processes.

72
Q

What is good hepatoprotection?

A

Milk Thistle: Strong antioxidant properties and protects liver from P1 metabolites

Mycotherapy: Shiitake/Maitake

73
Q

Oestrogen Metabolism: - Name three key oestrogen liver genes

A
  1. CYP1A1
    Crucial because it converts oestrogens into 2OH, which are neutral and beneficial to the body.
  2. CYP1B1
    Converts oestrogens to 4OH oestrogens and can promote the synthesis of harmful molecules called quinones, which damage DNA and can initiate cancer.
  3. COMT
    Involved in methylation of 2OH and 4OH before detoxification of the oestrogens occurs.
74
Q

How is oestrogen eliminated?

A

Oestrogens are then detoxified by sulfation and glucuronidation.

Oestrogen enters the bowel (in bile), where certain gut bacteria deconjugate it, allowing it recirculation via beta-glucuronidase enzymes. (Excess activity can lead to increased levels)

Raised BC is often due to overgrowth of bacterial such as E.Coli

Dietary recommendations for these SNPS:
Increase glucuronic acid-rich foods (orange peel, apple, broccoli)
Increase cruciferous veg (broccoli sprouts)
Increase fibre (elimination) and filtered water
Avoid dairy, excess alcohol and caffeine, non organic foods, plastic, antiperspirants and contraceptives

Address dysbiosis (weed, feed, seed)

75
Q

How can we optimise elimination?

A
  1. Remove anything damaging GIT (Alcohol/NSAIDS)
  2. Ensure good hydration
  3. Eat foods rich in mucilage (chia)
  4. Maximise fibre (soluble) to aid transit through GIT, increase stool bulk and provide prebiotics.
  5. Eradicate pathogens/SIBO
  6. Repopulate with pres (kefir) and pros (garlic)
  7. Support intestinal mucosa (quercetin (bone broth), NAC, slippery elm.
76
Q

How do we support kidney function?

A

They filter uric acid, creatine, hormone metabolites and P2 metabolites

  1. Stop drugs (NSAIDS)
  2. Avoid table salt and animal protein - they increase metabolic load
  3. Filtered water
  4. Address dysbiosis and intestinal permeability due to impact of circulating endotoxemia on kidneys
  5. Use dandelion leaf (alkalising, helps kidneys release toxins)
  6. Beetroot juice (improved vasodilation and microcirculation)
  7. Blueberries protect kidneys from gut-derived endotoxins.

nut 2 sem 1 (8 decks)

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