2. NUTRIGENOMICS & METABOLIC DETOXIFICATION Flashcards

This module covers: • Nutrigenomics. • Methylation. • Toxins • Liver detoxification: Phase I, II, III. • Oestrogen metabolism. • Optimising elimination. • Detoxification in clinical practice.

1
Q

Define genomics

A

Genomics is the study of genes. Determines how they interact and influence biological pathways, networks, and physiology.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Define nutrigenomics

A

Nutrigenomics is the study of the interaction of nutrition and genes, especially with regard to the prevention or treatment of disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the benefits of genetic testing in practice?

A

As a nutritional therapist, you can test for key inherited genetic differences that affect how well certain aspects of physiology work.
This can be used to formulate personalised nutrition and lifestyle plans to optimise health.
Genetic information used properly can be empowering in terms of understanding potential strengths and weaknesses.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the difference between a gene, a trait and an allele?

A

Gene - a sequence of DNA coding for a protein, our physical unit of heredity.
Trait - an inherited characteristic such as shyness.
Allele - a variant form of a gene responsible for the variation in which a trait can be expressed, e.g., eye colour.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is a phenotype?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is DNA and its structure?

A

Every cell nucleus contains 23 pairs of chromosomes, made up of DNA (or deoxyribonucleic acid).

DNA contains our genetic information and is made of two paired ‘nucleotide’ chains (the ‘double helix’).

DNA is ‘transcribed ‘into RNA which is translated into a protein from amino acids. This process determines the property, function and shape of the resulting protein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the structure of a nucleotide?

A

Each nucleotide contains a:
1. deoxyribose (sugar)
2. a phosphate group
3. and one of four bases:
- A (adenine)
- C (cytosine)
- T (thymine)
- G (guanine).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are codons? Give an example of what can happen if the translation is not coded correctly.

A

Nucleotides are organised into codons – a sequence of 3 nucleotides that ’code for’ a specific amino acid. Codons make up ’genes’, which relate to specific functions.

The codon ‘AUG’ codes for the amino acid methionine. However, if the translation is not coded correctly (e.g., to ‘AUC’) because of an inherited alteration in the DNA sequence, isoleucine is produced instead.
Methionine is required for methylation, which is needed for switching genes on and off. Low methionine increases the risk of cancerous cell changes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are single nucleotide polymorphisms (SNPs)?
Are all SNPs problematic?

A

SNPs are differences in single bases in the sequence of a gene (a genetic variation in humans).

SNPs are a normal occurrence. Many SNPs have very little effect.
Some SNPs can change enzyme or protein function leading to differences in phenotype.

Example: A SNP on genes for oestrogen metabolism can result in oestrogen dominance and increase the risk of breast cancer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How are SNPs classified?

A

Each gene is identified by an rs (‘reference SNP’) number. e.g., rs1801133 is the MTHFR gene.

Each SNP is further classified, by base change and position along from start of the gene e.g., rs1801133 C677T. C represents cytosine, changed to T (thymine) - potentially changing the resulting amino acid and insufficient conversion of folate into methylfolate.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Define chromosomal variants (wild, heterozygous, homozygous).

A

wild type - usually ‘normal / stable’
heterozygous - 1 chromosomal variant, usually indicating some potential change of function
homozygous - variants in both chromosomes, with greater change of function.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What would you recommend to a client with the ‘SLC23A1’ gene SNP?

A

The ‘SLC23A1’ gene codes for the production of a transporter which supports vitamin C absorption and distribution in the body. A SNP of this gene is associated with a higher demand for vitamin C.

Optimise dietary intake (e.g., with fresh raw fruit and vegetables, esp. peppers, kiwi fruit, papaya, currants, berries, citrus, tomatoes, crucifers) and consider supplementation.

Consider:
- the vitamin C SNP could also impair iron absorption (reducing conversion from the Fe3+ to Fe2+ state).
- stress management (stress increases vitamin C release into the blood).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Name areas where genetic information is especially useful for clinic.

A
  • Methylation (e.g., production of glutathione and homocysteine regulation).
  • Detoxification (each phase and the genes involved. e.g., caffeine / alcohol detoxification).
  • Neurotransmitter / hormone synthesis and metabolism (e.g., in relation to conditions of oestrogen excess).
  • Vitamin conversion / receptor function (vitamin D conversion - effect on bone density risk, vitamin A - reduced conversion of beta-carotene to vitamin A).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

TRUE or FALSE
Genes are deterministic.

A

FALSE
Genes only tell us the potential for physiological differences.
Never treat by SNP or look at SNPs in isolation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How do SNPs affect the activity of the BCO1 gene? What would you recommend to a client with the BCO1 gene SNP?

A

Gene BCO1 gene (beta-carotene oxygenase 1) - codes for the enzyme that converts beta-carotene to retinol.
Many SNPs affect its activity:
‒ BCO1 A379V TT alleles (= 32% reduction in enzyme activity).
‒ BCO1 R267S AT or TT plus BCO1 A379V CT or TT variant alleles (= 69% lower beta-carotene conversion).

Vitamin A deficiency symptoms: Impaired night vision, frequent infections, skin conditions (e.g., acne).

Increase preformed vitamin A from food (e.g., liver, fish oils) or supplements, especially if plant-based.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do SNPs affect the activity of the VDR gene? What would be your recommendations to a client with the VDR gene SNP?

A

VDR gene - codes for the vitamin D receptor.
At rs1544410, the A allele is associated with reduced bone density risk while the G allele is associated with a decreased risk of osteoporosis.

Vitamin D deficiency symptoms: Rickets and osteomalacia, osteoporosis, immune dysfunction (↑ infections, autoimmunity, allergies, asthma).

Ensure optimal vitamin D levels with regular testing, sun exposure, food sources (e.g., mushrooms, oily fish, eggs) and supplementation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What do FADS 1 and FADS2
code for?

A

Fatty acid desaturases are involved in EFA conversion. FADS 1 codes for Delta 5 Desaturase and FADS2 Delta 6 Desaturase.

FADS1 rs174537 GG genotype may increase the conversion of high dietary omega-6 to inflammatory AA (more so in African Americans).
FADS2 rs174570 T allele is associated with lower GLA, AA, and EPA levels.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What would be your recommendations to a client with the TNF gene SNP?

A

The TNF gene codes for the production of the pro-inflammatory cytokine (protein).
At rs1800629 the A allele is associated with ↑ TNF and ↑ risk of asthma, RA, psoriasis and cancer.

‒ Extra focus on ↓ pro-inflammatory foods (e.g., sugar, dairy, fried foods, high omega-6 foods), processed meats, alcohol.
‒ Increase anti-inflammatory foods / herbs - turmeric, catechins (green tea), echinacea, omega-3 rich foods (‘SMASH’, flax).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is methylation and its functions in the body?

A

Process of adding a methyl group (CH3) to a substrate:
It is involved in almost every metabolic process in the body and contributes to crucial functions, including:
– Gene regulation (turning genes on and off)
– DNA RNA synthesis (e.g., growth, repair, cancer prevention).
– Detoxification (e.g., hormones such as oestrogen).
– Energy production (CoQ10, carnitine and ATP).
– Myelination and neurotransmitter production (e.g., dopamine and serotonin, melatonin).
– Immune function (e.g., immune cell synthesis, inflammation).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Name FIVE dietary co-factors for methylation.

A

Folate, B12, B6, B2, choline, betaine (TMG) and zinc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is SAMe and what nutrient(s) does it rely on?

A

The ‘methyl’ (CH3) group:
- CH3 is provided to the body by the methyl donor known as SAMe (S-adenosylmethionine).
- SAMe is formed from the amino acid methionine.
- The system that produces SAMe is reliant on the active form of folate - methylfolate and vitamin B12.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Name FIVE disruptors of methylation.

A
  • Insufficient substrates (folate, methionine).
  • Lack of essential co-factors (B2, B12, B6, zinc) / malabsorption.
  • SNPs affecting enzyme activity (involved in methylation).
  • Specific nutrients depleting methyl groups (niacin).
  • Drugs (e.g., contraceptive pill, metformin = ↓ B vits).
  • Increased demand on processes described previously e.g., stress, imbalanced hormones, inflammation, need for repair etc.
  • Toxin exposure - aflatoxin (fungi on crops), air pollution, BPA (e.g., food packaging), phthalates (e.g., beauty products), heavy metals etc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What conditions can impaired methylation contribute to?

A
  • Cardiovascular disease.
  • Cancer (e.g., breast cancer).
  • Infertility and unexplained miscarriages.
  • Chronic fatigue and mood disorders.
  • Neurological disease (e.g., MS, Alzheimer’s).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What testing helps to assess for indicators of poor methylation?

A
  • Genetic testing - for methylation SNPs.
  • Homocysteine testing - if methylation is poor, homocysteine levels generally rise. Ideal levels: 5–8 µmol /
  • L. SAMe / SAH ratio in some tests may be more accurate.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the key outputs / functions of the folate cycle?

A
  • DNA synthesis / repair
  • formation of 5-Methyltetrahydrofolate (5-MTHF).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the key outputs / functions of the methionine cycle?

A

Synthesis of SAMe - the master methyl donor. e.g. COMT (helps detoxify adrenaline and dopamine), PEMT (creates phosphatidylcholine for cell membranes), DNA methylation etc. Via recycling reduces homocysteine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Name the gene that codes for the enzyme responsible for converting folate into a methylated form in the folate cycle. What key SNP is associated with its reduced activity?

A

MTHFR codes for the enzyme ‘methylenetetrahydrofolate reductase’ - converting folate into a methylated form.

Key SNP: The C667T (cytosine replaced by thymine) SNP at rs1801133 is associated with reduced activity of MTHFR.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What recommendations can we make to support the folate cycle? What drug is a folate antagonist?

A

‒ Optimise dietary folate.
‒ Consider a methylated folate supplement.
‒ Optimise vitamin B2 (riboflavin) - supporting the MTHFR gene.

Folate antagonist: methotrexate (used for inflammation and cancer).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Name the two key genes in the methionine cycle. What is their role and how their SNPs can affect it?

A

MTR / MTRR = code for the enzyme methionine synthase (MS), which ↑ the conversion of homocysteine to methionine.

  • MTR SNP: The A allele of rs1805087 in the MTR gene is associated with decreased MS activity.
  • MTRR SNP: The A66G SNP at rs1801394 =
    ↓ conversion of vitamin B12 to its methylated form.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What recommendations can we make to support the methionine cycle?

A
  • Vitamin B12 and folate foods are co-factors in the conversion of homocysteine to methionine. Consider supplementation of their methylated forms.
  • Ensure no mercury / lead toxicity - these can hinder the process.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the transsulphuration cycle and its key outputs?

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.
Production of sulphite / ammonia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Name the role of CBS gene in transsulphuration.

A

The CBS gene provides instructions for making an enzyme called cystathionine beta-synthase. This enzyme is responsible for converting homocysteine to cystathionine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Cystathionine is used to produce cysteine in transsulfuration. Why do we need cysteine?

A

Cysteine can be used to
a) make sulphate needed for sulphation (detoxification),
b) increase glutathione levels.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Is having a lot of cystathionine a good thing? What can be the result of having too much cystathionine?

A

Moderation is important. High cystathionine levels can lead to overload in certain negative substances, like ammonia (toxic impact, pressure on urea cycle) or high sulphites. Mo is a co-factor in the conversion of sulphite to sulphate. If this conversion doesn’t happen it can lead to negative symptoms after consuming sulphur in the diet (e.g. red wine, allium vegetables, brassica vegetables) or supplements that contain sulphur (NAC, cysteine, MSM).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What SNP is associated with transsulphuration cycle?

A

C669T SNP at rs234706 ↑ CBS activity = less homocysteine converted and potential ↓ SAMe.
Faster conversion to ammonia (pressure on urea cycle) increasing the need for glutathione (maybe not enough synthesized, maybe not enough sulphation if the sulphur is getting stuck at the sulphite level).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are the key outputs / functions of the biopterin cycle?

A

Tetrahydrobiopterin (BH4) ia a crucial coenzyme involved in conversion of amino acids (e.g. tryptophan) to the neurotransmitters dopamine, serotonin and melatonin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the key outputs / functions of the urea cycle?

A

Conversion of ammonia to urea. AND arginine to the vasodilator nitric oxide (CV health).

38
Q

What recommendations can we make to support the transsulfuration cycle?

A
  • Increase zinc, choline and TMG (e.g., beetroot).
  • Neutralise the ammonia (↓ animal protein), probiotics to ↓ bacterial production, supplement activated charcoal.
  • Limit sulphur-containing foods, e.g., eggs.
39
Q

What is needed for the synthesis and breakdown of serotonin, dopamine, and adrenaline in the biopterin cycle?

A

MTHFR is essential for 5-MTHF, thus biopterin (BH4) and synthesis of serotonin, dopamine, adrenaline etc.

SAMe-dependent enzyme COMT breaks down dopamine, adrenaline and noradrenaline. COMT also converts active oestrogen to less active oestrogen.

40
Q

Some SNPs are associated with ↓ COMT activity. What would be the result of excessive catecholamines and their fast metabolism?

A

SNPs: rs4680 - the A allele is associated with ↓ COMT activity:
‒ AA = excessive catecholamines (dopamine, noradrenaline, and adrenaline) will heighten the stress response. Also associated with ↑ oestrogen (and hence breast cancer, etc.).
‒ GG = fast metabolism of catecholamines (feeling flat, depressed, unmotivated).

41
Q

How can we support the biopterin cycle and the production of neurotransmitters?

A
  • Choline, betaine, folate and B12-rich foods support the production of SAMe.
  • Avoid exogenous oestrogens (e.g., avoid plastic, antiperspirants, dairy products, etc.).
  • Manage stress
42
Q

What is eNOS and what role does it play in the urea cycle? What would be the outcome of ↓ eNOS activity?

A

eNOS = endothelium-derived nitric oxide synthase.
eNOS is responsible for generating nitric oxide from arginine, which plays a key role as a vasodilator.

  • SNPs: At rs1799983 the T allele is associated with ↓ eNOS activity and nitric oxide linked to slower ammonia detoxification, ↑ free radical levels and ↑ risk of cardiovascular disease.
43
Q

What recommendations can we make to support the eNOS process in the urea cycle?

A

– Increase antioxidants (‘rainbow of colour’).
– Moderate intake of ammonia-generating foods (↓ animal protein).
– Support NO production with L-arginine, citruline and beetroot juice.

44
Q

What is detoxification and how can we support it?

A

Detoxification - the process of transforming fat-soluble toxins and xenobiotics into water-soluble compounds that can be eliminated via the urine or bile; takes place primarily in hepatocytes (functional liver cells).

In clinic, to support detoxification:
– Minimise the toxic load.
– Support elimination pathways (before promoting liver detoxification).
– Support detoxification pathways.

45
Q

Give TWO examples of endogenous toxins and what conditions they are associated with.

A
  • GI microbes:
    Toxic compounds such as aldehydes, alcohols and indoles released from undesirable bacteria and fungi.
    Fragments of dysbiotic bacteria called lipopolysaccharides (endotoxins) can enter the bloodstream (esp. if ↑ intestinal permeability) causing excessive immune reactions.
  • Waste products from normal metabolic processes e.g., urea if not properly metabolised in the liver.
  • Poorly detoxified / eliminated hormones (e.g., chronic constipation → ↓ oestrogen elimination).
46
Q

Give THREE examples of exogenous chemical toxins and what conditions they are associated with.

A
  • Bisphenols: e.g., bisphenol A (BPA), tinned and plastic packaging → T2D, infertility, oestrogen disruption.
  • Pesticides and herbicides: e.g., glyphosate + OCPs. Chemically-grown food, water (contamination) → Alzheimer’s, infertility, erectile dysfunction, RA, SLE, cancer.
  • Phthalates: Plastic products, beauty products → infertility, T2D, allergies.
  • Polybrominated diphenyl ethers (PBDEs): flame retardants, farmed fish → IR, child behavioural problems.
  • Polycyclic aromatic hydrocarbons (PAHs): air pollution / vehicle exhaust (diesel = worst) → T2D, ADHD, Alzheimer’s, atopic conditions, COPD.
  • Solvents: e.g., benzene, toluene, styrene. Vehicle exhausts, smoking, foods → Alzheimer’s, infertility, MS, RA, ↑ autism risk.
47
Q

Give TWO examples of exogenous metal toxins and what conditions they are associated with.

A
  • Aluminium: foil (and food), antiperspirants, vaccines → mitochondrial damage, Alzheimer’s.
  • Mercury: Amalgams, fish (esp. larger fish), water, vaccines, air pollution → chronic fatigue, neurological damage, Hashimoto’s, ADHD, infertility, SLE.
  • Arsenic: water, rice, chicken, fish, smoking → T2D, cancer, gout, peripheral neuropathy. AS3MT SNPs - associated with ↑ toxic reactions (i.e., in those with ↓ arsenic exposure).
48
Q

Name TEN symptoms and signs of ‘sluggish’ liver detoxification.

A
  • Headaches
  • ↓ concentration and brain fog.
  • Mood changes.
  • Yellowing of the whites of eyes.
  • Dark circles under the eyes.
  • Halitosis and a bitter taste.
  • Tongue: Esp. thick coatings on
    the tongue, e.g., a yellow coat.
  • Poor appetite and fatigue.
  • Alcohol intolerance.
  • Nausea, esp. in the morning.
  • Difficulty digesting fatty foods.
  • Gallstones.
  • Pale, fatty stools that float.
  • Dry skin and itching.
  • Offensive body odour.
  • A feeling of overheating.
  • Waking between 1 and 3 am.
  • Hormone imbalances.
49
Q

What testing for detoxification is available?

A
  • Hair analysis of toxic elements.
  • Urine heavy metals (e.g. ‘GPL-TOX’ - screens for 172 environmental pollutants).
  • Blood metals panel.
  • Stool panel.
  • Genetic profiling e.g., LifeCode GX Detox Panel.
50
Q

What role do antioxidants play in detoxification? Name THREE main groups.

A

Antioxidants play a central role in detoxification by converting free radicals / ROS to stable, non-toxic molecules.

They can be divided into three main groups:
1. Antioxidant enzymes.
2. Chain-breaking antioxidants - the chain of ROS can be broken when a molecule can accept or donate an electron without needing to rectify its gain or loss.
3. Transition metal-binding proteins.

51
Q

Antioxidant enzymes.
Describe the process of how these antioxidants convert ROS to stable, non-toxic molecules. Include the names of key antioxidants involved in this process and the nutrients needed at each stage.

A

A group of enzymes superoxide dismutase (SOD) catalyses the dismutation of superoxide radicals (O2−) to molecular oxygen (O2) and hydrogen peroxide (H2O2), providing cellular defence against ROS. Zinc, copper, manganese.

Hydrogen peroxide must then be detoxified by catalase or glutathione peroxidase.

Catalase: Converts hydrogen peroxide to H2O and O2. Iron.

Glutathione peroxidase: Same as for catalase. Note: Mercury can suppress selenium activity in the body. Selenium.

Glutathione reductase: Regenerates glutathione that has been oxidised. Vitamin B3.

52
Q

Name THREE chain-breaking antioxidants and their food sources.

A

Vitamin E: Sunflower seeds, almonds, pine nuts, olive oil, avocado, sweet potato, spinach.

Vitamin C: Peppers, kiwi fruit, papaya, currants, berries, citrus, crucifers, mangoes, tomatoes.

Flavonoids: e.g., quercetin (red onions, apples), anthocyanins (red grapes), catechins (green tea), kaempferol (kale, spinach).

Carotenoids: Yellow, orange, and red fruits and vegetables. Green vegetables.

53
Q

What are transition metal binding proteins and what nutrients they require?

A

Metallothionein (MTs) are cysteine-rich proteins that bind essential and toxic heavy metals (e.g., cadmium).

They are important for zinc and copper homeostasis, and also to reduce oxidative stress.

Require adequate levels of cysteine (e.g., in legumes, sunflower seeds, eggs, chicken) zinc, copper, and selenium.

54
Q

What is Detoxification Phase Zero? Describe how toxins enter the cell.

A

Phase zero - the entry of the toxin into the cell (primarily hepatocytes) or exit of the unmetabolized toxin from storage inside cells such as adipocytes:

⤷ Fat-soluble toxins diffuse through the cell membrane.

⤷ Water-soluble or charged toxins need to access or leave the cell through a transporter.

The main transporter families used for phase zero are (both with many different transporters):
- Solute carriers (SLC)
- ATP binding cassette carriers.

55
Q

Describe what happens in Phase I Detoxification.

A

Most toxins that arrive inside the hepatocytes are lipophilic.
The CYP450 + toxin/hormone reaction creates an active binding site on the toxin (often exposing an –OH / alcohol group). This makes them more water-soluble, but also more reactive for conjugation to occur (phase II). Therefore, in phase I, intermediates are formed which are very bioactive.

56
Q

How will the liver accommodate increased exposure to a certain toxin?

A

The liver can accommodate a wide range of chemical exposure. However:
Many of the CYP450 enzymes are produced in response to increased exposure to a certain toxin by producing more of the enzyme that degrades it. This can happen at the expense of other toxin biotransformation.

Induction of phase I enzymes without co-induction of phase II can = increased reactive intermediates, ↑ oxidative stress.

57
Q

Phase I to Phase II detoxification key considerations.

A

The progression of metabolites from phase I through to phase II must happen in quick succession to minimise damaging effects of intermediary products.

  • Genetic variations (SNPs), diet and availability of nutrient co-factors can influence an individual’s ability to metabolise toxins.
  • Phase II enzymes are generally less inducible than phase I.
  • Typically, phase I will be upregulated due to toxic load, while phase II will be slow due to overwhelm from heightened phase I activity and / or lack of co-factors (e.g., a poor, nutrient-depleted diet).
58
Q

Name FIVE ways to support phase I detoxification.

A

Reduce the toxic load to slow phase I:
1. Go organic to minimise intake of pesticides and other xenobiotics from the food chain.
2. Minimise exposure of xenobiotics in toiletries and household products.
3. Stop smoking and avoid caffeine.
4. Avoid chargrilled and smoked foods.
5. Reduce or ideally eliminate alcohol.
6. Avoid unnecessary medications.
7. Avoid use of plastics in contact with food.

59
Q

Name nutrients that are necessary to support phase I detoxification activity.

A

The B complex vitamins are vital co-factors for the action of the cytochrome P450 enzymes and other phase I enzyme families.
Alcohol depletes B vitamins and so should be avoided to optimise an individual’s B vitamin status.
Whole grains, legumes, mushrooms, sunflower seeds, pistachios, wild fish, eggs, sea vegetables.

Adequate amounts of the branched chain amino acids (BCAAs) leucine, isoleucine and valine are also necessary to support phase I activity. Quinoa, fish, eggs and meat.

60
Q

How can SNPs influence enzyme activity in Phase I? Give TWO examples of genes involved in phase I.

A

SNPs can influence enzyme activity - either turning it up (↑ metabolism) or down (↓ metabolism).
It has the potential to increase toxicity by speeding up the conversion of compounds to reactive intermediary products or by causing an accumulation of unmetabolised toxins.

CYP2E1 - ethanol
CYP17A1 - pregnenolone
CYP1A2 - caffeine
CYP19A1 - testosterone
CYP2C9 - warfarin
CYP1A1 - oestrogen

61
Q

What is phase I enzyme CYP1A1 responsible for?

A

Deactivating oestrogen. An SNP of this gene increases the risk of oestrogen dominance.
Detoxifying many toxins including polycyclic aromatic hydrocarbons (PAHs) and solvents. PAHs damage DNA increasing cancer risk. They are formed in chargrilled meat, smoked foods and cigarettes.

SNP: A G2453T SNP at Rs1799814 is associated with reduced activity of CYP1A1.

62
Q

What recommendations would you give to a client with a CYP1A1 SNP?

A
  • Avoid: Chargrilled meats and smoked food. Smoking and exposure to second-hand smoke. Industrial pollutants and synthetic oestrogens (e.g., parabens in beauty products, plastic).
  • Focus on plant foods (minimal animal protein), rich in colour (phytonutrients) including polyphenols (green tea, berries, apples, etc.). Also rosemary.
  • Sulphur-rich foods, especially cruciferous vegetables (e.g., broccoli sprouts for the high I3C content) and allium vegetables.
  • Consider supplementation with Indole-3-carbinol.
63
Q

What is phase I enzyme CYP1A2 responsible for? How does a SNP impact its activity? Include CYP1A2 SNP recommendations.

A

CYP1A2 gene encodes a member of the CYP450 family of enzymes, which metabolise nutrients and drugs, including caffeine.

  • SNP: The SNP at rs762551 impacts CYP1A2 activity. Individuals with the CC genotype are ‘slow’ caffeine metabolisers.
    Caffeine intake > 300 mg / day can be damaging to the brain, heart, liver and kidneys.

SNP recommendations: Avoid all caffeine intake from coffee, tea and foods such as chocolate.

64
Q

What is Phase II detoxification and what is it dependent on?

A

Phase II - 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 the kidneys or bowel:

There are six primary phase II detoxification pathways, which are all highly dependent on the necessary substrates to carry out their function. Amino acids are of central importance.

65
Q

Provide a summary of glucuronidation. Include:
what it detoxifies, what it is inhibited / enhanced by, what it requires.

A

Glucuronic acid is added to the phase I metabolite (UPD enzymes).
Detoxifies: Oestrogens, NSAIDs, morphine, hydrocarbons.
Inhibited by: Aspirin, smoking, contraceptive pill, fluoride.
Enhanced by: Citrus peel, brassica vegetables, turmeric.
Requires: Glucuronic acid (e.g., from apples, alfalfa, broccoli).

66
Q

Provide a summary of sulphation. Include:
what it detoxifies, what it is inhibited by, what it requires.

A

Sulphate is added to the phase I metabolite (SULT enzymes).
Detoxifies: Steroid hormones (e.g., oestrogen), food additives, industrial chemicals.
Inhibited by: NSAIDs, tartrazine, molybdenum deficiency.
Requires:
- Sulphur-containing amino acids (esp. cysteine and methionine)
- Sulphur-rich foods (brassica veg; onion, garlic)
- Molybdenum (legumes, leafy veg, whole grains).

67
Q

Provide a summary of acetylation. Include:
what it detoxifies, what it is inhibited and enhanced by.

A

An acetyl group is added to the phase I metabolite (NAT enzymes).
Detoxifies: Smoke, HAAs, halides, histamine, sulphonamides.
Inhibited by: Vitamin B and C deficiency.
Enhanced by: Vitamins B1, B5, vitamin C, butyric acid (SCFA).

68
Q

Provide a summary of methylation (detoxification pathway). Include:
what it detoxifies, what it is inhibited and enhanced by.

A

A methyl group (-CH3) is added to the phase I metabolite (COMT enzymes).
Detoxifies: Steroid hormones incl. oestrogens, dopamine, adrenaline, noradrenaline. Arsenic and urea.
Inhibited by: B12 and folate deficiency; a high sucrose diet can inhibit enzymes such as COMT.
Enhanced by: Methionine, betaine, choline, vitamins B2, B6, B12, folate, magnesium.

69
Q

Provide a summary of amino acid conjugation. Include:
what it detoxifies, what it is inhibited and enhanced by.

A

An amino acid (mostly glycine) is added to the phase I metabolite (amino acid transferases enzymes).
Detoxifies: Xenobiotics, drugs (e.g., aspirin and statins).
Inhibited by: Low protein diet.
Enhanced by: Glycine primarily (legumes, seaweed, cauliflower, bone broth, meat, fish, eggs), taurine, glutamine, arginine.

70
Q

Provide a summary of glutathione conjugation. Include:
what it detoxifies and requires, what it is inhibited and enhanced by.

A

Reactive phase I metabolites are reacted with glutathione (GST enzymes).
Detoxifies: Xenobiotics, paracetamol, heavy metals (esp. mercury).
Requires: Glycine, glutamine and cysteine for formation of glutathione.
Inhibited by: Selenium, B6, zinc, glutathione deficiency.
Enhanced by: Brassica veg (especially broccoli sprouts), turmeric, citrus peel, alpha-lipoic acid.

71
Q

What role does the transcription factor, Nrf2 (nuclear factor erythroid 2) play in detoxification? How can we support detoxification through Nrf2 activity?

A

Nrf2 is key to regulating the body’s detoxification and antioxidant system:
– Induction of Nrf2 increases endogenous antioxidants to protect against reactive intermediates, and promotes phase II pathways.
– Nrf2 induction is considered protective against various oxidative stress-related conditions such as cancer, kidney dysfunction, neurological disease, and cardiovascular disease.

  • Phytonutrients not only scavenge ROS (acting as direct antioxidants) but also regulate Nrf2 activity.

Phytochemicals / foods that can regulate Nrf2 activity:
‒ Curcumin (turmeric), broccoli constituents, garlic, epicatechins (e.g., green tea), lycopene (tomatoes), resveratrol (e.g., red grapes), isoflavones (legumes, alfalfa sprouts), rosemary, blueberry, pomegranate, naringenin (grapefruit).
‒ The effects of whole foods / herbs versus isolated bioactive compounds appear greater.

72
Q

Why is glutathione important for detoxification? What is the rate-limiting amino acid for glutathione synthesis? What have low levels of glutathione been associated with?

A

Glutathione - a crucial antioxidant that protects against reactive metabolites from phase I and is essential for glutathione conjugation in phase II.
- Cysteine is the rate-limiting amino acid for glutathione synthesis (sources include legumes, sunflower seeds, eggs, chicken).
- Glutathione is critical to mitochondrial protection.
- Low levels of glutathione have been associated with: neurodegenerative diseases, autoimmunity, CVD, liver diseases, and pulmonary diseases such as COPD.
- Glutathione binds and transports mercury out of cells and out of the brain across the blood-brain barrier.

73
Q

Name FOUR ways in which glutathione levels can be supported (increased).

A
  • Decrease depletion (decrease oxidative stress): decrease toxic load, optimise melatonin (sleep hygiene, vitamin B6 etc.), alpha-lipoic acid.
  • Milk thistle (silymarin).
  • NAC (also binds to methyl Hg) - 300–1000 mg x 2 daily.
  • Liposomal glutathione.
  • Resveratrol (e.g., red grapes, berries).
  • Cruciferous vegetables (glucosinolates boost glutathione).
  • Cordyceps mushroom.
74
Q

What is GSTM1 gene responsible for? How does a SNP impact its activity? Include recommendations.

A
  • GSTM1 is the most active member of the GST family and is responsible for the removal of xenobiotics, carcinogens and products of oxidative stress.
  • SNPs: An ‘absent’ gene is common, resulting in reduced capacity for liver detoxification.
  • Recommendations:
    – Focus on minimising toxic load, e.g., stop smoking, eat organic.
    – ↑ antioxidants (‘rainbow of colour’).
    – ↑ cruciferous vegetables (for the sulforaphane) and alliums.
    – Milk thistle, NAC, alpha-lipoic acid, selenium.

GSTM1 - glutathione S-transferase

75
Q

What is involved in Phase III detoxification?

A

Phase III - the removal and excretion phase where detoxified products are pumped into blood or bile for elimination:
This involves over 350 antiporter proteins (ATP-dependent pumps) that work on specific substrates.

76
Q

How to induce phase III metabolism?

A

Fasting (e.g., intermittent / vegetable broth). Being in a lipolytic state allows toxins stored in fat cells to be mobilised and eliminated.
Fasts and calorie restriction should be short-term (5–10 days) and toxin elimination should be supported with practices such as saunas.
Good hydration is essential, helping with elimination.
Bile production and flow can be supported with choleretic and cholagogue (burdock root) herbs. Dandelion root and globe artichoke leaf provide both actions and are also mild diuretics.

77
Q

What is the efficiency of excretion dependent on?

A

Efficiency of excretion is dependent on different factors, particularly influences from the diet and microflora.
Fibre binds conjugated xenobiotics, decreases stool transit time and reduces the amount of deconjugating enzymes in the stool.
Dysbiosis - undesirable bacteria can produce enzymes such as beta-glucuronidase that deconjugate phase II compounds, ↓ elimination. Deconjugated xenobiotics re-enter the blood and are sent back to the liver for processing.

78
Q

Name TWO hepatoprotective substances.

A

Milk thistle (Silybum marianum):
- A liver tonic that has strong antioxidant properties and has been shown to help protect the liver from the damaging effects of phase I metabolites.
Suitable for hepatoprotection e.g., high alcohol intake, pharmaceutical drugs and hepatitis. However, high doses can inhibit phase III.

Mycotherapy:
- Shiitake and maitake are hepatoprotective.
- Cordyceps - hepatoprotective and supports detoxification by increasing glutathione (phase II).

79
Q

Name TWO key oestrogen liver genes. Why are they important?

A
  • CYP1A1 is crucial because it converts oestrogens into 2OH oestrogens, which are neutral or even beneficial for the body.
  • CYP1B1 converts oestrogens to 4OH oestrogens and can promote the synthesis of harmful molecules called quinones, which damage DNA and potentially initiate cancer. Variations on CYP1B1 are associated with increased production of 4OH oestrogens.
80
Q

Describe the process of oestrogen elimination (what enzymes are involved, risk of SNPs, the role of gut bacteria).

A

COMT is involved in the methylation of 2OH and 4OH before the detoxification of oestrogens occurs.

Oestrogens are then detoxified by sulphation and glucuronidation. SULT / UGT SNPs increase the risk of hormone-related cancers e.g., breast cancer.

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

Raised beta-glucuronidase is often due to an overgrowth of bacteria such as E. coli and Clostridium perfringens. Detected on a Complete Digestive Stool Analysis (CDSA).
To combat this:
Optimise gut flora and ↑ glucuronic acid-rich foods, mung bean sprouts, orange peel (infused tea), apples, broccoli.

81
Q

How can we optimise oestrogen metabolism?

A
  • Increase intake of:
    Cruciferous vegetables, and focus on broccoli sprouts due to the high I3C content. DIM / I3C from cruciferous veg stimulate CYP1A1.
    Fibre (elimination), organic fruit and vegetables, filtered water.
  • Avoid: Dairy, excess alcohol and caffeine, non-organic meat and eggs, water from plastic bottles (due to BPA), anti-perspirants, hormonal contraceptives.
  • Address dysbiosis (e.g., weed, seed, feed protocol). Calcium D-glucarate has been shown to inhibit beta-glucuronidase.
82
Q

Name FIVE ways to support bowel elimination / ‘clean up the GIT’.

A
  • Remove anything damaging the GIT (e.g., alcohol, NSAIDs).
  • Ensure good hydration.
  • Eat foods rich in mucilage, which swells and lubricates the bowel (linseed, chia seeds, psyllium seed / husk). Always take with plenty of water.
  • Maximise fibre intake (soluble and insoluble) to aid transit through the GIT, increase stool bulk and provide prebiotics.
  • Ensure a healthy intestinal microflora:
    – Eradicate pathogens / SIBO with antimicrobials, e.g., berberine.
    – Repopulate the flora with probiotic foods (e.g., kimchi, sauerkraut, kombucha and kefir) and / or probiotic supplements. Increase prebiotic foods (e.g., chicory, garlic, asparagus, onions).
  • Support the intestinal mucosa, e.g., quercetin, bone broth, cabbage juice (glutamine), N-acetyl glucosamine (e.g., in shellfish). Slippery elm and / or marshmallow root (1 tsp powder in water - drink 3 x daily between meals).
83
Q

Why is supporting kidney function important for optimising elimination? How can we achieve this?

A

The kidneys play a vital role in elimination, filtering undesired products of metabolism such as uric acid, creatinine, hormone metabolites and phase II metabolites.

  • Stop drugs that damage the kidneys, esp. NSAIDS, paracetamol.
  • Avoid table salt and protein (esp. animal) diets as they increase the metabolic load on the kidneys.
  • Good intake of filtered water to aid waste removal via the kidneys.
  • Address GI dysbiosis and intestinal permeability due to the impact of circulating endotoxaemia on the kidneys.
84
Q

Name FOUR food sources that support kidney function.

A
  • Celery seed, nettle and dandelion leaf taken as herbal infusions support renal blood flow, increase urine output and encourage removal of conjugated toxins and acidic wastes.
    Nettle and dandelion leaf are alkalising (rich in minerals) helping the kidneys to release toxins.
  • Beetroot juice is especially rich in organic nitrates, which are converted to nitric oxide in the body = vasodilation and improved microcirculation. 250 ml x 2 per day.
  • Blueberries protect the kidneys from gut-derived endotoxins.
85
Q

How can we support skin to optimise elimination?

A
  • Toxin avoidance - especially anti-perspirants (to avoid inhibiting skin elimination).
  • Saunas - increase the elimination of toxins (incl. heavy metals, BPA and phthalates) by promoting cutaneous vasodilation and increasing perspiration. Every 2–4 days.
  • Wraps / poultices (i.e., rock salt, clay, mud) increase heat, which opens pores; the alkalinity absorbs acid wastes.
  • Epsom salt / seaweed baths combine warm water (opens pores) and alkalinity (draws out acid wastes).
  • Burdock root (tea daily) - ‘re-conditions’ the skin.
86
Q

What role does the lymphatic system play in elimination? How can we support lymphatic flow to optimise elimination?

A

The lymphatic system plays a vital role in elimination, filtering and removing harmful substances.

  • Exercise helps to mobilise and shift toxins and wastes. Mini trampolining is especially good!
  • Dry skin brushing (gently brushing the skin from the bottom of the feet and palms of the hands toward the heart).
  • Massage i.e., manual lymphatic drainage.
  • Abdominal breathing exercises (promote thoracic duct drainage).
  • Cleaver’s tea (especially in the spring and summer months).
87
Q

How can Castor Oil Packing be useful for detox support?

A

Castor oil contains rincinoleic acid, which increases blood flow to organs such as the liver, aiding detoxification and promoting lymphatic drainage:

  • It also acts on smooth muscle, relieving constipation and menstrual cramps.
  • For detox support, apply the castor pack over the liver.
88
Q

Name FIVE ways of general detoxification support in clinic.

A
  1. Reduce toxin burden - avoid dietary and environmental toxins.
  2. Assess GI integrity - ‘weed, seed, feed’ for dysbiosis, heal gut mucosa if indicated.
  3. Support eliminatory channels.
  4. Regular consumption of foods that support detoxification - brassica veg, allium veg, fibre-rich foods.
  5. Eat a rainbow of phytonutrients to ensure optimal antioxidant status.
  6. Good quality protein to provide adequate conjugates for phase II.
  7. Ensure optimal intake of B vitamins.
  8. Regular saunas - ↑ toxin excretion e.g., heavy metals, PCBs.
89
Q

What would be your recommendations for a deeper detox?

A

Combine the basic liver support principles with a water-fast (maximum 4 days unless supervised) or fasting-mimicking diet.

Water fast:
- Wholefoods only (mainly steamed veg) for several days prior to decrease toxin load.
- 2–3 litres of filtered water daily.
- Rest, limit exercise (gentle only).
- No vitamins, herbs, herbal teas.
- Limit medication to those needed.
- Reintroduce food with easy-to-digest soups and broths

90
Q

What detox approach would you recommend for depleted or highly toxic clients?

A

For depleted or highly toxic clients, a slower approach is needed.

Fasting mimicking diet (5-10 days)
- Low complex carbohydrate (no refined sugar).
- 500-800 kcal a day.
- 0.8 g protein / kg body weight.
- 8-10 portions of liver-supporting vegetables esp. cruciferous veg, onions and garlic, mung bean sprouts (glucuronic acid).
- Natural fats from plant foods.
- Reduced eating window - 8 hours
- Ensure good intake of filtered water.