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Nutrition two > Nutrigenomics and detoxification > Flashcards

Nutrigenomics and detoxification Flashcards

1
Q

What is meant by a gene? An allele? A phenotype? Genomics?

A
  • A gene is made up of DNA, our physical unit of hereditary
  • An allele is a variant form of a gene responsible for the variation in which a trait can be expressed eg eye colour, passed on at conception one from each parent
  • Phenotype is how genetic and environmental factors can come together to create appearance and behaviour
  • Genomics is the study of genes and how how they interact and express biological pathways and physiology
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2
Q

Describe a nucleotide and its make up, and a codon

A

-DNA contains our genetic information ,made up of two nucleotide chains (the double helix)
- Each nucleotide contains a deoxyribose (sugar) a phosphate group, and one of 4 bases:
A- Adenosine
C- Cytosine
T- Thiamine
G- Guanine
-A codon is a sequence of three nucleotides that ‘code for’ a specific amino acid. codons make up genes

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3
Q

How may the methylation process be impacted by incorrect translation coding and what implications might this have?

A
  • The codon ‘AUG’ codes for the amino acid methionine. If translation doesn’t happen correctly eg AUC in the DNA sequence then isoleucine is produced instead.
  • This is relevant as methionine is needed for methylation which is needed for switching genes on and off.
  • Low levels may increase the risk of cancerous cell changes
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4
Q

What is a SNP?

A

Single nucleotide polymorphism
-differences in single bases in the sequence of a gene
- (genetic variation that alter the effectiveness of that specific enzyme- may speed things up or slow things down
-

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5
Q

Which SNP is critical for methylation?

A
  • SNP on the MTHFR gene (rs1801133)
  • C667T means that C (cytosine) has been changed to T (thymine)
  • This could result in insufficient conversion of folate into methylfolate. (biologically active form- 5MTHF)
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6
Q

Which SNP is associated with an increased need for vitamin C and how would you address this in clinic?

A
  • SLC23A1 gene codes for production of a transporter which supports absorption and distribution throughout the body. SNP on this gene is associated with a higher demand of vitamin C
  • Optimise dietary intake, raw fruit and vegetables eg peppers, citrus, kiwi, tomatoes, berries and consider supplementation
  • give up smoking
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7
Q

3 examples of when genetic testing may be useful in clinic?

A
  • Methylation (eg production of gluthathione and homocysteine regulation)
  • Detoxification- details about each phase and the genes involved eg alcohol and caffeine detoxification can help to identify and offer targeted approach
  • Vitamin conversion/ receptor function eg vitamin D conversion effect on bone density risk and vitamin A (conversion of beta carotene)
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8
Q

What are three considerations for using nutrigenomics in clinic?

A

1) Genes only tell us the potential for physiological differences, SNPS are not deterministic and we should consider the whole person , symptoms and the way the systems are functioning together. Environment trumps genes- the most powerful tool we have
2) Consider the ethics of genetic testing, do we want to spring life changing information on a client , and data consent
3) Some SNPs work together to compensate for each other, so look at the bigger picture and never take a SNP in isolation

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9
Q

Which gene and SNP is implicated in vitamin A conversion and what would you do in clinic to address this?

A

-Gene BCO1 (beta carotene oxygenase 1) codes for the enzyme that converts beta carotene to retinol .
- Many SNPS effect its activity (BCO1 A379V TT alleles or BCO1 R267S AT or TT lower conversion for example)
- lower speed converters means individual will need much more dietary beta carotene
- Increase preformed vitamin A from foods liver , fish oils, or supplements and don’t rely on beta carotene if you want vitamin A to do a job, use a vitamin A supplement instead

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10
Q

Which SNP can cause a vitamin D deficiency and why? How would you approach this is clinic?

A
  • VDR gene codes for the vitamin D receptor
  • SNPs at rs1544410 the A allele is associated with reduced bone density while the G allele with a decreased risk of osteoporosis
  • ensure optimal D levels with regular testing, sun exposure, mushrooms, oily fish, eggs and supplementation
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11
Q

Which genes code for EFAs and how might SNPs effect conversion?

A
  • Fatty acid desaturases are involved in EFA conversion. FADS 1 codes for delta 5 desaturase and FADS2 for delta 6 desaturase
  • SNPs on FADS1 and FADS2 can mean fish isn’t converted to EPA and DHA as effectively and conversion of high dietary omega-6 to inflammatory arachidonic acid is increased
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12
Q

Which SNP can effect the inflammatory response and what might you do in clinic?

A

TNF gene codes for the production of the pro inflammatory cytokine
SNP at rs1800629 A allele is associated with increased TNF (cancer, RA, psoriasis, asthma)
- focus on anti inflammatory foods and herbs turmeric catechins in green tea, echinacea, SMASH omega 3s
- decrease sugar, dairy, fried foods, processed meats, alcohol, omega 6 foods

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13
Q

What are 4 things methylation is needed for ?

A

1) gene regulation- can switch genes on and off like a lightswitch . By bolting a methyl group onto some bad genes means they may have less of a health effect on us
2) DNA/RNA synthesis - the making of new cells , healthy growth and can reduce cancer risk
3) Detoxification- supports phase two in detoxifying hormones such as oestrogen through COMT
4) Energy production (CoQ10, carnitine and ATP)
5) Myelination and neurotransmitter production eg dopamine and serotonin into melatonin

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14
Q

What is methylation? What are some main co factors needed?

A

Methylation is adding a methyl group (CH3) to a substrate . It’s our chemical currency, helping the body with a number of processes.
- Folate needed from plant foods to convert to methylfolate
- B12 needed to convert methylfolate to SAMe
- B2 and B3 to convert 5, 10 methylene tetra hydrofolate to 5-MTHF (methylenetetrahydrofolate reductase)
- choline
- Zinc

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15
Q

What is the major methylation SNP to be aware of and how would you address this in clinic?

A

-MTHFR gene codes for the enzyme 5-MTHF which converts folate into methylated form.
A SNP C667T (cytosine replaced with thymine) is associated with decreased activity of MTHFR
- optimise dietary folate, consider a methylated folate supplement = this cuts out all the intermediate steps and makes it directly usable
- optimise B2 to support the MTHFR gene

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16
Q

Why might methylation be compromised, and what might this lead to?

A
  • insufficient substrates- folate, methionine
  • insufficient co factors (B2, B12, B6, Zinc) and malabsorption of these nutrients
  • Any high demand on the body including, high exercise, stress, inflammation, need for repair
  • Drugs such as OCP and metformin can decrease B vitamins
  • SNPs effecting enzyme activity

Can lead to cardiovascular disease, cancer, infertility and miscarriage, chronic fatigue , mood disorders, neurological diseases eg MS, alzheimer’s

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17
Q

What is a xenobiotic?

A
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18
Q

3 endogenous toxins?

A

GI microbes-
fragments of dysbiotic bacteria called lipopolysaccharides (endotoxins) can enter the bloodstream

  • waste products from normal metabolic processes eg urea if not properly metabolised in the liver
  • poorly detoxified/ eliminated hormones eg chronic constipation= decreased oestrogen elimination
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19
Q

What is detoxification?

A
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20
Q

3 ways to support detoxification?

A

Minimise the toxic load.
– Support elimination pathways
(before promoting liver detoxification).
– Support detoxification pathways.

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21
Q

3 exogenous chemical toxins

A
22
Q

3 exogenous metal toxins?

A
23
Q

Where is arsenic found and what SNP may effect ?

A
24
Q

5 signs and symptoms of sluggish liver detoxification?

A
25
Q

what role do antioxidants play in detoxification? what are the groups?

A
26
Q

Examples of antioxidant enzymes?

A
  • superoxide dismutase- convert superoxide to hydrogen peroxide ( needs zinc, copper, manganese )
  • Catalase- converts hydrogen peroxide to H2O and O2
    (needs Iron)
  • Glutathione peroxidase, same as catalase, needs selenium (mercury can suppress selenium)
  • Glutathione reductase- regenerates glutathione that has been oxidised (B3)
27
Q

Describe phase 0

A
28
Q

Describe phase 1

A

Primarily involves transformation enzymes known collectively as cytochrome p450 in the liver
- Most toxins that enter the hepatocytes are lipophilic and need to undergo phase 1 detoxification
- A reaction between the toxin and the CYP450 enzymes creates a binding site by exposing an -OH / alcohol group so that the toxin can become more water soluble, but also more reactive , ready to be conjugated in phase 2.
- As a result, phase 1 creates a lot of bioactive intermediates

29
Q

Describe the role of CYP450 enzymes , what problems may arise?

A
30
Q

what things need to be considered with phase 1- phase 2

A
  • Progression of metabolites from phase 1 to phase 2 must happen in quick succession to minimise damaging effects of intermediary products
  • SNPs, diet and availability of nutrient cofactors can influence the individual’s ability to metabolise toxins . SNPS may slow down phase 1 - overload of toxins. Too fast and their may be more damaging intermediate metabolites
  • Common for phase 1 to be upregulated due to toxic load, while phase 2 will be slow due to overwhelm from heightened phase 1 activity and or a lack of nutrient co factors
31
Q

How can you support phase 1 detoxification?

A
32
Q

Which co factors are needed for phase 1 detoxification?

A
33
Q

CYP1A1 SNP relevance and recommendations

A
34
Q

CYP1A2 SNP relevance and recommendations

A
35
Q

What is phase 2

A
36
Q

summary of 6 primary phase 2 detoxification pathways? what do they detoxify and would do they require/ enhanced

A

1) Glucuronidation
Detoxify: Oestrogen, NSAIDS, hydrocarbons
Needs: Glucuronic acid- apples, broccoli
brassica veg, citrus peel, turmeric

2) Sulphation
Detoxifies: steroid hormones eg oestrogen , food additives, industrial chemicals
Needs: Sulphur containing amino acids- cysteine and ,methione, sulphur rich foods- garlic onions, brassica veg
Molybdenum- legumes, leafy veg, whole grains

3) Acetylation
Detoxifies: smoke, HAAs, histamines
Needs: B1, B5, vitamin C, butyric acid (SCFA)

4) Methylation
Detoxifies: steroid hormones including oestrogen , dopamine, adrenalin, noradrenaline, arsenic.
Through COMT
Needs: methionine, betaine, choline, magnesium, B2, B6, folate, B12, TMG

5) Amino acid conjugation
Detoxifies: xenobiotics , drugs eg aspirin , statins
Needs: Glycine - legumes, bone broth, meat , fish, eggs
Taurine, glutamine, arginine
Limited by low protein diet

6) Glutathione conjugation
Detoxifies: xenobiotics, paracetamol, heavy metals (mercury
Needs: Glycine, cysteine and glutamine for glutathione
Brassica veg, turmeric, citrus peel, ALA

37
Q

How does Nrf2 gene expression support phase 2 and how can you regulate Nrf2 activity

A

The transcription factor, Nrf2 (nuclear factor erythroid 2) 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.

38
Q

What is the role of glutathione and what have low levels been associated with? why and how to increase cysteine

A
39
Q

How to increase glutathione levels?

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.

40
Q

Phase 2 SNP and what are the implications, recommendations for it?

A
41
Q

What is phase 3? How does this work?

A

The removal and excretion phase where detoxified products are pumped into the blood or bile for elimination :
A proportion of conjugated metabolites from the liver are pumped into bile and travel to the intestinal lumen for excretion

  • involves over 350 antiporter proteins (ATP- dependent pumps that work on specific substrates
42
Q

How can you induce and support phase 3?

A
  • fasting eg intermittent or vegetable broth as being in a lipolytic state allows stored toxins to be mobilised from fat cells and eliminated
  • Certain high dose isolated phytonutrients can inhibit eg curcumin and epicatechins , still include as valuable in detoxification process but focus on whole plant preparations
  • good hydration helps with elimination
  • Support bile production and flow with choleretic and cholagogue herbs- globe artichoke and dandelion root provide both actions and are also mild diuretics . Burdock root tea = cholagogue
43
Q

What can affect the efficiency of excretion in phase 3

A

• Efficiency of excretion is dependent on 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.

44
Q

Which liver genes are crucial for oestrogen metabolism?

A

CYP1A1 responsible for converting oestrogens to 2-OH oestrogens, neutral and even beneficial form
CYP1B1 responsible for converting oestrogens to 4-OH oestrogens, more harmful route as can increase synthesis of quinones which cause DNA damage and increase the risk of cancer . SNPS on CYP1B1 can increase 4-OH oestrogens

COMT involved in methylation of 2-OH and 4-OH before detoxification of these oestrogens occur

45
Q

3 stages of oestrogen metabolism/ detoxification

A

1) CYP1A1 converts oestrogens to 2-OH oestrogens , which are neutral and sometimes beneficial
CYP1B1 converts oestrogens to 4-OH oestrogens which are more harmful as can increase synthesis of quinones- can damage DNA and increase risk of cancer

COMT is involved in methylation of 2OH and 4OH before the detoxification of these oestrogens occur

2) Oestrogens are then detoxified through sulphation and glucuronidation. SNPS in UGT and SULT can increase teh risk of hormone cancers

3) Oestrogens can then enter the bowel in bile to be eliminated.
Can become deconjugated by beta- glucuronidase enzyme (increased with e-coli and clostridium perfringens )leading to re-circulation

46
Q

How to combat raised beta glucuronidase

A
  • Optimise gut flora
  • Increase glucuronic acid rich foods- mung bean sprouts, orange peel infused tea, apples, broccoli
  • Calcium d- glucorates supplement can help to escort BG out
47
Q

How to optimise oestrogen metabolism and what to avoid?

A
48
Q

How to support bowel elimination

A

1) Remove anything damaging to the GIT eg alcohol, NSAIDS
2) Ensure good hydration
3) Eat foods rich in mucilage- linseeds, chia seeds, psyllium husk
4) Maximise fibre intake to aid transit through GIT and provide prebiotics
5) Ensure healthy microbiome- eradicate pathogens and repopulate with prebiotics and probiotics
6) Support intestinal mucosa- quercetin, bone broth , cabbage juice- glutamine- N-acetyl glucosamine. slippery elm / marshmallow root (1tsp powder in water)

49
Q

How do you support kidneys with elimination?

A
  • stop drugs that damage the kidneys NSAIDS, paracetamol
  • avoid table salt and animal protein diets- increase metabolic load on the kidneys
  • good intake of filtered water to aid waste removal via kidneys
  • Address GI dysbiosis and intestinal permeability due to impact of circulating endotoxemia on the kidneys
  • Celery seed, nettle and dandelion leaf as infusions support renal blood flow, increase urine output and help with removal of toxins
  • Beetroot juice is rich in organic nitrates- converted to nitric oxide in the body- vasodilation and microcirculation 250mlx 2 per day
  • blueberries protect kidneys from gut derived endotoxins
50
Q

What is the role of the kidneys in elimination?

A

They play a vital role, filtering undesired products of metabolism such as uric acid, creatinine, hormone metabolites and phase 2 metabolites

51
Q

How can you support the skin to optimise elimination?

A
  • toxin avoidance, antiperspirants will inhibit skin elimination
  • saunas increase the elimination of toxins by promoting cutaneous vasodilation and increase perspiration. every 2-4 days
  • burdock root tea reconditions the skin
    epsom salt/ seaweed baths opens pores and draws out acidic waste
52
Q

How might you optimise lymphatic flow for elimination?

A
  • exercise to mobilise and shift toxins and wastes
  • dry skin brushing
  • massage- manual lymphatic drainage
  • abdominal breathing exercises- promotes thoracic duct drainage

Nutrition two (10 decks)

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