Nutrigenomics and Detoxification Flashcards
Define genomics
Genomics is the study of genes. Determines how they interact and influence biological pathways, networks, and physiology.
Define nutrigenomics
Nutrigenomics is the study of the interaction of nutrition and genes, especially with regard to the prevention or treatment of disease.
What are the benefits of genetic testing in practice?
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.
What is the difference between a gene, a trait and an allele?
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.
What is a phenotype?
How genetic and environmental influences come together to create physical appearance and behaviour.
What is DNA and its structure?
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.
What is the structure of a nucleotide?
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).
What are codons? Give an example of what can happen if the translation is not coded correctly.
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.
What are single nucleotide polymorphisms (SNPs)?
Are all SNPs problematic?
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 are SNPs classified?
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.
Define chromosomal variants (wild, heterozygous, homozygous).
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.
What would you recommend to a client with the ‘SLC23A1’ gene SNP?
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).
Name areas where genetic information is especially useful for clinic.
- 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).
TRUE or FALSE
Genes are deterministic.
FALSE
Genes only tell us the potential for physiological differences.
Never treat by SNP or look at SNPs in isolation.
How do SNPs affect the activity of the BCO1 gene? What would you recommend to a client with the BCO1 gene SNP?
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 do SNPs affect the activity of the VDR gene? What would be your recommendations to a client with the VDR gene SNP?
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.
What do FADS 1 and FADS2
code for?
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.
What would be your recommendations to a client with the TNF gene SNP?
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).
What is methylation and its functions in the body?
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).
Name FIVE dietary co-factors for methylation.
Folate, B12, B6, B2, choline, betaine (TMG) and zinc.
What is SAMe and what nutrient(s) does it rely on?
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.
Name FIVE disruptors of methylation.
- 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.
What conditions can impaired methylation contribute to?
- Cardiovascular disease.
- Cancer (e.g., breast cancer).
- Infertility and unexplained miscarriages.
- Chronic fatigue and mood disorders.
- Neurological disease (e.g., MS, Alzheimer’s).
What testing helps to assess for indicators of poor methylation?
- 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.
What are the key outputs / functions of the folate cycle?
- DNA synthesis / repair
- formation of 5-Methyltetrahydrofolate (5-MTHF).
What are the key outputs / functions of the methionine cycle?
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.
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?
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.
What recommendations can we make to support the folate cycle? What drug is a folate antagonist?
‒ Optimise dietary folate.
‒ Consider a methylated folate supplement.
‒ Optimise vitamin B2 (riboflavin) - supporting the MTHFR gene.
Folate antagonist: methotrexate (used for inflammation and cancer).
Name the two key genes in the methionine cycle. What is their role and how their SNPs can affect it?
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.
What recommendations can we make to support the methionine cycle?
- 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.
What is the transsulphuration cycle and its key outputs?
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.
Name the role of CBS gene in transsulphuration.
The CBS gene provides instructions for making an enzyme called cystathionine beta-synthase. This enzyme is responsible for converting homocysteine to cystathionine.
Cystathionine is used to produce cysteine in transsulfuration. Why do we need cysteine?
Cysteine can be used to
a) make sulphate needed for sulphation (detoxification),
b) increase glutathione levels.
Is having a lot of cystathionine a good thing? What can be the result of having too much cystathionine?
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).
What SNP is associated with transsulphuration cycle?
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).
What are the key outputs / functions of the biopterin cycle?
Tetrahydrobiopterin (BH4) ia a crucial coenzyme involved in conversion of amino acids (e.g. tryptophan) to the neurotransmitters dopamine, serotonin and melatonin.
