L2 Detoxification & Neutrigenomics Flashcards
1 - Genomics
2 - Allele
3 - Phenotype
1 = study of genes
2 = genetic variation eg eye colour
3 = genetic & environmental factors together
1- SNP
2 - Wild Type
3 - Heterozygous
1 - variation on DNA base, normal but influences how genes interact with environment
2 - Natural variant (stable)
3 - Gene variant inherited by one parent
COMMON SNPs:
1 - BCO1
2 - VDR
3 - FADS-1
4 - FADS-2
5 - TNF
1 - reduces beta-carotene conversion
2 - impacts Vit-D synthesis: A allele = <bone density & G allele = >osteoarthritis risk
3 - Fatty-acid 5 Desaturase = > O:6 to Inflammatory AA conversion (African Americans more common)
4 - Fatty-acid 6 Desaturase = < levels of anti-inflammatory EPA, DHA, ALA
5 - > inflammatory TBF cytokines
Processes that require METHYLATION
Gene regulation
DNA/RNA synthesis
Immune (tissue repair/inflammation/WBCs/illness)
Detoxification
Energy production
Myelination & NS
Methylation = a currency constantly being spent
METHYLATION consists of 2 cycles
Folate cycle
Methionine cycle
What is the Folate Cycle
Various enzymes (coded by MTHFR gene - can have SNP) convert Folate into its methylated (active) form 5-MTHF (Methylfolate)
Which Nutrients support Methylation
B6, B2, B3, Choline, Betaine, Zn, B12
What is Methylfolate (5-MTHF) need for in the body?
Building Neurotransmitters e.g; Serotonin, Dopamine, Noradrenaline
What is SAMe
The grandparent methyl-donor created from Methionine.
SAMe donates its methly group (processes below) & becomes Homocysteine which then needs to be converted back to Methionine (needs B12!)
Builds; hormones, neurotransmitters (GABA, Serotonin, Dopamine) - mood!, Joints, liver function, addictions/alcoholics
What is the Methionine Cycle
Also the SAMe cycle! Methionine creates SAMe (Grandparent Methyl donor!)
Methionine has Sulphur added to it creating SAMe
SAMe donates its methly group & becomes Homocysteine which then needs to be converted back to Methionine (needs B12!)
Homocysteine Doesn’t have Methyl group on its sulphur as it gave it to various processes. Enzyme Methionine Synthase (coded by MTR & MTRR genes) creates reactions to get it back.
Needs B12 and 5-MTHF (Methylfolate) a which donates its methyl group to make Homocysteine back to Methionine
Enzymes catalysing the process coded by genes:
MTR - SNP = < MS activity
MTRR - SNP = < B12 conversion to Methylated B12
What is Homocysteine?
Doesn’t have Methyl group on its sulphur. Enzyme reactions to get it back that needs B12 and 5-MTHF (Methylfolate) which donates its methyl group to make Homocysteine back to Methionine
Methylation disrupters
- Age
- Poor gut health (low HCI)
- Low folate, B12
- < co-factors
- SNPs
- Increased demand on processes (at expense of others
- > toxins
- Hormone imbalances eg oestrogen dominance
- Drugs - OCP, HRT, metformin
What is the Transulphuration Cycle?
Another Homocysteine output route, converting it to Cystathione (via CBS gene) and onto:
- Sulphate (detoxification of oestrogen) via Cysteine & SulphITE (wine, garlic)
- Glutathione (antioxidant) via Cysteine
- Urea via Amonia (protein)
How to support Transulphuration
- Increase Zn, Choline & TMG (beets)
- Reduce ammonia (<meat, >probiotics to reduce self synthesis
- Reduce sulphur containing foods (wine, eggs, brassicas, garlic
What is COMT?
MTHFR (from folate cycle) gene that provides instructions for making a methyl dependent enzyme - catechol-O-methyltransferase.
20-30% Europeans have SNP which limits catechol removal
2 enzyme types,
1 creates in nerve cells & breaks down neurotransmitters
1 created in liver/kidneys/blood & converts some hormones inc oestrogen to its less active form
Common SNPs:
AA (worrier) = excess catecholamines, ie low COMT activity - not broken down = > oestrogen’s. higher dopamine levels; lower pain threshold, <stress tolerance, >oestrogen
GG (warrior) = fast catecholamine breakdown = lower dopamine levels, depression; higher pain threshold, > stress resiliency
Supporting COMT
Choline, B Vits, Folate, B12, support SAMe, avoid xeno-oestrogens
Reduce foods that >catechols (high protein)
Increase Mg
Reduce alcohol (triggers dopamine release)
Increase brassicas
Support phase II detoxification
What is Urea Cycle & eNOS?
eNOS = Endothelium Derived Nitric Oxide Synthanase creates NO (vasodilator) from arginine
SNPs can <eNOS activity & NO + slow down ammonia detoxification = >toxic load, free radicals, BP & CVD risk
Supporting eNOS
Eat rainbow (antioxidants)
Limit ammonia (animal protein)
> NO production with beet juice & L-arginine
What is a toxin?
A poison produced in organisms that is active @ low levels
What are Endogenous toxins?
INTERNAL
GI microbes
Dysbiotic bacteria, LPS
Metabolites
Poorly detoxed - recirculated hormones
What are Exogenous toxins?
External, chemicals, eg:
BPAs/Plastics
Pesticides
Flame retardants
Farmed fish
Air pollution
Solvents
Smoked foods
Heavy metals - Aluminium, Mercury, Arsenic
Antioxidant enzymes produced in humans & nutrients needed
Superoxidase Dismutase (Zn, Cu, Manganese)
Catalase (Fe)
Glutathione Peroxidase (Se)
Glutathione Reductase (B3)
Antioxidants from plants
Vit E (sunflower seeds, almonds, olive oil, avocado, sweet potato, spinach)
Vit C (peppers, citrus peel, kiwi, berries, crucifer, mango
Flavonoids (quercetin, catechins, GLV
Carotenoids
What are Metallothioneins & role in detoxification?
They are cysteine (legumes, eggs, chicken, sunflower seeds) rich proteins that bind to toxic heavy metals
Reduce OS
Help Zn & Copper homeostasis
Detoxification phase Zero
Toxin entry into cell
Fat Sol via diffusion
Water Sol via transporter
Detoxification- Phase 1
- Makes fat sol toxins water sol for elimination
- CYP450 enzymes create active binding site (they become more reactive)
- SNPs can influence CYP450, faster or slower not good
Common Phase 1 SNPs
CYP2E1 - alcohol
CYP1A2 - caffeine
CYP1A1 - oestrogen
What’s Phase 2 detoxification
6 detox pathways add functional groups thru chemical reactions to deactivate toxins to make them safe for elimination
Phase 2 - Step 1
GLUCURONIDATION
Requires; GLUCURONIC acid (apples, alfalfa, broccoli)
Enhanced by; citrus, brassica, turmeric
Phase 2 - Step 2
SULPHATION
Key! Needs;
- sulphur containing AA’s (cysteine & methionine)
- Sulphur rich foods (eggs, onion, garlic, brassicas)
Molybdenum (legumes, GLV, whole grains)
Phase 2 - Step 3
ACETYLATION
Inhibited by; Vits B & C deficiencies
Needs; B1, B5, C, butyric acid (SCFA)
Phase 2 - Step 4
METHYLATION
Inhibited by; < Folate or B12
Needs; Methionine, Betaine, Choline, B2, B6, B12, Folate, Mg
Phase 2 - Step 5
AMINO ACID CONJUGATION
Inhibited by low protein diet
Needs; GLYCINE (legumes, seaweed, cauliflower, bone broth, meat, fish, eggs
Phase 2 - Step 6
GLUTATHIONE CONJUGATION
Inhibited by; deficient Se, B6, Zn, Glutathione
Enhanced by; Brassicas, turmeric, citrus peel, alpha-lipoic acid
Self synthesised by cysteine
What is Glutathione, where does it come from & what is it for?
A crucial antioxidant
From legumes, sunflower seeds, eggs, chicken
Protects mitochondria
Binds & transports mercury out of cells & x-bbb
Low levels assoc; neuro-degenerative, autoimmune, CVD, liver disease, COPD
SNP common
How to support Glutathione?
< OS
< toxic load
> alpha-lipoid acid (grandfather antioxidant, recycles oxidised glutathione)
Milk thistle
NAC
Reservatrol
Brassicas
Cordyceps
