DETOXIFICATION

The human body is exposed to thousands of toxins every single day which need to be processed,

neutralized and eliminated. Substances such as nutrients, food additives, pesticides, medication, air

pollution, alcohol and hormones are transformed from being fat-soluble to water soluble, allowing them

to be more easily excreted from the body via urine and bile.

The detoxification process in the body is governed primarily by a family of enzymes known as the GST

family of enzymes.

GST enzymes are responsible for making harmful compounds in the body more water soluble and

therefore more easily excreted from the body through sweat and urine.

There are specific vegetables that help the GST enzymes to function. These are the cruciferous and

allium vegetables. Hence the reason why they help increase the activity of your detoxification system,

aiding the removal of harmful substances from your body.

Detoxification occurs predominantly (although not

solely) in the liver in two major phases:

Phase I Reactions

Phase II Conjugation

And then there is the less well-known third phase:

Phase III Antiporter Activity

Your Genetic Detox + Genetic Nutrition,

Plus Action Plan

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DETOXIFICATION

Phase I Reactions

Phase I is made up of a family known as the CYP450 Family of enzymes. You can think of these enzymes

as the first line of defense. The method of protection is to use oxygen to modify toxic compounds,

however a significant side effect of Phase I detoxification is the production of free radicals as the toxins

are transformed from their original state, causing them to be more reactive, volatile and potentially

damaging to the body.

The act of modification within Phase I is known as Biotransformation. Biotransformation describes

substrates such as chemical compounds such as drugs and steroid hormones to be primed for

conjugation (conversion and elimination) via the oxidation (oxygen). This process supports the

conversion of environmental pro-carcinogens to reactive intermediates, but still having a carcinogenic

effect due to the volatility of Phase I. Another example is that CYP enzymes are involved in the oxidative

metabolism of innate oestrogens, which may otherwise play a critical role in the formation of breast and

prostrate cancer.

So once Phase I has achieved biotransformation, many of these modified toxins go on to the next phase

(Phase II) within the detoxification sequence to support clearance of volatile compounds from the body.

We can now see that increased Phase I enzyme activity is both good and bad. Because it increases the

metabolism of environmental toxins which is essentially a good thing. But can also significantly leads to

higher circulating free radicals.

Within detoxification this is the most significant detail, which can and does typically under-pin why so

many people struggle with detoxification.

The importance of understanding the background of the individual’s basic health blueprint toward

Oxidative Stress and further more Inflammation cannot be over-looked.

These TWO factors alongside the presence and functionality of Phase I and Phase II enzymes heavily

determines the success of any detox, as well as reaction state known as a Healing Crisis especially when

raised Phase I increases the potency of certain prescription medications.

For this reason ALL gene enzyme variants within the Phase I enzyme activity are reported as negative.

Inducers of Phase I activity:

Cigarette smoke, charred food, caffeine, alcohol, cruciferous vegetables, and St John’s Wort.

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DETOXIFICATION

Phase II Conjugation

Foods which influence Phase II conjugation are those we typically consider when influencing the liver for

detoxification.

Kale, cruciferous vegetables, spring onions, celery, garlic etc typically upregulate the enzymes involved

within Phase II detoxification.

During Phase II, substrates made volatile via Phase I are then de-activated and made water-soluble. This

is a crucial process that prepares them for excretion which occurs courtesy of bile (stored within the

gall-bladder) deposited into small intestine. Or via the kidneys to urine.

Foods to support Phase II Conjugation

Cauliflower

Broccoli

Onion

Garlic

Purple sprouting

Green tea, and other teas

Olive oil

Apple (Granny Smith)

Mung beans

Sesame

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DETOXIFICATION

Six Conjugation Pathways within Phase II Liver Detoxification:

There are 6 conjugation pathways within Phase II of liver, all of which must be functioning

adequately to achieve complete and successful detoxification from within the liver.

1. Glucoronidation (UGT)

Substrates are conjugated with glucuronic acid via UDP-glucuronosyltransferase

2. Sulphonation (SULT)

Substrates are conjugated via suphontransferase enzymes

3. Glutathione conjugation (GST)

Substrates are conjugated with glutathione via glutathione transferase enzymes.

4. Amino acid conjugation (GLYAT)

Substrates are conjugated with glycine via glycine N-acyltransferase in the

mitochondria of liver and kidney cells. This process affects mitochondrial ATP

production.

5. Acetylation (NAT)

Substrates are conjugated via the addition of an acetyl group by the N-terminal

acetyltransferase enzymes.

6. Methylation (MT)

Substrates are conjugated by the addition of a methyl group via methyltransferase

enzyme.

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DETOXIFICATION

Phase III Transporter

Phase III involves the transportation of the now inert substances. This can be across cellular barriers

within the liver into bile for elimination. As well as the conjugated and now inert substances across

blood-brain barrier or removal of xenobiotics from the blood within the kidney and small intestine.

Phase III strongly influences the absorption, distribution and elimination of xenobiotics and

pharmaceutical drugs.

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DETOXIFICATION

7

LIFESTYLE FACTORS INFLUENCING DETOXIFICATION

Lifestyle factors and habits that negatively influence toxicity burden:

o Eating a standard western diet.

o Eating without fasting between meals.

o Over-eating.

o Exposure to heavy metals like mercury and lead

o Petrochemicals, residues, pesticides, and fertilizers.

o Food allergies, environmental allergies.

o Mould and mycotoxins.

o Medications

o Internal Toxins; bacteria, fungus, viruses and yeast

o Hormonal and metabolic toxins that aren’t eliminated properly.

o Mental, emotional, and spiritual.

(isolation, loneliness, anger, jealousy and hostility)

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DETOXIFICATION

Toxic exposure is both generated from within as well as through lifestyle

choices:

INTERNAL EXTERNAL Oxidative stress Smoking

Stress Alcohol

Dysbiosis from bacterial, fungal, viral infections

Diet: sugar, trans-fats, food chemicals, herbicides, pesticides

Hormones and other inflammatory chemicals Air pollution

Histamine Household detergents

Emotions Cosmetics

Radiation

Water with chlorine and fluorine

Mould, pollen and certain algae

Heavy metals (aluminum, lead, mercury)

Electrical smog

INTERNAL VS EXTERNAL OFF-SETTING

Whole food, lifestyle, and an informed elimination diet

alongside an increase in the correct nutrients to match

genetic requirements can significantly cut the internal

noise down, in the form of inflammation and oxidative

stress.

Eat: Cleansing foods, brassica family, beetroot

Increased phytonutrient intake

Support the body with: Quality nutrients, protein

powders and antioxidants

Consume: Organic foods

Avoid allergenic foods: Elimination diet

Reduce environmental exposure, including electrical

smog

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DETOXIFICATION

Do Environmental Toxins have the same impact on everyone?

No, there is a spectrum of vulnerability which is reflected clearly within each individual genetic profile.

Phase I, Phase II, Phase III all play specific roles within the downstream and net clearance of toxins from

our tissues. There are also lots of other factors to consider throughout this process.

Not only is oxidative stress and our ability to deal with oxidation hugely important, but our ability deal

with inflammation from a genetic perspective is also hugely influential upon our ability to successfully

move volatile compounds around the body.

Therefore, there is a small group of people whose threshold can be so much lower than the rest of us,

when it comes to our capacity to detoxify. These people have been termed ‘the canaries in the coal-

mine’, since they react more acutely to the toxins we are all exposed to.

This remains an important consideration within any detox programme. However, if you are one of the

sub-section who finds it difficult to shift toxins due to a combination of genetic factors, then your

Genetic Detox will be even more vital in creating a precision programme to lessen this challenge.

Gene SNP / SNV = Potentially the Weakest Link

in the chain

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DETOXIFICATION

DOSE IS NOT ALWAYS THE POISON!!

In terms of toxicology we used to think of DOSE being THE poison..

However, we now know that when low levels of toxins are presented in the body together the affects

can be far more harmful than one singular dose of a high-level poison.

External Exposure + Internal Exposure = TOTAL Toxic Burden (& cellular mayhem!!)

1+1 = Exponential Harm

PLUS, GENETICALLY SOME OF US ARE GIVEN A SMALLER BUCKET!!

How big and how full is your bucket?

o Clean diet

o Clean air

o Clean water

Vs

o Pesticides

o Alcohol

o Caffeine

o Sugar

o Allergenic food

What this means is that some of us have a Genetic predispositions to having a smaller bucket!, and

therefore do not have optimal functioning detoxification pathways, running the risk of filling up that

bucket more quickly.

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DETOXIFICATION

Signs of Poor Detoxification:

Symptoms of poor detoxification results from Internal + External toxicity burden MINUS the rate at

which the liver can eliminate toxins. Primarily this is determined by the individual’s genetic

detoxification strengths and weaknesses. Second to this, detoxification pathways are influenced

greatly (induced or inhibited) by nutrition and lifestyle habits.

Poor detoxification can look like this:

• Gastro-Intestinal Tract:

Halitosis, bitter taste, bloating, fatty stools, constipation, diarrhea, intolerance to

fatty foods, swollen liver, gallbladder problems

• Immune System:

Food allergies, skin issues, asthma, recurrent infections

• Endocrine System:

Infertility, PMS, weight gain, depression, anxiety, mood swings

• Nervous system:

Recurrent headaches, dementia, poor memory and concentration, neuralgia

• Musculo-Skeletal System:

Muscle aches and weakness, arthritis

• Other:

Sensitivity to chemical and odours, chronic fatigue, lethargy, anaemia and

premature ageing

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DETOXIFICATION

GENETIC RESULTS: PHASE I

ADH1B Alcohol Dehydrogenase 1B, Beta Polypeptide

ADH1B Variant Result Description Rs1229984 Arg48His Conversion of ethanol to acetaldehyde

Rs2066702 Arg370Cys Conversion of ethanol to acetaldehyde

Variants on this gene affects metabolism of a wide variety of substrates such as ethanol, retinol,

alcohols, hydroxysteroids, lipid peroxidation products.

ADH1C Alcohol Dehydrogenase 1C, Gamma Polypeptide

ADH1C Variant Result Description i6060959 IIe350Val High enzyme activity and rate of conversion of

ethanol to acetaldehyde. Increased risk of acetaldehyde toxicity.

Rs1693482 Arg272GIn High enzymatic activity and rate of conversion of ethanol to acetaldehyde. Increased risk of acetaldehyde. Most common genotype in Caucasions

Variants on this gene affects metabolism of a wide variety of substrates such as ethanol, retinol,

alcohols, hydroxysteroids, lipid peroxidation products.

Low enzyme activity may increase vulnerability to ethanol intoxication, however high enzyme activity

may increase the risk of acetaldehyde toxicity. Acetaldehyde is significantly more toxic than alcohol and

is carcinogenic in humans.

ALDH2 Aldehyde Dehydrogenase 2 Family (mitochondrial)

ALDH2 Variant Result Description Rs671 Glu457 Detoxification of acetaldehyde

Variants on this gene affects alcohol metabolism. Low enzyme activity or absence of this active form

increases the chance of acute alcohol intoxication. With the increased exposure of acetaldehyde in

those with the inactive form to greater susceptibility to many types of cancer.

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CYP1A1 Cytochrome P450, Family 1, Subfamily A, Polypeptide 1

CYP1A1 Variant Result Description Rs1048943 A4889G Normal enzyme activity. Lower risk of oxidative

Rs1799814 1295C>T Conversion of ethanol to acetaldehyde

Primarily the role of this enzyme is involved in oestrogen metabolism. However, variants on this enzyme

also affect how we metabolise drugs and the synthesis of cholesterol, steroids and other lipids. It is

unduced by chemicals released from burnt food and other substances; coal, tobacco, wood, chargrilled

meat.

Variant associated with up-regulation can lead to good oestrogen metabolism, but also result in high

amounts of circulating pro-carcinogens. Particularly when Phase II detoxification pathways are not

working adequately.

CYP1A2 Cytochrome P450, Family 1, Subfamily A, Polypeptide 2

CYP1A2 Variant Result Description Rs762551 -163A Normal (slow) metabolism of substrates such as

caffeine and paracetamol and other pharmaceutical drugs

Variants on this enzyme affect how we metabolise chemicals released from burnt food and other

substances; coal, tobacco, wood, chargrilled meat and caffeine and paracetamol. These are metabolized

into carcinogenic intermediates that need to then pass through our system.

The most common variants are associated with up-regulated enzyme activity and increased metabolism

of environmental toxins which may increase the risk of oxidative damage.

CYP1B1 Cytochrome P450, Family 1, Subfamily B, Polypeptide 1

CYP1B1 Variant Result Description Rs10012 R48G Some up-regulation of enzyme activity. Increased

risk of oxidative damage and some cancers, particularly if COMT activity is low and GSTM1 id null

Rs1056836 L432V Normal CYP1B1 enzyme activity. Lower risk of oxidative damage

Rs1800440 N453S Normal CYP1B1 enzyme activity. Lower risk of oxidative damage

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Variants on this enzyme affect how we metabolise chemicals released from burnt food and other

substances; coal, tobacco, wood, chargrilled meat and caffeine and paracetamol. These are metabolized

into carcinogenic intermediates that need to then pass through our system.

CYP2A6 Cytochrome P450, Family 2, Subfamily A, Polypeptide 6

CYP2A6 Variant Result Description Rs1801272 479T>A Normal metabolism of nicotine, and of

anticoagulant and other pharmaceuticals

Variants on this enzyme affect how we metabolise warfarin and other pharmaceutical drugs, as well as

nicotine, aflatoxin and nitrosamines from cigarette smoke

Variants are associated with down-regulation, with slower metabolisers not able to efficiently

metabolise warfarin or nicotine. This can exert greater effect and therefore influence dosage.

CYP2C19 Cytochrome P450, Family 2, Subfamily C, Polypeptide 19

CYP2C19 Variant Result Description Rs12248560 -806C>T Normal metabolism of anticoagulants and other

pharmaceutical drugs

Rs4244285 681G>A Down-regulated CYP2C19 enzyme activity and slower metabolism of substrates

Rs4986893 Trp212Ter CYP2C19*1 genotype. Normal CYPC19 enzyme activity and metabolism of substrates

Variants on this enzyme affect how we metabolise a wide variety of pharmaceutical drugs including

anticonvulsants, proton pump inhibitors, antidepressants, sedatives and antimalarials. This can exert

greater effect and therefore influence dosage.

CYP2C9 Cytochrome P450, Family 2, Subfamily C, Polypeptide 9

CYP2C9 Variant Result Description Rs1057910 1359L Normal enzyme activity and metabolism of anti-

inflammatories and anticoagulant drugs

Rs1799853 R144C Normal enzyme activity and metabolism of ibuprofen and warfarin

Variants on this enzyme affect how we metabolise a wide variety of pharmaceutical drugs including

anticonvulsants, blood sugar lowering drugs, anti-inflammatories, and anticoagulants. Variants are

15

associated with a down-regulated enzyme activity and slower metabolism of certain drugs, most notably

ibuprofen and warfarin.

Warfarin may also be impacted by a the -1639G>A variant on the VKORC1 gene which controls the

activation of vitamin K. This can exert greater effect and therefore influence dosage.

CYP2D6 Cytochrome P450, Family 2, Subfamily D, Polypeptide 6

CYP2D6 Variant Result Description Rs1065852 T100C Normal enzyme activity and substrate

metabolism including many common clinical drugs

Rs1135840 S486T Increased (rapid) enzyme activity and substrate metabolism

Rs16947 R296C Increased (rapid) enzyme activity and substrate metabolism

Rs28371706 T1071 Normal (extensive) enzyme activity and substrate metabolism including many common clinic drugs

Rs35742686 2549delA Normal (extensive) enzyme activity and substrate metabolism

Rs3892097 1846G> Normal (extensive) enzyme activity and substrate metabolism

Rs5030655 1707delT Normal (extensive) enzyme activity and substrate metabolism

Variants on this enzyme affect how we metabolise as many as 25% of commonly prescribed drugs as

well as lipids, hormones and toxins. To include antidepressants, antispsychotic, analgesics and anti-

tussives, beta adrenergic, blocking agents, antiarrythmics and antiemetics.

Poor metabolisers do not clear codeine to morphine and thus experience no analgesic effect.

Rapid metabolisers (3+ functional alleles) experience morphine toxicity.

CYP2E1 Cytochrome P450, Family 2, Subfamily E, Polypeptide 1

CYP2E1 Variant Result Description Rs2031920 Rsal Normal enzyme activity and alcohol metabolism

Metabolises endogenous substrates that are carbon based, such as ethanol, acetone, and acetal. As

well as exogenous substrates including benzene, tetrachloride, ethylene glycol and nitrosamines.

This enzyme is involved in varied liver processes, such as gluconeogenesis, hepatic cirrhosis, diabetes

and cancer – accountable for up to 10% of ethanol oxidation in the liver.

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CYP3A4 Cytochrome P450, Family 3, Subfamily A, Polypeptide 4

CYP3A4 Variant Result Description Rs2740574 -392G>A Normal enzyme activity and metabolism of

pharmaceutical drugs. Lower risk of oxidative damage

The CYP3A4 enzyme is involved in the metabolism of approximately half the drugs in use today. To

include acetaminophen, codeine, cyclosporine A, diazepam and erythromycin. It also metabolises some

steroids and converts oestradiol to oestriol.

Inhibited by grapefruit, antifungals, and antibiotics.

MAOA Monoamine Oxidase A

MAOA Variant Result Description Rs3027399 G82315C Wild genotype. High MAOA activity and rapid

metabolism of monoamine neurotransmitters

Rs6323 R297R Low MAOA activity and slow metabolism of monoamine neurotransmitters

Rs909525 C42795T Low MAOA activity and slow metabolism of monoamine neurotransmitters

MAOA enzymes deactivate certain neurotransmitter activity. Men only carry ‘one allele’ inherited from

their mother, and therefore will not inherit a ‘balancing’ allele.

MAOA enzyme is responsible largely for the breakdown of serotonin, melatonin, noradrenalin and

adrenalin. It also metabolises dopamine, tyramine and tryptamine equally with another gene that we

will be looking at next, MAOB

MAOA has been nicknamed one of the ‘warrior genes’, because variants have been associated with

anger and aggression due to slower neurotransmitter breakdown – which may in turn be amplified if

COMT variants are also present.

Conversely, a combination of wild allele has been labelled the ‘worrier’ genotype, associated with low

mood due to rapid breakdown of neurotransmitters.

MAOB Monoamine Oxidase B

MAOB Variant Result Description Rs1799836 A118723G Possible reduced MAOB enzyme leading to

breakdown of substrates.

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MAOB enzymes deactivate certain neurotransmitter activity. Like MAOA, men only carry ‘one allele’

inherited from their mother, and therefore will not inherit a ‘balancing’ allele.

MAOB is the main enzyme responsible for the breakdown of phenethylamine, benzylamine, histamine

and some pharmaceuticals. It also metabolises dopamine, tyramine, and tryptamine equally with MAOA

PON1 Paraoxonase 1

PON1 Variant Result Description i6060365 L55M Associated with low PON1 enzyme activity

Rs6323 R297R Low MAOA activity and slow metabolism of monoamine neurotransmitters

Rs662 Q192R Reduced PON1 activity and reduced ability to detoxify inflammatory oxidants, as well as dietary carcinogens

Variants on this enzyme decrease activity and therefore increase risk of exposure to harmful chemicals,

oxides lipids and the development of atherosclerosis. Since Pon1 enzymes are responsible for the

detoxification of organophosphates (the base for insecticides herbicides, and nerve agents), oxidized

lipids and also aromatic esters. It is associated with HDLs and may protect against development of

atherosclerosis.

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DETOXIFICATION

GENETIC RESULTS PHASE II

COMT Catechol-O-Methyltransferase

COMT Variant Result Description Rs4633 H62H Associated with low COMT activity

Rs4680 V158M Approximately 4X lower COMT activity leading to slow methylation and deactivation of substrates

The COMT gene is responsible for breaking down and inactivating dopamine, adrenalin and noradrenalin

by transferring a methyl group from SamE to itself rendering it more agreeable for excretion.

Because there is competition between SamE and SAH for the binding site on COMT, a build-up of SAH

with reduce COMT activity.

COMT is also involved in oestrogen metabolism.

Reduced COMT may lead to reduced function and excess methyl groups causing irritability, heightened

stress response, hyperactivity, abnormal behavior and heightened pain sensitivity. Individuals with

normal COMT activity and variants on VDR causing low activity may have low dopamine levels and

increased need for methyl donors and dopamine precursors.

All this may lead to imbalance between noradrenalin levels and dopamine levels, which have been

implicated in conditions such as ADD/ADHD and Parkinson’s disease.

GSTM1 Glutathione S-Transferase Mu 1

GSTM1 Variant Result Description Rs366631 -A1998G Associated with low PON1 enzyme activity

GSTM1 is a member of a class of enzymes which function in the detoxification of certain carcinogenic

compounds, therapeutic drugs, environmental toxins and products which can create oxidative stress in

the body. Over 50% of the population have a NULL genotype, with both copies absent.

GSTP1 Glutathione S-Transferase Pi 1

GSTP1 Variant Result Description Rs1138272 A1114V Normal GSTP1 enzyme activity. Normal

glutathione conjugation of substrates

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Rs1695 I105V Associated with decreased glutathione conjugation activity

GSTP1 are a family of enzymes that play an important role in detoxification of xenobiotcs and therefore

play a role in susceptibility to cancer and other diseases.

GSTT1 Glutathione S-Transferase (GST) Theta 1

GSTT1 Variant Result Description Rs11550605 Thr104Pro

GSTT1 is a member of a family of proteins that that play an important role in detoxification of certain

drugs pesticides, herbicides, and carcinogens. GSTT1 is also often entirely absent 50-6-% om Asians,

15% om White populations, 15-20% in African and less than 10% in Hispanic populations. This gene is

associated with cancer.

NAT1 N-Acetyltransferase 1

NA1 Variant Result Description Rs4986782 R187Q

Variants on this gene affect metabolism of various prescription drugs, caffeine, other xenobiotics and

function in folate catabolism. Slow activity has been linked to various forms of cancer including lung,

bladder, breast and pancreas.

NAT2 N-Acetyltransferase 2

NA2 Variant Result Description Rs1799930 G590A Normal to slow acetylation of substrates

Rs1799931 G857A Rapid acetylation of NAT2 substrates

Rs1801279 G191A Rapid acetylation of NAT2 substrates

Rs1801280 T341C Rapid NAT2 enzyme activity and acetylation of substrates

NAT2 variants both activate and deactivate various pharmaceutical drugs and carcinogens, as well as

detoxifies caffeine.

Variants are associated with slow activity and increased incidence of cancer and drug toxicity. For

accurate assessment consider the four SNP panel in orchestra.

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SULT1A1 Sulfotransferase Family, Cytosolic, 1A, Phenol-Preferring, Member 1

SULT1A1 Variant Result Description i6018900 Arg213His Associated with possible reduced sulfotransferase

activity

Rs1042157 C973T Associated with decreased sulphonation of compounds including steroid hormones, catecholamines and phenolic drugs

The Sulfotransferase family binds to and therefore helps eliminate many steroid hormones,

neurotransmitters, drugs, fat soluble vitamins as well as xenobotic compounds. Decreased activity of

this enzyme results in impaired sulphoconjugation.

SULT1E1 Sulfotransferase Family, 1E, Member 1

SULT1E1 Variant Result Description Rs11569705 Asp22Tyr Associated with normal SULT1E1 enzyme activity

and sulfonation of substrates

Rs34547148 Ala32Val Normal SULT1E1 sulphation of substrates

SULT1E1 is expressed in much of human tissue, to include the liver, the jejunum, the mammary

epithelium cells, endometrium and testis, This enzyme helps to control levels of oestrogen receptor

within these tissues and the activation / inactivation of oestrogen.

Impairment of this enzyme can lead to the growth of tumors in hormone sensitive cancers such as

breast or endometrial cancers.

SULT2A1 Sulfotransferase Family, Cytosolic, 2A, dehydroepiandrosterone (DHEA),

Member 1

SULT2A1 Variant Result Description Rs11569680 Lys227Glu Normal enzyme activity

Rs182420 C47868938T Associated with decreased enzyme activity

Sulfotransferases aid in the metabolism of drugs and endogenous compounds by converting toxic

compounds into more hydrophilic water-loving sulphates to then be easily excreted. This enzyme also

plays a role in catalyzing the sulphation of steroids, particularly DHEA, and bile acids in the liver and the

adrenal glands. It is thought this plays a significant role in the inherited adrenal androgen excess in

women with polycystic ovary syndrome.

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TPMT Thiopurine S-Methyltransferase

TPMT Variant Result Description Rs1142345 Tyr240Cys Normal enzyme activity and metabolism of

thiopurine drugs

Rs1800460 Ala154Thr Normal enzyme activity and metabolism of thiopurine drugs

Rs1800462 Ala80Pro Normal enzyme activity and metabolism of thiopurine drugs

Variants on this enzyme can result in sensitivity and toxicity to thiopurine drugs.

UGT1A1 UDP Glucuronosyltransferase Family 1, Member A1

UGT1A1 Variant Result Description Rs4148323 G211A Associated with UGT1A1 enzyme activity

Rs4148324 T179333G Associated with UGT1A1 enzyme activity and glucoronidation substrates

UGT1A1 is an enzyme of the glucuronidation pathway, that transforms steroids, bilirubin, hormones,

and drugs into water-soluble excretable metabolites. The most common deficiency of UGT1A1 enzyme

is Gilbert’s syndrome, characterized by intermittent unconjugated hyperbilirubinemia.

Decreased enzyme activity also leads to inactivation of oestrogens and reduced detoxification of

environmental toxins, carcinogens and their relative metabolites.

UGT1A6 UDP Glucuronosyltransferase Family 1, Member A6

UGT1A6 Variant Result Description Rs17863783 Val209Val Normal enzyme activity

UGT1A6 is an enzyme of the glucuronidation pathway, that transforms steroids, bilirubin, hormones,

and drugs into water-soluble excretable metabolites.

22

DETOXIFICATION

GENETIC RESULTS: PHASE III

ABCB1 ATP-Binding Cassette, Subfamily B, Member 1

ABCB1 Variant Result Description Rs104542 3435T> Slower antiporter activity. May support

detoxification

Rs1128503 1236T>C Slower antiporter activity. May support detoxification

Also, known as the Multi Drug Resistance 1 (MDR1), this gene is member of a family of genes involved in

the clearance and decreased drug accumulation in multi-drug resistant cells. Mediating the resistance

to anticancer drugs.

This protein is also an integral part of the blood-brain barrier transportation system, shuttling a variety

of drugs from the brain back into the blood.

The wild genotype (CC) is associated with lower bioavailability and plasma levels of certain drugs due to

more effective detoxification.

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24

METHYLATION

Methylation can be a complex topic for many. It is a process by which ‘methyl groups’ in the form of

active nutrients, are then added to molecules. This process occurs within almost EVERY biochemical

reaction in the body. So, as you can imagine, virtually all of our biological processes involve methylation

to complete task in hand. And that methylation not only occurs billions of time every second, but also

contributes to numerous bodily functions, including:

• Detoxification

• DNA integrity

• Energy production

• Inflammation control

• Immune function

• Gene expression vs suppression

• Neurotransmitter balance

• Telomere protection (ageing)

Environmental factors such as diet, chemical or drug exposure and STRESS are all known to play a role in supporting or hampering methylation activity.

The Role of Genes in Methylation:

The purpose of understanding a genetic variant in the context of methylation provides guidance on how

to support the weakness. This can be ‘bottleneck-ing’ or ‘bypass-ing’ the genetic variant, thus

influencing health.

This report provides genotype variations organized within by the following methylation sub-cycles:

• The Folate Cycle

• The Methionine Cycle

• The Transsulphuration Pathway

• The BH4 Cycle / Neurotransmitter Metabolism

• The Urea Cycle

Let’s consider the result of impaired methylation. What does this mean to human health?

25

Impaired methylation may contribute to major conditions, including:

• Cardiovascular disease

• Unexplained miscarriages

• Problems during pregnancy

• Mood and psychiatric disorders

• Cancer

• Free radical damage (premature ageing)

• Diabetes

• Infertility

• Neural tube defects

• Adult neurological conditions

• Chronic fatigue syndrome

26

METHYLATION

FOLATE CYCLE

Folate is vitamin B9. Folate is ‘naturally’ occurring dietary folate and folic acid. Folic acid is a

‘monoglutamate’ form of the vitamin, which is found in supplements and fortified foods.

Folate requires vitamin B3 as a co-factor to convert it into a usable form of DHF.

Within the Folate Cycle a number of conversions take place (viewed in the table above), requiring active

enzymes within relevant genes and nutrients to complete. Absorption of folate may then be impacted

by variants on the GCPII gene, and the RFC1 or DHFR genes.

5-MTHF then feed both the Methionine and BH4 Cycles, therefore a complete breakdown and

utililisation of Folate is required in order to be made full use of.

Therefore, variants on the MTHFR can lead to low levels of transmitters and strain on the BH4 Cycle.

With the amount of BH4 then affecting the function of the urea cycle.

For management of good folate levels, ensure adequate intake of all B vitamins, particularly B2, B3, and

B6 as co-factors.

DHFR Dihydrofolate Reductase

DHFR Variant Result Description Rs1643649 A16352G Supports neurotransmitter synthasis

Rs70991108 19bp DEL

Anti-folate drugs such as methotrexate target DHFR to deplete cells of reduced folate resulting in the

suppression of purine and pyrimidine synthases.

Variants on the DHFR gene may down regulate activity and ay protect against certain cancers (colorectal

cancer and childhood leukaemia), similar to the action of methotrexate. However, the consequent

deficiency of folate can increase susceptibility to megoblastic anaemia, neural defects and spina bifida.

27

GCPII Glutamate Carboxypeptidase II

GCPII Variant Result Description Rs202700 C1561T Normal intestinal absorption of dietary folate

Variants are associated with down regulation of the gene resulting in impaired intestinal absorption of

dietary folate resulting in lower blood folate levels and consequent hyperhomocysteinemia.

MTHFD1 Methylenetetrahydrofolate Dehydrogenase 1

MTHFD1 Variant Result Description Rs1076991 C105T Associated with increased risk of NTD’s in

combination with G1958A

Rs1950902 R134K Risk of disruption to nucleotide synthesis and reduced 5-MTHF levels

Rs2236225 G1958A May impact 5-MTHF levels and increase demand for chlorine as a methyl-group donor

Variants have been linked to increased risk of folate sensitive neural tube defects and endometriosis

related infertility due to choline depletion.

MTHFR Methylenetetrahydrofolate Reductase (NAD(P)H)

MTHFR Variant Result Description Rs1801131 A1298C Reduced gene function may result in lower 5-

MTHF and BH4 depletion

Rs1801133 C677T Reduced gene function impacting 5-MTHF levels and THF and methionine regeneration

MTHF catalyzes the conversion of folate to ‘active folate’, which then donates to the Methionine Cycle

which support DNA synthesis and repair, vital for healthy cell division, as well as metabolism of

neurotransmitters, phospholipids and proteins such as myelin.

MTHFR activity can be supported by increasing the intake of folate (B9) and the cofactors B2, B3, B12

and zinc.

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RFC1 Reduced Folate Carrier 1

RFC1 Variant Result Description Rs1051266 A80G Reduced ability to take up, retain, and metabolise

folate – possible raised homocysteine levels

A transporter of folate gene, involved in the regulation of intracellular concentrations of folate.

SHMT1 Serine Hydroxymethyltransferase 1

SHMT1 Variant Result Description Rs1979277 C1420T

This is a B6 dependent enzyme.

TYMS Thymidylate Synthetase

TYMS Variant Result Description Rs2790 Neutral genotype – no impact on DNA synthesis

or repair

Variations on this gene impact DNA stability, replication and repair. Absence of which affects risk of

certain cancers.

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METHYLATION

METHIONINE CYCLE

AHCY S-Adenosylhomocysteinase

AHCY Variant Result Description i5000928 A344G Impact on conversion of SAH to homocysteine

Rs819147 AHCY-01 Impact on conversion of SAH to homocysteine

Rs819171 AHCY-19 Impact on conversion of SAH to homocysteine

Genetic deficiency of AHCY activity in humans has been reported in only a few cases, metabolic effects

of AHCY deficiency include elevated blood levels of SAH, SAMe and Methionine.

BHMT Betaine-homocysteine S-methyltransferase

BHMT Variant Result Description Rs3733890 R239Q Less effective ‘short cut’ conversion of

homocysteine to methionine

Rs567754 BHMT/2 No impact on short cut homocysteine to methionine conversion

Rs651852 BHMT/8 No impact on short cut homocysteine to methionine conversion

BHMT is not B12 dependent as in the ‘long’ route when recycling homocysteine to methionine. Rather

this is the ‘short’ route and is dependent on adequate levels of betaine and zinc.

The activity of this gene product can be affected by cortisol levels (stress) and may play a role in

ADD/ADHD by affecting norepinephrine levels.

FUT2 Fucosyltransferase 2

FUT2 Variant Result Description Rs1047781 A385T Secretor genotype – susceptibility to H.Pylori

infection and gastritis linked to reduced B12 absorption

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Rs601338 W143X Secretor genotype – susceptibility to H.Pylori infection and gastritis linked to reduced B12 absorption

FUT2 is the secretor gene within the gastrointestinal mucosa. Absorption of B12 requires the secretion

of the glycoprotein intrinsic factor.

The FUT2 secretor status has been linked with both H. pylori infection and gastritis.

B12 malabsorption and low levels of serum vitamin B12 have higher prevalence of H. pylori infection.

MAT1A Methionine Adenosyltransferase 1, Alpha

MTHFD1 Variant Result Description i5007205 C164A Associated with normal MAT activity and

conversion of methionine to SAMe

i5007206 C1070T Associated with normal MAT activity and conversion of methionine to SAMe

i5007207 T914C Associated with normal MAT activity and conversion of methionine to SAMe

i5007208 C790T Down regulation of MAT activity which may lead to hypermethioninemia

Rs1985908 T1297C Associated with normal MAT activity and conversion of methionine to SAMe

MAT serves to form SAMe, which is the master methyl donor. Variants on the MAT genes, particularly

inactive MAT activity may lead to hypermethioninemia, low SAMe and therefore slow methylation.

MTR 5-Methyltetrahydrofolate-Homocysteine Methyltransferase

MTR Variant Result Description Rs1805087 A2756G Neutral genotype – no impact on MTR or B12

levels

Variants of MTR can result in UP-regulation of the gene and increased usage and therefore deficiency of

methylcobalamin / B12. MTR activity can be supported by supplementing the methylated form of B12.

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MTRR 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase

MTRR Variant Result Description i6015189 H595Y Neutral genotype does not impact B12 or

homocysteine

Rs162036 K350A Reduced ability to recycle B12 impacting MTR conversion of homocysteine

Rs1801394 A66G Neutral genotype does not impact B12 or homocysteine

MTRR regenerates MTR with use of SAMe as donor. I also converts vitamin B12 into its methylated

usable form.

Variants in MTRR can result in down-regulation of the gene activity and high homocysteine levels.

PEMT Phosphatidylethanolamine N-Methyltransferase

PEMT Variant Result Description Rs7946 G5465A Potential for reduced do novo choline synthesis

and higher homocysteine

PEMT supports the conversation of the inactive to the active form of choline, a significant source

relative to dietary intake.

Oestrogen induces the expression of this gene, allowing premenopausal women to make more of their

required choline.

Variants in PEMT alter this endogenous synthesis of choline, impacting conversion of homocysteine to

methionine via the short cut. This may lead to high homocysteine, particularly when there are variants

on MTHFR, MTR and MTRR genes.

TCN2 Transcobalamin II

TCN2 Variant Result Description RS1801198 C776G Likely to have reduced ability to absorb

cobalamin (Vitamin B12)

This gene affects the absorption of B12 via it’s binding protein to cobalamin. Transporting it from the

intestine into the blood cells.

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METHYLATION

TRANSSULPHURATION CYCLE

CBS Cystathionine Beta Synthase

CBS Variant Result Description Rs1801181 A360A One variant allele may cause up-regulated CBS

Rs234706 C699T CBS activity

Rs234715 C12646A Normal genotype, normal CBS activity

Rs2851391 A13637G Partially impaired CBS activity may lead to impaired conversion of homocysteine

Rs4920037 C19150T Associated with normal CBS activity

CBS catalyzed the conversion of homocysteine from the Methionine cycle to cystathionine, the first step

in the transsulphuration pathway. Requiring vitamin B6 and heme as co-factors.

Variants on CBS cause the ‘gate’ between homocycsteine to cystathionine to be left open, draining

homocysteine, while preventing it from being recycled into methionine. This further depletes B6, B12

whilst preventing the generation of SAMe.

Homocysteine is instead pulled down and converted into ammonia and cysteine.

High levels of ammonia puts pressure on the urea cycle and causes low BH4, disrupting

neurotransmitter metabolism.

High cysteine converts to toxic sulphites, putting pressure on SUOX.

CBS should always be considered alongside variants on MTHFR, MTR, BHMT, MUT to determine risk.

CTH Cystathionine Gamma-Lyase

CTH Variant Result Description Rs1021737 G1112T Compromised CTH activity

CTH encodes an enzyme that converts cystathionine to cysteine. The second step in the third cycle,

transsulphuration pathway requiring vitamin B6 as a co-factor.

The most abundant antioxidant in the human body, Glutathione is synthesized via the CTH gene from

available cysteine. Glutathione is important for a variety of biological functions including protection of

cells from oxidative damage by free radicals, detoxification of xenobiotics and membrane transport. All

this is vital for health.

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GSS Glutathione Synthetase

GSS Variant Result Description Rs6060124 G11705T Associated with normal glutathione synthesis

Rs6088659 A5997G Normal GSS activity, normal glutathione synthesis

GSS catalyses the second step in the synthesis of glutathione synthesis. Variants on this gene may cause

glutathione deficiency.

MUT Methylmalonyl CoA Mutase

MUT Variant Result Description i6060254 G1595A Associated with low circulation of B12 and

elevated homocysteine

MUT is a mitochondrial enzyme that converts Co-enzyme A to Succinyl-CoA, with B12 as co-factor.

Succinyl-CoA is an important enzyme within the Krebs cycle, crucial for energy, heme and P450 enzymes

discussed in Phase I of detoxification above.

SUOX Sulfite oxidase

SUOX Variant Result Description Rs705703 C5444T No variant alleles, normal SOUX activity

Variants on SOUX may result in sulphite sensitivity and neurological abnormalities. When present with

an up-regulation on CBS this is more pronounced. Sulphites are ingested via foo that we eat, but also a

natural by-product of the methylation cycle. Sulphur dioxide can cause irritation in the lungs, severe

asthma attacks in those who suffer from asthmas, as well as nausea, hives, and even more severe

allergic reactions.

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METHYLATION

BH4 CYCLE / NEUROTRANSMITTER METABOLISM

COMT Catechol-O-methyltransferase

COMT Variant Result Description Rs4633 H62H Low COMT activity, susceptibility to mood swings

Rs4680 V158M Low COMT activity, inefficient breakdown of catecholamines

Rs769224 P199P Low COMT activity, enzyme activity

COMT is responsible to breaking down and inactivating catecholamines dopamine, epinephrine, and

norepinephrine. This is completed by transferring a methyl group from the SAMe, rendering the

molecule amenable for secretion.

Because SAH and SAMe complete for binding sites, then a build-up of SAH will also reduce COMT

activity.

Variants on COMT lad to a reduced function, with excess methyl groups causing irritability, heightened

stress responses, hyperactivity, abnormal behavior and heightened pain sensitivity.

The balance between norepinephrine levels and dopamine levels has been implicated in ADD/ADHD and

other conditions such as Parkinson’s disease.

Those with normal COMT activity and variants on VDR causing low activity will also have low dopamine

levels and increased need for methyl donors and dopamine precursors.

MAOA Monoamine Oxidase A

MAOA Variant Result Description Rs3027399 G82315C Associated with aggressive behaviour

Rs6323 R297R Low enzyme activity, higher levels of neurotransmitters in the brain is associated with outward anger, anxiety and higher risk taking

Rs769224 P199P Associated with less aggressive behavior especially together with GG genotype for rs6323

This gene influences dopamine, norepinephrine and serotonin.

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Nicknamed the Warrior gene, since variants on this gene have been associated with anger and

aggression due to slower neurotransmitter breakdown. Wild Type alleles on this gene are associated

with faster breakdown of neurotransmitters which have been linked to low mood.

A combination of MAOA and COMT variants may cause severe neurotransmitter imbalances leading to

mood disorders, poor memory and concentration and aggressive behavior.

The combination of rs3027399 G, rs6323 G, rs909525 T, indicate a ‘NON-Warrior’ haplotype, since there

is no suggestion of a slowing of this enzyme function.

MAOB Monoamine Oxidase B

MAOB Variant Result Description Rs1799836 A118723G May be susceptible to negative moods due to

inefficient norepinephrine catabolism

MAOB plays an important role in the metabolism of neuroactive and vasoactive amines, including

histamine, and noradrenalin in the central nervous system as well as peripheral tissues.

Preferentially this protein degrades benzylamine and phenylethylamine.

QDPR

QDPR Variant Result Description Rs1031326 A690G Possible BH4 deficiency

Rs11722315 G17953T Reduced BH4 synthesis

Variants on this gene result in BH4 deficiency. When considered alongside CBS up-regulation creates

excess ammonia this further depletes BH4

VDR Vitamin D Receptor

VDR Variant Result Description Rs1544410 Bsml Normal VDR activity, normal dopamine synthesis

Rs731236 Taql Normal levels of vitamin D3, normal dopamine production

Rs7975232 Apal Low VDR activity leading to low dopamine synthesis

This gene is responsible for the receptor site of vitamin D3, the active form of vitamin D. This receptor

mediates an increase in dopamine production.

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Variants of Taq1, BsmI and ApaI lead to lower vitamin D levels causing low dopamine production. This is

good for those with COMT variants since there will be less circulating dopamine in need of breaking

down.

Individuals with variants of COMT but normal VDR activity will have higher dopamine level and low need

and tolerance for methyl donors and dopamine precursors, and the greatest susceptibility to mood

swings.

UREA CYCLE

NOS3 Nitric Oxide Synthase 3

NOS3 Variant Result Description Rs1799983 D298E

Rs3918188 C19635A Partially compromised NOS activity may result in higher levels of free radicals and ineffective ammonia detoxification

NOS synthesizes nitric oxide from L-arginine with the help of BH4.

Without adequate BH4, NOW generates the free radicals peroxynitrite and superoxide instead of nitric

oxide.

Variants on NOS cause low enaymatic activity.

Together with up-regulated CBS, down-regulated SUOX and variants on MTHFR will have an additive

effect and cause excess ammonia.

SOD2 Superoxide Dismutase 2, Mitochondrial

SOD2 Variant Result Description Rs2758331 G816T Affects ability to neutralize superoxide

Rs4880 A16V Affects ability to neutralize superoxide

SOD2 variants can result in a predisposition to oxidative stress. Ensure adequate intake of the co-factor

manganese.

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FOOD AND NUTRIENT RESPONSES

FADS1 FATS / FAT GENE rs174548 Function; Acetylcholine, rs174537 Function: Arachadonic Acid; GLA conversion

rs174548 Function; Acetylcholine

CG C alleles are associated with increased phosphatidylcholine levels. G Allele is associated with lowered phosphatidylcholine and low acetylcholine levels. Homozygous GG is associated with higher requirement for choline and phosphatidylcholine. In those susceptible to depression, excessive supplementation of phosphatidylcholine can induce depression. 2-5p of lecithin is fine.

rs174537 Function: Arachadonic Acid; GLA conversion

GT GG allele is associated with enhanced conversion of DGLA to AA due to increased enzymatic efficiency, systemic inflammation and inflammatory disorders and higher arachidonic acid levels. GT alleles are associated with intermediate AA levels and somewhat higher LDL and cholesterol levels. TT is associated with low AA levels and lower LDL and cholesterol levels.

FADS2 Function: conversion of ALA to EPA

rs1535 AG

G Alleles are associated with lower conversion. Homozygous GG is a low converter with 29% poorer conversion of ALA to EPA. Heterozygous AG is an intermediate converter, with 18% poorer conversion of ALA to EPA

VITAMIN B6

NBPF3 rs4654748

CT

The C allele is associated with lower B6 plasma levels, and increase in dietary B6 intake. 46% of the population is CT, resulting in low levels. CC results in double the lower plasma levels than a healthy cohort.

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VITAMIN B12

rs602662 AG

AG and GG alleles result in 15% lower plasma B12 due to malabsorption.

rs492602 CT CC alleles is associated with higher plasma levels of B12 than normal

VITAMIN D VDR

Taq1 rs731236 TT

Associated with D3 receptor activity. C and G alleles are associated with a HIGHER requirement and appears to correlate more with the development of infectious and auto-immune and other non-skeletal health outcomes.

Bsm1 rs1544410 GG Decreased risk of low bone density disorder

Fok1 rs3948464 CC T allele has poorer calcium absorption compared to the C allele. The TT genotype has higher bone turnover and increased cone loss and is associated with a lower BMD and osteoporosis in the lumbar spine. Ensure adequate calcium and vitamin D intake and reduce caffeine. Test vitamin D levels regularly.

VITAMIN C SLC23A2

rs12479919 CC

T alleles are associated with low absorption or plasma levels of vitamin C

ZINC SLC30A8

rs13266634 CT

C alleles are associated with less active transporter leading to low zinc transportation and plasma levels

VITAMIN K KVKORC1

rs9923231 CT

CC alleles are associated with normal active vitamin K levels. T alleles are associated with reduced active vitamin K levels. CT is linked with Warfarin sensitivity.

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LACTOSE PERSISTANCE LCT

rs4988235 CT

Likely to be lactose intolerant as an adult.

VITAMIN E

rs6025 GG

GG Homozygous are at a normal risk associated with thrombosis. A alleles raise the risk of blood clotting, in particular, thrombosis and pre-eclampsia

IRON HFE / TMPRSS6 (Genetic Variation: C282Y & H63D ) Hereditary hemochromatosis is a genetic disorder in which there is excessive accumulation of iron in the body, leading to iron overload. In individuals with the disorder, the daily absorption of iron from the intestines is greater than the amount needed to replace losses. Since the normal body cannot increase iron excretion, the absorbed iron accumulates in the body. Individuals who carry the genes for hereditary hemochromatosis may have no symptoms or signs and the disease is treatable if detected early. Severe symptoms and signs of iron overload include sexual dysfunction, heart failure, joint pains, liver cirrhosis, diabetes mellitus, fatigue, and hypermelanotic pigmentation.

HFE rs1800562 GG A and G Alelle lead to lowered hepcidin levels and increased, diminished iron homeostasis feedback loop, and a potential of increased iron absorption. Avoid excessive dietary intake of iron rich foods.

HFE rs1799945 CC NORMAL (lower serum iron and hemoglobin levels and correlates with higher risk for iron deficiency and iron deficiency anaemia).

TMPRSS6 rs4820268 AG G alleles are associated with lower serum iron levels and correlates with higher risk from iron deficiency anaemia.

SODIUM ACE / AGT

AGT rs699 CT Associated with INCREASED risk of hypertension

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VITAMIN A: Beta-Carotene Conversion BCMO1

rs12934922 AA

Reduction of conversion from beta-carotene to vitamin A, may need preformed vitamin A.

rs7501331 CT Associated with LOWERED conversion of beta-carotene to vitamin A

rs11645428 GG Variant, reducing conversion leading to higher beta-carotene levels

rs6420424 AG Variant, reducing conversion leading to higher beta-carotene levels

rs6564851 GT Variant, reducing conversion leading to higher beta-carotene levels

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VERY HIGH SENSITIVITY: You have 10 variants. No refined carbohydrates or grains, max 20% of calories from carbs; 1.75-2.25 cups daily of fresh fruit,

squash, root vegetables (not white potatoes), legumes. Consume minimum 28g fibre daily. Eliminate grains for 6 weeks, 3 times a year.

CARBOYDRATE SENSITIVITY: ADRB2, PPARG, TCF7L2, ACE, FAB2 ADRB2 Variant Rs1042713 GG, 2

Commentary: The G allele is associated with obesity and insulin resistance in the presence of refined and excessive carbohydrate intake. Elimination of all refined carbohydrates and overall reduction in carbohydrate intake is recommended. For optimal weight loss, consider a high-fat diet.

PPARG Variant Rs1801282 CC, 2

Commentary: C allele plays a role in the unfavourable formation of fat cells and lipid metabolism as well as the development of type 2 diabetes. Elimination of all refined carbohydrates and overall reduction in carbohydrate intake is recommended.

TCF7L2 Variant Rs7903146, rs12255372 TT TT, 4

Commentary: The T allele is associated with impaired glucose homeostasis in the presence of refined and or excess carbohydrates. Elimination of all refined carbohydrates and overall reduction in carbohydrate intake is recommended. Higher risk of type 2 diabetes

ACE Variant Rs4341 GG, 2

Commentary: G allele indicates the SNP is deleted. Incrementing a reduction of ACE by 150% and 200% for both alleles respectively, which in turn increases the general sensitivity to carbohydrates. Elimination of all refined carbohydrates and overall reduction in carbohydrate intake is highly recommended.

COELIAC PREDISPOSITION: HLADQA1 / DQB1 rs2187668 Stabilised rs2395182 Stabilised rs7775228 Compromised rs4639334 No Call rs4713586 No Call rs7454108 Bad

GENETIC MACRONUTRIENTS

CARBOHYDRATE

CARBOYDRATE SENSITIVITY: ADRB2, PPARG, TCF7L2, ACE, FABP2

COELIAC PREDISPOSITION: HLADQA1 / DQB1

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GENETIC MACRONUTRIENTS

VERY High Sensitivity

Focus 1.75-2.75 cups daily of fresh fruit, squash, root vegetables (beets, carrots, etc. – not white potatoes), and legumes; consume a maximum, of 1/2 cup at a time and overall maximum of 20% of calories from carbohydrate daily. (2cups is roughly equivalent to 500ml in volume; ¾ cup is roughly equivalent to 200ml in volume Avoid grains for a period of 6 weeks three times a year, refined carbohydrate, fruit juice, and sugars (e.g. bread, pasta, biscuits, and including sweeteners like honey, agave, or brown rice syrup), limit foods naturally high in sugars (like bananas, dates, and dried fruit); eliminate dairy – use coconut milk as a substitute. 0.75 cup raw or frozen berries daily for antioxidants (berries are best!); ½ cup is about 70g of fruit. Eat meals 4-5 hours apart and incorporate a snack in between meals when going longer than 5-6 hours between meals’ always leave at least 2-3 hours between a meal and snack; for weight loss, consider intermittent fasting plan of two large meals per day (e.g. lunch and dinner) with no snacks. Eat a wide variety of fruit and carbohydrate sources from across the spectrum. Incorporate cinnamon, cinnamon tea, fresh ginger, and ginger tea into the diet to optimise insulin receptor sensitivity if tests well. Limit consumption of browned and burned carbohydrates.

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FATS / SATURATED FAT

OVER-ALL SENSITIVITY: ADRB2, ADRB3, APOA2, PPARG, TCR7L2, FTO, FABP2,

APOC3, LPL

SENSITIVITY: You have 4 variants. No processed trans/oxidized fats; dietary fat 30-45% of total calories; approximately 65-100g fat daily for women

SATURATED FAT SENSITIVITY: FABP2, FTO, TCF7L2 SENSITIVITY: You have (2) 1+ variant.

Saturated fat up to 8-10% of total calorie intake-preference for organic, grass-fed sources.

FAT SENSITIVITY: ADRB2, ADRB3, APOA2, APOC3, PPARG, TCF7L2, FTO, LPL ADRB2 Variant Rs1042714 GG, 0

Commentary: The C allele is associated with higher levels of obesity in the presence of dietary fats. Reduction of total fats and elimination of processed/ trans/ oxidative fats is recommended

ADRB3 Rs4994 TT, 0

Commentary: C allele is associated with higher levels of obesity in the presence of processed, trans and oxidative fats.

APOA2 Rs5082 TT, 0

Commentary: CC genotype demonstrated higher body mass index scores and a higher incidence of obesity, but only if they consumed a diet high in saturated fat. The C allele is associated with a greater inflammatory response to unhealthy fats. Elimination of processed/ trans / oxidative fate is highly recommended.

PPARG Rs1801282 CC, 2

Commentary: The C allele plays a role in the unfavourable formation of fat cells and lipid metabolism as well as the development of type 2 diabetes. Reduction of processed/ trans / oxidative fate is highly recommended.

APOC3 Rs5128, not in 23&Me No Call

Commentary: The C allele is associated with a impaired ability to transport triglycerides from the blood into the cells for use as energy along with obesity ad metabolic syndrome in the presence of excess dietary fats. Reduction of processed/ trans / oxidative fate is highly recommended.

TCR7L2 Rs7903146 TT, 2

Commentary: This gene codes for blood glucose homeostasis. Genetic variants are associated with type 2 diabetes. The T allele is associated with metabolic syndrome in the presence of excess dietary saturated fats. Reduction of saturated fats and elimination of processed trans/oxidative fats is recommended.

LPL Rs328 CG, 0

Commentary: CC Homozygous (but not Heterozygous) are associated with a somewhat increased sensitivity to dietary fats. Reduction of total fats and elimination of processed/trans. Oxidative fats is recommended.

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Follow up testing

Depending on the number of genetic markers present within your profile, you may wish to consider

some follow up testing. This can be completed at home easily, via Functional Medicine home test kits.

The required samples are returned to the lab via courier, and results emailed to you within 1-4 weeks.

Genetic polymorphisms / enzyme deletions heavily influence the outcome of health. The following are

tests which can measure the outcome of specific enzyme deletions which may be present in your profile.

GSH (reduced glutathione) to GSSG (oxidized glutathione); a ratio marker for oxidative stress and cellular

toxicity.

Heavy metal toxicity can be assessed using a comprehensive element profile (urine). This could also

assess nutrient elements.

Urinary d-glucarate can be used to asses exposure to industrial toxins or xenobiotics and indicates high

CYP450 activity.

Detoxification enzymes – reduced glutathione, glutathione peroxidase, SOD (superoxide dismutase) can

be measured.

Urinary porphyrins, by products of damaged haemoglobin, can be clues to damage done by chemical or

heavy metal toxins.

Urinary organophosphates – specific compounds such as sulphates, pyroglutamate and orotate can be

measured.

A comprehensive stool analysis can indicate dysbiosis, and can also detect beta-glucuronidase which can

cause reversal of glucuronidation.

Nutrition and Lifestyle

Substances that up-regulate Phase I, such as alcohol, smoking, caffeine, charred foods and certain

medications can have a deleterious effect upon the balance of P1 and P2 activity, because the Phase II

may not be able to keep up with the increased demand.

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The result would be an increase in activated intermediates and free radicals, which can react with and

damage proteins, RNA and DNA, further promoting a cycle of unbalanced detoxification in the

individual.

Your Healthy Detoxification Programme should include a number of the following

action steps:

• Exclude foods and that are likely to contain toxins or food allergens.

• Eliminate or reduce toxic household and personal care produce.

• Avoid excess exposure to environmental pollutants such as exhaust fumes.

• Optimise nutritional needs including adequate protein, nutritional cofactors and antioxidants.

• Encourage the use of organic.

• Ensure adequate hydration

• Include regular appropriate exercise; yoga, or massage to increase circulation and metabolism

• Use of steam baths, saunas or Peat mud baths to induce sweating

• Address gut infections and imbalanced ecology

• Reduce heavy metal exposure both in the environment and from within the body