Orthomolecular Flashcards
*What nutrient is reduced by statins?
CoQ10
*Why do statins reduce CoQ10?
Statins’ role is to decrease body’s cholesterol synthesis. Both cholesterol and CoQ10 use the same metabolic pathway (Mevalonate Pathway). Statins inhibit HMG-CoA enzyme - required for pathway to progress.
(Aceytl-CoA to HMG-CoA to Mevalonic Acid to Cholesterol and CoQ10)
*What two nutrients does the Mevalonate Pathway metabolise?
CoQ10 and cholesterol
*Why is alpha-lipoic acid so effective as an antioxidant?
Universal antioxidant:
1. Functions in water soluble and fat soluble environments
2. Functions both intra-cellularly and extra-cellularly.
3. Regenerates other antioxidants eg vits C and E, glutathione.
*What are THREE key ways that chondroitin protects cartilage?
- Reduces enzymes that degrade cartilage.
- Inhibits inflammatory cytokines therefore reduces inflammation.
- Increases HLA production - lubricant in joints. NB Glucosamjne is the building block.
*Outline TWO ways that N-acetyl glucosamine can be of benefit for IBD.
- Protects / heals the mucosal barrier in GI tract through the production of mucins.
- Reduces ability of pathogenic bacteria to form biofilms.
*Briefly explain why betaine (TMG) can reduce the risk of cardiovascular disease.
Acts as a methyl donor to ensure homocysteine levels do not build up (highly inflammatory) as can damage vascular endothelium and cause atherosclerosis. Need homocysteine to either recycle back to methionine or convert to cysteine. Homocysteine can be remethylated to methionine by betaine-homocysteine
methyltransferase (BHMT). This enzyme uses betaine as
a methyl donor.
*Outline TWO ways in which phosphatidylserine is beneficial for Alzheimer’s disease
- Reduces hypothalmic inflammation to reduce damage.
- Reduces acetylcholinesterase to maintain acetyl choline levels (vital for memory and processing). Increases availability of ACH.
- Helps with production of other neurotransmitters:
a) dopamine
b) noradrenaline
c) seratonin.
Orthomolecular compound meaning?
Substances that are already found in our body ie we can make them ourselves but they deteriorate with age. Therapeutic doses can reduce chronic disease. NB Must be used in:
- correct dosage
- healthy environment ie good diet, sleep, exercise to work.
What is orthomolecular medicine?
Practice of restoration and maintenance of health through use of nutrients that are normally present in the body by providing optimal amounts of substances.
Nine orthomolecular compounds
CoQ10
Alpha-lipoic acid
Glucosamine
Chondroitin sulphate
MSM
Betaine TMG
Phosphodylserine
Phosphodylcholine
Myo-inositol
How does orthomolecular medicine fit in with naturopathy?
Focus of orthomolecular medicine is prevention therefore aligns
with core naturopathic philosophy “prevention is preferable to cure”.
Concept builds on the idea that creating an optimal nutritional environment in the body will reduce disease.
What can accelerate ageing process?
- Free radical exposure
- Chronic inflammation
- Toxic exposure.
Reversing or slowing it down is one goal of orthomolecular therapy.
Where can you find co-enzyme Q10?
Mitochondria (of every cell).
Plays a key role in ATP production (electron transport chain).
What are the two forms of Co-Q10?
Ubiquinone - oxidised form (lost electrons)
Ubiquinol - reduced form (gained electrons)
The two forms inter-convert.
Ubiquitous - everywhere in the body and in many foodstuffs!
How can the body’s Co-Q10 levels decline?
- Ageing
- Drugs (eg statins)
- Smoking
- Disease eg CVD
How much CoQ10 do you get from diet?
3 to 6 mg per day
TWO plant and TWO animal sources of CoQ10
Plant sources:
Nuts (eg peanuts, pistachios)
Sesame seeds
Olive oil
Fruit and vegetables including oranges, strawberries, avocado,
broccoli, cauliflower
Animal sources:
Meat
Poultry
Fish (eg herring, sardines, mackerel, trout)
Eggs.
What destroys CoQ10 in food?
Frying 14-32%. Destroys up to a third.
What age does coq10 levels decline?
40 (can be earlier if crap diet)
Which body areas use up the most coQ10?
Muscle cells and esp the heart.
Muscles need ATP in high quantities for muscle contraction.
Five uses for CoQ10
- Energy production
- Antioxidant
- Peridontal health
- Male and female fertility
- CV health
How is CoQ10 used for energy?
Electron transport chain (complex 2 of 4) which supports mitochondrial function and energy production.
Great for fibromyalgia and chronic fatigue.
What makes CoQ10 such a great antioxidant?
- Potent fat-soluble antioxidant that inhibits the peroxidation of cell membrane lipids.
- Neutralises free radicals produced by mitochondria and ageing
- Enhances SOD
NB CoQ10 naturally decreases with age while t ROS increases and imitochondrial function is impaired.
Mitochondrial dysfunction, associated with;
- fibromyalgia,
- Type 2 diabetes,
- CVD
- neurodegenerative diseases
- cancer.
NB Also for AI conditions - another chronic ageing disease. And lime disease.
What would be a disease of mitochondrial dysfunction?
Fibromyalgia.
Ageing?!!
How can CoQ10 help with peridontal health?
Low CoQ10 common in people with gum disease.
Lipopolysaccharides from the bacteria Porphyromonas
gingivalis trigger oxidative stress and mitochondrial dysfunction.
How does CoQ10 help with male fertility?
Protects sperm from oxidative stress (highly vulnerable)
200-300 mg for 6 months increases sperm health. Spermatogenesis 64-72 day cycle.
How does CoQ10 help with female fertility?
Impaired mitochondrial performance (low CoQ10) can drive age-associated oocyte (egg cell) deficits leads to infertility.
100–600 mg for ovarian health.
CoQ10 can lower blood pressure. How?
Poss via stabilisation of vascular membranes and antioxidant capabilities.
Increases superoxide dismutase function which is known to preserve nitric oxide.
Role of CoQ10 and heart health
- Crucial for cardiac muscle function.
- Protects against endothelial dysfunction and hence atherosclerosis.
- Reduces LDL oxidation.
- Inhibits NF-kB activation that follows ROS (is secondary to)
- Increases SOD to preserve NO activity to reduce BP.
- Stabilisation of vascular membranes and antioxidant capabilities.
How does superoxide dismutase aid heart health?
Preserves activity of nitric oxide (NO) - potent vasodilator ie protects it from peroxidation.
SOD found in all the healthy foods: leafy greens, cruciferous, nuts, seeds, wholefoods eg beans, lentils.
What therapeutic uses can CoQ10 be used for CV health?
- Hypertension
- Angina pectoris
- Congestive heart failure (build up of fluid in body as hart unable to pump correctly)
- Post-myocardial infarction.
Three signs of low CoQ10
- Cardiovascular disease
- Myopathy
- Depression
Cholesterol functions x 7
- Vitamin D and calcium synthesis
- Cell membrane integrity esp in brain
- Sex hormones - oestrogen, progesterone, testosterone
- Cortisol and related hormones
- Aldosterone for mineral and fluid balance
- Bile salts and acids needed for digestion
- Lipoproteins needed for triglyceride transport
CoQ10 contraindications?
- May decrease the effects of warfarin
- Can cause diarrohea if taken in a large dose… better to split throughout the day.
What is alpha lipoic acid?
- Organosulphur compound (synthesised by plants and animals).
- Naturally-occurring, short-chain fatty acid.
TWO forms of ALA?
- R-form (natural) - x 10 more potent
- S-form (synthetic).
Food sources of ALA
Widely available:
Plant sources: Brassicas, spinach, potato, carrots, beets, tomatoes, peas, brewer’s yeast.
Animal sources: Red meat (lamb, beef) and organ meats.
ALA role in energy production
-
Krebs cycle
Key co-enzyme to convert dietary carbs into energy ie pyruvate into acetyl CoA. - Fuels cells such as spermatozoa.
Great for:
1. Fatigue and chronic fatigue syndrome
2. Mitochondrial support
3. Sperm health (male fertility)
ALA as antioxidant
- Potent fat-soluble / water soluble antioxidant. Exogenous forms scavenge free radicals intra- and extra-cellularly.
- Anti-inflammatory.
- Regenerates antioxidants: vits C, E, glutathione and CoQ10.
- Up-regulates the expression of glutathione.
- Improves spermatozoa motility and provides antioxidant protection.
Five antioxidant uses of ALA
- Infertility (600 mg daily)
- Diabetes, diabetic neuropathy
- Alzheimer’s — slows cognitive decline (600 mg daily for 1+year).
- Multiple sclerosis.
- Healthy aging.
Insulin-improving function (positive outcomes) of ALA x4?
Supplementation improves:
1. Insulin sensitivity
2. Insulin resistance
3. Fasting blood glucose
4. HbA1c
Which metals can Alpha Lipoic Acid chelate x5?
CLIMZ
Copper
Lead
Iron
Mercury
Zinc.
Used for:
- infertility
- Alzheimer’s
- peripheral neuropathy.
How does ALA work for peripheral neuropathy?
- Reduces oxidation of myelin sheath.
- Improves neuropathic sensory symptoms including pain,
burning, numbness, prickling of the feet and legs.
600 mg per day.
How does ALA aid weight Loss x3
- Reduces oxidative stress promoting fat storage.
-
Suppresses appetite by influencing AMPK (AMP-activated protein
kinase) enzyme in hypothalamus (where appetite is regulated). - Increases energy expenditure and reduces fat synthesis.
Dosage: 1800 mg daily
Best way to take ALA
Empty stomach.
Rare adverse effects: rashes, hives,
GI symptoms (abdominal pain, diarrhoea)
What is Biotin good for?
Hair, skin, nails…
TWO contraindications of ALipA
ALA = B B (blood sugar)
- Biotin and ALA may compete for transport across cell membranes due to similar chemical structures. Be mindful of biotin deficiency when using high doses of ALA.
- Increased risk of hypoglycaemia in medicated diabetic
patients due to additive effect. Monitor blood glucose closely.
Define HbA1c
Haemoglobin A1c. Levels should be 6 or below.
Glycated hemoglobin.
What is glucosamine (chemically)?
Glucosamine = aminosugar
sugar molecule with a nitrogen
What is a glycan?
Glycan = polysaccharide
What is glucosamine used for in the body?
Synthesis of:
1. Glycoproteins
2. Glycolipids
3. Glycosaminoglycans (GAGs) - also known as mucopolysaccharides.
Where can glucosamine be found?
Widespread in body.
High concentrations in joints and cartilage.
Specifically in structural components of:
1. Tendons
2. Ligaments
3. Cartilage
4. Synovial fluid
5. Mucous membranes
6. Structures in the eye, blood vessels and heart valves.
Ie all the cushioning elements…
TWO supplementary forms of glucosamine
- Glucosamine sulphate:
sourced from marine exoskeletons
(not suitable for vegetarians, vegans, seafood allergies).
Better absorbed hence result in higher tissue concentrations. Sulphate is found in synovial fluid and is required for GAG synthesis. - Glucosamine hydrochloride: Synthetically created from corn.
Which two forms of glucosamine are naturally present in the human body?
- Glucosamine-6-Phosphate (G6P)
- N-Acetyl-Glucosamine (NAG) - converted to hyaluronic acid
What is N-Acetyl-Glucosamine (NAG) converted to?
Hyaluronic acid (HLA) - important component of synovial fluid
Two therapeutic uses of glucosamine
- Osteoarthritis
- IBD / intestinal permeability
How is glucosamine useful for osteoarthritis?
- Stimulates metabolism of chondrocytes in:
~ articular cartilage
~ synovial cells in the synovial tissue.
This slows joint degeneration and prevents joint space narrowing. - Decreases inflammation by inhibiting cytokines eg =IL-1.
- Pain reduction comparable to NSAIDs (2 weeks). Glucosamine sulphate (4-8 weeks).
NB Less effective for severe, long-standing osteoarthritis.
More effective combined with chondroitin and MSM.
1500 mg daily or in three divided doses.
Which glucosamine products for joints and which for gut health?
Joints: Sulphate and hydrochloride
Gut: Healing and sealing gut lining: NAG
Mucins?
Group of proteins found in mucus.
Form a barrier and prevent microbial overgrowth.
How does glucosamine support IBD and gut lining?
NAG:
1. Supports GI epithelial barrier by enhancing mucin functionality (dramatically altered with IBD).
2. Reduces biofilm formation eg candida associated with IBD.
3. Aids in intestinal permeability.
Dosage: 3–6 g daily for children; 6 g daily for adults in
three divided doses. Administered orally or rectally.
Cautions with glucosamine?
- Seafood allergies (shells of crustaceans)
- Mild adverse GIT: nausea, heartburn, diarrhoea, constipation
- Drowsiness, skin reactions and headaches.
- Warfarin: potential increase in anticoagulant effect leading to increased risk of bleeding and bruising.
What is chondroitin sulphate?
Type of GAG (glycos-amino-glycan).
Extracellular matrix component eg cartilage and joint connective tissue.
Provides resistance to compression, partially by thickening synovial fluid.
How does chondroitin help with osteoarthritis?
Protects cartilage from degradation by:
- Reducing degradative enzymes and inflammatory such as COX-2.
- Increasing hyaluronic acid synthesis — enhancing joint lubrication.
Think chondroitin is for cartilage
Dosage: 200–400 mg two to three times a day (or as single dose)
Chondroitin contraindications and issues?
- Low absorption: only 8–18% of orally administered.
- Asthma: Usually well tolerated but some concern that might exacerbate asthma as patients have higher concentrations of chondroitin antibodies in the airway.
- Potential increase in anticoagulant effect of warfarin, leading to increased risk of bleeding and bruising.
MSM stands for?
Methyl sulfonyl-methane (MSM)
What is MSM?
Source of sulphur used by plants to create amino acids:
- cysteine
- methionine.
FOUR Functions of MSM?
- Alone or in combo with glucosamine / chondroitin
can reduce pain and swelling and improve joint function. - General anti-inflammatory properties by inhibiting secretion of cytokines (IL-6 and TNF-α) and COX-2.
- Cartilage-protective Sulphur is component of cartilage and so exerts a protective effect.
- MSM = methyl donor.
Dosage: 500 mg three times a day.
How to dose MSM?
Start at low dose and work up so don’t feel too gassy, loose bowel movements ie detox programme.
How does MSM help with CV health?
- Reduces homocysteine levels (donates methyl groups and therefore aids methylation cycle)
- Reduces lipid peroxidation (protects vascular endothelium from damage).
Dosage: 3g per day (benefits observed at 28 days)
What is methylation?
Homocysteine should go into making methionine. If doesn’t, levels build up. Homocysteine test = cheap epigenetic test! Continuous cycle.
Want good methylated B complex to aid methylation.
Dysregulation of DNA methylation = hallmark of cancer.
MSM therapeutic benefits?
- Tissue repair
- Inflammation and seasonal allergies (NF-kB down regulator)
- Osteoarthritis
- Heart disease
- Skin: acne esp if needs to detox / liver a bit unhealthy /or hormonal health. Anti-inflammatory.
Adverse MSM side effects
Nausea, diarrhoea, bloating. Poss insomnia.
What is betaine / TMG?
Chemical form of betaine = tri-methyl glycine (TMG) and it occurs naturally in the body.
NB Betaine hydrochloric acid is something different (HCL production)
How is TMG formed?
Choline (tetra-methyl glycine).
Main purpose of betaine TMG?
Methyl donor facilitating the conversion of homocysteine to methionine.
Elevated homocysteine = CVD risk factor so betaine can be used therapeutically to support vascular endothelial health
and prevent atherosclerosis.
Name TWO methyl donors
MSM and TMG (facilitates the conversion of homocysteine to methionine and also supports liver detox).
Homocysteine score uses?
- CVD risk biomarker
- Indicator of how well someone is methylating
Optimal blood levels = below 9 µmol / L,
Excess of 14 µmol / L linked to high risk of health concerns.
Food sources of betaine?
Plant sources: Beets (1–2 cups per day i.e. 250–500 ml per day), wheat bran, quinoa, spinach, sweet potato.
Animal sources: Seafood, turkey.
How does betaine / TMG help with CV health?
Homocysteine can be remethylated to methionine by
betaine-homocysteine methyltransferase (BHMT).
This enzyme uses betaine as a methyl donor.
Take with 1 mg of folate daily.
What therapeutic uses can betaine/TMG be used for?
- Atherosclerosis
- Alzheimer’s.
- Can increase muscle mass
- Fatty liver disease
Dosage: 6 g daily (3g twice per day).
For best results pair with 1 mg of folate daily
Fatty liver disease signs?
- Floating stools
- Pale yellow pasty stools,
- Can’t eat fats
- Nausea esp after richer foods.
What is DMG?
Dimethyl glycine (DMG) is trimethyl glycine (betaine) after it has donated one methyl group during the methylation of homocysteine and only exists for seconds at a time.
Primary therapeutic role of DMG?
Autism
.
What is Phosphatidylserine (PS)?
Most abundant fat-soluble phospholipid in brain.
serine = amino acid
Food sources of Phosphatidylserine (PS)?
- White beans
- Barley
- Carrots
- Mackerel, herring
- Organ meats.
Lecithin granules - can add to a smoothie or overnight oats. Full of PS. Often from soya which could be GM. Check sourcing. Sunflower lecithin also. Or just eat lots of sunflower seeds.
What are Phosphatidylserine (PS) functions?
Important in neuronal membrane functions:
- maintenance of cell’s internal environment
- secretory vesicle release
- cell-to-cell communication
- cell growth regulation.
Although the body is able to synthesise phosphatidylserine,
it requires substantial energy expenditure
Which part of the brain does Alzheimer’s affect
Hippocampus
FOUR therapeutic uses of Phosphatidylserine (PS)?
- Alzheimer’s disease
- Depression
- ADHD
- Stress and insomnia
How does Phosphatidylserine (PS) help with Alzheimer’s?
- Improves neuronal membrane functioning (fluidity ChatGPT)
- Increases acetylcholine, norepinephrine, serotonin and dopamine.
- Has been found to preserve glucose metabolism during Alzheimer’s disease, and also reduce acetylcholinesterase activity and hippocampal inflammation.
- Increases cognitive function (including non-Alzheimer’s related cognitive decline) and memory.
- More effective in patients with less severe symptoms.
Dosage: 300 mg daily or 100 mg three times a day.
How does Phosphatidylserine (PS) help with depression and insomnia?
Cortisol regulation.
More effective combined with fish oil (depression).
200 mg for stress and 400 mg for sleep.
Contraindications for Phosphatidylserine (PS)?
Possible additive effects when combined with cholinergic (Parkinson’s) drugs which also increase acetylcholine.
May decrease effectiveness of anticholinergic drugs (depression).
What is phosphatidylcholine (PC)
Major structural component of cell membranes, maintaining their integrity and fluidity.
Difference between phosphatdyl-choline and -serine? (Also inositol).
All phospholipids with different structures and functions.
Joint
1. Cell signalling.
2. Cell membrane integrity
2. Both vital to brain health ie cognition.and memor
Phosphatidylcholine is
1. Neuro and hepato- protective
2. Provides choline for achetylcholine
3. Major structural component of cell membranes
4. Immunity and hormone function
2. involved in cell signaling and membrane integrity.
3. Most abundant in body
Phosphatidylserine
,1. Depression
2. Insomnia
3. Stress (removes cortisol
4. Memory
5. Neuro-protective
6. Most aabundant fat-soluble phospholipid in brain.
Inositol
Insulin sensitivity eg PCOS, T2DM.
How is phosphatidylcholine (PC) synthesised?
- Dietary choline
- Or through methylation of another phospholipid — phosphatidyl-ethanolamine.
How much phosphatidylcholine (PC) is made in body?
Not very much! While the body can synthesise a small amount of choline, dietary intake is essential to meet body demands .
How is choline stored in the body?
As phosphodylcholine in body tissues (95%)
Food sources of phosphatidylcholine (PC)?
Plant sources: tree nuts, ground nuts, brassicas, wheatgerm, spinach, peas.
Animal sources: eggs, fish, beef, chicken, pork, liver.
NB Also lecithin granules.
Therapeutic uses of phosphatidylcholine (PC)?
- Liver health
- Brain health
- Ulcerative colitis
How does phosphatidylcholine (PC) aid liver health?
- Prevents fat accumulation in liver.
- Hepatoprotective reducing chemical and oxidative damage.
Consider for: non-alcoholic fatty liver disease, alcoholic
hepatic steatosis, drug-induced liver damage and hepatitis.
Dosage: Minimum 800 mg daily
How does phosphatidylcholine (PC) aid neurological health?
- Neuro-protective role as essential component of
neuronal membranes - Supplies choline for synthesis of acetylcholine (neurotransmitter involved in memory and protective against cognitive decline and dementia).
Dosage: 1–9 grams / day in divided doses
Stereoisomer?
Stereo-isomer =
2+ compounds that only differ in configuration of their atoms
What is myo-inositol?
- Most predominant of NINE different stereoisomer forms of inositol
- A six-carbon sugar alcohol.
- Accounts for 90%+ of cellular inositol.
Primary function of myo-inositol?
Part of phospholipid
- Provides structure to cells
- Acts as intracellular second messenger
- Regulates insulin and a number of other hormones
Insulin, structure, messenger.
Second messenger because primary message given by a neurotransmitter or hormone
Food sources of myo-inositol?
Synthesised in the body and also from:
MEGA - melon, eggs, grains, aubergine).
Plant sources: whole grains, beans, fresh fruit (e.g. prunes,
melon, oranges) and vegetables (e.g. okra, aubergine)
Animal sources: grass-fed meats, eggs.
Therapeutic uses of Myo-inositol
Think it’s a sugar therefore good for diabetes.
- PCOS
- Diabetes and gestational diabetes
- Anxiety and depression
PCOS and myo-inositol
- PCOS is characterised by insulin resistance and ↑ androgens.
Myo-inositol improves insulin sensitivity
- secondary messenger of insulin signalling
- promotes mobilisation of GLUT4 vesicles (also chlorella). - Increases SHBG to reduce bioavailable testosterone.
- Improves menstrual cycle regularity, oocyte quality, overall female fertility.
Dosage: 2–3 g daily. It should be used with folate.
How does myo-insoitol aid blood glucose?
- Improves insulin sensitivity (secondary messenger; GLUT4 mobilisation)
- Helps regulate blood glucose.
How does myo-insoitol aid anxiety and depression?
- Inositol linked to number of CNS receptor signalling systems inc neurotransmitters serotonin and dopamine.
- Decreases anxiety symptoms and panic attack frequency.
- Decreases depression symptoms including PMS associated.
Dosage: 12–18 g daily.
Mycotherapy?
Mycotherapy = use of mushrooms and their compounds as medicines or health-promoting agents.
Myco = mushroom
How many medicinal mushrooms?
1,000 medicinal (20k in total)
Fungi = one of seven kingdoms of living organisms.
Why mushrooms so good for the planet?
Fungi create a mycelial (root-like) network that releases enzymes and acids to externally digest dead organisms.
Mushrooms move the nutrients back into the life cycle (i.e. into soil).
Also grow quickly and in any direction (via their filaments).
What are the main therapeutic mushrooms x7?
Chaga
Cordeceps
Lion’s Mane
Maitake
Reiishi
Shiitake
Turkey Tail
Four therapeutic compounds contained in mushrooms
- Beta-glucans
- Triterpenes
- Sterols
- Lectins
What are beta-glucans?
Polysaccharides that sometimes contain protein (1,3 and 1,6 beta-glucans = most common).
Most important role of beta-glucans (found in mushrooms; oats also)?
Support optimal immune function by promoting immunomodulation and exert anti-tumour activity ie flag pathogenic cells to the immune system.
Stimulate macrophages, neutrophils, monocytes, natural killer (NK) cells and dendritic cells.
Triterphenes primary purpose?
- Hepato-protective (so is phosphatidylcholine)
- Anti-tumour.
Eg reishi
Sterols primary therapeutic purpose?
Anti-cancer properties.
Sterols such as ergosterol (vit D precursor).
Sub-group of steroids.
Lectins primary purpose
Agglutinate tumour cells, preventing their proliferation.
Also immune-modulatory.
Agglutination = clumping together
How many types of triterpenes do reishi have?
120
Any drug interactions with mushrooms?
No.
Which is the mushroom of eternal youth?
Reishi - x4 but also B vitamins
Shitake
- Anti-cancer “drug”.
- Gout ie preventative (also Quercetin, barleygrass
Generic side effects of mushrooms?
If have too much… nausea, loss of appetite,
Lion’s mane
Brain and gut connection.
Maitake
PCOS
Which vitamin improves the absorption of beta glucans?
Vit C
Which mushrooms to avoid if have AI diseases?
Cordyceps
Oyster mushroom
Nature’s statin!
What diseases are associated with mitochondrial dysfunction?
- Fbromyalgia,
- Type 2 diabetes,
- CVD
- Neurodegenerative diseases
- Cancer.
