Transcript Phytonutrients

Phytonutrients
What are functional
foods?
• International food information council “those foods that
provide health benefits beyond basic nutrition”
Bioactive
Nutraceutical
• Considered non-essential for
growth and development
• Decrease risk of chronic diseases
dietary
supplements
• Regulated as foods
• Safety of supplement regulated by FDA
only after they have entered the market
• DSHEA states that a dietary supplement is
“adulterated” only if it presents a
“significant or unreasonable risk of illness
or injury”
Dietary supplement health &
education act of 1994
Definition of a supplement:
“Is a product (other than tobacco) that is intended to supplement the
diet that bears or contains one or more of the following dietary
ingredients: a vitamin, a mineral, an herb or other botanical, an amino
acid, a dietary substance for use by man to supplement the diet by
increasing the total daily intake, or a concentrate, metabolite,
constituent, extract, or combinations of these ingredients.”
• Is intended for ingestion in pill capsule, tablet, or liquid form
• Is not represented for use as a conventional food or as the soled
item of a meal or diet
• Is labeled as a “dietary supplement”
• Includes products such as an approved new drug, certified antibiotic,
or licensed biologic that was marketed as a dietary supplements or
food before approval, certification, or license (unless the Secretary
of Health and Human Services waives this provision).
the challenge of assessing dietary
supplements
• Need surrogate endpoints!
• Example assessment of risk of cancer,
inflammation
• Bioactive components decrease inflammation
via multiple mechanisms, i.e. activation of
transcription factor and other epigenetic
regulations
• Act as antioxidant etc.
Cytochrome p450
• The superfamily of monooxygenases that catalyze
the oxidation of organic substance.
• Heme proteins
• Substrates include metabolic intermediate, lipids,
steroidal hormones, as well as xenobiotic
substances such as drugs and other toxic
chemicals.
• Major enzymes involved in drug metabolism
• The most common reaction catalyzed by
cytochromes P450 is a monooxygenase reaction:
RH + O2 + NADPH + H+ → ROH + H2O + NADP+
Cyclooxygenase
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enzymes that are responsible for the formation of the paracrine
hormones, eicosanoids: prostaglandins, leukotrienes and
thromboxanes.
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Act on 20 carbon polyunsaturated fatty acids
The target of non-steroidal, antiinflammatory drugs, such as aspirin
and ibuprofen
Inflammation,
asthma, allergy
Regulate synthesis of cAMP
production  fever, pain,
blood flow, and uterine
contraction
Produced by
platelets,
important in
clotting and
blood flow
Glycemic index & glycemic load
• The glycemic index (GI) is a
measure of how quickly 50 gram
of available carbohydrate (minus
fiber) in a particular type of food
will increase blood sugar
(glucose), compared to white
bread or pure glucose
• A practical limitation of the
glycemic index is that it does not
take into account the quality or
quantity of carbohydrate actually
consumed in a meal.
• Glycemic load takes quantity
into account by multiplying the
glycemic index by the
carbohydrate content of the
actual serving.
secondary
metabolites
• phytonutrients content
vary by location,
harvest & storage
• Sometimes
phytonutrient cocktail
is better than isolated
nutrient – SYNERGY
carotenoids
• Yellow and orange fruits, dark
green leafy vegetables
• α and β-carotene and β cryptoxantin –
precursor to Vitamin A
• lycopene, lutein, and zeaxantin – not
precursors to vit A
• Foods rich in carenoids may be safer than purified
supplements
• Typical western diet contains about 6 mg/day of
carotenoids, 60% from animal sources
• Bioavailability enhanced by fat
lycopenes
• accumulates in certain
tissues, such as
prostate
• Lycopene commonly in
plasma associated with
LDLs
• Lutein and zeaxantin
have high binding
affinity to HDLs –
accumulate in macula
lutea of retina, act as
photoreceptors
the benefits of salmon…
astaxanthin
Plant sterols & stanols
• Most abundant Sterols = β-sitosterol,
stigmasterol, campesterol
• Inhibit growth of various forms of lung, stomach,
ovarian and breast cancer.
• Stanols = sitostanol, campestanol
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Sterols essential component cell membrane
Have sterol ring – differ in side chain.
Stanols are saturated form of sterol
Phytosterol absorption from intestine is a fraction
of cholesterol
Sterols and stanols cont…
• Cholesterol lowing effect
by lowering absorption
• FDA authorized
health claims – must
contain at least 0.65 g of
plant sterols or 1.70 g
stanol esters (esters have
higher lipid solubility and are
more easily incorporated into
foods)
• Typical diet  .15 - .4
g/day of sterols and
stanols
• To achieve 1.5 g/day, use
supplement
Disruption of lipid rafts
NT
Sterol X
TNF
A
B
C
• nSMase (green), lipid raft (red), colocalization of nSMase (yellow)
• (A) Control, (B) TNFα (200 ng/ml), (C) Compound X isolated from AKBB (5 μg/ml) and TNFα
Disruption of lipid rafts by compounds in AKBB
β-sitosterol
Cholesterol
Ursolic acid
Polyphenols
• 1) flavanoids,
2) phenolic acids
• Secondary metabolites
– more than 8000
• Hydroxyl groups might provide
reducing power or antioxidant
potential (ROS)
• Usually lots of conjugated double
bonds
• Usually in free form or Ο-glycosides
How do we measure antioxidant
power?
• Assays for measuring radical quenching
ability:
ORAC measures sample’s ability to
inhibit peroxyl radical oxidization of
the fluorescent probe, fluorescein.
Compared to tocopherol.
• Antioxidants can also chelate metals such
as iron. Ferric reducing antioxidant power
FRAP assay.
1) flavonoids
• Teas, berries, colorful fruit, red wine,
dark chocolate, ginger, licorice
ginseng
• Antiinflammatory, antioxidative,
antiallergenic, anticarcinogenic
• Low molecular weight, two aromatic
rings joined by 3 C chain that often
incorporates O into a ring.
• Subclasses: flavones, flavonols,
flavanols, flavanones, anthocyanins
• Proanthocyanins sometimes called
tannins are oligomers of polymers of
flavanol units
• US ingest 20 mg/day
• Database: USDA data base for the
flavonoid content of selected foods
and Phenol explorer
Anthrocyanins in Alaskan Cranberries and
Blueberries
mg/g of fresh weight
1.8
1.6
Cranberry
1.4
AK Cranberry
1.2
Blueberry
1
AK Blueberry
0.8
0.6
0.4
0.2
0
Anthocyanins
Flavonoid metabolism…
• Free flavonoids can be absorbed across the
small intestinal mucosa, flavonoid glycosides
require hydrolysis by digestive enzymes
• Flavonoids then undergo methylation and/or
conjugation to glucuronic acid or sulfate
before excretion
• Conjugates excreted in the bile undergo
deconjugation in the gut, catalyzed by
microbiota, releasing flavonoid that may be
reabsorbed
2) Phenolic acids
• Second largest subclass of
polyphenols – COOH group
• makes up about 1/3rd of total
polyphenolics in diet.
• groups based on R group on C
ring: 1) hydroxycinnamic acids
2) hydroxybenzoic acids
• Hydroxycinnamic acid esters shown to inhibit
5’lipoxygenases
• Caffeic acid and ellagic acid shown to lower
triglyceride levels and elevate insulin, lower ROS, and
proinflammatory cytokines.
• Typical diet range rom 0.025 – 1 g/day
• Little known about bioavailability and metabolism.
Phytoestrogens
• Majority phytoestrogens belong •
to 4 subclasses: isoflavanoid,
coumestans, isoflavones,
lignans, stilbenes
• Composed of a planar
aromatic ring system with one
or more hyroxyl
• Phytoestrogens proposed to
mimic estrogen and act as
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weak agonist, promoting
estrogen signaling in the
absence of estrogen.
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favorably affect hormonedependent cancers,
menopausal symptoms,
glycemic control and
weight maintenance,
decrease thrombus and
platelet aggregation, lower
TGL, LDL.
Recommended as alt to
hormone replacement
therapy.
No safety info
Estrogens function
in growth,
reproduction, and
maintenance and
integrity of
skeleton and
CNS.
ESTRADIOL
Phytoestrogens cont…
• Founds in licorice, kudzu, soy,
red clover, saw palmetto
• Wine, grapes and peanuts
good source of resveratrol
• Flax seed, whole grain
products, vegies, tea good
source of lignans.
• FDA approved health claim of
25 g or more soy flour for CVD
Indole-3-carbinol
• A chemically, mechanistically, and
phylogenetically separate
phytoestrogen is indole-3-carbinol
• does not mimic estrogen,
but alters alters estrogen
metabolism via a different
mechanism.
• Acid condensate of I-3-C binds to
aryl hydrocarbon receptor which is
capable of upregulating expression
of cytochrome P450, which is
involved in endogenous estrogen
metabolism
Isothiocyanates
• More than 120 have been identified
• When cell wall is disrupted by chewing,
chopping, etc, a hydrolytic enzyme,
myrosinase, releases a bioactive
isothiocyanate, a thiocyanate or a nitrile
• Cabbage, brocolli, bok choy…
• Shown to slow progression of common
cancers with as little as
3 – 5 servings each week
• Proposed to increase
detoxification of carcinogens
Organosulfurs
• Contains a derivative of
cysteine
called alliin, released when allium
vegetables are crushed.
• the enzyme allinase produces a lipid-soluble,
unstable intermediate called allicin that
decomposes to produce allyl sulfides,
including diallyl sulfide (DAS, DAD and
DATS)
• Onions, leaks, chives, scallions, garlic
(richest source)
Organosulfides cont…
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Antithrobotic effect via platelet inhibition
May inhibit COX and prostaglandin synthesis
Free radical scavenging activity
Causes apoptosis of human bladder cancer cells
through caspase activity.
• Protects DNA from oxidation and prevents DNA
mutagenesis.
• Like cruciferous veggies, alliums contains
selenocysteine methyl transferase which is what
allows the plant to take up inorganic selenium.
• Acute exposure to DAS, DAT inhibit cytochrome
P450 but chronic exposure upregulates
Polyols
• Sugar alcohols are used as
sweeteners – Xylitol,
Sorbitol, Mannitol
• Fewer calories (1.5 – 3
kcal/g) and lower glycemic
index due to reduced
absorption by intestine
• Excessive consumption of
sugar alcohols lead to
osmotic diarrhea – >50g of
sorbitol or 20 g mannitol
Stevia
• A natural zero calorie South
American
herb
• Steviol contains two hydroxyl groups
• Sugar residues are esterified to one or both
of the –OH groups to form glycosides which
are 200 – 450 times sweeter than sucrose.
• Microflora in intestine release sugars and
steviol
• May lower blood pressure