Phytochemical lecture for nutritional biochem

1. Phytonutrients

4. 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

5. 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”

6. 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).

7. 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.

10. 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+

11. Cyclooxygenase
• enzymes that are responsible for the formation of the paracrine
hormones, eicosanoids: prostaglandins, leukotrienes and
thromboxanes.
• Act on 20 carbon polyunsaturated fatty acids
• The target of non-steroidal, antiinflammatory drugs, such as aspirin
and ibuprofen
Produced by
platelets,
important in
clotting and
blood flow
Inflammation,
asthma, allergy
Regulate synthesis of cAMP
production  fever, pain,
blood flow, and uterine
contraction

12. 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.

13. secondary metabolites
• phytonutrients content
vary by location,
harvest & storage
• Sometimes
phytonutrient cocktail
is better than isolated
nutrient – SYNERGY

14. 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

16. 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

17. the benefits of salmon…
astaxanthin

18. 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
• 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

19. 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

20. NT TNF Sterol X
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

21. Disruption of lipid rafts by compounds in AKBB
β-sitosterol
Cholesterol
Ursolic acid

22. 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

23. 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.

24. 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

25. 0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
mg/goffreshweight
Anthocyanins
Cranberry
AK Cranberry
Blueberry
AK Blueberry
Anthrocyanins in Alaskan Cranberries and
Blueberries

26. 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

27. 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.

28. 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
weak agonist, promoting
estrogen signaling in the
absence of estrogen.
• favorably affect hormone-
dependent 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

29. ESTRADIOL
Estrogens function
in growth,
reproduction, and
maintenance and
integrity of
skeleton and
CNS.

30. 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

31. 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

32. 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

33. 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)

34. Organosulfides cont…
• 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

35. 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

36. 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