Are Phytochemicals Essential Nutrients

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Are Phytochemicals Essential Nutrients? Garry
Duthie Molecular Nutrition Group Rowett Research
Institute
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Lecture Plan
What are phytochemicals? Main types of
phytochemicals Why they may be important for
health Possible mechanisms of action The issue of
bio-availability Future research
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What are phytochemicals ?
Phytochemicals Also called Phytoprotectants Pl
ant bioactive compounds
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Phytochemicals

• Compounds in plants not recognised as nutrients
• (ie. Not essential dietary factors such as
  vitamins, minerals, amino acids and fatty acids)
• No deficiency syndromes
• May affect mammalian biological functions

/- Health
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What do they do in plants?
structure pollination colour to stems, leaves,
flowers fruits growth development of the
plant inhibition of the growth of competing
plants pathogen and predator resistance
Remember, they evolved to benefit the plant, not
us!
TOXIC
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Lecture Plan
What are phytochemicals? Main types of
phytochemicals Why they may be important for
health Possible mechanisms of action The issue of
bioavailability Salicylic acid- a well known
phytochemical
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Main types of phytochemicals

• Terpenoids
• Alkaloids
• Sulphur compounds
• Phenolics/polyphenols

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Terpenoids (25,000)
Carotenoids
Plant sterols

• active ingredients in essential oils (e.g. in
  herbs and spices)
• powerful insect anti-feedants or attractants
• carotenoids essential in photosynthesis
• protect from UV damage
• orange, red and yellow colours
• sources include tomatoes, peas, citrus fruits,
  carrots

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Alkaloids (12,000)

• discourage attack by fungi, herbivores and
  pathogens
• toxic substances, naturally present in plants,
  including food plants, e.g. solanine in green and
  sprouting potatoes.
• basis of many modern day prescription drugs e.g.
  codeine, morphine, atropine also of heroin and
  cocaine.
• historic use as poisons
• food sources include coffee, chilli, contaminated
  rye

caffeine
capsaicin
lysergic acid
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Sulphur compounds (1,000s)
(e.g. glucosinolates found in Brassicas, and
derivatives of the sulphur amino acid cysteine,
found in the onion family)
Function uncertain Unpleasant taste to discourage
grazers? Breakdown products give hot flavour to
mustard and horseradish
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Phenolics/polyphenols (8,000)

• Skeletal function
• UV protection
• Antioxidant function
• Pollination
• Astringency
• Immune system
• Colouration (reds, purples, blues)

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Phenolics and polyphenols are products of the
plant phenylpropanoid pathway
Acetophenones
Benzoic acids
Styrenes
o-hydroxylation and lactonisation
side-chain elongation
side-chain degradation
Coumarins
Cinnamic acid
reduction
conjugation
Cinnamyl alcohols
X CO2R, CONHR
elongation and malonyl addition
O
O
Stilbenes
Styrylpyrones
Xanthones
Flavonoids
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Food sources of phenolics
Usually attached to sugars
Variation Species Variety
Light Ripeness Processing
Storage
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Examples of well-known phenolics

• Salicylic acid
• Phytoestrogens

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Salicylic acid used as an analgesic and
anti-inflammatory
Salicylic acid
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Main food sources of SA in NE Scotland

• Herbs and spices also very rich sources
• May protect against colon cancer

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Phytoestrogens eg isoflavones
Pulses - The collective noun for the dried edible
seeds of leguminous vegetables. Include peas,
beans, lentils and peanuts Soya principle
source of isoflavones in human diet.
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Structural Similarity Phytoestrogens Oestrogens
Phytoestrogen
Oestradiol
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Phytoestrogens-health benefits?

• Phytoestrogens compete with oestradiol to bind
  with oestrogenic receptors, and modify steroid
  metabolism.
• These and other potential actions (e.g. possible
  inhibition of the receptor) appear to allow the
  alteration of the growth and proliferation of
  hormone-dependent cancer cells. Picture remains
  unclear.
• Benefits also proposed with respect to menopausal
  symptoms, and possibly osteoporosis.
• A lowering effect of phytoestrogens in soya on
  blood cholesterol levels has been demonstrated.
  This may contribute to a protective effect
  against CHD.

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Lecture Plan
What are phytochemicals? Main types of
phytochemicals Why they may be important for
health Possible mechanisms of action The issue of
bio-availability Future research
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Are they important ?
We are living longer!
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Are they important ?
Diseases of middle age will increase!
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Epidemiology suggests role for fruit and
vegetables
Cancer
CVD
Pomerleau et al. (2003) Public Health Nutrition
6(5) 453-461
Riboli and Norat (2003) Am J Clin Nutr.
78559S-569S
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Main Questions?

• How much in the diet?
• Available from the food matrix?
• Bio-availability and metabolism in vivo?
• Prevent early disease events in nutritional
  amounts?
• Mechanism of action?

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Events in the progression of disease
Van der Greef J et al. Current Opinion in
Chemical Biology 2004, 8559565
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Mechanisms of action?
Anticancer effects of phytochemicals?
Exposure to carcinogen Metabolic activation of
carcinogen Initiation (interaction between the
carcinogen and DNA) Promotion (multiplication and
growth of abnormal cells) Tumour growth
Sites of potential action of phytochemicals
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Mechanisms of action?
Anticancer effects of phytochemicals?
Inhibition of metabolic activation of
carcinogen Eg some sulphur compounds,
glucosinolates and phenolics induce Phase II
detoxification mechanisms Inhibition of
initiation Eg some phenolics prevent oxidative
damage to DNA or promote DNA repair
mechanisms Inhibition of promotion Eg some
phenolics, alkaloids and terpenpoids inhibit COX
2 transcription and promote apoptosis
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Mechanisms of action?
Anti-heart disease effects of phytochemicals?
Damage to artery endothelium Oxidation of
LDL Macrophage uptake of oxLDL Monocyte
adherence Platelet activation Coagulation HEART
ATTACK!
Sites of potential action of phytochemicals
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Mechanisms of action?
Anti-heart disease effects of phytochemicals?
Prevention of oxidation of LDL Polyphenols and
terpenoids act as antioxidants by bind Fe or
directly scavenge ROS Prevention of monocyte
adherence Sulphur compounds modulate chemotactic
factors by affecting prostanoid
production Inhibiton of platelets and
vasodilation Phenolics, akaloids and sulphur
compounds inhibit COX 1 and/or increase NO
production
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Mechanisms of action?
However, These effects are reported in cell
culture or in animal models using high
amounts Do they occur in us at nutritionally
relevant amounts ?
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Lecture Plan
What are phytochemicals? Main types of
phytochemicals Why they may be important for
health Possible mechanisms of action The issue of
bio-availability Future research
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Bioavailability
Broadly this is the absorption and utilisation of
a dietary compound Are phytochemicals
bio-available?
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Potential biological effects of phenolics
Numerous Eg.
vasodilation gene expression
intracellular signalling enzyme modulation
ANTIOXIDANT EFFECTS ?
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The polyphenol story
Many phenolics are good electron donors
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Structure activity relationships
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Antioxidant activity of polyphenols
Some better than vit E!!!
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So are they antioxidants in biological systems ?
Epidemiology Experimental - cell
culture Experimental animal models Intervention
studies- lacking
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The polyphenol story
Epidemiology Heart disease
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The polyphenol story
Epidemiology Cancer
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Cell culture evidence
Some protect against DNA damage eg
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Experimental Animal models
Results generally negative eg.
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Do they pass the test?
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Rapid metabolism and clearance
Rapid removal from liver
Formation of numerous metabolites
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The polyphenol story
Experimental Animal models
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Main points
Some polyphenols have a low bioavailability Some
are rapidly metabolised cf response to
xenobiotics Methylation, glucuronidation and
sulphation likely to reduce antioxidant
potency But metabolites MAY have other
bio-activities Other phytochemicals may be
bioavailable eg salicylates
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Human studies - bioavailability, plasma, urine,
faeces
Plasma concentrations
Urinary concentrations
Huge inter-individual variation
Need to know why!
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Summary
F V and beverages rich source of
phytochemicals Type and form dependent on
numerous factors Bioavailability and metabolism
not known for many Large inter-individual
variation in absorbtion Many may be toxic and
rapidly metabolised and excreted So are they
essential nutrients -you decide
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Further reading Duthie GG, Gardner PT and Kyle
JAM (2003) Plant polyphenols are they the new
magic bullet. Proceedings of the Nutrition
Society 62, 599-603. Paterson J, Baxter G,
Lawrence J and Duthie G (2006) Is there a role
for dietary salicylates in health? Proceedings of
the Nutrition Society, 65, 93-96.
G.Duthie_at_rowett.ac.uk