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TitleNutraceuticals a Guide for Healthcare Professionals, 2nd Edition
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Total Pages449
Table of Contents
                            Cover
Table of contents
Preface
Acknowledgements
About the author
Abbreviations
1  Introduction
	Foods or medicines? The relationship between nutraceuticals, foods and medicines
	The use of nutraceutical supplements – demographic trends
	Safety
	Scientific evidence
	Market trends
	Major nutraceuticals and their applications
	Overview
	References
2  Monographs – general and specific properties
	Glucosamine
	Chondroitin
	Methylsulfonylmethane
	Coenzyme Q10
	Melatonin
	Carnitine
	Acetyl-L-carnitine
	Octacosanol/policosanol
	S-Adenosyl methionine
	Polyunsaturated fatty acids
	n-3 Fatty acids from fish oils
	Gamma-linolenic acid
	Flaxseed/alpha-linolenic acid
	Conjugated linoleic acid
	Flax lignans
	Pycnogenol
	Resveratrol
	Grape seed proanthocyanidin extract
	Lycopene
	Lutein
	Zeaxanthin and astaxanthin
	Alpha-lipoic acid
	Dehydroepiandrosterone
	Soy isoflavones
	Tea
	Creatine
	References
3  Source, manufacture and analysis of major nutraceuticals
	References
4  Metabolism, bioavailability and pharmacokinetics of nutraceuticals
	Metabolism data
	Bioavailability data
	Pharmacokinetic data
	References
5  Joint health
	Prevalence of joint disease
	Glucosamine and chondroitin
	Methylsulfonylmethane
	S-Adenosyl methionine
	Fish oils
	Linolenic acid
	Cetylated fatty acids
	Miscellaneous nutraceuticals
	Conclusions
	References
6  Cardiovascular health
	Black and green tea
	Soy
	n-3 and n-6 Essential fatty acids
	Flax lignans
	Coenzyme Q10
	Lycopene
	Octacosanol/policosanol
	Pycnogenol
	Melatonin
	Resveratrol
	Grape seed proanthocyanidin extract
	Lutein
	Carnitine
	Dehydroepiandrosterone
	Conclusions
	References
7  Eye health
	Age-related macular degeneration
	Lutein and zeaxanthin
	Other eye conditions
	Conclusions
	References
8  Mental health
	Acetyl-L-carnitine
	Phosphatidylserine
	Docosahexaenoic acid
	Soy isoflavones
	Other nutraceuticals
	Treatments for depression
	Conclusions
	References
9  Sleep enhancement
	Melatonin
	Miscellaneous
	References
10  Cancer prevention
	Epidemiological evidence for soy
	Tea
	Lycopene
	Flaxseed
	n-3 Polyunsaturated fatty acids
	Coenzyme Q10
	Melatonin
	Conjugated linoleic acid
	Overall conclusions
	References
11  Nutraceuticals and bone health
	Osteoporosis
	Melatonin
	L-Carnitine
	Polyunsaturated fatty acids
	Conjugated linoleic acid
	Soy isoflavones
	Conclusions
	References
12  Respiratory health
	Asthma
	Other respiratory conditions
	Other effects of nutraceuticals on respiratory conditions
	Conclusion
	References
13  Women’s health
	Menopausal symptoms
	Soy isoflavones
	Cardiovascular disease
	Cognitive function
	Osteoporosis
	Conclusions
	References
14  Weight management
	Obesity
	Nutraceuticals
	Conclusions
	References
15  Skin health
	Grape seed proanthocyanidin extract
	Carotenoids
	Polyunsaturated fatty acids
	Tea
	Soy isoflavones
	Coenzyme Q10
	Glucosamine
	Melatonin
	Activity of nutraceuticals on hair growth
	References
16  Oral health
	Tea
	Pycnogenol
	Coenzyme Q10
	References
17  Enhancement of sporting performance
	Creatine
	Carnitine
	Acetyl-L-carnitine
	Octacosanol
	Conjugated linoleic acid
	Other nutraceuticals
	Conclusion
	References
18  Animal health
	Cardiovascular disease
	Joint disease
	Periodontal disease
	Cognitive dysfunction
	Cancer
	Conclusions
	References
19  Meta-analyses and systematic reviews of nutraceutical clinical trials
	References
20  Synergism, beneficial interactions and combination products
	Glycoaminoglycan supplementation in arthritis, liver injury and pain
	Beneficial interactions between nutraceuticals and medicines
	Combination products
	Commercially available combinations
	Conclusions
	References
21  Minor nutraceuticals and their therapeutic applications
	Theanine
	Cetyl myristoleate
	Reduced form of nicotinamide adenine dinucleotide
	Superoxide dismutase
	Polyamines
	Other candidates
	References
22  Safety, adverse effects and interactions of nutraceuticals
	Safety data
	General adverse effects
	Drug interactions
	Carnitine and acetyl-L-carnitine
	Soy isoflavones
	Catechins
	Melatonin
	Glucosamine
	Conclusions
	References
23  Quality of nutraceuticals
	Glucosamine and chondroitin products
	Other nutraceuticals
	Non-formulated products
	Possible contaminants in nutraceuticals
	Analytical issues
	Other quality issues
	Cost comparisons of different products
	Conclusions
	References
24  Conclusions
	Future trends influencing consumers
	Future trends facing manufacturers
	Scientific community, regulatory authorities and consumer organisations
	New horizons
	Overall
	References
Index
                        
Document Text Contents
Page 2

Nutraceuticals

00 Prelim 2/3/07 18:51 Page i

Page 224

Mode of action

Tea polyphenols have been proposed to act via a number of different
mechanisms to exert their cancer chemopreventive effects. Studies have
shown that EGCG acts speci�cally on certain cancer cells through
induction of apoptosis, cell cycle arrest and inhibition of cell growth,
but does not cause these effects in normal cells.52,53 The inhibition of
cell growth is thought to be caused by the involvement of tea poly-
phenols in the activation of genes, via signalling mechanisms.54

Inhibition of growth factor signalling, for example, by blocking the
binding of epidermal growth factor (EGF) to its receptor, can inhibit cell
growth and promote apoptosis. EGCG has been shown to inhibit the
activities of the EGF receptor and prevent binding of EGF to the
receptor,53 thereby preventing cell proliferation.

Tea polyphenols such as EGCG and thea�avins are known to be
antioxidant.51,56,57 Their antioxidant activities include scavenging of free
radicals57 and inhibition of reactive oxygen species (ROS).54 Tea poly-
phenols may also prevent the formation of ROS by inhibiting activity
of the enzyme xanthine oxidase, which is involved in their formation.58

Other studies have suggested that tea polyphenols act through their
pro-oxidant activity in the induction of apoptosis. One investigation
using human lung cancer H661 cells demonstrated that EGCG induced
apoptosis and was inhibited by the enzyme catalase, but found that
catalase did not inhibit the growth inhibition activity of EGCG.51,55

Tea polyphenols may cause induced apoptosis, cell growth
inhibition and antioxidant activity through increasing levels of p53,
which regulates cell cycle arrest and apoptosis and therefore has a funda-
mental role in protecting cells from tumorigenesis. Antioxidants increase
levels of p53 by promoting biosynthesis and also alter the redox
potential, which results in the activation of p53.53

The activities of transcription factors such as AP-1 are induced by
tumour promoters.57 AP-1 is involved in the regulation of transforming
growth factors, apoptosis and also in direct repression of p53.53 EGCG
and thea�avins have been shown to inhibit the activation of AP-1.57 This
inhibition may be caused by decreased activation of mitogen-activated
protein kinase pathways, in particular jun N-terminal kinase, which thus
prevents successful AP-1 binding.51 Tea polyphenols have been shown
to prevent cell transformation and cell growth by inhibiting the activity
of AP-1.56

Administration of both green and black tea to rats was shown to
induce the phase II enzymes cytochrome P450 1A1, 1A2 and 2B1.54,58

Tea 201

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Page 225

Levels of UDP-glucuronosyl transferase, a phase II enzyme, were
increased significantly after drinking tea. This enzyme system detoxifies
environmental chemicals such as heterocyclic amines, which are known
to be mutagenic. Animals consuming tea produced detoxified metabo-
lites of heterocyclic amines together with increased UDP-glucuronosyl
transferase enzymes.54

Urokinase is a u-plasminogen activator involved in metastasis that
is regularly expressed in human cancers. EGCG has been proposed to
inhibit urokinase and hence to have a chemopreventive effect.50,52,57

Using molecular modelling, EGCG was shown to block various amino
acids needed for the catalytic activity of urokinase.57

EGCG has also been found to inhibit the activity of the enzyme
topoisomerase I, which is involved in the relaxation of DNA, but not
topoisomerase II in colon cancer. The concentration of EGCG needed
to inhibit the activity of topoisomerase I was less than that required to
inhibit cell growth.55

Inhibition of tumour necrosis factor alpha (TNF-�) could be the
mechanism of action of tea polyphenols.50,51,55 One investigation has
supported this mechanism and shown the importance of TNF-� in
cancer. It also indicated that ECG, EGCG and EGC all inhibited TNF-
� release from human stomach cancer cells in the cell line KATO-III.50

Angiogenesis involves the formation of new blood vessels; these
provide oxygen and nutrients to a tumour, which are essential for
tumour growth and mestastasis. Polyphenols in green tea have been
shown through in vivo and in vitro studies to be antiangiogenic. Tea
polyphenols have been shown to inhibit the expression of vascular
endothelial growth factor and matrix metalloproteinase-2, which are
both important proangiogenic factors. Tea polyphenols have also been
shown to inhibit the growth of endothelial cells, which are required for
angiogenesis to occur.59

The therapeutic effects of tea

Early research into the chemopreventive effects of tea reported that
application of EGCG to mouse skin inhibited tumour promotion.60,61

Later studies have involved both green and black tea, decaffeinated tea
and also fractionated tea, specifically individual components such as
EGCG.

202 Cancer prevention

10 Chapter 10 2/3/07 19:09 Page 202

Page 448

brain function, 175, 266–7
cancer prevention, 192–200
on coronary heart disease, 119–21
for hair loss, 295
levels and metabolites, 72t, 193–4
menopause, 259–69, 273
osteoporosis, 240–2
phytoestrogen chemistry, 262
prices, 395
production and analysis, 62t
quality of products, 386, 387t, 390
ratio to soy proteins, 265
safety, 270–1
skin, 293–4

lignans with, 351
lunasin, 200
market trends, 13
Novasoy products, 14
oil, cardiovascular disease, 130
phosphatidylserine, 173, 174
protein

for arthritis, 105–6
on bone, 241
on cardiovascular disease, 119, 124,

145–6, 266
meta-analyses of trials, 330–1t

sauce, seasonal allergic rhinitis, 254
spermatozoa, catechins on, 376
spermidine, 295, 360t, 365
spermine, 365
spinach, 75

age-related macular degeneration and,
158

cataract, 161–2
sports see athletes
sprinting, creatine, 302
squalene monooxygenase, resveratrol on,

140–1
stability of products, 393
stanols, 365

meta-analyses of trials, 331t
statins, 112

coenzyme Q10 and, 133, 373
red yeast rice, 4

sterols, 331t, 350, 361t, 365, 387t
stomach carcinoma, 198, 203
Streptococcus mutans, tea on, 297–8
strokes, �-carotene, 134–5
structure-modifying agents

glucosamine as, 88, 91–2
S-adenosyl methionine as, 99

sudden cardiac death, animals, 312–13
sugar cane, policosanol from, 137, 138

sulfate moiety, glucosamine formulations,
89

6-sulfatoxymelatonin, 24
sulfur, organic see

methylsulfonylmethane
sulindac, epigallocatechin gallate with,

203–4, 344
sunflower oil, cardiovascular disease,

130
sunscreens, tea extracts, 293
supercritical fluid extraction, 63
superoxide dismutase, 360t, 364–5
supplements, 4

diet vs, asthma, 250
regulations, 5
for weight loss, 280

Sweden, Lithuania vs, coronary heart
disease, 134

synergy, 339–58
synovial fluid, glucosamine levels, 89
synovial membrane, rheumatoid arthritis,

86

t1-2 see half-lives
Tagetes erecta (marigold), 159
tamoxifen, 45f, 46

genistein with, 344
tea, 47–52, 330t, 403

adverse effects, 375–6
cancer prevention, 200–6
coronary heart disease and, 113–19,

146
dental caries, 297–9
osteoporosis, 273
quality of products, 388–9
skin preparations, 293
synergisms, 344
theanine, 113, 359–63
see also catechins; green tea

telogen effluvium, 295
temperature, tea, cancer and, 206
temperature (body), melatonin on, 307
terrorism, 392
testosterone, 198, 230
theaflavins, 49, 52, 114, 200–6
theanine, 113, 359–63
thearubigins, 49, 344
thrombosis

fish oil PUFAs on, 128
Pycnogenol on, 139–40

TNFa (tumour necrosis factor alpha), 86,
202, 217, 350

tofu, 193, 269, 271, 374

Index 425

25 Index 2/3/07 19:15 Page 425

Page 449

tomato products, 40, 136, 207, 209–11,
329t

see also lycopene
topical formulations

cetylated fatty acids, 104–5
polyunsaturated fatty acids, 292–3

topoisomerases, 195, 202, 262
Toulouse, lutein and cryptoxanthin, 143
trabecular bone see cancellous bone
traceability of nutraceuticals, 392
trans-cis isomers, CLA, 219–20, 284–5,

371–2
transcription factors, bone and, 231
transforming growth factor beta, genistein

on, 195
trends, demographic, 6–9

see also market trends
triacylglycerol, 128, 129, 266
trials, clinical, 10–12, 94, 129, 330–1t,

405
tricyclic antidepressants, nutraceutical

interactions, 373
tuberculosis, �-sitosterol and

�-sitosterolin on, 350
tubulin, 157
tumour necrosis factor alpha, 86, 202,

217, 350
tuna, eye health, 163, 164
tyrosine kinase inhibitors, isoflavones as,

262

ubidecarone see coenzyme Q10
ubiquinone see coenzyme Q10
UDP-glucuronosyl transferase, tea on, 202
ultraviolet light, 291
United Kingdom, legislation, 5
United States of America, legislation, 5
unpalatability, soy extracts, 265
urinary excretion

glucosamine, 20
melatonin, 187

urokinase, tea on, 202
UV (ultraviolet light), 291

vaginal dryness, soy isoflavones, 264
valerolactone metabolites

catechins, 78
see also hydroxyphenyl valerolactone

analogues
valproic acid, 373
varicose veins, grape seed

proanthocyanidin extract, 142

vascular endothelium see endothelium
vascular function, 121–2, 340t, 345

aortic compliance, 126
microvascular disorders, GSPE, 142

vegetable oils, cardiovascular disease and,
125–6

vegetarians, carnitine, 26
venous insufficiency

grape seed proanthocyanidin extract,
142

Pycnogenol on, 139
ventricular arrhythmias, 312–13
very low-density lipoproteins, fish oil

PUFAs on, 128
vinpocetine, 177
vitamin(s), 2, 160
vitamin C

cognitive function in dogs, 322
synergism with �-carotene, 342

vitamin D, 230
vitamin E, fish oil and, 33
vitamin K2, 269
VLDL (very low-density lipoproteins), fish

oil PUFAs on, 128

warfarin
glucosamine and, 378
interactions, 372

weight management, 279–89
green tea, 283–4
see also lean body mass

Weight Watchers, 279
wheat germ, policosanol from, 137
wheat germ oil extract, octacosanol, 27–8
wines, 37, 141–2, 272
WOMAC index, 90
women, 232, 259–78

see also menopause

xanthine oxidase, inhibition, 201

Yellow Card Scheme, 9–10

zeaxanthin, 41–2
bioavailability, 73t
eye health, 156–62, 164
levels and metabolites, 71t
pharmacokinetics, 76t
production and analysis, 62t
quality of products, 387t

zidovudine, carnitine and, 373

426 Index

25 Index 2/3/07 19:15 Page 426

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