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VITAMINS, MINERALS AND HERBAL
SUPPLEMENTSGEK2501: Assistant Prof. Pieter Eichhorn (Email: [email protected])
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Objectives of lecture:
1.
to classify the functions of the key vitamins
and minerals, and identify their main
dietary sources
2. to differentiate the pharmacological effects
of four common herbal supplements, and
also appraise the evidence for such effects
2
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Discovery of Vitamines
In 1906, English biochemist Sir Frederick Gowland Hopkinsdiscovered that certain food factors were important to health.
In 1912, Casimir Funk originally coined the term Vitamine
after "vita" meaning life and "amine" because vitamins were
once thought to contain amino acids.
Together, Hopkins and Funk formulated
the vitamin hypothesis of deficiency disease -
that a lack of vitamins could make you sick.
Casimir Funk 1884-1967 (Isolated Thiamine-Vitamin B1)
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A vitamin is defined as a biologically active organic
compound that is not synthesised within the body, but is
available in the diet in small amounts and is carried at
small concentrations in the circulatory system to act ontarget organs or tissues; it is essential for normal health
and growth; absence of a particular vitamin causes a
deficiency disease or disorder. RJ Kutsky
VITAMINS
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Discovery dates of Vitamins
Vitaminevitamin. The early years of discovery
http://www.clinchem.org/content/43/4/680.long
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VITAMIN GROUPS and NOMENCLATURE
At present there are thirteen distinct vitamins that arerecognized. Vitamin A, B1, B2, B3, B5, B6, B7, B9, B12, C, D, E,
K .
Why are Vitamins named like this? Vitamins used to be
labeled all the way to U, but have been reclassified over time.
For example: -Vitamin PP (Niacin, still sometimes called
this) is now called Vitamin B3.
-Vitamin O (Carnitine; found to be
synthesized in the body)
-Retinol, Retinal, and four carotenoids: the
carotenes alpha-carotene, beta-carotene, gamma- carotene; and the xanthophyll beta-cryptoxanthin,
are all classified as Vitamin A because they share
common functionality and all are convertible to the
active form of the vitamin in the body).
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Vitamins are classified as being
water soluble or fat soluble and sub-
classified by their biological andchemical activity. Not by their
structure.
Vitamins
Water
Soluble
FatSoluble
B
C
A
D
E
K
B1- thiamineB2-riboflavin
B3-niacin
B6-pyridoxine
B9-folic Acid
B12-cobalamin
C-ascorbic acid
D-cholecalciferol
E-tocopherols
K-phylloquinone
A-retinol
VITAMIN GROUPS
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VITAMIN GROUPS
I.Water-soluble vitamins: B and C complexesB complex vitamins include: thiamine (B1)
riboflavin (B2)
niacin (B3)
pyridoxine (B6)
folic acid (B9)
cyanocobalamin (B12)
C complex vitamins include: ascorbic acid (C)
Excess: excreted in the urine; little or no storage in the body, thus
need to be continually supplied in the diet.
Exceptions: folic acid and vitamin B12are stored in the liver. It
may take several years to deplete these stores, before signs and
symptoms of deficiency become manifest.
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VITAMIN DIETARY
SOURCES
FUNCTION RDA DEFICIENCY
DISORDER
B1
THIAMINE
Lean pork,
water melons,
fish, cereals.
Used in the production of
energy from carbohydrates.
Promotes growth and muscle
tone; health of heart, skin
and nerves
1-5
mg
Beriberi (weakness of
leg muscles, nerve
damage, heart
failure), less
concentration, fatigue
B2
RIBOFLAVIN
Bean sprouts,
dairy
products,
whole grains
maintains health of skin,
hair and nails; helps
metabolism of
carbohydrates, fat and
protein
1.5-2
mg
Itching and irritation
of eyes, skin and
mucous membranes
B3
NIACIN
Beef liver,
poultry, corn,
lentils,
mushrooms,
peanuts,
salmon/tuna
Helps release energy from
carbohydrates; maintains
health of digestive system
and nerves
13-18
mg
Pellagra (diarrhoea,
dermatitis,
depression), muscular
weakness/fatigue
B5
PANTOTHENIC
ACID
Meat, brocoli,
avocados.
Require to synthesize
coenzyme-A and help to
metabolize proteins,
carbohydrates and fats.
1-5
mg
Wide range of
symptoms including:
fatigue, apathy, may
in severe cases lead to
hepatic
encephalopathy9
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VITAMIN DIETARY
SOURCES
FUNCTION RDA Deficiency Disorder
B6PYRIDOXINE
Meat, fish,
Cereals, egg
yolk, avocados,
nuts, oatmeal
supports the central nervous
system by promoting the
synthesis of hormones and
neurotransmitters
1.5-
2.6
mg
Nerve damage
(peripheral numbness),
difficulty in
concentrating, short-
term memory loss
B7
BIOTIN
Raw egg yolk,
liver, peanuts,
leafy green
vegetables.
Involved in the synthesis of
fatty acids.
35-70
ug
Alopecia, conjunctivitis,
dermatitis, depression,
hallucination.
B9
FOLIC ACID
Dark green
leafy
vegetables,
cereals,
*legumes,
wheat germ,
yeast
Promotes production and
health of red blood cells;
maintains normal brain
function
400 -
1000
!g
Megaloblastic anaemia,
digestive disorders loss
of appetite; irritability,
headaches
B12
COBALAMIN
Clams/oysters,
dairy products,
egg yolk, organ
meats liver
and kidney
Promotes health of the
nervous system and blood cell
maturation
2-5
ug
Nerve damage
(numbness and tingling
of the extremities),
unsteady gait10
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VITAMIN DIETARY
SOURCES
FUNCTION RDA DEFICIENCY
DISORDER
C
Ascorbic
Acid
Berries, citrus fruits
(oranges,
grapefruit, lemons),
green leafy
vegetables, melons,
peppers, potatoes
Biological
antioxidant;
maintains health
and promotes
repair of body
tissues; keeps
bones and teeth
healthy; facilitates
the absorption of
dietary iron
70 - 150 mg Scurvy (bleeding,
inflamed gums, loose
teeth, poor wound
healing,)
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Please refer to Harvard Health Publications for complete information.
http://www.health.harvard.edu/staying-healthy/listing_of_vitamins
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II. FAT-SOLUBLE VITAMINS
Vitamins A, D, E and K occur in the lipid componentsof both plant and animal foods. Released when these
foods are digested, and are then absorbed in the intestine,
and storedin the liver and adipose tissue.
As fat-soluble vitamins are not excreted in the urine,
excess intake over time, especially of vitamins A and D,
can cause toxicity.
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VITAMIN DIETARY SOURCES FUNCTION RDA Deficiency
Disorder
A
Retinol
Carrots, broccoli, egg
yolk, fish liver oils,
pumpkins, sweet
potatoes, swiss cheese
promotes - good vision,
health of the immune
and reproductive
systems and of skin,
hair, bones and teeth
development
3000-10000
IU
Night Blindness,
dry skin, poor
development of
bones and teeth
D
Calciferol
Egg yolk, high-fat fish
and fish oils, milk or
margarine
facilitates proper
calcium and phosphorus
absorption; promotes
growth and maintains
health of bones
400 IU Rickets,
osteomalacia
E
Tocopherols
Nuts and seeds, peanuts
and peanut butter,
wheat germ, vegetable
oils
biological antioxidant
that protects against
harmful effects of free
radicals; stabilizes cell
membranes
12-18mg Pancreatitis
* Vitamins does
not prevent
wrinkles *
K
Phylloquinone
Green leafy vegetables
Kale,broccoli, brussel
sprouts, cabbage; olive
oil, soybean
needed for the
production of blood
clotting factors in the
liver. (K/C)oagulation
120 ug Nose bleeds,
internal
hemorrhage13
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VITAMIN GROUPS and NOMENCLATURE
Vitamin wheel
Please note vitamin B3 is referred to here as PP
Vitamin K is mostly found in
green leafy veggies, kale,
sprouts.
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Vitamin C(ascorbic acid)
The name Ascorbic acid is derived from the Latin word forscurvy-scorbutus.
Very common among sailors on long sea journeys as food
was perishable. The derogatory word Limeys referring to
people from England was originated as cooks in the Royal
Navy put lime juice in sailors daily ration of watered down
rum. Scurvy caused by vitamin Cdeficiency
Vitamin C plays a critical role in the
maintenance of a normal mature collagen
network in humans by acting as a co-factor for
two enzymes lysyl and prolyl hyroxylase.
These two enzymes are required for the
hydroxylation (-OH) of proline and lysineamino acids in collagen. Effect ive
hydroxylation is required for stability of
collagen during collagen cross-linking.
Defective collagen formation impairs effective
wound healing.
Vitamin C
regulates
hydroxylation
of proline and
lysine
residues inpro-collagen
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Vitamin D(calciferol *** calciferol denotes D2and D3)
Ricketsis the softening and weakening of the bones due to prolonged vitamin D deficiency.
However, lack of calcium in the diet may also lead to rickets.
While both major forms of Vitamin D, Vitamin D2and Vitamin D3can be obtained from
dietary sources or vitamin supplements vitaminD3(cholecalciferol) is synthesizedin the
human skin from 7-dehydrocholesterol upon exposure to ultraviolet-B (UVB) radiation from
sunlight.
Rickets
caused by
vitamin D
deficiency
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Vitamin D
Nevertheless both forms are inactive. Vitamin D is carried to the liver where its converted to the
hormone calcidiol(25 dihydroxyvitamin). Part of the calcidiol is converted by the kidneys tocalcitriol(1,25 dihydroxyvitamin), the biologically active form of vitamin D.
Calcitriol circulates as a hormonein the blood regulating the concentration of calcium and phosphate
in the blood stream promoting growth and remodeling of bone.
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ESSENTIAL MINERALSThese are :
Macrominerals:
calcium potassium
phosphorus magnesium
sodium iron
Microminerals:
zinc copper
selenium fluoride
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MINERALS
These are chemical elements that are required byliving organisms for normal bodily functions. They
may be classified as:
1. macrominerals(required in amounts >100 mg/day)
2. microminerals(trace elements) - required in
amounts < 100 mg/day.
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Macro-
mineral
Sources Functions Result of
deficiency
Result of excess
Calcium Beans,
broccoli,
Cheese,
dark green
veggies (like
spinach andkale),
milk
Key constituent of
bones, teeth;
regulates nerve and
muscle function, and
also blood clotting
In children: rickets
In adults:
osteomalacia.
Osteoporosis may
follow.
Formation of stones
in kidneys, gall
bladder
Phosphorus Dairy
products,
meats, leafy
vegetables,
most fruits
Component of bone
tissue; forms
compounds that are
needed for energy
conversion eg.
adenosine
triphosphate (ATP)
Anaemia, de-
mineralisation of
bones, weakness
Interferes with
absorption of
calcium,
magnesium, zinc,
iron
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Macrominerals
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Macro-mineral Sources Functions/Uses Result of
deficiency
Result of
excess
Sodium
(extracellularfluid)
Processed
foods, table
salt
Regulates plasma
volume, maintains
acid-base balance,
nerve and electrical
potential generated
by activity of Na+/K+
ATPase (
sodium
pump
); thus
maintains muscle and
nerve function
Hyponatraemia -
low blood
pressure, muscle
weakness,
paralysis
Hyper-
natraemia -
dehydration,
hypertension
Potassium
(intracellular fluid)
Fruits, all
vegetables,
milk
Main base ion of
intracellular fluid;
maintains electrical
potential of the
nervous system and
thus maintains
function of nerve andmuscle tissues
Muscular
weakness or
paralysis; mental
confusion
Irregular heart
rate and
rhythm, cardiac
arrest
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Macro-
mineral
Sources Functions Result of
deficiency
Result of
excess
Magnesium Green leafy
vegetables,shellfish, nuts
Essential for bone
health; needed forfunctioning of muscle
and nerve tissue and
also of ~90 enzymes
Anxiety, insomnia,
fatigue, depressedmuscle contraction
Unusual
Iron Liver, meat,
green leafy
vegetables,
meat, peas,
whole grain
Anaemia, impaired
immunity
Long-term intake in
excess leads to iron
deposition in body
tissues (liver,
spleen), reduced
absorption of
calcium and
magnesium,
increased
susceptibility to
infection
Essential for
transfer of
oxygen
between tissues
in the body
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Micro-
mineral
Sources Functions Result of
deficiency
Result of excess
Zinc Dairy
products,
eggs, liver,
red meat,
whole
grain
Co-factor in > 200 enzyme
systems, including the
antioxidant enzyme,
superoxide dismutase (SOD);
strong immune system
Growth
retardation in
children, poor
immunity
If taken in excess
over a long period,
it leads to
deficiency of
copper absorption
Cooper Legumes,
nuts and
seeds,
whole
grains,
organ
meats,
drinkingwater
Part of many enzymes; needed
for iron metabolism
Very rare.
Results in
hematological
and
neurological
disorders.
Upset stomach,
nausea diarrhea.
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Microminerals
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Micro-
mineral
Sources Functions Result of
deficiency
Result of excess
Selenium Meats,
seafood,
grains
Antioxidant Hypothyroidism Hair and nail loss,
skin rashes, fatigue
Fluoride Drinking
water
(either
fluoridated
or
naturally
containing
fluoride),fish, and
most teas
Involved in formation of bones
and teeth; helps prevent tooth
decay
Tooth decay Fluorosis, mottling
of teeth,
calcification of
ligaments.
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Microminerals
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Magnesium
Our body contains at any one time 24 grams of magnesium.
Over 350 enzymes require magnesium for their catalytic function.
Including all enzymes that utilize and/or synthesize ATP.
98% of the ATP that runs our body & cellular functions MUST be
attached to Mg.
Very difficult to overdose on Mg as it is freely filtered through our
kidneys.
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FOUR
TRADITIONAL
HERBAL
SUPPLEMENTS:
GARLIC
GINKGO
BILOBA
GINSENGAND
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1. GARLIC (Allium sativum)
Garlic has been extensively studied scientifically and shown tohave multiple beneficial pharmacological effects on
cardiovascular system by lowering overall cholesterol levels and
reducing blood pressure in hypertensive patients.
*47 hypertensive patients and showed that garlic significantlyreduces mean systolic/diastolic blood pressure by an average of
12/9 mmHg versus.* (Garlic for hypertension: Cochrane database)The authors state that garlic was "free from side effects" and that no serious side effects were reported.
There were 3 cases "where a slight smell of garlic was noted."
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1A.What are the active chemicals in Garlic?
Raw garlic bulbs contain the compound, alliin, which is converted
by the enzyme, allinase, to the active compound, allicin (which givesodour to garlic).
Biological Function:
When the garlic plant comes under attack Allicin is synthesized and
protects the garlic from antifungal and antiviral infections.
Commercially available garlic capsules are enteric-coated to
protect allinase from being inactivated in the acid pH of the
stomach.
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1B. Benefits of consuming Garlic?
. Lowers blood pressure (by 12/9 mmHg)
. Anti-oxidant (inhibits oxidation of LDL-cholesterol)
. Inhibits platelet aggregation
. Enhances fibrinolytic* (clot-dissolving) activity
. Reduces serum cholesterol levels by 5-8%
. Protects the elastic properties of blood vessels
USE:
prevention of atherosclerosis and its effects
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1C. Adverse effects of consuming Garlic?
Daily consumption in excess of 5 cloves (or equivalent) may cause:
-nausea-heartburn
-hypotension
-allergy in the form of contact dermatitis.
1D. Precaution on use of garlic productsUse with caution in patients on oral *anticoagulants.
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2. GINKGO BILOBA
The root and kernels of Ginkgo
bilobahave been used in TCM for
a very long time. In the 1960s, a
concentrated extract of G biloba
leaves was developed. Today, a leafextract with standardised amounts
of the active constituents -
ginkgolides A, B, C and bilobalide -
is in clinical use.
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2A. Some pharmacological effects of ginkgolides
I.Increase blood flow: due to vascular relaxation mediated by nitric
oxide, and also reduced blood viscosity.
II.Scavenge free radicals:In vitrostudies showed that ginkgo has
free radical-scavenging properties.
III. Inhibit platelet activity: Ginkgolide B was found to inhibit the
activity of platelet activating factor (PAF) which promotes
platelet aggregation.
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2B. Evidence of Ginkgo function in Clinical trials
a. In patients with intermittent claudication ( decreased blood
flow during exercise)
At least 1 study showed that ginkgo increased pain-free
walking distance by 40% compared to 20% in placebo-
treated subjects.
b. In patients with cerebral insufficiency and Alzheimers-typedementia.
At least 2 large-scale clinical trials (of 6 months and 1-year
duration) have indicated that ginkgo is useful in mild to
moderately severe dementia.
c. Studies of patients undergoing coronary artery by-pass
surgery showed that ginkgo reduced free radical production
in these patients. 33
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2C. Adverse effects of ginkgo products
Rare: gastrointestinal disturbances,
headache
allergic skin rash.
More serious:drug interaction with aspirin or anti-coagulant agents
increased risk of bleeding
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3. GINSENG
There are different species from different countries:Panax
ginseng(China or Korea),Panax quinquefolium(America).
Siberian ginseng is not true ginseng but belongs to a different
genus,Eleutherococcus senticosus.
The active ingredients in Panax species are the ginsenosidesor
panaxosides (saponin glycosides), which are found mainly in the
roots.
The counterpart ingredient inE senticosusis the eleutherosides
(which have yet to be standardised, unlike the ginsenosides).
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3A. Pharmacological benefits of ginseng
anti-platelet activity anti-stress activity,
energy- and mind-enhancing actions
blood pressure regulation
Of note: Siberian ginseng has been used by Russian cosmonauts
and Olympic athletes as a herbal tonic to promote general health
and well-being, and to reduce physical and mental stress.
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3B. Standardised formulation ofPanax ginsengand suggested
Dossage
(1g crude root = 200mg of extract = 14mg of ginsenosides)
1-2g/day of root extract of Panax ginseng, or 2-3g/day of root extract
of Siberian ginseng
Ginsana G115-each gelatin capsule contains 100 mg root extract;the active ginsenosides make up 7% by weight (=7 mg).
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3C.Clinical trials with ginseng have reported:
1.
improved mental function and physical performance
2. significant enhancement of immune function and quality of life
3. significant reductions in HbA1c* and fasting blood glucose
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3D.Adverse effects of Ginseng
1.Ginseng has weak oestrogenic properties and can cause breast
swelling and pain and also menstrual irregularities, including
excessive bleeding.
2.Insomnia and nervousness (due to excessive brain stimulation)
3.
Hypertension, from high doses (>3g/day)
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4. And. Salicylic Acid.
Used as early as 3000 BC, the
ancient Egyptians used willowbark to reduce pain and fever
In 1897, Felix Hoffmann (a young
chemist working for Bayer)
independently made ASA in a
more chemically pure, stable andmore palatable form.
Two years later, on March 6, 1899,
aspirin was trademarked under
the Imperial Office of Berlin.
40
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Other infamous Bayer products
The effects of heroin will be covered in detail in the GEK2501 lecture: Drugs of abuse.
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4A Pharmacological effects and uses of Aspirin
Analgesic (minor pain)
Antipyretic (reduces fever)
Anti-inflammatory
Antiplatelet (targets thromboxane and platlet
aggregation)
4B. Mechanism of ActionAspirinis non-steroidal anti-inflammatory drug
(NSAIDs) that irreversible binds and inhibitsthe
enzyme cycloxygenase 1 and 2 (COX1/2). But primarily
COX1. COX enzymes produces hormones called
prostoglandins. Some prostoglandins are involved in the
response mechanism required for signaling pain and
inflammation. 42
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4A Pharmacological effects and uses of Aspirin
Analgesic (minor pain)
Antipyretic (reduces fever)
Anti-inflammatory
Antiplatelet (targets thromboxane and platlet
aggregation)
4B. Mechanism of ActionAspirinis non-steroidal anti-inflammatory drug (NSAIDs) that
irreversible binds and inhibitsthe enzyme cycloxygenase 1 and 2
(COX1/2). But primarily COX1. COX enzymes produces
hormones called prostoglandins. Some prostoglandins are involved
in the response mechanism required for signaling pain andinflammation.
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4C. Evidence of benefit:
In short, too many to count. It truly is a wonder drug.
ex. Cancer, heart attacks, strokes, not to mention the
day to day use in treatment of headaches, pain, and
fever.
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4D. Clinical Evidence
Too many to list:
One example is the use of low dose Aspirin in the prevention of
cancer.
In 2011 a meta-analysis study of eight clinical trials that
compared the risk of cancer death among participants
who took daily aspirin for 4 years or more to those who took no
Aspirin found that, overall, Aspirin use lowered the risk of dyingfrom cancer by approximately 20%.
(NCI.2011)
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4E. Side Effects
The biggest risk is gastrointestinal bleeding.
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The following problems can occur:
1.Allergy to some component of the herbal remedy
2.
Contamination with poisonous chemicals e.g. Residual
herbicide
3. Adulteration with potentially harmful Western drug(s) e.g.
steroid.
4. Misidentification of a plant species, causing a toxic variety to
be used
5.
Interactions between the herbal remedy and a Westerndrug(s), with undesirable outcomes
What dangers to health should consumers
beware of when taking herbal products?
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How does one evaluate the claims of health
supplements?
The gold standard by which Western-trained
scientists and medical practitioners accept a particular
treatment or drug for its therapeutic efficacy is from the
positive outcome of random double blind placebo-
controlled cross-over trials with the drug.
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SHOULD I TAKE A HERBAL REMEDY
FOR A PARTICULAR HEALTH
PROBLEM?
When in doubt, always ask your doctor. He/She has your
medical records, knows your medical history - illnesses,
medications and allergies - and is best able to advise you.
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*** Over 68000 people in the United States alone overdosed
on vitamin and mineral supplements last year resulting in
hospitalization and critical care.***
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END OF LECTURE
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3. Retinol is:
(A) Also known as vitamin B2
(F)
(B) Is a water soluble vitamin
(F)
(C) Is mostly found in Carrots
(T)(D) is required as deficiency may lead to night blindness
(T)