VITAMINS, MINERALS AND HERBAL

SUPPLEMENTS
GEK2501: Assistant Prof. Pieter Eichhorn (Email: pieter_eichhorn@nus.edu.sg)

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

Discovery of Vitamines
In 1906, English biochemist Sir Frederick Gowland Hopkins
discovered 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)

VITAMINS
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 on
target organs or tissues; it is essential for normal health
and growth; absence of a particular vitamin causes a
deficiency disease or disorder. RJ Kutsky

Discovery dates of Vitamins

Vitaminevitamin. The early years of discovery

http://www.clinchem.org/content/43/4/680.long

VITAMIN GROUPS and NOMENCLATURE

At present there are thirteen distinct vitamins that are
recognized. 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, gammacarotene; 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).

VITAMIN GROUPS
Vitamins are classified as being
water soluble or fat soluble and subclassified by their biological and
chemical activity. Not by their
structure.

Water
Soluble

B1- thiamine
B2-riboflavin
B3-niacin
B6-pyridoxine
B9-folic Acid
B12-cobalamin

C-ascorbic acid

A
D
E
K

A-retinol

Vitamins
Fat
Soluble

D-cholecalciferol
E-tocopherols
K-phylloquinone

VITAMIN GROUPS
I.Water-soluble vitamins: B and C complexes
B 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 B12 are stored in the liver. It
may take several years to deplete these stores, before signs and
symptoms of deficiency become manifest.

VITAMIN

DIETARY
SOURCES

FUNCTION

RDA

DEFICIENCY
DISORDER

B1
THIAMINE

Lean pork,
water melons,
fish, cereals.

Used in the production of

1-5
energy from carbohydrates. mg
Promotes growth and muscle
tone; health of heart, skin
and nerves

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

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
9
encephalopathy

B5
Meat, brocoli,
PANTOTHENIC avocados.
ACID

VITAMIN

DIETARY
SOURCES

FUNCTION

RDA

Deficiency Disorder

B6
PYRIDOXINE

Meat, fish,
Cereals, egg
yolk, avocados,
nuts, oatmeal

supports the central nervous

system by promoting the
synthesis of hormones and
neurotransmitters

1.52.6
mg

Nerve damage
(peripheral numbness),
difficulty in
concentrating, shortterm 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 gait
10

VITAMIN
C
Ascorbic
Acid

DIETARY
SOURCES
Berries, citrus fruits
(oranges,
grapefruit, lemons),
green leafy
vegetables, melons,
peppers, potatoes

FUNCTION
Biological
antioxidant;
maintains health
and promotes
repair of body
tissues; keeps
bones and teeth
healthy; facilitates
the absorption of
dietary iron

RDA

DEFICIENCY
DISORDER

70 - 150 mg

Scurvy (bleeding,
inflamed gums, loose
teeth, poor wound
healing,)

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 components
of both plant and animal foods. Released when these
foods are digested, and are then absorbed in the intestine,
and stored in 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

3000-10000
IU

Night Blindness,
dry skin, poor
development of
bones and teeth

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

D
Calciferol

Egg yolk, high-fat fish

and fish oils, milk or
margarine

facilitates proper
400 IU
calcium and phosphorus
absorption; promotes
growth and maintains
health of bones

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
hemorrhage

13

VITAMIN GROUPS and NOMENCLATURE

Vitamin K is mostly found in

green leafy veggies, kale,
sprouts.

Vitamin wheel
Please note vitamin B3 is referred to here as PP

Vitamin C
(ascorbic acid)
The name Ascorbic acid is derived from the Latin word for
scurvy-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.
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 lysine
a m i n o a c i d s i n c o l l a g e n . E ff e c t i v e
hydroxylation is required for stability of
collagen during collagen cross-linking.
Defective collagen formation impairs effective
wound healing.

Scurvy caused by vitamin C

deficiency

Vitamin C
regulates
hydroxylation
of proline and
lysine
residues in
pro-collagen

15

Vitamin D
(calciferol *** calciferol denotes D2 and D3)

Rickets
caused by
vitamin D
deficiency

Rickets is 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 D2 and Vitamin D3 can be obtained from
dietary sources or vitamin supplements vitamin D3 (cholecalciferol) is synthesized in the
human skin from 7-dehydrocholesterol upon exposure to ultraviolet-B (UVB) radiation from
sunlight.

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 to
calcitriol (1,25 dihydroxyvitamin), the biologically active form of vitamin D.
Calcitriol circulates as a hormone in the blood regulating the concentration of calcium and phosphate
in the blood stream promoting growth and remodeling of bone.

17

ESSENTIAL MINERALS
These are :
Macrominerals:
calcium
phosphorus
sodium

potassium
magnesium
iron

Microminerals:
zinc
selenium

copper
fluoride

18

MINERALS
These are chemical elements that are required by
living 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.

19

Macrominerals
Macromineral

Sources

Calcium

Beans,
broccoli,
Cheese,
dark green
veggies (like
spinach and
kale),
milk

Phosphorus

Dairy
products,
meats, leafy
vegetables,
most fruits

Functions

Result of
deficiency

Result of excess

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

Component of bone
tissue; forms
compounds that are
needed for energy
conversion eg.
adenosine
triphosphate (ATP)

Anaemia, demineralisation of
bones, weakness

Interferes with
absorption of
calcium,
magnesium, zinc,
iron

20

Macro-mineral

Sources

Functions/Uses

Result of
deficiency

Result of
excess

Sodium
(extracellular
fluid)

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

Hypernatraemia 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 and
muscle tissues

Muscular
weakness or
paralysis; mental
confusion

Irregular heart
rate and
rhythm, cardiac
arrest

21

Macromineral

Sources

Functions

Result of
deficiency

Result of
excess

Magnesium

Green leafy
vegetables,
shellfish, nuts

Essential for bone

health; needed for
functioning of muscle
and nerve tissue and
also of ~90 enzymes

Anxiety, insomnia,
fatigue, depressed
muscle 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

22

Microminerals
Micromineral

Sources

Zinc

Dairy
products,
eggs, liver,
red meat,
whole
grain

Cooper

Legumes,
nuts and
seeds,
whole
grains,
organ
meats,
drinking
water

Functions

Result of
deficiency

Result of excess

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

Part of many enzymes; needed

for iron metabolism

Very rare.
Results in
hematological
and
neurological
disorders.

Upset stomach,
nausea diarrhea.

23

Microminerals
Micromineral

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.

24

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.

25

FOUR
TRADITIONAL
HERBAL
SUPPLEMENTS:

GARLIC
GINKGO
BILOBA
GINSENG
AND

26

1. GARLIC (Allium sativum)

Garlic has been extensively studied scientifically and shown to

have 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 significantly
reduces 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."

27

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 gives
odour 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.

28

1B. Benefits of consuming Garlic?

. Lowers blood pressure (by 12/9 mmHg)
. Anti-oxidant (inhibits oxidation of LDLcholesterol)
. 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

29

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 products
Use with caution in patients on oral *anticoagulants.

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2. GINKGO BILOBA
The root and kernels of Ginkgo
biloba have been used in TCM for
a very long time. In the 1960s, a
concentrated extract of G biloba
leaves was developed. Today, a leaf
extract with standardised amounts
of the active constituents ginkgolides A, B, C and bilobalide is in clinical use.

31

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 vitro studies 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.

32

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 placebotreated subjects.
b. In patients with cerebral insufficiency and Alzheimers-type
dementia.
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

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

34

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 ginsenosides or
panaxosides (saponin glycosides), which are found mainly in the
roots.
The counterpart ingredient in E senticosus is the eleutherosides
(which have yet to be standardised, unlike the ginsenosides).

35

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.

36

3B. Standardised formulation of Panax ginseng and 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).

37

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

38

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)

39

4. And. Salicylic Acid.

Used as early as 3000 BC, the

ancient Egyptians used willow
bark to reduce pain and fever
In 1897, Felix Hoffmann (a young
chemist working for Bayer)
independently made ASA in a
more chemically pure, stable and
more palatable form.
Two years later, on March 6, 1899,
aspirin was trademarked under
the Imperial Office of Berlin.

40

Other infamous Bayer products

The effects of heroin will be covered in detail in the GEK2501 lecture: Drugs of abuse.

41

4A Pharmacological effects and uses of Aspirin

Analgesic (minor pain)

Antipyretic (reduces fever)
Anti-inflammatory
Antiplatelet (targets thromboxane and platlet
aggregation)

4B. Mechanism of Action

Aspirin is non-steroidal anti-inflammatory drug
(NSAIDs) that irreversible binds and inhibits the
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
42
inflammation.

4A Pharmacological effects and uses of Aspirin

Analgesic (minor pain)
Antipyretic (reduces fever)
Anti-inflammatory
Antiplatelet (targets thromboxane and platlet
aggregation)
4B. Mechanism of Action
Aspirin is non-steroidal anti-inflammatory drug (NSAIDs) that
irreversible binds and inhibits the 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.

43

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.

44

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 dying
from cancer by approximately 20%.
(NCI.2011)

45

4E. Side Effects

The biggest risk is gastrointestinal bleeding.

46

What dangers to health should consumers

beware of when taking herbal products?
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 Western
drug(s), with undesirable outcomes

47

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 placebocontrolled cross-over trials with the drug.

48

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.

*** Over 68000 people in the United States alone overdosed

on vitamin and mineral supplements last year resulting in
hospitalization and critical care.***

49

END OF LECTURE

50

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)

51