Intravita Manual (Encrypted) (2) (1) 11 Dec 2019 59254 PDF

Intravenous Micronutrient
Supplementation (IMS)
Training
For Medical Practitioners
w w w. i n t r a v i t a . c o m
Contents
PAGE
CHAPTER 1: INTRODUCTION 4
1. Global Malnutrition in underdeveloped countries 4
2. Clinical micronutrient deficiencies in developed countries 9
3. Micronutrient deficiencies associated with degenerative disease, 11
4. DNA damage, mitochondrial decay and certain cancers 11
5. World Health Organization (WHO) – carcinogenic and other hazards In food 12
CHAPTER 2: INTRAVENOUS MICRONUTRIENT SUPPLEMENTATION (IMS) 13

TO ENHANCE HEALTH & WELLNESS
1. Global parenteral nutrition 14
2. Why intravenous micronutrient supplementation (IMS)? 15
3. Metabolism 17
4. Metabolic syndrome 18
CHAPTER 3: ESSENTIAL MICRONUTRIENTS – VITAMINS 19

1. Fat soluble vitamins 20
1.1 Vitamin A 20
1.2 Vitamin D 22
1.3 Vitamin E 28
1.4 Vitamin K 30
1. Water soluble vitamins 32
2.1 Thiamine (Vitamin B1) 32
2.2 Ribovlavin (Vitamin B2) 35
2.3 Niacin (Vitamin B3) 37
2.4 Pantothenic Acid (Vitamin B5) 38
2.5 Pyridoxine (Vitamin B6) 39
2.6 Biotin (Vitamin H) 40
2.7 Cobalamin (Vitamin B12) 42
2.8 Folic Acid 46
2.9 Ascorbic Acid (Vitamin C) 49
CHAPTER 4: GLUTATHIONE THE ‘MASTER’ ANTIOXIDANT 53

1. What is glutathione? 54
2. What are some of the functions of glutathione? 54
3. How is glutathione synthesized in the body? 55
4. Glutathione depletion 55
5. Glutathione as a depigmentation agent 56
CHAPTER 5: ESSENTIAL MICRONUTRIENTS – MINERALS 59

1. Calcium 60
2. Magnesium 64
3. Selenium 67
4. Zinc 69
2 2017 © Copyright to IntraVita Limited

CHAPTER 6: ESSENTIAL MICRONUTRIENTS – AMIN0 ACIDS 70
1. Arginine 73
2. Carnitine 74
3. Cysteine 75
4. Glutamine 77
5. Taurine 78
6. Methionine 79
7. Ornithine 80
8. Phenylalanine 81
9. Choline 84
10. Glysine 86
11. Lycine 87
CHAPTER 7: SAFETY AND EFFICACY OF IVS 88

1. Efficacy 89
2. Regulation in the United Kingdom of IMS under the MHRA 89
3. Reliability of micronutrient laboratory testing 90
4. Safety aspects 90
5. Contraindications to IMS 90
A) Absolute contraindications 90
B) Relative contraindications 92
6. Adverse reactions to IMS 93
7. Osmolarity of an admixture 94
8. Complications of IMS 99
CHAPTER 8: MEDICAL HISTORY AND INFORMED CONSENT 101

Medical questionnaire 102
Consent 109
CHAPTER 9: PRACTICAL FUNDAMENTALS 113

Consumables 114
Equipment 115
Administration methods 116
CHAPTER 10a: INTRAVITA IMS PROTOCOLS 118
CHAPTER 10b: IMS PROTOCOLS 120
CHAPTER 11: CHECK LIST & ADVERSE REACTION REPORTING 145
REFERENCES 146
ABOUT THE AUTHOR 174
2017 © Copyright to IntraVita Limited 3

CHAPTER 1: INTRODUCTION
1. GLOBAL MALNUTRITION IN UNDERDEVELOPED

COUNTRIES
In the developing world particularly, Vitamin A deficiency is a severe

nutritional dilemma [1] affecting about 250 million people worldwide of which
half are children under the age of 5 years old and an estimated half a million
children will go blind each year due to Vitamin A deficiency. [2]
Due to the lack of dietary milk and eggs in poorer developing countries,
Vitamin A pills and fortification of household sugar is a proposed solution. [1]
The Thyroid gland utilizes Iodine to produce hormones vital for body
development and brain function and Iodine deficiency occurs mainly in
countries that are landlocked and in areas naturally lacking Iodine in the soil.
Iodine deficiency is the “leading preventable cause of mental retardation in the
world” [1], can lower a person’s I.Q. by 10-15 points [3] and is affecting 1.9 billion
people of which 740 million have visible goiters [4, 2]
Map of Vitamin A Deficiency Source: Bassett & Winter-Nelson, 2010

A lthough the goal of Universal Map of Iodine Deficiency Source:
iodized salt is still not achieved, up Bassett & Winter-Nelson, 2010
from 25% in 1990 to two thirds of the “About one-fifth of perinatal mortality
world’s population at present, the and one-tenth of maternal mortality
impact of iodized salt has resulted in developing countries is attributable
in a reduction of nearly 50% in the to iron deficiency. There is also a
incidence of infants born with severe growing body of evidence indicating
brain damage and severe goiters. [3] that iron deficiency anaemia in early
World Health Organization: “Iron childhood reduces intelligence in
deficiency is one of the most mid-childhood. In its most severe
prevalent nutrient deficiencies in form, this will cause mild mental
the world, affecting an estimated retardation. There is also evidence
two billion people [5]. Young children that iron deficiency decreases fitness
and pregnant and postpartum and aerobic work capacity through
women are the most commonly and mechanisms that include oxygen
severely affected because of the transport and respiratory efficiency
high iron demands of infant growth within the muscle”.
and pregnancy. Iron deficiency may,
however, occur throughout the life
span where diets are based mostly on
staple foods with little meat intake or
people are exposed to infections that
cause blood loss (primarily hookworm
disease and urinary schistosomiasis)”.

Areas at high risk of Iron deficiency

Medium deficiency
Widespread zinc deficiency
WHO: “Using food availability data, it is estimated that zinc

deficiency affects about one-third of the world’s population, with
estimates ranging from 4% to 73% across subregions. Although
severe zinc deficiency is rare, mild-to-moderate zinc deficiency is
quite common throughout the world [6]. Worldwide, zinc deficiency
is responsible for approximately 16% of lower respiratory tract
infections, 18% of malaria and 10% of diarrhoeal disease.”

2. CLINICAL MICRONUTRIENT DEFICIENCIES IN DEVELOPED
COUNTRIES
Although in the developed world clinical thiamin (vit B1), riboflavin (vit B3),
deficiency of micronutrients is less pyridoxine (vit B6), niacin, cobalamin
common, an increased risk of chronic (vit B12), folate, ascorbic acid (vit C) and
diseases such as cardio-vascular disease, vitamin E may delay the progression of HIV
cancer, chronic renal failure and age- disease. [20, 21]
related macular degeneration has been
However, specific diets such as a
linked with suboptimal intake of vitamin
vegetarian diet and not “a single dietary
C, vitamin E and folate. [7, 8] An increased
bullet” [22] might lower the risk of a number
intake of folate and decreased intake of
of diseases such as diabetes mellitus,
homocysteine is associated with a reduced
obesity, hypertension, hyperlipidaemia
risk of cardio-vascular disease. [9] Although
and cancer. [21] Vegetarians differ in
B vitamin supplementation reduces total
many ways from the rest of the population
plasma homocystein concentration that
because they tend to come from higher
is associated with a marked reduction in
social classes, consume less alcohol, smoke
exercise electrocardiography abnormalities,
less and have a lower BMI. [23]
no effect was demonstrated on other end
points. [10] There are many similarities between the
Mediterranean-style diet and that of the
Although high beta-carotene intake has
American Heart Association (Step I and
been associated with a reduced risk of
Step II) diets but the Mediterranean diet
lung cancer in rats [11], a high intake of
is more specific in relation to the oils and
beta-carotene in smokers is linked to and
the forms and types of fat-containing
increased risk in lung cancer. [12, 13, 14]
foods. [24, 25] Effects of the Mediterranean
In various populations clear associations diet score on survival revealed no strong
exist between obesity and micronutrient associations for any of the individual
deficiencies. [15] Such deficiencies may dietary components [26] but rather that of
influence several physiological body the overall pattern is protective. [27]
functions, impair the immune system and
More than half of the population in the
increase the risk of comorbidities. [16]
USA use dietary supplements resulting
Consumers of dietary vitamin-mineral
in health benefits such as increased bone
supplements experienced a beneficial
mineral density and decreased fractures
effect on appetite regulation are leaner and
in postmenopausal women. [28] However,
have lower body fat than non-consumers.
“the present evidence is insufficient to
[17] Weight gain, obesity and metabolic
recommend either for or against the use of
syndrome may be linked to Vitamin D
multivitamins-minerals by the American
deficiency. [18]
public to prevent chronic disease.” [28]
In a Cochrane systematic review of
However, in developed countries cheap
gastro-intestinal cancer, vitamin
and tasty dietary sources of energy are
supplementation showed to have no effect,
abundant in fats and carbohydrates but
but the micronutrient Selenium showed a
micronutrient deficient – energy-dense
protective effect. [19]
and nutrient poor diets – and mostly
Multivitamin supplementation including consumed by the poor [29, 30, 31, 32]

% ingesting less than the
Nutrient Population Group
EAR from food
Mineral
Iron Women 14 – 50 years old 16
Magnesium All 56
Zinc All 12
Vitamins
B6 Women > 71 years old 49
Folate Adult women 16
E All 93
C All 31
Less than the EAR is used as a measure of inadequacy in populations [33, 34] The RDA is defined as 2
standard deviations above the EAR. Data are from Moshfeg et al. [31]
2. CLINICAL MICRONUTRIENT DEFICIENCIES IN DEVELOPED

COUNTRIES
The Aimes hypothesis proposes that A major contributor to the aging process
“DNA damage and late onset disease and its associated degenerative diseases
are consequences of a triage allocation including cancer and neural decay is
response to micronutrient scarcity. mitochondrial decay. [29, 35] This decay,
Episodic shortages of micronutrients that takes place in the mitochondrial
were common during evolution. Natural membranes via oxidative damage to DNA,
selection favors short-term survival at the RNA, proteins and lipids leads to functional
expense of long-term health. I hypothesize decline of mitochondria, cells and tissues
that short-term survival was achieved and eventually organs such as the brain.
by allocating scarce micronutrients by [29, 36, 37] Mitochondrial decay in old rats
triage, in part through an adjustment can be prevented via supplementation with
of binding affinity proteins for required (1) acetyl carnitine (ALC) that transports
micronutrients. If this hypothesis is fatty acids into the mitochondria and
correct, micronutrient deficiencies that (2) Lipoic acid (LA) that is reduced to a
trigger the triage response would accelerate potent antioxidant in the mitochondria
cancer, aging and neural decay but would and inducer of enzymes required for
leave critical metabolic functions, such as glutathione synthesis. [29, 35 – 40]
ATP production, intact.” [27]

3. MICRONUTRIENT DEFICIENCIES ASSOCIATED WITH
DEGENERATIVE DISEASE, DNA DAMAGE, MITOCHONDRIAL DECAY
AND CERTAIN CANCERS:
Magnesium deficiency [34] Vit B12 deficiency

Common [33]
Colorectal cancer [41, 42]
Cognitive dysfunction [61]
Hypertension
Multiple sclerosis [62]
Osteoporosis Chromosome breaks [63]
Diabetes 25% of Dutch adults > 75 years old showed

moderate to severe deficiency [82] – reversed
Metabolic syndrome [43, 44]
by Vitamin B12 intakes at levels many times
higher than the RDA [82]
Vitamin D deficiency
Folate deficiency
More prevalent in dark skinned people – less
Chromosome breaks [63, 64, 65]
UV activation of Vitamin D in the skin [45, 46]
Several cancers [66, 67]
Also prevalent in Caucasians [47]
Estimated 29% of cancer mortality in males [48] Thiamine deficiency

Brain dysfunction & diabetes [68]
Cancers of breast, colon, pancreas and the
prostate [48 – 53]
Niacin deficiency
Cognitive dysfunction [54, 55] Genotoxic [68, 69]
Calcium deficiency Choline deficiency

Chromosome breaks [56] Increases DNA damage in lymphocytes [70]
Diabetes [57]
Heme synthesis in mitochondria requires
pyridoxine, pantothenate, zinc, riboflavin, iron,
Potassium deficiency
copper and biotin – deficiencies are likely to
Elderly men: table salt containing potassium
cause a deficit of heme and therefore a deficit
associated with 40% decrease in cardio-
of complex IV. The latter keeps oxidants to a
vascular disease vs. normal table salt [58]
minimum [71]
Omega-3 fatty acid deficiency

Iron deficiency
Melanoma & other cancers [59]
It is them most common micronutrient
Cognitive dysfunction [60]
deficiency in the world, especially in
underdeveloped countries, leading to iron
deficiency anaemia [72]

Associated with poor cognitive development in 5. WORLD HEALTH ORGANIZATION
toddlers [73] (WHO) – CARCINOGENIC & OTHER
Diminished immune system [74] HAZARDS IN FOOD
Neuro-muscular abnormalities [75]
Aerobic capacity and physical work Pesticides residues may induce adverse
performance is decreased in dietary iron health effects including cancer, effects on
deficiency in the absence of anaemia [76] reproduction, immune or nervous systems.
Hereditary haemachromatosis is a known risk [83]
factor for cancer [77]
Other carcinogenic substances are formed
Zinc deficiency during red meat processing and inorganic
Common in adults – 12% are below the EAR [33] arsenic from contaminated drinking water
Causes complex IV deficiency – oxidative and tobacco smoke. [83]
damage to DNA [78]
Associated with cancer [79]

Biotin deficiency
Common – deficiency in 40% of pregnant
women who do not take a multivitamin
supplement [80]
Heme deficiency [81,82]
Prevention of micronutrient
overconsumption
Mineral toxicity: iron, zinc, copper & selenium
[29]
Vitamin A [29]
However, excess consumption is far less of

a public health problem than micronutrient
deficiencies [33]
Ascorbic acid deficiency

76% of smokers have an inadequate intake [33]

CHAPTER 2:
INTRAVENOUS MICRONUTRIENT
SUPPLEMENTATION (IMS) TO
ENHANCE HEALTH & WELLNESS

1. GLOBAL PARENTERAL NUTRITION
Market dynamics [1,2]
The global market for Parenteral Nutrition is forecast to reach US$ 8.7 billion by 2020 and it
is mainly driven by the growing popularity of health nutrition therapy at home for:
1. Elderly: preference for home IV nutritional therapy
2. Chronic diseases:
• Cancer radiation therapy and chemotherapy therapy induced anaemia and malnutrition
due to loss of appetite and nutrients
• Gastro-intestinal disorders such as Crohn’s Disease and Ulcerative Colitis
• AIDS
3. Parenteral feeding induced loss of upper respiratory tract immunity concerns
Number of new cancer cases diagnosed worldwide for the years:

2012: 13.4 million
2020: 18.2 million
2030: 22.6 million
Risk Concerns
• Infection linked to both Parenteral Feeding and IV Nutrition
• Allergy and anaphylaxis
• ‘Over’ treatment with micronutrients
North America Parenteral Nutrition market, by type of nutrition, 2013 - 2024 (USD Billion)
2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024
Parenteral Nutrition Market Analysis, By Nutrition Type and segment forecasts to 2024.
Adapted from Grand View Research Parenteral Nutrition Market Analysis Report 2024 [83]

2. WHY USE INTRAVENOUS MICRONUTRIENT SUPPLEMENTATION
(IMS) TO ENHANCE HEALTH & WELLNESS?
Intravenous micronutrient supplementation Why then is IMS so popular and preferred to

for non-medicinal indications such oral micronutrient supplementation by so
as rehydration, immune boosting, re- many people around the world?
energizing, de-stressing and many more,
has become very popular worldwide except
Theoretical Basis for Intravenous
for the Europe. IMS was introduced to the
Micronutrient Supplementation
UK during 2014/2015. [3] At the moment, Serum concentrations achieved with
no market analysis of the ‘informal’ IMS IMS are much higher than with oral and
market is available. However, thousands of intramuscular administration. [4]
clinics advertise IMS via the worldwide web
in many countries around the world Oral Vitamin C reaches a peak plasma
limit due to GI absorption saturation and
Why has IMS become so popular on a increased renal clearance of the vitamin.
global scale and where did it start? [8, 9] Pharmacokinetic modeling predicts
that even doses as high as 3 g ascorbic
In the 1960s a physician from Baltimore
acid taken every 4 hours would produce
in the USA, Dr. John Myers, treated with
peak plasma concentrations of only 220
intravenous vitamins and minerals various
micromol/L [10]. Daily increase from
medical conditions such as acute asthma
200mg to 2,500mg resulted in a plasma
attacks, migraines, fatigue (including
concentration increase of 25% (from 1.2
chronic fatigue syndrome) fibromyalgia,
to 1.5mg/dL). The highest oral plasma
acute muscle spasm, upper respiratory
concentration reported is 9.3 mg/dL.
tract infections, chronic sinusitis, seasonal
Intravenous administration of 50g/day
allergic rhinitis, cardio-vascular disease,
resulted in a mean peak plasma level of
depression and other disorders. He also
80 mg/dL. [11] At plasma concentrations of
treated healthy patients for non-clinical
10 - 15mg/dL Vitamin C showed anti-viral
indications with his IV ‘cocktails’. [4,5]
effects [90] and at plasma concentrations of
However, the international popularity of IV 88 mg/dL in vitro vitamin C destroyed 72%
micronutrient supplementation is owed to of the histamine present in the medium. [12]
Dr. Alan R Gaby, another physician from the
IV administration of magnesium can double
USA. [3,4] He took over Dr. Myers’ patients in
or triple the serum levels in contrast to
1984 and continued to treat various medical
minor changes in serum levels after oral
and non-medical conditions with his
administration. [13,14] Magnesium ions
modified version of the Myers’ cocktail. [4].
induce relaxation of both vascular [15] and
Today one can even step into any clinic bronchial [16] smooth muscle.
in Bangkok, Kuala Lumpur, Jakarta,
Intracellular micronutrient deficiencies
Manila, Hong Kong and many more
are very difficult to establish because as
cities in the Far East and ask for an IV
with most micronutrients, the plasma
Myers’ cocktail. Recent advances in IMS
concentrations correlate poorly with
include the addition of amino acids to the
intracellular concentrations, currently an
modified Myers’ cocktail. [3] Amino acids
“unmet need for improved biomarkers of
are especially effective for recovery after
trace element status.” [17] This includes
strenuous exercise and sporting events. [6]
biomarkers for zinc, selenium, iron and
“ Clinicians are encouraged to think iodine. [17]
of micronutrients not as nutritional
The intracellular magnesium concentration
supplements alone but also as therapeutic
in myocardial cells are 10-times higher
agents and nutraceuticals.” [7]
than the extracellular concentration.[18]

The homeostasis is maintained via an hypokalaemia in patients deficient in
active-transport system but in a study magnesium and potassium resulting in
of cardiomyopathy patients the mean muscle cramps. [4,21]
myocardial magnesium concentration was
6. Hypokalaemia may induce digoxin-
65% lower than in healthy controls. [18]
induced cardiac arrhythmias. [4]
Dependence on regular IMS injections may
7. Other cause of hypokalaemia may
be due to:
include potassium depleting diuretics,
1. A genetically determined impairment beta-agonists, glucocorticosteroids,
in the capacity to maintain normal diarrhea and vomiting and
intracellular concentrations [4,19] malnourished patients. [4]
2. An inborn error of metabolism that can 8. Potassium delivery via an IV push may
be controlled only by maintaining a trigger arrhythmia and is therefore
higher than normal concentration of a contra-indicated [4]
particular nutrient [4,20]
9. Intravenous calcium is contraindicated
3. A nutrient renal leak [4,20] in hypercalcaemia, cardiac disease, and
in patients taking digoxin. [4]
Side Effects and Precautions of IMS
10. Anaphylactic reactions have been very
1. Some patients experience a sensation
rare. Nine deaths in the world literature
of warmth and generalized cutaneous
are attributed to thiamine (Vit B1). [23]
vasodilation or flushing followed by
In the United Kingdom between 1970
rapid injection of magnesium or calcium
and 1984 four anaphylactoid reactions
[21] and niacin (nicotinic acid) [22] The
occurred for every 1 million ampoules of
sensation originates in the mouth neck
IV B vitamins. [24]
or chest and migrates via the abdomen
to the vaginal area in women and rectal 11. Alcoholics are usually magnesium
area in men. Some women experience a deficient and animal studies suggest
sensation of sexual pleasure and even that thiamine supplementation in the
orgasm in association with the vaginal presence of hypokalaemia increases the
warmth. Some patients find the feeling severity of hypokalaemia. [25]
of warmth over bearing. [4]
12. Hypomagnesaemia can lead to
2. In some cases visual acuity and spontaneous release of histamine
colour perception becomes sharper [26] and increased the incidence of
immediately after injection and may experimentally induced anaphylaxis in
last for a few days. [4] animals. [26]
3. Hypotension leading to lightheadedness 13. Magnesium sulfate may cause headache

and even syncope can follow rapid for about 24-48 hours (due to sulfates)
magnesium injection. If any of these [4]
symptoms occur, the infusion must
In summary, intravenous micronutrient
be stopped until the symptoms have
supplementation bypasses GI absorption
subsided, usually after 1-2 minutes.
and biotransformation in the liver, ensures
Persistent hypotension may follow even
bioavailabilty of the micronutrients in
in cases of very slow injection. [4]
high concentrations (not bound to plasma
4. In elderly or frail patients slow injection proteins) and gives desired results quickly,
of lower doses is advised. [4] in contrast with oral or intramuscular
administration routes.
5. Magnesium activates the membrane
pump that promotes intracellular
uptake of potassium and may cause

3. METABOLISM
http://upload.wikimedia.org/wikipedia/commons/thumb/5/5d/Metaboly…y_
labeled).svg/790px-Metabolism_pathways_(partly_labeled).svg.png
WHAT IS METABOLISM?
“Metabolism is an organized but chaotic chemical assembly line. Raw materials, half-finished
products, and waste materials are constantly being used, produced, transported, and excreted.
The “workers” on the assembly line are enzymes and other proteins that make chemical reactions
happen.” [28,29]
Metabolism includes chemical reactions that are taking place to convert or use energy: (1)
Macronutrients in food are digested into micronutrients - fats into lipids, carbohydrates into
glucose and proteins into amino acids to release energy, (2) excess nitrogen is transformed into
waste products and excreted in the urine and (3) conversion of chemicals into other substances
and transporting them intracellular. [28]
Many factors can disrupt our metabolism. One important factor is the link between chronic
disruption of our circadian rhythm and developing lung cancer [30] and decreases in cognitive
flexibility, accelerated weight gain and obesity and changes in metabolic hormones in non-
invasively chronic circadian disrupted mice. [31] In humans, epidemiological studies link short
sleep duration and circadian disruption with higher risk of metabolic syndrome and diabetes via
decreased resting metabolic rate and increased plasma glucose concentrations. [32]
Widespread contamination of the environment by endocrine-disrupting chemicals (EDCs) such

as pesticides, plasticizers, antimicrobials and flame-retardants can disrupt hormonal balance and
result in developmental and reproductive abnormalities, obesity, metabolic syndrome and diabetes
type 2. [33]

4. METABOLIC SYNDROME RISK FACTORS
The five conditions described below are metabolic risk factors. One can have a single risk factor
by itself, but they tend to occur together. At least three metabolic risk factors are required to be
diagnosed with metabolic syndrome:
1. A large waistline. This also is called abdominal obesity or “having an apple shape.” Excess fat
in the stomach area is a greater risk factor for heart disease than excess fat in other parts of
the body, such as on the hips.
2. A high triglyceride level (or on medication to treat high triglycerides).
3. A low HDL cholesterol level (or on medication to treat low HDL cholesterol).
4. Hypertension (or on medicine to treat high blood pressure).
5. High fasting blood sugar (or on medication to treat high blood sugar). [34]
6. Other conditions that may pay a role in metabolic syndrome is a fatty liver, Polycystic
Ovarian Syndrome, gallstones and sleep apnoea. [34]

CHAPTER 3:
ESSENTIAL
MICRONUTRIENTS - VITAMINS
Vitamins are organic molecules, some are water-soluble and some
are fat-soluble and the most prominent function is to serve as
cofactors (co-enzymes) for enzymatic reactions. They generally
cannot be synthesized by mammalian cells and must be supplied in
the diet. [1] Vitamins are susceptible to acid, heat and air.

1. FAT SOLUBLE VITAMINS
Route of Supplementation: Orally Drug interactions
1.1. Vitamin A Orlistat (Alli®, Xenical®), a weight-loss

treatment, can decrease the absorption of
Vitamin A is the name of a group of fat-
vitamin A, other fat-soluble vitamins, and
soluble retinoids, including retinol, retinal,
beta-carotene, causing low plasma levels in
and retinyl esters. [2] Vitamin A is involved
some patients [13]
in immune function, vision, reproduction,
and cellular communication [2,3] Vitamin Several synthetic retinoids derived from
A also supports the normal differentiation vitamin A are used orally as prescription
and functioning of the conjunctival medicines. Examples include the psoriasis
membranes and cornea, [3] supports cell treatment acitretin (Soriatane®) and
growth and differentiation, playing a bexarotene (Targretin®), used to treat the
critical role in the normal formation and skin effects of T-cell lymphoma. Retinoids
maintenance of the heart, lungs, kidneys, can increase the risk of hypervitaminosis A
and other organs [4]. when taken in combination with vitamin A
supplements [13].
Most people with cystic fibrosis have
pancreatic insufficiency, increasing
their risk of vitamin A deficiency due to
difficulty absorbing fat [5,6].
Although high beta-carotene intake has

been associated with a reduced risk of
lung cancer in rats [7], a high intake of
beta-carotene in smokers is linked to and
increased risk in lung cancer. [8,9,10]
“The Age-Related Eye Disease Study

(AREDS), a large randomized clinical
trial, found that participants at high risk
of developing advanced AMD (i.e., those
with intermediate AMD or those with
advanced AMD in one eye) reduced their
risk of developing advanced AMD by 25%
by taking a daily supplement containing
beta-carotene (15 mg), vitamin E (400 IU
dl-alpha-tocopheryl acetate), vitamin C (500
mg), zinc (80 mg), and copper (2 mg) for 5
years compared to participants taking a
placebo” [11,12]
Vitamin A deficiency is a known risk factor

for severe measles [11] and chronic intakes
of excess vitamin A lead to increased
intracranial pressure (pseudotumor
cerebri), dizziness, nausea, headaches, skin
irritation, pain in joints and bones, coma,
and even death [2,3]

1.2. Vitamin D
“Vitamin D is a fat-soluble vitamin that 6. Best indicator of Vit D status is the
is naturally present in very few foods, serum concentration of 25(OH)D. It
added to others, and available as a reflects vitamin D produced cutaneously
dietary supplement. It is also produced and that obtained from food and
endogenously when ultraviolet rays from supplements [14]
sunlight strike the skin and trigger vitamin 7. Stored in the liver and fat [14]
D synthesis. Vitamin D obtained from
sun exposure, food, and supplements is
biologically inert and must undergo two
hydroxylations in the body for activation.
The first occurs in the liver and converts
vitamin D to 25-hydroxyvitamin D
[25(OH)D], also known as calcidiol. The
second occurs primarily in the kidney
and forms the physiologically active
1,25-dihydroxyvitamin D [1,25(OH)2D], also
known as calcitriol” [11, 14].
Vitamin D sources
1. Sunlight: 5 – 30 minutes sun exposure of

the face, arms, legs or back without sun
blocker between 10:00 and 15:00 twice a
week.
2. Tanning beds: moderate use of 2% - 6%

UVB radiation emission [15,16]
Vitamin D Functions
1. Promotes calcium absorption in the GI

tract and maintains adequate serum
calcium and phosphate concentrations
enabling normal mineralization of bone
and to prevent hypocalcaemic tetany.
[14]
2. Needed for bone growth and bone

remodeling by osteoblasts and
osteoclasts [14,17].
3. Prevention of rickets in children and

osteomalacia in adults [14].
4. Together with calcium, vitamin D

also helps protect older adults from
osteoporosis. [11]
5. Cell growth modulation, neuromuscular

and immune function and reduction in
inflammation [14, 18, 19]

D3
DBP
D3 Circulation
Skin
D3
Liver
7-dehyrocholesterol
25-OHase
P1Ca2+ and Intestine
Pre-D3 other factors
24-OHase
25-(OH)D3
D3 +/-
24,25(OH)2D3
Parathyriod glands PTH Kidney Diatary sources
+ Excretion of vitamin D
1a,24,25(OH)2D3
1a-OHase
24-OHase
Inestine 1a25(OH)2D3 Tumour microenviroment

Increases absorbtion ¥ Inhibits proliferation
of Ca2+ and P1 ¥ Induces differentiation
¥ Inhibits angiogenesis
Bone
Increases bone Immune cells
mineralization Induces differentiation

Vitamin D deficiency
1. More prevalent in dark skinned people 10. Animal and epidemiology studies
– less UV activation of Vit D in the skin suggest that Vit D may play some role in
[20,21] but people of African American prevention and treatment of type 1 [ 39]
ancestry, for example, have reduced and type 2 diabetes [40], hypertension
rates of fracture and osteoporosis [41], glucose intolerance [42] and
compared with Caucasians [14] multiple sclerosis [43]
2. Also prevalent in Caucasians [22] 11. type 1 [ 39] and type 2 diabetes [40],
hypertension [41], glucose intolerance
3. Estimated 29% of cancer mortality in [42] and multiple sclerosis [43]
males [23]
4. Cancers of breast, colon, pancreas

and the prostate [23 – 28] and strong
evidence that Vit D has a protective
effect against colon and breast cancer
[29,30] however, in smokers the risk
of pancreatic cancer may be threefold
higher in patients with high Vit D levels
(> 40 ng/ml) [29, 30, 31,32]
5. Cognitive dysfunction [33,34]
6. As many as half of older adults in the

United States with hip fractures could
have serum 25(OH)D levels <30 nmol/L
(<12 ng/mL) [17].
7. Fat malabsorption in association with

inflammatory bowel disease including
some forms of liver disease, cystic
fibrosis, celiac disease, and Crohn’s
disease, as well as ulcerative colitis
(inflamed terminal ileum) [14, 16, 35].
8. Obese individuals may become vitamin

D deficient over time post gastric
bypass surgery without a sufficient
intake from food or supplements, since
part of the upper small intestine where
vitamin D is absorbed is bypassed and
vitamin D mobilized into the serum
from fat stores may not compensate
over time [36,37].
9. More than 40 million adults in the

United States have or are at risk of
developing osteoporosis [38]

25
70%-100%
36%-65%
43%-63%
61% Northern Russian Federation
Canada Europe
92%
45%-98% 78%-98%
27%-91%
57%-64%
Europe
2017 © Copyright to IntraVita Limited

United States 36%
Asia
Middle East
78%-100% 90%
60%
North Africa
Prevalence of vitamin D 20%-59%
South
deficiency (25[OH]D America
South Africa
7%-20%
<20ng/mL)
In general population 25%-65% 31%
In pregnant women Australia
100%
80% 56%
60%
New Zealand
40%
20%
0%
Vitamin D toxicity
“Vitamin D toxicity can cause non-specific symptoms such as anorexia, weight

loss, polyuria, and heart arrhythmias. More seriously, it can also raise blood levels of
calcium which leads to vascular and tissue calcification, with subsequent damage
to the heart, blood vessels, and kidneys [44]. The use of supplements of both calcium
(1,000 mg/day) and vitamin D (400 IU) by postmenopausal women was associated
with a 17% increase in the risk of kidney stones over 7 years in the Women’s Health
Initiative [141]. A serum 25(OH)D concentration consistently >500 nmol/L (>200 ng/
mL) is considered to be potentially toxic” [45, 46]
Medication Interactions
1. Corticosteroids (prednisone): impair calcium absorption and vitamin D

metabolism leading to osteoporosis in long term use [47,48].
2. Orlistat (brand names Xenical® and alliTM) and the cholesterol-lowering drug
cholestyramine (brand names Questran®, LoCholest®, and Prevalite®) can
reduce the absorption of vitamin D and other fat-soluble vitamins [49,50].
3. Phenobarbital and phenytoin (brand name Dilantin®), for prevention and control
of epileptic seizures, increase the hepatic metabolism of vitamin D to inactive
compounds and reduce calcium absorption [51].

1.3 Vitamin E Rare inherited disorders require large doses
of supplemental Vit E (100mg/kg or 5 – 10 g/
“Vitamin E” is the collective name for day [52]
a group of fat-soluble compounds with
distinctive antioxidant activities but Alpha- Vitamin E and Health
(or α-) tocopherol, absorbed from the small
intestine and stored in the liver, is the only Vitamin E may prevent or delay coronary
form that is recognized to meet human heart disease via inhibition of LDL
requirements. [52] oxidation [149] and possibly prevention of
thromboembolism [55].
Vitamin E is a fat-soluble antioxidant that
stops the production of reactive oxygen Vitamin E might also block the formation
species (ROS) formed when fat undergoes of carcinogenic nitrosamines formed in
oxidation. [45] Environmental sources of the stomach from nitrites in foods and
free radicals include cigarette smoke, air may protect against cancer by enhancing
pollution and UV from the sun. [45] immune function [56]
“In addition to its activities as an It may protect against prostate cancer in
antioxidant, vitamin E is involved in smokers [54] and may reduce the risk of
immune function and, as shown primarily
women < 65 years of age developing colon
by in vitro studies of cells, cell signaling,
cancer.
regulation of gene expression, and other
metabolic processes [52]. Alpha-tocopherol Large-dose vitamin E supplements (400 IU)
inhibits the activity of protein kinase C, may increase the risk of prostate cancer
an enzyme involved in cell proliferation [52].
and differentiation in smooth muscle cells,
platelets, and monocytes [149]. Vitamin E “The Age-Related Eye Disease Study
repletes endothelial cells lining the interior (AREDS), a large randomized clinical trial,
surface of blood vessels are better able to found that participants at high risk of
resist blood-cell components adhering to developing advanced AMD (i.e., those with
this surface. Vitamin E also increases the intermediate AMD or those with advanced
expression of two enzymes that suppress AMD in one eye) reduced their risk of
arachidonic acid metabolism, thereby
developing advanced AMD by 25% by taking
increasing the release of prostacyclin
a daily supplement containing vitamin E
from the endothelium, which, in turn,
(400 IU dl-alpha-tocopheryl acetate), beta-
dilates blood vessels and inhibits platelet
aggregation” [45, 53]. carotene (15 mg), vitamin C (500 mg), zinc
(80 mg), and copper (2 mg) compared to
Vitamin E deficiency participants taking a placebo over 5 years
[155]. A follow-up AREDS2 study confirmed
Frank Vitamin D deficiency is rare and
the value of this and similar supplement
people with fat-malabsorption disorders are
formulations in reducing the progression
more likely to become deficient. Deficiency
of AMD over a median follow-up period of 5
symptoms include peripheral neuropathy,
years” [45,59].
ataxia, skeletal myopathy, retinopathy, and
impairment of the immune response [53, Vitamin D may be associated with
54]. slower progression of age-related lens
opacification [60]
People that pass greasy stools or have
chronic diarrhea due to Crohn’s disease Excessive Vitamin E may increase the risk
cystic fibrosis or an inability to secrete of haemorrhagic stroke [61].
bile from the liver, may need water-soluble
forms of vitamin E, such as tocopheryl
polyethylene glycol-1000 succinate [52].

Medication Interactions
“Vitamin E can inhibit platelet aggregation and antagonize vitamin K-dependent clotting factors.
As a result, taking large doses with anticoagulant or antiplatelet medications, such as warfarin
(Coumadin®), can increase the risk of bleeding, especially in conjunction with low vitamin K
intake. The amounts of supplemental vitamin E needed to produce clinically significant effects
are unknown but probably exceed 400 IU/day” [45, 61]

1.4 Vitamin K
Vitamin K functions as a coenzyme for Medication Interactions
vitamin K-dependent carboxylase, an Warfarin: antagonize the activity of vitamin
enzyme required for the synthesis of K, leading to the depletion of vitamin
proteins involved in haemostasis (blood K-dependent clotting factors [72]
clotting) and bone metabolism, and other
diverse physiological functions [62, 63]. Cephalosporin antibiotics destroys Vitamin
Prothrombin(clotting factor II) is a vitamin K producing bacteria in the gut [73]
K-dependent protein in plasma that is
Orlistat [74] and cholestyramine [75]
directly involved in blood clotting. [64]
can potentially reduce the absorption of
“Like dietary lipids and other fat- Vitamin K.
soluble vitamins, ingested vitamin K is
incorporated into mixed micelles via the
action of bile and pancreatic enzymes, and
it is absorbed by enterocytes of the small
intestine [65]. From there, vitamin K is
incorporated into chylomicrons, secreted
into the lymphatic capillaries, transported
to the liver, and repackaged into very low-
density lipoproteins [66, 65]. Vitamin K is
present in the liver and other body tissues,
including the brain, heart, pancreas, and
bone. Vitamin K is rapidly metabolized and
excreted.” [45, 66, 67, 68].
Most U.S. diets contain an adequate amount

of vitamin K [69]
Prothrombin time (the time it takes

for blood to clot) is the only clinically
significant indicator of vitamin K status
and ordinary changes in vitamin K
intakes have rarely been shown to alter
prothrombin time [63].
Vitamin K Deficiency
Bleeding is the classic sign of deficiency

and because Vitamin K required for the
carboxylation of osteocalcin in bone,
vitamin K deficiency could also reduce
bone mineralization and contribute to
osteoporosis [70]
Other Benefits
Matrix Gla-protein (MGP) is a vitamin

K-dependent protein that may play a role in
the prevention of vascular calcification [63,
71]

2. WATER-SOLUBLE VITAMINS
B VITAMINS
Route of Supplementation: Orally and Intravenously
2.1. THIAMINE (Vitamin B1)

Vitamin B1 plays a critical role in energy metabolism and, therefore, in the growth,
development, and function of cells [76]
Thiamin is absorbed by the small intestine through active transport at nutritional doses
and by passive diffusion at pharmacologic doses [76]. Bacteria in the large intestine also
synthesize free thiamin and also the active thiamin diphosphate (TDP) that serves as an
essential cofactor for five enzymes involved in glucose, amino acid, and lipid metabolism
[76, 77].
Heating, water, pasteurization of milk and processing reduce the thiamin content in food.
[77, 78]

Recommended Dietary Allowances (RDAs) for Thiamin
Age Male Female Pregnancy Lactation
Birth - 6 months 0.2 mg 0.2 mg
7-12 months 0.3 mg 0.3 mg
1-3 years 0.5 mg 0.5 mg
4-8 years 0.6 mg 0.6 mg
9-13 years 0.9 mg 0.9 mg
14-18 years 1.2 mg 1.0 mg 1.4 mg 1.4 mg
19-50 years 1.2 mg 1.1 mg 1.4 mg 1.4 mg
51 + years 1.2 mg 1.1 mg
Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin
B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998. [79]
Selected Food Sources of Thiamin

Food Mg (Per serving) Percent DV*
Breakfast cereals, fortified with 100% of the DV for thiamin, 1 serving 1.5 100
Rice, white, long grain, enriched, parboiled, ½ cup 1.4 73
Egg noodles, enriched, cooked, 1 cup 0.5 33
Pork chop, bone-in, broiled, 3 ounces 0.4 27
Trout, cooked, dry heat, 3 ounces 0.4 27
Black beans, boiled, ½ cup 0.4 27
English muffin, plain, enriched, 1 muffin 0.3 20
Mussels, blue, cooked, moist heat, 3 ounces 0.3 20
Tuna, Bluefin, cooked, dry heat, 3 ounces 0.2 13
Macaroni, whole wheat, cooked, 1 cup 0.2 13
Acorn squash, cubed, baked, ½ cup 0.2 13
Rice, brown, long grain, not enriched, cooked, ½ cup 0.1 7
Bread, whole wheat, 1 slice 0.1 7
Orange juice, prepared from concentrate, 1 cup 0.1 7
Sunflower seeds, toasted, 1 ounce 0.1 7
Beef steak, bottom round, trimmed of fat, braised, 3 ounces 0.1 7
Yogurt, plain, low fat, 1 cup 0.1 7
Oatmeal, regular and quick, unenriched, cooked with water, ½ cup 0.1 7
Corn, yellow, boiled, 1 medium ear 0.1 7
Milk, 2%, 1 cup 0.1 7
Barley, pearled, cooked, 1 cup 0.1 7
Cheddar cheese, 1½ ounces 0 0
Chicken, meat and skin, roasted, 3 ounces 0 0
Apple, sliced, 1 cup 0 0
*DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers
compare the nutrient contents of products within the context of a total diet. The DV for thiamin is 1.5 mg for
adults and children age 4 and older. Foods providing 20% or more of the DV are considered to be high sources
of a nutrient. [78]

Thiamin deficiency
May be due to poor diet, lower absorption or Thiamin levels in plasma are up to 76%
higher excretion due to alcohol dependence lower in people with type 1 diabetes than in
or HIV/AIDS [77]. healthy volunteers and 50%–75% lower in
people with type 2 diabetes [88,89]
“In its early stage, thiamin deficiency can
cause weight loss and anorexia, confusion, Bariatric surgery for weight loss is
short-term memory loss, and other mental associated with some risks, including
signs and symptoms; muscle weakness; severe thiamin deficiency due to
and cardiovascular symptoms (such as an malabsorption that can lead to beriberi
enlarged heart) [45, 79]. or Wernicke’s encephalopathy [90] and
these patients must have micronutrient
The most common effect of thiamin supplementation [91].
deficiency is beriberi, which is
characterized mainly by peripheral Autopsy studies have shown that
neuropathy and wasting [76,77]. People transketolase and other thiamin-dependent
with this condition have impaired sensory, enzymes have decreased activity in the
motor, and reflex functions. In rare cases, brains of people with Alzheimer’s disease
beriberi causes congestive heart failure [92,93].
that leads to edema in the lower limbs
Medicine Interactions
and, occasionally, death [76,77]. Although
beriberi is rare in the United States and The loop diuretic, furosemide may be linked
other developed countries, people in to decreases in thiamin concentrations,
these countries do occasionally develop possibly to deficient levels, as a result of
the condition [80,81]. Administration of urinary thiamin loss [94].
supplemental thiamin, often parenterally,
quickly cures beriberi “[77]. Patients with colorectal cancer treated
with 5-Fluoroucil are at risk of developing
Wernicke-Korsakoff syndrome beriberi and Wernicke’s encephalopathy
[82] (peripheral neuropathy [77] , [95,96]
encephalopathy, psychosis, short
term memory loss, confabulation) is a
manifestation of thiamin deficiency in
chronic alcoholics and in patients whom
have severe gastrointestinal disorders,
rapidly progressing haemotological
malignancies, drug use disorders or AIDS
[82]. Parenteral thiamin does not lead to
recovery in 25% of patients [83]
“Up to 20%–30% of older adults have

laboratory indicators that suggest some
degree of thiamin deficiency [82, 79].
Possible reasons include low dietary
intakes, a combination of chronic diseases,
concomitant use of multiple medications,
and low absorption of thiamin as a natural
result of aging [84,85]. Some small studies
have found that the risk of deficiency is
particularly high in elderly people who
reside in an institution” [45,86,87].

2.2. RIBOFLAVIN (Vitamin B2)
“This vitamin is an essential component of two major coenzymes, flavin mononucleotide
(FMN; also known as riboflavin-5’-phosphate) and flavin adenine dinucleotide (FAD).
These coenzymes play major roles in energy production; cellular function, growth, and
development; and metabolism of fats, drugs, and steroids [97,98,99]. The conversion of the
amino acid tryptophan to niacin (sometimes referred to as vitamin B3) requires FAD [99].
Similarly, the conversion of vitamin B6 to the coenzyme pyridoxal 5’-phosphate needs
FMN. In addition, riboflavin helps maintain normal levels of homocysteine, an amino acid
in the blood”[97].
Most Riboflavin from the diet is absorbed in the proximal small intestine and free
riboflavin produced by bacteria in the large intestine is absorbed from the large intestine.
Small amounts is stored in the liver, heart and kidneys [98,99,100]
Selected Food Sources of Riboflavin

Food Mg (Per serving) Percent DV*
Beef liver, pan fried, 3 ounces 2.9 171
Breakfast cereals, fortified with 100% of the DV for riboflavin, 1 serving 1.7 100
Oats, instant, fortified, cooked with water, 1 cup 1.1 65
Yogurt, plain, fat free, 1 cup 0.6 35
Milk, 2% fat, 1 cup 0.5 29
Beef, tenderloin steak, boneless, trimmed of fat, grilled, 3 ounces 0.4 24
Clams, mixed species, cooked, moist heat, 3 ounces 0.4 24
Mushrooms, portabella, sliced, grilled, ½ cup 0.3 18
Almonds, dry roasted, 1 ounce 0.3 18
Cheese, Swiss, 3 ounces 0.3 18
Rotisserie chicken, breast meat only, 3 ounces 0.2 12
Egg, whole, scrambled, 1 large 0.2 12
Quinoa, cooked, 1 cup 0.2 12
Bagel, plain, enriched, 1 medium (3½"–4" diameter) 0.2 12
Salmon, pink, canned, 3 ounces 0.2 12
Spinach, raw, 1 cup 0.1 6
Apple, with skin, 1 large 0.1 6
Kidney beans, canned, 1 cup 0.1 6
Macaroni, elbow shaped, whole wheat, cooked, 1 cup 0.1 6
Bread, whole wheat, 1 slice 0.1 6
Cod, Atlantic, cooked, dry heat, 3 ounces 0.1 6
Sunflower seeds, toasted, 1 ounce 0.1 6
Tomatoes, crushed, canned, ½ cup 0.1 6
Rice, white, enriched, long grain, cooked, ½ cup 0.1 6
Rice, brown, long grain, cooked, ½ cup 0 0
*DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers
compare the nutrient contents of products within the context of a total diet. The DV for riboflavin is 1.7 mg for
adults and children age 4 and older. Foods providing 20% or more of the DV are considered to be high sources
of a nutrient. [101]

Riboflavin Deficiency
“Riboflavin deficiency is extremely rare in the United States. May be caused by thyroid
hormone insufficiency [194]. Signs and symptoms of Ariboflavinosis include skin
disorders, hyperemia and edema of the mouth and throat, angular stomatitis, cheilosis,
hair loss, reproductive problems, sore throat, itchy and red eyes, and degeneration of the
liver and nervous system.” [45,97,98,99,102].
Anemia and cataracts can develop if riboflavin deficiency is severe and prolonged [97].
At risk groups:
1. Vegetarian athletes if all animal products are excluded from the diet [103]
2. Pregnant and lactating women and their infants who rarely consume meats or dairy
products [98]. Deficiency increase the risk of pre-eclampsia [104]
3. Vegans [105]
4. People that consume little amounts of milk [105]
5. People with Infantile Brown-Vialetto Laere syndrome (SLC52A3 gene mutation), a

neurological disorder that can begin at any age, have riboflavin deficiency and is
associated with deafness, bulbar palsy and respiratory problems [106]
6. Migraine: 200mg - 400mg/day reduced the frequency of attacks and severity of the
pain in children and in adults [107,108]
There are no reported riboflavin clinical interactions with medications [45].
Recommended Dietary Allowances (RDAs) for Riboflavin

Age Male Female Pregnancy Lactation
Birth - 6 months 0.3 mg 0.3 mg
7-12 months 0.4 mg 0.4 mg
1-3 years 0.5 mg 0.5 mg
4-8 years 0.6 mg 0.6 mg
9-13 years 0.9 mg 0.9 mg
14-18 years 1.3 mg 1.0 mg 1.4 mg 1.6 mg
19-50 years 1.3 mg 1.1 mg 1.4 mg 1.6 mg
51 + years 1.3 mg 1.1 mg
Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin
B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998.
[99]

2.3. NIACIN (Nicotinic acid and nicotinamide - Vitamin B3)
www.en.wikipedia.org
Both nicotinic acid and nicotinamide can serve as dietary source of vitamin B3. The active
forms of vitamin B3 is NAD+ and NADP+ and both function as cofactors for numerous
dehydrogenases [109]
Niacin is not a true vitamin since it can be derived from tryptophan (amino acid) but it is
inefficient as a sole source of niacin synthesis and the process requires vitamins B1, B2
and B6 [109]
Foods containing niacin: liver, meat, peanuts and other nuts and whole grains. [109]
Niacin deficiency (and tryptophan) [109]
1. Leads to glossitis, dermatitis, weight loss, diarrhea, depression and dementia
2. Pellagra: “3-Ds” (depression, dermatitis and diarrhea)
Causes of niacin deficiency [109]
1. Hartnup disorder – impaired tryptophan absorption
2. Malignant carcinoid syndrome – altered tryptophan metabolism resulting in excess

serotonin synthesis
3. Isoniazid – formerly a primary anti tuberculosis chemotherapeutic agent
Pharmacological effects of Nicotinic acid
In doses of 2-4 g/day nicotinic acid (not nicotinamide) lowers plasma LDL cholesterol and
triglycerides levels but increases plasma HDL cholesterol [113, 206] and causes depletion
of glycogen stores and fat reserves in skeletal and heart muscle and elevation of blood
glucose and uric acid production [109].
Side effect: flushing (strong cutaneous vasodilatation) [110]
Contra-indications: diabetics and gout sufferers. [109]

2.4 PANTOTHENIC ACID (Vitamin B5)
www.wikipedia.org
Formed from beta-Alanine and pantoic acid [109]
Functions [109, 111]
• Vitamin B5 plays a role in breakdown of fats and carbohydrates for energy.
• Critical to the manufacture of red blood cells
• Plays a role in sex and stress-related hormones produced by the adrenal glands
• Maintains a healthy GI tract
• Assists in the usage of other vitamins, especially riboflavin (Vit B2)
• Is sometimes called the “anti-stress” vitamin, but no concrete evidence exists.
• Vit B5 is needed to synthesize cholesterol.
Vitamin B5 Deficiency
Very rare and may include symptoms of fatigue, insomnia, depression, irritability,
vomiting, abdominal pain, burning feet and upper respiratotory infections, muscle cramps
and dizzy spells. [109, 112,113]
In addition, hypoglycaemia or increased insulin sensitivity and very rarely adrenal

insufficiency and hepatic encephalopathy [112,113]
Toxicity is unlikely.
Research
1. Promising pilot study showed very good results in 96% healing of diabetic foot
ulceration [114]
2. Improvement of the lipid profile in the blood and the liver [115]
3. Patients treated with alpha-lipoic acid for diabetic peripheral neuropathy improved
even more after additional Vitamin B5 were given [116]

2.5. PYRIDOXINE, pyridoxal and pyridoxamine are collectively known as
VITAMIN B6 [109]
Pyridoxine Pyridoxal
All 3 compounds are converted to the biologically active form of Vitamin B6 known as
pyridoxal phosphate (PLP)

Functions
A cofactor in all of the enzymes that carry out transamination reactions required for the
synthesis and breakdown of amino acids [109]
In 2009 the US FDA ruled that pyridoxine must be regulated as a pharmaceutical drug
because it is the active ingredient in Pyridorin, a drug designed to prevent progression of
diabetic nephropaty [117]
PLP is a cofactor for the synthesis of:
• Neurotransmittiers serotonin, dopamine, norepinephrine, epinephrine and GABA
• Heme
• Methionine and systein metabolism
• Conversion of tryptophan to niacin
• Glycogen homeostasis [109]
Causes of Vitamin B6 deficiency
Alcoholism is the leading cause
Isoniazid and penicillamine complex with pyridoxal and PLP leading to seizures due to
reduction in GABA synthesis [109]
Effects of Vit B6 deficiency
Due to its role in heme synthesis, Vit B6 deficiency can result in microcytic hypochromic
anaemias (similar to iron deficiency and lead poisoning) [109]
Two critical enzymes requires PLP in the metabolism of metionine to cysteine. Deficiency
in PLP can lead to homocysteinemia/uria, a risk factor in coronary artery disease.
Other symptoms include nervousness, insomnia, skin eruptions, loss of muscular control,
muscular weakness, anaemia, dermatitis, arm and leg cramps, hair loss, slow learning and
water retention [109]
2.6. BIOTIN (Vitamin H) [109, 118]
Biotin is a cofactor and is required for carbohydrate, fat and amino acid metabolism.
Recommended for strengthening hair and nails.

Bacteria in the intestine can synthesize biotin and it is important for normal embryonic
growth [119]
Biotin Effects
• May improve blood sugar control in combination with chromium
• May improve the symptoms of peripheral neuropathy following diabetes or or ongoing

kidney dialysis.
• May help to restore taste among people that have lost their sense of taste [120]
Biotin Deficiency
Low biotin levels are present in alcoholics, achlorhydria (partial gastrectomy) and
dysbiosis [121].
Very rare and symptoms include hair loss, dry scaly skin, cheilitis, glosssitis, dry eyes,
loss of appetite, fatigue, insomnia and depression.
Usually after long courses of antibiotic therapy that depletes intestinal bacteria or
following excessive consumption of raw eggs (egg white protein avidin preventing biotin
intestinal absorption) [109, 121]
Autosomal recessive inherited disorder that leads to biotin deficiency is called biotinidase (BTD)
and it renders patients with this disorder highly susceptible to candidiasis. Symptoms include
seizures, hypotonia, hearing and vision loss, ataxia, skin rashes and alopecia [109]

2.7. COBALAMIN (Vitamin B12)
Food
B12 is tightly attached
to animal protein in Mouth
animal products. Saliva contains carrier
proteins that attach to B12 in
the stomach to protect B12
from destruction by stomach
acids.
Stomach
Liver 1. Strong acids free B12 from
animal protein.
60% of B12 stored in
the liver and 30% 2. Parietal cells make Intrinsic
stored in muscles Factor (IF) that helps B12 to be
absorbed.
Gallbladder
Releases B12 and bile into
Panaceas
the intestines in response to
fatty meals. Secretes enzymes that digest
carrier proteins to free B12
and allow it to bind with IF
into the duodenum.
Enterohepatic Circulation
Blood vessels take nutrients
from the intestines to the
liver. This is how the body Duodenum
conserves B12. It is constantly Alkaline enviroment in
reabsorbed and stored in the the beginning of the small
body. intestine where B12 attaches
to Intrinsic Factor (IF).
Ileum
End of the small intestine where
Colon 1.5-2 mcg of the B12-IF complex
Lots of actuve B12 is made by is absorbed into the blood every
bacteria but it is not absorbed 4-6 hours. This is also where 1%
and passes out with feces. of free B12 is absorbed and where
B12 is reabsorbed with bile for
Anus storage in the liver.
Vitamin B12 is required for proper red cell formation, neurological function and DNA
synthesis [122-126].

Vitamin B12 as hydroxycobalamin is synthesized
exclusively by microorganisms and is found
in the liver of animals bound to protein as
methylcobalamin [109]
Vitamin B12 is a chelator of cyanide and is used

in cyanide poisoning [127]
Hdroxocobalamin is most generally used

for vitamin B12 replacement therapy and is
considered the “drug of choice” for vitamin
B12 deficiency by the Martindale Extra
Pharmacopoeia (Sweetman, 2002) and the
World Health Organization (WHO) Model
List of Essential Drugs. This preference for
hydroxocobalamin in many countries is due to
its long retention in the body and the need for
less-frequent IM injections in restoring vitamin
B12 (cobalamin) serum levels. Furthermore, IM
administration of hydroxocobalamin is also the
preferred treatment for pediatric patients with
intrinsic cobalamin metabolic diseases; vitamin
B12-deficient patients with tobacco amblyopia
due to cyanide poisoning; and patients with
pernicious anemia who have optic neuropathy
[128-131]
Causes of deficiency
• Vegetarians (dietary deficiency)
• Older adults: atrophic gastritis affects 10%

– 30% and leads to decrease in hydrochloric
acid secretion in the stomach and decreased
absorption of Vitamin B12 [126]
• The liver can store up to six years worth of

Vitamin B12 so that deficiencies are rare.
Inadequate secretion of intrinsic factor (IF)
associated with conditions that destroy
the gastric mucosa, gastric atrophy such
as multiple sclerosis, iron deficiency and
subtotal gastrectomy leads to malabsorption
of Vitamin B12 and megaloblastic anaemia
[109]
• Competition for Vitamin B12 by intestinal

parasites or bacteria.

Pathophysiology of Vitamin B12
Effects of Vitamin B12 Deficiency
• Megaloblastic anaemia (pernicious anaemia)
• Progressive demyelination of nerve cells
• Elevation in levels of circulating homocysteine that leads to production of defective

collagen and elastin with a negative impact on arteries, bone and skin [109]
• Deep vein thrombosis is associated with homocysteinemia that causes the activation
of the intrinsic coagulation cascade
• Symptoms include fatigue, weakness, constipation, loss of appetite and weight loss
[122,124]. Numbness, tingling of the feet [126] imbalance, depression, confusion,
dementia, poor memory and glossitis.

Normal red blood cell (RBC)
Macrocyric RBC
Platelet
Neutrophil

Platelet
Macrocyric, hypochromic RBC
Cigar shape cells
Peripheral blood smear in Pernicious anemia
Platelet
Macrocyric RBC
Hypersegmented polymorphonuclear neutropil
Interactions with medications
1. Chloramphenicol: bacteriostatic antibiotic can interfere with red blood cell response to
supplemental Vit B12 [132]
2. Proton pump inhibitors: omeprazole and lansoprazole, etc., slow gastric acid release
and may interfere with VIt B12 absorption from food [132]
3. H2-receptor antagonists: cimetidine, famotidine and ranitidine slow the release of

hydrochloric acid into the stomach and interfere with Vitamin B12 absorption from
food [133]
4. Metformin: might reduce absorption of Vitamin B12 due to altered intestinal motility,
increased bacterial overgrowth, etc. [133]

2.8. FOLIC ACID (folate)
Folic acid (folate) is a water-soluble B vitamin that functions as a coenzyme in DNA and
RNA synthesis and amino acid metabolism. [134]
Role of Vitamin B12 and Folate in DNA Synthesis
“One of the most important folate-dependent reactions is the conversion of homocysteine

to methionine in the synthesis of S-adenosyl-methionine, an important methyl donor
[134-136]. Another folate-dependent reaction, the methylation of deoxyuridylate to
thymidylate in the formation of DNA, is required for proper cell division. An impairment
of this reaction initiates a process that can lead to megaloblastic anemia, one of the
hallmarks of folate deficiency’” [45,136].
Folate deficiency
“Isolated folate deficiency is uncommon; it usually coexists with other nutrient

deficiencies because of its strong association with poor diet, alcoholism, and, sometimes,
malabsorption disorders [136]. Megaloblastic anemia, which is characterized by large,
abnormally nucleated erythrocytes, is the primary clinical sign of a deficiency of folate or
vitamin B12 [134,136].
Symptoms of megaloblastic anemia include weakness, fatigue, difficulty concentrating,

irritability, headache, heart palpitations, and shortness of breath [135].

Folate deficiency can also produce soreness and shallow ulcerations in the tongue
and oral mucosa; changes in skin, hair, or fingernail pigmentation; and elevated blood
concentrations of homocysteine [134-136].
“Women with insufficient folate intakes are at increased risk of giving birth to infants
with neural tube defects (NTDs) although the mechanism responsible for this effect is
unknown [135]. Inadequate maternal folate status has also been associated with low infant
birth weight, preterm delivery, and fetal growth retardation“[137].
Homocysteine Metabolism
Homocysteine is methylated to form the essential amino acts methionine in two

pathways. The reaction of homocysteine remethylation catalysed by the vitamin b12
dependant methionine synthase captures a metal group from the folate-dependent one
carbon pool (5-methyltetrahydrofolate). A second pathway requires betaine (N,N,N-
trimethylglycine) as a methyl donor for the methylation of homocysteine catalysed
by betaine homocysteine methyltransferase. The catabolic pathway of homocysteine,
known as the transsulfuration pathway, converts homocysteine to the amino acid
cysteine via two vitamin b6 (PLP)-dependent enzymes. Cystathionine-β-synthase
catalyse the condensation of homocysteine with serine to form cystathionine is then
converted to cysteine, a-ketobutyrate, and ammonia by cystathionine-y-lyase. TH4-folate,
Tetrahydrofolate.

Groups at risk of deficiency
1. Alcoholics [134]
2. Women of childbearing age [135]
3. Pregnant women [135]
4. Malabsorption disorders [136]
Folic acid may increase the risk of prostate cancer [138] and reduce the risk of stroke in
women via decrease in levels of homocysteine [139]. Low folate status has been linked to
depression and poor response to antidepressants [140].
Interactions with medicines
Methotrexate: folate antagonist [141]
Anti-epileptic medication: Phenytoin, carbamazepine and valproate can reduce

serum folate levels and folic acid supplementation may reduce serum levels of these
medications [141,142].
Sulfasalazine: used to treat ulcerative colitis inhibits intestinal absorption of folate [141].
Recommended Dietary Allowances (RDAs) for Folate
Age Male Female Pregnant Lactating
Birth to 6 months* 65 mcg DFE* 65 mcg DFE*
7–12 months* 80 mcg DFE* 80 mcg DFE*
1–3 years 150 mcg DFE 150 mcg DFE
14–18 years 400 mcg DFE 400 mcg DFE 600 mcg DFE 500 mcg DFE
19+ years 400 mcg DFE 400 mcg DFE 600 mcg DFE 500 mcg DFE
* Adequate Intake (AI)
* Institute of Medicine. Food and Nutrition Board (1998). Dietary Reference Intakes:
Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and
Choline . Washington, DC, National Academy Press. [135]
Differential diagnosis: Vitamin B12 deficiency versus Folate deficiency [109]
Deficiency Characteristics
1. Homocysteinaemia: increased risk of atherosclerosis & DVT

2. Megaloblastic anaemia: due to folate trapping at the methionine synthase reaction
Vitamin B12
Effect: reduction in measurable methionine in blood & urine AND dramatic increase in
measurable methylmalonic acid which is NOT seen in folate deficiency.
1. Homocysteinaemia
2. Megaloblastic anaemia: due to loss of purine nucleotide and thymidine nucleotide
Folate synthesis
Effect: reduction in measuirable serum & urine methionine and NO associated methylmalonic
acidaemia.

2.9. L-ASCORBIC ACID (Vitamin C)
L-ascorbic acid is water-soluble and humans are unable to synthesize vitamin C

endogenously. It is a reducing agent in a number of reactions [109, 143]. Vitamin C is
required for biosynthesis of collagen, L-carnitine, certain neurotransmitters and protein
metabolism [143]

Vitamin C is also an important physiological antioxidant [144] and has been shown to
regenerate other antioxidants within the body, including alpha-tocopherol (vitamin E)
“Oral vitamin C produces tissue and plasma concentrations that the body tightly controls.
Approximately 70%–90% of vitamin C is absorbed at moderate intakes of 30–180 mg/
day. However, at doses above 1 g/day, absorption falls to less than 50% and absorbed,
unmetabolized ascorbic acid is excreted in the urine [45, 145]. Pharmacokinetic modeling
predicts that even doses as high as 3 g ascorbic acid taken every 4 hours would produce
peak plasma concentrations of only 220 micromol/L “[146]. This is important in terms
of the much higher serum ascorbic acid concentrations possible with intravenous
administration versus oral supplementation.
“High levels of vitamin C (millimolar concentrations) are maintained in cells and tissues,
and are highest in leukocytes, eyes, adrenal glands, pituitary gland, and brain. Relatively
low levels of vitamin C (micromolar concentrations) are found in extracellular fluids, such
as plasma, red blood cells, and saliva” [45, 145]
Recommended Dietary Allowances (RDAs) for Vitamin C [147]
0–6 months 40 mg* 40 mg*
7–12 months 50 mg* 50 mg*
1–3 years 15 mg 15 mg
14–18 years 75 mg 65 mg 80 mg 115 mg
19+ years 90 mg 75 mg 85 mg 120 mg
Smokers Individuals who smoke require 35 mg/day more vitamin C than nonsmokers.
* Adequate Intake (AI)
* DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA)
to help consumers compare the nutrient contents of products within the context of a
total diet. The DV for vitamin C is 60 mg for adults and children aged 4 and older. The FDA
requires all food labels to list the percent DV for vitamin C. Foods providing 20% or more of
the DV are considered to be high sources of a nutrient.
Tolerable Upper Intake Levels (ULs) for Vitamin C [147]
0–12 months Not possible to establish* Not possible to establish*
1–3 years 400 mg 400 mg
4–8 years 650 mg 650 mg
9–13 years 1,200 mg 1,200 mg
14–18 years 1,800 mg 1,800 mg 1,800 mg 1,800 mg
19+ years 2,000 mg 2,000 mg 2,000 mg 2,000 mg
* Formula and food should be the only sources of vitamin C for infants.

Note: Plasma vitamin C levels is the standard assessment for vitamin C status [145]
however, intracellular leukocyte vitamin C concentration, could be a more accurate
indicator of tissue vitamin C levels, but is more difficult to assess and the results
Vitamin C Deficiency
Scurvy symptoms timeline:
1. Fatigue, malaise inflammation of gums [145]
2. Impaired collagen synthesis results in connective tissue weakness causing petechiae,

ecchymosis, purpura, arthralgia, poor wound healing, hyperkeratosis and corkscrew
hairs [143,145]
3. Depression [147]
4. Iron deficiency anaemia due to increased bleeding and decreased nonheme iron
absorption [148]
Groups at risk of Vitamin C Inadequacy
1. Smokers and passive smokers: lower plasma and leukocyte levels than nonsmokers
[147].
2. Malabsorption
3. Cancer and end-stage renal disease and chronic hemodialysis [149,150]
Vitamin C and Health
Most case-control studies have found an inverse association between dietary vitamin
C intake and cancers of the lung, breast, colon or rectum, stomach, oral cavity, larynx or
pharynx, and esophagus [145, 151]
“It is uncertain whether supplemental vitamin C and other antioxidants might interact
with chemotherapy and/or radiation [152]. Therefore, individuals undergoing these
procedures should consult with their oncologist prior to taking vitamin C or other
antioxidant supplements, especially in high doses “ [153]
G6PD Deficiency
Glucose-6-phosphate dehydrogenase is an enzyme that keeps glutathione in its reduced

form (GSH). Consumption of substances with strong oxidizing capacity can result in
haemolytic anaemia in adults. Extremely large oral doses or 40g to 100g i.v. can cause
erythrocyte haemolysis. Large doses of water-soluble Vitamin K3 can cause haemolysis
[154]
Cardio-vascular effects:
1. Reduce monocyte adherence to endothelium
2. Improve endothelium-dependant nitric oxide production and vasodilatation
3. Reduce vascular smooth-muscle-cell apoptosis which prevents plaque instability in

atherosclerosis [151, 155]

“In trials involving marathon runners, skiers, and soldiers exposed to extreme physical
exercise and/or cold environments, prophylactic use of vitamin C in doses ranging from
250 mg/day to 1 g/day reduced cold incidence by 50%” [45]
Health Risks from Excessive Vitamin C
1. Kidney stones in individuals with renal disease and pre-existing hyperoxaluria

[147,156]
2. In individuals with hereditary haemochromatosis, chronic consumption of high doses

of vitamin C could exacerbate iron overload and result in tissue damage [145,147]
Chemotherapy and radiation
“The safety and efficacy of the use of vitamin C and other antioxidants during cancer
treatment is controversial [152, 157,158]. Some data indicate that antioxidants might
protect tumor cells from the action of radiation therapy and chemotherapeutic agents,
such as cyclophosphamide, chlorambucil, carmustine, busulfan, thiotepa, and doxorubicin
[153,157,159,160]. At least some of these data have been criticized because of poor study
design [161]. Other data suggest that antioxidants might protect normal tissues from
chemotherapy- and radiation-induced damage [157,159] and/or enhance the effectiveness
of conventional cancer treatment [162]. However, due to the physiologically tight control
of vitamin C, it is unclear whether oral vitamin C supplements could alter vitamin
C concentrations enough to produce the suggested effects. Individuals undergoing
chemotherapy or radiation should consult with their oncologist prior to taking vitamin C
or other antioxidant supplements, especially in high doses” [153].
The combination niacin–simvastatin (Zocor®) therapy’s increase in HDL may be

attenuated by vitamin C in combination with other anti-oxidants [163,164].

CHAPTER 4:
GLUTATHIONE

GLUTATHIONE: THE ‘MASTER’ ANTIOXIDANT
1. What is glutathione?
A tripeptide composed of the amino acids glutamic acid, cysteine, and glycine. Is found
in all cells in the body, in the bile, in the epithelial lining fluid of the lungs, and, at much
smaller concentrations, in the blood. The active form is the chemically reduced form,
called “GSH” that serves as a substrate for enzymes, including the glutathione peroxidases
and the glutathione-S-transferases [1-5]
2. What are some of the functions of glutathione (GSH)?

Maintains proper oxidation-reduction (redox) potential inside cells. Redox affects the
oxidation state of sulfur in enzymes, and thus affects the rates of biochemical reactions in
cells.
1. Scavenges peroxides and oxidizing free radicals directly and also serves as the basis
for the antioxidant network.
2. Performs Phase II detoxication in the liver of heavy metals (such as mercury),

organophosphate pesticides, chlorinated hydrocarbon solvents, estradiol,
prostaglandins, leukotrienes, acetaminophen, and other foreign and endogenous
toxins.
3. Stores and transports cysteine throughout the body.
4. Transports amino acids, especially cysteine into kidney cells.
5. Regulates the cell cycle, DNA and protein synthesis and proteolysis, and gene
expression.
6. Regulates signal transduction.
7. Participates in bile production.
8. Protects thyroid cells from self-generated hydrogen peroxide

In carrying out several of the above functions, GSH plays very important roles in (1)
maintaining mitochondrial function and integrity, (2) regulating cell proliferation, and (3)
supporting the immune system [1-5]
3. How is glutathione (GSH) synthesized in the body?

1. The first step involves the ATP-powered enzyme glutamate cysteine ligase (formerly
called gamma-glutamylcysteine synthetase).
2. The second step makes use of the ATP-powered enzyme glutathione
4. Glutathione depletion
1. Chronic fatigue syndrome [6]
2. GSH deficiency is of great significance in the pathogenesis of Diabetes Mellitus. [7]
3. Glutathione depletion may contribute to the production of phototoxicity by UVB, UVA

and by PUVA [8}

5. Glutathione as a depigmentation agent
1. “The skin melanin index was significantly lower with GSSG treatment than with
placebo from the early weeks after the start of the trial through to the end of the study
period (at 10 weeks, P,0.001). In addition, in the latter half of the study period GSSG-
treated sites had significant increases in moisture content of the stratum corneum,
suppression of wrinkle formation, and improvement in skin smoothness. There were
no marked adverse effects from GSSG application. Conclusion: Topical GSSG is safe
and effectively whitens the skin and improves skin condition in healthy women” [9]
2. “Glutathione is an ubiquitous compound found in our bodies. Aside from its many
ascribed biologic functions, it has also been implicated in skin ligh- tening. We review
in vitro and in vivo studies that show evidence of its involvement in the melano- genic
pathway and shed light on the its anti-mela- nogenic effect. Proposed mechanisms of
action include: (a) direct inactivation of the enzyme tyrosinase by binding with the
copper-containing active site of the enzyme; (b) mediating the switch mechanism
from eumelanin to phaeomelanin production; (c) quenching of free radicals and
peroxides that contribute to tyrosinase activation and melanin formation; and d)
modulation of depigmenting abilities of melanocytotoxic agents. These concepts
supported by the various experimental evidence presented form basis for future
research in the use of glutathione in the treatment of pigmentary disorders” [10]

Notes:

CHAPTER 5:
ESSENTIAL MICRONUTRIENTS –
MINERALS

1. CALCIUM
Calcium, the most abundant mineral in the body and is required for vascular contraction
and vasodilation, muscle function, nerve transmission, intracellular signaling and
hormonal secretion. Though less than 1% of total body calcium is needed to support these
critical metabolic functions [1].
“Bone itself undergoes continuous remodeling, with constant resorption and deposition of
calcium into new bone. The balance between bone resorption and deposition changes with
age. Bone formation exceeds resorption in periods of growth in children and adolescents,
whereas in early and middle adulthood both processes are relatively equal. In aging
adults, particularly among postmenopausal women, bone breakdown exceeds formation,
resulting in bone loss that increases the risk of osteoporosis over time” [1].
Tolerable Upper Intake Levels (ULs) for Calcium [1]
0–6 months 1,000 mg 1,000 mg
7–12 months 1,500 mg 1,500 mg
1–8 years 2,500 mg 2,500 mg
9–18 years 3,000 mg 3,000 mg 3,000 mg 3,000 mg
19–50 years 2,500 mg 2,500 mg 2,500 mg 2,500 mg
51+ years 2,000 mg 2,000 mg
Hypocalcaemia results primarily from medical problems or treatments, including

renal failure, surgical removal of the stomach, and use of certain medications (such as
diuretics). Symptoms of hypocalcaemia include numbness and tingling in the fingers,
muscle cramps, convulsions, lethargy, poor appetite, and abnormal heart rhythms [2]. If
left untreated, calcium deficiency leads to death.

Solar UVB radiation
7-dehydrocholesterol Previtamin D3
Vitamin D replacement
Skin
Ergocalciferol = Vit D2
Cholecalciferol = Vit D2
Diet Vitamin D3 Alfacalcidol= 1α(OH)-D2
Calcitriol = 1,25(OH)-D2
Dietary Vit D
Average daily intake 500iu.
recommended ended in take 400iu.
25(OH)-D
25-hydroxylase activity is essentially
unregulated. 25(OH)-D is the major circulating
1α-hyroxylation metabolite, acting as a store.
Stimulated by Inhibited by
PTH 1,25(OH)2-D 25(OH)-D
Low PO4 High PO4
PTH Effects in the kidney
Possibility GH and Insulin.
1. Stimulates 1-OHase
Extra-renal 1α-hydroxylation in
2. Decreases PO4 resorption in proximal tubule via
macrophages, e.g. in sarcoidosis.
increases in intracellular (and urinary) CAMP.
3. Increases Ca resorption in distal tubule.
PTH production
Main situmulus is low Ca2+.
Inhibted by 1,25(OH)2-D.
1125(OH)2-D effects on kidney
Mg required for synthesis,
increases Ca resorption in distal release and action of PHT.
tubule, upregulating calbindin.
1125(OH)2-D
Parathyroid
hormone
Vit D effects on bone?

Unsure id direct effect
Calcitonin production
Main situmulus is high Ca2+ (ionize
d>1.115)- also glucagon, gastrin,
PTH effects on bone β-adrenergic agonists (? reason for low
Acts on osteoblast cell Ca in acute illness)
membrane to increase
1125(OH)2-D effects on gut permeability to calcium,
activating a pump which
increases Ca2+ and PO4 absorption by
drives calcium into ECF.
upregulating intracellular calbindin
proteins.
Calcitonin Calcitonin effects on bone
• Inhibits osteoiast resorption
• Thereby lowers Ca and PO4
• No effect on Mg
Response to hypocalcaemia
Rise in PTH, causing:
• Increased renal Ca absorption; Response to hypophosphatemia
• Increased renal PO4 excretion; 1. Increased G I absorption of PO4 and calcium;
• Mobilization of calcium and PO4 from bone; 2. rise in calcium inhibits PTH release, causing:
• Increased 1α-hyroxylation, causing: • Increased renal PO4 resorption;
• Increased GI absorption and calcium and PO4 • Reduced renal calcium reorption.

Groups at Risk of Calcium Inadequacy
1. “Postmenopausal women due to decrease in estrogen production have increased
bone resorption and decrease calcium absorption [3]. Increased calcium intakes
during menopause do not completely offset this bone loss [4]. Hormone replacement
therapy (HRT) with estrogen and progesterone helps increase calcium levels and
prevent osteoporosis and fractures. Estrogen therapy restores postmenopausal bone
remodeling to the same levels as at premenopause, leading to lower rates of bone loss”
[5].
2. The “female athlete triad” refers to the combination of disordered eating, amenorrhea,
and osteoporosis. Exercise-induced amenorrhea generally results in decreased bone
mass [6,7].
3. Lactose intolerance and milk allergy: approximately 25% of U.S. adults have a limited
ability to digest lactose, including 85% of Asians, 50% of African Americans, and 10% of
Caucasians [8].
4. Vegetarians and more so vegans obtain insufficient dietary calcium intakes [9]
5. In two large prospective epidemiological trials, men and women who consumed
700–800 mg per day of calcium had a 40%–50% lower risk of developing left-side colon
cancer [10].
6. Calcium oxalate kidney stones linked to supplemental calcium intake and not to high
intake of dietary calcium intake [1,11].
Health risks of excessive Calcium
1. Hypercalcemia commonly associated with hyperparathyroidism or malignancy, can
cause renal insufficiency, vascular and soft tissue calcification, hypercalciuria and
kidney stones [1].
2. Increased risk of prostate cancer [1].
3. High calcium intake can cause constipation. It might also interfere with the absorption
of iron and zinc, though this effect is not well established [1].
4. Possibly an increased risk of cardiovascular disease [12].
1. Calcium can decrease absorption of the following drugs when taken together:
biphosphonates (to treat osteoporosis), the fluoroquinolone and tetracycline classes of
antibiotics, levothyroxine, phenytoin (an anticonvulsant), and tiludronate disodium (to
treat Paget’s disease) [13-15].
2. Thiazide-type diuretics can interact with calcium carbonate and vitamin D
supplements, increasing the risks of hypercalcemia and hypercalciuria [14]
3. Both aluminum- and magnesium-containing antacids increase urinary calcium
excretion. Mineral oil and stimulant laxatives decrease calcium absorption.
Glucocorticoids, such as prednisone, can cause calcium depletion and eventually
osteoporosis when they are used for months [14].

2. MAGNESIUM
“Magnesium is the fourth most abundant cation in the body and plays an important
physiological role in many of its functions. Magnesium balance is maintained by renal
regulation of magnesium reabsorption. The exact mechanism of the renal regulation is
not fully understood. Magnesium deficiency is a common problem in hospital patients,
with a prevalence of about 10%. There are no readily available and easy methods to assess
magnesium status. Serum magnesium and the magnesium tolerance test are the most
widely used. Measurement of ionised magnesium may become more widely available with
the availability of ion selective electrodes” [16].
Magnesium
intake
15 mmol/day Body disribution
Bone 750 mmol
Soft tissue 450 mmol

Urine
30% 5-10 mmol/day
absorbed
ECF 15 mmol
70% excreted
Less than 1% of total magnesium is in blood serum, and these levels are kept under tight
control [17].

“Magnesium deficiency and hypomagnesaemia can result from a variety of causes
including gastrointestinal and renal losses. Magnesium deficiency can cause a wide
variety of features including hypocalcaemia, hypokalaemia and cardiac and neurological
manifestations. Chronic low magnesium state has been associated with chronic
alcoholism and a number of chronic diseases including diabetes, hypertension, coronary
heart disease, and osteoporosis [16]. Therapeutic uses of Magnesium include asthma,
myocardial infarction, and pre-eclampsia [16]. Symptoms include loss of appetite, nausea,
vomiting, fatigue, and weakness. As magnesium deficiency worsens, numbness, tingling,
muscle contractions and cramps, seizures, personality changes,
“Hypermagnesaemia is less frequent than hypomagnesaemia and results from failure
of excretion or increased intake. Hypermagnesaemia can lead to hypotension and other
cardiovascular effects as well as neuromuscular manifestations “[16].
Magnesium-loading (“tolerance test”) in which urinary magnesium is measured after
parenteral infusion of a dose of magnesium) is arguably the best method to assess
magnesium status in adults. To comprehensively evaluate magnesium status, both
laboratory tests and a clinical assessment might be required [18,19]
Tolerable Upper Intake Levels (ULs) for Supplemental Magnesium [17]
Birth to 12 months None established None established
4–8 years 110 mg 110 mg
9–18 years 350 mg 350 mg 350 mg 350 mg
19+ years 350 mg 350 mg 350 mg 350 mg
Magnesium containing medicines

1. Laxatives [20]
2. Reflux due to acid indigestion [20]
Groups at risk of Magnesium Deficiency [17,21]
1. People with gastro-intestinal diseases
2. Type 2 diabetics
3. Alcoholics
4. Older adults
5. Migraine sufferers [22]
Excessive Magnesium
1. Laxative induced diarrhea. Can be fatal. [23]
2. Symptoms include hypotension, nausea, vomiting, facial flushing, retention of urine,
ileus, depression, and lethargy before progressing to muscle weakness, difficulty
breathing, extreme hypotension, irregular heartbeat, and cardiac arrest [24].

Bisphosphonates
Magnesium-rich supplements or medications can decrease the absorption of oral
bisphosphonates, such as alendronate (Fosamax®), used to treat osteoporosis [25]. Use
of magnesium-rich supplements or medications and oral bisphosphonates should be
separated by at least 2 hours [26]
Antibiotics
Magnesium can form insoluble complexes with tetracyclines, such as demeclocycline
(Declomycin®) and doxycycline (Vibramycin®), as well as quinolone antibiotics, such as
ciprofloxacin (Cipro®) and levofloxacin (Levaquin®). These antibiotics should be taken at
least 2 hours before or 4–6 hours after a magnesium-containing supplement [26]
Diuretics
Chronic treatment with loop diuretics, such as furosemide (Lasix®) and bumetanide
(Bumex®), and thiazide diuretics, such as hydrochlorothiazide (Aquazide H®) and
ethacrynic acid (Edecrin®), can increase the loss of magnesium in urine and lead to
magnesium depletion [61]. In contrast, potassium-sparing diuretics, such as amiloride
(Midamor®) and spironolactone (Aldactone®), reduce magnesium excretion [27]
Proton pump inhibitors
Esomeprazole magnesium (Nexium®) and lansoprazole (Prevacid®), when taken for
prolonged periods (typically more than a year) can cause hypomagnesemia [28].

3. SELENIUM
Selenium is a trace element that is naturally present in many foods, added to others,
and available as a dietary supplement. Selenium, which is nutritionally essential for
humans, is a constituent of more than two dozen selenoproteins that play critical roles in
reproduction, thyroid hormone metabolism, DNA synthesis, and protection from oxidative
damage and infection [29]
Groups at Risk of Selenium Inadequacy

People undergoing kidney dialysis
Selenium levels are significantly lower in patients undergoing long-term hemodialysis
than in healthy individuals. Hemodialysis removes some selenium from the blood [30]
People living with HIV
Selenium levels are often low in people living with HIV, possibly because of inadequate
intakes (especially in developing countries), excessive losses due to diarrhea, and
malabsorption [31]
Note: there is a very narrow clinically safe range for selenium intake
Selenium deficiency
Symptoms: lethargy, dizziness, motor weakness and paresthesias, and an excess risk of
amyotrophic lateral sclerosis [32].
Selenium toxicity
Symptoms: ataxia, hypotonia, hyperreflexia, dyasthesia, paralysis, tremors, convulsions
and even suicidal ideation [32]

4. ZINC
Zinc is the second most abundant trace metal in the human body and functions as a
cofactor in over 300 different enzymes and it interacts with insulin. It promotes wound
healing, regulates immune function, serves as a cofactor for numerous antioxidant
enzymes and is necessary for protein synthesis and the processing of collagen [32]. It
plays a role in wound healing, DNA synthesis, taste and smell [33]
Zinc Deficiency
In severe cases, zinc deficiency causes hair loss, diarrhea, delayed sexual maturation,
impotence, hypogonadism in males, and eye and skin lesions.
Plasma or serum zinc levels are the most commonly used indices for evaluating zinc
deficiency, but these levels do not necessarily reflect cellular zinc status due to tight
homeostatic control mechanisms [34]
Groups that are at risk of Zinc inadequacy [33]
1. Gastrointestinal disorders
2. Vegetarians
3. Pregnant and lactating women
4. People with sickle cell disease
5. Alcoholics
Zinc and health

Severe zinc deficiency depresses immune function [35], and even mild to moderate
degrees of zinc deficiency can impair macrophage and neutrophil functions, natural killer
cell activity, and complement activity [36,37]

Antibiotics
Both quinolone antibiotics (such as Cipro®) and tetracycline antibiotics (such as
Achromycin® and Sumycin®) interact with zinc in the gastrointestinal tract, inhibiting
the absorption of both zinc and the antibiotic [38] Taking the antibiotic at least 2 hours
before or 4–6 hours after taking a zinc supplement minimizes this interaction [39]
Penicillamine
Zinc can reduce the absorption and action of penicillamine, a drug used to treat
rheumatoid arthritis [87]. To minimize this interaction, individuals should take zinc
supplements at least 2 hours before or after taking penicillamine [40]
Diuretics
Thiazide diuretics such as chlorthalidone (Hygroton®) and hydrochlorothiazide (Esidrix®
and HydroDIURIL®) increase urinary zinc excretion by as much as 60% [41]. Prolonged use
of thiazide diuretics could deplete zinc tissue levels, so clinicians should monitor zinc
status in patients taking these medications.

CHAPTER 6:
ESSENTIAL MICRONUTRIENTS –
AMINO ACIDS

AMINO ACIDS
“Amino acids play central roles both as building blocks of proteins and as intermediates
in metabolism. The 20 amino acids that are found within proteins convey a vast array of
chemical versatility.” [1]

“The precise amino acid content, and the sequence of those amino acids, of a specific
protein, is determined by the sequence of the bases in the gene that encodes that protein.
The chemical properties of the amino acids of proteins determine the biological activity
of the protein. Proteins not only catalyze all (or most) of the reactions in living cells, they
control virtually all cellular processes. In addition, proteins contain within their amino
acid sequences the necessary information to determine how that protein will fold into a
three dimensional structure, and the stability of the resulting structure” [1]
“Humans can produce 10 of the 20 amino acids. The others must be supplied in the food.
Failure to obtain enough of even 1 of the 10 essential amino acids, those that we cannot
make, results in degradation of the body’s proteins—muscle and so forth—to obtain the
one amino acid that is needed. Unlike fat and starch, the human body does not store
excess amino acids for later use—the amino acids must be in the food every day” [1]
“The 10 amino acids that we can produce are alanine, asparagine, aspartic acid, cysteine,
glutamic acid, glutamine, glycine, proline, serine and tyrosine. Tyrosine is produced from
phenylalanine, so if the diet is deficient in phenylalanine, tyrosine will be required as
well” [1]
“The essential amino acids are arginine (required for the young, but not for adults),
histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan,
and valine. These amino acids are required in the diet. Plants, of course, must be able
to make all the amino acids. Humans, on the other hand, do not have all of the enzymes
required for the biosynthesis of all of the amino acids” [1]

1. ARGININE
Arginine is a conditionally (may be required depending on the health status) semi-

essential α-amino acid that is used in the biosynthesis of proteins [2]
Function
Arginine plays an important role in cell division, the healing of wounds, removing
ammonia from the body, immune function, and the release of hormones [2-4]
Arginine (8%) in dental products (e.g., toothpaste) provides effective relief from sensitive
teeth by depositing a dentin-like mineral, containing calcium and phosphate, within the
dentin tubules and in a protective layer on the dentin surface [5]
Arginine is effective at increasing growth hormone levels and the combined effect of
arginine before exercise attenuates the GH response [6,7]
Intravenous infusion of arginine reduces blood pressure in patients with hypertension as
well as normal subjects [8]

2. CARNITINE
L-Carnitine, derived from an amino acid, is found in nearly all cells of the body. Its name
is derived from the Latin carnus or flesh, as the compound was isolated from meat. It
plays a critical role in energy production. It transports long-chain fatty acids into the
mitochondria so they can be oxidized (“burned”) to produce energy [9]
Secondary carnitine deficiencies (non-genetic) may occur due to certain disorders (such
as chronic renal failure) or under particular conditions (e.g., use of certain antibiotics) that
reduce carnitine absorption or increase its excretion [9,10] There is scientific agreement
on carnitine’s value as a prescription product for treating such deficiencies [11]
A meta-analysis of double-blind, placebo-controlled studies suggests that supplements of
acetyl-L-carnitine may improve mental function and reduce deterioration in older adults
with mild cognitive impairment and Alzheimer’s disease [12]
The authors of a systematic review and meta-analysis that included 14 randomized
clinical trials concluded that propionyl-L-carnitine significantly increases peak walking
distance in patients with claudication [13].
A recent analysis of two multicenter clinical trials of subjects with either type 1 or type
2 diabetes found that treatment with acetyl-L-carnitine (3 grams/day orally) for one year
provided significant relief of nerve pain and improved vibration perception in those with
diabetic neuropathy [14]
A recent meta-analysis of end stage renal disease and haemodialysis studies concludes
that carnitine supplements may aid anaemia management but not blood-lipid profiles,
and that their effects on exercise capacity or heart stability are inconclusive [15]

3. CYSTEINE
When taken as a supplement, it is usually in the form of N-acetyl-L-cysteine (NAC). The

body makes this into cysteine and then into glutathione, a powerful antioxidant [16]
NAC can help prevent side effects caused by drug reactions and toxic chemicals,
and helps break down mucus in the body. It seems to have benefits in treating some
respiratory conditions, such as bronchitis and COPD [16].
Indications
1. Acetaminophen poisoning: Intravenous (IV) NAC to people who have taken an overdose
of acetaminophen (Tylenol), to help prevent or reduce liver and kidney damage [17,18]
2. Angina: Taking NAC along with nitroglycerinhas been more effective than taking
either one alone in reducing chest pain, heart attack, and the risk of death. However,
the combination can also cause a severe headache. [19]
Possible Interactions
1. Medications that suppress the immune system -- Treatment with NAC may potentiate
the effects of some medications that suppress the immune system, such as
azathioprine (Imuran), cyclophosphamide (Cytoxan), or prednisone (Deltasone).
2. Nitroglycerin and isosorbide -- NAC may strengthen the effect of nitroglycerin and
isosorbide (Isordil. But this combination may also raise the risk of side effects, such as
severe headaches, and may lead to abnormally low blood pressure.
3. Oxiconazole -- Using NAC on the skin strengthens the effect of oxiconazole (Oxistat),
an antifungal medication used for athlete’s foot.
4. Activated charcoal -- may make NAC less effective [16]

4. GLUTAMINE
Indications
1. Glutamine is the most abundant amino acid (building block of protein) in the body. The
body can make enough glutamine for its regular needs. But during times of extreme
stress, like heavy exercise or an injury, your body may need more glutamine than it
can make. Most glutamine is stored in muscles, followed by the lungs where much of
the glutamine is made [20]
2. Glutamine is important for removing excess ammonia (a common waste product in the
body). It also helps your immune system function and may be needed for normal brain
function and digestion [21]
3. Several studies show that adding glutamine to enteral nutrition (tube feeding) helps
reduce the rate of death in trauma and critically ill people [21]
4. Athletes who train for endurance events (like marathons) may reduce the amount of
glutamine in their bodies. It is common for them to catch a cold after an athletic event.
For this select group of athletes, one study showed that taking glutamine supplements
resulted in fewer infections. The same is not true, however, for exercisers who work
out at a moderate intensity [20]
5. Glutamine seems to help reduce stomatitis (an inflammation of the mouth) caused by
chemotherapy [21]
Contraindications
1. People with kidney disease, liver disease, or Reye syndrome (a rare, sometimes fatal
disease of childhood that is generally associated with aspirin use) should not take
glutamine [21]
2. Many elderly people have decreased kidney function, and may need to reduce their
dose of glutamine [21]
Possible interactions
Lactulose: Glutamine supplementation can increase ammonia in the body, so taking
glutamine may make lactulose less effective [22]

5. TAURINE
Taurine is the most abundant intracellular sulphur-containing amino acid [23]
Is synthesized from methionine and cysteine in the presence of vitamin B6 [23] and
can be obtained mainly from eggs, meat and seafood. High concentrations of taurine are
found in the heart and retina, whereas smaller amounts are found in the brain, kidneys,
intestine and skeletal muscle [24]
Functions
1. Taurine plays a role in bile salt formation and fat digestion [25]
2. Involved in the maintenance of homeostasis of intracellular Na+ and intracellular Ca2+

concentrations and in the balance of neurotransmitters [25]
3. Taurine deficiency is associated with anxiety, epilepsy, hyperactivity and depression;

taurine supplementation can relieve these symptoms [26]
4. Recently, it was shown to be an effective agent in the treatment of alcoholism, fatigue

and myotonia [27]
5. Taurine has also been reported to protect visual function during diabetes [28]
6. It crosses the blood-brain barrier [29]
7. Acts as an anti-oxidant [30]
8. Taurine levels were found to be significantly lower in vegans than in a control group
on a standard American diet. Plasma taurine was 78% of control values, and urinary
taurine was 29% [31]
9. Taurine has an observed safe level of supplemental intake in normal healthy adults
at up to 3 g/day [32]. Even so, a study by the European Food Safety Authority found no
adverse effects for up to 1,000 mg of taurine per kilogram of body weight per day [33]
10. “The amounts of guarana, taurine, and ginseng found in popular energy drinks are far
below the amounts expected to deliver either therapeutic benefits or adverse events”
[34]
11. Taurine is also used in some contact lens solutions [35]

6. METHIONINE
commons.wikimedia.org
As an essential amino acid, methionine is not synthesized de novo in humans and other
animals, who must ingest methionine or methionine-containing proteins [36]
Loss of methionine has been linked to senile greying of hair. Its lack leads to a buildup of
hydrogen peroxide in hair follicles, a reduction in tyrosinase effectiveness, and a gradual
loss of hair color [37]
Methionine is an intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin,

phosphatidylcholine, and other phospholipids.
Improper conversion of methionine can lead to atherosclerosis [38]

7. ORNITHINE
L-Ornithine is one of the products of the action of the enzyme arginase on L-arginine,
creating urea.
L-Ornithine supplementation attenuated fatigue in subjects in a placebo-controlled

study using a cycle ergometer. The results suggested that L-ornithine has an antifatigue
effect in increasing the efficiency of energy consumption and promoting the excretion of
ammonia [39,40,41]
Weightlifting supplement
Amino acid supplements, including L-ornithine, are frequently marketed to bodybuilders

and weightlifters through the claim that it will increase levels of human growth hormone
(HGH). However, a clinical study has shown that these supplements do not increase levels
of HGH with low dose (2 grams per day divided into two doses) supplementation [42]
Cirrhosis
L-Ornithine L-aspartate (LOLA), a stable salt of ornithine and aspartic acid, has been used
in the treatment of cirrhosis [43]

8. PHENYLALANINE
The body changes phenylalanine into tyrosine, another amino acid that is needed to make
proteins and brain chemicals, including L-dopa, epinephrine, norepinephrine, and thyroid
hormones. Because norepinephrine affects mood, different forms of phenylalanine have
been proposed to treat depression [44,45]
Symptoms of phenylalanine deficiency include:
1. Confusion
2. Lack of energy
3. Depression
4. Decreased alertness
5. Memory problems
6. Lack of appetite [46]
Phenylketonuria (PKU) occurs in people who are missing an enzyme that the body needs
to use phenylalanine. That causes high levels of phenylalanine to build up. If it is not
treated before 3 weeks of age, PKU can cause severe, irreversible intellectual disability [47]
Newborns are tested for PKU during the first 48 to 72 hours of life. Older, untreated
children become hyperactive with autistic behaviors, including purposeless hand
movements and rhythmic rocking [47]
People with PKU must eat a diet that avoids phenylalanine and take tyrosine supplements
for optimal brain development and growth. Compliance with treatment in people with
PKU has a greater impact on cognition during the first 12 years of life compared to the
influence beyond 12 years [47,48]

Precautions
DL-phenylalanine should not be used in people taking antipsychotic drugs, as it may

cause or worsen symptoms of tardive dyskinesia (TD). TDs are involuntary movements of
the tongue, lips, face, trunk, and limbs that can occur in people taking antipsychotic drugs
long term [44,49]
Doses higher than 5,000 mg a day may be toxic and can cause nerve damage. High
quantities of DL-phenylalanine may cause mild side effects such as nausea, heartburn,
and headaches [44,49]
Possible interactions
Monoamine Oxidase Inhibitors: Monoamine oxidase inhibitors (MAOIs) are an older class
of antidepressants drugs that are rarely used now. They include phenelzine (Nardil),
isocarboxazid (Marplan), and tranylcypromine sulfate (Parnate). Taking phenylalanine
while taking MAOIs may cause a severe increase in blood pressure (hypertensive crisis).
This severe increase in blood pressure can lead to a heart attack or stroke. People taking
MAOIs should avoid foods and supplements containing phenylalanine.
Baclofen: Phenylalanine may reduce absorption of baclofen (Lioresal), a medication used

to relieve muscle spasms. Avoid taking Baclofen with a meal, especially one that is high in
protein, or with phenylalanine supplements.
Levodopa: A few case reports suggest that phenylalanine may reduce the effectiveness of
levodopa (Sinemet), a medication used to treat Parkinson disease. Some researchers think
phenylalanine may interfere with the absorption of levodopa and worsen the person’s
condition.
Selegiline: L-phenylalanine and the selective MAO inhibitor selegiline (Eldepryl,

Deprenyl) may strengthen the antidepressant effects of phenylalanine. They should not be
taken together.
Antipsychotic or neuroleptic drugs: L-phenylalanine may worsen TD, a side effect

of these neuroleptic drugs. These drugs include phenytoin (Dilantin), valproic acid
(Depakene, Depakote), and carbamazepine (Tegretol), among others.
Opiate analgesia: markedly potentiated by phenylalanine [49]

9. CHOLINE
Choline is similar to the B vitamins. It can be made in the liver. It is also found in foods
such as liver, muscle meats, fish, nuts, beans, peas, spinach, wheat germ, and eggs.
Choline is used for liver disease [50], including chronic hepatitis and cirrhosis [51]. It is
also used for depression [52], memory loss, Alzheimer’s disease and dementia [53, 54],
Huntington’s chorea [55], Tourette’s disease, cerebellar ataxia [56,57], epilepsy [58], and
schizophrenia [59].
Athletes use it for bodybuilding [60] and delaying fatigue in endurance sports
[61,62,63,64,65] Choline supplementation reduces urinary carnitine excretion [66].
Choline is taken by pregnant women to prevent neural tube defects in their babies and it
is used as a supplement in infant formulas [67].
Other uses include lowering cholesterol [68], and controlling asthma [69,70].
How does it work?
Choline is similar to a B vitamin. It is used in many chemical reactions in the body.

Choline seems to be important in the nervous system. In asthma, choline might help
decrease oedema and inflammation.

10. GLYCINE
Glycine is not an essential amino acid because the body can make it from other
chemicals. It is a building block for protein. The primary sources are protein-rich foods
including meat, fish, dairy, and legumes.
Glycine is used for treating schizophrenia [71,72,73,74] and stroke [75].
How does it work?
1. Protein synthesis
2. Neurotransmitter

12. LYSINE [76]
Lysine, or L-lysine, is an essential amino acid, meaning it is necessary for human health,
but the body cannot make it. Amino acids like lysine are the building blocks of protein.
Lysine is important for proper growth, and it plays an essential role in the production of
carnitine, a nutrient responsible for converting fatty acids into energy and helping lower
cholesterol. Lysine appears to help the body absorb calcium, and it plays an important
role in the formation of collagen, a substance important for bones and connective tissues
including skin, tendons, and cartilage. Most people get enough lysine in their diet.
Although athletes, burn patients, and vegans who do not eat beans may need more.
Lysine deficiency
1. Fatigue
2. Nausea
3. Dizziness
4. Loss of appetite
5. Agitation
6. Bloodshot eyes
7. Slow growth
8. Anaemia
9. Reproductive disorders
Indications
1. Oral lysine is more effective at preventing an HSV outbreak (cold sores and genital
herpes) than it is at reducing the severity and duration of an outbreak [77,78,79,80,81]
2. May help prevent bone loss [82,83]
3. May help muscle tissue recover after endurance exercise [76]
Effects
1. Can increase absorption of calcium [84]
2. Aminoglycoside antibiotic use with lysine may increase risk of nephrotoxicity [76]
3. High levels of Arginine may lower lysine levels in the body [76]

CHAPTER 7:
SAFETY AND EFFICACY OF
INTRAVENOUS MICRONUTRIENTS
(VITAMINS, MINERALS AND AMINO
ACIDS) SUPPLEMENTATION (IMS)
FOR NON-MEDICINAL INDICATIONS

1. EFFICACY detoxification, etcetera [12].
Evidence of intravenous micronutrient

supplementation (IMS) efficacy is based At the beginning of 2015, the Medicines and
mainly on anecdotal clinical experience Healthcare products Regulatory Agency
with limited clinical trial publications on (MHRA) in the UK permitted intravenous
combination intravenous micronutrient micronutrients (vitamins, minerals and
therapy [1,2] in peer review journals. amino acids) to be prescribed off-license for
In the first controlled study on fibromyalgia non-medicinal indications [12]. Medicinal
clinically significant improvements were claims of IMS on clinic websites are strictly
noted in response to the “Myers’ Cocktail” forbidden by the MHRA [12] and promotion
as most of the subjects experienced relief of Prescription Only Medicines (POM) are
of symptoms compared to the baseline also disallowed by the MHRA, for example
but no statistically significant differences BOTOX TM.
were demonstrated between placebo and Important factors to take into consideration
intravenous micronutrient therapy [3]. when choosing a trainer and supplier of IMS
However, several studies have products in the UK are:
demonstrated that intravenous magnesium 1. Products must be manufactured in
can abort acute asthmatic attacks [2,4,5,6,7]. a EU Good Manufacturing Practice
Intravenous magnesium therapy is very (GMP) facility. Products originating
beneficial in cardio-vascular disease from countries such as Canada, South
especially as a physiologic calcium blocker Africa, India as well as USA Food and
and cardiac antiarrhythmic agent [8,9] Drug Administration (FDA) approved
products are illegal in the UK and EU
Studies on oral combination micronutrient and according to the MHRA website “
supplementation have demonstrated to make, assemble or import human
encouraging positive health affects such medicines, you need a manufacturer’s
as accelerated wound healing [10] and license, issued by the MHRA. To qualify
prevention of acute radiation-induced for a manufacturer’s license, you need
defect in wound healing by supplemental to show the MHRA that you comply
Vitamin A in rats [11]. with EU GMP and pass regular GMP
However, pioneering physicians like Myers, inspections of your site.” [13].
Gaby, Schrader, together with thousands 2. Products should be preservative free to
of other physicians around the world have minimize the risk of allergic reactions
administered hundreds of thousands of [1,2,14].
intravenous nutrition supplementations
safely and effectively for medicinal and 3. Ensure that the product supplier has
non-medicinal indications [1,2]. product liability insurance in place.
Cosmetic or aesthetic insurance
2. REGULATION IN THE UNITED companies do not routinely cover
KINGDOM OF INTRAVENOUS product liability [12].
MICRONUTRIENT
4. Post training support by product
SUPPLEMENTATION UNDER suppliers is very important [12].
THE MHRA
5. Practitioner’s insurance cover that
In the United Kingdom, intravenous
includes IMS is mandatory [12].
nutrition therapy is a relatively new
procedure with about (250+ practitioners 6. Reliable product suppliers must carry
trained since April 2015) non-NHS large stock inventories to ensure
practicing clinicians including doctors, timeous product delivery [12].
dentists and nurse prescribers offering 7. Calculated safe osmolarities for each
intravenous micronutrient supplementation product or admixture is mandatory to
for non-medicinal indications such as avoid potential complications [12].
(1) immune system boosting, (2) athletes
8. Proper training should be available from
& anti-fatigue support, (3) energy boost,
a qualified medical practitioner [12].
(4) mood support, (5) fat burning and
3. RELIABILITY OF [1] and infection [19]
MICRONUTRIENT LABORATORY Preservatives such as benzyl alcohol [1,14],
TESTING and methylparabens [2] as well as Vitamin
B1 are the most likely agents to cause
Many micronutrient serum levels do allergic and possible anaphylactic reactions
not correlate well with tissue levels and [20,21]. Calcium Gluconate derived from
for example serum magnesium levels shellfish also poses a risk to patients who
do not drop below the ‘low normal’ are allergic to shellfish [12]
range until the patient is very seriously
magnesium depleted and already at high In Selenium the margin between
risk of a cardiogenic event [1]. Schrader therapeutic benefit and toxicity is fairly
[1] recommends a “loading” test dose to narrow especially when renal function is
determine magnesium deficiency [15,16] impaired [15].
Patients at risk of developing
According to Shenkin [17] “plasma
hypoglycaemia such as diabetics and
concentration of the micronutrient provides
postprandial reactive hypoglycaemia
only a crude, if any, indication at all of the
requires extra attention and precautions
micronutrient status” and “ biochemical
when given intravenous vitamin C [12]
tests can not be used to optimize tissue
because the latter has a blood glucose
function.”
lowering effect in general.
In the United Kingdom (1) Genova
Diagnostics (GDX) offers Diagnostic
Laboratory Testing for Wellness & 5. CONTRAINDICATIONS TO IMS
Preventive Medicine (www.gdx.net) A) Absolute contraindications
and (2) Regenerus Laboratories “provide
1. Preservatives: known hypersensitivity
simple easy access to world leading
to a preservative contained in a
laboratories that deliver the broadest
pharmaceutical manufactured product
range of functional, nutritional, genetic,
such as methylparabens or benzyl
autoimmune for diagnostic and research
alcohol (patch test confirmation) [1,14]
testing services, to support health
may cause an allergic reaction. It is
professionals and the general public.” (www.
unlikely to develop an allergic reaction
regeneruslabs.com). Testing however, is
to a pure micronutrient per se [1].
quite expensive.
2. Thiamine certainly has potential to
4. SAFETY ASPECTS evoke anaphylactic reactions [20,21] and
For ASA category 1 and 2 patients patients with a history of a previous
(American Society of Anesthesiologists’ “sensitization” reaction should not be
classification) [18] the need for laboratory administered Vitamin B1.
testing of micronutrients may not
3. High doses of certain micronutrients
be needed. Importantly, patients of
such as magnesium may cause
compromised health taking several
unpleasant reactions such as dermal
different medications, in particular cardio-
vasodilatation (flushing) and even
vascular patients and patients with
hypotension [22] and extra precaution
advanced complicated diabetes should
is required in patients with known
not be routinely treated for non-medicinal
low blood pressure and hypertensive
indications and definitely not without
patients on vasodilator medication [1,2]
proper laboratory investigations.
4. Niacin may cause severe dermal
The most important safety risk factors
vasodilatation [23] and is
associated with intravenous micronutrient
contraindicated in diabetics and gout
supplementation are (1) allergic reactions,
sufferers [24].
(2) osmolarity of the multi-nutrient mixture
5. Avoid intravenous calcium in

hyperparathyroidism [25]. might protect normal tissues from
chemotherapy- and radiation-induced
6. Avoid glutamine in patients with renal
damage [33,36] and/or enhance the
disease, liver disease and Rye syndrome
effectiveness of conventional cancer
[26,27,28]. Glutamine supplementation
treatment [38]. However, due to the
can increase ammonia in the body
physiologically tight control of vitamin
tissues, so taking glutamine may make
C, it is unclear whether oral vitamin
lactulose less effective [28]
C supplements could alter vitamin
7. DL-phenylalanine should not be used C concentrations enough to produce
in people taking antipsychotic drugs, the suggested effects. Individuals
as it may cause or worsen symptoms undergoing chemotherapy or radiation
of tardive dyskinesia (TD). TDs are should consult with their oncologist
involuntary movements of the tongue, prior to taking vitamin C or other
lips, face, trunk, and limbs that can antioxidant supplements, especially in
occur in people taking antipsychotic high doses” [39].
drugs long term [29,30]
8. Extremes of tonicity [31]: pump that promotes intracellular
• Hypertonic upper limit for uptake of potassium and may cause
peripheral intravenous infusion is hypokalaemia in patients deficient in
900 mOsmol/L Admixtures of greater magnesium and potassium resulting in
than 600mOsmol/L to 900 mOsmol/L muscle cramps [2,40].
causes chemical irritation of the 11. Poorly controlled diabetes
vein’s intima resulting in phlebitis mellitus:“Diabetic patients frequently
and thrombophlebitis and should be develop a constellation of electrolyte
administered via central venous route disorders. These disturbances are
[31] particularly common in decompensated
• Hypotonic lower limit for peripheral diabetics, especially in the context of
intravenous infusion is 154 mOsmol/L diabetic ketoacidosis or nonketotic
(0.45% Sodium Chloride) Very hypotonic hyperglycemic hyperosmolar syndrome.
intravenous solutions cause red blood These patients are markedly potassium-
cell expansion due to influx of water, magnesium- and phosphate depleted.
hemolysis and eventually hemolytic Diabetes mellitus (DM) is linked to both
anaemia [31]. hypo- and hyper-natremia reflecting
the coexistence of hyperglycemia-
9. Patients receiving chemotherapy and
related mechanisms, which tend to
radiation therapy: obtain approval from
change serum sodium to opposite
the patient’s oncologist:
directions. The most important causal
factor of chronic hyperkalemia in
“The safety and efficacy of the use
diabetic individuals is the syndrome
of vitamin C and other antioxidants
of hyporeninemic hypoaldosteronism.
during cancer treatment is controversial
Impaired renal function,
[32,33,34]. Some data indicate that
potassiumsparing drugs, hypertonicity
antioxidants might protect tumor cells
and insulin deficiency are also involved
from the action of radiation therapy
in the development of hyperkalemia” [41]
and chemotherapeutic agents, such
as cyclophosphamide, chlorambucil, 12. Pregnant women: routine intravenous
carmustine, busulfan, thiotepa, and micronutrient supplementation is
doxorubicin [35,33,36,37]. At least some not appropriate in pregnant and
of these data have been criticized lactating mothers in the absence
because of poor study design [38]. of a medical indication. However,
Other data suggest that antioxidants should a women inadvertently have
received anintravenous micronutrient

supplementation without the prior 2. Vitamin C ascorbic acid: reduce the dose
knowledge of her being pregnant, in patients with G6PD deficiency [51],
several case reports in the literature chronic renal disease and pre-existing
have confirmed that total parenteral hyperoxaluria [52,53].
nutrition (TPN) - although infrequently
used in pregnancy [42] - promote foetal 3. Arginine: reduce the dose in
growth and is well tolerated by the hypotensive patients or patients taking
mother [43]. Hypertonic solutions can hypotensive medication [54].
supply total caloric/metabolic needs 4. N-acetyl-L-cysteine (NAC) may
without unacceptable side effects [44].
potentiate immunosuppressive
13. Lactating mothers: “because drugs such as azathioprine (Imuran),
micronutrient status of the lactating cyclophosphamide (Cytoxan) or
woman is critical for the secretion of prednisone (Deltasone) [55]. NAC
adequate micronutrient concentrations may also potentiate the effect of
in breast milk, and for the micronutrient nitroglycerin and isosorbide (Isordil™)
status of her infant, more attention
causing severe headaches and
should be paid to the micronutrient
hypotension [55].
status of lactating women. Provision
of multiple micronutrient supplements 5. Reactive hypoglycaemia: ensure
and/or food fortification with patients are having a snack prior to the
micronutrients may be advisable for supplementation. Interestingly, Vitamin
the majority of lactating women in C “Further Improves the Protective
developing countries and industrialized Effect of Glucagon-Like Peptide-1 on
countries—not least to prevent their Acute Hypoglycemia-Induced Oxidative
further depletion through the secretion
Stress, Inflammation, and Endothelial
of large amount of these micronutrients
Dysfunction in Type 1 Diabetes” [56]
in breast milk. “ [49]
6. Atopic dermatitis and other hyper
Dietary fortification and oral multiple allergenic conditions.
micronutrient supplements may not
7. Hypotonic solutions and red blood cell
always be sufficient thus making it
fragility disorders [1]:
appropriate to administer specifically
indicated intravenous micronutrient • Thalassemia Major
supplementation.
• G6PD deficiency [1,51]
14. Poorly controlled asthma: intravenous
• Spherocytosis
magnesium can abort acute asthmatic
attacks [2,4,5,6,7] and the use of multiple • Sickle cell anaemia
intravenous micronutrients may be of
8. HIV+, Hepatitis B+ and Hepatitis C+
considerable benefit in both acute and
patients: protection of practitioner, staff
chronic asthma [50]. Even pulmonary
function improved progressively the and other patients visiting the clinic.
longer the patients received it [50]. 9. Opioid drug addiction: extra precaution
15. Hypokalaelmia {1,2] • Constipation, nausea and vomiting
causing hypokalaemia [57]
B) Relative contraindications • Immune suppression and prone to
1. Glutamine: reduce the dose in elderly bacterial infections [58]
patients due to associated reduced renal • Impaired liver functions
and liver function [26,27,28].

Cardiac effects: induced dermal vasodilation
A) Vasodilatation and hypotension [59] Symptoms & signs
B) Bradycardia • Dermal flushing (redness)
C) ECG changes: Syndrome of QT • Skin warm
prolongation and torsade de pontes
• Strong rapid pulse
[60] (mortality rate 17%) linked to
methadone [61], hypokalaemia and • Dizziness
diminished liver functions [62] Intervention
10. Opiate analgesia: markedly potentiated • Terminate the infusion or IV push
by phenylalanine [63,64]
• Put the patient in Trendellenburg
position
6. ADVERSE REACTIONS TO IMS [1]
• The effect is usually transient ad self
1. Nervous patients (needle phobia)
limiting
vasovagal (syncope) reaction:
• Observation of vital signs: blood
• Symptoms & signs
pressure, respiratory rate and pulse
• Palor rate/character
• Cold clammy skin • If the patient is in agreement, the
• Slow faint pulse treatment may be resumed but at a very
slow drip rate
• Hypotension
4. Nausea and vomiting due to rapid
• Dizzyness
injection/infusion [2].
• Syncope
5. Headache due the sulfates in
Intervention: Magnesium Sulfate [1,2].
• Terminate the infusion or IV push 6. Anaphylaxis – Life threatening
• Put the patient in Trendellenburg emergency
position (lying down flat, feet above the The patient must NEVER be left unattended.
level of the head) Coughing or sneezing may be warning
• Oxygen 40% 3-6 L/min signs of a sensitization reaction and MUST
be documented in the patient’s clinical
records.
pressure, respiratory rate and pulse
rate/character Symptoms and signs
• If the patient is in agreement, the • Urticaria – skin redness and itching

treatment may be resumed but at a very white dermal hives
slow drip rate. • Conjunctival hyperaemia
2. Hypotension and syncope following • Bronchospasm with wheezing and
infusion or intravenous push of coughing
magnesium
• Anxiety and irritability
• Symptoms & signs as in 1 above
• Rapid pulse rate
• Intervention as in 1 above
• Hypotension
3. Hypotension and flushing due to niacin
• Angioneurotic glottis oedema
[23], calcium and magnesium [40]

• Confusion 3. Isotonic
• Shock Denoting a solution having the same
• Death tonicity as another solution with which
it is compared.
Intervention
4. Hypertonic
• Terminate the infusion or IV push
Having a higher concentration of
• Call for help from other clinic staff and solute particles per unit volume than
call 999 for an ambulance a comparison solution, regardless of
• Put patient in Trendellenburg position kinds of particles. It is a solution in
which cells shrink due to efflux of
• Inject adrenaline 0.5ml of 1:1,000 into
water.
the thigh muscle & repeat every 10
minutes 5. Hypotonic
• Administer Oxygen 40% @ 3-6 L/minute Having a lower concentration of

solute particles per unit volume than
• Hand the patient over to the paramedics
a comparison solution, regardless of
Dr. Schrader’s recommendation [1]: kinds of particles. A solution in which
“For true anaphylaxis, give 5,000 to 10,000 U cells expand due to influx of water and
of aqueous heparin rapidly IV and institute may even result in haemolysis.
standard emergency procedures. Heparin
interrupts the complement cascade and has
the bility to stop anaphylaxis rapidly. Give
adrenaline if heparin fails.”
According to doctor Schrader [1] he had
never seen an anaphylactic reaction in
over 20,000 intravenous micronutrient
supplementations and the allergic
reactions witnessed by him could always
be traced back to preservatives.
7. OSMOLARITY OF AN
ADMIXTURE
Definitions [31]
Note: Osmolarity and tonicity may be used
interchangeably
1. Osmolarity
The concentration of the solute in a
solution per unit of solvent, usually
expressed as mOsmol/ml or mOsmol/L.
Osmoloarity is often used in reference
to blood.
2. Tonicity
The number of particles found in
solution. Tonicity is often used in
reference to intravenous fluid.

(c) Isotonic solutions
Cells retain their normal size and
shape in the isotonic solutions (same
solute/water concentration as inside
cells; water moves in and out).
(c) Hypotonic solutions

Cells take on water by osmosis until
they become bloated and burst (lyse)
in a hypotonic solution (contains a
lower concentration of solutes than
are present in cells).

How to calculate the osmolarity of a solution?
Rx Kinetics [31] and McGuff Compounding Pharmacy Services, Inc. [65] are examples of
North American companies that offer osmolarity calculation computer software.
Manual calculation of osmolarities involve the following process [66]:
Example 1 [66]
Calculate the osmolarity of blood if the concentrations of solutes are:
[Na+] = 0.140 mol/L
[Glucose} = 180 mg/100ml
[BUN] (blood urea nitrogen) = 20mg/100ml
Solution [66]
[Na+] = 0.140 mol/l but each Na+ ion pairs with a negative ion X- such as Cl- to give 2
Osmol of particles
NaX osmolarity = 0.140 mol X 2 Osmol = 0.280 Osmol/L

1L 1 mol
Glucose osmolarity = 0.180g X 1000ml X 1 mol X 1 Osmol = 0.00999 Osmol

100ml 1L 180.2g 1 mol
BUN osmolarity = 0.020g X 1000ml X 1mol X 1 Osmol = 0.0071 Osmol/L

100ml 1L 28.01g 1 mol
Blood osmolarity = (0.280 + 0.00999 + 0.0071) Osmol/L = 0.297 Osmol/L = 297 mOsmol/L [66]
Exampe 2 [66]
Calculate the osmolarity of an intravenous admixture that contains:
500ml sterile water

NaHCO3 8.4% 50 ml
KCl 10ml of 2 mmol/ml
Heparin 5000 units 0.5ml
Pyridoxine 1ml
Thiamine 1ml

Solution
Calculation steps [31]

1. Multiply the volume in millitres (ml) of each micronutrient (and also for 0.9% Sodium
Chloride if used instead of Water for Injection) with the value of mOsm per millitre
(mOsm/ml) of the micronutrient (or 0.9% Sodium Chloride).
2. Add up together the volumes of each micronutrient (and 0.9% Sodium Chloride if used
instead of Water for Injection) to obtain the total volume of the admixture in millitres
(ml)
3. Add up together the mOsm obtained in step 1 for each of the components in order to
determine the total number of milliosmoles in the admixture
4. Divide the total number of milliosmoles by the total volume then multiply by 1,000 to
obtain an estimate of the osmolarity of the admixture in units of milliosmoles per litre.
Calculation table [66]
Intravenous
Volume (ml) Times mOsmol/ml Equals mOsmol
Additives
Sterile Water 500.00 x 0.00 = 0.00
NaHCO3 50.00 x 2.00 = 100.00
KCl 10.00 x 4.00 = 40.00
Heparin 0.50 x 0.46 = 0.23
Pyridoxine 1.0 x 1.11 = 1.11
Thiamine 1.0 x 0.62 = 0.62
TOTAL 562.50 141.96
Osmolarity = 141.96 mOsmol X 1000ml = 252 mOsmol/L [66]

562.5ml 1L
Normal blood or plasma osmolarity is between 300 – 310 mOsmol/L [1,31, 59) and the
osmolarity of IV solutions should ideally be as close as possible to the osmolarity of blood
(isotonic) in order to prevent pain and irritation of the vein and prevents complications
related to red cell fragility such as sickle cell disease [1,31,65].
Hypotonic and hypertonic solutions may be infused into large veins in small volumes due
to rapid dilution and distribution [31]. Both hypotonic and hypertonic solutions can cause
sclerosis of the vein intima [1]

Extremes of tonicity [31]:
Hypertonic upper limit for peripheral intravenous infusion is 900 mOsmol/L
Admixtures of greater than 600mOsmol/L to 900 mOsmol/L causes chemical irritation of
the vein’s intima resulting in phlebitis and thrombophlebitis and should be administered via
central venous route [31]
Hypotonic lower limit for peripheral intravenous infusion is 154 mOsmol/L (0.45% Sodium
Chloride)
Very hypotonic intravenous solutions cause red blood cell expansion due to influx of water,
hemolysis and eventually hemolytic anaemia [31].
According to Schrader [1] the safe upper limits of osmolarity for IV solutions (approximate) are:
Large vein Medium vein Any vein

IV Push (mOsm/L) 1400 950 400
IV Infusion (mOsm/L) 1200 600 400
Osmolarity Calculation Worksheet for Commonly Used Nutrients in the USA [1]
Intravenous additives mOsm/mL Multiply Nutrients added ml Equals Total mOsm
Amino Acids (FreAmine III 8.5%) 0.81 X ml =
Ascorbic Acid 500 mg/mL 5.80 X ml =
B-6 (Pyridoxine) 100 mg/mL 1.11 X ml =
B-12 (hydroxocobalamine) 1000 mcg* 0.31 X ml =
B-Complex 100 mg/mL 2.4 X ml =
Sodium Bicarbonate 8.4% 2.00 X ml =
Calcium Gluconate 10% 100 mg./mL 0.72 X ml =
Sodium EDTA 150 mg./mL 1.34 X ml =
Folic Acid 10 mg./mL 0.20 X ml =
Germanium 100 mg./mL ** 0.25 X ml =
Glutathione 100 mg./mL *** 0.38 X ml =
Heparin 5,000 U/mL 0.46 X ml =
HCl (hydrochloric acid) 2 mg./mL) 0.11 X ml =
Lactated Ringer’s 0.28 X ml =
Magnesium Sulfate 500 mg./mL 4.06 X ml =
Magnesium Chloride 200 mg./mL 2.95 X ml =
Mineral Mix (Dr. Shrader’s)** 0.57 X ml =
Molybdenum 500 mcg./mL ** 0.80 X ml =
Pantothenic acid 250 mg./mL 0.85 X ml =
Potassium chloride 2 mEq/mL ** 4.00 X ml =
Selenium 200 mcg./mL ** 0.09 X ml =
Taurine 50 mg./mL. 0.50 X ml =
Zinc 10 mg./mL ** 0.50 X ml =
0.9% Sodium Chloride 0.31 x ml =
Sterile water for injection 0.00 X ml = 0.00
TOTALS FOR ADDITIVES ml =
* Do not mix with copper (becomes deactivated)

** Do not ever give as an intravenous push
*** Do not mix with vitamin C – is reduced by vitamin C. Give an intravenous push for an appropriate effect [1]

DESIRED OSMOLARITY RANGE = 280 to 310 mOsm/L (0.280 - 0.310 mOsm/ml)
Osmolarity of common additives:
DILUENTS mOsmol/ml
Sterile Water 0.00
0.9% Sodium Chloride 0.31
Ringer’s Lactate 0.28
Calculation of the volume of water in millilitres required to create a desired osmolarity of

310 mOsm/L
Total mOsm of Additives – (Total millilitres of additives ) = milliltres of water to add

0.310
*A negative number for the answer indicates a hypo-osmolar (hypotonic) solution. To

calculate the number of millitres of Sodium Cjloride 0.9% to add to bring the hypotonic
solution to the desired osmolarity, divide this absolute number by 0.031, and add that
amount of Sodium Chloride.
If Sodium Chloride 0.9% is used as the IV solution then calculate the Sodium Chloride
osmolarity as another additive, and the “millitres of water to add” as 0 (zero) osmolarity.
See Table 1 [1]
8. COMPLICATIONS OF INTRAVENOUS MICRONUTRIENT

SUPPLEMENTATION
1. Hypertonic solutions (large volumes) [1, 31,65]
• May result in an increase in extracellular fluid resulting in circulatory overload
• Dehydration of tissue cells (fluid shift from tissue cells to intravascular compartment)
• Damage to the vascular endothelium
• Phlebitis and thrombophlebitis
2. Hypotonic solutions (large volumes) [1,31,65]

• Fluid shifting into red blood cells causing swelling
• Hemolysis
• Over hydration of tissue cells
• Phlebitis
• Death due to cardiac arrest and cerebral edema
3. Infection [19]

Example of a therapeutic application of hyperosmolar therapy

CHAPTER 8:
MEDICAL HISTORY & CONSENT
FORM

MEDICAL HISTORY QUESTIONANAIRE & INFORMNED CONSENT
FORM FOR INTRAVENOUS MICRONUTRIENT SUPPLEMENTATION
(IMS) FOR NON-MEDICINAL INDICATIONS
This is your medical history form, to be completed prior to your first INTRAVENOUS
MICRONUTRIENT SUPPLEMENTATION session.
All information will be kept confidential. This information will be used for the
evaluation of your health and readiness to begin the supplementation program.
This form is extensive, but please try to complete it as accurate and complete as
possible. Please take your time and complete it carefully and thoroughly, and then
review it to be certain you have not left anything out. Your answers will help us design
a supplementation that meets your individual needs.
If you have questions or concerns, we will help you with those after this form is
completed. We realize that some parts of the form will be unclear to you. Do your best
to complete the form. Your questions will be thoroughly addressed afterwards. It might
be helpful for you to keep a written list of questions or concerns as you complete the
medical history form.
Date: / / DOB: / /
First Name: Last Name:
Landline Number: Mobile Number:
Address:
Emergency Contact
Name: Number:
GP/Consultant contact details
Name: Number:
I give/do not give my permission to inform my GP about the intravenous micronutrient

supplementation that I am about to receive.
Sign: Date: / /
Place:

Gender:
Male Female
Occupation:
What is your purpose for having this intravenous micronutrient

supplementation (IMS)?
Have you had any Intravenous Micronutrient Supplementation before?
Yes No
Are you scared of needles/needle phobic?
Yes No
Do you faint easily when you have blood taken?
Yes No

Women only answer the following:
Any menstrual period problems?
Are you pregnant?
Significant childbirth - related problems?
Are you breastfeeding?
Comments:
Are you on any type of hormone replacement therapy? Yes No
Men only answer the following:
Do you have Prostate problems?
Do you have Erectile dysfunction?
Are you taking hormone replacement i.e. testosterone?
When was your last PSA bloodtest?
Comments:

Men and women answer the following:
List any prescription medications you are now taking:
List any self-prescribed medications, dietary supplements, or vitamins you are taking:
Date of last complete physical examination: / /
Normal Abnormal Never Can’t Remember
Comments:
List any other medical or diagnostic test you have had in the past two years:
List hospitalizations, including dates of and reasons for hospitalization:
List any drug or other causes of allergies including seafood (shellfish):

PAST MEDICAL HISTORY
Check those questions to which you answer yes (leave the others blank).
Heart attack if so, how many years ago? ________
Rheumatic Fever
Heart murmur
Diseases of the arteries
High blood cholesterol
Anaemia or other blood disorders i.e. Sickle Cell disease, Thalassaemia
G6PD deficiency
Varicose veins
Arthritis/Gout of legs or arms
Diabetes or abnormal blood-sugar tests
Phlebitis (inflammation of a vein)
Deep vein thrombosis/blood clot in the leg
Dizziness or fainting spells
Epilepsy or seizures
Stroke
Scarlet Fever
Infective endocarditis
Infectious mononucleosis
Nervous or emotional problems
Thyroid problems
Parathyroid problems
Adrenal gland problems
Pancreas/digestion problems
Stomach/duodenum ulcer
Pneumonia
Bronchitis
Continue on next page

Emphyzema
Asthma or Hay fever
Abnormal chest X-ray
Other lung disease
Kidney disease
Broken bones/osteoporosis
Liver disease
Jaundice or gall bladder problems
Allergies including to sea food?
Leukemia or cancer
Other
Comments:
Signature:

FAMILIAL DISEASES
Have you or your blood relatives had any of the following (include grandparents,
aunts and uncles, but exclude cousins, relatives by marriage and half-relatives)?
Check those questions to which you answer yes (leave the others blank).
Heart attacks under age 50
Strokes under age 50
High blood pressure
Elevated cholesterol
Diabetes
Asthma or hay fever
Skin allergies
Congenital heart disease (existing at birth but not hereditary)
Heart operations
Red blood cell disorders i.e. Sickle Cell, Thalassaemia, Anaemia
Glaucoma
Kidney disease
Obesity (20 or more pounds overweight)
Leukemia or cancer under age 60
Comments:
Signature:

CONSENT TO INTRAVENOUS MICRONUTRIENT SUPPLEMENTATION
Before you choose to use the services of
Please read the following information FULLY AND CAREFULLY:
WHY INTRAVENOUS MICRONUTRIENT SUPPLEMENTATION?
The main benefits may include:
1. Injectable micronutrients are not affected by stomach, or intestinal absorption

problems
2. Total amount of infusion/injection is available to the tissues.
3. Nutrients are forced into cells by means of a high concentration gradient.
4. Higher doses of nutrients can be given than possible by mouth without intestinal
irritation.
I understand that I have the right to be informed of the procedure, any feasible
alternative options, and the risks and benefits. Except in emergencies, procedures
are not performed until I have had an opportunity to receive such information and
to give my informed consent.
GOAL: The basic goal is to encourage people to become (1) knowledgeable about and
responsible for their own health, (2) and to bring it to a personal optimum level, (3)
to delay the aging process and to (4) enhance your metabolism.
INTRAVENOUS MICRONUTRIENT SUPPLEMENTATION (IMS) is designed to improve

your optimum health, absent of other non-nutritional complicating factors, and
requires a sincere commitment from you, possible lifestyle changes, and a positive
attitude. It is not intended to make a medical diagnosis and to recommend any
medicinal treatment(s).
No comment or recommendation should be construed as inferring or implying a

medical diagnosis. Since every human being is unique, we cannot guarantee any
specific result from INTRAVENOUS MICRONUTRIENT SUPPLEMENTATION (IMS)
protocols and programmes. Medication and or medical conditions may have a
negative impact on the positive effects of IMS.
HEALTH CONCERNS: If you suffer from a medical or pathological condition, you need
to consult with an appropriate healthcare provider such as your GP or Consultant.
If you are under the care of another healthcare provider, it is important that you
inform your other healthcare providers of your use of nutritional supplements.
Nutritional therapy may be a beneficial adjunct to more traditional care, and it
may also alter your need for medication, so it is important you always keep your
physician informed of changes in your nutritional program.

If you are using medications of any kind, you are required to alert
to such use, as well as to discuss any potential
interactions between medications and nutritional products with your pharmacist.
If you have any physical or emotional reaction to INTRAVENOUS MICRONUTRIENT

SUPPLEMENTATION (IMS), discontinue use immediately, and contact your IMS
PRACTITIONER to ascertain if the reaction is adverse or an indication of the natural
course of the body’s adjustment to the supplementation.
Laboratory testing may be done to determine areas of dysfunction, not to diagnosis

or treat. Lab testing can assist in revealing nutrient deficiencies and weaknesses,
however in many cases nutrient blood tests are not a true reflection of body tissue
levels.
COMMUNICATION: Every client is an individual, and it is not possible to determine

in advance how your system will react to the supplements you need. It is sometimes
necessary to adjust your program as we proceed until your body can begin to
properly accept products required to correct possible imbalances. It is your
responsibility to do your part by following healthy dietary guidelines, exercise your
body if possible, get plenty of rest, and learn more about nutrition health benefits.
You should request your other healthcare provider, if any, to feel free to contact

for answers to any questions they may have regarding nutritional therapy.
I understand that:
1. The procedure involves inserting a needle into a vein and injecting the selected
IMS protocol
2. Alternatives to intravenous therapy are oral supplementation and / or dietary

and lifestyle changes
3. Several supplementation sessions may be required
4. Risks of intravenous therapy include but not limited to:
• Occasionally to commonly: discomfort, pain and bruising at injection site
• Rarely: inflammation in the vein used, phlebitis, metabolic disturbances
• Extremely rarely: severe allergic reaction, anaphylaxis, systemic infection,

cardiac arrest and possible death
I am aware that other unforeseeable complications could occur. I do not expect

to anticipate and or explain all risk
and possible complications. I rely on them to exercise judgment during the course of
treatment with regards to my procedure. I understand the risks and benefits of the
procedure and have had the opportunity to have all of my questions answered.

I understand that I have the right to consent to or refuse any proposed treatment at
any time prior to its performance. At any stage during the infusion/injection, I have
the right to request that the procedure is terminated, however I accept that I will
not be re-imbursed once supplementation has commenced.
My signature on this form affirms that I have given my consent to an INTRAVENOUS

MICRONUTRIENT SUPPLEMENTATION (IMS) protocol as specified below (please
tick):
PROTOCOL SESSIONS
Wellness Formula (Modified Myers’ A)
Wellness Formula (Modified Myers’ B*) *Multi Nutrient single 100ml Vial
Super Wellness
Age Defiance
Athlete Sport
Detox Fat Burning
Mood Support
Hair Tonic
Immuno Booster
ATP Energizer
Other:
Comments:
Patient Name:
Signature: Date: / /
Practitioner Name:
Practitioner Signature: Date: / /
Place:

CUSTOMER RE-CONSENT FORM & CHANGE IN MEDICAL HISTORY
Session 2 Change in medical history? Yes No
Patient Signature: Date: / /

CHAPTER 9:
PRACTICAL FUNDAMENTALS

CONSUMABLES
Schrader W. A., THE DEFINITIVE GUIDE FOR INTRAVENOUS THERAPY with NUTRIENTS including Complete
Instructions for Sterile Compounding of Preservative-free Nutrients and Allergens (FULLY REVISED JANUARY 2013)
Copyright © TXU1-146-180: April 2003 by W.A. Shrader, Jr., MD. P. 19
Syringes
5ml: Withdrawing solutions and Glutathione 600mg IV push
10ml: Withdrawing solutions Glutathione 1,200mg IV push
20ml: Withdrawing solutions and IV push
50 ml (60ml): Withdrawing solutions and WELLNESS PROTOCOL (MODIFIED MYERS’) IV
push
Needles
2.1. Pink colour 18 gauge needles enables easy drawing up of solutions due to the large
gauge of the needle.
No-Kor 1-11/2” needles are the safest, because unlike standard ‘cutting’ needles, No-Kor
needles don’t “core” out a piece of rubber from a stopper thus preventing small pieces
of rubber ending up in the bottle, IV bag or via intravenous injection/infusion into the
patient.
2.1. Other ‘cutting’ needles:
18 gauge (pink) needles
21 gauge (green) needles
23 gauge (blue) needles are used for intramuscular injections and are not ideal for
aspiration of large volumes. Using a smaller than 21 gauge needles i.e. 23 gauge (blue)
needles make drawing up of solutions very difficult.
Intravenous Injection/Push
3.1. Winged (Butterfly) 25 gauge (orange), 23 gauge (blue) and 21 gauge (green) needles
can be used for short duration IV injection/push i.e. Glutathione or intravenous
Methylcobalamin (Vitamin B12). The 23 gauge can be used for volumes up to 30ml and
the small 25 gauge in case larger veins can’t be located. For volumes of 50 or 60 ml 23
gauge and 21 gauge ‘butterflies’ can be used.
NB: Avoid placing winged needless over joints i.e. the wrist or elbow. However, if no other
option is available, the joint must be rendered incapable of flexion (elbow) or extension
(wrist). It is not advisable to place winged needless into leg veins.
Intravenous Infusion
4.1. Cannulas (Venflons) are preferred in case of infusions of more than 60 ml i.e. infusion
bags. This is the preferred method because it affords the operator a free hand versus an IV
push.
NB: winged needless can be used for IV infusions of more than 60 ml if a cannula is not
available, however if placed near a join then the joint has to be rendered incapable of
flexion (elbow) or extension (wrist). It is not advisable to place cannulas into leg veins.

Giving Sets
Standard adult infusion giving sets are used to connect the IV solution bag to the cannula
(or winged needle set).
Intravenous Solutions
The main aim of selecting an intravenous solution is for the admixture to be as close as
possible to being isotonic.
6.1. Sterile Water for Injection (WFI): 5ml and 10ml ampoules, 20ml glass bottles or 100ml
plastic bottles.
NB: Glutathione is always reconstituted with WFI and it is always injected via a separate
IV push. It is never mixed together with Vitamin C because the latter inactivates
glutathione.
Large volumes of Water for Injection can result in admixtures being too hypotonic. Always
calculate the osmolarity of the admixture.
WFI is only used for dilution purposes.
6.2. Sodium Chloride 0.9%: 100ml or 250ml bags.
NB: Large volumes of 0.9% Sodium Chloride can result in admixtures being too hypertonic.
Always calculate the osmolarity of the admixture.
Sundries
7.1. Alcohol swabs
7.2. Tourniquet
7.3. Gauze
7.4. Hypoallergenic tape
7.5. Clean worktop sheets
7.6. Clinical waste (sharps) plastic containers
7.7. Latex free gloves
7.8. Emergency drug tray
EQUIPMENT
8.1. IV Drip Stands
8.2. Electronic blood pressure & pulse rate device or a sphygmomanometer
8.3. Thermometer
8.4. Glucometer
8.5. Comfortable reclining chairs or beds
8.6. Pillows for support of the patient’s arm

ADMINISTRATION METHODS
1. Intravenous injection
1.1. Single substances of small volumes i.e. methylcobalamin (Vitamin B12) 1ml or
glutathione 600mg in 5 ml WFI are injected slowly at a rate of 1ml/minute.
1.2. Always inject a small “test dose” of 0.1ml and wait 2 minutes to make sure the patient
is not having an allergic rection.
1.3. The osmolarity is usually high and WFI can be used to dilute the substance i.e.
methylcobalamine 1ml can be diluted with 5 ml WFI and not with 0.9% Sodium Chloride.
2. Intravenous push
2.1. Several substances included in the admixture of volumes ranging from 10-60ml.
2.2.See osmolarity ranges in Chapter 10.
2.3. Inject a small ‘test dose” of 2 ml and wait 2 minutes to see if the patient is not
developing an allergic reaction. Continue administration at 1-2 ml/minute.
2.4. WFI can be added to reduce osmolarity in case of vein discomfort.
3. Intravenous infusion
3.1. Volumes greater than 60ml are infused using a 100ml or 250ml bag, giving set and a
cannula.
3.2. See osmolarity ranges in Chapter 10.
3.3. Inject a small “test dose” and wait 2 minutes to make sure the patient is not
developing an allergic reaction. Continue initially at a slow drip rate that can be increased
later to 3-8ml/minute if the patient is comfortable.
4. Intramuscular injections
Intramuscular injections are given when a slower effect or a prolonged effect (depot
formula) is required versus a rapid intravenous effect.
4.1. Risks of intramuscular injections:
4.1.1. Intra-arterial injection leading to vasospasm and tissue necrosis
4.1.2. Nerve trauma: deltoid muscle (radial nerve damage); gluteal muscle (sciatic nerve
damage)
4.1.3. Transient but painful muscle spasm
4.1.4. Quadriceps muscle injection is the safest
4.1.5. Maximum safe intramuscular dose is 3 ml in order to avoid localized muscle fibre
damage, fibrosis and possible necrosis
4.1.6. Always aspirate before IM injection to avoid accidental intra arterial injection –
arterial blood is bright red (oxygenated) versus venous dark red blood
4.2. The ideal needle gauge for intramuscular injections is 23g (blue)

4.3. Some scar tissue is created following every intramuscular injection and a different
injection site should be used for the next IM injection
4.4. Substances warmed up to body temperature before injection causes less discomfort
and muscle spasm
4.5. Avoid injection near to areas of existing infection
5. Intradermal injections
Minute amounts (0.01ml)of an antigen or a substance are injected into the
epidermis in order to challenge the patient’s immune response. Signs of an allergic
reaction include itching of the skin, skin rash and wheel formation.
Indicated for:
5.1. Patients with known allergies to certain substances
5.2. Substances containing preservatives i.e. methyl parabens and benzyl alcohol. Benzyl
alcohol patches can also be used to test for sensitivity to benzyl alcohol.
5.3. A negative test result after 5 minutes is required to continue with the treatment.
However, a negative test result does not guarantee that an allergic reaction will not take
place at the next treatment because the patient may have been sensitized.
5.4. At risk patients must always have an allergy test prior to treatment.

CHAPTER 10a:
INTRAVITA INTRAVENOUS
MICRONUTRIENT SUPPLEMENTATION
PROTOCOLS

INTRAVITA INTRAVENOUS MICRONUTRIENT SUPPLEMENTATION PROTOCOLS
WELLNESS AGE IMMUNO ATHLETE DETOX FAT
NUTRIENT MOOD SUPPORT HAIR TONIC 0ne 20ml ampoule ATP ENERGIZER
Mod. Myers’ A DEFIANCE BOOSTER SPORT BURNING
DOSE MINERALS DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE
Magnesium sulphate 1000mg/2ml 1000mg/2ml 2000mg/4ml 1000mg/2ml 2000mg/4ml 1000mg/2ml 1000mg/2ml Magnesium-DL-
1000mg/2ml 500mg
50% 500mg/ml 1 ampoule 1 ampoule 2 ampoules 1 ampoule 2 ampoules 1 ampoule 1 ampoule hydrogenaspartate
Calcium Gluconate
100mg 100mg 300mg 300mg 300mg 100mg 100mg
1000mg/10ml 10%
1 ml 1 ml 3ml 3ml 3ml 1 ml 1 ml
100mg/ml
100mcg/2ml 100mcg/2ml 200mcg/4ml 100mcg/2ml 100mcg/2ml 100mcg/2ml
100mcg/2ml Selenium
1 vial 1 vial 2 vials 1 vial 1 vial 1 vial
6mg 6mg 6mg 6mg 6mg
300mg/10ml Zinc
2ml 2ml 2ml 2ml 2ml
VITAMINS
1500mg 1500mg 2250mg 2250mg 2250mg 1500mg 1500mg Ascorbic Acid Vitamin
750mg/5ml Ascorbic acid 10mg
10ml 2 vials 10ml 2 vials 15ml 3 vials 15ml 3 vials 15ml 3 vials 10ml 2 vials 10ml 2 vials C
1000mcg 1000mcg 1000mcg 1000mcg 1000mcg 1000mcg 1000mcg
1000mcg/ml Hydroxycobalamin Riboflavin Vitamin B2 50mg
2ml 1 vial 2ml 1 vial 2ml 1 vial 2ml 1 vial 2ml 1 vial 2ml 1 vial 2ml 1 vial
2ml 2ml 2ml 2ml 2ml 2ml 2ml Nicotinamide Vitamin
B1 B2 B3 B5 B6 Vitamin B Complex 50mg
1 vial 1 vial 1 vial 1 vial 1 vial 1 vial 1 vial B3
Dexpanthenol 500mg 500mg 500mg 500mg 500mg 500mg 500mg Dexp[anthenol
500mg/2ml 50mg
(Vitamin B5) 2 ml 2 ml 2 ml 2 ml 2 ml 2 ml 2 ml Vitamin B5
Pyridoxine (Vitamin 100mg 100mg 100mg 100mg 100mg 100mg 100mg Pyridoxine Vitamin
100mg/5ml 50mg
B6) 5ml 1 vial 5ml 1 vial 5ml 1 vial 5ml 1 vial 5ml 1 vial 5ml 1 vial 5ml 1 vial B6
AMINO ACIDS Thiamine 50mg
2420 mg/20ml Arginine 1 ampoule 1 ampoule 1 ampoule Adenocylcobalamine 1000mcg
2017 © Copyright to IntraVita Limited

1000mg/5ml Carnitine 1 ampoule 1 ampoule 1 ampoule 1 ampoule Argenine 500mg
300mg/5ml Choline 1 ampule Carnetine 500mg
100mg/3ml Cysteine 1 ampoule 1 ampoule
1000mg/20ml Glutamine 1 ampoule 1 ampoule 1 ampoule 1 ampoule 1 ampoule
1000mg/5ml Glycine 1 ampoule Glycine 500mg
2000mg/20ml Lysine 1 ampoule 1 ampoule 1 ampoule
750mg/5ml Methionine 1 ampoule 1 ampoule
2500mg/20ml Ornithine 1 ampoule 1 ampoule
250mg/20ml Phenylalanine 1 ampoule
1000mg/20ml Taurine 1 ampoule 1 ampoule 1 ampoule Taurine 500mg
600mg 1200mg 1200mg 1200mg 1200mg 1200mg 1200mg 1200mg

600mg/5ml WFI Glutathione
5ml 1 vial 10ml 2 vials 10ml 2 vials 10ml 2 vials 10ml 2 vials 10ml 2 vials 10ml 2 vials 10ml 2 vials
119
INTRAVITA INTRAVENOUS MICRONUTRIENT
SUPPLEMENTATION PROTOCOLS
WELLNESS
NUTRIENT
Mod. Myers’ B
MINERALS DOSE
Magnesium Chloride
40mg
Calcium Chloride 40mg
Potassium Chloride 15mg
Selenium 50mcg
Zinc 5mg
VITAMINS
Ascorbic acid 300mg
Hydroxycobalamin 1000mcg
Dexpanthenol
500mg
(Vitamin B5)
Pyridoxine (Vitamin
100mg
B6)
Riboflavin Vitamin B2 10mg
Niacin Vitamin B3 100mg

CHAPTER 10b:
INTRAVENOUS MICRONUTRIENT
SUPPLEMENTATION PROTOCOLS

Side Effects and Precautions of IMS (from chapter 7 p.90-93)
5. CONTRAINDICATIONS TO IMS than 600mOsmol/L to 900 mOsmol/L

causes chemical irritation of the
A) Absolute contraindications vein’s intima resulting in phlebitis
1. Preservatives: known hypersensitivity and thrombophlebitis and should be
to a preservative contained in a administered via central venous route
pharmaceutical manufactured product [31]
such as methylparabens or benzyl • Hypotonic lower limit for peripheral
alcohol (patch test confirmation) [1,14] intravenous infusion is 154 mOsmol/L
may cause an allergic reaction. It is (0.45% Sodium Chloride) Very hypotonic
unlikely to develop an allergic reaction intravenous solutions cause red blood
to a pure micronutrient per se [1]. cell expansion due to influx of water,
2. Thiamine certainly has potential to hemolysis and eventually hemolytic
evoke anaphylactic reactions [20,21] and anaemia [31].
patients with a history of a previous 9. Patients receiving chemotherapy and
“sensitization” reaction should not be radiation therapy: obtain approval from
administered Vitamin B1. the patient’s oncologist:
3. High doses of certain micronutrients
such as magnesium may cause “The safety and efficacy of the use
unpleasant reactions such as dermal of vitamin C and other antioxidants
vasodilatation (flushing) and even during cancer treatment is controversial
hypotension [22] and extra precaution [32,33,34]. Some data indicate that
is required in patients with known antioxidants might protect tumor cells
low blood pressure and hypertensive from the action of radiation therapy
patients on vasodilator medication [1,2] and chemotherapeutic agents, such
as cyclophosphamide, chlorambucil,
4. Niacin may cause severe dermal
carmustine, busulfan, thiotepa, and
vasodilatation [23] and is
doxorubicin [35,33,36,37]. At least some
contraindicated in diabetics and gout
of these data have been criticized
sufferers [24].
because of poor study design [38].
5. Avoid intravenous calcium in Other data suggest that antioxidants
hyperparathyroidism [25]. might protect normal tissues from
6. Avoid glutamine in patients with renal chemotherapy- and radiation-induced
disease, liver disease and Rye syndrome damage [33,36] and/or enhance the
[26,27,28]. Glutamine supplementation effectiveness of conventional cancer
can increase ammonia in the body treatment [38]. However, due to the
tissues, so taking glutamine may make physiologically tight control of vitamin
lactulose less effective [28] C, it is unclear whether oral vitamin
C supplements could alter vitamin
7. DL-phenylalanine should not be used C concentrations enough to produce
in people taking antipsychotic drugs, the suggested effects. Individuals
as it may cause or worsen symptoms undergoing chemotherapy or radiation
of tardive dyskinesia (TD). TDs are should consult with their oncologist
involuntary movements of the tongue, prior to taking vitamin C or other
lips, face, trunk, and limbs that can antioxidant supplements, especially in
occur in people taking antipsychotic high doses” [39].
drugs long term [29,30]
8. Extremes of tonicity [31]: pump that promotes intracellular
• Hypertonic upper limit for uptake of potassium and may cause
peripheral intravenous infusion is hypokalaemia in patients deficient in
900 mOsmol/L Admixtures of greater magnesium and potassium resulting in

muscle cramps [2,40]. micronutrients may be advisable for
the majority of lactating women in
11. Poorly controlled diabetes
developing countries and industrialized
mellitus:“Diabetic patients frequently
countries—not least to prevent their
develop a constellation of electrolyte
further depletion through the secretion
disorders. These disturbances are
of large amount of these micronutrients
particularly common in decompensated
in breast milk. “ [49]
diabetics, especially in the context of
diabetic ketoacidosis or nonketotic
Dietary fortification and oral multiple
hyperglycemic hyperosmolar syndrome.
micronutrient supplements may not
These patients are markedly potassium-
always be sufficient thus making it
magnesium- and phosphate depleted.
appropriate to administer specifically
Diabetes mellitus (DM) is linked to both
indicated intravenous micronutrient
hypo- and hyper-natremia reflecting
supplementation.
the coexistence of hyperglycemia-
related mechanisms, which tend to 14. Poorly controlled asthma: intravenous
change serum sodium to opposite magnesium can abort acute asthmatic
directions. The most important causal attacks [2,4,5,6,7] and the use of multiple
factor of chronic hyperkalemia in intravenous micronutrients may be of
diabetic individuals is the syndrome considerable benefit in both acute and
of hyporeninemic hypoaldosteronism. chronic asthma [50]. Even pulmonary
Impaired renal function, function improved progressively the
potassiumsparing drugs, hypertonicity longer the patients received it [50].
and insulin deficiency are also involved
15. Hypokalaelmia {1,2]
in the development of hyperkalemia”
[41]
B) Relative contraindications
12. Pregnant women: routine intravenous
micronutrient supplementation is 1. Glutamine: reduce the dose in elderly
not appropriate in pregnant and patients due to associated reduced renal
lactating mothers in the absence and liver function [26,27,28].
of a medical indication. However,
should a women inadvertently have
2. Vitamin C ascorbic acid: reduce the dose
received anintravenous micronutrient
supplementation without the prior in patients with G6PD deficiency [51],
knowledge of her being pregnant, chronic renal disease and pre-existing
several case reports in the literature hyperoxaluria [52,53].
have confirmed that total parenteral 3. Arginine: reduce the dose in
nutrition (TPN) - although infrequently hypotensive patients or patients taking
used in pregnancy [42] - promote foetal
hypotensive medication [54].
growth and is well tolerated by the
mother [43]. Hypertonic solutions can 4. N-acetyl-L-cysteine (NAC) may
supply total caloric/metabolic needs potentiate immunosuppressive
without unacceptable side effects [44]. drugs such as azathioprine (Imuran),
13. Lactating mothers: “because cyclophosphamide (Cytoxan) or
micronutrient status of the lactating prednisone (Deltasone) [55]. NAC
woman is critical for the secretion of may also potentiate the effect of
adequate micronutrient concentrations nitroglycerin and isosorbide (Isordil™)
in breast milk, and for the micronutrient causing severe headaches and
status of her infant, more attention hypotension [55].
should be paid to the micronutrient
5. Reactive hypoglycaemia: ensure
status of lactating women. Provision
patients are having a snack prior to the
of multiple micronutrient supplements
and/or food fortification with supplementation. Interestingly, Vitamin

C “Further Improves the Protective • Slow faint pulse
Effect of Glucagon-Like Peptide-1 on
• Hypotension
Acute Hypoglycemia-Induced Oxidative
Stress, Inflammation, and Endothelial • Dizzyness
Dysfunction in Type 1 Diabetes” [56] • Syncope
6. Atopic dermatitis and other hyper Intervention:
allergenic conditions.
7. Hypotonic solutions and red blood cell
fragility disorders [1]:
position (lying down flat, feet above the
• Thalassemia Major level of the head)
• G6PD deficiency [1,51] • Oxygen 40% 3-6 L/min
• Spherocytosis • Observation of vital signs: blood
• Sickle cell anaemia pressure, respiratory rate and pulse
rate/character
8. HIV+, Hepatitis B+ and Hepatitis C+
patients: protection of practitioner, staff • If the patient is in agreement, the
and other patients visiting the clinic. treatment may be resumed but at a very
slow drip rate.
9. Opioid drug addiction: extra precaution
2. Hypotension and syncope following
• Constipation, nausea and vomiting
infusion or intravenous push of
causing hypokalaemia [57]
magnesium
• Immune suppression and prone to
• Symptoms & signs as in 1 above
bacterial infections [58]
• Intervention as in 1 above
• Impaired liver functions
3. Hypotension and flushing due to niacin
Cardiac effects: [23], calcium and magnesium [40]
induced dermal vasodilation
A) Vasodilatation and hypotension [59]
Symptoms & signs
B) Bradycardia
• Dermal flushing (redness)
C) ECG changes: Syndrome of QT
prolongation and torsade de pontes • Skin warm
[60] (mortality rate 17%) linked to • Strong rapid pulse
methadone [61], hypokalaemia and
• Dizziness
diminished liver functions [62]
Intervention
10. Opiate analgesia: markedly potentiated
by phenylalanine [63,64] • Terminate the infusion or IV push
6. ADVERSE REACTIONS TO IMS [1] position
1. Nervous patients (needle phobia)
• The effect is usually transient ad self
vasovagal (syncope) reaction:
limiting
• Symptoms & signs
• Palor pressure, respiratory rate and pulse
rate/character
• Cold clammy skin
• If the patient is in agreement, the

treatment may be resumed but at a very standard emergency procedures. Heparin
slow drip rate interrupts the complement cascade and has
the bility to stop anaphylaxis rapidly. Give
4. Nausea and vomiting due to rapid
adrenaline if heparin fails.”
injection/infusion [2].
According to doctor Schrader [1] he had
5. Headache due the sulfates in
never seen an anaphylactic reaction in
Magnesium Sulfate [1,2].
over 20,000 intravenous micronutrient
6. Anaphylaxis – Life threatening supplementations and the allergic
emergency reactions witnessed by him could always
The patient must NEVER be left unattended. be traced back to preservatives.
Coughing or sneezing may be warning
signs of a sensitization reaction and MUST
be documented in the patient’s clinical
records.
Symptoms and signs
• Urticaria – skin redness and itching
white dermal hives
• Conjunctival hyperaemia
• Bronchospasm with wheezing and
coughing
• Anxiety and irritability
• Rapid pulse rate
• Hypotension
• Angioneurotic glottis oedema
• Confusion
• Shock
• Death
Intervention
• Call for help from other clinic staff and
call 999 for an ambulance
• Put patient in Trendellenburg position
• Inject adrenaline 0.5ml of 1:1,000 into
the thigh muscle & repeat every 10
minutes
• Administer Oxygen 40% @ 3-6 L/minute
• Hand the patient over to the paramedics
Dr. Schrader’s recommendation [1]:
“For true anaphylaxis, give 5,000 to 10,000 U
of aqueous heparin rapidly IV and institute

WELLNESS PROTOCOL (MODIFIED MYERS’ COCKTAIL A)
Patient’s Name: DOB: / /
Signature: Treatment Number:
∗*ADMIXTURE FOR INTRAVENOUS INFUSION
NUTRIENT mg mg/ml ml mOsm/ml mOsmVol lot No Exp.Date
Magnesium sulphate 1000mg 500mg/ml 2 4.06 8.12
Calcium Gluconate 10% 100mg 100mg/ml 1 0.70 0.70
Selenium 100mcg 50mcg/ml 2 0.02 0.04
Ascorbic Acid Vitamin C 1500mg 150mg/ml 10 1.45 14.5
Vitamin B Complex 2 1.07 2.14
Dexpanthenol Vitamin B5 500mg 250mg/ml 2 1.22 2.44
Pyridoxine Vitamin B6 100mg 20mg/ml 5 0.22 1.1
1000mcg/
Hydroxylcobalamin B12 1000mcg 1 0.31 0.31
ml
Sub Total 25 29.35
Sterile Water for Injection 25 0 0
IV Push Total 50 29.35
Sterile water for Injection 100 0 0
Infusion Total 125 29.35
0.9% Sodium Chloride 25 0.31 7.75
IV Push Total 50 37.1
0.9% Sodium Chloride 250 0.31 77.5
Infusion Total 175 106.85
Final Osmolarity with Water For Injection 25ml added (IV push) Final Osmolarity with 0.9% Sodium Chloride 25ml added
Total mOsmVol x 1000 = 29.35 x 1000 = 587mOsm/L Total mOsmVol x 1000 = 37.1 x 1000 = 742mOsm/L
Total Vol ml 50 Total Vol ml 50
NB: 600 mOsm/L is the maximum osmolarity upper range NB: Osmolarity is too high (maximum 600mOsmol/L)
Final osmolarity with Water for Injection 100ml added Final Osmolarity with 0.9% Sodium Chloride 250ml added
Adding 100ml: Total mOsmVol x 1000 = 29.35 x 1000 =373mOsm/L Adding 100ml: Total mOsmVol x 1000 = 160.85 x 1000=388mOsm/L
NB: near isotonic = best option NB: hypertonic and may be injected via a large vein
Separate Intravenous Push
Glutathione 600mg in 5ml Water for Injection (WFI) administered as a separate intravenous push at the
beginning and always prior to administering the intravenous infusion admixture∗* IV Push
NB: glutathione is never added to the admixture! Vitamin C inactivates it.
Gutathione Dose

EMERGENCY PREPAREDNESS: Staff CPR trained: Yes No Emergency tray including adrenaline ready Yes No
Start time: End time: Treatment time:
Cannula gauge Drip rate/min: Tip intact on removal of cannula ?
Butterfly gauge Drip rate/min:
Vital signs before infusion: Blood Pressure: mmHg. Pulse rate: b/min Temperature. (optional)
Blood glucose: Check infusion line for air bubbles, leaks, blood clot obstruction:
Action taken:
Vital Sign During Infusion Time Time Time Time Time Time Time Time
Pulse Rate b/min
Blood Pressure
Drip Rate drops/min
1. Cannulation discomfort scale: No pain 0 1 2 3 4 5 6 7 8 9 10 Extremely painful
2. Infusion discomfort scale: No pain 0 1 2 3 4 5 6 7 8 9 10 Extremely painful
3. Injection site: Bruised? Yes No Swollen? Yes No
4. Coughing: Yes No Yes

5. Sneezing: No 6. Nausea: Yes No 7. Vomiting: Yes No
8. Headache:
Yes No 9. Dermal vasodilatation: Yes No 10. Dizzy: Yes No
11. Fainted: Yes No 12. Infusion discontinued? Yes No Why?
Vital signs on discharge: Blood Pressure: mmHg. Pulse rate: b/min Temperature. (optional)
Practitioner notes:
Patient signature: Date: / /
Practitioner signature: Time:

WELLNESS PROTOCOL (MODIFIED MYERS’ COCKTAIL B)
∗*MULTI NUTRIENT SINGLE 100ML VIAL
Magnesium Chloride 1000mg
Calcium Chloride 100mg
Selenium 100mcg
Ascorbic Acid Vitamin C 300mg
Riboflavin Vitamin B2 10mg
Dexpanthenol Vitamin B5 100mg
Pyridoxine Vitamin B6 100mg
Hydroxylcobalamin B12 1000mcg
Niacin Vitamin B3 100mg
Zinc 5mg
Sub Total 100ml 54.8
0.9% Sodium Chloride 250ml 0.31 77.5
Total Volume 350ml 132.3
Final Osmolarity with 0.9% Sodium Chloride 250ml added
Total mOsmVol x 1000 = 132.3 x 1000 = 378 mOsm/L

Total Vol ml 270
Hypertonic but safe to inject into a large vein
Glutathione 600mg in 5ml Water for Injection (WFI) administered as a separate intravenous push at the
beginning and always prior to administering the intravenous infusion admixture∗* IV Push
Gutathione Dose

Action taken:
Pulse Rate b/min
Blood Pressure
Drip Rate drops/min

8. Headache:
Practitioner notes:

AGE DEFIANCE PROTOCOL
Zinc 6mg 3mg/ml 2 0.50 1
Vitamin B Complex *∗ *∗/2ml 2 1.07 2.14
Hydroxylcobalamin B12 1000mcg 1000mcg/ml 1 0.31 0.31
Cysteine 100mg 33.3mg/ml 3 0.63 1.89
Glutamine 1000mg 50mg/ml 20 0.35 7
Glycine 1000mg 200mg/ml 5 0.17 0.85
Carnetine 1000mg 200mg/ml 5 0.32 1.6
Ornithine 2500mg 125mg/ml 20 0.32 6.4
Sub total 80 48.09
Total 180 48.09
0.9% Sodium Chloride 100ml 100 0.31 31.0
Total 180 79.09
Total 330 125.59
Final Osmolarity with Water For Injection 100ml added Final Osmolarity with 0.9% Sodium Chloride 100ml added
NB: hypotonic but safe if administered via a large vein NB: hypertonic - safe if administered via a large vein = best
option
Final Osmolarity with Water for Injection 250ml added Final Osmolarity with 0.9% Sodium Chloride 250ml added
NB: extremely hypotonic = contraindicated NB: hypertonic but safe if injected via a large vein = best option
Glutathione 2 X 600mg in 5ml Water for Injection (WFI) = 1,200mg in 10ml WFI administered as a IV Push
separate intravenous push at the beginning and always prior to administering the intravenous
infusion admixture* Gutathione Dose

Action taken:
Pulse Rate b/min
Blood Pressure
Drip Rate drops/min

8. Headache:
Practitioner notes:

IMMUNO BOOSTER PROTOCOL
Vitamin B Complex ∗* *∗/2ml 2 1.07 2.14
Argenine 2420mg 121mg/ml 20 1.27 25.4
Gluamine 1000mg 200mg/ml 20 0.35 7
Lysine 2000mg 100mg/ml 20 0.62 12.4
Taurine 1000mg 50mg/ml 20 0.34 6.8
Sub Total 118 98.76
Total 218 98.56
Total 218 129.76
368 176.26
NB: hypertonic - safe if administered via a large vein = best option NB: hypertonic
NB: hypotonic NB: hypertonic but safe if administered via large vein
Glutathione 2 X 600mg in 5ml Water for Injection (WFI) = 1,200mg in 10ml WFI administered as a
separate intravenous push at the beginning and always prior to administering the intravenous IV Push
infusion admixture∗*
Gutathione Dose

Action taken:
Pulse Rate b/min
Blood Pressure
Drip Rate drops/min

8. Headache:
Practitioner notes:

ATHLETE SPORT PROTOCOL
Argenine 2420mg 121mg/ml 20 1.27 25.4
Glutamine 1000mg 200mg/ml 20 0.35 7
Taurine 1000mg 50mg/ml 20 0.34 6.8
Sub total 95 78.76
Total 195 78.76
Sodium Chloride 100ml 100 0.31 31.0
Total 195 109.76
Sodium Chloride 250ml 250 0.31 77.5
Total 345 156.26
NB: hypertonic - safe if administered via a large vein = best option NB: hypertonic but safe if administered via a large vein
NB: hypotonic NB: hypertonic
infusion admixture*∗
Gutathione Dose

Action taken:
Pulse Rate b/min
Blood Pressure
Drip Rate drops/min

8. Headache:
Practitioner notes:

MOOD SUPPORT PROTOCOL
Glutamine 1000mg 50mg/ml 20 0.27 5.4
Ornithine 2500mg 125mg/ml 20 0.32 6.4
Taurine 1000mg 50mg/ml 20 0.34 6.8
Phenylanlanine 250mg 12.5mg/ml 20 0.35 7
Sub total 128 77.56
Total 228 77.56
Total 228 108.56
Total 378 156.06
NB: isotonic = best option NB: hypertonic
NB: extremely hypotonic = contraindicated NB: hypertonic – safe if administered via a large vein
separate intravenous push at the beginning and always prior to administering the intravenous infusion IV Push
admixture∗*
Gutathione Dose

Action taken:
Pulse Rate b/min
Blood Pressure
Drip Rate drops/min

8. Headache:
Practitioner notes:

DETOX FAT BURNING PROTOCOL
Vitamin B Complex ∗* *∗/2ml 2 1.07 2.14
Glutamine 1000mg 50mg/ml 20 0.27 5.4
Choline 300mg 60mg/ml 5 0.47 2.35
Lysine 2000mg 100mg/ml 20 0.62 12.4
Methionine 750mg 37.5mg/ml 20 0.5 10
Sub total 98 65.47
Sterile water for Injection 100ml 100 0 0
Total volume 198 65.47
NB: isotonic = best option NB: hypertonic
NB: extremely hypotonic = contraindicated NB: hypertonic but safe if administered via a large vein
separate intravenous push at the beginning and always prior to administering the intravenous infusion IV Push
admixture*
Gutathione Dose

Action taken:
Pulse Rate b/min
Blood Pressure
Drip Rate drops/min

8. Headache:
Practitioner notes:

HAIR TONIC PROTOCOL
Arginine 2420mg 121mg/ml 20 1.27 25.4
Cysteine 100mg 33.33mg/ml 3 0.63 1.89
Methionine 750mg 37.5mg/ml 20 0.5 10
Lysine 2000mg 100mg/ml 20 0.62 12.4
Sub total 98 80.04
Sterile water for Injection

100 0 0
100ml
NB: hypertonic = best option NB: hypertonic
NB: extremely hypotonic = contraindicated NB: hypertonic but safe if administered via a large vein
infusion admixture*
Gutathione Dose

Action taken:
Pulse Rate b/min
Blood Pressure
Drip Rate drops/min

8. Headache:
Practitioner notes:

ATP-ENERGISER PROTOCOL
Magnesium-DL- 500mg 25mg/ml

hydrogenaspartate
Ascorbic Acid Vitamin C 10mg 0.5mg/ml
Riboflavin Vitamin B2 50mg 2.5mg/ml
Nicotinamide Vitamin B3 50mg 2.5mg/ml
Dexp[anthenol Vitamin B5 50mg 2.5mg/ml
Pyridoxine Vitamin B6 50mg 2.5mg/ml
Thiamine 50mg 2.5mg/ml
Adenocylcobalamine 1mg 0.05mg/ml
Taurin 500mg 25mg/ml
Argenine 500mg 25mg/ml
Glycine 500mg 25mg/ml
Carnetine 500mg 25mg/ml
Sub total 20ml 74.1
Final Osmolarity with 0.9% Sodium Chloride 250ml added
Total mOsmVol x 1000 = 151 x 1000 = 561 mOsm/L

Total Vol ml 270
NB: hypertonic but safe if administered via a large vein
infusion admixture*
Gutathione Dose

Action taken:
Pulse Rate b/min
Blood Pressure
Drip Rate drops/min

8. Headache:
Practitioner notes:

PROTOCOL
Sub total
Sterile water for injection ml 0 0
Total volume
Sterile water for Injection 100ml 100 0 0
Total volume
0.9% Sodium Chloride ml 0.31
Total volume
Total volume
Total mOsmVol x 1000 = x 1000 = mOsm/L Total mOsmVol x 1000 = x 1000 = mOsm/L
Total Vol ml Total Vol ml
Isotonic? Yes No Hypotonic? Yes No Hypertonic? Yes No Isotonic? Yes No Hypotonic? Yes No Hypertonic? Yes No
Total mOsmVol x 1000 = x 1000 = mOsm/L Total mOsmVol x 1000 = x 1000 = mOsm/L
Total Vol ml Total Vol ml
Isotonic? Yes No Hypotonic? Yes No Hypertonic? Yes No Isotonic? Yes No Hypotonic? Yes No Hypertonic? Yes No
Glutathione 600mg in 5ml Water for Injection (WFI) x = mg in ml WFI administered

as a separate intravenous push at the beginning and always prior to administering the intravenous IV Push
infusion admixture*
Gutathione Dose
144 2017Continue onto

© Copyright next page Limited
IntraVita
Action taken:
Pulse Rate b/min
Blood Pressure
Drip Rate drops/min

8. Headache:
Practitioner notes:

CHAPTER 11:
CHECK LIST & ADVERSE REACTION
REPORTING

1. Patient consultation
1. Comprehensive medical history
2. Discussion of the advantages and disadvantages of IMS
3. Exclusion criteria?
4. Selection of a suitable IMS protocol
5. Special attention to patients with needle phobia – suitable?
6. Obtain informed consent
7. Discuss the patient’s right to terminate consent at any time
8. Allow for a sensible “cooling off” period for the patient to reconsider
2. Clinic readiness for IMS

1. Staff are all CPR trained?
2. Emergency protocol is in place?
3. Emergency allergy/anaphylaxis medicine tray is ready?
4. All equipment is in working order?
5. Valid shelf life for all substances and consumables?
6. Clinic and clinician insurance are valid?
3. Patient readiness for IMS

7. Patient signed informed consent?
8. Last food intake was less than 2 hours ago? Provide the patient with a snack to eat
and some fluid to drink (Dioralyte™ electrolyte sachet) to prevent hypokalaemia and
hypoglycaemia
9. Special attention to diabetics: blood glucose before and after IMS
10. Sit or lie the patient down
11. Locate a suitable vein
12. Vital signs: blood pressure, pulse rate and temperature (optional)
13. Placement of winged needle or cannula
14. Injection of test dose – wait 2 minutes to exclude an allergic reaction
15. Continue with IV injection/push /infusion
16. Monitor the patient – never leave the patient unattended. Early intervention of side
effects and complications is very important because the injection of any intravenous
substance potentially carries the risk of an allergic reaction
17. Documentation: Contemporaneous record keeping is essential for clinical governance
and it can be used for audit purposes as well. It also is very important for medico-legal
purposes. The patient feed back section of treatment record is important
18. Patient discharge is minimum 30 minutes after IMS and only if the discharge vital
signs have been recorded and the patient have signed the document
19. Adverse reactions must be reported to IntraVita Ltd or directly to the MHRA (see BNF
Yellocard Form) and copy IntraVita Ltd

REFERENCES

References
CHAPTER 1
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3. McNeil, D. (December 2006). In raising the world’s I.Q., the secret’s in the salt. The New
York Times, Retrieved November 29, 2010 from http://www.nytimes.com/2006/12/16/
health/16iodine.html?_r=1&fta=y
4. Leathers, H., & Foster, P. (2009). The world food problem: toward ending undernutrition
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5. Stoltzfus RJ, Dreyfuss ML. Guidelines for the use of iron supplements to prevent and
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6. Prasad AS. Discovery of human zinc deficiency and studies in an experimental human
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Stampfer MJ (1998) Folate and vitamin B6 from diet and supplements in relation to risk
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62. Ehret GB, Voide C, Gex-Fabry M, Chabert J, Shah D, Broers B, Piguet V, Musset T, Gaspoz
JM, Perrier A, Dayer P, Desmeules JA. Drug-induced long QT syndrome in injection drug
users receiving methadone: High frequency in hospitalized patients and risk factors.
Arch Intern Med 2006; 166:1280-1287.
Metab. 2009;98(4):331-7.
65. McGuff EDTA Dosage and Osmolarity Software. www.mcguff.com
66. How to calculate the osmolarity of a solution? Socratic chemistry. www.socratic.org

Author Dr Jacques Otto
Qualifications:
Qualified as a medical doctor (MBChB) in 1981 from the University of Pretoria in South
Africa. Post graduate qualifications include: Master in Family Medicine (M Prax Med
Pretoria), Master in Medical Pharmacology (M Pharm Med Pretoria), Master of Philosophy
in Medical Law (M Phil Med Law Glasgow), Member of the Faculty of Family Medicine
(College of Medicine of South Africa MFGP CMSA), Diploma in Forensic Medicine (CMSA
Dip For Med), Post Graduate Diploma in Dentistry – Sedation (University of Stellenbosch
PDD-S), Certificate in Aviation Medicine (Medical Military Institute South African Defence
Force)
Sports achievements:
1986: 10 km best 30 min 46 sec
1985: 16 km best 46 min 21 sec
1986: Half marathon best 67 min 21 sec
1987: Marathon best 2hours 19 min 05 seconds
Pharmaceutical industry:
1990 – 1993 Abbott Laboratories South Africa (Scientific Affairs Manager)
Intravenous Micronutrient Supplementation Experience:

2010: Panacee Clinic (www.panacee.com) in Bangkok International Antiaging Consultant
2015: Skymark YoungThai Medical Tourism (Sino-Thai) International Antiaging Consultant
2014: Co founder NeoPharmaUk Ltd (www.neopharmauk.co.uk)
2014: Founder Dr. Otto Laboratories (IVMNS product GMP manufacturer)
2015: Co founder Intravita Ltd (www.intravita.com)

Email: info@intravita.com | Phone: 01621 814 301
IntraVita Limited
104 Oak Road, Tiptree
Colchester
Essex
United Kingdom
w w w. i n t r a v i t a . c o m
CO5 0NA
reconsent
PROTOCOL SESSIONS
Wellness Formula (Modified Myers’ A)
Wellness Formula (Modified Myers’ B*) *Multi Nutrient single 100ml Vial
Super Wellness
Age Defiance
Anti Fatigue (Sports)
Detoxifying Fat Burner
Mood Support
Hair Tonic
Immuno Booster
ATP Energizer
Other:
Comments:
Patient Name:
Signature: Date: / /
Practitioner Name:
Place:

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CHAPTER 2: INTRAVENOUS MICRONUTRIENT SUPPLEMENTATION (IMS) 13

CHAPTER 3: ESSENTIAL MICRONUTRIENTS – VITAMINS 19

CHAPTER 4: GLUTATHIONE THE ‘MASTER’ ANTIOXIDANT 53

CHAPTER 5: ESSENTIAL MICRONUTRIENTS – MINERALS 59

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CHAPTER 7: SAFETY AND EFFICACY OF IVS 88

CHAPTER 8: MEDICAL HISTORY AND INFORMED CONSENT 101

CHAPTER 9: PRACTICAL FUNDAMENTALS 113

CHAPTER 10a: INTRAVITA IMS PROTOCOLS 118

CHAPTER 10b: IMS PROTOCOLS 120

CHAPTER 11: CHECK LIST & ADVERSE REACTION REPORTING 145

ABOUT THE AUTHOR 174

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1. GLOBAL MALNUTRITION IN UNDERDEVELOPED

In the developing world particularly, Vitamin A deficiency is a severe

Map of Vitamin A Deficiency Source: Bassett & Winter-Nelson, 2010

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WHO: “Using food availability data, it is estimated that zinc

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2. CLINICAL MICRONUTRIENT DEFICIENCIES IN DEVELOPED

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Magnesium deficiency [34] Vit B12 deficiency

Diabetes 25% of Dutch adults > 75 years old showed

Estimated 29% of cancer mortality in males [48] Thiamine deficiency

Calcium deficiency Choline deficiency

Omega-3 fatty acid deficiency

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However, excess consumption is far less of

Ascorbic acid deficiency

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Number of new cancer cases diagnosed worldwide for the years:

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Intravenous micronutrient supplementation Why then is IMS so popular and preferred to

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3. Hypotension leading to lightheadedness 13. Magnesium sulfate may cause headache

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Widespread contamination of the environment by endocrine-disrupting chemicals (EDCs) such

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Route of Supplementation: Orally Drug interactions

1.1. Vitamin A Orlistat (Alli®, Xenical®), a weight-loss

Although high beta-carotene intake has

“The Age-Related Eye Disease Study

Vitamin A deficiency is a known risk factor

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1. Sunlight: 5 – 30 minutes sun exposure of

2. Tanning beds: moderate use of 2% - 6%

1. Promotes calcium absorption in the GI

2. Needed for bone growth and bone

3. Prevention of rickets in children and

4. Together with calcium, vitamin D

5. Cell growth modulation, neuromuscular

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Inestine 1a25(OH)2D3 Tumour microenviroment

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4. Cancers of breast, colon, pancreas

Map of Vitamin A Deficiency Source: Bassett & Winter-Nelson, 2010