As natural healthcare practitioners, we all understand the pivotal and complex role that magnesium plays. Required for over 300 biochemical reactions and metabolic functions including cellular signalling, function & energy production, it is no surprise magnesium is one of the most used supplements in a clinician’s toolbox. Magnesium supplementation is, however, not as straightforward as we are led to believe. With considerations such as carrier, dose and bioavailability to consider, are we really doing clients (and magnesium) justice with a standard ‘go-to’ product? In this educational webinar, Dr Nina Bailey not only discusses magnesium in clinical practice but, importantly, also uncovers the perils and pitfalls of the magnesium supplement ‘scene’, in the quest to provide clinical excellence, and the important supplemental factors that must be considered to optimise magnesium status and provide clinical efficacy. Dr Bailey discusses: 1. A brief overview of the clinical implications of magnesium deficiency 2. Magnesium in practice: -Supporting digestive complaints and overcoming malabsorption -The importance of magnesium for structural support -Supporting energy levels and insulin sensitivity 3. How to ensure clinically effective dosing and supplementation

1. Dr Nina Bailey BSc, MSc, PhD, RNutr
1
OPTIMISING MAGNESIUM USE IN
CLINICAL PRACTICE

2. Magnesium functions
Role in active transport of ions across cell membranes - e.g. transport of
potassium and calcium which are essential for the conduction of nerve
impulses, muscle contraction, maintaining vasomotor tone and for normal
heart rhythm.
Plays a structural role - e.g. bones, proteins, enzymes, mitochondria,
DNA and RNA.
Plays a role in immunological functions - e.g. macrophage activation and
lymphocyte proliferation.
Magnesium is the second most abundant intracellular cation after potassium,
and is the fourth most abundant cation in the human body.
Acts as a cofactor for enzymes - e.g. those involved in protein synthesis, muscle and nerve
transmission, blood glucose and blood pressure regulation.
Magnesium is required for over 300 biochemical reactions.

3. Enzyme function (many involved in energy)
ATP-Mg (as the primary source of energy in cells, ATP must be bound to a magnesium ion to be biologically
active)
Protein kinase B (plays a crucial role in multiple cellular processes such as glucose metabolism, apoptosis, cell
proliferation, transcription and cell migration.
Hexokinase (glycolysis)
Creatine kinase (plays a major role in the production of energy)
Protein kinase (involved in phosphorylation –’switching on’)
ATPases & GTPases (involved in de-phosphorylation – ‘switching off’)
Na+ /K+-ATPase (involved in sodium/potassium regulation)
Ca2+-ATPase (involved in calcium regulation)
Adenylate cyclase (intracellular signalling – catalyses ATP into the secondary messenger cAMP)
Guanylate cyclase (involved in vasodilation [and therefore blood pressure regulation])
Phosphofructokinase (activated by magnesium and then phosphorylates fructose 6-phosphate in glycolysis
and therefore ATP production)
Creatine kinase (catalyzes the conversion of phosphocreatine, the energy reservoir for regeneration of ATP)
5-Phosphoribosyl-pyrophosphate synthetase (converts ribose 5-phosphate into phosphoribosyl
pyrophosphate (PRPP) which provides the ribose sugar for the synthesis of purines and pyrimidines, used in
the nucleotide bases that make up DNA & RNA)
ATP, adenosine triphosphate; GTP, guanosine triphosphate; K, potassium; Mg, magnesium; Na, sodium; Ca, calcium.
Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012 Feb;5(Suppl 1):i3-i14.
Magnesium functions

4. Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012 Feb;5(Suppl 1):i3-i14.
Magnesium functions
ATP is the monetary system of the body and the currency responsible for making all
metabolic reactions possible.
For ATP to be biologically active, it must be bound to a magnesium ion.
ATP is required for glucose utilisation, synthesis of fat, proteins, nucleic acids and
coenzymes, muscle contraction/relaxation & methylation, all magnesium-dependent
processes.
Long-term magnesium deficiency may have adverse effects on:
• Bone density
• Brain function
• Digestive system
• Nerve and muscle function

5. Magnesium and NMDA
The N-methyl-D-aspartate receptor (NMDA) is a glutamate receptor and ion channel
protein. When activated (e.g. by glutamate), it allows positively charged ions to flow
through the cell membrane.
The NMDA receptor is important for controlling synaptic plasticity and memory function.
Magnesium sits within the NMDA receptor
and must be removed to allow its activation,
thereby playing a regulatory role in NMDA’s
activity.
When magnesium levels are low, calcium and
glutamate freely activate the receptor -
leading to enhanced calcium influx, causing a
series of events that ultimately damages
mitochondria and can lead to cell death.

6. While glutamate is the primary excitatory neurotransmitter, gamma-aminobutyric acid
(GABA) is the chief inhibitory neurotransmitter that serves to balance glutamate .
Therefore both neurotransmitters work together to control many processes, including
the brain's overall level of excitation.
Magnesium and GABA
In addition to low magnesium status, an imbalance between GABA and glutamate is
exacerbated by dietary factors, stress & inflammation.
Glutamate decarboxylase
catalyzes the decarboxylation
of glutamate to
GABA (requires pyridoxal-5-
phostaphate and magnesium
as cofactors).

7. Serotonin
IDO
IFN-g, TNF-a,
IL-1, IL-6
Kynurenine
Quinolinic acid
NMDA agonist
3-Hydroxykynurenine
+
+
KMO
5-HTP
Neuronal damage Depression
Kynurenic acid
NMDA antagonist
NMDA receptor
Tryptophan
Sleep disturbance
IDO : indoleamine 2,3-dioxygenase
KMO : kynurenine monooxygenase
Glutamate
+
Cortisol
Low Mg

8. Magnesium and glutamate and GABA
These conditions are either associated with low magnesium
status, or respond to magnesium intervention:
• neurodegenerative disease
• epilepsy
• migraine
• CFS/FMS
• chronic pain
• brain trauma
• depression
• schizophrenia
• sleep disorders
• addiction
• osteoporosis
Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett. 2006 May 29;580(13):2994-3005.

9. Magnesium and addiction
Stress increases the vulnerability of an individual to addiction and low magnesium
status increases the risk of relapse
Nechifor M. Magnesium in drug abuse and addiction. Magnesium in the Central Nervous System [Internet]. Adelaide (AU):
University of Adelaide Press; 2011. https://www.ncbi.nlm.nih.gov/books/NBK507260
Magnesium supplementation:
 decreases dopamine synthesis and release in brain
 decreases the activity of glutamate NMDA receptors
 increases glutamate metabolism (as the main excitatory
amino acid involved in addiction) by enhancing
glutamate decarboxylase activity
 increases GABAergic activity

10. Magnesium and migraine
• Maintenance of normal plasma levels of magnesium ions is required for proper
function of blood vessels ; hypomagnesemia is a factor predisposing migraine
patients to vascular spasm (where blood vessels suddenly tighten causing pain)
• A decrease in magnesium levels is observed during migraine attacks which may be
related to an increase in urinary excretion of magnesium ions during a migraine
attack, contributing to hypomagnesemia
Chiu HY, Yeh TH, Huang YC, Chen PY. Effects of Intravenous and Oral Magnesium on Reducing Migraine: A Meta-analysis of Randomized
Controlled Trials. Pain Physician. 2016 Jan;19(1):E97-112.
• In a 2016 meta analyse (21 studies), intravenous magnesium
was shown to significantly relieve acute migraine within 15 –
45 minutes, 120 minutes and 24 hours after the initial infusion
• Oral magnesium significantly alleviated the frequency and
intensity of migraine

11. Magnesium plays a central role in mineral homeostasis, regulating PTH
secretion and action and vitamin D activation.
Magnesium and bone health
Castiglioni S, Cazzaniga A, Albisetti W, Maier JA. Magnesium and osteoporosis: current state of
knowledge and future research directions. Nutrients. 2013 Jul 31;5(8):3022-33.

12. Magnesium and osteoporosis
• Magnesium intake is found to be positively correlated with greater bone
mineral density in both men and women
• Low serum magnesium is associated with low bone density in both pre-
and postmenopausal women
• Magnesium intake reduces the risk of osteoporotic fractures in middle-
aged men and women
• Magnesium supplements improve bone mineral density in osteoporotic
women and in young people
Tranquilli A. L., Lucino E., Garzetti G. G., Romanini C. Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal
women. Gynecological Endocrinology. 1994;8(1):55–58.
Orchard T. S., Larson J. C., Alghothani N., et al. Magnesium intake, bone mineral density, and fractures: results from the Women’s Health Initiative Observational Study. The
American Journal of Clinical Nutrition. 2014;99(4):926–933.
Carpenter T. O., DeLucia M. C., Zhang J. H., et al. A randomized controlled study of effects of dietary magnesium oxide supplementation on bone mineral content in healthy
girls. The Journal of Clinical Endocrinology & Metabolism. 2006;91(12):4866–4872.

13. Magnesium and insulin sensitivity
• Magnesium is required for glucose utilisation and insulin signalling
• Magnesium depletion is common in both insulin resistant individual and
in diabetics
• Low intracellular magnesium levels will result in defective tyrosine
kinase activation and reduced insulin receptor activation and signalling
• Magnesium improves the ability of b-cells
to compensate for variations in insulin
sensitivity in non-diabetic individuals
• Magnesium may help lower blood glucose
levels via increased GLUT4 mRNA expression,
independent to insulin secretion
https://www.coursepics.com/lesson/tyrosine-kinase-receptor/

14. Magnesium and insulin sensitivity
• Magnesium supplementation improves insulin sensitivity, b-cell function,
and fasting glucose levels, in both diabetic and non-diabetic subjects
• Magnesium supplementation reduces blood pressure, hyperglycaemia,
and hypertriglyceridaemia, all of which are related to metabolic syndrome
• Optimising magnesium status may delay the progression from impaired
glucose regulation to type II diabetes and aid in the treatment of diabetes
Ozcaliskan Ilkay H, Sahin H, Tanriverdi F, Samur G. Association Between Magnesium Status, Dietary Magnesium Intake, and Metabolic Control in Patients with Type
2 Diabetes Mellitus. J Am Coll Nutr. 2018 Aug 30:1-8.
Zghoul N, Alam-Eldin N, Mak IT, Silver B, Weglicki WB. Hypomagnesemia in diabetes patients: comparison of serum and intracellular measurement of responses
to magnesium supplementation and its role in inflammation. Diabetes Metab Syndr Obes. 2018 Aug 2;11:389-400.
Mooren FC, Krüger K, Völker K, Golf SW, Wadepuhl M, Kraus A. Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects - a double-blind,
placebo-controlled, randomized trial. Diabetes Obes Metab. 2011 Mar;13(3):281-4.
Simental-Mendía LE, Sahebkar A, Rodríguez-Morán M, Guerrero-Romero F. A systematic review and meta-analysis of randomized controlled trials on
the effects of magnesium supplementation on insulin sensitivity and glucose control.
Pharmacol Res. 2016 Sep;111:272-282.

15. Digestive disorders and magnesium
A number of factors that influence the health of the stomach and small
intestine, leading to malabsorption issues, include:
• damage to the intestine (infection, inflammation or surgery)
• leaky gut syndrome
• irritable bowel syndrome
• Crohn’s disease
• hypochlorhydria
• chronic pancreatitis
• coeliac disease
• cystic fibrosis
• prolonged use of antibiotics/PPIs
• dysbiosis/SIBO
Low magnesium status is common in these conditions, predisposing individuals to
further health issues. While supplementation is beneficial, choosing a supplement
to overcome absorption barriers is essential.

16. Factors relating to magnesium deficiency
• Reduced intake
– food choices, cooking methods, processing, etc
• Reduced absorption (including hypochlorhydria)
– bowel disease, low vitamin D status, drugs (e.g. PPIs)
• Loss of magnesium
– diarrhoea, sweating, laxatives, drugs (e.g. diuretics)
• Increased requirements
– pregnancy & stress
• SNPs
– transcellular transporters TRPM6 and TRPM7
• Underlying health conditions
– diabetes, hypertension, menopause, osteoporosis
Sufficiency
Deficiency
Insufficiency

17. Deficiency of magnesium is linked to various
disorders and systems
Symptoms that may indicate low magnesium status
• Anxiety/irritability/nervousness
• Low energy/fatigue/feeling of weakness
• Sleep disturbances
• Headaches
• Muscle tension/weakness/cramps
• ‘Restless leg’ syndrome
• Low mood
• PMS & hormonal imbalances
• Carbohydrate craving
• Cardiac arrhythmia /atrial fibrillation

18. Factors affecting magnesium status where magnesium
supplementation is advised
Reduced intake (via diets high in heavily refined and/or processed foods, diets low
in whole foods)
Reduced absorption ( bowel diseases, vitamin D deficiency, malabsorption issues)
Drugs that lower magnesium absorption (proton pump inhibitors, antihistamines
[specifically H2 Receptor Antagonists])
Magnesium loss via digestive tract (via the use of laxatives, diarrhoea or vomiting)
Increased renal loss (diabetes, alcohol use, renal disease, use of diuretics)
Regular and/or intensive sports (where magnesium is lost via excessive sweating)
Increased requirements (pregnancy, stress, anxiety, menopause, increasing age
[age 40+])
Preexisting health conditions (cardiovascular disease, diabetes, osteoporosis)

19. Health conditions and diseases associated with low magnesium
status for which magnesium therapy is or may be beneficial
Arrhythmia Migraine Parkinson’s
Stroke Depression Schizophrenia
Myocardial infarction Epilepsy Bipolar disorder
Hypertension Muscle cramps Addiction
Coronary disease Brain injury Stress
Vascular calcification COPD Asthma
Diabetes Cancer Cystic fibrosis
Chronic fatigue syndrome Fibromyalgia Alcoholism
Preeclampsia Osteoporosis Liver disease
Health conditions and diseases associated with low magnesium status to which magnesium therapy is, or may be beneficial (Geiger &
Wanner 2013; de Baaij et al., 2015)
Geiger H, Wanner C. Magnesium in disease. Clin Kidney J. 2012 Feb;5(Suppl 1):i25-i38.

20. Magnesium sources
• Magnesium is widely distributed in foods of both plant
and animal origin
• As chlorophyll is the magnesium chelate of porphyrin,
green leafy vegetables are particularly rich in magnesium
• Vegetables, grains, legumes and nuts (and some fish and seafood)
generally have a higher magnesium content (60-2700 mg/kg) compared to
animal products such as meat and dairy (<280 mg/kg)
• Refined wheat, barley, rye or rice flour have less magnesium compared to
whole grain products
• In addition, tap & bottled water can also make a significant contribution to
dietary intake of magnesium (higher in hard water than soft water ~ 30
mg/L)

21. • Oxalic acid interferes with magnesium absorption - steaming (but not
boiling) leafy green vegetables can significantly reduce oxalic acid
concentrations.
Foods high in oxalates include spinach, leafy greens, nuts, tea, coffee and
cacao.
Organic greens which may be naturally higher in magnesium due to
differences in fertilisers used.
• Phytic acid interferes with magnesium absorption in the gut – soaking
beans and grains before cooking can significantly reduce phytic acid
concentrations.
Foods high in phytates include
wholegrain, nuts and legumes.
• Soaking nuts, and sprouting seeds
and legumes helps to reduce levels
of oxalic and phytic acid.

22. Given that the UK population fails to achieve the 5-a-day in terms of fruit
& vegetable intake, it is likely (as seen in USA where intake of
magnesium <50% requirements) that intake may be insufficient to
sustain adequate requirements:
– 8% of children aged 11 to 18 met their 5-A-Day (mean consumption:
2.8 portions per day)
Why dietary sourced magnesium may not always be enough to maintain sufficiency
– 25% of adult males & 28% of adult females aged 19 to 64 met their 5-A-Day (mean
consumption: 4 portions per day)
– 34% of adult males & 35% of adult females aged 65+ met their 5-A-Day (mean
consumption: 4 portions per day)
– the average mean consumption of oily fish in all age groups
remained well below the recommended one portion (140g)
per week (13–29 g per week in children & 54–87g per week
in adults)
.
National Diet and Nutrition Survey. Results from Years 5-6 (combined) of the Rolling
Programme (2012/13 – 2013/14)

23. Average daily intake of magnesium as a % of the Reference Nutrient Intake (RNI) from food
sources only and proportion of participants with average daily intakes below the Lower
Reference Nutrient Intake (LRNI)
Males (age) Females (age)
4-10 11-18 19-64 65+ 4-10 11-18 19-64 65+
Mean % RNI 128 81 98 88 116 67 87 84
% with intake below LRNI 0 27 12 16 3 48 11 15
The synergistic relationship between vitamin D and magnesium also sheds light on
the low status of magnesium that is common in the UK
Vitamin D enhances magnesium absorption (and reabsorption) and magnesium is
essential for the absorption and metabolism of vitamin D to calcitrol. Thus,
suboptimal vitamin D and/or magnesium levels will have a number of potential health
consequences. (Uwitonze & Razzaque 2018).
National Diet and Nutrition Survey. Results from Years 5-6 (combined) of the Rolling Programme (2012/13 – 2013/14)
Uwitonze AM, Razzaque MS. Role of Magnesium in Vitamin D Activation and Function. J Am Osteopath Assoc. 2018 Mar 1;118(3):181-189.

24. The synergistic relationship that exists between vitamin D and magnesium also sheds
light on the low status of magnesium that is common in the UK.
Approx 1/5th of those tested had suboptimal vitamin D level below 25 nmol/L.
Thus suboptimal vitamin D levels and/or magnesium will have a number of potential
health consequences. (Uwitonze & Razzaque 2018).
National Diet and Nutrition Survey. Results from Years 5-6 (combined) of the Rolling Programme (2012/13 – 2013/14)
Uwitonze AM, Razzaque MS. Role of Magnesium in Vitamin D Activation and Function. J Am Osteopath Assoc. 2018 Mar 1;118(3):181-189.
Mean concentrations of 25(OH)D (nmol/L)
and % below 25 nmol/L*
Males (age) Females (age)
11-18 19-64 65+ 11-18 19-64 65+
25(OH)D (nmol/L)
Mean concentration
45 42.4 43.4 47.8 45.3 47.9
% below 25 nmol/L 17 22 21 15 15 9
*According to the National Osteoporosis Society 30-50 nmol/L is considered to be sufficient within the UK

25. • Processing is known to remove many nutrients found in food, so
avoid/restrict processed and refined foods
• Be aware that sodium and calcium both compete with magnesium
for ion channels
• Manage stress and anxiety – both result in loss of magnesium
• Reduce the consumption of coffee,
carbonated drinks and especially
alcohol – not only do they increase
magnesium excretion but they can also
reduce magnesium absorption.
Avoiding deficiency

26. Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012 Feb;5(Suppl 1):i3-i14
The normal adult human body contains approximately 1,000
mmols of magnesium (~24.4 g).
~30% of magnesium in the bones is exchangeable, functioning
as a reservoir to stabilise the serum concentration (which
makes up less than 1% total magnesium).
This serum concentration is regulated by the balance and
interplay between intestinal and renal transport coupled with
this bone exchange.
• Normal total serum magnesium concentration (healthy individuals) is in the
range of 0.7–1.1 mmol/l. In order to maintain these levels, a minimum daily
magnesium intake of about 3.6 mg/kg (~300mg for a 85kg person) is necessary.
• Hypomagnesaemia is usually defined as serum magnesium <0.7 mmol and
symptoms usually occur when serum magnesium levels fall below 0.5 mmol/l.
• The reference range for the RBC test is between 1.65 and 2.52 mmol/l.

27. M de Francisco AL, Rodríguez M. Magnesium - its role in CKD. Nefrologia. 2013;33(3):389-99.
de Baaij JH, Hoenderop JG, Bindels RJ. Regulation of magnesium balance: lessons learned from human genetic disease. Clin Kidney J. 2012 Feb;5(Suppl 1):i15-i24.
Magnesium regulation
‘Excess’ magnesium cannot be
stored and ingested magnesium is
only retained for current needs, a
higher absorption is usually followed
by a higher excretion of the mineral
and so an individual’s magnesium
status is influential.
A daily net uptake of ∼100 mg in the
intestine results in a balanced 100
mg excretion in the kidney, whereas
in times of magnesium shortage,
other tissues such as bone and
muscle provide magnesium to
restore blood magnesium levels.

28. Tissue
Body weight
(kg)
Concentration
(mmol/kg)
Content
(mmol)
% total body
magnesium
Serum 3 0.85 2.6 0.3
Red blood cells 2 2.5 5 0.5
Soft tissues 22.7 8.5 193 19.2
Muscles 30 9 270 27
Bone 12.3 43.2 530 53
Total 70 64 1000 100
Distribution of magnesium in the adult human being, molar mass of magnesium = 24.305
Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012 Feb;5(Suppl 1):i3-i14
Approximately 55-70% of serum
magnesium exists in the ionised, free,
physiologically active form, which is
important for its physiological functions,
with 5-15% complexed with serum anions
and 20-30% albumin-bound.

29. Positive effects of magnesium supplementation are more likely to
be observed in those who are compromised or depleted in some
way.
As 99% of magnesium is intracellular within bones, muscles and
brain tissue, accurate determination of actual levels of magnesium
is challenging.
• Serum – a common test, but as serum only represents 1% total magnesium the test
result can show ‘normal’ but intracellular magnesium levels may be low
• RBC – measures intracellular concentrations and so is more reflective of actual
magnesium status
• Ionic - most accurate of the blood tests (60% of magnesium exists in the ionised state) –
less common due to complex procedure and cost
• Exa Test – measures magnesium from a cheek swab (represents soft tissue) and again is
less common due to the specialist nature of the test
• Loading/Tolerance Test – moderately accurate – measures magnesium in the urine after
oral exposure with a known amount of magnesium – requires 24 hour urine collection –
less common

30. Magnesium absorption
• Magnesium absorption in human
intestines starts approximately 1 hour
after intake, with absorption reaching
a plateau after 2 to 5 hours before it
then declines
• At 6 hours, magnesium absorption is about 80% complete
• Fast transit time and damaged mucosal tissue reduce the time of
interaction between diet and the mucosa, increasing the risk of impaired
magnesium absorption
• Physical factors influenced by the diet include pH, the amount of
magnesium consumed, volume and viscosity of the meal and
gastrointestinal transit time

31. Magnesium absorption
The majority of magnesium is
absorbed in the small intestine,
although some (but not much) is
also taken up via the large intestine.
Intestinal absorption is not directly proportional to magnesium intake
but is dependent mainly on current magnesium status – the lower the
intracellular magnesium level, the more is absorbed, so relative
magnesium absorption is high when intake is low and vice versa.
This implies that under normal circumstances (i.e. there are no
underlying causes that would stop absorption), unless you are deficient,
most magnesium passes through unabsorbed.

32. Magnesium supplementation considerations
• Soluble vs insoluble
• Salt vs chelate
• Optimising absorption pathways
• Choosing carriers for enhanced benefits
• Synergistic benefits of using multiple carriers
• Elemental magnesium fraction
• Buffered vs blends vs fully reacted
• Fractional absorption & split dosing

33. Choosing absorbable and synergistic ‘carriers’
Magnesium ions are highly reactive, unstable and easily form
compounds with other substances – hence magnesium
supplements are never ‘pure’ magnesium.
Magnesium ions bind with negatively charged molecules
(anions) to form salts or can bind with amino acids to form
amino acid complexes.
Organic complexes Bisglycinate, taurate
Organic soluble salts Citrate, lactate, gluconate
Inorganic soluble salts Chloride, sulfate
Inorganic insoluble salts Oxide, carbonate, hydroxide
Increasingbioavailability

34. Choosing absorbable and synergistic ‘carriers’
For magnesium to be absorbed via an ion channel, it must first be
liberated from its carrier – in the case of insoluble magnesium,
this is a pH-dependent process and the ability to break this bond
is dependent on the ability to produce adequate stomach acid -
thus individuals with hypochlorhydria should avoid inorganic
insoluble salts.
Organic forms (carbon containing) are, by nature, more
bioavailable than inorganic – we choose both organic and soluble
forms of magnesium.
Symptoms of hypochlorhydria
Bloating &/or wind, especially after meals
Heartburn, indigestion
Abdominal tightness
Bad breath
Undigested food in stools
Constipation
Abdominal tightness / cramping
Anaemia

35. Magnesium
source
Magnesium
content
Solubility Bioavailability
Oxide 60% Insoluble Low
Sulfate 20% Moderately soluble Low
Hydroxide 41% Insoluble Low
Carbonate 28.5% Insoluble Low
Chloride 25% Soluble High
Citrate 16% Soluble High
Gluconate 6% Soluble High
Glycinate 10% Soluble High
Aspartate 8% Soluble High
Taurinate 6.5% Soluble High
Many cheap competitive products will use oxide or blends of oxide, with the focus
on delivering a product with a high elemental fraction, while disregarding its
extremely poor bioavailability estimated at ~4%.
Comparison of element fractions from different magnesium sources

36. Magnesium ions are liberated by the acidic environment of the
stomach and the ‘free’ ions move through the gastrointestinal
tract
The magnesium ions liberated from magnesium salts then have
two pathways to absorption:
Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012 Feb;5(Suppl 1):i3-i14
 Paracellular transport accounts for the
majority (80%–90%) of magnesium
uptake and is pH dependent.
 Transcellular transport is a minor
route of uptake and occurs when
magnesium intake is low (and occurs
mainly in the caecum and colon).

37. While paracellular transport accounts for the majority
of uptake, there are barriers to overcome:
Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012 Feb;5(Suppl 1):i3-i14
– pH dependent (as unstable ions move along the
gut, they start to bind other substances (thus
shifting from soluble back to insoluble)
– A ‘hydrogen shell’ forms around any remaining
‘free’ magnesium ions which become too large
to fit through the ion channel
– While tight junction proteins are capable of removing the water from
magnesium’s hydrogen shell (thereby allowing the ion to then pass through)
these proteins do require a very specific pH (between 5.5 and 6.5) to be able
to function
– Magnesium transport is mainly restricted to areas that lack the tightening
claudins (and hence are more ‘leaky’) such as the ileum and distal parts of
the jejunum

38. Overwhelming a single pathway of absorption with a
single source of magnesium will significantly limit
magnesium uptake. This can be overcome by simply
increasing the routes of passage.
We use three form of magnesium and choose the most
absorbable and synergistic carriers. By combining
magnesium citrate salt with magnesium chelates (glycine
and taurine) which target pathways related to protein
uptake not ion channels (meaning magnesium gets a
‘free-pass’):
– Dipeptide channels (for peptides composed of two
amino-acid residues)
– Amino acid transporters (for single amino acids)
Gly
Mg
Gly
Magnesium
bisglycinate targets
dipeptide channels
Tau
Mg
Magnesium taurinate
targets amino acid
transporters

39. However, magnesium citrate salts are a great source of
soluble bioavailable magnesium (with a high elemental load)
but you need to keep the pH low!
Taurine and glycine (as pH buffers) also help keep the pH lower
for longer along the gastrointestinal tract, which can aid in the
paracellular absorption of ions from magnesium citrate.
Gly Tau
MgMg Mg
Gly
Magnesium
bisglycinate
targets dipeptide
channels
Magnesium
taurinate targets
amino acid
transporters
Magnesium citrate creates free
magnesium ions that target
paracellular and transcellular
routes of uptake
Mg

40. Magnesium chelates are lower in elemental magnesium than
magnesium citrate but they bypass ion channels leading to
efficient, unopposed absorption
• The bond between the magnesium ion and its amino acid ‘carrier’ molecule
is highly resistant to the acidic environment of the gastrointestinal tract; as
a result absorption of chelated magnesium is not a pH dependent process
as magnesium is not required to be released as a ‘free-ion’
• Magnesium chelates prevent the formation of magnesium ions, resulting in
no formation of insoluble compounds with phosphates, phytates or tanins
which would render magnesium unabsorbable (and primed for excretion)
• As there are more dipeptide channels than there are ion channels,
magnesium complexes do not have to compete for ion channels used by
other minerals (magnesium, for example, competes with calcium)
Herroeder S, Schönherr ME, De Hert SG, Hollmann MW. Magnesium--essentials for anesthesiologists. Anesthesiology. 2011 Apr;114(4):971-93.

41. Triple Magnesium targets 4 different, unopposing
pathways:
Magnesium citrate targets:
paracellular ion channels
transcellular ion channels
Using two different chelate forms increases uptake via
different amino acid specific pathways:
Magnesium bisglycinate targets dipeptide channels
Magnesium taurate targets amino acid transporters
Mg
Paracellular
transport
Amino acid
transport
Dipeptide
channels
Transcellular
transport

42. • While a product may have a label claim of magnesium citrate,
magnesium bisglycinate or magnesium taurate, unless it clearly
states that the product contains fully reacted magnesium, much
of your elemental claim will come from magnesium oxide
• Magnesium oxide delivers an impressive 60% elemental
magnesium, but is both inorganic and insoluble, meaning that it
is extremely poorly absorbed (~4%) and most simply passes
through the gastrointestinal tract (often resulting in unpleasant
laxative side effects)
• Many magnesium formulas use magnesium oxide as a base to
boost the label claim for the elemental amount of magnesium –
unsurprisingly this is seldom disclosed on the packaging
Triple magnesium is great, but only if they are fully
reacted magnesium forms!!

43. – Magnesium blends simply blend
magnesium oxide with a carrier such as
citrate.
– Fully reacted magnesiums form complexes
and are directly bound to the carrier. Only
fully reacted products contain no
magnesium oxide.
– Buffered products combine fully
reacted magnesium with magnesium
oxide (better than blends, but not as
good as fully reacted).
Mg Citrate
Oxide
Mg
Citrate
Mg
Citrate
Mg
Oxide
So we can see how fully reacted magnesium is the superior choice!

44. The net intestinal magnesium absorption is affected by:
– the absorption capacity of a specific segment of intestine
– the length of that intestinal segment
– transit time (total and by segment)
– mucosal integrity
– pH of the lumen
– gastric emptying
– size of meal
– use of motility and antimotility drugs
As a result of the above, taking all of your magnesium in one go may well limit its
absorption. For example, the capability of the duodenum and jejunum to absorb
magnesium is high, but because these segments are short and transit time through them
is rapid their actual contribution to total magnesium absorption is much lower than the
ileum, which has a lower capacity to absorb but is significantly longer in length and has a
slower transit time.

45. What about dose?
Site Magnesium
absorption
(mg/day)
% absorption
of intake
Fractional
absorption
rate
Segment
length
Transit
time
Stomach 0 0 n/a n/a n/a
Duodenum 15 5 High ~26 cm Rapid
Jejunum 30 10 High ~2.5 m Rapid
Proximal ileum 45 15 Low Long Slow
Distal ileum 30 10 Low Long Slow
Colon/ceacum 15 5 Low Long Slow
Total 135 45
Herroeder S, Schönherr ME, De Hert SG, Hollmann MW. Magnesium--essentials for anesthesiologists. Anesthesiology. 2011 Apr;114(4):971-93.
Could split dosing overcome barriers for efficient absorption?

46. Split dosing increases magnesium uptake and
retention more effectively than single dosing
The relative absorption of magnesium is inversely related to the ingested dose
– so the quantity of magnesium in the digestive tract is the major factor
controlling the amount of magnesium absorbed:
– Magnesium absorption is not the same as magnesium retention
– High plasma levels can lead to increased magnesium excretion
– Low dose magnesium taken several times a day is better absorbed and
retained
– Low elemental magnesium is also less likely to cause diarrhoea
(reduced even more by using chelates and fully reacted forms)
Taking 300 mg magnesium as 3 x 100 mg will raise magnesium status more
effectively than one single 300 mg dose!

47. THE EVIDENCE MAGNESIUM LOAD
Study LOW MEDIUM HIGH
Study 1 Magnesium intake 23mg 243mg 550mg
(n=8) Magnesium absorbed 75.8% 44.3% 23.7%
Magnesium absorbed 17.4mg 107.7mg 130.4mg
Study 2 Magnesium intake (mg/d) 32mg 102mg 304mg
(n=13) % magnesium absorbed 48% 29% 20%
15.4mg 29.6 60mg
Study 3 Magnesium intake (mg/d) 36mg 273mg 974mg
(n=8) % magnesium absorbed 65% 21% 11%
Magnesium absorbed 23.4mg 57.3mg 107mg
Study 1: Graham LA, Caesar JJ & Burgen ASV (1960) Gastrointestinal absorption and excretion of Mg-28 in man. Metabolism-Clinical and Experimental 9, 646-659.
Study 2: Roth P & Werner E (1979) Intestinal absorption of magnesium in man. International Journal of Applied Radiation and Isotopes 30, 523-526.
Study 3: Fine KD, Santa Ana CA, Porter JL, Fordtran JS. Intestinal absorption of magnesium from food and supplements. J Clin Invest. 1991 Aug;88(2):396-402.

48. It’s not just about magnesium but the synergistic benefits of the
carrier molecule!
 Glycine is a highly versatile amino acid and is involved in collagen formation,
creatine formation (muscles), glutathione production, haemoglobin
production, and is an inhibitory neurotransmitter
– the two glycine molecules occupy the reactive sites of magnesium, preventing it from
forming insoluble complexes (i.e. with phytates)
– glycine helps lower the luminal acidity thereby improving paracellular transport of
magnesium ions
– has no laxative effects
 Taurine acts as an antioxidant, helps improve insulin sensitivity but best
known for its cardiovascular benefits and for its positive influence on bone
metabolism
– taurine helps lower the luminal acidity thereby improving paracellular transport of
magnesium ions
– has no laxative effects
 Citrate feeds into the citric acid cycle to help support energy
– fully reacted citrate overcomes the high level of insoluble magnesium ions associated with
buffers and blends and therefore has no laxative effects

49. Take-home messages
Magnesium levels can be restored via supplementation
Excess magnesium cannot be stored, making ‘mega dosing’ unnecessary and
wasteful
• Focus instead on minimising barriers to absorption and optimising uptake
• Higher magnesium plasma levels lead to increased magnesium excretion
• Urinary magnesium excretion is a marker of magnesium retention
• Higher amounts of magnesium often lead to gastrointestinal problems
(osmosis)
• Lower dosages of magnesium are better absorbed and less is excreted
• Better to take smaller amounts of highly bioavailable magnesium forms
For optimal outcomes, it is best to take magnesium supplements
• at lower dosages (65 mg per serving)
• several times a day (2–3 times)
• for a long period of time (minimum 3–6 months)

50. Igennus Triple Magnesium summary
• Soluble vs insoluble
– we only use soluble magnesium
• Salt vs chelate
– we use a synergistic blend to optimise uptake
• Optimising absorption pathways
– Triple Magnesium targets 4 different unopposing
pathways
• Choosing carriers for enhanced benefits
– it’s not just about magnesium but the synergistic
benefits of the carrier molecules

51. Igennus Triple Magnesium summary
• Synergistic benefits of using multiple carriers
– acting as buffers, our chelates help create the optimal
environment to aid magnesium uptake from citrate
• Elemental magnesium fraction
– we avoid using magnesiums with a high (but insoluble)
elemental fraction, choosing instead to focus on carriers with
proven enhanced absorption
• Buffered vs blends vs fully reacted
• with fully reacted magnesium, you can be confident that you
are not getting hidden magnesium oxide
• Fractional absorption & split dosing
• we advocate split dosing to enhance uptake and retention of
our magnesiums

52. • ADVANCED TRIPLE MAGNESIUM BLEND:
combining magnesium citrate, taurate and
bisglycinate enhances magnesium absorption by
utilising multiple magnesium uptake pathways,
avoiding saturation. Taurine and glycine are highly
effective carriers for magnesium.
• FULLY REACTED FORMULA: only fully reacted (not
blended or buffered) magnesium forms are free
from poorly absorbed magnesium oxide. The
enhanced solubility of these fully reacted
magnesium forms optimises absorption potential.
• MULTIPLE HEALTH BENEFITS: magnesium supports
normal energy release, muscle function, electrolyte
balance, nervous system function and normal
psychological function.
• CONSISTENT PRODUCT QUALITY GUARANTEED:
manufactured in the UK in GMP-accredited
facilities.

53. • FULL TRANPARENCY: unlike many of our
competitors who combine two or more
magnesium sources without disclosing the
ratios (which can mislead consumers into
thinking a product is high in a specific
magnesium), we list the bulk and elemental
amounts of each of our magnesiums.
• NO UNNESSESARY FILLERS: we choose to
encapsulate our magnesiums to avoid the use
of bulking agents commonly found in tablets.
• SPLIT DOSING FOR ENHANCED UPTAKE: as the
relative absorption of magnesium is inversely
related to the ingested dose, magnesium
absorption is significantly improved by taking
smaller doses throughout the day.
• WE DELIVER 52 % RI: because it’s not how
much you take, but how much you retain.
Excess magnesium cannot be stored and our
ethos is to focus on efficacy of delivery by
tripling our magnesium with the most
absorbable and synergistic ‘carriers’ that target
multiple, unopposed uptake pathways.

54. Dr Nina Bailey
Head of Nutrition
ninab@igennus.com
Get in touch