2. MAGNESIUM Mg At. No. 12 Atomic Mass: 24

3. Magnesium

4. Learning Objectives Dietary sources Daily Requirements Metabolism
Important functions and
Deficiency diseases

5. Introduction Mg acts as a cofactor in numerous enzymatic reactions,.
It performs many intracellular physiological functions.
Imbalance in Mg status—primarily hypomagnesaemia is commonly seen in clinical practice.
Common unwanted effects are neuromuscular, cardiac or nervous disorders.
Measuring total serum magnesium is a feasible and affordable way to monitor changes in magnesium status.

6. Introduction
Mg salts dissolve easily in water and are much more soluble than the respective calcium salts and is readily available to organisms
Mg plays an important role in plants and animal.
In plants, it is the central ion of chlorophyll .
In vertebrates, Mg is the fourth most abundant cation and is essential, especially within cells, being the second most common intracellular cation after K
Both these elements are vital for numerous physiological functions

7. Magnesium salts are used as antacids or laxatives in the form of magnesium hydroxide [Mg(OH)2], magnesium chloride (MgCl2), magnesium citrate (C6H6O7Mg) or magnesium sulphate (MgSO4).

8. Body content and Distribution
Total Mg in the average 70 kg adult person is about 24 g.
99% of total body Mg is located in bone, muscles and non-muscular soft tissue ..
Approximately 50–60% of it resides as surface substituent's of the hydroxyapatite mineral component of bone.

9. Body content and Distribution
Most of the remaining Mg is contained in skeletal muscle and soft tissue .
one third of skeletal Mg is exchangeable, serving as a reservoir for maintaining physiological extracellular Mg levels
Mg content of bone decreases with age.
Bone provides Mg to large exchangeable pool of buffers occurring due to acute changes in serum magnesium concentration . .

10. Blood Magnesium exists in blood partly bound to proteins.
Under conditions of physiological pH roughly 1/3 is “protein-bound”
The remainder 2/3rd is ionic.
C.S. Fluid: Concentration of Mg is high than in plasma.

11. Normal plasma levels:
Normal range of serum magnesium is 1 to 3.5 mg/dl
About 70% of magnesium exists in free state and remaining 30% is protein bound (primarily albumin)
Small amount is complexed with anions like phosphate & citrate

12. Magnesium is a cofactor in >300 enzymatic reactions.
Mg acts as a counter ion for the energy-rich ATP.
ATP is required universally for glucose utilization, synthesis of fat, proteins, nucleic acids and coenzymes, muscle contraction, methyl group transfer and many other processes.
interference with magnesium metabolism influences these functions .

13. Remember that
ATP metabolism, muscle contraction and relaxation, normal neurological function and release of neurotransmitters are all Mg dependent functions.
It is also important to note that Mg helps regulate vascular tone, heart rhythm, platelet-activated thrombosis and bone formation

14. Requirement
Humans need to consume Mg regularly to prevent its deficiency .
Values of ≥300 mg are usually recommended with adjusted dosages for age, sex and nutritional status.
Generally the recommendation is 310–360 mg and 400–420 mg for adult women and men, respectively.
Other recommendations in the literature suggest a lower daily minimum intake of 350 mg for men and 280–300 mg magnesium for women (355 mg during pregnancy and lactation).

15. Recommended Dietary Allowances
Infants 0 – mg
0.5 – mg
Children 1 – mg
4 – mg
7 – mg

16. Recommended Dietary Allowances
Adults Male Female
11 –
15 –
19 –
23 –
Pregnancy and Lactation mg

17. DIETARY SOURCES Drinking water accounts for ∼10% of daily Mg intake.
Green leafy vegetablesare the major source of Mg.
Nuts, seeds and unprocessed cereals are also rich sources.
Legumes, fruit, meat and fish have an intermediate Mg concentration.
Low Mg concentrations are found in dairy products

18. ABSORPTION
Average daily intake in humans is mg, much of which is obtained from green vegetables.
Roughly 1/3 of dietary Mg is absorbed
Remainder is passively excreted in feces.

20. ABSORPTION
Absorption takes place primarily in small intestine beginning within hour after ingestion
Continues at a steady rate for 2 to 8 hours
By that time 80% of total absorption has taken place .

21. Absorption and Homeostasis
Mg is absorbed in the gut and stored in bone mineral,
About 24–76% is absorbed in the gut and the rest is eliminated in the feces and urine.
Mg is mainly absorbed in the small intestine ,although some is also taken up via the large intestine .
Two transport systems for Mg in the gut are known.
Majority of Mg is absorbed in the small intestine by a passive mechanism, which is driven by an electrochemical gradient and solvent drag.
Mg homeostasis is maintained by intestine, bone and the kidneys.

22. METABOLISM
A minor, yet important, regulatory fraction of Mg is transported via the trans cellular transporter transient receptor potential channel melastatin member (TRPM) 6 and TRPM7
Intestinal absorption is not directly proportional to Mg intake but is dependent mainly on Mg status.
The lower the Mg level, the more of this element is absorbed in the gut, thus Mg absorption is high when intake is low and vice versa.
When intestinal Mg concentration is low, active transcellular transport prevails, primarily in the distal small intestine and the colon

23. Figure Legend:
A schematic overview of magnesium absorption pathways in the intestine, showing proteins associated with Mg2+ transport in enterocytes. In the intestinal epithelia, paracellular Mg2+ transport occurs via unidentified claudins, occuring concurrently with transcellular Mg2+ transport via transient receptor potential channel melastatin member 6 (TRPM6) and TRPM7 to facilitate Mg2+ absorption. 23

24. FACTORS AFFECTING ABSORPTION
Size of Mg load: Absorption is doubled when normal dietary Mg requirement is doubled and vice versa.
Dietary calcium: Increased absorption in calcium deficient diets.
Decreased absorption occurs in presence of excess of Ca.
A common transport mechanism from intestinal tract for both Ca and Mg suggested.

25. FACTORS AFFECTING ABSORPTION
Motility and mucosal state: In hurried bowel, absorption is decreased.
Absorption decreases in damaged mucosal state.
Vit-D: helps in increased absorption.
Parathormone: increases absorption.
Growth hormone: increases absorption

26. OTHER FACTORS: High protein intake increases absorption.
Fatty acids, phytates and phosphates decrease absorption.

27. Excretion
Magnesium is lost from the body in feces, sweat and urine. 2/3rd of orally taken Mg is lost through these routes
Sweat loss: Currently it is drawing attention; 0.75 mEq of Mg is lost daily in perspiration in normal health with normal diet. Loss is much increased with visible frank sweating.
Urine: Regulation of Mg balance is principally dependant on renal handling of the ion. In a normal healthy adult with normal diet 3 to 17 mEq are excreted daily.

28. EXCRETION
The kidneys are crucial in magnesium homeostasis ,as serum Mg concentration is primarily controlled by its excretion in urine.
Mg excretion follows a circadian rhythm, with maximal excretion occurring at night .
Under physiological conditions, ∼2400 mg of Mg in plasma is filtered by the glomeruli.

29. Of the filtered load, ∼95% is immediately reabsorbed and only 3–5% is excreted in the urine i.e. ∼100 mg.
Renal excretion of the filtered load may vary from 0.5 to 70%.
On one hand, the kidney is able to conserve Mg during Mg deprivation by reducing its excretion;
on the other hand, Mg might also be rapidly excreted in cases of excess intake . While reabsorption mainly depends on Mg levels in plasma.

30. Role of Hormones
Hormones play only a minor role (e.g. parathyroid hormone, anti-diuretic hormone, glucagon, calcitonin),
estrogen being an exception to this rule.

31. Hypomagnesaemia
Serum Mg concentrations ≤0.61 mmol/L (1.5 mg/dL) is considered as low.
Hypomagnesaemia is common in hospitalized patients .
A particularly high incidence of hypomagnesaemia is observed in intensive care units.
In these severely ill patients, nutritional magnesium intake was probably insufficient.

32. Role of drugs
Certain drugs have been associated with magnesium loss putting one at an increased risk for acute hypomagnesaemia.
Such medications include aminoglycosides,, digoxin, furosemide, amphotericin B and cyclosporine .
It is observed that in patients with severe hypomagnesaemia, mortality rates increase.
Therefore, assessment of magnesium status is advised, particularly in those who are critically ill.

33. Role of diseases
Deficiencies might also be triggered by increased Mg excretion in some medical conditions such as diabetes mellitus, renal tubular disorders, hypercalcaemia, hyperthyroidism or aldosteronism or in the course of excessive lactation or use of diuretics.

34. Clinical signs of hypomagnesaemia
Clinical signs of hypo- and hypermagnesaemia overlap often and are rather non-specific.
Manifestations of hypomagnasaemia might include tremor, agitation, muscle fasciculation, depression, cardiac arrhythmia and .
Early signs of magnesium deficiency include loss of appetite, nausea, vomiting and fatigue .

35. As Mg deficiency worsens, numbness, tingling, muscle contractions, cramps, seizures, sudden changes in behavior caused by excessive electrical activity in the brain, personality changes ,abnormal heart beat and coronary spasms might occur.

36. Severe hypomagnesaemia is usually accompanied by other imbalances of electrolytes such as low levels of calcium and potassium in the blood.
However, even in patients with severe hypomagnesaemia, clinical signs associated with magnesium deficiency may be absent .

37. Hypermagnesaemia
As the kidneys play a crucial role in Mg homeostasis, in advanced chronic kidney disease, the compensatory mechanisms start to become inadequate and hypermagnesaemia may develop.

38. Symptomatic hypermagnesaemia may be caused by excessive oral administration of Mg salts or Mg-containing drugs such as some laxatives and antacids , particularly when used in combination in the elderly and when renal function declines .
In addition, hypermagnesaemia may be seen when MgSO4 is given as an infusion for the treatment of seizure prophylaxis in eclampsia or erroneously in high doses for Mg supplementation .

39. Clinical signs of hypermagnesaemia
Serum magnesium concentrations, as reported in the literature, vary widely among patients with similar signs and symptoms.
In the beginning, no immediate clinical signs may be present and hypermagnesaemia might stay undetected for sometime .

40. Moderately elevated serum Mg levels may be associated with hypotension, cutaneous flushing, nausea and vomiting, but these symptoms mostly occur only upon infusion of MgSO4
At higher concentrations, Mg might lead to neuromuscular dysfunction, ranging from drowsiness to respiratory depression, hypotonia, areflexia and coma in severe cases.

41. Cardiac effects of hypermagnesaemia may include:
Bradycardia
uncharacteristic ECG findings such as complete heart block
Atrial fibrillation and
Asystole.
However, these findings are neither diagnostic nor specific for this metabolic abnormality.

42. FUNCTIONS 1. Constituent of Bones and Teeth:
About 70% of body magnesium is present as apatites in bones, dental enamel and dentin.
2. Is involved in active transport across cell membrane and helps maintain the electrical potential in nerves and muscle.

43. Functions 3. Magnesium acts as a co-factor
More than 300 enzymes requires magnesium as a cofactor
It is essential for peptidases, ribonucleases, glycolytic enzymes & co-carboxylation reactions
4. Magnesium influences the secretion of PTH by the parathyroid glands & hypomagnesaemia may cause hypoparathyriodism

44. FUNCTIONS
5. Magnesium exerts an effect on neuromuscular irritability similar to that of Ca2+, high levels depress nerve conduction & low levels may produce tetany (Hypomagnasemic tetany) Thus it helps maintain the electrical potential in nerves and muscle

45. FUNCTIONS
6. Insulin-dependent uptake of glucose is reduced in Mg2+ deficiency, magnesium supplementation improves glucose tolerance
7. Magnesium is required for DNA replication process (DNA Polymerase III )

46. 8. Neuromuscular Irritability:
Mg exerts an effect on neuromuscular irritability similar to that of Ca,
High levels depress nerve conduction and
Low levels may produce tetany (hypomagnasemic tetany).

47. THANKS