FNH 351 - Bone nutrients - magnesium

what are the metabolic functions of magnesium?

1. bone mineralization

2. enzymatic reactions

3. other roles:

   1. Blood clotting, reduced platelet aggregation

   2. Second messenger signaling

   3. Ion channel regulation (K and Ca channels)

   4. Antagonism of intracellular calcium

   5. Insulin production, release, and action signalling

how is magnesium involved in bone mineralization/structural component of bone?

50-60% of total body Mg is in the bones in the form of Mg(OH)2 and Mg3(PO4)2). Found on bone surface as available pool to maintain plasma Mg concentration. Together with calcium and phosphorus → forms bone crystal lattice. Mg likely deposited at time of bone formation and important for mineralization

how does magnesium function in enzymatic reactions?

it is a structural cofactor to stabilize enzyme of allosteric activator.

• It assists in stabilization of ATP and transfer of phosphate group

• enzymatic roles including in glucose, fat, protein, vitamin, and nucleic acid metabolism

• needed for hydroxylation of vitamin D in the 25-position (25-hydroxylase)

how is mg digestion

no digestion needed

how is mg absorbed?

• Where: small intestine

• How: in form of Mg2+

  1. Saturable, carrier-mediated, active transport via TRPM6 inhibited by high cytosolic Mg concentration

  2. Paracellular diffusion (main mechanism at high intakes) increases as Mg concentration in lumen increases

• Efficiency varies (30 – 60%); depending on Mg intake

what are the enhancers of mg bioavailability

• Vitamin D

• Protein

• Carbohydrates – fructose and oligosaccharides

what are the inhibitors of mg bioavailability?

• Phytic acid (whole-grain breads, seeds, legumes)

• Non-fermentable fiber (e.g. cellulose) increases the bulk of intestinal content reduces transit time → reduced time available for Mg absorption

• Unabsorbed fatty acids (in case of fat malabsorption; form soaps with Mg)

• Phosphorus (forming non-bioavailable complex Mg3(PO4)2)

how is mg transported?

→ In enterocyte

• Crosses cytosol

→ Across the basolateral membrane

• Na+-ATPase pump

→ Transport in blood, including hepatic portal vein

1. Free Mg2+ (50-55%) = physiologically active form

2. Bound to protein, mainly albumin (20-30%)

3. Complexed with sulfate, phosphate, and citrate (5-15%)

(1 and 3 in eq’m)

plasma m is tightly maintained. What is its homeostasis regulated at?

intestinal absorption and urinary excretion

how is mg excreted?

• Excretion mainly through kidney

• Fecal Mg

• minor losses (sweat)

what is Mg excretion thru kidney affected by?

• dietary Mg intake

• plasma Mg concentration

• PTH

what factors promote urinary Mg excretion?

• Diuretic medications

• Protein

• Alcohol

• Caffeine

what Mg is excreted through feces?

• unabsorbed Mg

• endogenous Mg sources

how is Mg homeostasis regulated?

serum Mg concentration underlies tight homeostatic regulation

what are the nutrient-nutrient interactions with Mg?

1. P and Mg

2. Ca and Mg

3. K+ and Mg

what is the nutrient-nutrient interaction between P and Mg?

Mg inhibits P absorption: with increasing Mg intake → decreasing P absorption due to formation and precipitation of Mg3(PO4)2

what is the calcium and Mg nutrient-nutrient interaction?

1. Low Mg associated with hypocalcemia: Mg2+ cofactor for 25-hydroxylase

2. Excess Mg interferes with calcium function:

   • Mg2+ reduces Ca2+ flux across membranes and activates Ca2+-ATPase pumps → reduce intracellular [Ca2+]

   • Mg2+ competes with Ca2+ for binding sites on troponin C and myosin → alters muscle contraction

   • Compete for reabsorption in the kidney

what is the nutrient-nutrient interaction btwn K and Mg?

• [Mg2+] influences extra-/intra-cellular potassium (K+) balance

  • Mg2+ depletion → increasing K+ efflux from cells and subsequent renal K+ excretion

what do non-specific symptoms of mg deficiency cause? what are they?

Delayed diagnosis

• Fatigue, lethargy, weakness

• Anorexia, nausea, vomiting

how is mg deficiency diagnosed?

• Plasma/serum magnesium concentration

• Routinely measured indicator, but not sensitive and debated cutoff

what are the metabolic consequences of Mg deficiency?

Magnesium deficiency leads to decreased serum concentration of calcium, potassium, and 1,25-(OH)2-D

what are symptoms of Mg deficiency?

1. neuromuscular impairment (e.g., tremors, latent tetany)

2. cardiovascular symptoms (e.g., rapid heart rate, higher blood pressure)

3. central nervous system

what can mg excess be caused by?

• Excessive magnesium from food sources does not cause toxicity, due to efficient renal excretion.

• Excessive intake possible from high-dose supplements.

what are symptoms of mg excess?

• Nausea, vomiting

• Depression

• Muscle weakness

• Paralysis