Electrolytes

• Recommended daily intakes
• Low-sodium salt (LoSalt)
• Food sources
  • Typical daily intake
• Supplements
  • Amount needed
    • Sodium and potassium
      • References
    • Magnesium and calcium
      • References
  • When to take
• Potassium
  • ECG
    • References
  • Deficiency symptoms
    • References
• Magnesium
  • Atrial fibrillation
  • Calcium/magnesium ratio
    • References
  • ECG
    • References
  • Deficiency symptoms
    • References
  • Cardiovascular
    • References

Recommended daily intakes

Data from NHS - click on electrolyte name for source.

Molecular weight of salt (NaCl) is 23+35.5 = 58.5. So salt contains 23/58.5*100 = 39% sodium.
Molecular weight of KCl is 39+35.5 = 74.5. So KCl contains 39/74.5*100 = 52% potassium.

Low-sodium salt (LoSalt)

LoSalt contains 34.6% potassium and 13.3% sodium (66% KCl and 34% NaCl)

3.5g of potassium would be provided by 100/34.6*3.5 = 10g of LoSalt.

10g of LoSalt would provide 1.3g of sodium.

BNF recommend 2-4 g KCl daily (in divided doses) for prevention of hypokalemia (patients on normal diet). This would be provided by 3-6 g LoSalt daily.
3-6 g LoSalt would provide 0.4-0.8 g Na.

Food sources

Electrolyte content of foods in mg/100g. From Cofids spreadsheet.

Typical daily intake

Typical daily intake for Monica, assuming 5 portions of veg/fruit.

Note that the ratio of calcium to magnesium is about 5, much higher than the recommended 2, so any supplementation needs to tkae this into account. See notes on supplements and calcium/magnesium ratio below.

Supplements

Amount needed

Sodium and potassium

RDI for potassium is 3.5g, but typical daily intake from food is only 2.3g, so need supplement of 3.5 - 2.3 = 1.2g.

1.2g of potassium would be provided by 100/34.6*1.2 = 3.5g of LoSalt.

Target daily intake for sodium is at least 2.4g.
Food typically provides 0.9g.
3.5g of LoSalt provides 3.5*13.3/100 = 0.5g.
So need sodium supplement of at least 2.4-0.9-0.5 = 1.0g, which would be provided by 1.0*100/39 = 2.6g of salt.

So suggested supplement is 3.5g of LoSalt and 2.5g of ordinary salt.

Potassium supplement for treatment of mild to moderate hypokalemia: "Providing 60 to 80 mmol/day in divided doses over days to weeks is usually sufficient. Oral supplementation can irritate GI mucosa leading to bleeding and/or ulceration but is associated with a lower risk of rebound hyperkalemia. It should be taken with plenty of fluids and food. Potassium chloride is the preferred formulation for replacement therapy in most cases. Increasing dietary potassium is not usually adequate to treat hypokalemia because most of the potassium contained in foods is coupled with phosphate. A majority of cases of hypokalemia involve chloride depletion and respond best to replacement with potassium chloride." (Castro and Sharma 2023)
60 to 80 mmol is 2.3 to 3.1 g potassium = 6.6 to 9.0 g of LoSalt.

References

Hypokalemia. Castro and Sharma 2023
Potassium - Fact Sheet for Health Professionals. NIH

Magnesium and calcium

The NHS recommended daily amount for calcium is 700mg for adults (any age). The BDA allows up to 1000mg if on osteoporosis drug treatment (not sure if this include HRT). US recommended daily amount for age >70 years is 1200mg.

Magnesium intake from food is low: 210mg when RDI for women is 270mg. Intake may also be significantly reduced by taking calcium supplements.

Recommended ratio of calcium to magnesium total intakes is around 2:1 (see below).

With a calcium intake of 1000mg from food and supplement of 1200mg, the total magnesium intake should be about (1000+1200)/2 = 1200mg, and the magnesium supplement should be about 1000mg. This is likely to cause major problems with diarrhoea.
With a calcium intake of 1000mg from food and supplement of 600mg, the total magnesium intake should be about (1000+600)/2 = 800mg, and the magnesium supplement should be about 600mg.

References

Calcium. NHS
Calcium. British Dietetic Association
Calcium - Fact Sheet for Health Professionals. NIH

When to take

Calcium in the form of calcium carbonate needs stomach acid for absorption, and so should be taken with a meal.

Magnesium in the form of magnesium citrate ionizes easily and so does not need to be taken with a meal. Some web pages recommend taking with a meal to avoid diarrhoea. Unabsorbed magnesium can cause diarrhoea, so it's best to take magnesium as 3 doses spread throughout the day.

Zinc is absorbed best on an empty stomach, but can cause stomach upsets, so it might be better taken with a meal.

Calcium and magnesium may compete for absorption, so it might be better to not take them at the same meal.
Calcium inhibits iron absorption, although this may only be for a short duration. So they may be OK together.
Calcium inhibits zinc absorption, so they probably shouldn't be taken at the same meal.

Magnesium and zinc compete for absorption, although only at high doses, so they should be OK together.

Iron and zinc compete for absorption, so they probably shouldn't be taken at the same meal.

Magnesium and iron are OK together.

So it's possible that no other supplement can be taken at the same meal as calcium. If calcium is taken in two doses (say with breakfast and evening meal), then the only remaining meal for the other supplements is lunch.

Maybe keep iron and zinc apart, but ignore the other possible interactions.

Potassium

ECG

Hypokalemia (low serum potassium) can produce several changes in the ECG (LITFL):

• Increased P wave amplitude
• Prolongation of PR interval
• Widespread ST depression and T wave flattening/inversion
• Prominent U waves (best seen in the precordial leads V2-V3)
• Apparent long QT interval due to fusion of T and U waves (= long QU interval)

With worsening hypokalemia:

• Frequent supraventricular and ventricular ectopics
• Supraventricular tachyarrhythmias: AF, atrial flutter, atrial tachycardia
• Potential to develop life-threatening ventricular arrhythmias, e.g. VT, VF and Torsades de Pointes

Earliest change is decrease in T wave amplitude (Levis 2012).

"The ECG changes that occur are T-wave flattening initially, followed by ST depression and the appearance of a U wave that can be difficult to distinguish from the T wave. The U wave is often seen in the lateral precordial leads of V4 to V6. Prolongation of the PR and QT interval can also occur." (Castro and Sharma 2023)

Note that the "digitalis effect" or "digoxin effect" can produce similar changes in the ECG (Digoxin effect LITFL):

• Downsloping ST depression with a characteristic “reverse tick” or “Salvador Dali sagging” appearance
• Flattened, inverted, or biphasic T waves
• Shortened QT interval

with additional features:

• Mild PR interval prolongation, up to 240 ms (due to increased vagal tone)
• Prominent U waves
• Peaking of the terminal portion of the T waves
• J point depression (usually in leads with tall R waves e.g. V4-6)

The features that distinguish the digitalis effect from hypokalemia are the downsloping ST depression and the shortened QT interval. Neither of these features are apparent in Monica's GP ECG, although the ST segment is depressed.

ST depression up to 0.1mV is considered normal. (Kashou et al. 2023). Monica's ST depression is typically about 0.1mV, so might be considered normal.

References

Hypokalaemia. LITFL
ECG Diagnosis: Hypokalemia. Levis 2012
Hypokalemia ECG Changes. Manual of medicine. 2021
Hypokalemia. Castro and Sharma 2023
Digoxin Effect. LITFL
ST Segment. Kashou et al. 2023

Deficiency symptoms

"A slight decrease in the potassium level in blood usually causes no symptoms.
A larger decrease can cause muscle weakness, cramping, twitches, and even paralysis.
Abnormal heart rhythms may develop. They may develop even when the decrease is slight if people already have a heart disorder or take the heart medication digoxin." (MSD Manuals)

"Hypokalemia can result in a variety of cardiac dysrhythmias. Although cardiac dysrhythmias or ECG changes are more likely to be associated with moderate to severe hypokalemia, there is a high degree of individual variability and can occur with even mild decreases in serum levels. This variability is dependent on concomitant factors such as magnesium depletion, digitalis therapy, among others. Moreover, characteristic ECG changes do not manifest in all patients." (Castro and Sharma 2023)

"Hypomagnesemia often occurs with and may worsen hypokalemia especially in the presence of chronic diarrhea, alcoholism, genetic disorders, diuretic use and chemotherapy. Both promote the development of cardiac dysrhythmias. The combination of hypokalemia and hypomagnesemia are associated with an increased risk of torsades de pointes, particularly in individuals receiving QT-prolonging medications. Additionally, hypomagnesemia can increase urinary potassium losses thus lowering the serum potassium level, as well as, prevent urinary potassium reabsorption thereby impeding potassium repletion." (Castro and Sharma 2023)

"Hypokalemia should be suspected in any patient presenting with arrhythmia. The early diagnosis of hypokalemia based on clinical presentation and changes in ECG is extremely important for timely intervention. Therefore, for the effective management of arrhythmia in acute care settings, clinicians should be familiar with different ECG manifestations of hypokalemia. Moreover, after potassium replacement, even with normal serum potassium levels, clinicians should be aware of intracellular potassium depletion, which may warrant monitoring for recurrent hypokalemia and further potassium supplementation." (Kyaw and Maung 2022)

References

Hypokalemia. Castro and Sharma 2023
Hypokalemia (Low Level of Potassium in the Blood). MSD Manuals
Hypokalemia-Induced Arrhythmia: A Case Series and Literature Review. Kyaw and Maung 2022

Magnesium

Atrial fibrillation

See my old notes.

Calcium/magnesium ratio

It seems to be generally accepted that total intake of calcium and magnesium should be in a ratio of around 2:1.

"current evidence suggests that reduction in disease risk can occur with a dietary Ca:Mg ratio between 1.70 to 2.60" (Fouhy et al. 2023)
FOG: So with 1200mg/day Ca intake, Mg intake should be between 462mg/day and 706mg/day.

"Studies showed that a calcium to magnesium intake ratio <2.8 is critical for optimal health, supporting a long-held but non–evidence-based recommendation that the calcium to magnesium ratio should be close to 2." (Rosanoff et al. 2016).
FOG: So with 1200mg Ca intake, Mg intake should be at least 1200/2.8 = 429mg.

"In humans, it has long been known that hypomagnesemia often presents with hypocalcemia and that calcium intake affects magnesium retention and vice versa"  (Rosanoff et al. 2016).

"Two comprehensive reviews of pre-1970 human studies on the impact of calcium intake on magnesium balance showed that with magnesium intakes <4 mg · kg−1 · d−1, there was magnesium loss regardless of calcium intake; however, when magnesium intakes were ≥5 mg · kg−1 · d−1, increases in calcium intake resulted in less magnesium retention" ... "Although these findings are not entirely consistent and no dietary magnesium intakes were measured, these clinical trials indicate that high calcium supplementation may affect urinary magnesium excretion in women aged ≥24 y." (Rosanoff et al. 2016).
FOG: For a body wieght of 55 kg, 4 mg/kg/day is 220 mg/day and 5 mg/kg/day is 275 mg/day.
FOG: "high calcium supplementation" seems to mean ≥ 750mg. So maybe these earlier studies were looking at Ca/Mg ratios ≥ 750/275 = 2.7.

"With regard to magnesium intakes affecting calcium balance, earlier studies showed that healthy adults with both low magnesium and low calcium intakes had a negative calcium balance, which was attenuated and reversed when magnesium intake improved" "More recently, a randomized trial of magnesium supplementation ... found that increasing magnesium intake from [264 mg/d to 528 mg/d] did not increase urinary excretion of calcium" " Another randomized trial ... also found that magnesium supplementation at [250 mg/d] did not change urinary excretion of calcium, but it reduced fractional absorption of calcium by 23.5%, which was not caused by direct competition between the 2 minerals" "However, a third trial ... found that supplementation of 250 mg magnesium (as MgO) significantly elevated the urinary excretion of calcium. Note that the [population studied] has a low calcium to magnesium ratio" (Rosanoff et al. 2016)

FOG: There is nothing in the Rosanoff paper (or in other academic papers) to suggest that Ca and Mg directly compete for absorption, so it should be OK to take them in the same meal.

"A high dietary Ca:Mg ratio (>2.60) may affect body magnesium status while, on the other hand, high intakes of magnesium could adversely impact individuals with an exceedingly low dietary Ca:Mg ratio (<1.70). Thus, a Ca:Mg ratio range of 1.70–2.60 (weight to weight) has been proposed as an optimum range." (Costello et al. 2021)

"there is correlation between low serum Mg, serum Ca, and arrhythmias. Ca: Mg ratio is higher in arrhythmia than normal persons." Patients with arrhythmias had mean Ca/Mg ratio of 6.2, whereas control group had mean of 4.2.(Patel et al. 2021)

"If high calcium intakes in humans can indeed impair magnesium balance when magnesium intakes are low, the clear implication is that calcium, when supplemented, should be given in conjunction with a balanced dose of magnesium; some authorities recommend a 2:1 ratio of calcium to magnesium (by weight) as most appropriate, both for supplementation and the total daily intake". (DiNicolantonio et al. 2017)

"In this Chinese population with a low Ca/Mg intake ratio (a median of 1.7 vs around 3.0 in US populations), intakes of Mg greater than US Recommended Daily Allowance (RDA) levels (320 mg/day among women and 420 mg/day among men) were related to increased risks of total mortality for both women and men." "Among men with a Ca/Mg ratio >1.7, increased intakes of Ca and Mg were associated with reduced risks of total mortality, and mortality due to coronary heart diseases." "Among women with a Ca/Mg ratio ≤1.7, intake of Mg was associated with increased risks of total mortality, and mortality due to cardiovascular diseases and colorectal cancer." (Dai et al 2013)

"Low magnesium intakes coupled with high calcium intakes and high calcium-to-magnesium (Ca:Mg) intake ratios have been associated with increased risk for multiple chronic conditions such as cardiovascular disease and metabolic syndrome, as well as some cancers (colorectal, prostate, esophageal), and total mortality." (Fouhy et al. 2023)

"Dietary calcium and magnesium are important for bone, perhaps not independently. The Ca:Mg intake ratio appeared most protective within a range of 2.2–3.2, suggesting that a balance of these nutrients may be considered in recommendations for osteoporosis." (Fouhy et al. 2023)

References

Perspective: Characterization of Dietary Supplements Containing Calcium and Magnesium and Their Respective Ratio—Is a Rising Ratio a Cause for Concern? Costello et al. 2021
Essential Nutrient Interactions: Does Low or Suboptimal Magnesium Status Interact with Vitamin D and/or Calcium Status? Rosanoff et al. 2016
Association between a Calcium-to-Magnesium Ratio and Osteoporosis among Puerto Rican Adults. Fouhy et al. 2023
Modifying effect of calcium/magnesium intake ratio and mortality: a population-based cohort study. Dai etl. 2013
Decreased magnesium status may mediate the increased cardiovascular risk associated with calcium supplementation DiNicolantonio et al. 2017.
Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment. Seelig 1990
Correlation of magnesium and calcium in the management of cardiac arrhythmia: Perspectives for better outcome. Patel et al. 2021

ECG

Hypomagnesaemia (low serum magnesium) can produce several changes in the ECG:

• Widened QRS complex
• Prolonged P wave
• Prolonged PR interval
• Prolonged QTc interval (corrected QT interval)
• Prolonged Tpec (corrected T peak-to-end interval)
• Prolonged Tpe/QT ratio
• Peaked T waves (with mild to moderate deficiency)
• Diminution of the T wave (with severe deficiency)
• Prominent U wave (most commonly found with bradycardia or severe hypokalaemia)
• Atrial and ventricular ectopy
• Predisposition to ventricular tachycardia and torsades de pointes

Conclusions from Yang 2021: "In patients with isolated hypomagnesemia, P wave duration, QTc, Tpec, and Tpe/QT ratio suggesting atrial depolarization and ventricular repolarization dispersion were significantly increased compared with normal magnesium levels in the same patients after restoration to normal levels."

From LITFL: "Patients with hypomagnesaemia often have concurrent hypokalaemia and/or hypocalcaemia and associated ECG features of these conditions."

References

Hypomagnesaemia. LITFL
Hypomagnesemia. Gragossian et. al. 2023
The ECG Characteristics of Patients With Isolated Hypomagnesemia. Yang et al. 2021
U Wave. LITFL

Deficiency symptoms

"Early signs of magnesium deficiency include weakness, loss of appetite, fatigue, nausea, and vomiting. Afterwards, muscle contractions and cramps, numbness, tingling, personality changes, coronary spasms, abnormal heart rhythms, and seizures can occur when magnesium deficiency worsens." (Florentini et al. 2021)

"Early signs of magnesium deficiency include loss of appetite, nausea, vomiting, fatigue and weakness. As magnesium deficiency worsens, numbness, tingling, muscle contractions, cramps, seizures, sudden changes in behaviour caused by excessive electrical activity in the brain, personality changes, abnormal heart beat and coronary spasms might occur. 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" (Jahnen-Dechent and Ketteler 2012)

References

Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency. Florentini et al. 2021
Magnesium basics. Jahnen-Dechent and Ketteler 2012

Cardiovascular

Magnesium supplements can reduce blood pressure, but by only a few mmHg (Florentini et al. 2021).

"Magnesium deficiency reduces cardiac Na-K-ATPase, determining greater levels of sodium and calcium and lower levels of magnesium and potassium in the heart. Consequently, the vasoconstriction in the coronary arteries increases, inducing coronary artery spasms, heart attack, and cardiac arrhythmia. Higher magnesium serum levels were significantly linked to a lower risk of CVD, as shown by a systematic review and meta-analysis of prospective studies" (Florentini et al. 2021)

"magnesium deficiency reduces cardiac Na-K-ATPase, leading to higher levels of sodium and calcium and lower levels of magnesium and potassium in the heart. This increases vasoconstriction in the coronary arteries, which can induce coronary artery spasms, myocardial infarction and arrhythmias" (DiNicolantonio et al. 2018)

"Low magnesium levels can also enhance endothelial cell dysfunction, potentially increasing the risk of atherosclerosis and thrombosis" (Florentini et al. 2021)

"Magnesium is required for the formation and activation of ATP and is essential for heart muscle contraction and oxidative phosphorylation in heart mitochondria." (DiNicolantonio et al. 2018)

"Hypomagnesaemia may induce arrhythmias including torsades de pointes ventricular tachycardia" (DiNicolantonio et al. 2018)

"magnesium contributes to the regulation of vascular tone, heart rhythm, platelet-activated thrombosis and bone formation" "Magnesium is a cofactor in >300 enzymatic reactions and thus it is essential for many crucial physiological functions, such as heart rhythm, vascular tone, nerve function and muscle contraction and relaxation." (Jahnen-Dechent and Ketteler 2012)

"Magnesium also affects the electrical activity of the myocardium and vascular tone, which is why patients with hypomagnesemia are at risk for cardiac arrhythmias. In addition, when magnesium is low, there is inhibition of renal outer medullary potassium channels, leading to increased urinary excretion and depletion of intracellular potassium levels; this reduces the threshold required for generating an action potential in the cardiac myocyte. Moreover, reduced intracellular potassium levels also prolong the time to repolarize the cell membrane, increasing the risk of arrhythmias." (Gragossian et al. 2023)

Cardiovascular manifestations include: Atrial and ventricular premature systoles; Atrial fibrillation; Ventricular arrhythmias, including torsades de pointes; Cardiac ischemia (Gragossian et al. 2023)

References

Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency. Florentini et al. 2021
Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. DiNicolantonio et al. 2018
Magnesium basics. Jahnen-Dechent and Ketteler 2012
Hypomagnesemia. Gragossian et. al. 2023
Magnesium: The Forgotten Electrolyte—A Review on Hypomagnesemia