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Calcium and COVID-19

11 February 2021

Studies suggesting that hypocalcaemia may be an indicator of poor clinical outcome in severe COVID-19 patients have prompted further questions around the therapeutic relevance of calcium in this context. We explore this emerging area of research, the potential role of Aquamin and why maintaining calcium intake is more important than ever.

Hypocalcaemia explained.

A recognised condition, hypocalcaemia refers to a calcium deficiency in the body; specifically, low levels of calcium in the blood1. It can cause many different symptoms from confusion, memory loss, and muscle spasms, to depression, hallucinations and weak or brittle nails and bones – all of which vary in terms of intensity depending on the stage and severity of the disease1.  

Hypocalcaemia has long been associated with increased risk of acute respiratory failure and mortality among critically ill patients. However, new research has recently been carried out to investigate the predictive value of hypocalcaemia among severe COVID-19 patients2-3.

Research findings

Together, the studies identify hypocalcaemia as one of the distinctive biochemical features of COVID-19 patients1-3. To date, key findings include:

  • Higherincidence of hypocalcaemia with both low ionized and total calcium levels in different cohorts of more seriously ill Covid-19 patients.
  • A link between hypocalcaemia and a worse prognosis and clinical outcome.
  • A strong association between lower calcium and higher inflammatory response with increased disease severity.
  • Sufficient evidence to suggest that hypocalcaemia represents a novel possible treatment target worth testing in this clinical setting. 

COVID-19 concerns

Reviewed together, these findings offer a compelling argument for considering early calcium supplementation. To understand why, it’s important to also look at key physiological responses that are known to take place in severe COVID-19 patients. 

Some of these patients will experience an event known as a cytokine storm; where an acute immune response 4 to the virus leads to the massive and unrestrained production of different pro-inflammatory cytokines – such as interferons, interleukins, growth factors and TNF-alpha – as well as chemokines. Although this cellular communication is a normal part of the immune response – as is inflammation – this level of overactivity can have a negative impact on the body.   

This is because uncontrolled cytokine secretion triggers an influx of various immune cells and results in extensive damage to vital organs including the lung, liver and kidney5. In other words, the body starts to attack its own cells and tissues rather than fighting off the virus. 

An equally important feature among severe COVID-19 patients is the release of elevated levels of unbound fatty acids due to the depletion of calcium and albumin, both of which normally bind fatty acids and so prevent a dangerously excessive build up in the body known as lipotoxicity. 

There are also serious implications for obese patients who are already considered higher risk; obesity is recognised as the second strongest independent predictor for COVID-19 hospitalisation, after old age6. This is due to the impact on lipolysis – the process by which stores of fat (referred to as adipose tissue) are broken down into fatty acids and glycerol, before being released into the blood and used by the tissues to generate energy. In obese patients, acute lipolysis of large adipose tissue amounts can overwhelm the ability of calcium and albumin to bind these fatty acids, potentially causing organ failure and death.

In addition, the high levels of unbound fatty acids released during severe COVID-19 infection can also induce hypalbuminaemia (low levels of albumin in the blood, as well as the cytokine storm and hypocalcaemia. 

Aquamin response

The next step is to examine whether Aquamin’s proven mode of action can play a positive role by helping to reduce any of the identified COVID-19 risk factors.  

Hypocalcaemia

Aquamin offers a highly bioavailable source of calcium to help prevent against a lowering of calcium levels in the blood and a worse prognosis for Covid-19 patients. It has been shown to have a calcium bioavailability that is three to four times higher than any other typical source of calcium7. 

Inflammation

Aquamin has been shown to encourage a general reduction in the levels of inflammation in the blood8-15.  Of particular relevance is the fact that it reduces levels of TNF-alpha, IL-1beta13 and NFkB14 – all of which are involved in the cytokine surge due to COVID-19 infection. 

Although the precise mechanism of Aquamin in this context is the subject of ongoing research, the fact that it consistently outperforms calcium-only experiments suggests that its unique marine multi-mineral complex plays an important role in regulating inflammation13-15. For example:

  • The lanthanide metal ions in Aquamin are more effective than calcium in upregulating expression of the extracellular-calcium-sensing receptor (responsible for mediating many of the effects of calcium) and may be responsible for the anti-inflammatory effects seen. 
  • Several of the trace elements in Aquamin, such as copper, zinc, selenium, manganese and molybdenum, are key components of antioxidant enzymes. So, the varied effects of Aquamin may be due to increased antioxidant activity and a subsequent reduction in general inflammation. 

Lipolysis

Intake of a combination product containing Aquamin and albumin may help to reduce levels of free fatty acids in the blood and reduce the risk of acute lipolysis, particularly among overweight or obese individuals. 

Consideration should also be given to including Vitamin D in such a product. This essential nutrient performs a number of different functions in the body but its role in boosting the immune system and aiding calcium uptake is of most interest in this context – not least because low levels of vitamin D have also been associated with a poor outcome for COVID-19 patients. 

Conclusion

The therapeutical relevance of calcium may lie in early supplementation to ensure normal levels before COVID-19 infection. Such supportive care could help to prevent the development of severe symptoms in some individuals. Given the growing body of scientific evidence to support the beneficial effects of Aquamin – particularly its high calcium bioavailability – we believe it is worthy of further investigation to evaluate its value as part of a forward-thinking nutritional strategy.

References

  1. Fong J and Khan A. (2012) Hypocalcemia: updates in diagnosis and management for primary care. Can Fam Physician. 58(2):158-62.
  2. di Filippo et al., (2020). Hypocalcemia is a distinctive biochemical feature of hospitalized COVID-19 patients. Endocrine 68(3):475-478 
  3. Liu et al., (2020). Prevalence and predictive value of hypocalcemia in severe COVID-19 patients. Journal of Infection and Public Health 13:1224–1228
  4. Cytokine Storm David C. Fajgenbaum, M.D., and Carl H. June, M.D. N Engl J Med 2020;383:2255-73
  5. Singh et al, (2020). Hypocalcemia and hypoalbuminemia during COVID-19 infection: Opportunities for therapeutic intervention. Journal of Infection and Public Health 13:1887
  6. Huang et al., (2020). Hypoalbuminemia predicts the outcome of COVID‐19 independent of age and co‐morbidity. J Med Virol. 1-7
  7. https://www.nutraingredients.com/Product-innovations/Aquamin-marine-multi-minerals-for-your-health-importance-of-calcium-bioavailability
  8. Aslam et al., (2021) A MULTI-MINERAL INTERVENTION TO MODULATE COLONIC MUCOSAL PROTEIN PROFILE: Results from a 90-day trial in healthy human subjects. Manuscript under review. 
  9. Aslam et al., (2020). Ulcerative Colitis-Derived Colonoid Culture: A Multi-Mineral-Approach to Improve Barrier Protein Expression. Frontiers Cell Devel Biol
  10. Heffernan et al., (2020). Mineral rich algae with pine bark improved pain, physical function and analgesic use in mild-knee joint osteoarthritis, compared to Glucosamine: A randomized controlled pilot trial. Complementary Therapies in Medicine. Vol 50, May 2020, 102349
  11. Frestedt et al. (2008). A natural mineral supplement provides relief from knee osteoarthritis symptoms: a randomized controlled pilot trial. Nutrition Journal 7:9
  12. O’Gorman et al. (2012) Evidence that marine-derived, multi-mineral, Aquamin, inhibits the NFκB signalling pathway in vitro. Phytotherapy Res 26(3):630-32. 
  13. Ryan et al. (2011). Evidence that the marine-derived multi mineral, Aquamin, has anti-inflammatory effects on cortical glial-enriched cultures Phytotherapy Res 25(5): 765-7
  14. O’Gorman et al. (2012) Evidence that marine-derived, multi-mineral, Aquamin, inhibits the NFκB signalling pathway in vitro. Phytotherapy Res 26(3):630-32. 
  15. Aslam M and Varani J. (2016) The Western-Style Diet, Calcium Deficiency and Chronic Disease. J Nutr Food Sci, 6:3
AndrewB - February 2021