Primary (essential) hypertension - or high blood pressure (BP) - is a serious medical condition that significantly increases the risks of cardiovascular, brain, kidney and other diseases. High BP stretches arteries beyond their healthy limit, and this chronic overstretching of the arteries can lead to scarring, high risk of rupture, formation of blood clots and the build-up of plaque.² It is therefore a major cause of premature death, with approximately 1.13 billion people worldwide being affected.¹

 At the time of the National Health Survey from 2017–18, approximately one in five Australians aged 18 years and over (4.3 million people) had a measured high BP reading.³ Of these, 1 in 4 (25%) men had uncontrolled high BP compared with 1 in 5 (20%) women. Moreover, the proportion of those with uncontrolled high BP increases with age from 5-10% among 18–34-year-olds to nearly 50% in 85-year-olds and over.⁴

Endothelial dysfunction and impact on blood pressure

Primary hypertension has no discernible cause but is linked to genetics, dietary, lifestyle, psychological and environmental factors,^5,6 many of which are preventable and/or treatable. It also involves the endothelium which plays an important role in maintaining healthy cardiovascular function. As a metabolically active tissue, its cells quickly adapt to local changes by releasing specific vasoactive mediators - particularly nitric oxide (NO), which is a potent vasodilator with anti-platelet, anti-proliferative, anti-atherogenic, anti-inflammatory, antifibrinolytic, and anti-apoptotic properties.⁷

Endothelial dysfunction on the other hand not only leads to diminished bioavailability of NO and attenuated vasodilatation, it is also associated with inflammation and increased activation of reactive oxygen species (ROS). This in turn promotes a cascade of detrimental processes that eventually lead to hypertension.^6,8,9

Figure 1 | Pathways from endothelial dysfunction to hypertension.⁸

Mechanisms of action of magnesium

Magnesium (Mg) is a key cardiovascular regulator which maintains electrical, metabolic and vascular homeostasis,¹⁰ and as such is an indispensable mineral for the treatment of essential hypertension. It is an important cation for the activity of many enzymes related to energy metabolism,¹¹ it modulates inflammatory and oxidative processes involved in hypertension,¹⁰ acts as a natural calcium antagonist, potentiates the production of local vasodilatory mediators (i.e. nitric oxide), alters vascular responses to a variety of vasoactive substances (endothelin-1, angiotensin II, and catecholamines), stimulates the production of aldosterone, balances the effects of catecholamines in acute and chronic stress, regulates the turnover of collagen and elastin in the vascular wall and protects the elastic fibres from calcium deposition, thereby maintaining their elasticity.^12,13

Conversely, Mg deficiency is associated with decreased expression and/or activity of various antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase), lowered levels of important antioxidants (vitamin C, vitamin E, and selenium), raised production of aldosterone, increased vascular inflammatory response, development of insulin resistance and hyperglycaemia, and detrimental changes in lipid metabolism, all of which contribute to the development of hypertension.^12,13

Evidence to supporting magnesium

An inverse relationship between Mg intake and BP has been suggested.

• A meta-analysis of 34 randomized, double-blind, placebo-controlled trials from 2016 involving 2028 participants demonstrated a significant antihypertensive effect of Mg. Both systolic and diastolic BP was reduced by 2.00 mm Hg and 1.78 mm Hg respectively in both normotensive and hypertensive adults when Mg was taken at a median dose of 368 mg/d for a median duration of 3 months. This reduction was achieved with a serum Mg elevation of 0.05 mmol/L when compared with placebo.¹⁴
• According to a meta-analysis from 2012, a mean dose of 410 mg/d Mg taken for a mean duration of 11.3 weeks was shown to reduce both SBP and DBP by 3–4 mm Hg and 2-3 mm Hg respectively. Effect size increased in line with increased dosage.¹⁵

Clinical application

The discussed research findings highlight the need for practitioners to consider the considerable array of benefits Mg has to offer when supporting their hypertensive patients.

Blood Pressure Modulating Mechanisms of Action of Magnesium 

• Direct hypotensive effect
• Calcium channel inhibitory effect
• Heart muscle relaxant effect
• Vasodilatory effect involving NO availability
• Support of mitochondrial energy metabolism
• Modulation of inflammatory processes in hypertension
• Modulation of oxidative processes in hypertension
• Balancing effect on catecholamines in acute and chronic stress
• Maintenance of blood vessel elasticity

Based on research findings, practitioners should consider the following treatment approaches:

• Supplement with organic forms of Mg such as Mg citrate, Mg amino acid chelate and Mg aspartate - which have superior bioavailability when compared to inorganic salts - at a dose of 370 to 410 mg per day of elemental Mg for at least 12 weeks.^16-18
• Encourage patients to include Mg rich foods in their diet, such as unrefined whole grains, legumes, beans, nuts, and green leafy vegetables such as spinach.^10,19-21
• Identify patients at risk of Mg deficiency and supplement accordingly. Clinical signs and symptoms of Mg deficiency include loss of appetite, feeling stressed, hyperirritability, fatigue, weakness, insomnia, and muscular cramps, amongst others. Meanwhile profuse sweating, intense prolonged physical exercise, alcohol use, gastrointestinal and endocrine disorders, renal problems and stress all increase requirements for Mg.^22,23 If patients present with such signs alongside raised blood pressure, magnesium supplementation should be considered a priority.
• Prescription of other cardiovascular-specific nutrients such as coenzyme Q10 to further capitalise on the health benefits of magnesium supplementation.

References

• 1 - World Health Organization. Hypertension. 2019. Available from: https://www.who.int/news-room/fact-sheets/detail/hypertension
• 2 - Linus Pauling Institute. Oregon State University. What is Blood Pressure. 2019. Available from: https://lpi.oregonstate.edu/mic/health-disease/high-blood-pressure
• 3 - Australian Bureau of Statistics. National Health Survey: First Results, 2017-18. ABS cat. no. 4364.0.55.001. Canberra: Australian Bureau of Statistics. 2018. Available from: https://www.abs.gov.au/statistics/health/health-conditions-and-risks/national-health-survey-first-results/latest-release
• 4 - Australian Institute of Health and Welfare. High Blood Pressure. 2019. Available from: https://www.aihw.gov.au/reports/risk-factors/high-blood-pressure/contents/high-blood-pressure
• 5 - Pizzorno MT, Murray JE. Textbook of Natural Medicine. 5th ed. Volume 1. St. Louis: Elsevier; 2020.
• 6 - Dinh QN, Drummond GR, Sobey CG, Chrissobolis S. Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension. Biomed Res Int. 2014;2014:406960.
• 7 - Jamwal S, Sharma S. Vascular endothelium dysfunction: a conservative target in metabolic disorders. Inflamm Res. 2018 May;67(5):391-405.
• 8 - Brandes RP. Endothelial dysfunction and hypertension. Hypertension. 2014 Nov;64(5):924-8.
• 9 - Dharmashankar K, Widlansky ME. Vascular endothelial function and hypertension: insights and directions. Curr Hypertens Rep. 2010 Dec;12(6):448-55.
• 10 - Severino P, Netti L, Mariani MV, Maraone A, D'Amato A, Scarpati R, et al. Prevention of Cardiovascular Disease: Screening for Magnesium Deficiency. Cardiol Res Pract. 2019 May 2;2019:4874921.
• 11 - Banjanin N, Belojevic G. Changes of Blood Pressure and Hemodynamic Parameters after Oral Magnesium Supplementation in Patients with Essential Hypertension-An Intervention Study. Nutrients. 2018 May 8;10(5):581.
• 12 - Kostov K, Halacheva L. Role of Magnesium Deficiency in Promoting Atherosclerosis, Endothelial Dysfunction, and Arterial Stiffening as Risk Factors for Hypertension. Int J Mol Sci. 2018 Jun 11;19(6):1724.
• 13 - Zhu D, You J, Zhao N, Xu H. Magnesium Regulates Endothelial Barrier Functions through TRPM7, MagT1, and S1P1. Adv Sci (Weinh). 2019 Jul 30;6(18):1901166.
• 14 - Zhang X, Li Y, Del Gobbo LC, Rosanoff A, Wang J, Zhang W, Song Y. Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension. 2016 Aug;68(2):324-33.
• 15 - Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr. 2012 Apr;66(4):411-8.
• 16 - Walker AF et al. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Magnes Res. 2003;16(3):183-91.
• 17 - Ranade VV, Somberg JC. Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. Am J Ther. 2001 Sep-Oct;8(5):345-57.
• 18 - Coudray C et al. Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Magnes Res. 2005;18(4):215-23.
• 19 - Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015 Sep 23;7(9):8199-226.
• 20 - Gropper SS & Smith JL. Advanced Nutrition and Human Metabolism. 6th ed. Australia: Wadsworth CENGAGE Learning; 2013.
• 21 - National Health and Medical Research Council (NHMRC) Nutrient Reference Values for Australia and New Zealand. Magnesium. 2006, pp.201-205.
• 22 - Braun L. Cohen M. Herbs & Natural Supplements - An evidence-based guide. 4th ed. Volume 2. Sydney: Churchill Livingstone; 2015, pp.677-694.
• 23 - Guerrera MP, Volpe SL, Mao JJ. Therapeutic uses of magnesium. Am Fam Physician. 2009 Jul 15;80(2):157-62.