Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through C-quality evidence.

Class
Qualifying studies
Minimum requirements
A
Systematic review or meta-analysis of human trials
 
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study

Blood pressure homeostasis is a clear indication of health. Approximately 9 million deaths due to high blood pressure occur each year. (16) This makes essential hypertension the most prominent disease worldwide. Uncontrolled blood pressure increases the risk for heart-related problems such as stroke, coronary artery disease, and heart failure. When left untreated, high blood pressure may lead to chronic kidney disease, disability, and even death. (4)

Interventions aimed at lowering blood pressure improve comorbidities and outcomes. Patients with uncomplicated grade 1 hypertension experience decreased risk of stroke and death when lowering blood pressure by an average of 3.6 mmHg systolic, and 2.4 mmHg diastolic. (23) Targeting reductions in blood pressure, as well as underlying mechanisms, is key to an integrative treatment plan.

Based on current research findings presented below, the ingredients in this protocol have demonstrated efficacy in improving blood pressure profile.

 

Magnesium

300-450 mg of elemental magnesium, total per day, 1 to 6 months (5)(26)

  • An inverse correlation between levels of circulating magnesium and the incidence of hypertension has been clearly identified (12)
  • Meta-analysis of three trials (14,876 participants, 6.7 year follow up) found that every 0.1 mmol/L incremental increase in circulating Mg levels was associated with 4% (RR, 0.96; 95% CI: 0.94, 0.99) reduction in hypertension incidence (25) 
  • Patients with insulin resistance, prediabetes, and other chronic noncommunicable diseases supplemented with 365 to 450 mg per day of magnesium had an overall decrease in blood pressure with a mean reduction in systolic by 4.18 mmHg and diastolic by 2.27 mmHg (5)
  • Supplementation with a median dose of 368 mg per day of magnesium for a median duration of three months increased serum magnesium by 0.05 mmol/L and resulted in decreasing systolic blood pressure by 2.0 mmHg and diastolic blood pressure by 1.78 mmHg (26)
  • Supplementation with magnesium decrease systolic and diastolic blood pressure by 3-4 mm Hg and 2-3 mm Hg respectively across trials with a range of 120-973 mg per day supplementation for 3-24 weeks; supplementation with more than 370 mg per day demonstrated an increased effect size (14)
Magnesium in the Fullscript catalog

Garlic (Allium sativum)

300-960 mg, total per day, minimum 8 to 12 weeks (15)(18)(22)

  • Findings across multiple meta-analysis and systematic reviews found supplementation with garlic resulted in a decrease in systolic and diastolic blood pressure (19)(24)(20)
  • Analysis found a higher impact for blood pressure lowering effects in subgroups with hypertension than normotensive subjects (19)(24)(20)
  • Systolic blood pressure decreased in patients with uncontrolled hypertension after being treated for 12 weeks when compared to placebo; patients with systolic blood pressure more than 140 mmHg experienced more benefits from supplementation (18)
Garlic in the Fullscript catalog

Vitamin C

500 mg total per day, minimum 6 weeks (7)(10)(11)(13)

  • Supplementation improved blood pressure as shown by an average weighted mean difference for systolic blood pressure decreased by 4.09 and diastolic blood pressure by 2.30 (10)
  • Risk of cardiovascular disease and stroke decreased as shown by a decrease in systolic blood pressure when supplemented with vitamin C (7)
  • Supplementation decreased average systolic and diastolic blood pressure with 1-month supplementation, additionally state-trait anxiety inventory and visual analogue mood scale (11)
  • Pooled analysis found a decrease in systolic blood pressure by 3.84 mm Hg and diastolic blood pressure by 1.48 mm Hg (13)
Vitamin C in the Fullscript catalog

Melatonin

 2-3 mg, 1-2 hours prior to sleeping, minimum 3 weeks (21)(9)(3)

  • Untreated essential hypertension in men demonstrated a decrease in systolic and diastolic blood pressure by 5 mmHg and 4 mmHg respectively when given 2.5 mg of melatonin 1 hour before bed for 3 weeks; this effect was best in patients with essential hypertension (21)
  • Nocturnal hypertension was decreased with the most effect being seen between 2 am and 5 am in males given 2 mg of controlled-release melatonin 2 hours before bedtime when compared to placebo (9)
  • Nocturnal blood pressure decreased in women aged 47 to 63 with treated essential hypertension when given 3 mg of slow-release melatonin for 3 weeks 1 hour before bedtime when compared to placebo (3)
Melatonin in the Fullscript catalog

Potassium 

950-3500 mg (30-90 mmol) total per day, minimum 4 weeks (1)(2)(6)(8)

  • Intake of at least 90 mmol (3500 mg) per day of potassium correlated with reduction of blood pressure by 4.48 mmHg (systolic) and 2.96 mmHg (diastolic) (6)
  • Decreased blood pressure in normotensive and hypertensive patients with hypertensive patients having a more significant reduction (1)(17)
  • Elderly patients with untreated hypertension experienced a decrease in supine blood pressure when supplemented with 60 mmol (2346 mg) per day of potassium chloride for 4 weeks (8)
  • Improvements in blood pressure were observed after 6 weeks of supplementation with potassium; 30 mmol of potassium citrate per day resulted in a decrease in mean blood pressure by 5.22 mmHg, while potassium chloride demonstrated a decrease by 4.70 mmHg (2)
Potassium in the Fullscript catalog

Disclaimer

The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

View protocol on Fullscript
References
  1. Binia, A., Jaeger, J., Hu, Y., Singh, A., & Zimmermann, D. (2015). Daily potassium intake and sodium-to-potassium ratio in the reduction of blood pressure: a meta-analysis of randomized controlled trials. Journal of Hypertension, 33(8), 1509–1520. https://pubmed.ncbi.nlm.nih.gov/26039623/ (A)
  2. Braschi, A., & Naismith, D. J. (2008). The effect of a dietary supplement of potassium chloride or potassium citrate on blood pressure in predominantly normotensive volunteers. The British Journal of Nutrition, 99(6), 1284–1292. https://pubmed.ncbi.nlm.nih.gov/18053306/ (B)
  3. Cagnacci, A., Cannoletta, M., Renzi, A., Baldassari, F., Arangino, S., & Volpe, A. (2005). Prolonged melatonin administration decreases nocturnal blood pressure in women. American Journal of Hypertension, 18(12 Pt 1), 1614–1618. https://pubmed.ncbi.nlm.nih.gov/16364834/ (C)
  4. Cicero, A. F. G., Grassi, D., Tocci, G., Galletti, F., Borghi, C., & Ferri, C. (2019). Nutrients and Nutraceuticals for the Management of High Normal Blood Pressure: An Evidence-Based Consensus Document. High Blood Pressure & Cardiovascular Prevention: The Official Journal of the Italian Society of Hypertension, 26(1), 9–25. https://pubmed.ncbi.nlm.nih.gov/30671873/ (F)
  5. Dibaba, D. T., Xun, P., Song, Y., Rosanoff, A., Shechter, M., & He, K. (2017). The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition, 106(3), 921–929. https://pubmed.ncbi.nlm.nih.gov/28724644/ (A)
  6. Filippini, T., Violi, F., D’Amico, R., & Vinceti, M. (2017). The effect of potassium supplementation on blood pressure in hypertensive subjects: A systematic review and meta-analysis. International Journal of Cardiology, 230, 127–135. https://pubmed.ncbi.nlm.nih.gov/28024910/ (A)
  7. Fotherby, M. D., Williams, J. C., Forster, L. A., Craner, P., & Ferns, G. A. (2000). Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons. Journal of Hypertension, 18(4), 411–415. https://pubmed.ncbi.nlm.nih.gov/10779091/ (C)
  8. Fotherby, M. D., & Potter, J. F. (1992). Potassium supplementation reduces clinic and ambulatory blood pressure in elderly hypertensive patients. Journal of Hypertension, 10(11), 1403–1408. https://pubmed.ncbi.nlm.nih.gov/1336526/ (C)
  9. Grossman, E., Laudon, M., Yalcin, R., Zengil, H., Peleg, E., Sharabi, Y., Kamari, Y., Shen-Orr, Z., & Zisapel, N. (2006). Melatonin reduces night blood pressure in patients with nocturnal hypertension. The American Journal of Medicine, 119(10), 898–902. https://pubmed.ncbi.nlm.nih.gov/17000226/ (C)
  10. Guan, Y., Dai, P., & Wang, H. (2020). Effects of vitamin C supplementation on essential hypertension: A systematic review and meta-analysis. Medicine, 99(8), e19274. https://pubmed.ncbi.nlm.nih.gov/32080138/ (A)
  11. Hajjar, I. M., George, V., Sasse, E. A., & Kochar, M. S. (2002). A randomized, double-blind, controlled trial of vitamin C in the management of hypertension and lipids. American Journal of Therapeutics, 9(4), 289–293. https://pubmed.ncbi.nlm.nih.gov/12115017/ (C)
  12. Han, H., Fang, X., Wei, X., Liu, Y., Jin, Z., Chen, Q., Fan, Z., Aaseth, J., Hiyoshi, A., He, J., & Cao, Y. (2017). Dose-response relationship between dietary magnesium intake, serum magnesium concentration and risk of hypertension: a systematic review and meta-analysis of prospective cohort studies. Nutrition Journal, 16(1), 26. https://pubmed.ncbi.nlm.nih.gov/28476161/ (A)
  13. Juraschek, S. P., Guallar, E., Appel, L. J., & Miller, E. R., 3rd. (2012). Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition, 95(5), 1079–1088. https://pubmed.ncbi.nlm.nih.gov/22492364/ (A)
  14. Kass, L., Weekes, J., & Carpenter, L. (2012). Effect of magnesium supplementation on blood pressure: a meta-analysis. European Journal of Clinical Nutrition, 66(4), 411–418. https://pubmed.ncbi.nlm.nih.gov/22318649/ (A)
  15. Nakasone, Y., Nakamura, Y., Yamamoto, T., & Yamaguchi, H. (2013). Effect of a traditional Japanese garlic preparation on blood pressure in prehypertensive and mildly hypertensive adults. Experimental and Therapeutic Medicine, 5(2), 399–405. https://pubmed.ncbi.nlm.nih.gov/23404465/ (C)
  16. Noubiap, J. J., Nansseu, J. R., Nyaga, U. F., Sime, P. S., Francis, I., & Bigna, J. J. (2019). Global prevalence of resistant hypertension: a meta-analysis of data from 3.2 million patients. Heart , 105(2), 98–105. https://pubmed.ncbi.nlm.nih.gov/30087099/ (A)
  17. Poorolajal, J., Zeraati, F., Soltanian, A. R., Sheikh, V., Hooshmand, E., & Maleki, A. (2017). Oral potassium supplementation for management of essential hypertension: A meta-analysis of randomized controlled trials. PloS One, 12(4), e0174967. https://pubmed.ncbi.nlm.nih.gov/28419159/ (A)
  18. Ried, K., Frank, O. R., & Stocks, N. P. (2010). Aged garlic extract lowers blood pressure in patients with treated but uncontrolled hypertension: a randomised controlled trial. Maturitas, 67(2), 144–150. https://pubmed.ncbi.nlm.nih.gov/20594781/ (B)
  19. Ried, K., Frank, O. R., Stocks, N. P., Fakler, P., & Sullivan, T. (2008). Effect of garlic on blood pressure: a systematic review and meta-analysis. BMC Cardiovascular Disorders, 8, 13. https://pubmed.ncbi.nlm.nih.gov/18554422/ (A)
  20. Ried, K. (2016). Garlic Lowers Blood Pressure in Hypertensive Individuals, Regulates Serum Cholesterol, and Stimulates Immunity: An Updated Meta-analysis and Review. The Journal of Nutrition, 146(2), 389S – 396S. https://pubmed.ncbi.nlm.nih.gov/26764326/ (A)
  21. Scheer, F. A. J. L., Van Montfrans, G. A., van Someren, E. J. W., Mairuhu, G., & Buijs, R. M. (2004). Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension, 43(2), 192–197. https://pubmed.ncbi.nlm.nih.gov/14732734/ (C)
  22. Sobenin, I. A., Andrianova, I. V., Fomchenkov, I. V., Gorchakova, T. V., & Orekhov, A. N. (2009). Time-released garlic powder tablets lower systolic and diastolic blood pressure in men with mild and moderate arterial hypertension. Hypertension Research: Official Journal of the Japanese Society of Hypertension, 32(6), 433–437. https://pubmed.ncbi.nlm.nih.gov/19390538/ (B)
  23. Sundström, J., Arima, H., Jackson, R., Turnbull, F., Rahimi, K., Chalmers, J., Woodward, M., Neal, B., & Blood Pressure Lowering Treatment Trialists’ Collaboration. (2015). Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis. Annals of Internal Medicine, 162(3), 184–191. https://pubmed.ncbi.nlm.nih.gov/25531552/ (A)
  24. Wang, H.-P., Yang, J., Qin, L.-Q., & Yang, X.-J. (2015). Effect of garlic on blood pressure: a meta-analysis. Journal of Clinical Hypertension , 17(3), 223–231. https://pubmed.ncbi.nlm.nih.gov/25557383/ (A)
  25. Wu, J., Xun, P., Tang, Q., Cai, W., & He, K. (2017). Circulating magnesium levels and incidence of coronary heart diseases, hypertension, and type 2 diabetes mellitus: a meta-analysis of prospective cohort studies. Nutrition Journal, 16(1), 60. https://pubmed.ncbi.nlm.nih.gov/28927411/ (A)
  26. Zhang, X., Li, Y., Del Gobbo, L. C., Rosanoff, A., Wang, J., Zhang, W., & Song, Y. (2016). Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension, 68(2), 324–333. https://pubmed.ncbi.nlm.nih.gov/27402922/ (A)