Why 24-Hour Blood Pressure Control MattersNovember 2016
By Carol Stanton
Getting blood pressure under control is essential, but it is only part of the solution.
Over the past decade, it has become clear that daily variations in blood-pressure patterns are also tremendously important, especially in older adults.1,2
In healthy people, blood pressure dips somewhat at night, providing at least temporary relief to the pounding damage being done to blood vessels.3 But in those whose pressure does not fall at night (so-called “non-dippers”), the damage to blood vessels continues around the clock.3
As a result, non-dippers have a significantly higher risk of cardiovascular disease and death compared to normal dippers, even when both have the same blood pressure during the day.3 About 35% of adults with hypertension are “non-dippers,” meaning that they are at constantly elevated risk for bad outcomes.3
The implications of these findings—coupled with a recent study2 showing optimal systolic target levels—are clear. Most people need to establish more ambitious blood pressure targets—ideally 120 mmHg or lower for the systolic reading. And many people who need to lower their blood pressure also need to find both a daytime and a nighttime solution.1
Fortunately, natural compounds are available that not only help lower blood pressure, but can provide around-the-clock management. These natural compounds have blood pressure-lowering properties that are akin to those of many prescription drugs.
Life Extension® has long maintained that the recommended target for systolic blood pressure should be closer to 115 mmHg (as opposed to 140 mmHg). A recent study in the New England Journal of Medicine4 supports Life Extension’s recommended blood pressure targets.
This study revealed that millions of people have been lulled into a false sense of security by current recommended blood-pressure parameters. In fact, they are at significantly increased risk of cardiovascular disease and death, and should be taking active measures to lower their blood pressure into a safer range.
Making matters worse, natural fluctuations in blood pressure can cause readings to vary widely, making blood pressure difficult to manage successfully. Blood pressure control works best by utilizing different drug classes of medications at relatively reduced doses rather than using one drug at a maximal dose. This strategy also helps reduce the risk of side effects associated with the maximal tolerated dosing of a single drug.
Blood Pressure Basics
When it comes to lowering blood pressure, at-home monitoring is essential to ensure that optimal 24-hour protection is achieved. The availability of low-cost and reliable at-home blood pressure monitors makes this easy.
Lifestyle changes such as losing weight and increasing cardiovascular fitness through exercise can help support healthy blood-pressure levels.
The older drug classes of medication often have side effects that patients find frustrating and bothersome. Side effects can include nighttime urinary frequency with the use of diuretics, or cold hands/feet and sexual dysfunction with the use of beta-blockers. However, some of the newer classes of antihypertensive drugs like angiotensin II receptor blockers generally are better tolerated by patients in comparison with older medications like diuretics and beta-blockers. In fact, some people may only need to take one angiotensin II receptor blocker like telmisartan (40 to 80 mg a day) to achieve good results. This drug also has additional, potential benefits for vascular health.5-10
However, in general the best strategy for control of hypertension is the use of low doses of several different classes (different mechanisms of action) of medications.
Natural Approaches to Blood Pressure Control
In addition to, or in lieu of prescription drugs, several natural compounds are available that not only help lower blood pressure but help keep it down around the clock. Each compound has a different but complementary mechanism of action:
- Flavonoids block a receptor for the angiotensin hormone that can elevate blood pressure.
- Stevioside slows calcium signaling in order to relax blood vessels.
- Time-release melatonin provides control over nighttime blood pressure elevations.
These compounds work by multiple, clinically validated mechanisms to control blood pressure both day and night to maximally lower the risks of blood pressure-related health problems. Let’s look at each individually.
Blocking Angiotensin II
Quercetin, myricitrin, and myricetin are flavonoid molecules found in small amounts in a variety of plant foods.11,12 These flavonoids have been shown to help block the receptor for angiotensin II,13 which is a hormone that triggers the constriction (narrowing) of arteries.14
Much like a finger over a garden hose, the narrowing of arteries raises pressure within them. Thus, blocking the angiotensin receptors is an effective way of bringing down blood pressure by helping to relax the arteries.
In addition to controlling high blood pressure, angiotensin receptor blockers have numerous other benefits, including enhancing insulin sensitivity, increasing the utilization of fat as energy, and improving mitochondrial function.15-17
Experimental studies using assessment of receptor docking (i.e. the ability of a molecule to bind to a receptor) suggest that both quercetin and myricetin are effective at blocking angiotensin II receptors.13 Life Extension has recommended a class of drugs called angiotensin receptor II blockers for antihypertensive management over the past several years given the typically good tolerability and efficacy of this drug class.
A lab study demonstrated that myricetin inhibited the arterial contracting response to angiotensin by 43% compared with the natural condition—an effect that significantly reduced systolic blood pressure in hypertensive rats.18
Multiple clinical studies have demonstrated quercetin’s and myricitrin’s blood pressure-lowering effects in humans as well. In both healthy adults and in those who were overweight or obese, 150 mg a day of quercetin significantly reduced systolic blood pressure compared with subjects’ baseline values or with placebo.19,20
And in those with “prehypertension” and early hypertension (both conditions should be treated, according to the latest New England Journal of Medicine results), one study found that 162 mg a day of quercetin reduced systolic blood pressure by 3.9 mmHg compared to a placebo,21 and a second study showed that 730 mg a day of quercetin reduced systolic and diastolic blood pressure by 7 mmHg and 5 mmHg respectively compared with baseline values.22
Quercetin and myricitrin have also been found to lower blood pressure in type II diabetics, a population that is at an especially high risk for hypertension, as a result of complications from the disease. In women with type II diabetes, 500 mg a day of quercetin lowered systolic pressure by 5.3 mmHg compared with a placebo.23 And 600 mg a day of leaf powder from myricitrin-containing extract produced an 11 mmHg decrease in systolic blood pressure compared with baseline!24
Natural Calcium-Channel Blocker
Stevioside is a molecule derived from the leaves of Stevia rebaudiana, a plant that has gained popularity in recent years because its sweet-tasting leaves are often used as non-caloric sweeteners.25,26
Studies reveal that the stevia plant has an even sweeter benefit: it naturally lowers blood pressure. Stevioside blocks calcium channels in the smooth muscle cells of the arteries.27-29 When intracellular calcium levels rise, it causes the cells to constrict, which narrows arteries and increases blood pressure. Thus, blocking calcium channels is a distinct—and extremely effective—means of reducing blood pressure.
Calcium channel-blocking medications are a reliable means of lowering blood pressure, and are often used in combination with angiotensin II receptor blockers (ARBs). In the same way, combining stevioside with flavonoids such as quercetin, myricitrin, and myricetin provides a similar dual mechanism of action.
Numerous studies demonstrate stevioside’s blood pressure-lowering effects. A meta-analysis published in 2015 included data from 788 patients taking doses of stevioside ranging from 750 to 1,500 mg a day.30 Individuals supplementing with stevioside demonstrated a decrease in systolic blood pressure of 4.5 mmHg in all studies. And, among studies in which supplementation was continued for a year or longer, the mean reduction was an impressive 11.9 mmHg.
Nighttime Blood Pressure Control
Lowering high blood pressure is critical, but providing an around-the-clock blood pressure-lowering effect is equally important.
Melatonin is a hormone intimately involved with regulating the human circadian rhythm, or day/night cycle. It has multiple effects both in the brain and in the body as a whole that include reduction of nighttime blood pressure.31-33 This is an essential feature for the 35% of “non-dippers” with hypertension.
Melatonin receptors lower blood pressure by dilating (opening) blood vessels34 and by inhibiting signals from the sympathetic nervous system (the “Fight or Flight” reflex).34,35 Animal studies show that melatonin can reverse the elevated blood pressure induced by high-fat and high-salt diets, while also reducing other manifestations of metabolic syndrome. It also protects the kidneys and other organs from the long-term consequences of elevated blood pressure.36-38
But not all melatonin is equally effective in its blood pressure benefits. A meta-analysis report on 7 studies involving 211 total subjects evaluated the difference between immediate-release melatonin formulations (5 mg a day) and controlled-release melatonin formulations (ranging from 2-3 mg a day).32
What these studies found was that controlled-release melatonin in particular was most effective at controlling nighttime blood pressure. Only controlled-release melatonin had significant effects on systolic blood pressure, reducing it by an average of 6.1 mmHg, while immediate-release melatonin produced only an insignificant 0.3 mmHg reduction.32
Controlled-release melatonin also lowered diastolic blood pressure significantly by an average of 3.5 mmHg, while the immediate-release formulation lowered diastolic pressures by just 0.2 mmHg.32
High blood pressure is a “silent killer,” producing no symptoms in most victims, while causing severe and often irreversible damage to blood vessels and the major organs they serve.39
A recent study supports what Life Extension has been saying for decades: that ideal systolic blood pressure targets should be under 120 mmHg—far below the 140 mmHg target maintained by mainstream medicine.
Natural compounds have been identified that work in similar ways as two classes of antihypertensive drugs—while also providing nighttime blood pressure relief.
The flavonoids quercetin, myricitrin, and myricetin bind to angiotensin receptors, preventing a rise in blood pressure. Stevioside blocks calcium channels in arterial wall smooth muscle, allowing vessels to relax and reducing blood pressure. And melatonin, only in time-release form, eases nighttime blood pressure to complete the cycle of protection.
These natural compounds can form part of the plan for everyone with systolic blood pressure readings of 120 mmHg or higher.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Elliott HL. 24-hour blood pressure control: its relevance to cardiovascular outcomes and the importance of long-acting antihypertensive drugs. J Hum Hypertens. 2004;18(8):539-43.
- Pierdomenico SD, Pierdomenico AM, Coccina F, et al. Circadian blood pressure changes and cardiovascular risk in elderly-treated hypertensive patients. Hypertens Res. 2016.
- Verdecchia P, Schillaci G, Porcellati C. Dippers versus non-dippers. J Hypertens Suppl. 1991;9(8):S42-4.
- Sprint Research Group, Wright JT, Jr., Williamson JD, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015;373(22):2103-16.
- Yusuf S, Teo K, Anderson C, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008;372(9644):1174-83.
- Goyal SN, Bharti S, Bhatia J, et al. Telmisartan, a dual ARB/partial PPAR-gamma agonist, protects myocardium from ischaemic reperfusion injury in experimental diabetes. Diabetes Obes Metab. 2011;13(6):533-41.
- Iwai M, Inaba S, Tomono Y, et al. Attenuation of focal brain ischemia by telmisartan, an angiotensin II type 1 receptor blocker, in atherosclerotic apolipoprotein E-deficient mice. Hypertens Res. 2008;31(1):161-8.
- Iwanami J, Mogi M, Tsukuda K, et al. Low dose of telmisartan prevents ischemic brain damage with peroxisome proliferator-activated receptor-gamma activation in diabetic mice. J Hypertens. 2010;28(8):1730-7.
- Yuen CY, Wong WT, Tian XY, et al. Telmisartan inhibits vasoconstriction via PPARgamma-dependent expression and activation of endothelial nitric oxide synthase. Cardiovasc Res. 2011;90(1):122-9.
- Myojo M, Nagata D, Fujita D, et al. Telmisartan activates endothelial nitric oxide synthase via Ser1177 phosphorylation in vascular endothelial cells. PLoS One. 2014;9(5):e96948.
- Ross JA, Kasum CM. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr. 2002;22:19-34.
- Hobbs CA, Swartz C, Maronpot R, et al. Genotoxicity evaluation of the flavonoid, myricitrin, and its aglycone, myricetin. Food Chem Toxicol. 2015;83:283-92.
- Laskar MA, Choudhury MD. In silico screening of some plant based natural products as angiotensin receptor blockers against cardiovascular diseases. World Journal of Pharmacy and Pharmaceutical Science. 2015;4(1):1248-57.
- Taubman MB. Angiotensin II: a vasoactive hormone with ever-increasing biological roles. Circ Res. 2003;92(1):9-11.
- Kurokawa H, Sugiyama S, Nozaki T, et al. Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway. Atherosclerosis. 2015;239(2):375-85.
- Shiota A, Shimabukuro M, Fukuda D, et al. Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice. Cardiovasc Diabetol. 2012;11:139.
- Sugimoto K, Kazdova L, Qi NR, et al. Telmisartan increases fatty acid oxidation in skeletal muscle through a peroxisome proliferator-activated receptor-gamma dependent pathway. J Hypertens. 2008;26(6):1209-15.
- Godse S, Mohan M, Kasture V, et al. Effect of myricetin on blood pressure and metabolic alterations in fructose hypertensive rats. Pharm Biol. 2010;48(5):494-8.
- Pfeuffer M, Auinger A, Bley U, et al. Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms. Nutr Metab Cardiovasc Dis. 2013;23(5):403-9.
- Egert S, Bosy-Westphal A, Seiberl J, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr. 2009;102(7):1065-74.
- Brull V, Burak C, Stoffel-Wagner B, et al. Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial. Br J Nutr. 2015;114(8):1263-77.
- Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in hypertensive subjects. J Nutr. 2007;137(11):2405-11.
- Zahedi M, Ghiasvand R, Feizi A, et al. Does Quercetin Improve Cardiovascular Risk factors and Inflammatory Biomarkers in Women with Type 2 Diabetes: A Double-blind Randomized Controlled Clinical Trial. Int J Prev Med. 2013;4(7):777-85.
- Sales DS, Carmona F, de Azevedo BC, et al. Eugenia punicifolia (Kunth) DC. as an adjuvant treatment for type-2 diabetes mellitus: a non-controlled, pilot study. Phytother Res. 2014;28(12):1816-21.
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- Mutoh T, Shibata S, Korf HW, et al. Melatonin modulates the light-induced sympathoexcitation and vagal suppression with participation of the suprachiasmatic nucleus in mice. J Physiol. 2003;547(Pt 1):317-32.
- Leibowitz A, Volkov A, Voloshin K, et al. Melatonin prevents kidney injury in a high salt diet-induced hypertension model by decreasing oxidative stress. J Pineal Res. 2016;60(1):48-54.
- Qiao YF, Guo WJ, Li L, et al. Melatonin attenuates hypertension-induced renal injury partially through inhibiting oxidative stress in rats. Mol Med Rep. 2016;13(1):21-6.
- Cano Barquilla P, Pagano ES, Jimenez-Ortega V, et al. Melatonin normalizes clinical and biochemical parameters of mild inflammation in diet-induced metabolic syndrome in rats. J Pineal Res. 2014;57(3):280-90.
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