Blood Pressure Management

Nutrients to Support Healthy Blood Pressure Levels

Nutritional approaches to hypertension management mirror many of the strategies of pharmaceutical therapies. The inclusion of specific dietary compounds with blood pressure lowering (hypotensive) or cardioprotective properties can significantly support cardiovascular health.

Several dietary compounds can also lower blood pressure through the mechanism of anti-oxidation. Hypertension is associated with an increase in oxidative stress and the activity of pro-oxidant enzymes. Oxidative stress can inactivate the vasodilation signal nitric oxide (NO) by converting it into the peroxynitrite free radical. Several hypotensive antioxidants appear to function by reducing this oxidative damage, and by preserving the bioavailability of NO.

Cardioinhibitory & Cardiotonic nutraceuticals

Magnesium. As early as the 1950’s the hypotensive effects of magnesium were a focus of speculation based on findings showing that drinking hard water (which is high in magnesium and other minerals) is associated with lower cardiovascular mortality (Mizushima 1998). Dozens of observational studies have demonstrated that magnesium intake is associated with lower blood pressure, and that hypertensive individuals have lower intakes of magnesium than those with normal blood pressures (Mizushima 1998). Magnesium may lower blood pressure both by acting like a natural calcium channel blocker and serving as a cofactor for the production of the vasodilator prostaglandin E1 (Houston 2008).

Interventions using magnesium have shown modest effects on blood pressure. An analysis of twelve controlled trials containing over 500 patients demonstrated that supplemental magnesium for 8 to 26 weeks led to an average decrease in diastolic blood pressure of 2.2 mmHg (Dickinson 2006). A comprehensive analytical review of 44 human studies of supplemental magnesium showed that it may enhance the blood pressure lowering effect of anti-hypertensive medications in early-stage hypertensive subjects. Patients treated with medications continuously over 6 months saw significant further decreases in both systolic and diastolic blood pressure with magnesium supplementation as low as 230 mg per day (Rosanoff 2010).

Supplementation with 300 to 500 milligrams of elemental magnesium each day is vital for those taking diuretic drugs. Absorption of magnesium into the bloodstream is not particularly effective. Higher blood magnesium levels may be achieved by taking 2,000 mg daily of a compound called magnesium threonate, even though its elemental magnesium is relatively low (Slutsky 2010).

Hawthorn (Crataegus laevigata; Crataegus monogyna; Crataegus oxyacantha) is a traditional cardiovascular tonic that has been in use since the Middle Ages. Hawthorn extracts are believed to exhibit mild blood pressure lowering activity by multiple mechanisms, including the dilation of coronary and peripheral blood vessels, the inhibition of ACE, anti-oxidative and anti-inflammatory effects, and mild diuretic activity (Graham 1939; Furey 2008). It also improves cardiac oxygen consumption (Pittler 2008).

Three trials have supported the potential blood pressure lowering activity of Hawthorn extracts. A small randomized controlled study of 36 untreated, mildly hypertensive, middle-aged subjects compared standardized hawthorn extract (500 mg) and magnesium (600 mg), both separately and in combination for 10 weeks. There was a small decrease in diastolic blood pressure in the hawthorn group after 10 weeks of supplementation (Walker 2006). In a second larger study, 92 middle aged hypertensive participants were randomized to take standardized hawthorn extract or placebo 3 times daily for 4 months. Hawthorn demonstrated a significant decrease in both systolic and diastolic blood pressure (Asgary 2004). In the third study, a group of 39 patients with type 2 diabetes took hawthorn extract in conjunction with existing blood pressure or blood sugar lowering drugs. Test participants randomized to 1,200 mg hawthorn extract/day for 16 weeks saw a 2.6 mmHg drop in diastolic blood pressure from baseline values, while the control group saw no change (Walker 2006).

Regulation of blood volume

Potassium is one of the most abundant electrolytes in the body. Due to their antagonistic roles in metabolism, the balance of sodium and potassium plays a critical role in blood pressure regulation. Potassium increases excretion of sodium from the kidneys, (reducing blood volume) and reduces the sensitivity of blood vessels to vasoconstriction by angiotensin II (Krishna 1993).

Evidence from observational studies and clinical trials consistently indicate that high levels of potassium are associated with lower blood pressure (Houston 2008). Four comprehensive reviews of potassium trials report average reductions in systolic blood pressure of 2.4-5.9 mmHg and diastolic of 1.6-3.4 mmHg, when supplementing with potassium for 2-8 weeks (Cappuccio 1991; Whelton 1997; Geleijnse 2003; Dickinson 2006). The degree of blood pressure lowering appears to be dose dependent, with the largest decreases in blood pressure occurring at the high end of the dosage range (daily doses of 1.9-4.7 g were used in the trials).

The adequate intake (AI) of potassium is 4.7 g/day for adults. Most adults have a median dietary intake substantially lower than this (2.8 - 3.3 g/day in men and 2.2-2.4 g/day in women) (Food and Nutrition Board 2005). Less than 3 percent of the population consumes the AI (Nicklas 2009). It should be noted that the amounts of potassium in over-the-counter supplements is typically <100 mg/day, so individuals with high blood pressure should consume potassium rich foods to ensure adequate intake.

Calcium. In addition to magnesium and potassium, population-based studies suggest a role for calcium in the prevention of hypertension, possibly through its ability to promote sodium excretion, balance the concentrations of other minerals (particularly magnesium and potassium), and its role in the activity of smooth muscle cells in blood vessels (Hamet 1995; Resnick 1991). In a review of 40 randomized controlled trials an average daily calcium dose of 1,200 mg was associated with a reduction in systolic (1.9 mmHg) and diastolic (1.0 mmHg) blood pressure. In persons with habitually low calcium intake (< 800 mg /day), the hypotensive effect was even greater (2.6/1.3 mm Hg) (van Mierlo 2006).

Antioxidants

CoQ10. As a critical component of mitochondrial function and energy production, CoQ10 has a central role in proper cardiac function (Adrash 2008). Within blood vessels, CoQ10 may directly contribute to the functionality of vascular smooth muscle cells, allowing them to properly dilate (Digiesi 1992). As a lipid-soluble antioxidant, CoQ10 may quench free radicals and spare levels of vasodilatory nitric oxide (Rosenfeldt 2007).

In two separate reviews of human CoQ10 studies (a total of 12 studies comprising 328 hypertensive patients), all showed improvements in blood pressure (Ho 2009; Rosenfeldt 2007). Three randomized, controlled trials of CoQ10 (100-120 mg/day for up to 8 weeks) demonstrated mean decreases in systolic and diastolic blood pressure of 11 mmHg and 7 mmHg, respectively, while open label trials revealed slightly larger average decreases (-13.5/-10.3 mmHg) (Rosenfeldt 2007).

CoQ10 (at 200 mg/day) has also been shown to improve blood pressure and blood sugar control in type 2 diabetics when combined with the cholesterol-lowering drug fenofibrate (Chew 2008). CoQ10 may lead to modest reductions in diastolic blood pressure in chronic kidney disease patients when combined with fish oil (Mori 2009).

Carotenoids. Epidemiological evidence suggests that the risk of hypertension decreases as the concentration of four serum carotenoids (α- and β-carotene, lutein/zeaxanthin, and β-cryptoxanthin) increases (Hozawa 2009). In addition, lycopene is a carotenoid that has demonstrated hypotensive activity in a human intervention study: A small crossover study of 31 patients with stage 1 hypertension taking 250 mg of a lycopene-enriched tomato extract for 8 weeks demonstrated significant reductions in blood pressure (-10/-4 mmHg), while no changes in blood pressure were observed during the placebo period. Thiobarbituric acid–reactive substances (TBARS), a marker oxidative stress, also decreased during the test period (Engelhard 2006).

Chlorogenic acid from green coffee (unroasted coffee beans) is a hypotensive antioxidant, likely increasing the availability of nitric oxide for vasodilation by inhibiting enzymes that form reactive oxygen free radicals (Chen 2009). The roasting of coffee reduces the effects of chlorogenic acid on blood pressure. Still, the activity of chlorogenic acid remaining in roasted coffee is enough to counteract some of the hypertensive effects of caffeine, explaining why coffee consumption raises blood pressure less than does an equivalent amount of caffeine alone (Noordzij 2005). Green coffee bean (GCE) extract supplements are available to provide standardized doses of chlorogenic acid with minimal amounts of caffeine.

Two multi-center, randomized controlled trials investigated the effects of different doses of chlorogenic acid on volunteers with mild hypertension. In the first, 117 male volunteers were randomized into 3 dosage groups (46 mg, 93 mg, or 185 mg) of green coffee extract versus placebo once per day for 28 days. At study end, average reductions in systolic blood pressure from baseline (4.7 mmHg and 5.6 mmHg for the medium and high dose groups, respectively) varied significantly from placebo. Differences in diastolic blood pressure from the placebo group were also observed in the medium and high-dose groups (-3.2 mmHg and- 3.9 mmHg, respectively) (Kozuma 2005). The second trial, with a similar design and duration, tested four doses of green coffee bean extract standardized to chlorogenic acid (0 mg, 82 mg, 172 mg, or 299 mg), in 203 pre- and stage 1 hypertensive volunteers (male and female). Green coffee bean extract had an anti-hypertensive effect on systolic blood pressure in a dose-dependent manner (ranging from -2.7 mmHg to -3.3 mmHg for the low and high doses, respectively). Diastolic blood pressure reduction was consistent across all dosages (approximately 3 mmHg) (Yamaguchi 2008).

Vitamin C is an essential water-soluble antioxidant vitamin in humans. It is thought to exert hypotensive effects through an improvement in endothelial function, a reduction in arterial stiffness, and its ability to bind the angiotensin receptor (thereby lowering its ability to bind angiotensin II (Leclerc 2008). Higher plasma levels of vitamin C are associated with lower blood pressure (Bates 1998). In observational studies, individuals with the highest plasma ascorbic acid (vitamin C) concentrations had 4.66 mmHg lower systolic blood pressure and 6.04 mmHg lower diastolic blood pressure than those with the lowest concentrations (Block 2008).

Intervention studies with vitamin C in hypertensive adults have shown mixed results. Several small studies have shown modest reductions in systolic (1.8 to 4.5 mmHg) and diastolic blood pressure (2.8mm Hg) at doses of 500 mg to 2000 mg/day (Mahajan 2007; Sato 2006; Ward 2005; Duffy 1999; Fotherby 2000; Hajjar 2002), while others failed to reveal significant effects (Kim 2002; Ghosh 1994; Magen 2004).

Vasodilators

Grape Seed Extract contains oligomeric procyanidins (OPCs) that support vasodilation through an increase in nitric oxide (NO) production and ACE inhibition (Clouatre 2010). Two 4-week studies of standardized grape seed extract (150 mg or 300 mg) in pre-hypertensive patients with metabolic syndrome demonstrated a marked reduction in systolic and diastolic blood pressure. The reduction averaged -12/-7 mmHg between the two studies and did not significantly differ between the two dosages (Siva 2006; Sivaprakasapillai 2009). Another trial is underway as of August 2011 (ClinicalTrials.gov 2011).

Pomegranate contains several bioactive antioxidant polyphenols, including punicalagins. Pomegranate juice consumption (50 ml {1.7 oz.} of juice per day) has been associated with decreases in systolic blood pressure of 8 mmHg in a 2 week study (Aviram 2001), and 21 mmHg in 1 year study (Aviram 2001).

In addition to its potent antioxidant activity (it has been shown to reduce LDL oxidation and increase levels of the cellular antioxidant glutathione) (Aviram 2004), pomegranate polyphenols also function as ACE inhibitors. Reductions in ACE activity by 36% have been demonstrated after 2 weeks of pomegranate juice consumption (Aviram 2001).

L-arginine is an amino acid that serves as the main raw material for the production of the vasodilator nitric oxide (NO). Low cellular levels of L-arginine and nitric oxide are evident in individuals genetically predisposed to hypertension, likely due to inefficient transport of L-arginine across the cellular membrane (Schlaich 2004). Test diets rich in arginine-containing foods, or supplemented with arginine, demonstrated decreases in blood pressure (6.2 mmHg systolic, 5.0-6.8 mmHg diastolic) when compared to control diets in a short-term human study (Siani 2000). Reductions in systolic and diastolic blood pressure were also observed in a pilot trial where kidney transplant patients were supplemented with 18 g/day of arginine (Kelly 2001), as well as in a small controlled trial with diabetic patients (Martina 2008).

Soy isoflavones have been suggested to increase arterial vasodilation, improve endothelial function, and decrease blood pressure, possibly by reducing oxidative stress and increasing the availability of nitric oxide (Mahn 2005). Two analyses of 25 randomized controlled trials confirm the effect of isoflavone intake on reductions in blood pressure. In the first analysis, 14 clinical trials with 789 participants (both with normal blood pressure and pre-hypertension) revealed that a daily ingestion of 25–375 mg of purified soy isoflavones for 2–24 weeks decreased systolic blood pressure by an average of 1.92 mmHg compared with placebo (Taku 2010). Decreases in systolic blood pressure were greater in studies of longer duration (3.45 mmHg in studies longer than 3 months).

A second analysis of 11 trials (with a total of 549 participants) looked at isoflavone intake from soy protein, revealing a similar average reduction of systolic (2.5 mmHg) and diastolic (1.5 mmHg) blood pressure when compared to placebo (Liu 2011). These trials used a narrower range of isoflavone dosage (65-153mg/day). Within the trials utilized in this analysis, the blood pressure lowering effects of soy isoflavones were greatest in both hypertensive patients and in trials lasting longer than 3 months.

Olive leaf (Olea europaea) has traditionally been used to treat high blood pressure, atherosclerosis, and diabetes (Janicke 2003). The leaves contain the active compounds oleuropein, and oleacein, which may function as a vasodilator and ACE inhibitor, respectively (Somova 2003). They also contain ursolic and oleanic acids, two compounds that have been shown to promote normal heart rhythm and lower cardiac output (acting as beta blockers) in rats (Somova 2004). Olive leaf extract has also shown calcium channel-blocking activity (Scheffler 2008).

Despite traditional usage, controlled human clinical trials on olive leaf extract have, until recently, been equivocal (Cherif 1996; Scheller 1955). Two recent studies using a standardized commercial extract, however, have produced promising results (Perrinjaquet-Moccetti 2008). The first was an open-label, controlled study using 20 pairs of identical twins with borderline hypertension. Supplementation with 1,000 mg of olive leaf extract over eight weeks resulted in a decrease of up to 19/10 mmHg within pairs. Within pairs of subjects, differences in blood pressure could be observed at a lower dosage of 500 mg (Perrinjaquet-Moccetti 2008). In the second study, 148 stage-1 hypertensive patients were randomized to captopril (a prescription ACE Inhibitor) or olive leaf, 500 mg twice daily. After 8 weeks, mean reductions in systolic blood pressure from baseline were -11.5 and -13.7 mmHg in olive and captopril groups, respectively. Reductions in diastolic blood pressure were -4.8 and -6.4 mmHg, respectively, indicating that olive leaf extract was nearly as effective as the prescription drug for lowering blood pressure. The olive leaf extract group also demonstrated reductions in serum total cholesterol (2.8%) and triglycerides (7.8%), as well as a borderline statistically significant reduction in LDL-cholesterol (2.9%) (Susalit 2011).

Other Hypotensive Dietary Factors

Vitamin D has several direct and indirect effects on cardiovascular health. It contributes to the maintenance of blood pressure by suppressing the production of renin in the kidneys (lowering angiotensin II production) (Li 2003). It can also suppress parathyroid hormone and pro-inflammatory cytokines, which are both associated with cardiovascular disease. The endothelial cells, which line the insides of blood vessels, have receptors for vitamin D, which suggests a direct effect of vitamin D on vascular metabolism. Several observational studies have revealed an increased risk for hypertension when comparing persons with the lowest and highest vitamin D intake. An analysis of 18 intake studies revealed a 16% reduction in the risk of hypertension for every 16 ng/ml increase in serum vitamin D (Burgaz 2011). According to data from the National Health and Nutrition Examination Survey (NHANES), nearly 75% of light-skinned, and up to 90% of dark-skinned Americans are vitamin D insufficient (Adams 2010).

Interventions using vitamin D have demonstrated modest results for lowering blood pressure. A review of 11 randomized, controlled vitamin D intervention trials, including over 700 subjects, demonstrated a small reduction in systolic (3.6 mmHg) and diastolic (3.1 mmHg) blood pressure at daily doses of 800-2,500 IU (Witham 2009). Supplemental D2 and D3 exhibited an average systolic blood pressure reduction of 6.2 mmHg, while alfacalcidol, (a synthetic, activated analogue of vitamin D3), had no effect. A second review of vitamin D trials, including 2 newer studies, revealed a mean systolic blood pressure reduction of 2.44 mmHg (Wu 2010).

Life Extension suggests that all individuals maintain a blood 25-hydroxyvitamin D level of 50 – 80 ng/ml. Doing so often requires daily supplementation with 5,000 – 8,000 IU of vitamin D. Supplemental doses should always be based upon an individual’s blood test results.

Vitamin K. Atherosclerosis is a leading cause of disability and death in civilized societies. Many factors are involved in the initiation and progression of atherosclerosis. Vascular assaults including homocysteine or oxidized low-density lipoprotein (LDL) can initially damage the inner arterial lining (the endothelium) (Mallika 2007). To repair this damage, the endothelium accumulates collagen that forms a cap over the injury site (Lafont 1999).

These endothelial collagen caps attract calcium that accumulates (calcifies) and forms a hard material resembling bone; this is why atherosclerosis is sometimes referred to as “hardening of the arteries.” Ultimately, this process suppresses vascular flexibility and also causes narrowing of the passage through which blood must flow, leading to increased blood pressure. Calcification of the coronary arteries markedly increases heart attack risk as well (Bellasi 2007).

Studies reveal that vitamin K plays an indispensible role in the balance of calcium deposition as it relates to both skeletal and vascular health. Vitamin K ensures that adequate calcium remains in the bones for strength while keeping calcium out of the arteries to maintain flexibility (Schurgers 2001; Doherty 2003; Beulens 2008). A substantial volume of research shows that insufficient vitamin K2 accelerates arterial calcification (Beulens 2008). Indeed, animal models indicate that supplemental vitamin K is able to reverse arterial calcification (Schurgers 2007).

Garlic’s promotion of cardiovascular health has been substantiated by several human trials, particularly its hypotensive activity and ability to induce favorable blood lipid profiles. Garlic also reduces systolic and diastolic blood pressure in hypertensive individuals, as well as systolic blood pressure in persons with normal blood pressure. A recent review and analysis of 11 controlled human trials showed a mean decrease of 4.6 mmHg for systolic blood pressure in the garlic group compared to placebo, while the mean decrease in the hypertensive subjects was 8.4 mmHg for systolic and 7.3 mmHg for diastolic (Ried 2008).

Fish Oil is a source of the omega-3 fatty acids Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA), which are made to a very limited degree in the human bodyfrom alpha-linolenic acid, but are nonetheless essential for several metabolic processes. Aside from reductions in the risk of cardiovascular mortality and non-fatal cardiovascular events (Marik 2008), fish oil fatty acids show reductions in blood pressure. In an analysis of 36 clinical trials on the effects of omega-3 supplementation in over 2,000 individuals with normal and high blood pressure, a median intake of 3.7 g/day of fish oil demonstrated an average blood pressure reduction of 2.1 mmHg (systolic) and 1.6 mmHg (diastolic) (Geleijnse 2002). The effects were greater in hypertensive individuals, with average reductions of 4 mmHg (systolic) and 2.73 mmHg (diastolic). Omega-3 fatty acids from fish oil have also demonstrated modest hypotensive activities in diabetic patients. A review and analysis of five small randomized controlled trials revealed a mean blood pressure reduction of 1.69/1.79 mmHg (Hartweg 2007).

Sesame lignans (including sesamin and sesamolin) are found in sesame seeds and present in sesame oil. Several animal studies have reported that sesame lignans suppress the development of hypertension (Matsumura 1998; Kita 1995; Nakano 2002). When used as a substitute for other types of cooking oil, sesame oil (about 35 g/oil day as part of meal preparation) exhibited significant reductions in systolic (20 mmHg) and diastolic (18 mmHg) blood pressure in 40 middle-aged, diabetic, hypertensive patients after a period of 45 days. These changes disappeared after switching back to groundnut or palm oils (Sankar 2006). A larger study of similar design (356 hypertensive patients on the calcium channel blocker nifedipine) produced similar reductions in systolic and diastolic blood pressure from baseline values. Sesame oil further increased the hypotensive efficacy of nifedipine (reducing blood pressures by an average of almost 15/10 mmHg over the drug alone) (Sankar 2005). A small randomized controlled trial of purified sesamin supplementation (30 mg, 2 times/day for 4 weeks) in 25 middle aged, pre-hypertensive subjects decreased systolic blood pressure by 3.5 mmHg and diastolic by 1.9 mmHg (Sankar 2005).

Sesame lignans may lower blood pressure due to their suppression of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE). A 30% reduction in 20-HETE levels has been observed in humans after 5 weeks of sesamin supplementation (39 mg/day) (Wu 2009). Sesame lignans may also lower blood pressure through antioxidant activity (sparing nitric oxide from oxidation) (Miyawaki 2009).

Whey protein peptides have antioxidant potential and display blood pressure lowering properties (Chitapanarux 2009; Laviolette 2010; Marshall 2004). They also contribute to blood vessel relaxation and reduced “stiffness” (Pal 2010). The discovery that antioxidant status directly affects angiotensin availability further explains how whey proteins may fight elevated blood pressure (Zhou 2010). Human studies of whey-rich or whey-enriched milk products demonstrate convincing reductions in blood pressure compared with placebo- or casein-supplemented patients (Pal 2010; Kawase 2000; Pins 2006).

In recent years, scientists have found that whey proteins exert substantial direct angiotensin-converting enzyme (ACE)-inhibiting effects (Vermeirssen 2002; Manso 2003; Vermeirssen 2003). In the human stomach and intestine, some whey protein breaks down into very specific short amino acid chains (peptides) that function as efficient ACE-inhibitors (Abubakar 1998; Parrot 2003; Vermeirssen). Laboratory studies consistently show that blood pressure is reduced in hypertensive animals given whey protein derivatives (Yamamoto 1999; Costa 2005). This effect is attributed, in part, to ACE inhibition. The ACE-inhibitory effect is substantially less powerful than those of prescription drugs. However, some people encounter side effects with those drugs (FitzGerald 2004). Whey protein derivatives, by contrast, can be used for long periods of time without adverse side effects. Other studies suggest that these active milk components also inhibit the release of other vessel-constricting molecules such as endothelin-1, offering a second pathway for blood pressure control (Maes 2004).