Managing Essential Hypertension

A Review of Evidence-Based Strategies
Elaine Lewis, HBSc, ND
Monique Aucoin, BMSc, ND
Kieran Cooley, Bsc, ND, MSC CAND

Primary hypertension (HTN) is one of the most prevalent and preventable diseases facing North America. The disorder is linked to premature mortality, disability and morbidity, often in the form of cardio- and cerebrovascular events, in addition to increased medication and disease burden for other chronic health conditions.1 Alongside rising incidence rates, recent estimates of prevalence remain high, with self-reported diagnosis ranging from 20-35% of the adult population and use of anti-hypertensive medications ranging from 52-74% in the United States.2 In Canada, an estimated 23% of the population has been diagnosed with HTN, while a further 17% of adults remains undiagnosed.3 A concerted public health strategy has identified targets to reduce the prevalence of HTN to 13% of adults, and to improve effective control to 78%,4 though the means of achieving this for various populations remain unclear. The recently released guidelines for effective diagnosis and treatment of HTN by the National Institute for Health and Care Excellence (NICE) and the Canadian Hypertension Education Program clearly outline approaches to diagnosis and management through lifestyle and pharmacologically-focused strategies informed by best evidence and based on the presentation of individual patients. Generally, the conventional approach outlined in the guidelines advocates initiating monotherapy with a thiazide diuretic (Grade A); a beta-blocker (in patients younger than 60 years, Grade B); an angiotensin-converting enzyme (ACE) inhibitor (in non-black patients, Grade B); a long-acting calcium-channel blocker (CCB) (Grade B); or an angiotensin receptor blocker (ARB) (Grade B) if non-emergent, and, notably, not initiating calcium, magnesium or potassium supplementation (Grade B) at the outset for patients with systolic blood pressure (SBP) >160 mm Hg, or diastolic blood pressure (DBP) >100 mm Hg. A clear outline of lifestyle (physical exercise, diet, sodium intake, alcohol consumption, stress management and weight reduction) and the corresponding evidence levels is also presented in these guidelines.

Notably, however, efficient and effective strategies to increase awareness and implementation of guidelines (print & interactive guidelines, and expert seminars), as well as the subsequent impact on treatment approaches to HTN have not been highly successful in the past.5 Though recent studies have demonstrated naturopathic medicine as a whole to be effective for prevention and treatment of cardiovascular disease6 and hypertension,7 clear, evidence-based assessments of available treatment options may be beneficial to the naturopathic profession, with respect to providing guidance on achieving targets, effective dosing strategies and reasonable clinical expectations or implementation of potentially cost-effective integrative treatment approaches. (Refer to Table 1 for a summary of evidence-based treatments for HTN.)

Table 1.Summary of evidence-based treatments for hypertension

Reference	Study Design and Intervention	Study Population	Change in Blood Pressure (Systolic)	Change in Blood Pressure (Diastolic )	Other Results	Safety and Other Comments
Olive Oil (OO)
Perona et al; 20048	RCT, crossover design; OO diet or sunflower oil diet (C) for 4 weeks; 60 g/day	n = 62 Hypertensive and medically treated, or normotensive	Among hypertensives: OO: 136 ± 10mm Hg; C: 150 ± 8mm Hg		Small reduction in BP in normotensives; not statistically significant
Ruiz-Gutierrez et al; 19969	Crossover design; OO or high-oleic sunflower oil (C); for 4 weeks	n = 16 HTN	Baseline: 161.21 ± 14.1 mm Hg; OO: 151.25 ± 10.3 mm Hg; C: 155.11 ± 7.07 mm Hg	Baseline: 94.93 ± 5.02 mm Hg; OO: 84.91 ± 8.11 mm Hg; C: 90.12 ± 8.88 mm Hg		Small study; moderate HTN
Ferrara et al; 200010	RCT, crossover design; OO diet or sunflower oil diet (C) for 6 months; 40 g for men, 30 g for women daily	n = 23 Mild-to-moderate HTN (<165/104)			Reduction of medication −48% (OO) vs −4% (C) (P < .005); medication eliminated  in 8 hypertensives vs 0 controls
Thomsen et al; 199511	Crossover design; OO diet (30% of calories) vs isocaloric PUFA diet (C) for 3 weeks	n = 16 Type 2 diabetes; normotensive	OO: 129 ± 11 mm Hg; C: 124 ±8 mm Hg (P = 0.02)	OO: 76 ± 11 mm Hg; C: 73 ± 8 mm Hg (P = 0.02)
Rasmussen et al; 199312	Crossover design; High-carbohydrate diet  vs isocaloric, high-fat diet (30% MUFA) for 3 weeks	n = 15 Type 2 diabetes; normotensive	Daytime systolic: High-fat diet: 131 ± 3 mm Hg; High-CHO diet: 137 ± 3 mm Hg (P < 0.04)	Daytime diastolic: High-fat diet: 78 ± 2; High-CHO diet: 84 ± 2 mm Hg (P < 0.02)
DASH Diet
Conlin et al; 200014	RCT with placebo run-in; 3 diets: Control; Control + fruits and vegetables (FV); DASH diet; 8 weeks	n = 133 Unmedicated; Stage 1 HTN	DASH: -11.4 mm Hg (P < .001); FV: -7.2 mm Hg (P < .001)	DASH: -5.5 mm Hg (P < .001); FV: -2.8 mm Hg (P = .013)	At the end of the study normal BP seen in 70% of DASH, 45% of FV and 23% of control subjects
Sacks et al; 200115	RCT with placebo run-in; 2 diets: Control or DASH diet; Subgroups in each (high-, medium- or low-sodium) for 30 days, each in random order	n = 412 Unmedicated; HTN or pre-HTN	Low-sodium DASH vs high sodium (C) in patients with HTN: -11.5 mm Hg; patients without HTN: -7.1 mm Hg		In both control and DASH diets, reduction of sodium produced significant, stepwise decreases in SBP and DBP
Blumenthal et al; 201016	RCT Control diet vs DASH diet vs DASH diet + weight management (DASH-WM) (500-calorie deficit, weekly CBP supervised exercise 3 times per week); 4 months	n = 144 BMI = 25-40 Unmedicated; SBP 130-159 mm Hg, or DBP 85-99 mm Hg	DASH diet: 11.2 mm Hg; DASH-WM: 16.1 mm Hg; C: 3.4 mm Hg	DASH diet: 7.5 mm Hg; DASH-WM: 9.9 mm Hg; C: 3.8 mm Hg	At the end of the study, HTN present in 38.8% of C, 15.2% of DASH, and 12.2% of DASH-WM groups	Very intense intervention with many visits per week: 2 times with nutritionist, 1 time for CBT, 3 times for exercise
Garlic
Ried et al; 200817	Meta-analysis of 11 RCTs using garlic-only supplements; 600 to 900 mg per day	n = 283 (garlic) versus 282 (C)	-4.6 ± 2.8 mm Hg for garlic vs C; Studies with baseline HTN: -8.4 ± 2.8 mm Hg	Studies with baseline HTN: -7.3 ± 1.5 mm Hg		Many studies were of short duration (7 of 11 were 12 weeks)
Reinhart et al; 200818	Meta-analysis of 10 RCTs	n = 139 in 3 studies, with mean baseline SBP>140 mm Hg n = 262 in 7 studies, with mean baseline SBP <140 mm Hg	Studies with baseline HTN: -16.3 mm Hg (95% CI -6.2 to -26.5); Non-significant when  mean baseline SBP <140 mm Hg	Studies with baseline HTN: -9.3 mm Hg (95% CI -5.3 to -13.3); Non-significant when mean baseline SBP <140 mm Hg		Studies analyzed mean baseline values, but may have included a range of patients
Nakasone et al; 201319	RCT; DB, PC 4-week run-in, 12-week intervention; 300 mg as dried garlic homogenate or placebo	n = 34 with pre-HTN n = 47 with mild HTN	Pre-HTN: no change HTN: −6.6 ± 2.3 mm Hg (garlic) vs −0.7 ± 1.4 mm Hg (placebo); (P < 0.05)	Pre-HTN: no change HTN: −4.6 ± 1.5 mm Hg (garlic) vs −0.5 ± 1.0 mm Hg (placebo); (P < 0.05)		18% of subjects in each group reported side effects including gastric distress, headaches, and abdominal pain
Ried et al; 201320	RCT; DB, PC, dose-response 12 week intervention; Placebo, 1, 2 or 4 capsules of aged garlic extract daily (240/480/960mg)	n = 84 Medicated but uncontrolled systolic HTN	2 capsules garlic vs C at 12 weeks: −11.8 ± 5.4mm Hg (P = 0.006) 4 capsules garlic vs C at 8 weeks:  -7.4 ± 4.1 mm Hg (borderline significance); (P = 0.07)	No significant change	1 capsule garlic vs C at 12 wks: Decrease in SBP, but not statistically significant	3 subjects withdrew with GI AEs (2 in 4-capsule group; 1 in C group); weak effect in 4-capsule group may have been due to lower tolerability and compliance
CoQ10
Ho et al; 200921	Meta-analysis of 3 DB, PC, RCTs 100-120 mg CoQ10 daily; 4-12 weeks	n = 96 Primary HTN Washout of all medication	Mean decreases of 11 mm Hg (95% CI 8, 14)	Mean decrease of 7 mm Hg (95% CI 5, 8)		Reviewers had concerns about quality of blinding, author credibility
Burke et al; 200122	RCT; DB, PC 60 mg CoQ10 BID; 12 weeks	n = 80 Isolated systolic HTN Washout of all medication	Mean decrease of 17.8 ± 7.3 mm Hg for CoQ10 vs C
Young et al; 201223	RCT; DB, PC, crossover 100 mg CoQ10 BID, in combination with previous HTN medication; 12 weeks	n = 30 Metabolic syndrome: SBP >140; Type 2 diabetes: >130	No statistically significant reduction for CoQ10 vs placebo (P = 0.60)	No statistically significant reduction for CoQ10 vs placebo (P = 0.12)		No adverse events reported
Fish Oil
Bao et al; 199824	Randomized, open-label Daily fish meal (3.65 g omega-3), weight reduction; combination or control; 16 weeks	n = 69 Overweight, medicated for HTN; SBP >125, <180; DBP <110	Relative to control: Daily fish meal: -6.0 mm Hg; Weight Reduction: -5.5 mm Hg; Combo: -13.0 mm Hg	Relative to control: Daily fish meal: -3.0 mm Hg; Weight Reduction: -2.2 mm Hg; Combo: -9.3 mm Hg		Participants in all groups were encouraged to decrease salt intake
Mori et al; 199925	RCT; DB, PC 4 g/day of purified EPA, DHA, or OO (placebo); 6 weeks	n = 59 Overweight, mildly hyperlipidemic men; normotensive	24-hour SBP, DHA vs placebo: -5.8 mm Hg	24-hour DBP, DHA vs placebo: -3.3 mm Hg		OO used as placebo; Suggests DHA may be the active constituent
Prisco et al; 199826	RCT; DB, PC 4 g/day fish oil (2.04 g EPA and 1.4 g DHA) or 4 g/day OO as placebo All ate a Mediterranean diet; 16 weeks	n = 32 16 with HTN (unmedicated); 16 normotensive	HTN + FO: From 154 ± 4 to 148 ± 5 mm Hg; HTN + OO: no change; Normotensives: no change	HTN + FO: From 97 ± 8 to 92 ± 6 mm Hg; HTN + OO: no change; Normotensives: no change		Occasional fish aftertaste in 3 subjects; full effect only seen at 16 weeks; OO used as placebo
Lungershausen et al; 199427	RCT; DB, cross-over 4 g/day of 85% n-3 fatty acid concentrate or corn oil; 6 weeks of each	n = 43 Taking beta-blocker and/or diuretic; Baseline SBP = 132 ± 2 mm Hg; DBP = 76 ± 1 mm Hg	Within-individual difference: -3.1 ± 1.0 mm Hg (P < 0.01)	Within-individual difference: -1.8 ± 0.6 mm Hg (P < 0.01)
Toft et al; 199528	RCT; DB 4 g EPA+DHA or 4 g corn oil as placebo; 16 weeks	n = 78 Untreated HTN	Fish oil relative to control: -3.8 mm Hg (from -6.6 to -1.0); (P = 0.04)	Fish oil relative to control: -2.0 mm Hg (from -4.3 to 0.3); (P = 0.10)	Reduction larger in patients with low baseline plasma n-3 fatty acids	Mild abdominal discomfort in 6 subjects in FO group and 3 subjects in C group
Exercise
Fagard et al; 200729	Meta-analysis of 72 RCTs	Dynamic aerobic endurance training: 105 study groups; Resistance training: 12 study groups	Aerobic: -3.3 mm Hg (P < 0.001) Resistance: -3.2 mm Hg (P = 0.10); Aerobic, baseline HTN:    -6.9 mm Hg (P < 0.001)	Aerobic: -3.5 mm Hg (P < 0.01); Resistance: -3.5 mm Hg (P < 0.01); Aerobic, baseline HTN:    -4.9 mm Hg (P < 0.001)
Cornelissen et al; 201130	Meta-analysis of 28 RCTs Dynamic or static resistance training; 2 to 3 sessions per week (median: 3); 6 to 52 weeks	33 study groups, n = 1012 Baseline BP: Optimal BP in13 studies; pre-HTN in15 studies; HTN in 5 studies	Normotensive and pre-HTN: -3.9 mm Hg (from -6.4 to -1.2); HTN: -4.1 mm Hg (from -0.63 to +1.4); not significant	Normotensive and pre-HTN: -3.9 mm Hg (from -5.6 to -2.2); HTN: -1.5 mm Hg (from -3.4 to +0.40); not significant	Isometric handgrip training: SBP -13.5 mm Hg (from -16.5 to -10.5); DBP: -2.7 mm Hg (from -3.8 to -1.7)	Many studies had limitations in description of randomization, blinding ; No serious AEs in any study
HIBISCUS SABDARIFFA
Herrera-Arellano et al; 200432	RCT Hibiscus calyx infusion QD (std 9.6 mg anthocyanins) vs captopril as control (25 mg BID); 4 weeks	n = 70 (38 experimental, 32 control) Mild-to-moderate HTN; Unmedicated 1 month prior to study	Hibiscus: -14.15 mm Hg ± 11.76 (P < 0.03); Captopril: -16.43 mm Hg ± 9.56 (P < 0.001)	Hibiscus: -11.18 mm Hg ± 6.91 (P < 0.06); Captopril: -13.12 mm Hg ± 7.23 (P < 0.01)	Therapeutic effectiveness: 0.7895 (hibiscus) vs 0.8438 (captopril) (p > 0.560) Significant natriuretic effect (urinary sodium excretion) (P < 0.001) with NS excretion of chlorine and potassium	100% tolerability
Herrera-Arellano et al; 200733	RCT; DB Hibiscus calyx dried extract QD (std 250 mg anthocyanins) vs 10 mg lisinopril as control; 4 weeks	n = 193 (100 experimental, 93 control) Stage I-II HTN	Hibiscus: -17.14 mm Hg (P < 0.05); Lisinopril: -23.31 mm Hg (P < 0.001)	Hibiscus: -11.97 mm Hg (P < 0.05); Lisinopril: -15.39 mm Hg (P < 0.001)	Significant increase in chlorine (P < 0.001) and NS increase in sodium urinary excretion with no change in potassium excretion (experimental group)	Tolerability and safety of 100% in hibiscus group; 65.12% effectiveness
Mozaffari-Khosravi et al; 200935	RCT; DB 240 mL hibiscus tea (2 g dry herb) BID vs black tea (control) BID; 4 weeks	n = 60 (27 experimental, 23 control) Diabetics with mild HTN; unmedicated	Hibiscus: -21.4 mm Hg (P < 0.001); Black tea: +8.7 mm Hg (P = 0.002)	Hibiscus: -1.1 mm Hg (P = 0.5); Black tea: +3.3 mm Hg (P = 0.5)	Significant reduction in pulse pressure	No AEs reported
McKay et al; 200936	RCT; DB, PC 240 ml hibiscus tea (1.25 g dry herb) TID vs placebo tea; 6 weeks	n = 65 (35 experimental, 30 placebo) Pre- & mild HTN; Unmedicated	Hibiscus: -7.2 ± 11.4 mm Hg (P < 0.05); Placebo: -1.3 ± 10.0 mm Hg	Hibiscus: -3.1 ± 7.0  mm Hg (P < 0.05); Placebo: -0.5 ± 7.5 mm Hg	Higher baseline SBP showed greater response to hibiscus tea; Mean arterial pressure significantly lower in hibiscus group after 6 wks, -4.5 ± 7.7 (P < 0.05)	No AEs reported
VITAMIN D
Witham et al; 200938	Meta-analysis & systematic review of 11 RCTs	n = 545 Mean baseline SBP >140 mm Hg	-3.6 mm Hg (95% CI, -8.0 to 0.7) (P = 0.1)	-3.1 mm Hg (95% CI, -5.5 to -0.6) (P = 0.01)	Unactivated Vitamin D (vitamin D2, D3 & UVB radiation) caused more significant reduction (-6.2; P = 0.05) compared to activated forms (calcitriol, 1-alpha calcidiol)	No AEs reported
Larsen et al; 201239	RCT; DB, PC 75 µg (3000 IU) cholecalciferol vs placebo; 20 weeks	n = 112 (55 experimental, 57 placebo) Mild-to-moderate HTN	24-hr SBP: -3.0 mm Hg (P = 0.26); Vit D-insufficient pts: -4.0 mm Hg (P = 0.05)	24hr DBP: -1.0 (P = 0.18); Vit D-insufficient pts: -3.0 (P = 0.01)	Similar BP reductions in day and night-time readings	No AEs reported
Forman et al; 201340	RCT; DB, PC 1000, 2000, 4000 IU cholecalciferol vs placebo; 3 months, 2 winters	n = 283 (68 in 1000 IU Vit D group; 73 in 2000 IU group; 70 in 4000 IU group; 72 in placebo group) Black adults	Baseline vs 3 mo: 4000 IU: -4.0 mm Hg; 2000 IU: -3.4; 1000 IU: -0.66; Placebo: 1.7	Baseline vs 3 mo: 4000 IU: -1.8 mm Hg; 2000 IU: -2.5; 1000 IU: -2.5; Placebo: 0.7; Not statistically significant	3-month SBP change per 1000 IU/d: -1.4 mm Hg (P = 0.04); DBP change per 1000 IU/d: -0.5 mm Hg (P = 0.37)	No AEs reported
MAGNESIUM
Kass et al; 201241	Meta-analysis & systematic review of 22 trials 120-973 mg Mg (mean daily dose 410 mg); 3-24 weeks	n = 1173	Overall SBP decrease 3-4 mm Hg   Overall effect = 0.32 (95% CI 0.23-0.41)	Overall DBP decrease 2-3 mm Hg   Overall effect = 0.36 (95% CI 0.27-0.44)	Crossover trials attained greater effect size and reduction of SBP & DBP	General AE = diarrhea, mild abdominal or bone pain. 1 case of visual impairment, 1 case of MI, 1 case of blood coagulation defect
Kawano et al; 199842	RCT; crossover Mg oxide, 20 mmol (480 mg)/day vs placebo; 8 weeks	n =60 >Stage I HTN	Mg: -3.7 ± 1.3 mm Hg (P < 0.01) Office BP; -2.0 ± 0.8 mm Hg (P < 0.05) Home BP; -2.5 mm Hg ± 0.8 (P < 0.01) 24-hr BP	Mg: -1.7 ± 0.7 mm Hg (P < 0.05) Office BP; -1.4 ± 0.6 mm Hg (P < 0.05) Home BP; -1.4 ±0.6 mm Hg (P < 0.05) 24-hr BP		No AEs reported
Witteman et al; 199443	RCT; DB Mg aspartate HCl, 20 mmol (480 mg)/day; 6 months	n = 91 (47 experimental, 44 placebo) Women with mild-to-moderate HTN; Unmedicated	-2.7 mm Hg (95% CI -1.2,6.7) (P = 0.18)	-3.4 mm Hg (95% CI 1.3, 5.6) (P = 0.003)	Blood pressure reductions not associated with baseline Mg status	Well tolerated; no diarrhea with Mg
Wirell et al; 199444	RCT; DB, crossover Mg aspartate, 15 mmol (365 mg) TID vs placebo; 8 weeks	n = 39 (19 experimental, 20 placebo) Moderate HTN Beta-blocker meds	Supine systolic: -7.0 mm Hg (P = 0.005); Standing systolic: -6.0 (P = 0.028) when Mg-supplemented after placebo		Serum potassium significantly higher in intervention group, with no change to urine potassium	Slight increase in defecation (both groups)
CRATAEGUS LAEVIGATA (HAWTHORN)
Walker et al; 200245	RCT; DB i) 600 mg Mg; ii) 500 mg hawthorn extract; iii)  i+ii; iv) placebo; 10 weeks	n = 36 Mild HTN	After stress, hawthorn: -7.2 mm Hg (NS); After stress, placebo: -14.9 mm Hg (NS); After exercise, hawthorne: -10.2 mm Hg (NS); After exercise, placebo: -12.2 mm Hg (NS)	After stress, hawthorn: -1.7 mm Hg (NS); After stress, placebo: -7.8 mm Hg (NS); After exercise, hawthorne: -13.1 mm Hg (NS); After exercise, placebo: -1.0 mm Hg (NS)	Trend toward reduced anxiety (P = 0.094) and reduced resting DBP (P = 0.081) in hawthorn extract group	No AEs reported
Walker et al; 200646	RCT; DB 1200 mg hawthorn (6 g dried herb) vs placebo; 16 weeks	n= 79 (39 hawthorn, 40 placebo) Diabetes Anti-hypertensive and/or diabetic meds	Hawthorn: -3.6 mm Hg (P = 0.096); Placebo: -0.8 mm Hg (P = 0.771)	Hawthorn: – 2.6 mm Hg (P = 0.035); Placebo: -0.5 mm Hg (P = 0.645)		Minor digestive upset in both hawthorn and placebo groups (greater at baseline than at 16 weeks).

RCT = randomized controlled trial; DB = double-blind; PC = placebo-controlled; C = control; HTN = hypertension; AE = adverse event; NS = non-significant; CBT = cognitive behavioral therapy

Olive Oil

The evidence to support the use of olive oil in hypertension comes from several small, open-label trials that utilized olive oil as the main fat source in the participants’ diet. Large reductions in blood pressure (up to ~10 mm Hg for both DBP and SBP) were seen in studies using hypertensive patients, with one study showing a very significant reduction in medication use. Studies involving normotensive individuals demonstrated smaller reductions. The most recent study which showed the greatest reduction used a dose of 60 grams (4 tbsp) daily.8 Larger studies, utilizing more precise dosing, randomization, and blinding are needed. A study investigating the mechanism of action found that oleic acid is the active constituent through its effect on cell membrane structure and adrenoreceptor signaling pathways.13

DASH Diet

The DASH diet (Dietary Approaches to Stop Hypertension) includes an abundance of vegetables and fruit, whole grains, low-fat dairy products, lean meat or fish, legumes, nuts and seeds, and healthy fats, with limited sweets, red meat, and saturated and trans fats. In large, randomized, controlled studies (RCTs), the DASH diet produced reductions of approximately 11 mm Hg for SBP and 6 mm Hg for DBP in patients with hypertension.14 The benefits are further enhanced when the DASH diet is combined with reduced sodium intake or weight loss.15,16 The DASH diet studies have been criticized because the food was prepared for the participants; however, the diet is based on simple healthy eating strategies. A free guide to eating the DASH Diet is available at the National Institute of Health’s website: http://www.nhlbi.nih.gov/health/public/heart/hbp/dash/.

Garlic

Two large meta-analyses of high-quality RCTs have shown a significant benefit of garlic in patients with hypertension.17,18 While they included different studies, both found that when analyzing studies in which subjects had a mean baseline SBP of >140 mm Hg, a mean reduction of 8 and 16.3 mm Hg, respectively, was observed. In contrast, studies involving pre-hypertension individuals observed small or non-significant benefits, suggesting that this may not be a highly effective intervention for pre-hypertension. A recent study used garlic supplementation in patients with medicated, uncontrolled systolic hypertension and reported significant reductions, suggesting a potential benefit for this population.17 Gastrointestinal discomfort was the most frequently reported side effect. Animal studies have observed garlic to have angiotensin I-converting enzyme (ACE) properties, as well as induction of endothelium-dependent and -independent arterial relaxation and vasodilation.19

Coenzyme Q10

A Cochrane review from 2009 combined the data of 3 RCTs and showed a large hypotensive benefit of coenzyme Q10 (11/7 mm Hg reduction).21 The authors expressed concerns about the quality of blinding and the credibility of one of the studies’ lead authors, and thus felt that the data was insufficient to draw conclusions. A fourth RCT that was excluded from the meta-analysis because of its short pre-intervention washout period (10 vs 14 days) also showed a very large hypotensive benefit (18 mm Hg).22 One recent high-quality RCT failed to show BP benefits of CoQ10. This study used patients with metabolic syndrome and the patients maintained their medication regimens throughout the study.23 It may be that the benefits of CoQ10 are not realized when used in combination with pharmacotherapy. CoQ10’s mechanism of action is unclear; however, it is thought to have a direct action on the vascular epithelium to decrease peripheral resistance.21

Fish Oil

Fish oil supplementation and increased dietary fish intake have shown benefit in reducing blood pressure in both medicated and unmedicated hypertensive individuals. One study compared fish oil, weight loss, and a combination of the 2.24 Both interventions showed statistically significant benefit (6/3 and 5.5/2 mm Hg reductions, respectively), and the combined effect exceeded the sum of their individual effects (13/9 mm Hg). One study25 comparing EPA and DHA found that only DHA achieved statistically significant results compared to placebo; however, the placebo used in this study was olive oil, which has its own effects on BP. Another study observed continued improvement between week-8 and week-16 assessments, suggesting that the full benefits of supplementation may be seen only after extended use.26 The hypotensive effects of fish oil in patients who are normotensive at baseline are unclear, with one study showing benefit and another showing a lack of benefit.25,26 Both of these studies used olive oil as a control. The studies reviewed used approximately 4 grams of combined EPA and DHA daily.

Exercise

Two large meta-analyses of RCTs have shown beneficial effects of exercise on blood pressure.29,30 Aerobic exercise significantly reduces BP by 3/3 mm Hg in normotensive patients, and by 7/5 mm Hg in hypertensive patients.29 Among studies using resistance training, statistically significant reductions were seen in normotensive patients but not in hypertensive patients; however, this may be due to the small number of studies examined.30 When considering the different types of resistance exercise studied, isometric handgrip training yielded the largest benefit (13.5/2.7 mm Hg reduction).30 Despite the presence of controls, many studies lack adequate descriptions of randomization and blinding.

Hibiscus Sabdariffa

The use of Hibiscus sabdariffa in tea and extract forms have shown excellent benefit in reducing both systolic and diastolic blood pressure in both medicated and unmedicated populations, diabetics with HTN and in varying HTN stages.31 Some studies have compared its use to the common pharmaceutical ACE inhibitors, captopril and lisinopril, and have exhibited a comparable hypotensive effect.32,33 Generally, Hibiscus sabdariffa has a negligible impact on electrolyte balance, though urinary sodium and chlorine excretion have been shown to elevate with its consumption.34 Tolerability of this herb is very high, with no reported cases of adverse effects under 300 mg/kg/day, although very high doses may be hepatotoxic.31 Proposed mechanisms include antioxidant effects of its anthocyanins to reduce LDL-C oxidation and atherosclerosis, diuretic effects from inhibition of acetylcholinesterase, and vasodilator effects from nitric oxide-cGMP and calcium inhibition in smooth muscle cells.34

Vitamin D

The use of vitamin D for essential HTN stems from observational data noting an association between low vitamin D status and risk of cardiovascular disease and HTN.35 The exact physiological mechanism for its hypotensive effect is largely unknown, though theories implicating improved calcium absorption and metabolism are generally accepted. Current evidence shows a small but statistically significant effect of vitamin D on both systolic and diastolic blood pressure reduction. A recent systematic review and meta-analysis confirms the literature trend that increased doses are more protective, with the highest studied dose, 2000 IU of cholecalciferol, exhibiting the greatest reduction. A mean reduction of 3.6 mm Hg for systolic, and of 3.1 mm Hg for diastolic was exhibited when combining studies using various doses and durations of treatment. Interestingly, unactivated forms of vitamin D (vitamin D2, D3, and UVB radiation) significantly outweighed the activated calcitriol/1-alpha calcidiol forms for systolic reduction only, with a mean decrease of 6.2 mm Hg reported in the meta-analysis of 11 studies.36

Magnesium

Magnesium is a commonly utilized supplement for the management of HTN, theoretically due to its impact on smooth muscle relaxation via calcium ion antagonism, and associations between high dietary magnesium intake and cardiovascular protection.41 Studies generally report a mild hypotensive effect of magnesium, with an unclear association to baseline magnesium status. A recent meta-analysis41 outlines a systolic decrease of 3-4 mm Hg and a diastolic decrease of 1-2 mm Hg with oral supplementation of magnesium. There is no current evidence to preferentially support a certain form of magnesium; commonly studied sources include Mg oxide, Mg aspartate, Mg chloride, Mg hydroxide, Mg lactate, Mg citrate and Mg pidolate. Common adverse effects include mild gastrointestinal upset, such as diarrhea and abdominal pain.41 A major limitation to many studies include a lack of investigation into baseline magnesium status and dietary magnesium intake, which may confound the impact of the BP-lowering ability of supplementation.

Crataegus Laevigata (Hawthorn)

Minimal evidence exists to support the use of Crataegus laevigata (hawthorn) for essential HTN, although some hypotensive effects are exhibited. Although non-significant results were elicited in the 2 studies outlined in Table 1, a trend towards systolic and diastolic lowering can be seen. This research suggests that a dose of 500-1200 mg hawthorn extract daily may achieve blood pressure reductions of ~3-10 mm Hg systolic and ~2-13 mm Hg diastolic.45,46 Caution must be exercised in the interpretation of these results, given that both studies were conducted by the same study team and robust supportive literature does not yet exist.

Table 2. Suggested dosing of anti-HTN agents 

Intervention	Evidence-based dose recommendation
Olive oil	30-60 g QD (2-4 tbsp)
DASH diet	Adopt the DASH Diet
Garlic	500-900 mg QD
CoQ10	50-60 mg BID
Fish oil	4 g combined EPA and DHA
Exercise	Aerobic exercise 3 times per week
Hibiscus sabdariffa	240 ml tea (1-2 g dried herb) BID
Vitamin D	2000-4000 IU QD
Magnesium	>370 mg QD
Crataegus (hawthorn)	500-1200 mg QD

Conclusions

There are many interventions used within the naturopathic medical sphere for essential HTN management that are well supported and documented in the scientific literature to date. In assessing the evidence closely, typical populations studied include patients with mild-to-moderate HTN, pre-HTN, and HTN with comorbid diabetes, all of whom commonly seek naturopathic care.

Some trends exist when assessing the literature on naturopathic approaches to HTN management. The evidence suggests that typically, naturopathic interventions exhibit decreased efficacy as blood pressure approaches the normal range, which may be protective against hypotension. All interventions discussed in this paper appear to be generally well tolerated, with the exception of minor adverse effects, usually gastrointestinal in nature.

Naturopathic interventions fare quite well at reducing blood pressure, achieving comparable results to first-line anti-hypertensive medications within 2-3-month timeframes. Recent Cochrane review data show a BP-lowering effect of about 8/4 mm Hg using thiazides, ACE inhibitors, angiotensin receptor blockers, and renin inhibitors, and many of the naturopathic interventions discussed above achieved similar or larger reductions. While some interventions yielded only small changes in blood pressure, it is important to note that these changes can have protective effects. It has been observed that reductions in resting SBP and DBP of 3 mm  Hg can decrease coronary heart disease risk by 5%, stroke by 8%, and all-cause mortality by 4%.30 Given the widespread tolerability of the interventions discussed here, it is important for naturopathic physicians to consider the implementation of these strategies to prevent and treat HTN, especially in the well-studied pre-, mild and moderate stages. (See Table 2 for suggested dosing of the agents discussed in this article.)  

 

Elaine Lewis, HBSc, ND is a naturopathic physician and research resident, graduating from CCNM. Prior to her medical studies, she attended McMaster University, earning her Honors Bachelor of Science in Behavioral Neuroscience. She is a member of the Ontario and Canadian Associations of Naturopathic Doctors and is licensed by the Board of Directors of Drugless Therapy – Naturopathy. As the research resident, she is involved in various projects that contribute evidence to the naturopathic profession, including work on hypertension, IBS, food allergies, arthritis and pediatrics. Elaine emphasizes the impact of evidence-based naturopathic medicine by using this model in her teaching and patient care. Beyond her role as the research resident, she mentors students in a variety of courses, and lectures externally to organizations and healthcare providers. Elaine practices in Mississauga at Back to Play Chiropractic and in North York at the Integrated Healthcare Centre. For more information, visit: www.elainelewisnd.com.

 

Monique Aucoin, BMSc, ND is a naturopathic physician and the Clinical Trial Coordinator at The Canadian College of Naturopathic Medicine. She is currently involved in the design and implementation of studies investigating the efficacy and safety of natural health products in the treatment of irritable bowel syndrome, depression and ADHD, as well as synthesis research into complementary/alternative medical approaches for cardiometabolic disorders. In addition to her research work, Monique has a private practice in Brampton where she sees patients of all ages, with a special interest in mental health and stress management. She is passionate about helping people to understand the root cause of their illness and restore balance using simple and effective treatments. For more information, visit www.MoniqueAucoinND.com or follow Monique on Twitter @MoniqueAucoinND.

 

Kieran Cooley, BSc, ND, MSc Cand is an associate director of research, assistant professor in CCNM’s department of research and clinical epidemiology. Kieran’s experience includes a broad range of clinical trials and collaborations investigating naturopathic medicine  and various natural health products. This includes a recent collaboration evaluating the effectiveness of naturopathic  medicine for cardiovascular disease risk, published in the Canadian Medical Association Journal (CMAJ). A recipient of the SickKids Training Award in Complementary/Alternative Health Care, he has previously investigated behavioral disorders in children, with a focus on ADHD. Kieran was a distinguished invitee to a recent symposium on microbiota and is collaborating on a number of projects relating to digestion, probiotics, and gut health. His qualitative research has explored experiences with adverse reaction reporting, as well as practitioner and patient experiences with naturopathic medicine and Aboriginal health issues and HIV+ in community health settings. He also has  contributed to systematic reviews and cost-effectiveness studies on complementary and alternative medicines. Kieran is committed to fostering an evidence-based approach to naturopathic medicine and a long life of learning and sharing.

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