Therapeutic Advances in Cardiovascular Disease, July 28, 2010
Mark C. Houston MD, MS, FACP, FAHA
Macronutrient and micronutrient deficiencies are very common in the general population and may be even more common in patients with hypertension and cardiovascular disease due to genetic, environmental causes and prescription drug use. The Hypertension Institute in Nashville, TN, has evaluated micronutrient deficiencies and oxidation status, in a group of hypertensive versus normotensive patients. There are significant differences in numerous intracellular micronutrients and oxidation status between these two groups. Replacement of the micronutrient deficiencies, as well as high-dose therapy of selected nutraceuticals in combination with optimal diet, exercise and weight management resulted in control of blood pressure to goal levels in 62% of the hypertensive population over a period of 6 months with complete tapering and discontinuation of antihypertensive drugs.
These deficiencies will have an enormous impact on present and future cardiovascular health and outcomes such as hypertension, myocardial infarction, stroke and renal disease and overall health costs. It is estimated that the annual savings in drug costs alone for the treatment of hypertension could be as much as US$10 billion.
Optimal nutrition, nutraceuticals, vitamins, antioxidants, minerals, weight loss, exercise, smoking cessation and moderate restriction of alcohol and caffeine in addition to other lifestyle modifications can prevent and control hypertension in many patients. An integrative approach combining these lifestyle suggestions with the correct pharmacologic treatment will best achieve new goal blood pressure levels, reduce cardiovascular risk factors, improve vascular biology and vascular health, reduce cardiovascular target organ damage and reduce healthcare expenditure.
The transition from the Paleolithic diet to our modern diet has produced an epidemic of nutritionally related diseases including hypertension, atherosclerosis, coronary heart disease (CHD), myocardial infarction (MI), congestive heart failure (CHF), cerebrovascular accidents (CVA), renal insufficiency (RI), renal failure (RF), type 2 diabetes mellitus (DM), metabolic syndrome and obesity.
Humans have evolved from a preagricultural, hunter–gatherer society to a commercial agriculture with highly processed, refrigerated and fast foods that have imposed an unnatural and unhealthy nutrition. The human genetic makeup is 99.9% that of our Paleolithic ancestors, yet our nutritional, vitamin and mineral intakes are vastly different. The macronutrient and micronutrient variations contribute to the higher incidence of hypertension and other CVDs through a complex nutrient–gene interaction. Poor nutrition, coupled with obesity and a sedentary lifestyle have resulted in an exponential increase in nutritionally related diseases. In particular, the high sodium/potassium ratio of modern diets has contributed to hypertension, stroke, CHD, CHF and renal disease. In addition, the relatively low intake of omega-3 polyunsaturated fatty acids (PUFA), increase in omega-6 PUFA saturated fat and trans fatty acids, has contributed to the increased incidence of CHD, hypertension, DM and hyperlipidemia.
Studies demonstrate a consistent association between a high protein intake and a reduction in BP. The protein source is an important factor in the BP effect, animal protein being less effective than nonanimal protein. However, lean or wild animal protein with less saturated fat and more essential omega-3 and omega-6 fatty acids may reduce BP, lipids and CHD risk. Low protein intake coupled with low omega-3 fatty acid intake may contribute to hypertension in animal models.
Omega-3 PUFA significantly lower BP. The studies on the effects of fish oil on BP have shown a dose-related response in hypertension as well as a relationship to the specific concomitant diseases associated with hypertension. Studies indicate that DHA is very effective in reducing BP and heart rate. However, formation of EPA and ultimately DHA from ALA is decreased in the presence of increased linoleic acid in the diet (omega-6 fatty acid). The ideal ratio of omega-3 fatty acid to omega-6 fatty acid is between 1:1 to 1:2 with a polyunsaturated to saturated fat ratio greater than 1.5 to 2:0.
Omega-9 Fatty Acids such as olive oil is rich in monounsaturated fats (MUFA), which have been associated with BP and lipid reduction in Mediterranean and other diets. In one study, the need for antihypertensive medications was reduced by 48% in the MUFA group versus 4% in the PUFA (omega-6 FA) group. Extra virgin oil has 5 mg of phenols in 10 g of olive oil, a rich polyphenol antioxidant. About four tablespoons of extra virgin olive oil is equal to 40 g.
Reduce or eliminate refined sugars and simple carbohydrates. Increase fiber, vegetables, beans, and legumes. Soluble fibers such as guar gum, guava, and oat bran reduce BP and reduce the need for antihypertensive medications in hypertensive subjects, diabetic subjects and hypertensive–diabetic subjects.
Magnesium supplements showed a significant reduction in BP over an 8-week period documented by 24-hour ambulatory BP, home and office BP. Magnesium competes with sodium for binding sites on vascular smooth muscle and acts like a calcium channel blocker, increases prostaglandin E (PGE), binds in a necessary-cooperative manner with potassium, inducing vasodilation and BP reduction. Magnesium is an essential cofactor for the delta-6-desaturase enzyme that is the rate-limiting step for conversion of linoleic acid to gamma-linolenic acid (GLA). GLA elongates to form dihomogamma-linoleic acid (DGLA), the precursor of prostaglandin E1, a vasodilator and platelet inhibitor. Magnesium regulates systolic and diastolic BP, intracellular calcium, sodium, potassium and pH, as well as left ventricular mass, insulin sensitivity and arterial compliance.
Low serum zinc levels correlate with hypertension as well as CHD, type II DM, hyperlipidemia, elevated lipoprotein a, 2-hour postprandial plasma insulin levels and insulin resistance.
Tea: Green and Black
Green tea, black tea and extracts of active components in both teas have demonstrated reduction in BP.
Seaweed Wakame (Undaria pinnatifida) is the most popular edible seaweed in Japan. In humans, 3.3 g daily of dried Wakame for 4 weeks significantly reduced both the systolic BP and the diastolic BP. Seaweed and sea vegetables contain almost all of the seawater's 77I minerals and rare earth elements, fiber and alginate in a colloidal form.
A potent water-soluble antioxidant that recycles vitamin E, improves ED and produces a diuresis. Numerous epidemiologic, observational and clinical studies have demonstrated that the dietary intake of vitamin C or plasma ascorbate concentration in humans is inversely correlated to systolic and diastolic BP and heart rate. Long-term epidemiologic and observational follow-up studies in humans also show a reduced risk of CVD, CHD and CVA with increased vitamin C intake.
Epidemiological, clinical and experimental investigations all demonstrate a relationship between the plasma levels of vitamin D3, the active form of vitamin D, and BP, including a vitamin-D-mediated reduction in BP in hypertensive patients. Vitamin D may have an independent and direct role in the regulation of BP and insulin metabolism. Vitamin D3 influences BP by its effects on calcium-phosphate metabolism, RAAS, immune system, control of endocrine glands and ED. Vitamin D3 markedly suppresses renin transcription by a Vitamin D receptor (VDR)-mediated mechanism in cell cultures. Its role in electrolytes, volume and BP homeostasis indicates that Vitamin D3 is important in amelioration of hypertension.
Low serum vitamin B6 levels are associated with hypertension in humans.
Over 4000 naturally occurring flavonoids have been identified in such diverse substances as fruits, vegetables, red wine, tea, soy and licorice. Flavonoids (flavonols, flavones and isoflavones) are potent free radical scavengers that inhibit lipid peroxidation, prevent atherosclerosis, promote vascular relaxation and have antihypertensive properties. In addition, they reduce stroke and provide cardioprotective effects that reduce CHD morbidity and mortality.
Coenzyme Q-10 (CoQ-10)
CoQ-10 is a potent lipid phase antioxidant, free radical scavenger, cofactor and coenzyme in mitochondrial energy production and oxidative phosphorylation that lowers systemic vascular resistance (SVR), lowers BP and protects the myocardium from ischemic reperfusion injury. Serum levels of CoQ-10 decrease with age and are lower in patients with diseases characterized by oxidative stress such as hypertension, chronic heart disease, hyperlipidemia, DM, atherosclerosis and in those who are involved in aerobic training, patients on total parenteral nutrition, those with hyperthyroidism and patients who take statin drugs.
Oral administration of CoQ-10 in hypertensive patients takes time to reach its peak level, usually at about 4 weeks, then BP remains stable. The antihypertensive effect is gone within 2 weeks after discontinuation. Approximately 50% of patients on antihypertensive drugs may be able to stop between one and three agents. Both total dose and frequency of administration may be reduced. Even high doses of CoQ-10 have no acute or chronic adverse effects.
Other favorable effects on cardiovascular risk factors include improvement in the serum lipid profile and carbohydrate metabolism with reduced glucose and improved insulin sensitivity, reduced oxidative stress, reduced heart rate, improved myocardial LV function and oxygen delivery and decreased catecholamine levels.
Natural Antihypertensive Compounds
Categorized by Antihypertensive Class A's, many of the natural compounds in food, certain nutraceutical supplements, vitamins, antioxidants or minerals function in a similar fashion to a specific class of antihypertensive drugs. Although the potency of these natural compounds may be lower than the antihypertensive drug, when used in combination with other nutrients and nutraceuticals, the antihypertensive effect is magnified. In addition, many of these nutrients and nutraceuticals have varied, additive or synergistic mechanisms of action in lowering BP.
It is clear from the clinical studies presented that replacement of deficiencies of micronutrients and macronutrients as well as treatment with higher therapeutic doses of vitamins, minerals and antioxidants can lower BP as well as improve vascular health and function. Nutritional treatment although very effective in reducing BP, may take longer than pharmacologic therapies. In some cases, it may be 4–6 months before the maximal antihypertensive effect is seen. In my hypertensive patients (n=671), compared with the general population, there were significant differences in many of the micronutrients tested as well as a significantly higher oxidative stress, a lower oxidative defense and higher incidence of insulin resistance as measured by the glucose-insulin test. Replacement of these deficiencies as well as high-dose therapy of selected supplements and nutraceuticals in combination with optimal diet, exercise and weight management resulted in control of BP to goal levels in 62% of the hypertensive population over a period of 6 months with complete tapering and discontinuation of antihypertensive drugs.
- Potassium/sodium ratio >5 : 1
- Magnesium 1000 mg
- Calcium 1000 mg
- Zinc 25–30 mg
- Protein: total intake (30% total calories): nonanimal sources preferred but lean or wild animal protein in moderation is acceptable; whey protein; soy protein (fermented is best); cold water fish; poultry
Fats: 30% total calories Omega-3 fatty acids PUFA (DHA, EPA, cold water fish); 2–3 g Omega-6 fatty acids PUFA (canola oil, nuts); 1 g Omega-9 fatty acids MUFA (extra virgin olive oil) (olives) 4 tablespoons or 5–10 olives; Saturated FA (lean, wild animal meat) <10%>
- Carbohydrates (40% total calories): reduce or eliminate refined sugars and simple carbohydrates, increase fiber, vegetables, beans, and legumes
- Alcohol Restriction <20>
- Caffeine Restriction <100>
- Vitamin C 250–500 mg daily
- Vitamin E (mixed tocopherol/tocotrienols) 400–800 IU daily
- Vitamin B6 100 mg daily
- Coenzyme Q-10 60 mg daily
- Lipoic acid (with Biotin) 100–200 mg daily
- Vascular biology (ED and VSMD) plays a primary role in the initiation and perpetuation of hypertension, CVD and TOD.
- Nutrient–gene interactions are a predominant factor in promoting beneficial or detrimental effects in cardiovascular health and hypertension.
- Nutrition (natural whole food, nutraceuticals) can prevent, control and treat hypertension through numerous vascular biology mechanisms.
- Oxidative stress initiates and propagates hypertension and CVD.
- Antioxidants can prevent and treat hypertension.
- Whole food and phytonutrient concentrates of fruits, vegetables and fiber with natural combinations of balanced phytochemicals, nutrients, antioxidants, vitamins, minerals and appropriate macronutrients and micronutrients are generally superior to single component or isolated artificial or single component natural substances for the prevention and treatment of hypertension and CVD.
- However, there is a role for the selected use of single and component nutraceuticals, vitamins, antioxidants and minerals in the treatment of hypertension based on scientifically controlled studies as a complement to optimal nutritional, dietary intake from food and other lifestyle modifications.
- Exercise, weight reduction, smoking cessation, alcohol and caffeine restriction as well as other changes in lifestyle must be incorporated.
- The annual cost savings for this type of integrative treatment of hypertensive patients could be as much as US$10 billion.