Potassium in nutrition and human health: Difference between revisions
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Potassium ranks as the most abundant cation (positive ion) inside animal [[Cell (biology)|cells]] (intracellular), and as such contributes critically in numerous important ways to the optimal functioning of cells and therefore to optimal functioning of the organ systems and individuals they compose. Among other metabolic functions, potassium plays a role in the synthesis of proteins and in the biochemical transformations required for carbohydrate metabolism. | Potassium ranks as the most abundant cation (positive ion) inside animal [[Cell (biology)|cells]] (intracellular), and as such contributes critically in numerous important ways to the optimal functioning of cells and therefore to optimal functioning of the organ systems and individuals they compose. Among other metabolic functions, potassium plays a role in the synthesis of proteins and in the biochemical transformations required for carbohydrate metabolism. | ||
By influencing the electrical potential difference across the cell membrane, the ratio of the [[concentration]]s of potassium in intracellular fluid (ICF) to that in the cells' surrounding extracellular fluid (ECF) has important effects on the rate of transmission of electrical activity (pulses) along nerve fibers and skeletal muscle cells, which, among other things, affects the degree of contraction of the smooth muscles of arteries and arterioles (vascular tone). Inasmuch as extracellular potassium varies in the 3-6 mmol/L range, while intracellular potassium concentrations average about 145 mmol/L, small changes in extracellular potassium concentration have a greater effect on the ICF-to-ECF potassium concentration ratio than similar small changes in intracellular potassium concentration. Subsequent sections discuss the implication of changes in the ICF-to-ECF potassium concentration ratio in human physiology. | By influencing the electrical potential difference across the cell membrane, the ratio of the [[concentration]]s of potassium in intracellular fluid (ICF) to that in the cells' surrounding extracellular fluid (ECF) has important effects on the rate of transmission of electrical activity (pulses) along nerve fibers and skeletal muscle cells, which, among other things, affects the degree of contraction of the smooth muscles of arteries and arterioles (vascular tone).<ref name=moczydlowski2009>Moczydlowski EG. (2009) Electrophysiology of the Cell Membrane. In: Boron WF, Boulpaep EL (editors), Medical Physiology, 2nd ed. Saunders/Elsevier: Philadelphia. ISBN 9781416031154.</ref> Inasmuch as extracellular potassium varies in the 3-6 mmol/L range, while intracellular potassium concentrations average about 145 mmol/L, small changes in extracellular potassium concentration have a greater effect on the ICF-to-ECF potassium concentration ratio than similar small changes in intracellular potassium concentration. Subsequent sections discuss the implication of changes in the ICF-to-ECF potassium concentration ratio in human physiology. | ||
In healthy persons whose daily consumption of potassium does not vary greatly, the amount of potassium consumed equals the amount excreted, by the kidney and gastrointestinal tract predominantly. Physiologists refer to that equality as ''zero'' net external body potassium balance. Of the major electrolytes, potassium has the highest ratio of potassium consumed to the amount of potassium in the extracellular compartment, a characteristic the presents a challenge in maintaining extracellular potassium concentrations within a set range in the face of variations in daily potassium intake, a challenge met by efficient excretion and somewhat less efficient conservation, mediated by homeostatic mechanisms not completely elucidated.<ref name=youn2009>Youn JH, McDonough AA. (2008) [http://dx.doi.org/10.1146/annurev.physiol.010908.163241 Recent Advances in Understanding Integrative Control of Potassium Homeostasis.] ''Annu.Rev Physiol'' 71:381-401. ISBN 18759636.</ref> | In healthy persons whose daily consumption of potassium does not vary greatly, the amount of potassium consumed equals the amount excreted, by the kidney and gastrointestinal tract predominantly. Physiologists refer to that equality as ''zero'' net external body potassium balance. Of the major electrolytes, potassium has the highest ratio of potassium consumed to the amount of potassium in the extracellular compartment, a characteristic the presents a challenge in maintaining extracellular potassium concentrations within a set range in the face of variations in daily potassium intake, a challenge met by efficient excretion and somewhat less efficient conservation, mediated by homeostatic mechanisms not completely elucidated.<ref name=youn2009>Youn JH, McDonough AA. (2008) [http://dx.doi.org/10.1146/annurev.physiol.010908.163241 Recent Advances in Understanding Integrative Control of Potassium Homeostasis.] ''Annu.Rev Physiol'' 71:381-401. ISBN 18759636.</ref> |
Revision as of 19:59, 26 February 2009
To maintain life and health, the diet of humans must contain the chemical element, potassium, in its ionic form (K+), consumed usually as potassium salts of organic acids in food (e.g., potassium citrate), among which non-grain plant foods (vegetables and fruits) supply the richest amounts. In 2004-2006, the Institute of Medicine of the National Academies of Science [1] and its Food and Nutrition Board [2] recommended that adult humans consume 4700 milligrams (mg) of potassium per day, which, calculated from the atomic mass of potassium (39.1 mg per mmol), corresponds to 120 millimoles (mmol) potassium per day: 4700 mg/39.1 mg/mmol=120 mmol. That recommended intake of potassium substantially exceeds estimates from recent surveys of average intakes by the general population, raising the possibility that a persisting state of suboptimal body potassium content, and rate of throughput of potassium, prevails in the general population. [3] [4] Subsequent sections will discuss potassium intake recommendations for children and special groups.
General considerations
Potassium ranks as the most abundant cation (positive ion) inside animal cells (intracellular), and as such contributes critically in numerous important ways to the optimal functioning of cells and therefore to optimal functioning of the organ systems and individuals they compose. Among other metabolic functions, potassium plays a role in the synthesis of proteins and in the biochemical transformations required for carbohydrate metabolism.
By influencing the electrical potential difference across the cell membrane, the ratio of the concentrations of potassium in intracellular fluid (ICF) to that in the cells' surrounding extracellular fluid (ECF) has important effects on the rate of transmission of electrical activity (pulses) along nerve fibers and skeletal muscle cells, which, among other things, affects the degree of contraction of the smooth muscles of arteries and arterioles (vascular tone).[5] Inasmuch as extracellular potassium varies in the 3-6 mmol/L range, while intracellular potassium concentrations average about 145 mmol/L, small changes in extracellular potassium concentration have a greater effect on the ICF-to-ECF potassium concentration ratio than similar small changes in intracellular potassium concentration. Subsequent sections discuss the implication of changes in the ICF-to-ECF potassium concentration ratio in human physiology.
In healthy persons whose daily consumption of potassium does not vary greatly, the amount of potassium consumed equals the amount excreted, by the kidney and gastrointestinal tract predominantly. Physiologists refer to that equality as zero net external body potassium balance. Of the major electrolytes, potassium has the highest ratio of potassium consumed to the amount of potassium in the extracellular compartment, a characteristic the presents a challenge in maintaining extracellular potassium concentrations within a set range in the face of variations in daily potassium intake, a challenge met by efficient excretion and somewhat less efficient conservation, mediated by homeostatic mechanisms not completely elucidated.[6]
Disturbances relating to body potassium deficiency may result from:
- prolonged inadequate consumption of potassium-containing foods;
- inappropriately large rates of excretion of potassium in urine;
- inappropriately large excretion rates of potassium in feces.
Disturbances relating to body potassium excess may result from:
- drugs and kidney diseases that impair the kidney’s ability to excrete potassium in urine;
- deficiency of hormones that act to promote kidney and gastrointestinal excretion of potassium.
Subsequent sections will elaborate on the above concepts.
Requirements for potassium consumption by humans
Humans must regularly consume potassium because the body does not store it (as it does fat, say), while the kidney continues to excrete it in the urine even when potassium intake ceases. Potassium-rich foods include leafy green vegetables, vine fruits (e.g., squash, tomatoes, cucumbers, etc.), root vegetables, and tree fruits (see below).
The Institute of Medicine of the National Academies of Science[1] and its Food and Nutrition Board[2] recommend as "Adequate Intake" (AI)[7] of potassium, in mmol/day, as 77 and 97 for children ages 1-3 and 4-8 years, respectively, and as 115 and 120 for children 9-13 and 14-18 years, respectively. For adult men and women, ages 19 to >70 years, they recommend an AI of potassium as 120 mmol/day, and the same amount for pregnant women as young as 14 years, increasing to 130 mmol/day for lactating women.
The Institue of Medicine of the National Academies of Science claims:
The AIs for potassium are based on a level of dietary intake that should maintain lower blood pressure levels, reduce the adverse effects of sodium chloride intake on blood pressure, reduce the risk of recurrent kidney stones, and possibly decrease bone loss. [1] |
The claim reflects concerns about inadequate potassium consumption as
- contributing to hypertension (abnormally high arterial blood pressure) through its effects to constrict the small arteries (arterioles) that deliver blood to muscles and other organs, and to promote renal retention of sodium chloride);
- mitigating the effect of dietary sodium chloride ('salt') in contributing to hypertension, to kidney stone formation, and to osteoporosis (soft, fracture-prone bones).
• Actual consumption of potassium by Americans, 2003-2004 and 2005-2006
The U.S. Department of Agriculture released in 2008 the results of the National Health and Nutrition Examination Survey (NHANES) data for 2005-2006, giving the average values for the consumption of various nutrients, including potassium. [4] The table below shows the average values for potassium consumption by Americans (2005-2006) with the recommended amounts given in the preceding section.
Recommended “Adequate Intake” identical for men and women, and therefore not adjusted for differences in body size or lean body mass between men and women.
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Note that average consumption of potassium by adults falls well below recommended amounts, with American women consuming half the recommended amount on average, and American men about two-thirds. Those findings do not indicate improvement in achieving "adequate intakes" over the findings reported for years 2003-2004. [3]
Children and adolescents showed a similar range of insufficiencies of potassium consumption in the two reports. [3] [4]
Without increasing total energy (calorie) intake, Americans could increase potassium consumption to achieve "adequate intake" by reducing intake of potassium-poor foods and increasing intake of potassium-rich foods.
Potassium Content of Foods
Understanding the biological effects of dietary potassium ions (cations) requires an associated understanding of the nature of the negatively charged ions (anions) that accompany potassium in foods, balancing potassium’s positive charge, thus maintaining electroneutrality. In natural diets not subjected to commercial processing that includes addition of potassium salts—typically potassium chloride—a variety of organic anions (e.g., citrate, fumarate) accompany the potassium ions in foods, in amounts sufficient to nearly balance the positive charge of the potassium ions (i.e., in near chemical equivalent amounts). Following their absorption by the gastrointestinal tract, the body converts a large fraction of those organic anions to bicarbonate (an acid-neutralizing substance, or base), as an end-product of metabolism.[8] Thus, diets with differing amounts of potassium exert potassium-induced biological effects associated and often interacting with the effects of the differing amounts of acid-neutralizing base, bicarbonate, as generated by the body from the potassium-accompanying organic anions. Physiologists often cannot dissect out the specific effects of the co-ions potassium and bicarbonate, when, for example, a person increases their dietary intake of potassium-rich foods, which typically contain bicarbonate-generating organic anions in abundance (see Table 1 and accompanying text).
Table 1 shows the potassium content of the major food groups, indicating the relation of potassium content to the net acid (or bicarbonate) load supplied to the body by each food group (see comments following table). [NB: Bcause potassium ions have a single charge (univalent), 1 millimole (mmol) of potassium equals 1 milliequivalent (meq) of potassium.]
In Table 1, positive (+) and negative (–) values of net acid load represent acid-producing and bicarbonate-producing equivalents, respectively, in the units specified. Values of net acid load: calculated first for individual food items then averaged per food group, as per compositional values in:[9]. Acid load calculations: as described in:[10] Note that net acid-producing foods tend to have much higher ratios of protein-to-potassium than do net bicarbonate-producing foods (regression of net acid load against Protein/Potassium, r=0.48, p=0.05). Note the relatively low values of protein and potassium in the cereal grain group, of which whole grains comprised six of the seven items in the group.
Table 1 reveals a number of important aspects of food potassium:
- Per unit energy content (kilocalories, abbrev: kcal), non-cereal-grain plant foods provide the most abundant source of potassium.
- The top five plant-food sources of potassium (meq/kcal): root vegetables (celeriac, rutabaga, turnips, carrots, parsnips, sweet potato, potato, yams, onions); vegetable fruit (aka vine fruit) (tomatoes, zucchini, eggplant, cucumbers); leafy greens (spinach, lettuce, kale, chard); stalks (celery, broccoli stalks); mushrooms (not strictly a plant).
- The food sources richest in potassium also supply bicarbonate to the body, as indicated by negative values of "net acid load".
- The potassium content in acid-producing foods (animal-source foods and cereal grains) average about one-fifth that of plant-source foods, which do not contain sufficient quantities of bicarbonate-generating organic anions to neutralize the acid generated from protein and other sustances they contain.
- The ratio of protein-to-potassium in plant-source foods falls short of animal-source foods by a factor of 10.
- Legumes provide moderate amounts of potassium with little or no acid or bicarbonate load.
Table 2 lists selected food sources of potassium, showing amounts of potassium for standard portions, in descending order of amount of potassium per 100 kilocalorie of food source. Raw data for the calculations: taken from [11]
[...in progress...]
Potassium deficiency in type 2 diabetes mellitus and in the metabolic syndrome
Potassium deficiency — or at least suboptimal body content of potassium — may play an important role in causing, sustaining or aggravating type 2 diabetes mellitus and/or metabolic syndrome.
The metabolic syndrome, a serious disturbance of body metabolism and physiology, consists of resistance of certain cell types of the body (e.g., fat cells, skeletal muscle cells) to the ability of the hormone insulin to promote cellular entry of the energy-rich molecule, glucose. Patients with the syndrome may show the following abnormalities: high blood pressure (or use of drugs to control hypertension); high levels of serum triglycerides; low levels of high-density lipoprotein (HDL) cholesterol; overweight, in particular visceral obesity (obesity manifested by abnormally increased abdominal girth); and, detectable levels of the protein, albumin, in the urine (microalbuminuria). The abnormalities of triglyceride levels typically associate with other blood fat disturbances (dyslipidemia) that foster atherosclerosis (buildup of plaques in artery walls that predispose to reduced blood flow to vital organs (e.g., the heart) and to formation of blood clots that can break off and plug vital vessels to the brain, causing stroke). The biochemical factors that promote clot formation are also stimulated in the metabolic syndrome, and the syndrome appears to be one of a chronic state of inflammation, the typical body response to tissue injury. Overweight and obese children show a strong correlation between biochemical markers of inflammation and the metabolic syndrome and insulin resistance, suggesting early-in-life involvement of inflammation related to overweight.[12]
An etimated 50 million Americans have the metabolic syndrome.[13]
Studies in humans using a technique called nuclear magnetic resonance spectroscopy found cellular potassium deficiency in patients with type 2 diabetes mellitus and in patients with hypertension.[14][15] The use of such a state-of-the-art technique enabled discovery of intracellular potassium deficiency not likely expected from routine clinical tests.
In addition, the studies indicated more acidity in the cells of patients with hypertension, especially those also having diabetes.[15]
A longitudinal study of nearly two thousand men and women in Finland (ages 35-64 years) found no evidence of an association of potassium intake (indexed as 24-hour urinary potassium excretion) and the incidence of type 2 diabetes.[16] Higher sodium chloride intakes did predict the incidence of type 2 diabetes among the subjects. Yet, from the study data reported, one cannot tell if the authors performed the same type of data analysis for potassium as they did for sodium, nor did they examine whether the ratio of sodium-to-potassium had a stronger association with diabetes incidence than did sodium alone. If the latter, that might suggest that higher potassium intakes, to lower the sodium-to-potassium ratio, might mitigate or eliminate the association with diabetes incidence.
Another studied showed that a dietary pattern emphasizing fruit (a potassium-rich food), and deemphasizing foods not especially rich in potassium, reduced the risk of type 2 diabetes.[17]
Studies of close to 500 women (teachers) in Iran showed that increasing intake of fruits and vegetables — potassium-and alkali-rich foods — proportionately decreased the chances of the participants having metabolic syndrome, by 30-35%.[18] The investigators also found that higher fruit and vegetable intakes associated with lower levels of a conventional biomarker of inflammation, a common concomitant of the metabolic syndrome.
Patients with the adrenal gland disorder, primary aldosteronism, have excessively high levels of aldosterone, a hormone that acts on the kidney to cause it to retain sodium and waste body potassium in the urine. They have low levels of the fat-cell-secreting hormone, adiponectin, resulting in insulin resistance. The patients commonly have the metabolic syndrome. Among patients with the metabolic syndrome, the lower their potassium levels the lower their adiponectin levels and the greater their insulin resistance. Though only a study of correlation, the study provides further suspicion that potassium deficiency may play a role in the pathogenesis of the metabolic syndrome.[19]
Clinical identification of the metabolic syndrome
- From: Source: National Cholesterol Education Program, Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), National Heart, Lung, and Blood Institute, National Institutes of Health, May 2001, [20] and the Grundy Report in 2004. [21]
- See Table 1, page 435 of Grundy et al.[21]
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Potassium Intake, Blood Pressure Regulation, and Risk of Heart Disease and Stroke
Intervention-type research in humans has found that raising potassium intakes reduces blood pressure in the arteries (arterial hypertension).[22] [23] In both the population at large and in people with “high blood pressure” (aka “hypertension”), increasing potassium intake by 30-60 meq/day within the range of low (e.g., 30 meq/day) to high (e.g., 200 meq/day) intakes——either from food or prescribed supplements——tends to lower blood pressure.[24] The degree of blood pressure-lowering depends on a variety of factors, including amount of increase in potassium intake and ancestry.
Because people with higher blood pressures have greater risks of death from heart disease (e.g., heart attacks) and stroke (blockage or leakage of blood vessel in the brain),[25] dietary potassium’s effect in helping keep blood pressures lower in part justified setting the recommended intake of potassium at 120 meq/day---substantially higher than the population average---for American adults by the Institute of Medicine in 2005.[1]
These correspondences in part helped justify the Institute of Medicine’s recommendation to American adults to increase their intake of potassium to 120 meq/day:
The IOM makes no statement whether 120 meq/day potassium intake ‘’optimizes’’ cardiovascular health, but it sets no upper limit restrictions on potassium intake from food, which could reach 200-300 meq/day. Diets that potassium-rich include diets emphasizing the available abundant variety of potassium-rich vegetables and fruits, and deemphasizing fatty animal-source foods (like fatty hamburger meat) and high-fat-or-high-refined-carbohydrate foods with little-or-no additional nutrient content (like vegetable oil or pancake syrup)—diets considered health-fostering in many ways besides mitigating high blood pressure tissue injury.
Research has not determined optimal potassium intake ranges for maximal protection against heart disease and stroke and other detrimental effects of hypertension.
Dietary Potasium and Risk of Osteoporosis
[...in progress...]
Dietary Potassium and Risk of Kidney Stones
[...in progress...]
References
- ↑ 1.0 1.1 1.2 1.3 Otten JJ, Hellwig JP, Meyers LD (editors) 2006) Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. National Academies Press. Pages 370-379. ISBN 0-309-65646-X
- ↑ 2.0 2.1 Panel on Dietary Reference Intakes for Electrolytes and Water. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Food and Nutrition Board. Institute of Medicine of The National Academies (2004) Dietary Reference Intakes For Water, Potassium, Sodium, Chloride, and Sulfate “Potassium” pp. 186-268. The National Academies Press, Washington, D.C.
- ↑ 3.0 3.1 3.2 What We Eat in America, NHANES 2003-2004, Tables. 1. Nutrient Intakes: Mean Amounts Consumed per Individual, One Day, 2003-2004 (Downloadable PDF File)
- ↑ 4.0 4.1 4.2 Nutrient Intakes: Mean Amounts Consumed per Individual, One Day, 2005-2006. U.S. Department of Agriculture, Agricultural Research Services, Fast Facts, Reports/Articles, and Tables (2005-2006).
- ↑ Moczydlowski EG. (2009) Electrophysiology of the Cell Membrane. In: Boron WF, Boulpaep EL (editors), Medical Physiology, 2nd ed. Saunders/Elsevier: Philadelphia. ISBN 9781416031154.
- ↑ Youn JH, McDonough AA. (2008) Recent Advances in Understanding Integrative Control of Potassium Homeostasis. Annu.Rev Physiol 71:381-401. ISBN 18759636.
- ↑ Note:
- The Food and Nutrition Board of the U.S. Institute of Medicine establishes values for “Adequate Intake” (AI) for nutrients when insufficient data precludes establishing a “Recommended Dietary Intake” (RDA) for that nutrient. It bases AI values how much of the nutrient a group (or groups) of apparently healthy people consume, as determined by observation or experiment. Determination of AI values requires judgments of state of health, in particular in reference to the nutrient’s health effects.
- ↑ Note: If one consumes citric acid, for example, the body metabolizes it to carbon dioxide and water. If it consumes potassium citrate, it metabolizes it to potassium bicarbonate.
- ↑ Souci SW, Fachmann W, Kraut H. (2000) Food Composition and Nutrition Tables. Stuttgart, Germany: Medpharm GmbH Scientific Publishers
- ↑ Sebastian A, Frassetto LA, Sellmeyer DE, Merriam RL, Morris RC, Jr. (2002) Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors. American Journal Clinical Nutrition 76:1308-16
- ↑ U.S. Department of Health and Human Services. Dietary Guidelines for Americans 2005. Washington, D.C. Agriculture Department, Human Nutrition Information Service and Health and Human Services Department
- ↑ Oliveira AC, Oliveira AM, Adan LF, Oliveira NF, Siklva AM, Ladeia AM. (2008) [http://dx.doi.org/10.1038/oby.2008.43 C-reactive Protein and Metabolic Syndrome in Youth: A Strong Relationship?> Obesity 16:1094-1098. PMID 18356840
- ↑ Metabolic Syndrome: What is the Metabolic Syndrome? American Heart Association, 2007.
- ↑ Resnick LM, Barbagallo M, Dominguez LJ, Veniero JM, Nicholson JP, Gupta RK (2001). "Relation of cellular potassium to other mineral ions in hypertension and diabetes". Hypertension 38 (3 Pt 2): 709–12. PMID 11566962.
- Note: Type 2 diabetic patients had the lowest intracellular potassium concentrations, comparing with normal volunteers and patients with hypertension without diabetes.
- ↑ 15.0 15.1 Resnick LM, Gupta RK, Bhargava KK, Gruenspan H, Alderman MH, Laragh JH (1991). "Cellular ions in hypertension, diabetes, and obesity. A nuclear magnetic resonance spectroscopic study". Hypertension 17 (6 Pt 2): 951–7. PMID 2045175.
- ↑ Hu,G.; Jousilahti,P.; Peltonen,M.; Lindstrom,J.; Tuomilehto J. (2005) Urinary sodium and potassium excretion and the risk of type 2 diabetes: a prospective study in Finland. Diabetologia 48:1477-1483. PMID 15971060
- ↑ Heidemann C, Hoffmann K, Spranger J, Klipstein-Grobusch K, Mohlig M et al. (2005). A dietary pattern protective against type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)--Potsdam Study cohort. Diabetologia 48(6):1126-34 PMID 15889235
- ↑ Esmaillzadeh A, Kimiagar M, Mehrabi Y, Azadbakht L, Hu FB, Willett WC. (2006) Fruit and vegetable intakes, C-reactive protein, and the metabolic syndrome. American Journal of Clinical Nutrition 84:1489-1497. PMID 17158434
- ↑ }Fallo F, Della MP, Sonino N, Bertello C, Ermani M, Vettor R, Veglio F, Mulatero P. (2007) Adiponectin and insulin sensitivity in primary aldosteronism. Am J Hypertens. 20:855-61 PMID 17679033
- ↑ http://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.htm#Step8
- ↑ 21.0 21.1 Grundy SM, Brewer HB, Jr., Cleeman JI, Smith SC, Jr., Lenfant C. (2004) Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109: 433–438.
- ↑ 22.0 22.1 Cappuccio FP, MacGregor GA. (1991) Does potassium supplementation lower blood pressure? A meta-analysis of published trials. ‘’J Hypertens’’ 9:465-73
- ↑ 23.0 23.1 Whelton PK, He J, Cutler JA, Brancati FL, Appel LJ, Follmann D, Klag MJ. (1997)Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. ‘’JAMA’’ 277:1624-32
- ↑ Cite He MacGregor Others
- ↑ van den Hoogen PCW, Feskens EJM, Nagelkerke NJD, Menotti A, Nissinen A, Kromhout D, The Seven Countries Study Research Group. (2000) The Relation between Blood Pressure and Mortality Due to Coronary Heart Disease among Men in Different Parts of the World. ’’The New England Journal of Medicine’’ 342:1-8 Abstract and Full-Text Here
- ↑ Hansen TW, Jeppesen J, Rasmussen S, Ibsen H, Torp-Pedersen C. (2005) Ambulatory Blood Pressure and Mortality: A Population-Based Study. ‘’Hypertension’’ 45:499-504
- ↑ van den Hoogen PCW, Feskens EJM, Nagelkerke NJD, Menotti A, Nissinen A, Kromhout D, The Seven Countries Study Research Group. (2000) The Relation between Blood Pressure and Mortality Due to Coronary Heart Disease among Men in Different Parts of the World. The New England Journal of Medicine 342:1-8 Abstract and Full-Text Here
- ↑ Khaw KT, Barrett-Connor E (1987). "Dietary potassium and stroke-associated mortality. A 12-year prospective population study". N. Engl. J. Med. 316 (5): 235–40. PMID 3796701.
- ↑ Green DM, Ropper AH, Kronmal RA, Psaty BM, Burke GL (2002). "Serum potassium level and dietary potassium intake as risk factors for stroke". Neurology 59 (3): 314–20. PMID 12177362. [e]