Evolutionary Approach to Medicine

Marcelo Turkienicz Berlim, MD, Alberto Mantovani Abeche, MD, Department of Gynecology and Obstetrics, Federal University of Rio Grande do Sul, School of Medicine, Porto Alegre, RS, Brazil

South Med J. 2001;94(1) 

In This Article

A Disease of Civilization

The transition of animal life from the oceans toward the numerous niches on the surface of our planet (specifically the progression of amphibians from the aquatic environment to land 300 million years ago[26]) has involved many cellular "stresses."[27] These stresses were a direct consequence of several ionic and osmotic patterns to which the cells of primitive organisms were submitted. Life in the ocean, which has a salt concentration (3.5% saline) about four times higher than our extracellular fluid (0.9% saline),[26] has involved osmoregulatory stresses different from those found in the development of life on earth. In the latter, there was the risk of dehydration and, in many areas of the planet, salt deficiency.[27]

Since their appearance 40,000 years ago, modern human beings (Homo sapiens sapiens) lived in this NaCl-poor environment,[26,28] consuming about 690 mg sodium/day.[29] Because of the development of agriculture 10,000 years ago, salt intake became even lower, as plants made up 90% of the diet.[26,29] For this reason, our forefathers developed a mainly renal regulatory mechanism for the conservation of extracellular fluid concentrations. This maintenance of ionic patterns in prehistoric times was achieved by high glomerular filtration rate (GFR) and by an almost full tubular reabsorption of NaCl considering the limited consumption of this salt, low extracellular volume, and/or changes in the blood pressure (BP).[30] In this way, the self-regulation of renal plasmatic flow and GFR was crucial to prevent an even greater variation in fluid and electrolyte intake from altering the milieu interieur stability.[26] Therefore, it could be suspected that the persistence of such an intricate control mechanism of BP in the human genome assumes that it has adaptive value.[31]

This is the context in which hypertension appears as one of the greatest public health problems in developed countries. It is defined as the chronic rise of BP above 140/90 mm Hg. It is a common asymptomatic clinical entity, and frequently leads to lethal complications if not treated properly. The etiology is unknown in 90% to 95% of patients, which is why it is called "essential hypertension."[32]

However, various studies (including observational epidemiologic studies, migration studies, animal experiments, and randomized controlled trials) showed the strong link between the daily intake of sodium and the prevalence and etiology of hypertension,[33,34] as well as the importance of sodium restriction in the treatment and prevention of hypertension,[35] though there is still some controversy on this subject.[36,37] In a recent observational epidemiologic study,[38] examination of salt intake and BP in 663 individuals showed that a 3 mm Hg increase in systolic and 1.8 mm Hg in diastolic BP (P < .01 for both) was associated with a 100-mmol higher 24-hour urinary sodium. Two recently published trials deserve mention.[39,40] Cappuccio et al[39] conducted a double-blind trial in which 47 untreated elderly patients were randomly assigned to a usual NaCl intake (10 g/day) or modest NaCl reduction (5 g/day). The authors reported that a reduction in dietary sodium intake of 83 mmol/day was significantly associated with a reduction of 3.2 mm Hg in diastolic BP and 7.2 mm Hg in systolic BP. On the other hand, Whelton et al[40] conducted a randomized, controlled trial with 975 hypertensive patients (aged 60 to 80 years). Obese individuals were randomly assigned to either usual care (ie, no active intervention), weight loss, sodium reduction, or combined sodium reduction and weight loss groups, and those who were in the normal weight category were assigned to either a usual care or sodium reduction group. At 30 months, 38% of those in the sodium reduction group vs 24% of those in the control group (P < .001) were free of an endpoint such as a BP-related clinical complication, BP >150/>90 mm Hg, or resumption of an antihypertensive drug.

Moreover, Denton et al[41] provided direct evidence in favor of a causal relationship between hypertension and high NaCl intake. They studied 26 chimpanzees that were fed a vegetarian diet with a very low sodium content for 1 year. After this period, salt was added in increasing amounts to the diet of 13 animals (5 g/day for 19 weeks, 10 g/day for 3 weeks, and then 15 g/day for 67 weeks). After the 19 weeks of the 5 g/day salt addition, mean systolic BP increased by 12 mm Hg (P < .05). After the addition of 10 g/day salt for 3 weeks and of 15 g/day for 62 weeks, mean diastolic BP increased by 10 mm Hg (P < .01), and mean systolic BP increased by 33 mm Hg (P < .001). Twenty weeks after the end of the salt supplementation period, BP returned to baseline values. In fact, migration studies showed that populations with a very low salt intake have no hypertension, yet if such people migrate to more industrialized societies (with high salt intakes), almost 30% of them will show a significant rise in BP.[26,28,33,34] Four recent meta-analyses of published trials[42,43,44,45] showed a significant relationship between BP and sodium intake in both normotensive persons and hypertensive patients. More impressive are the results of the "Dietary Approaches to Stop Hypertension -- Sodium" (DASH-Sodium) study, in which investigators randomly assigned 412 subjects with and without hypertension to either the "DASH diet" (rich in low-fat products, fruits, and vegetables) or a control diet at three levels of NaCl intake (8 g/day, 6 g/day, and 4 g/day) similar to that of the average American, both for 90 days. Then, the researchers changed the sodium level every 30 days. When individuals with hypertension went from the high-NaCl to the low-NaCl control diet, their systolic BP fell 8.3 mm Hg and diastolic BP fell 4.4 mm Hg. This drop is comparable with that achieved by pharmacotherapy. In the nonhypertensive individuals taking the control diet, going from high salt to low salt intake reduced systolic BP by 5.6 mm Hg and diastolic BP by 2.8 mm Hg.[46] In the future, according to He and Whelton,[33] prospective epidemiologic studies should be conducted to examine the relationship between daily salt intake and risk of coronary artery disease, stroke, renal disease, and left ventricular hypertrophy.

From the evolutionary perspective previously offered, we may notice that natural selection over generations has molded the adaptation of our forefathers to the low NaCl content in their environment.[28] However, in modern society access to salt is almost unlimited, with a sodium consumption of about 4,000 mg or more per/day (equivalent to 10 g NaCl).[29] Taking into account the fact that in the last 10,000 years the change in our genetic material was of at most 0.005%,[6] our genes are almost identical to those of our forefathers. Nevertheless, as stated by Eaton et al,[29] our genetically determined physiology and biochemistry now face circumstances vastly different from those that were selected by evolution, and this difference between the human organism and its life environment could account for the current high prevalence of chronic degenerative diseases such as hypertension, obesity, and atherosclerosis.

From all this, it could be concluded that the possible deleterious effects of a high sodium chloride diet are not unexpected and essential hypertension may be a consequence of renal maladaptation to excessive salt consumption, a feature of modern civilization.1,26,29,46 Finally, an intervention to lower BP in the general population -- based, for instance, on a modest reduction of dietary sodium intake -- should result in a large reduction in hypertension prevalence, as well as a substantial decrease in cardiovascular and renal events.34,48

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