Epidemiological studies, conducted mainly in Asian countries, indicate that high intakes of salted, smoked, and pickled foods increase the risk of stomach (gastric) cancer (6, 7). Although these foods are high in salt (NaCl), they may also contain cancer-causing agents (carcinogens), such as nitrosamines. Additionally, populations with high intakes of salted foods tend to have low intakes of fruits and vegetables, which are thought to protect against gastric cancer (8).
The risk of developing stomach cancer is increased by chronic inflammation of the stomach and infection by the bacteria Helicobacter pylori. High concentrations of salt may damage the cells lining the stomach, potentially increasing the risk of H. pylori infection and cancer-promoting genetic damage.
Although there is little evidence that salt (NaCl) itself is a cancer-causing agent, high intakes of certain salted foods, such as salted fish, may increase the risk of gastric cancer in susceptible individuals (7, 9, 10).
Osteoporosis
Nutrition is one of many factors contributing to the development and progression of osteoporosis. Increased salt (NaCl) intake has been found to increase urinary excretion of calcium (11). Salt intake has been associated with biochemical markers of bone loss (resorption) in some studies but not in others.
In general, cross-sectional studies have not found an association between sodium intake and bone mineral density (BMD) (12).
However, a 2-year study of postmenopausal women found that increased urinary sodium excretion (an indicator of increased sodium intake) was associated with decreased BMD at the hip (13). A longitudinal study in 40 postmenopausal women found that adherence to a low sodium diet (2 g/day) for six months was associated with significant reductions in sodium excretion, calcium excretion, and a marker of bone resorption (14).
Long-term prospective studies are needed to determine whether decreasing salt intake has clinically significant effects on BMD and fracture risk in individuals at risk of osteoporosis.
Kidney stones
Most kidney stones contain calcium as a main constituent. Increased dietary salt (NaCl) has been found to increase urinary calcium excretion, which has been found to increase the risk of developing calcium stones (15, 16).
A large prospective study that followed more than 90,000 women over a 12-year period found that women with a sodium intake averaging 4.9 g/day (12.6 g/day salt) had a 30% higher risk of developing symptomatic kidney stones than women whose sodium intake averaged 1.5 grams/day (4.0 g/day salt) (17).
However, a similar study in men did not find an association between salt intake and symptomatic kidney stones (18).
Clinical studies have shown that salt (NaCl) restriction reduces urinary calcium in individuals with a tendency to form calcium stones (19), and a five-year randomized controlled trial of two different diets in men with recurrent calcium stones found that a diet low in salt and animal protein significantly decreased stone recurrence compared to a low calcium diet (20).
High blood pressure
Effects of salt reduction on blood pressure
The largest and most rigorously designed observational study of salt (NaCl) and blood pressure was INTERSALT, which studied more than 10,000 men and women in 32 countries. Both cross-population and within-population analyses concluded that increased salt consumption is associated with higher blood pressure levels (21). Subsequent analyses that used more sophisticated statistical techniques made the relationships even stronger than previously reported (22).
Many randomized controlled trials have examined the effect of dietary salt reduction on blood pressure in individuals with abnormally high blood pressure (hypertension) and non-hypertensive individuals (probably pre-hypertensive).
In meta-analyses (23, 24, 25, 26, 27, 28), estimates of the magnitude of the effect of dietary salt reduction on blood pressure did not differ substantially, although the number and types of trials that were included differed substantially. One meta-analysis assessed the results of modest salt reduction from 20 trials in participants with high blood pressure and 11 trials in participants without high blood pressure (28): modest salt reduction (by 1.7 to 1.8 g/day sodium) decreased systolic and diastolic blood pressure by an average of 5.1/2.7 mm Hg in participants with hypertension and 2.0/1.0 mm Hg in participants without hypertension.
Of particular importance are the results of two large, 2-year hypertension prevention trials, called TONE (29) and TOHP-Phase II (30). TONE showed that modest reduction in salt intake by about 1.0 g/day resulted in better control of hypertension in older adults who initially were on blood pressure medication. TOHP-Phase II showed that a similar level of sodium chloride reduction not only reduced systolic and diastolic blood pressure by 1.2/1.6 mm Hg in overweight participants who did not have hypertension, but also reduced the onset of hypertension by 14% after four years.
Although some clinicians have questioned the value of modest blood pressure reductions in hypertensive patients, overviews of observational studies and randomized controlled trials suggest that reducing diastolic blood pressure by an average of 2 mm Hg would reduce the total number of individuals in the (U.S.) population developing hypertension by 17%, the risk of a heart attack by 5%, and the risk of brain infarction ('stroke') by 15% (31).
Thus, modest mean reductions in blood pressure may translate into significant public health benefits.
Salt sensitivity
The classification of individuals as ‘salt-sensitive’ or ‘salt-resistant’ ─ based on their blood pressure response to salt changes ─ has so far not been based on population samples and has not yet been shown to be highly reproducible over time (32). Most of the 'salt sensitivity' studies involved extreme manipulation of sodium intake (loading and depletion) over a short time span (a few days or up to a week). There is no evidence that these very short-term studies bear any relevance to blood pressure changes occurring from long-term, gradual, and moderate changes in salt intake.
Nonetheless, it is well known that certain subgroups of the population, such as people who already have hypertension, older individuals, and African Americans, tend to have greater average blood pressure responses to changes in sodium intake (33). Research examining a genetic basis for salt sensitivity may eventually lead to better and reliable classification of individuals for salt sensitivity (34). Additionally, diet quality and weight loss reduce blood pressure (35, 36, 37). Thus, environmental influences in addition to genetic factors likely contribute to salt sensitivity.
Dietary patterns and blood pressure
A randomized controlled trial, called the DASH (Dietary Approaches to Stop Hypertension) trial, demonstrated that a diet favoring fruits, vegetables, whole grains, poultry, fish, nuts, and low-fat dairy products substantially lowered blood pressure in individuals with elevated (hypertensive) blood pressure (systolic blood pressure/diastolic blood pressure: 11.4 mm Hg/5.5 mm Hg) and people with normal (normotensive) blood pressure (3.5/2.1 mm Hg) compared to a typical U.S. diet (38). The DASH diet was markedly higher in potassium and calcium, modestly higher in protein, and lower in total fat, saturated fat, and cholesterol than the typical U.S. diet. However, sodium levels were kept constant throughout the study in order to better evaluate the effects of other dietary components.
Subsequently, the DASH-sodium trial compared the DASH diet with a typical U.S. control diet at three levels of salt (NaCl) intake: low (2.9 g/day), medium (5.8 g/day), and high (8.7 g/day) (39). The DASH diet significantly lowered systolic and diastolic blood pressures in people with high and normal blood pressures at each level of salt intake compared to the control diet. Reduction of salt intake resulted in an additional lowering of systolic and diastolic blood pressures. The combination of the DASH diet and reduced salt intake lowered blood pressure more than either intervention alone.
Results of the DASH trials support the idea that healthful dietary patterns offer an effective approach to the prevention and treatment of hypertension (40).
Furthermore, a prospective cohort study in 88,517 middle-aged women followed for 24 years found that adherence to a DASH-style diet significantly lowered risk of coronary heart disease and stroke (41).
Target organ damage
Persistent (chronic) hypertension damages the heart, blood vessels, and kidneys, thereby increasing the risk of heart disease and stroke, as well as hypertensive kidney disease. In a number of clinical studies, salt (NaCl) intake has been significantly correlated with an abnormal thickening of the heart muscle ('left ventricular hypertrophy'), which is associated with increased mortality from cardiovascular diseases (42).
Research indicates that high salt intake may contribute to organ damage such as changes in the structure and function of large elastic arteries in ways that are independent of its effects on blood pressure (43, 44, 45, 46).
Cardiovascular disease
Only a few studies have investigated the effects of salt (NaCl) reduction on cardiovascular disease and on mortality, with mixed results (47, 48, 49, 50, 51, 52). In general, the studies suggest a direct association (47, 48, 49).
In the TONE study, there was a trend toward reduced cardiovascular disease in participants assigned to the salt reduction intervention (29).
Importantly, a study found that participants initially without hypertension who were enrolled in the sodium interventions of the two previous TOHP trials had 25% reduction in cardiovascular events 10–15 years later compared with the control groups (53). Subsequent analyses from this TOHP follow-up study showed that the sodium-potassium ratio was associated with increased risk of cardiovascular disease in a dose-response relationship (54), providing complementary evidence for the adverse association between salt (NaCl) intake and cardiovascular disease.