Appendix E-2.42 Evidence Portfolio

Sodium and Blood Pressure:

Part a: Overall effect of dietary intake of sodium on blood pressure

Three RCTs.

Evidence Summary 1 (ES1): In adults, 25–80 years of age with BP 120–159/80–95 mmHg, reducing sodium intake lowers BP. (Strength of evidence: High)

Part b: Comparison of different levels of dietary intake of sodium on blood pressure

One RCT

Evidence Summary 2 (ES2): In adults, 25–75 years of age with BP 120–159/80–95 mmHg, reducing sodium intake that achieves a mean 24-hour urinary sodium excretion of approximately 2,400 mg/day, relative to approximately 3,300 mg/day, lowers BP by 2/1 mmHg, and reducing sodium intake that achieves a mean 24-hour urinary sodium excretion of approximately 1,500 mg/day, lowers BP by 7/3 mmHg.  (Strength of evidence: Moderate)

Counseling to reduce dietary sodium and BP reduction

Two RCTs

Evidence Summary 3 (ES3): In adults, 30–80 years of age with or without hypertension, counseling to reduce sodium intake by an average of 1,150 mg/day reduces BP by 3–4/1–2 mmHg. (Strength of evidence: High)

Part c: Sodium and blood pressure in subpopulations: subgroups included men and women, African Americans and non-African Americans, and older and younger adults.

Three RCTs (3–6 months’ duration)

Evidence Summary 4 (ES4): In adults with prehypertension or hypertension, reducing sodium intake lowers BP in women and men, African American and non-African American adults, and older and younger adults. (Strength of evidence: High)

Sodium and blood pressure in subpopulations: adults with either prehypertension or hypertension.

Three studies

Evidence Summary 5 (ES 5): Reducing sodium intake lowers BP in adults with either prehypertension or hypertension when eating either the typical American diet or the DASH dietary pattern. The effect is greater in those with hypertension. (Strength of evidence: High)

Part d: Sodium and blood pressure in the context of dietary pattern changes

DASH-Sodium trial.

Evidence Summary 6 (ES6): In adults, 25–80 years of age with BP 120–159/80–95 mmHg, the combination of reducing sodium intake and eating the DASH dietary pattern lowers BP more than reducing sodium intake alone. (Strength of evidence: Moderate)

Part e: Sodium and blood pressure in the context of other minerals

No RCTs or meta-analyses met inclusion criteria that examined whether reducing sodium intake plus changing dietary intake of any other single mineral lowers BP more than reducing sodium intake alone.  

Evidence Summary 7 (ES7): Evidence from RCTs is not sufficient to determine whether reducing sodium intake and changing dietary intake of any other single mineral (e.g., increasing potassium, calcium, or magnesium) lowers BP more than reducing sodium intake alone

Cardiovascular disease (CVD), including stroke CVD mortality and all-cause mortality, congestive heart failure (CHF), chronic kidney disease (CKD), diabetes, cancer, and “other” outcomes, such as asthma and depression.

4 RCTs; 35 observational (cohort or case-control) studies

•  CVD, Stroke and Mortality (4 RCTS, 22 obs. studies)
•  Kidney disease (2 obs. studies)
•  Metabolic syndrome (2 obs. studies)
•  Diabetes (2 obs. studies)
•  Gastrointestinal cancer (8 obs. studies)

Conclusion 1: Although the reviewed evidence on associations between sodium intake and direct health outcomes has methodological flaws and limitations, the committee concluded that, when considered collectively, it indicates a positive relationship between higher levels of sodium intake and risk of CVD. This evidence is consistent with existing evidence on blood pressure as a surrogate indicator of CVD risk.

Conclusion 2: The committee determined that evidence from studies on direct health outcomes is inconsistent and insufficient to conclude that lowering sodium intakes below 2,300 mg per day either increases or decreases risk of CVD outcomes (including stroke and CVD mortality) or all-cause mortality in the general U.S. population.

Cardiovascular disease (CVD), including stroke CVD mortality and all-cause mortality, congestive heart failure (CHF), chronic kidney disease (CKD), diabetes, cancer, and “other” outcomes, such as asthma and depression.

4 RCTs; 35 observational (cohort or case-control) studies

•  CVD, Stroke and Mortality (4 RCTS, 22 obs. studies)
•  Kidney disease (2 obs. studies)
•  Metabolic syndrome (2 obs. studies)
•  Diabetes (2 obs. studies)
•  Gastrointestinal cancer (8 obs. studies)

Conclusion 1: The committee concluded that the available evidence suggests that low sodium intakes may lead to higher risk of adverse events in mid- to late-stage CHF patients with reduced ejection fraction and who are receiving aggressive therapeutic regimens. Because these therapeutic regimens were very different than current standards of care in the United States, the results may not be generalizable. Similar studies in other settings and using regimens more closely resembling those in standard U.S. clinical practice are needed.

Conclusion 2: The committee concluded that, with the exception of the CHF patients described above, the current body of evidence addressing the association between low sodium intake and health outcomes in the population subgroups considered is limited. The evidence available is inconsistent and limited in its approaches to measuring sodium intake. The evidence also is limited by small numbers of health outcomes and the methodological constraints of observational study designs, including the potential for reverse causality and confounding.

The committee further concluded that, while the current literature provides some evidence for adverse health effects of low sodium intake among individuals with diabetes, CKD, or preexisting CVD, the evidence on both the benefit and harm is not strong enough to indicate that these subgroups should be treated differently from the general U.S. population. Thus, the committee concluded that the evidence on direct health outcomes does not support recommendations to lower sodium intake within these subgroups to, or even below, 1,500 mg per day.

To ensure that the overall diet provides an adequate intake of other important nutrients and to cover sodium sweat losses

>400 citations

Adults (19-50 yrs): The AI for sodium is set for young adults at 1.5 g (65 mmol)/day (3.8 g of sodium chloride) to ensure that the overall diet provides an adequate intake of other important nutrients and to cover sodium sweat losses in unacclimatized individuals who are exposed to high temperatures or who become physically active as recommended in other DRI reports.

Older adults: The AI for sodium for older adults and the elderly is somewhat less, based on lower energy intakes, and is set at 1.3 g (55 mmol)/day for men and women 50 through 70 years of age, and at 1.2 g (50 mmol)/day for those 71 years of age and older

Children (1–18 yrs): Given that little data are available indicating that in normal children, inadequate sodium intakes result in specific identifiable markers, and that, as with adults, normal kidney function can maintain sodium balance at extremes of sodium intake, the AI is set based on meeting nutrient needs for other essential nutrients. The AI is thus extrapolated down from the adult AI of 1.5 g/day (65 mmol/day) using relative energy intake, that is, the average of median energy intake levels of the age groups for adults and for children as the basis for extrapolation.

Blood pressure, stroke and CHD; left ventricular mass; calcium excretion, bone mineral density, and kidney stones; pulmonary function; gastric cancer

>400 citations

Adults (19-50 yrs): Because the relationship between sodium intake and blood pressure is progressive and continuous without an apparent threshold, it is difficult to precisely set a UL, especially because other environmental factors (weight, exercise, potassium intake, dietary pattern, and alcohol intake) and genetic factors also affect blood pressure. For adults, a UL for sodium of 2.3 g (100 mmol)/day is set, equivalent to a total of 5.8 g/day of sodium chloride. In dose-response trials, this level was commonly the next level above the AI that was tested. The equivalent UL for chloride is 3.5 g. It should be noted that the UL is not a recommended intake and, as with other ULs, there is no demonstrated benefit to consuming levels above the AI.

Individuals who are most sensitive to the blood pressure effects of increased sodium intake (e.g., older persons, African Americans, and individuals with hypertension, diabetes, or chronic kidney disease): Their UL for sodium may well be lower. These groups also experience an especially high incidence of blood pressure-related cardiovascular disease.

Individuals who are unacclimatized to prolonged physical activity in a hot environment: Their needs may exceed the UL because of sodium sweat losses

Children and adolescents (1-18 yrs): The ULs for children are extrapolated from the adult UL of 2.3g (100 mmol)/day based on these estimated energy intakes, after rounding. Since the estimated energy intake for adolescents is in the same range as adults, the ULs for this age group are the same as those for adults.