Low-Calorie Sweetened Beverage Replacement May Improve Cardiometabolic Risk

John L. Sievenpiper, MD, PhD

New evidence supported the use of low- and no-calorie sweetened beverages (LNCSBs) as a replacement strategy for sugar-sweetened beverages (SSBs) over the moderate term in adults with overweight or obesity, who are additionally at risk for or have diabetes.

Specifically, data show using LNCSBs as an intended substitute for SSBs was associated with small improvements in body weight and cardiometabolic risk factors without evidence of harm and a similar direction of benefit as water substitution.

“Although water is considered to be the standard-of-care substitution for SSBs by authoritative bodies, with many health organizations recommending against the use of LNCSBs, the existing evidence confirms the intended benefits of LNCSBs as a substitute for SSBs over the moderate term,” wrote study author John L. Sievenpiper, MD, PhD, St Michael's Hospital.

investigators summarized evidence of the association of LNCSBs with intermediate cardiometabolic outcomes, using 3 pre-specified substitutions:

• LNCSBs for SSBS (intended substitution with caloric displacement)
• Water for SSBs (standard-of-care substitution with caloric displacement)
• LNCSBs for water (reference substitution without caloric displacement).

Investigators searched Medline, Embase, and the Cochrane Register of Controlled trials from inception through December 2021. They included randomized controlled trials of ≥2 weeks that investigated the association of LNCSBs, SSBs, and/or water with cardiometabolic risk factors.

The primary outcomes were body weight, with secondary outcomes including measures of adiposity, glycemic control, blood lipids, blood pressure, measures of nonalcoholic fatty liver disease (NAFLD), and uric acid.

Within the study, a total of 17 RCTs with 24 trial comparisons were included that assessed the association of the 3 prespecified substitutions with body weight, measures of adiposity, and cardiometabolic risk. The population consisted of 17733 adults (mean age, 33.1 years; 1341 women [77.4%]) with overweight or obesity who were at risk for or had diabetes.

Investigators observed LNCSBs were a substitute for SSBs in 12 trials (n = 601 participants), water was a substitute for SSBs in 3 RCTs (n = 429), and LNCSBs were a substitute for water in 9 RCTS (n = 974).

Data show the substitution of LNCSBs for SSBs was associated with reductions in:

• body weight (MD, -1.06 kg; 95% CI, -1.71 to -0.41 kg)
• body mass index (MD, -0.32; 95% CI, -0.58 to -0.07)
• percentage of body fat (MD, -0.60%; 95% CI, -1.03% to -0.18%)
• intrahepatocellular lipid (SMD, -0.42; 95% CI, -0.70 to -0.14)

However, investigators observed no significant differences when substituting water for SSBs in the primary outcome of body weight (MD, -0.01 kg: 95% CI, -0.95 to 0.98 kg) or any secondary outcomes.

In fact, a greater reduction in body weight (MD, -1.07 kg; 95% CI, -1.95 to -0.19 kg) was associated with LCSBs compared to water. No association was found between substituting LNCSBs for water with any outcome except glycated HbA1c (MD, 0.21%; 95% CI, 0.02% to 0.40%), and systolic blood pressure (MD, -2.63 mm Hg; 95% CI, -4.71 to -0.55 mm Hg).

Investigators noted the certainty of the evidence was moderate for LNCSBs as a substitute for SSBs, moderate for water as a substitute for SSBs, and low for LNCSBs as a substitute for water

The study, “Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk,” was published in JAMA Network Open.