A study on the early metabolic effects of salt and fructose consumption: the protective role of water

Mild increases in serum osmolarity have been associated with higher risks of noncommunicable diseases such as hypertension, chronic kidney disease, heart failure, and aging-related conditions. Proposed mechanisms include activation of the renin-angiotensin system (RAS), vasopressin, cortisol, and pathways related to fructose metabolism. While dehydration and heat stress are known to elevate serum osmolarity, dietary salt and sugar, particularly fructose, can also acutely raise serum osmolarity. Evidence suggests that the acute blood pressure effect of salt is driven more by changes in serum osmolarity than by sodium load per se, and that hydration can blunt salt-induced BP rises and metabolic effects by preventing osmolarity increases and polyol pathway–driven fructose generation. This study aimed to compare the early metabolic and hormonal responses to acute salt versus fructose intake and to test whether concomitant water intake (hydration) mitigates these osmolality-driven stress responses.

Background literature indicates that even mild elevations in serum osmolarity correlate with increased risks for hypertension, CKD, heart failure, and aging-related diseases. Mechanistically, osmotic stress may stimulate RAS, vasopressin, cortisol, and fructose metabolism pathways. Prior studies suggest the acute hypertensive effect of salt is largely osmolarity-mediated and can be attenuated by hydration. Hydration has also been shown to prevent salt-induced metabolic syndrome by blocking osmolarity-driven endogenous fructose production via the polyol pathway. These findings frame the hypothesis that both dietary salt and fructose can acutely raise osmolality and activate stress axes, and that water intake may blunt these effects.

Design and participants: Randomized, controlled, four-arm, acute intervention study including 44 healthy adults (BMI reported as 19–25 kg/m²; no systemic disease; no medications). Participants fasted overnight (no intake except water after midnight until the 08:00 intervention). Groups and interventions: Participants were randomly assigned (n=11 per group). Group 1: 500 mL lentil soup with added 3 g salt, consumed within 15 min. Group 2: 500 mL lentil soup with no additional salt, consumed within 15 min. Group 3: 500 mL of 100% pure apple juice, consumed within 5 min. Group 4: 500 mL of 100% pure apple juice plus 500 mL water, both consumed within 5 min. No other eating or drinking during the 2-hour study; no physical activity. Study beverages/foods: Lentil soup nutrient composition per 100 mL: energy 45.6 kcal, fat 0.20 g, saturated fat 0 g, carbohydrate 8.28 g, sugars 0 g, protein 2.46 g, fiber 1.75 g; lentils contain 30 mg sodium and 790 mg potassium per 100 g. Apple juice per 100 mL: energy 48 kcal, fat 0 g, carbohydrate 11.5 g, sugars 10.3 g, protein 0.5 g, fiber 0 g, salt 0; chosen for a higher fructose-to-glucose ratio and lack of antioxidant effects. Measurements and timing: Baseline labs before intake. BP measured every 15 min from 0 to 120 min. Blood drawn at each interval for plasma glucose and plasma sodium. Serum and urine osmolarity, serum uric acid, cortisol, FGF21, aldosterone, ACTH, and plasma renin activity (PRA) measured at baseline and at 120 min. Serum osmolality assessed via freezing-point depression osmometer (Knauer K-7400S). Cortisol and ACTH quantified by electrochemiluminescence immunoassay (Roche Cobas Pro). Uric acid measured colorimetrically. FGF21, aldosterone, PRA measured by competitive inhibition ELISA (USCN, Wuhan, China) with intra-/inter-assay CVs <10% and <12%. BP protocol: Omron HEM 907 oscillometric device; participants rested 5 min seated with arm at heart level before measurements; three readings 30 s apart were averaged each time point. Ethics: Approved by Koc University School of Medicine ethics committee (2022.009.IRB1.009). Written informed consent obtained. Statistical analysis: Data summarized as mean±SD or counts (%); repeated measures analyzed with linear mixed models including fixed effects for treatment, time, and treatment×time interaction, adjusted for baseline and demographic variables differing between groups. Normality assessed with Shapiro–Wilk. Bonferroni correction applied for multiple comparisons at each time point. Results presented as means with 95% CI.

- Both acute salt (Group 1) and fructose (Group 3) intake increased serum osmolality, peaking at ~75 min with a maximum rise of approximately 4 mOsm/L. - These osmolarity increases were associated with rises in systolic and diastolic BP, PRA, aldosterone, ACTH, cortisol, plasma glucose, uric acid, and FGF21. - Differential pathway activation: salt induced greater activation of the renin–angiotensin system (higher PRA/aldosterone responses), whereas fructose elicited greater increases in plasma glucose and FGF21. - Hydration blunted responses: co-ingestion of water with apple juice (Group 4) and consumption of soup without added salt (Group 2) largely prevented the rise in osmolality and attenuated the associated hormonal and hemodynamic stress responses. - BP details: At 30 min vs baseline, systolic BP increased significantly in Groups 1 and 3 only—Group 1 adjusted mean difference 4.2 mmHg (95% CI 2.0–6.3), Group 3 3.6 mmHg (95% CI 1.5–5.8)—and remained elevated over the follow-up; no consistent significant increases in Groups 2 and 4. Group 1 had higher systolic BP than Groups 2 and 4 at most post-baseline intervals; Group 3 exceeded Group 2 at 30 min and exceeded Group 4 at subsequent times. Diastolic BP showed smaller, time-dependent differences with significant effects at select intervals. - Overall, acute osmolality shifts promptly activate ACTH–cortisol, RAS, glucose metabolism, and uric acid pathways, which are mitigable by hydration.

The findings support the hypothesis that acute increases in serum osmolality, whether induced by salt or fructose, trigger a coordinated stress response involving the ACTH–cortisol axis, RAS activation, glucose handling, uric acid metabolism, and FGF21 signaling. The greater RAS stimulation with salt and the stronger glucose/FGF21 response with fructose highlight nutrient-specific pathways of osmotic stress. Crucially, preventing or minimizing the osmolality rise through concomitant water intake attenuated the hemodynamic and hormonal responses, aligning with prior evidence that hydration can blunt osmolarity-mediated effects of salt and fructose. Clinically, this suggests that maintaining hydration may mitigate acute BP elevations and metabolic stress following common dietary exposures to salt and sugary beverages, potentially reducing downstream cardiometabolic risk.

Acute ingestion of salt or fructose elevates serum osmolality and rapidly activates multiple stress and metabolic axes, increasing BP and circulating hormones/metabolites. Hydration substantially reduces these osmolality changes and blunts the associated responses, indicating a simple, practical strategy to mitigate early adverse effects of salt and fructose intake. Given the ubiquity of these nutrients in the diet, encouraging adequate water intake may have immediate benefits. Future research should include longer-term trials to determine whether hydration can prevent chronic cardiometabolic consequences of high salt and sugar consumption and to refine dietary and hydration recommendations.

A dedicated limitations section was not provided in the excerpt. The authors note that more studies are needed to determine whether hydration can block chronic effects of sugar and salt, implying the present study’s short duration and acute design limit generalizability to long-term outcomes.