Faculty Peer Reviewed
Sugared soft drinks are among the most heavily consumed drinks in the US. Carbonated soft drinks were first invented as a way to make “healthier” water that looked like natural carbonated waters that were found in European spas in the mountains. The name soda came from the use of bicarbonate of soda, which was used to produce carbonation (for an excellent review of the history of beverages, refer to Wolf et al.. Unfortunately, we no longer realize any health benefits from carbonated waters.
Recent data show that each American drinks greater than 35 gallons of caloric soft drinks yearly (for comparison, milk totals 21 gallons per capita per year, coffee 24, and beer 22, data available from the USDA website). Further, research suggests that increasing calorie intake from liquids is not associated with a proportional decrease in calorie intake from solids. As a result, soda represents substantial proportion of daily calories consumed and is a major contributor to the rising obesity epidemic.
Sugared soft drinks contain large amounts of either sucrose or high fructose corn syrup. Sucrose is a dimer of glucose and fructose, whereas high fructose corn syrup is a product in which about half of glucose is converted to fructose in order to increase the sweetness. Therefore, research to evaluate the impact of soft drinks on health has long focused on the effects of fructose. In addition to the effect on weight, there has been accumulating evidence that soft drinks and other sources of dietary sugar may also be associated with hypertension, independent of their effect on obesity.
Uric acid could be a link between soft drink intake and incident hypertension
Tappy and Lê recently published a thorough review of the metabolic effects of fructose. Briefly, fructose differs immensely from glucose. While glycolysis is a very controlled pathway, the fructose pathway is not as controlled. Almost all fructose absorbed from the diet is taken up by hepatocytes in the first pass by the liver, leaving only minuscule amounts detectable in the peripheral circulation. Since the phosphorylation of fructose upon entrance to the cell is essentially not a controlled step, it leads to rapid depletion of hepatocyte ATP. As a consequence, AMP accumulates, stimulating the purine degradation pathway and formation of uric acid. In addition, a fructose load stimulates the formation of triglycerides more than glucose, and has a direct effect on insulin resistance. The mechanisms by which fructose could therefore lead to increased blood pressure may include obesity through increased caloric intake, insulin resistance, or accumulation of uric acid.
Several animal studies have given insight into associations between uric acid levels and blood pressure. Others found that pathologic findings classically attributed to hypertension are seen in mice with hyperuricemia even after controlling blood pressure. In one model, hypertension resolves with treatment of hyperuricemia with allopurinol (for a review of the animal data, refer to Feig et al.(3). An observational study of soft drinks intake in adolescents found increased uric acid levels correlating with both blood pressure and soft drinks intake .
Although uric acid may cause hypertension and mediate some of the pathologic consequences classically associated with longstanding high blood pressure in mice, humans are more complex. Studies have been conflicting. Antagonizing or decreasing uric acid with vitamin C was not associated with a decreased risk of hypertension in the Nurses’ Health Study I and II and the Health Professionals Follow-up Study[5-8]. In addition, George et al. showed that although markers of endothelial dysfunction in patients with heart failure improved after reduction of hyperuricemia with allopurinol, they did not change after a similar reduction of hyperuricemia by means of an uricosuric agent, probenecid. This result highlights the possibility of uric acid being just a marker, or maybe even a biological response against endothelial dysfunction, rather than its cause.
Observational studies corroborate a small but significant association of soft drink intake and incident hypertension
In 2005, Winkelmayer et al. reported the observations made on prospective cohorts of the Nurses’ Health Study I and II, including almost 150,000 nurses who were not hypertensive at baseline . During the follow up period of 9-12 years, as intake of both sugared and diet cola drinks increased, incident hypertension increased with an adjusted odds ratios in the range of 1.16 to 1.44 for intakes of 4 or more cans per day. Forman et al. in the same cohorts and others failed to see an association between total fructose intake, vitamin C, and hypertension(5).
Relationships between soft drinks intake and metabolic syndrome were reported in a prospective observational study. The authors separated the diet versus the regular version of soft drinks in the analysis, and both were significantly associated with development of metabolic syndrome in the multivariate model (odds ratios of 1.53 for diet, 1.62 for regular, and 1.41 for both). When the components of the metabolic syndrome were split up, the association with hypertension was significant but small, much like in the Nurses’ Health Study (adjusted odds ratio 1.20).
The associations between soft drinks and high blood pressure, found in studies that were not specifically designed to address fructose intake, were corroborated by a recent, large, cross-sectional study based on the NHANES data. The adjusted odds ratio for having a systolic blood pressure of 160 mmHg or more increased in direct association with the amount of fructose intake, reaching 2.1 for individuals that took 74g/day of fructose or more.
Chen et al. also attempted to investigate the relationship of fructose intake and hypertension, but in a more controlled setting of subjects enrolled in a clinical study. Analyzing the subjects enrolled in the PREMIER trial, the authors found that a reduction of 1 serving of sugared drink per day was significantly associated with a decrease in systolic blood pressure of 0.7 mmHg and a decrease in diastolic blood pressure of 0.4 mmHg, in the fully adjusted model.
There is fair to good evidence that higher intakes of fructose, either in the form of sucrose or high fructose corn syrup, seem to increase one’s risk for hypertension. This increased risk is probably independent of the effect of higher caloric intake on obesity. The relationship between high fructose intake and hyperuricemia has received recent attention, bringing new light to a subject that was almost forgotten since the development of effective treatment of gout. Animal studies have brought hope that the cause of hypertension is an easily treatable metabolic derangement, but later clinical findings have been inconsistent. It is possible that metabolic effects of hyperuricemia will receive increasing attention from the research community.
Therefore, limiting or even completely avoiding sugared soft drinks are reasonable options. There have been some administrative attempts to reduce consumption by means of taxing soft drinks. On the one hand, laboratory data and observational studies suggest that that could be a good idea. On the other hand, such control of people’s habits has not been evaluated by studies addressing feasibility and impact on clinically important outcomes. It is clear that we don’t know enough, and it is always better to exercise caution in matters of health policy.
Dr. Ivan Saraiva recently completed his residency at NYU Langone Medical Center
Peer reviewed by David Goldfarb, MD, Nephrology, section editor, Clinical Correlations
Image courtesy of Wikimedia Commons
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