Multilayered Interplay Between Fructose and Salt in Development of Hypertension

Abstract

T he prevalence of hypertension escalated over the past decades reaching an epidemic level worldwide. 1 Currently, the prevalence of hypertension is ≈30% of the adult US population, according to the National Health and Nutrition Examination Survey data, with many of these subjects having insulin resistance and or other features of the metabolic syndrome. 2 In this regard, dietary fructose from sucrose or high-fructose corn syrup (HFCS) in food and beverages has been convincingly linked with hypertension in large epidemiological studies. 3 One of the largest report is the INTERMAP (International Study of Macro/Micronutrients and Blood Pressure), a cross-sectional epidemiological study on cross-cultural blood pressure (BP) differences analyzing 4680 men and women, aged 40 to 59 years, from Japan, China, United Kingdom, and the United States. INTERMAP has previously reported that intakes of vegetable protein, glutamic acid, total and insoluble fibers, total polyunsaturated fatty linoleic acid and n-3 fatty acids, phosphorus, calcium, magnesium, and nonheme iron were inversely related to BP. Direct positive associations of sugars (fructose, glucose, and sucrose) and sugar-sweetened beverages (especially combined with high sodium intake) were reported by the INTERMAP study. 4 In subjects whose 24-hour urinary sodium excretion was over the median, high-fructose intake (>2 SD, or 5.6% kcal) was associated with increased systolic/diastolic BP of 2.5/1.7 mm Hg. 5 Some studies have not reported an association of fructose intake with increased BP, 6,7 and this may relate to diets that are high in fruit (a major source of fructose), as fruits contain substances such as potassium, vitamin C, flavonols, and other components that block fructose-mediated metabolic effects. [8][9][10][11] However, when epidemiological studies evaluate the relationship of fructose from added sugars on BP, the findings are strong, 3 as noted by a recent meta-analysis. 12 Furthermore, when fructose is provided as a liquid, either alone or as part of an HFCS or sucrose-containing beverage, there is an acute BP raising effect. [13][14][15] Likewise, studies suggest that lowering sugar intake can reduce BP in hypertensive individuals. 16 Several articles have summarized the effects of fructose on BP. 17 One important finding is that fructose does not raise BP simply as a consequence of weight. Indeed, pair-feeding studies have shown that rats fed fructose will develop hypertension, as well as hypertriglyceridemia, hyperuricemia, hyperinsulinemia, and mild renal injury despite no difference in weight with control animals. 18-20 Furthermore, we have not observed metabolic effects from artificial sugars, 21 although one group did report that saccharin might induce insulin resistance in mice. 22 Rather, animals studies suggest fructose may induce hypertension by a variety of mechanisms, including fructose-induced salt and water retention, 23-25 insulin resistance, 26 increased serum uric acid levels, 27 decreased renal nitric oxide availability, 28 and, re...

Development of rat metabolic syndrome models: A review

“…The administration of high NaCl content (8% NaCl) for 2 weeks increased systolic blood pressure, plasma glucose levels, and liver gluconeogenesis [ 6 ]. Recent studies have suggested that a high-salt diet activates processes that result in fructose generation in the liver (endogenous fructose production) [ 46 ].…”

“…A high-salt diet will activate tonicity-responsive enhancer binding protein (TonEBP), a transcription factor that promotes kidney inflammation and osmolyte production in response to inflammation and osmotic stress. In turn, TonEBP activates the aldose reductase pathway, leading to endogenous fructose generation; this indicates a complex interplay in which salt and fructose synergize together to raise blood pressure ( Figure-4 ) [ 46 ].…”

“…MetS models can be developed using drugs or chemical substances, such as glucocorticoids, antipsychotics, alloxan, and streptozotocin (STZ) [ 6 , 7 ]. This method is suitable for drug-related MetS studies, but it needs a longer induction duration to meet the criteria for MetS models [ 46 ].…”

Impact of Uric Acid on Hypertension Occurrence and Target Organ Damage: Insights From the STANISLAS Cohort With a 20-Year Follow-up

“…Hyperuricemia prevalence also displays an increasing parallel tendency similar to that of noncommunicable diseases. The increase in hyperuricemia is believed to originate from diet changes and high fructose consumption in both low-income and developed countries (5)(6)(7).…”

A comprehensive policy for reducing sugar beverages for healthy life extension

“…The consumption of high-fructose corn syrup can have unfavorable effects including weight gain, insulin resistance, hypo-high-density lipoprotein cholesterolemia, and hypertriglyceridemia [3, 4]. Fructose from sucrose or high-fructose corn syrup enhances salt absorption in the gut and kidney and enhances intracellular angiotensin formation [5], whereas the fructose contained in fruits does not raise blood pressure because fruits’ high potassium, antioxidant vitamins such as vitamin C, various flavonols, and dietary fiber protect against this fructose-induced effect on blood pressure [6].…”