Fructose – Edible Sugar, Absorption Process, Fructose-Related Disorders. Diet for Fructose Intolerance

Fructose, classified as a hexose monosaccharide, is a simple sugar ubiquitously present in nature, with primary dietary sources including fruits, honey, and—to a lesser extent—vegetables. It is critical to note that the aforementioned food categories contain not only fructose itself but also other simple sugars, most notably glucose. These relationships have been systematically documented in a tabular format [1], which delineates the following: **Food Type** | **Total Carbohydrate Content per Serving (g)** | **Fructose Content per Serving (g)** – honey (1 tablespoon): 17 / 9; apple (medium-sized): 19 / 11; grapes (10 pieces): 4 / 4; banana (medium-sized): 14 / 6; tomato (medium-sized): 3 / 2; cucumber (medium-sized): 5 / 3. In highly industrialized nations, particularly those in Western Europe, the predominant sources of fructose remain sucrose—a disaccharide composed of equal parts glucose and fructose—and high-fructose corn syrup (HFCS), an industrially processed sweetener derived from maize [2]. The expanding utilization of HFCS in food manufacturing is attributed to its lower production costs, enhanced processing efficiency, and improved sensory attributes of the final products [3]. Nevertheless, a substantial body of research suggests potential associations between excessive HFCS consumption and the development of metabolic disorders, including type 2 diabetes mellitus, abdominal obesity, hypertension, cardiovascular diseases, nephrolithiasis, and dyslipidemia [3]. Furthermore, HFCS may exacerbate *de novo* lipogenesis within the liver, thereby promoting the onset of non-alcoholic fatty liver disease (NAFLD), a condition that progresses to cirrhosis in approximately 20% of cases [4]. Notably, pure fructose consumption does not appear to elicit comparable adverse effects [5], and alterations in lipid profiles induced by its intake have been found to be analogous to those observed with other simple sugars [6]. The precise maximum safe daily intake of fructose, however, remains undefined. Current dietary guidelines for the general population stipulate only broad recommendations concerning *added sugars*, whose contribution to total daily energy intake should not exceed 10% [7]. The term "added sugars" encompasses both saccharides incorporated during food processing and those naturally occurring in consumed items (e.g., glucose and fructose in honey or lactose in milk) [8].

The principal dietary source of fructose is the disaccharide sucrose, which undergoes enzymatic hydrolysis via the catalytic action of sucrase within the lumen of the small intestine, yielding equimolar quantities of fructose and glucose as the resultant monosaccharides [9]. Subsequent metabolic transformations occur predominantly in two distinct anatomical sites: 1) Within skeletal muscle tissue, where fructose undergoes phosphorylation to fructose-6-phosphate through the action of hexokinase, followed by its incorporation into the glycolytic pathway as an energy-yielding substrate; 2) In hepatic cells (hepatocytes), where fructose is initially converted to fructose-1-phosphate via the enzyme fructokinase (phosphofructokinase-1), then further metabolized to glycerol-3-phosphate—a versatile intermediate that may enter either glycolytic catabolism or gluconeogenic anabolism. It is critically important to emphasize that the vast majority of resultant metabolic derivatives originate from hepatic processing, as substantiated by extensive metabolic research [10, 11].

Hereditary fructose intolerance constitutes a rare, genetically determined disorder of carbohydrate metabolism, transmitted in an autosomal recessive inheritance pattern. This signifies that the fully symptomatic manifestation of the condition occurs exclusively when an offspring inherits one copy of the mutated allele from each parent—both of whom act as heterozygous carriers of the genetic defect [12]. The pathophysiological foundation of this disease complex lies in a congenital, complete or partial deficiency of two critical enzymes involved in fructose metabolism: **1.** phosphofructokinase (PFK), whose absence leads to the development of *essential fructosuria*—a condition characterized by elevated blood fructose levels and its urinary excretion; **2.** fructose-1-phosphate aldolase (aldolase B), the lack of which underpins *hereditary fructose intolerance*—a severe metabolic disorder with potentially fatal outcomes [13,10]. According to the most recent data from the World Health Organization (WHO), the estimated prevalence of hereditary fructose intolerance is approximately **1:40,000** live births, whereas the milder form—essential fructosuria—affects roughly **1:120,000** individuals in the general population [14]. The table below consolidates the key clinical features and diagnostic methodologies for both conditions, incorporating specific biochemical markers and associated symptomatic presentations [15]: • Hereditary Fructose Intolerance (HFI): - Enzymatic defect: Congenital deficiency or absence of aldolase B (fructose-1-phosphate aldolase). - Pathophysiological mechanism: Intracellular accumulation of toxic fructose-1-phosphate in hepatocytes and renal tubules, depleting ATP and arresting glycogenolysis and gluconeogenesis. - Clinical manifestations: Severe postprandial hypoglycemia, recurrent vomiting, hepatomegaly, jaundice, renal dysfunction, and failure to thrive upon weaning onto fructose- or sucrose-containing foods. - Diagnostic framework: Molecular genetic testing (ALDOB gene mutations) and dietary elimination trial (fructose tolerance challenge is contraindicated due to risk of fatal hypoglycemia). - Management: Strict, lifelong exclusion of dietary fructose, sucrose, and sorbitol. • Essential Fructosuria: - Enzymatic defect: Hepatic fructokinase (ketohexokinase, KHK) deficiency. - Pathophysiological mechanism: Impaired initial phosphorylation of fructose; intact fructose circulates harmlessly and is quantitatively excreted in urine. - Clinical manifestations: Completely benign and asymptomatic throughout life with normal longevity. - Diagnostic framework: Incidental identification of reducing substances in urine alongside normal fasting plasma glucose, confirmed by urine chromatography or KHK sequencing. - Management: No dietary modifications or clinical interventions required.

A personalized nutritional plan plays a pivotal role in managing the symptoms of fructose intolerance, particularly in cases stemming from aldolase B enzyme deficiency. The primary therapeutic approach involves implementing a strict elimination diet that minimizes the intake of products rich in fructose—a monosaccharide naturally found in fruits, vegetables, and sweetened processed foods [16]. Of paramount importance is the conscious avoidance of foods with documented high concentrations of this carbohydrate, including bee-derived honey, all varieties of fruit preserves (jams, purées, sugar-free spreads), and the majority of fruit species, whether fresh or dried [13].