Risk factors for lipid metabolism disorders in underage athletes: A review

INTRODUCTION

Lipids perform key metabolic functions in the child’s body, changing dynamically with age. If at an early stage their primary role is structural (formation of nervous tissue and myelin sheaths), then by adolescence, their energy and hormonal functions come to the fore [1]. During puberty, lipid metabolism is closely linked to the functioning of the endocrine system: tissue sensitivity to hormones regulating lipolysis changes, leading to alterations in the blood lipid profile [2]. Thus, the age-related dynamics of lipid metabolism reflect the general reorganization of the body at different stages of development.

The rate and direction of lipid metabolism depend on dietary patterns, energy expenditure, the functional state of the liver and adipose tissue, and are also largely determined by genetic predisposition. Disruption of the regulation of any of these components can lead to an imbalance in the lipid profile and contribute to the development of diseases such as atherosclerosis and obesity.

Analysis of medical statistics over the past 20 years reveals an alarming trend of increasing cardiovascular disease and mortality among young patients [3]. Current research demonstrates that pathological changes in the lipid profile can develop from an early age and persist throughout life, contributing to the early development of atherosclerosis [4].

In recent years, special attention has been paid to the study of lipid metabolism in adolescent professional athletes. Despite the proven cardioprotective effect of regular physical activity, studies show a high prevalence (20–35.8%) of dyslipidemia among elite athletes [5][6], and atherosclerosis is the cause of sudden cardiac death in young athletes (2–20%) [7]. The lipid profile of athletes is influenced by dietary patterns, the type of sport, and the level of physical loads. Diets high in saturated fats and trans fats can lead to elevated levels of low-density lipoproteins and triglycerides, while the intake of dietary supplements and certain medications, excessive training loads, and insufficient recovery contribute to the development of dyslipidemia [8][9]. Despite the high clinical significance of the problem, there are currently no standardized reference values for the lipid profile adapted to the age, gender characteristics, and specificity of sports activity in adolescent athletes.

Risk stratification for cardiovascular disease in children remains a complex task due to an insufficient evidence base and the lack of unified algorithms for children with lipid metabolism disorders, leading to late diagnosis and delayed initiation of therapy. Among the risk factors for atherosclerosis, modifiable factors (lifestyle, diet, intake of dietary supplements, homocysteine levels) and non-modifiable factors (genetic predisposition, elevated lipoprotein(a) levels, age and sex) are distinguished; the latter require particular attention in pediatric practice.

The aim of this work was to determine the directions for the prevention of lipid metabolism disorders in adolescent athletes.

An analysis of domestic and international scientific publications (PubMed, Scopus, Web of Science, Russian Science Citation Index (RSCI), CyberLeninka) was performed using the keywords: dyslipidemia, cardiovascular disease, athletes, children, adolescents, risk factors, lipoprotein(a), homocysteine, sports nutrition. The search depth was 10 years. Inclusion criteria: full-text articles in Russian or English; study groups — children and adolescents aged 6–18 years engaged in organized sports; study types — observational studies, systematic reviews, meta-analyses, position papers from expert societies. Exclusion criteria: studies on adults only (>21 years) without a pediatric subgroup, abstracts/conference proceedings, papers in other languages. Duplicates were automatically removed by DOI; when overlapping samples from the same cohort were identified, the publication with the most complete data was selected.

MAIN BODY

When assessing the lipid profile in adolescent athletes, it is of fundamental importance to distinguish between physiological age-related changes and pathological conditions. Puberty is characterized by transient insulin resistance caused by the effects of growth hormone and sex steroids, which is accompanied by a temporary decrease in high-density lipoprotein levels and an increase in triglycerides [10]. This physiological reorganization creates a background against which sports-related risk factors may have a potentiated effect.

Non-modifiable risk factors for the development of cardiovascular diseases

The genetic nature of lipid metabolism disorders is the most unfavorable factor, almost always leading to the atherosclerosis development. Familial hypercholesterolemia is an inherited autosomal dominant disorder caused by mutations in genes encoding the LDL (low-density lipoprotein) receptor (LDLR, 85%), apolipoprotein B-100 (APOB, 5%), and proprotein convertase subtilisin/kexin type 9 (PCSK9, 1%), accompanied by persistently elevated levels of total cholesterol and LDL. The disease manifests in two forms: heterozygous and homozygous, with the latter having a more severe course.

Differential diagnostic criteria for suspecting FH in a young athlete include [10]:

• LDL level ≥4.9 mmol/L in two consecutive tests while on a lipid lowering diet for 3 months;
• LDL level ≥4.0 mmol/L combined with early cardiovascular disease in a first degree relative (men <55 years, women <60 years) and/or high LDL level (≥4.9 mmol/L);
• LDL level ≥3.5 mmol/L combined with a genetically confirmed diagnosis of FH in one of the parents.

Lipoprotein(a), also known as Lp(a), is a significant and independent risk factor for early atherosclerosis [11]. In composition, it is similar to LDL, but in addition to apolipoprotein B it contains a specific apolipoprotein(a), which confers unique atherogenic properties to the molecule [12]. Due to its structural features, Lp(a) readily penetrates the vessel wall, becomes oxidized, and is taken up by macrophages, initiating a cascade of inflammatory reactions and accelerating intimal lipid infiltration. A critical mechanism of the pathogenic action of Lp(a) is its ability to impair fibrinolysis. Due to its similarity to plasminogen, it blocks the binding of plasminogen to fibrin, thereby suppressing clot dissolution. This property, combined with pro-inflammatory activity, increases the likelihood of thrombotic complications (myocardial infarction, stroke) upon destabilization of an atherosclerotic plaque [13].

The concentration of Lp(a) is more than 90% determined by heredity and remains relatively constant for a given individual [14]. Numerous studies demonstrate the stability of this parameter regardless of the intensity and variability of physical activity and dietary patterns, which distinguishes it from other lipid parameters. According to current recommendations, measuring Lp(a) once in a lifetime is sufficient for cardiovascular risk stratification [15][16]. Reference values vary by ethnicity: the highest levels are characteristic of African populations, while lower levels are found in Asian and European populations [17].

The data regarding childhood are conflicting. It was previously believed that the level of Lp(a) stabilizes by 2 years of age [18]; later observations of children with hyperlipidemia (n = 2740) showed an increase with age [19]. It has been demonstrated that in children and adolescents, an Lp(a) concentration exceeding 30 mg/dL serves as a marker of high risk for ischemic stroke (both first and recurrent) [13]. Although the general lipid profile in young athletes is being actively studied, data specifically on Lp(a) in this group are limited, which underscores the need for further research.

Thus, genetic factors create a baseline level of risk that is practically unchanged by training. However, in the majority of young athletes, the leading role is played precisely by modifiable factors, the analysis of which allows for effective primary and secondary prevention.

Modifiable risk factors for cardiovascular disease development

According to a cross-sectional study, endocrine pathology is the cause of secondary dyslipidemia in 52.7% of patients, with lipid metabolism disorders occurring in 25% of children with obesity or overweight [20]. Lipid metabolism disorders in athletes may also be secondary in nature, manifesting as a moderate increase in atherogenic lipids that is reversible with correction of diet and physical activity regimen.

Nutritional aspects of dyslipidemia formation in sports practice

Modern sports nutrition considers nutrition not only as a means of replenishing energy expenditure but also as an active tool for enhancing physical performance [21]. Nutritional support for adolescent athletes requires particular attention. The diet of a young athlete must be balanced to meet both high training demands and the needs of continued growth [22]. Differences in nutritional support between endurance sports and strength disciplines require a strictly personalized approach [23][24].

In speed-strength sports, such as weightlifting, the consumption of foods high in saturated fats (from red meat, eggs, butter, etc.) and simple carbohydrates (for rapid glycogen replenishment) is common. These sports are characterized by cycles of muscle mass gain followed by weight cutting. During weight cutting, especially using carbohydrate-restricted methods, not only insulin resistance develops but also a compensatory increase in hepatic lipogenesis upon the athlete’s return to normal nutrition (rebound effect), leading to an increase in very low-density lipoproteins and triglycerides [25]. High-carbohydrate diets with a high glycemic index, used by athletes to maintain high power output and rapid recovery between intense training sessions, are a proven risk factor for the development of hypertriglyceridemia [26].

Athletes engaged in rhythmic gymnastics, figure skating, and synchronized swimming strictly control their weight and are in a state of chronic low energy availability. As a result of this condition, lipolysis slows down, and the body begins to accumulate fat even with minimal caloric intake, exacerbating dyslipidemia against a background of energy depletion [27]. Even years after retirement, former athletes from aesthetic sports demonstrate higher rates of subclinical atherosclerosis and insulin resistance compared to control groups of similar age and athletes from sports not sensitive to weight control. This suggests that early nutritional disturbances have long-term consequences for lipid metabolism. Also, sports with a high risk and frequency of developing relative energy deficiency syndrome include cross-country skiing, running, and race walking (marathons) [28].

Nutrition is closely linked to the type of sports activity: in some disciplines, hypercaloric diets with excess fat predominate, while in others, chronic energy deficiency prevails. However, the specificity of the sport itself can independently influence the lipid profile.

The influence of sport type specificity on lipid metabolism

The type of sports activity acts as an independent factor influencing the lipid profile. This is related not only to dietary patterns but also to the nature of the training process. The highest triglyceride levels are observed in athletes engaged in sports with low energy expenditure (archery, equestrian sports, golf, shooting, sailing, etc.), which is explained by the predominance of low-activity training sessions that have minimal energy expenditure. In sports with a low motor component, muscles do not act as an effective “depot” and substrate utilizer, creating prerequisites for the development of insulin resistance and, consequently, elevated triglyceride levels [6].

In team sports and combat sports athletes, triglyceridemia likely has a different origin and is associated with high-intensity anaerobic work, which causes a significant release of catecholamines and cortisol, stimulating lipolysis and increasing free fatty acids in the blood [29][30]. Despite having greater muscle mass (an increased pool of metabolically active tissues that consume lipids), athletes engaged in strength sports experience short-term but extreme efforts that do not lead to significant fat utilization as an energy source during the training session itself, which contributes to the maintenance of a higher basal lipid level [31].

In contrast to the groups described above, cyclic sports athletes (track and field, swimming, rowing) against a background of high aerobic workload volume exhibit the most favorable lipid profile: decreased triglyceride levels and increased high-density lipoprotein (HDL) level, which is considered a protective factor against atherosclerosis. These features are associated with increased activity of lipoprotein lipase in muscles, which utilizes fatty acids for energy production [32].

Sports nutrition and dietary supplements as a risk factor for dyslipidemia in athletes

The use of dietary supplements and pharmacological agents can both mask and exacerbate dyslipidemia caused by diet and the type of sport. These agents are often used uncontrollably by young athletes and require separate analysis.

Modern high-performance sports are inextricably linked to the active use of specialized dietary supplements and sports nutrition. The range of substances used is extremely wide: from harmless vitamin-mineral complexes to potent pharmacological agents that directly interfere with the athlete’s metabolism. Unlike countries with a developed system of sports pharmacological support, in the Russian Federation there remains high availability of potentially dangerous fat burners and hormones through online sales without medical supervision. According to a survey conducted among high school students of sports schools (n = 225), 94% of respondents had used sports supplements within the last year, while only 24% were confident that these products had undergone certification, and awareness of how to purchase certified supplements was low
(22–25%) [33].

Depending on their effect on the athlete’s body, they are divided into two broad groups:

• Direct influence on metabolism. The goal of these agents is to enhance anabolic processes, accelerate fat burning, increase strength or endurance, bypassing natural physiological limitations. These include anabolic steroids, selective androgen receptor modulators, fat burners, cortisol blockers, and other drugs that alter hormonal status and metabolic exchange.
• Replenishment of deficits and energy. The goal is to provide the body with energy substrates and nutrients for metabolic support under conditions of increased resource expenditure. This is classic sports nutrition: protein powders, gainers, amino acids (branched-chain amino acids, essential amino acids), isotonic drinks, vitamin-mineral complexes, omega-3 fatty acids.

The use of sports nutrition and dietary supplements has a significant impact on the blood lipid profile. Moreover, this influence can be both direct and indirect.

The most common cause of severe dyslipidemia in strength sport athletes is the use of anabolic steroids [34]. Androgens are powerful inducers of the gene responsible for the synthesis of hepatic lipase. Under the influence of steroids, the activity of this enzyme sharply increases (2–3 times above reference values). Hyperactive hepatic lipase begins to utilize HDL too rapidly, causing their concentration to drop sharply. Androgens also suppress the expression of genes responsible for the synthesis of LDL receptors. With fewer receptors, the liver loses its ability to efficiently capture LDL from the blood, and the level of “bad” cholesterol rises. According to studies, androgens can significantly increase the level of Lp(a), although the mechanism is not fully understood but is thought to involve direct influence on the synthesis of this protein in the liver. Other evidence indicates that Lp(a) levels may increase by 20–30% or more [35]. Even after discontinuation of anabolic steroids, the lipid profile recovers slowly.

Fat burners mobilize fatty acids from adipocytes, causing the level of free fatty acids in the blood to rise. If the training session is of low intensity, the muscles do not utilize them, and they return to the liver, enhancing triglyceride synthesis [36]. Excess simple carbohydrates in dietary supplements (especially those with a high glycemic index), against the background of high-calorie diets, can lead to hepatic lipogenesis — the conversion of carbohydrates into fats [37].

The use of creatine may indirectly affect blood lipid levels. Creatine causes intracellular fluid retention, which can lead to hemodilution or, conversely, with insufficient fluid intake, to blood concentration. This may affect the concentration measurements of lipids in the analysis without altering their absolute amount. Most researchers do not find a significant effect of creatine on the lipid profile; however, some reports indicate its effect on the expression of genes related to cholesterol metabolism in the liver [38].

Thus, when assessing an athlete’s lipid profile, it is necessary to consider not only the type of sport but also their pharmacological and nutraceutical history. The use of sports nutrition and dietary supplements by young athletes requires special attention and close supervision by a sports physician or coach.

Along with classical lipid parameters and Lp(a), an additional risk factor sensitive to the level of physical activity is homocysteine. Its assessment expands screening capabilities, especially in athletes with a positive family history or signs of endothelial dysfunction.

Homocysteine as a risk factor for cardiovascular diseases

Homocysteine is a sulfur-containing amino acid formed in the body during the metabolism of the essential amino acid methionine. Normal plasma homocysteine levels are maintained by adequate intake of B vitamins. The most common cause of hyperhomocysteinemia is deficiency of folate (B₉), vitamin B₁₂, and vitamin B₆, and less commonly, a mutation in the MTHFR (C677T) gene that reduces the activity of a key enzyme in folate metabolism. The frequency of this mutation is detected in 8.2–13.5% of children [39].

With deficiency or genetic alterations, homocysteine metabolism is disrupted, and its blood level rises [40]. A meta-analysis of 27 publications showed that an increase in homocysteine level of 5 µmol/L increases the risk of coronary heart disease by 60% in men and by 80% in women [41]. High homocysteine levels have a damaging effect on blood vessels by directly damaging the endothelium, reducing its ability to produce the vasodilatory factor nitric oxide. Homocysteine also stimulates the formation of free radicals, which exacerbate vascular wall damage. Stimulation of cell growth in the arterial wall contributes to vessel thickening and stiffening. Simultaneously, homocysteine activates inflammatory processes in the atherosclerotic plaque and increases blood clotting, thereby enhancing the risk of thrombosis [42], which explains the high interest in studying the contribution of homocysteine to the development of cardiovascular disease.

The detection of elevated homocysteine levels requires the exclusion of renal failure, hypothyroidism, psoriasis, and oncological pathology. Smoking, excessive coffee consumption, alcohol consumption, low physical activity, and the use of medications (methotrexate, anticonvulsants such as carbamazepine and phenytoin) also contribute to the elevation of this parameter [43][44].

Normal homocysteine values vary depending on sex, age, and ethnicity. Based on available publications, the acceptable blood homocysteine level in children aged 3–6 years is 5.0–8.5 μmol/L, aged 6–10 years — 5.5–9.5 μmol/L, and in adolescents aged 10–18 years — 6.0–11.0 μmol/L (according to some sources, up to 12 μmol/L) [45].

Hyperhomocysteinemia occurs in 55% of athletes compared to 35% in the general population. The duration, intensity, and mode of physical activity have varying effects on homocysteine levels [46]: high-intensity training can increase homocysteine levels [47]. In the literature, data exist on the favorable effect of physical activity on blood homocysteine levels; however, studies evaluating this parameter in adolescent athletes are insufficient, which requires further investigation [48].

Risk stratification for atherosclerosis development in underage athletes

Summarizing the data on non-modifiable and modifiable factors, a practical risk stratification algorithm can be proposed that integrates all the considered components into a unified system (see figure). If two or more moderate-risk factors are present, the patient is classified as high risk. The use of anabolic steroids, fat burners, mass gainers, and high-carbohydrate/high-fat products (e.g., some protein bars) automatically elevate the risk to high, regardless of laboratory parameters.

CONCLUSION

Adolescent athletes are exposed to a broader range of cardiovascular disease risk factors than their peers who do not engage in intense physical activity. Nutritional disorders in youth sports have their own specific features: in strength disciplines, excessive consumption of saturated fats and simple carbohydrates predominates; in aesthetic disciplines, chronic energy deficiency prevails, leading to lipid metabolism disorders. The type of sport serves as an independent predictor of the lipid profile. The highest triglyceride levels are recorded in representatives of technical disciplines with low energy expenditure; the most favorable parameters are observed in athletes engaged in cyclic sports. The use of sports supplements and pharmacological agents can significantly affect lipid metabolism. The greatest danger is posed by anabolic steroids, which cause a persistent decrease in high-density lipoproteins and an increase in atherogenic fractions. Fat burners and high-carbohydrate mixtures can also adversely affect lipid metabolism.

Thus, cardiovascular risk assessment in adolescent athletes requires a comprehensive approach that takes into account dietary patterns, training specificity, and pharmacological history. Dyslipidemias in this population are predominantly secondary in nature and are potentially correctable with timely detection and appropriate intervention. The identified patterns dictate the need to include extended lipid screening and mandatory collection of nutritional, pharmacological, and family history in the protocol for in-depth medical examination of adolescent athletes.

Authors’ contributions. All authors confirm that their contributions meet the ICMJE criteria for authorship. The primary contributions are distributed as follows: Alexandra V. Krutova — conceptualization, work structuring, manuscript writing, editing; Valery А. Mukhortykh — literature work, writing the introduction and abstract; Tatyana A. Kiseleva — literature work, manuscript writing; Ilya V. Zyabkin — manuscript revision, final version approval.