High cholesterol in the young in athletes: causes and the link with exercise load and pharmacology

High cholesterol is associated with older age and a sedentary lifestyle, so a raised LDL in a 25-year-old athlete is often perceived as a lab error. In fact it may be caused by heredity, dietary features or pharmacology. The editorial team examines which factors most often alter the lipid profile in young athletes and how training affects it.

What “high cholesterol” is and why age is no protection

“High cholesterol” usually means a raised level of low-density lipoprotein cholesterol (LDL). It is LDL and other apoB-containing particles that penetrate the artery wall and are a causal factor of atherosclerosis — a position substantiated in detail in the ESC/EAS guidelines on dyslipidaemias.

Atherosclerosis develops over decades, and the key role is played by the cumulative “burden” of LDL over a lifetime. That is why a raised level at 20–30 is important, even if the short-term risk of a heart attack is low: every decade with high LDL adds to future risk.

In young people, risk is rarely calculated using scales such as SCORE2, since they are oriented to older ages. Instead, doctors assess the absolute values of LDL, family history, lipoprotein(a) and other factors. A very high LDL at a young age always requires a search for the cause.

Other components of the lipid profile — HDL cholesterol, triglycerides, apolipoprotein B and lipoprotein(a) — complete the picture. In athletes the most interesting changes often concern HDL, which is extremely sensitive to pharmacology.

Heredity: familial hypercholesterolaemia and Lp(a)

The most important cause that must not be missed is familial hypercholesterolaemia (FH). This is a genetic disease, most often linked to mutations in the LDL receptor gene, APOB or PCSK9. The heterozygous form, according to estimates by the European Atherosclerosis Society, occurs in about one person in 200–250 and largely remains undiagnosed.

In FH the LDL level is high from birth, regardless of lifestyle. An athlete with an ideal diet and a low body-fat percentage may have LDL twice the normal level. Without treatment such people have a significantly raised risk of an early heart attack, so diagnosis at a young age saves years of life.

Lipoprotein(a), or Lp(a), is another genetically determined factor. Its level is almost entirely determined by heredity and changes little under the influence of diet and training. The EAS consensus recommends measuring Lp(a) at least once in every adult.

Signs that should raise concern: a very high LDL, early heart attacks or strokes in first-degree relatives, xanthomas (deposits on tendons), a corneal arcus at a young age. In such cases genetic testing and examination of relatives are advisable.

The athlete’s nutrition and lifestyle

A diet high in saturated fat raises LDL. In strength athletes this is often linked to large amounts of fatty meat, butter and whole-milk dairy. Ketogenic and low-carbohydrate diets cause a significant rise in LDL in some people, and the reaction here is highly individual.

Paradoxically, sharp weight loss and a prolonged energy deficit can also temporarily change the lipid profile, in particular against the background of the mobilisation of fat stores. In addition, in relative energy deficiency in sport (RED-S), women have been described as having adverse lipid changes linked to low oestrogen levels.

Training itself generally affects lipids favourably. In the well-known STRRIDE study (Kraus et al., 2002) the volume of aerobic exercise determined the improvement of the lipoprotein profile: LDL particle size and HDL level increased. However, the effect of training on the LDL level itself is moderate, and high hereditary LDL is not compensated by sport.

Hypothyroidism, liver and kidney diseases and some drugs (isotretinoin for the treatment of acne, glucocorticoids, certain diuretics) also raise cholesterol. Isotretinoin is especially relevant for young people, in particular those treating steroid acne.

Anabolic steroids and other pharmacology

Anabolic-androgenic steroids are one of the most powerful “external” factors of dyslipidaemia in young men. The characteristic picture: a sharp decrease in HDL and a rise in LDL. The mechanism is linked to stimulation of hepatic lipase, which speeds up the breakdown of HDL.

The effect is especially pronounced with oral 17-alpha-alkylated steroids (stanozolol, methandienone, oxandrolone, etc.), which pass through the liver in high concentrations. In the study by Hartgens et al. (2004), strength athletes who used steroids showed a marked decrease in HDL and apoA-I, as well as a decrease in Lp(a) — which does not compensate for the overall adverse effect.

The Endocrine Society scientific statement (Pope et al., 2014) emphasises that the combination of dyslipidaemia, raised blood pressure, myocardial hypertrophy and erythrocytosis explains the increased cardiovascular risk in long-term AAS users. Lipid changes are usually reversible after stopping, but the atherosclerotic changes that have already formed are not.

Other drugs also affect lipids: aromatase inhibitors lower oestrogen, which in men supports HDL; growth hormone and insulin change fat metabolism; thyroid hormones, on the contrary, lower LDL, but with risks to the heart and bones. These effects are another reason why self-directed hormonal pharmacology is dangerous.

How to interpret an athlete’s test

The lipid profile is best taken in a stable state: not after prolonged fasting, not at the peak of “cutting”, not in the first week after an acute illness. Intense training the day before can affect triglycerides.

To assess the effect of pharmacology, context is important: a test taken against the background of steroid use does not show the person’s “true” lipid profile. It is worth telling the doctor about all drugs so that the result can be interpreted correctly.

If LDL is high even in a drug-free state, the first hypothesis should be a hereditary cause, not “I don’t train enough”. Especially when high values are present in parents or siblings as well.

• Take the test in a stable state, without acute illness and extreme diets.
• Tell the doctor about all supplements and hormonal drugs.
• Measure Lp(a) at least once in your life.
• With high LDL, find out the lipid profile of close relatives.

We cover diagnosis, target levels and treatment in more detail in a separate material on the prevention and diagnosis of high cholesterol in the young. We also recommend the articles on the effect of anabolic steroids on the heart and on the lipid panel for athletes.

Editorial conclusions

High cholesterol at a young age is not an “error”: a significant share of such cases is explained by familial hypercholesterolaemia, which is important to diagnose as early as possible.

A diet with large amounts of saturated fat and some diets raise LDL, whereas regular aerobic training improves the lipid profile but does not neutralise hereditary disorders.

Anabolic steroids, especially oral ones, substantially lower HDL and raise LDL, adding to other cardiovascular risks. These changes are usually reversible, but accumulated atherosclerosis is not.

Young athletes should determine their lipid profile and Lp(a) at least once, and with high values discuss the results with a doctor.

References

1. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188.
2. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Eur Heart J. 2013;34(45):3478–3490.
3. Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925–3946.
4. Kraus WE, Houmard JA, Duscha BD, et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002;347(19):1483–1492.
5. Hartgens F, Rietjens G, Keizer HA, Kuipers H, Wolffenbuttel BH. Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a). Br J Sports Med. 2004;38(3):253–259.
6. Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
7. Mountjoy M, Sundgot-Borgen J, Burke L, et al. International Olympic Committee (IOC) Consensus Statement on Relative Energy Deficiency in Sport (RED-S): 2018 update. Br J Sports Med. 2018;52(11):687–697.