Desmosterol (Normalized) Test

Your standard lipid panel tells you how much cholesterol is circulating in your blood. It does not tell you where that cholesterol came from. Some people run high cholesterol because their intestines absorb too much of it from food. Others run high because their liver is churning out too much internally. The treatment that works best depends on which pattern you have, and a standard panel cannot distinguish between them.

Desmosterol is the molecule your liver makes just before it converts that molecule into cholesterol. When your liver is synthesizing cholesterol at a high rate, more desmosterol escapes into the bloodstream. Dividing the desmosterol concentration by your total cholesterol gives you a ratio that reflects your rate of internal cholesterol production, independent of how much cholesterol happens to be in your blood at that moment. This ratio is what the desmosterol normalized value measures.

What This Ratio Tells You

Desmosterol (full name: 24-dehydrocholesterol) sits at the very end of one of two pathways your liver uses to build cholesterol. This pathway, called the Bloch pathway, is one of the final assembly lines the liver runs to produce finished cholesterol. An enzyme called DHCR24 converts desmosterol into finished cholesterol. When synthesis is running fast, DHCR24 cannot keep up, and desmosterol accumulates. That spillover is what shows up in your blood.

The normalized value divides your blood desmosterol (in micromoles per liter) by your total cholesterol (in millimoles per liter), then multiplies by 100 for a convenient scale. In a large clinical database of over 667,000 patients, the correlation between absolute desmosterol and the desmosterol/total cholesterol ratio was very high (about 0.94 on a scale where 1.0 is a perfect match), confirming that the ratio reliably tracks the same biology as the raw number while removing the influence of your overall cholesterol level.

Synthesizer Versus Absorber: Why It Matters for Treatment

Your body maintains a balance between making cholesterol internally (synthesis) and taking it in from the gut (absorption). A systematic review covering multiple metabolic disorders found that people can be classified as "cholesterol synthesizers" or "cholesterol absorbers" based on patterns of these sterol markers. When desmosterol and another synthesis marker called lathosterol are high relative to total cholesterol, and absorption markers like campesterol and sitosterol are low, you fit the synthesizer profile.

This distinction has direct implications for how you lower cholesterol. Statins work by blocking cholesterol synthesis, so they tend to be most effective in synthesizers. Ezetimibe and plant sterols work by blocking absorption, so they tend to help absorbers more. In a sub-analysis of a randomized trial of 1,734 people with a recent acute coronary event, adding ezetimibe to a statin was more effective at preventing cardiovascular events in the subgroup of patients who had higher cholesterol absorption markers. The main trial did not show a significant overall benefit of the combination, but this pattern-based finding illustrates why knowing your synthesis-versus-absorption profile may help guide therapy.

Fatty Liver Disease

The strongest disease association for elevated desmosterol comes from research on fatty liver disease, specifically the more advanced form called nonalcoholic steatohepatitis (NASH, now also referred to as metabolic dysfunction-associated steatohepatitis). In a study combining 110 obese patients undergoing liver biopsy with a population cohort of 717 men, those with biopsy-proven NASH had higher serum desmosterol and higher desmosterol/total cholesterol ratios than people with simple fat accumulation in the liver or normal livers.

The link between blood desmosterol and what was happening inside the liver was strong: serum desmosterol correlated with liver desmosterol content at about 0.67 (a moderately strong link, where 1.0 would be a perfect match). It also tracked with the severity of liver inflammation, scarring, fat accumulation, and elevated liver enzymes (ALT). This makes the desmosterol ratio a potential noninvasive window into how aggressively your liver's cholesterol factory is running and whether that overproduction is contributing to liver damage.

A separate study of 124 people with metabolic dysfunction-associated steatotic liver disease (MASLD, the updated name for the broader spectrum of fatty liver) and 43 healthy controls confirmed that cholesterol synthesis markers, including desmosterol, correlated positively with noninvasive steatosis scores like the Fatty Liver Index and the Triglyceride-Glucose Index. Higher synthesis marker levels were associated with more liver fat and worse metabolic profiles, though absolute desmosterol concentrations were not significantly different between MASLD patients and controls in this study.

Depression

In a population-based study of 3,117 adults, plasma desmosterol levels were significantly associated with the severity of depressive symptoms. People with the lowest desmosterol levels, below the fifth percentile (approximately 1.9 ng/mL), had nearly twice the odds of reporting at least moderately severe depressive symptoms compared to those with higher levels (odds ratio 1.9, 95% CI 1.2 to 2.9). The mechanism is not fully understood, and this is a single observational study, so it does not prove that low desmosterol causes depression or that raising it would help. But it raises the possibility that cholesterol synthesis disruption may be linked to mood regulation in ways that standard lipid panels would never reveal.

Age, Sex, and Genetics

Desmosterol levels are not the same in everyone, even among healthy people. The 667,000-patient database study found that age and sex significantly affected desmosterol and other non-cholesterol sterol levels. APOE genotype (a gene that influences how your body handles cholesterol) also played a role, with carriers of the APOE4 version showing higher cholesterol absorption patterns. These biological differences mean your result needs to be interpreted in the context of your age, sex, and potentially your APOE status.

Reference Ranges

No major medical guideline has published standardized clinical cutpoints for desmosterol normalized to total cholesterol. This is a research-grade marker, and the numbers below come from a single large US clinical laboratory database of 667,718 patients measured by gas chromatography. They are illustrative orientation, not universal targets. Your lab may report different numbers, possibly in different units.

The wide standard deviation (larger than the mean itself) tells you that this marker varies enormously between individuals. A single reading without context is hard to interpret. Compare your results within the same lab over time for the most meaningful trend.

When Results Can Be Misleading

Because this is a ratio that depends on total cholesterol in the denominator, anything that acutely changes your total cholesterol level can shift the ratio even if your actual synthesis rate has not changed. Acute illness, particularly infections, can drop total cholesterol sharply, which would artificially inflate the desmosterol ratio.

Cholesterol synthesis follows a circadian rhythm (a roughly 24-hour cycle), peaking overnight and declining during the day. A systematic review and dedicated time-course study confirmed that synthesis markers including lathosterol show this pattern. Whether desmosterol specifically shows the same degree of time-of-day fluctuation is less well characterized, but drawing blood at a consistent time (typically morning) is reasonable practice to reduce variability between readings.

Statins directly suppress cholesterol synthesis and will lower desmosterol. If you are taking a statin, your desmosterol ratio reflects your synthesis rate on that medication, not your natural baseline. This is not a "false" result, but if you are using desmosterol to understand your underlying metabolic type, a pre-statin measurement is more informative.

Because this is a Tier 3 research marker without consensus clinical thresholds, no single desmosterol reading should drive a major clinical decision on its own. Use it as one data point in a broader picture that includes standard lipids, ApoB, liver function, metabolic markers, and imaging when appropriate.