In this article

Blood tests don’t just measure single values: sometimes the ratio between two biomarkers can provide important insights. A ratio biomarker is simply one lab value divided by another, but this simple calculation can amplify subtle imbalances and reveal health patterns that individual numbers alone might miss. In this article, we’ll explain why these ratios are important, when they add (or don’t add) clinical value, and go through key examples. We’ll also touch on other calculated markers in lab reports and why they’re used.

Why Are Ratios Important?

Ratios can capture the balance between related biomarkers, often reflecting underlying physiology better than either number by itself. Many medical conditions are characterized by an imbalance between two measures rather than an absolute high or low in one. By comparing two related values, ratios can highlight these imbalances:

  • A ratio can sometimes serve as a surrogate marker for complex processes. The triglyceride-to-HDL cholesterol ratio (TG:HDL) is one well-known example. A high TG:HDL ratio suggests a pattern of abnormal lipid metabolism and insulin resistance. Studies have found TG:HDL to be a simple but effective indicator of insulin resistance and cardiometabolic risk, even more so than either triglycerides or HDL alone.
  • Ratios often represent the balance of “good” vs “bad” factors. In cardiovascular medicine, the ratio of apolipoprotein B to apolipoprotein A1 (ApoB/ApoA1) is a powerful predictor of heart disease risk. ApoB is the protein on “bad” cholesterol particles (LDL, VLDL, etc.), while ApoA1 is on “good” HDL particles. The ApoB:ApoA1 ratio thus indicates the balance between atherogenic (plaque-forming) and protective cholesterol in the blood. Research has shown that even if standard cholesterol levels are normal, a higher ApoB/ApoA1 ratio correlates with more severe artery disease and a higher risk of heart attack.

Ratios are important because they provide context. They can flag a risk or abnormality only evident when comparing two values. Clinicians often use ratio markers to get a more nuanced view of metabolism, organ function, or disease risk.

Limitations of Ratio Markers – When They Don’t Add Insight

Despite their value, not every ratio is clinically useful in every situation. In many cases, if both of the individual biomarkers are in a healthy, normal range, then their ratio will also fall in a normal range and does not provide additional insight. In other words, a ratio is most informative when one or both components are abnormal or at least near the edges of normal.

Because of this, labs and clinicians often don’t bother reporting or emphasizing a ratio if both constituent values are normal. In fact, experts note that it’s hard to even define a “healthy” reference range for some ratios, precisely because these ratios are mainly used to interpret abnormal results.

This is why your report will gray out certain ratios when both biomarkers are in the healthy range as this does not provide any additional clinical insight. The bottom line: ratios are most meaningful when something is off-balance in the first place.

It’s also worth noting that some ratios are only broadly useful and not definitive on their own. A ratio outside the ideal range often points to a potential issue but usually needs to be interpreted alongside the individual values and clinical context.

Below, we’ll go through specific ratio markers, explaining what they mean, why they’re measured, and how they’re interpreted (including their limitations). We’ll also mention some calculated non-ratio markers that are derived from formulas.

Examples of Important Ratio Biomarkers

AST:ALT (De Ritis) Ratio – Liver Health Indicator

What it is: The AST:ALT ratio compares two liver enzymes: aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Both AST and ALT leak into the blood when liver cells are damaged, but they can rise in different patterns depending on the cause of liver injury.

Why it’s useful: The AST:ALT ratio helps differentiate types of liver disease and the severity of liver damage. In healthy individuals, AST and ALT levels are usually similar, yielding a ratio around 1.0. But in liver disease, their proportions change. Typically, an AST/ALT > 2 (AST is more than twice ALT) is suggestive of alcoholic liver disease or alcoholic hepatitis. On the other hand, AST/ALT < 1 (ALT higher than AST) is often seen in acute viral hepatitis or non-alcoholic fatty liver disease – conditions where ALT tends to rise more prominently.

Limitations: As mentioned earlier, if AST and ALT are normal, the ratio ~1 doesn’t tell much. It’s also not a perfect test – many patients with alcoholic liver disease might not have the “textbook” >2 ratio, and other conditions can sometimes elevate AST more than ALT. The ratio should be interpreted carefully: a very high AST:ALT ratio could even be due to muscle injury (since AST is found in muscles too) or vitamin B6 deficiency affecting ALT levels.

TSH:T4 Ratio – Thyroid Function Insight

What it is: This ratio compares thyroid-stimulating hormone (TSH) to thyroxine (T4). TSH is the pituitary hormone that signals the thyroid gland, and free T4 is the main hormone produced by the thyroid. Normally, they have an inverse relationship: if T4 is low, TSH goes up (to stimulate the thyroid), and if T4 is high, TSH drops.

Why it’s useful: In certain situations, looking at the TSH:T4 balance can refine assessment of thyroid function. One particular use is in identifying subclinical hypothyroidism – a mild underactive thyroid state where T4 is still in the normal range but TSH is slightly elevated. In subclinical hypothyroidism, the TSH:T4 ratio will be higher than normal (because T4 is relatively low for that person’s TSH level). In fact, one study introduced a “subclinical hypothyroid index” defined by the TSH:FT4 ratio, and found it helpful for diagnosing early thyroid underactivity.

Limitations: If TSH and T4 are both well within their normal ranges, the ratio doesn’t carry much independent meaning. Also, there isn’t a universally agreed “normal” range for TSH:T4 ratio in practice – doctors interpret it relative to the context. Large variations in binding proteins or acute illness can also alter free T4 levels and thus the ratio.

Free T3:Free T4 Ratio – Thyroid Hormone Conversion

What it is: This is the ratio of free triiodothyronine (FT3) to free thyroxine (FT4). T4 is converted in the body to T3, the more active thyroid hormone. So this ratio essentially measures how much T3 activity you have relative to your T4 level.

Why it’s useful: The FT3:FT4 ratio is an indicator of T4-to-T3 conversion efficiency and overall thyroid hormone balance at the tissue level. Some patients can have normal T4 but low T3 (for example, in “low T3 syndrome” during chronic illness, or in some hypothyroid patients on T4-only therapy). A reduced FT3:FT4 ratio in such cases might suggest that tissues are not adequately converting T4 to T3. On the flip side, an abnormally high T3 relative to T4 could occur in certain thyroid disorders (like T3 toxicosis or Graves’ disease with dominant T3 secretion).

Limitations: The FT3:FT4 ratio can be influenced by factors like medications, acute illness, and age. There’s no strict normal range for the ratio used in routine practice – it’s evaluated in context. If both FT3 and FT4 are normal and the person is well, the ratio is usually in a normal middle zone and not particularly scrutinized.

Cortisol to DHEA-S Ratio – Stress and Adrenal Balance

What it is: This ratio compares cortisol (the body’s main stress hormone) to DHEA-S (dehydroepiandrosterone sulfate, an adrenal hormone that can counterbalance some effects of cortisol). Both are produced by the adrenal glands. Cortisol is catabolic (breaks down tissue, increases blood sugar, suppresses immune function), whereas DHEA and its sulfate form are anabolic and supportive of immune function.

Why it’s useful: The cortisol:DHEA-S ratio is considered a marker of HPA axis balance and stress. In a healthy young person, cortisol and DHEA levels are in good proportion, especially since DHEA-S is high in youth. With aging or chronic stress, DHEA-S levels decline significantly (by age 70, DHEA-S may be only 10–20% of young adult levels) while cortisol levels do not drop as much. The result is a higher cortisol-to-DHEA ratio, indicating a shift toward catabolic, stress-related physiology.

Moreover, studies in different fields have found that higher cortisol:DHEA ratios correlate with worse outcomes in contexts like chronic pain, depression, and critical illness. A review on pain and aging noted that an elevated cortisol-to-DHEA ratio (along with low DHEA) is associated with increased frailty, poorer immune function, osteoporosis progression, and even cognitive decline.

Limitations: There is natural variability in cortisol (which follows a diurnal rhythm) and DHEA-S (which also declines with age), so the ratio’s interpretation must consider age, time of day, and individual baseline. There’s not a single “normal range” used universally for cortisol:DHEA-S ratio; instead, one looks at whether it’s higher or lower than expected for a given context. Also, both values need to be abnormal or shifting for the ratio to be meaningful. If cortisol and DHEA-S are both normal, their ratio will usually be in a reasonable range.

What About Other Calculated Markers?

In addition to ratios, many blood test results are derived calculations rather than direct measurements. These are still valuable pieces of information in your report. Here are a few examples:

  • Calculated VLDL Cholesterol:Very low-density lipoprotein cholesterol (VLDL-C) is usually not measured directly. Instead, it is estimated from triglycerides, most commonly using the Friedewald equation (VLDL ≈ triglycerides ÷ 5, in mg/dL). This calculation is also used to derive LDL cholesterol (LDL = Total Cholesterol − HDL − VLDL). Calculated VLDL is useful for completing the lipid profile and estimating cardiovascular risk, but it becomes unreliable when triglycerides are very high or when samples are non-fasting. In those cases, calculated values may be suppressed or interpreted cautiously.
  • Iron Saturation and Total Iron-Binding Capacity (TIBC):Iron saturation and TIBC are calculated using serum iron and unsaturated iron-binding capacity (UIBC). These calculations assume that UIBC is within a physiologically meaningful range. When UIBC is very low (< 25 µg/dL), the assumptions behind these calculations break down, and TIBC and iron saturation may become misleading. For this reason, if UIBC is below this threshold, TIBC and iron saturation are not reported, and interpretation focuses instead on the directly measured values.
  • Free Androgen Index (FAI):The Free Androgen Index is a calculated marker derived from total testosterone and sex hormone–binding globulin (SHBG). It is intended as a rough estimate of androgen availability, primarily in specific clinical contexts. However, the calculation becomes unreliable when its inputs fall outside valid ranges. If SHBG is very low (< 9 nmol/L) or if total testosterone is extremely low or high (< 25.96 ng/dL or > 2018.8 ng/dL), the FAI calculation is not physiologically meaningful. In these cases, FAI is suppressed to avoid generating misleading results.
  • Free Testosterone (Calculated):Calculated free testosterone is derived from total testosterone, SHBG, and albumin using established equations (such as the Vermeulen method). While calculated free testosterone generally correlates well with reference methods, it shares the same fundamental limitation as FAI: it is only as reliable as its inputs. When SHBG or total testosterone values fall outside physiologically valid ranges, the calculation can produce distorted or non-interpretable results.

The reason calculated markers are used at all is to extract additional insight without requiring extra tests, but they are not universally applicable. When the assumptions behind a calculation are violated, reporting the value can create confusion rather than clarity. Suppressing calculated markers in those situations helps ensure that reported results remain clinically meaningful and appropriately interpreted.

Key Takeaways

  • Ratio biomarkers distill complex information from two related lab tests. They can be as clinically significant as the individual biomarkers by highlighting imbalances (e.g. cholesterol balance, liver enzyme patterns, thyroid feedback, stress hormones).
  • If both components are normal, the ratio will typically be normal too, and generally doesn’t add new clinical insight. This is why our system (and many clinicians) will not flag or focus on a ratio in that scenario. It avoids confusion and over-interpretation.
  • Ratios become important when one or both values are out of range. At that point, the ratio can help determine why and what to suspect: e.g. a high AST:ALT ratio points to a particular cause of liver injury, a high TSH:T4 ratio points to emerging hypothyroidism, etc. We automatically display these calculated ratios in such cases to give you and your healthcare provider extra context.
  • Always interpret ratios in context. A ratio out of range warrants a look at its constituents: Are one or both of the underlying labs high or low? Does that fit the person’s symptoms or risk factors? The ratio is a clue, not a diagnosis.

By understanding ratio biomarkers and calculated markers, you can better appreciate what your blood test report is conveying. These derived numbers are there to enhance understanding of your health, highlighting meaningful patterns or confirming that things are well-balanced. We hope this helps you make sense of why certain ratios show up on your report only under certain conditions.

Note: This article is for educational purposes. Always discuss your individual test results and their interpretation with qualified healthcare providers who know your complete health history.