Why Acute Biomarker Changes Are Not Proof of Benefit

Key terms

The US Food and Drug Administration defines a biomarker as a defined characteristic measured as an indicator of normal biological processes, disease processes, or responses to an exposure or intervention. [1] It adds that a biomarker is not an assessment of how an individual feels, functions, or survives. [1]

• Acute change: a response measured soon after one exposure.
• Clinical outcome: something that matters directly to a person, such as fewer infections, less pain, better function or longer life.
• Surrogate endpoint: a marker used in a trial in place of a clinical outcome, accepted only after careful validation.

For the broader idea, see Biomarker Changes vs Meaningful Health Outcomes and Biomarkers vs Clinical Outcomes.

Evidence labels used here

Established means consistent findings from good studies. Promising but limited means early or small studies. Mixed means studies disagree. Insufficient evidence means not enough to judge. Marketing claim means a statement without supporting evidence in the sources read. See How We Label Evidence in Biohacking.

Example 1: sauna and immune cells

In a study of 51 adults, a single sauna session raised total white blood cell count, and neutrophil and lymphocyte counts increased right after the session but returned to baseline later. [2] That is a real and interesting response. It is also temporary. The study measured blood cells, not infections, and it did not show that the change makes anyone healthier. The authors suggested that sauna-induced heat stress, along with immune activation, may partly mediate the health benefits of sauna, which is a hypothesis, not a result. [3] A change in a lab value is not proof of protection against illness. See also Claim Check: "Cold Plunges Boost Immunity".

Example 2: cold-water immersion after exercise

An umbrella review of 15 systematic reviews found post-exercise cold-water immersion reduced muscle soreness and lowered creatine kinase, a muscle-damage marker, [3] but had no significant effects on the inflammation markers C-reactive protein or interleukin-6 up to 72 hours. [4] The same review said chronic use may impair resistance training adaptations. [4] It also said the overall methodological quality was low to critically low, and certainty of evidence low to very low. [4]

A meta-analysis of 28 studies likewise found that cold-water immersion was superior to other recovery methods for muscle soreness. [5] Together these show that a marker can move one way while the long-term goal, such as strength gains, moves another. Soreness and a blood marker are different things from training results.

Why markers can mislead

• Stress responses are normal. Exercise, heat and cold all change blood measures. A change tells you something happened, not whether it helped.
• Short-term versus long-term. A response that is useful once may do harm when repeated, as the training-adaptation finding suggests.
• One marker is a narrow view. Different markers can behave differently in the same review. [4]
• Surrogates need proof. A meta-analysis of 48 randomized trials with 85,681 participants was needed to test whether albuminuria can stand in for kidney failure, and the authors described the result as further support for use as a surrogate endpoint in chronic kidney disease trials. [6] A cancer review noted that formal validation of surrogate markers was in several cases disappointing despite strong biological rationale. [7] Validation requires demonstrating that the marker and the final outcome carry the same information. [7]
• Wearable scores are further removed. A "recovery" or "readiness" score is calculated by a company's own formula and has no universal clinical meaning. See Heart-Rate Variability Explained.

How to read a claim

1. Ask what was actually measured, and whether it is a symptom or outcome or only a blood or device marker.
2. Ask whether the change lasted, and in whom.
3. Ask whether any trial linked the marker change to a better outcome.
4. Treat "boosts", "optimizes" and "detoxes" as marketing words, not evidence.

For planning a careful personal check, see How to Evaluate a Biohack.