Nutrition Notes

When Biomarkers Can be Misleading

Advances in medical testing technology have made it so that we can detect warning signs of various illnesses or pathological metabolic states in blood, urine, feces, breath, cerebrospinal fluid, and more. There’s no doubt that many of these developments have been lifesaving, but medical and nutrition professionals should remain cautious about putting too much stock in any one biomarker in isolation. Various measurements can be elevated or otherwise thrown off for numerous reasons that don’t necessarily indicate anything harmful. A patient’s health is best assessed by looking at the full picture, taking into account their diet, lifestyle habits, and other factors, rather than basing clinical judgments or prescribing medication based on one biomarker in isolation at one point in time.

As an example, hemoglobin A1c (HbA1c) is generally taken to be an average measurement of blood glucose during the previous three to four months. However, HbA1c may be less reliable than is commonly known. Heavy alcohol consumption may result in a lowering of HbA1c. Looked at in isolation, a lower HbA1c could be considered a sign of good blood glucose control, but with the alcohol connection in mind, this may not automatically be indicative of someone following a healthy diet. It’s not known for certain why high alcohol intake lowers HbA1c, but potential mechanisms include general malnutrition, shortened red blood cell lifespan, or chronic liver disease even in the absence of cirrhosis and splenomegaly. Additionally, alcohol consumption inhibits hepatic gluconeogenesis and glycogenolysis, which would result in lower blood sugar.

Beyond HbA1c, fasting glucose can also be quite misleading as an indicator of metabolic health and most especially carbohydrate sensitivity. The increasing popularity of low-carb and ketogenic diets has revealed a subset of individuals who may have higher-than-expected fasting blood glucose in relation to their very low carbohydrate intakes. There are a few reasons why this might occur, and they don’t automatically indicate something pathological.

On the other hand, having normal fasting glucose indicates very little about a patient’s metabolic health. Many people with normal fasting glucose are living with elevated insulin, yet measuring insulin is relatively uncommon in clinical practice. Without the insulin measurement, someone with normal fasting glucose may falsely believe they are metabolically healthy, but there’s a long list of conditions that may be driven by chronically high insulin even when blood glucose is normal. Measuring only glucose and eschewing an insulin test may prevent these patients from getting proper diagnoses and treatments because the root cause of their ailments will go unidentified.

Turning toward a different biomarker, accumulation of beta-amyloid proteins in cerebrospinal fluid is taken to be a warning sign of Alzheimer’s disease (AD) or proof of the condition already being present. However, a growing body of research raises serious questions about the relevance of this compound in the etiology of the disease. There are individuals who develop AD without significant amyloid plaque burden, and there are individuals who have significant plaque burden who show no signs or symptoms of the condition. So this may be less reliable an indicator than it’s generally thought to be.

No discussion of biomarkers would be complete without mentioning what is currently perhaps the most controversial one: LDL-cholesterol (LDL-C). Equally credentialed experts, including medical doctors and Ph.D. researchers, have diametrically opposed views on whether LDL-C, by itself, is an independent risk factor for heart attack or cardiovascular disease. Medical professionals from the Cleveland Clinic state their stance in no uncertain terms: “The fact is, elevated low-density lipoprotein (LDL), the bad cholesterol, is a major cause of heart disease.” Other MDs and PhDs state with equal fervor: “LDL-C does not cause cardiovascular disease,” and, “The hypothesis that high TC [total cholesterol] or LDL-C causes atherosclerosis and CVD has been shown to be false by numerous observations and experiments.”

When the experts don’t even agree, imagine how difficult it must be for patients to interpret the numbers on their lab printouts and make sense of what these might mean for their current health and future trajectory. Their understandable frustration may lead them to consult “Dr. Google,” which can be an even more precarious minefield to navigate. Doctors can help patients understand their biomarkers in the context of their total situation so that unwarranted fears are dispelled while at the same time appropriate gravity is given to situations that may be more serious than a patient realizes, and they can take proper actions where necessary.