The Optimal Range

Using a tighter optimal range to assess and treat dysfunction before it becomes a disease sounds simple enough. But there is a multitude of biomarkers out there, each with different characteristics, interactions, and significance.

To demonstrate what the use of Functional Blood Chemistry Analysis (FBCA) looks like in practice, let's review six representative blood biomarkers:

• Glucose
• Homocysteine
• Iron
• Thyroid-associated biomarkers
• Vitamin D
• Magnesium

We'll examine how "normal" levels of these blood biomarkers are often associated with dysfunction and disease and how levels that fall within the optimal range are associated with better patient outcomes. By examining these biomarkers in detail, we can gain a clearer picture of what optimal ranges are and why Functional Blood Chemistry Analysis is the best tool for guiding patients' blood biomarker levels back to healthier levels.

Healthy blood glucose levels are an excellent example of why functional ranges are so important. In 1979, patients needed to have a fasting plasma glucose of 140 mg/dl or higher to be diagnosed with diabetes — anything below that level was high but had no diagnostic status. However, if your fasting blood glucose was measured at, say, 140 mg/dL, you’d be at dire risk, at 135 mg/dL, you'd be told to "wait and see". In the past, that risk wasn’t properly recognized. Today, we understand it to be prediabetes.

Medical practitioners of all stripes recognize prediabetes as an important medical condition to be monitored and treated. Current guidelines recognize prediabetes as occurring between 100 and 125 mg/dL, with diabetes beginning at 126 mg/dL and higher. Recognizing this earlier, precursory stage before the relevant condition helps practitioners prevent diabetes from ever occurring in the first place.

But we can actually zoom in even closer and gain even greater impacts on our patients’ health. Current guidelines put the “normal” range at 70 to 99 mg/dL. Yet research suggests that even individuals in the higher portion of that range — from 90 to 99 mg/dL — are significantly more likely to progress to diabetes than those with less than 85 mg/dL.

Current research suggests that we should really be targeting a range of 75 to 86 mg/dL.

Homocysteine — an amino acid synthesized by the breakdown of other proteins — can be extremely harmful at elevated levels, especially to blood vessels. Under healthy conditions, its levels are kept down by vitamins B6, B12, and folate, which help to process this biomarker.

What constitutes "normal" levels of homocysteine in the blood has varied throughout time, with hyperhomocysteinemia ranging from 15 umol/L to over 100 umol/L. Today, normal homocysteine levels in the blood range from 0 to 21.3 umol/L for individuals over 80 years of age. But again, we find that this range includes the harmless, the worrying, and the outright harmful all at once.

Above 11 umol/L, homocysteine is associated with a significant decline in cognitive function in individuals over 80 years old. The mean level of 10.5 umol/L is associated with atherosclerotic regions in otherwise-healthy individuals’ carotid arteries. Again and again, elevated homocysteine levels are associated with oxidative stress and systemic inflammation, raising the chances for morbidity and mortality. Rather than settle for the normal range of homocysteine at ~10.5 umol/L, a more optimal goal is to shoot for 5-7.2 umol/L.

Iron-deficient blood is tied to a number of clinical symptoms, yet most of the time, these symptoms appear long after a drop in associated blood biomarker values. In fact, according to the Merck Manual’s stages of iron-deficiency anemia, it’s only at the fifth stage that the physical symptoms of anemia — fatigue, weakness, pallor, and so on — begin to manifest. Even in some of the earlier stages, serum iron and hemoglobin remain within normal limits. Since a low ferritin may be the earliest sign of iron insufficiency, research suggests a low end cut-off of 30 ng/mL. However, researchers suggest that a ferritin below 100 ng/mL may warrant further evaluation of iron insufficiency.

Keeping an eye on the relevant blood biomarkers like serum iron, hemoglobin and ferritin can help practitioners keep their patients well away from serious conditions like anemia.

Fluctuations in thyroid-associated biomarkers, such as T4, T3, and thyroid-stimulating hormone (TSH), can serve as important indicators of dysfunction and disease. They also serve as a good example of why focusing on optimal ranges results in better health outcomes than normal ranges. 

For example, the upper limit for TSH was once considered to be 10 uIU/mL, until the previous range accepted as “normal” — 4.5 to 9.9 uIU/mL — was revealed to be associated with dyslipidemia, vascular alterations, and diastolic dysfunction in young and middle-aged subjects. Now, the normal range is accepted as 0.45 to 4.5 uIU/mL, but therapeutic targets often aim for 0.3 to 3.0 uIU/mL. Even the higher limits of this reduced range are associated with negative health outcomes like obesity and increased risk for metabolic syndrome. The regular assessment of thyroid biomarkers can help practitioners guide patients away from these undesirable outcomes.

Considering that approximately 95% of healthy individuals maintain a TSH below 2.5 mU/L, and thyroid dysfunction is lowest with a TSH of 1-1.9 mU/L, a range of 1-2 mU/L is considered optimal for TSH. Individuals that fall above or below this optimal range can be further assessed and monitored for thyroid dysfunction before it progresses into metabolic dysfunction.

Vitamin D plays a huge role in our health, and yet most don’t have optimal vitamin D blood levels. Across the globe, roughly 1 billion people are deficient in vitamin D, and 50% of the world’s population have vitamin D insufficiency.

Vitamin D serves as an excellent example of how optimal blood biomarker levels can create a virtuous cycle for patients: Sufficient levels of vitamin D are associated with reduced levels of potentially worrisome biomarkers like homocysteine, CRP, AST, ALT, and others. But while conventional lab ranges accept 30 to 100 ng/mL as normal, low levels of this critical biomarker affect musculoskeletal health, immune regulation, skin health, cardiovascular integrity, apoptosis, and cell proliferation and differentiation. Vitamin D’s essential role in the body was highlighted during the COVID-19 pandemic when it was found that levels exceeding 30 ng/mL were associated with reduced severity and mortality.

Fortunately, vitamin D is easily accessed through diet, sun exposure, and supplementation; most patients are simply not structuring their diet and lifestyle in a way that meets their vitamin D needs. By prescribing such interventions, we can help patients reach the optimal goal of 50 to 90 ng/mL (or 125 to 225 nmol/L).

Like vitamin D, magnesium plays a crucial role in bodily functions, yet nearly half of the US suffers from magnesium insufficiency. Moreover, subclinical magnesium deficiency is detectable at the reference ranges supplied by major laboratories, which range from 1.5 mg/dL to 2.6 mg/dL.

In fact, research suggests that magnesium blood levels should be kept above 2 mg/dL. When levels dip below that point, patients’ health can suffer, particularly by putting them at increased risk of hypertension.