Weight Loss Resistance: 5 Essential Lab Tests to Help Determine the Root Causes

Weight loss resistance can be frustrating and tricky to navigate. Rarely is the solution to “eat less and exercise more.” In fact, this usually just makes the problem worse. It’s important to identify root causes and contributors to weight loss resistance, and we can start this investigation with specific lab testing. Let’s learn about 5 key lab tests to help determine the drivers of weight loss resistance. 

Test #1: Fasting Insulin

In cases of weight loss resistance, it’s important to assess blood sugar balance and insulin sensitivity. Measuring markers like fasting glucose and hemoglobin A1c (HbA1c) are the most common blood sugar markers to test. However, fasting insulin, the hormone that transports glucose (sugar) through our body, provides even more valuable insight into blood sugar regulation.

Fasting glucose doesn’t capture long-term trends in blood sugar levels, and HbA1c can be skewed when iron levels are low, which is something we see among a majority of our patients. That being said, fasting insulin is an early indicator of insulin resistance. As our cells become less sensitive or receptive to insulin, the pancreas compensates by pumping out more. This leads to elevated fasting insulin levels, often before we see changes to fasting glucose or HbA1c.

Since insulin is crucial for glucose transport, chronic imbalances can lead to insulin resistance, making it harder for the body to regulate blood sugar. In excess, insulin can also promote fat storage and the growth of fat cells, contributing to weight gain. Walking is a great way to combat these effects and help regulate insulin levels. If you aren’t able to get outside to walk throughout the day, consider a walking pad! Shop our favorite walking pad here, and use the code “functionalfueling” to save 20%.

Test #2: Free T3

Beyond insulin resistance, thyroid dysfunction plays a major role in metabolism and weight regulation. Hypothyroidism, or slow thyroid function, slows metabolism, making it harder for the body to convert food into usable chemical energy, often leading to weight gain.

Many doctors only test thyroid-stimulating hormone (TSH) to assess thyroid health. However, TSH is a brain hormone that signals thyroid activity; it doesn’t measure how well the thyroid actually produces thyroid hormones. 

T4 (thyroxine) is the inactive thyroid hormone produced by the thyroid. It is then activated into T3 (triiodothyronine), which is essential for energy production, weight regulation, digestion, menstrual cycle regulation, and more. T4 can also be converted into Reverse T3 by an alternate pathway. Reverse T3 is an inactive thyroid hormone and pumps the breaks on metabolism by blocking the activity of Free T3. 

Many people unknowingly slow their metabolism by consuming too few carbs or not enough calories for too long. This signals the body to conserve energy by downregulating thyroid function. A comprehensive thyroid panel that includes Free T3 and Reverse T3 can help you better understand your true thyroid function, metabolism, and hormone balance.

Test #3: High Sensitivity C-Reactive Protein (hs-CRP) and Oxidized LDL (oxLDL)

Chronic inflammation can be a major driver of weight loss resistance, as it can hinder metabolism, muscle growth, and fat loss. High-sensitivity C-Reactive Protein (hs-CRP) is produced by the liver in response to inflammation, and reflects inflammation throughout the entire body. Ideally, hs-CRP should remain below 0.9 mg/dL, but elevated levels suggest ongoing inflammation and often inflammation driven by gut dysbiosis.

Oxidized LDL (oxLDL) is not as commonly tested, but is a valuable marker of oxidative stress. OxLDL is formed from LDL cholesterol, when these compounds are oxidized by free radicals. Imagine the process of oxidation like rust build-up within our cells and tissues. High oxLDL is linked to metabolic dysfunction, which is a major barrier for healthy weight loss.

Inflammation can stem from factors like toxin exposure, an imbalanced diet, excessive exercise, and gut dysbiosis, to name a few. Identifying inflammation as a root cause of weight loss resistance helps create a more targeted approach to reduce inflammation, support metabolism, and improve weight loss outcomes.

Test #4: Cortisol

Cortisol, the body’s primary stress hormone, plays a crucial role in metabolism and energy regulation. Normally, it follows a daily pattern, peaking in the morning as part of the cortisol awakening response (CAR). However, chronic stress can lead to chronically high cortisol levels, contributing to inflammation, hormonal imbalances, and weight loss resistance.

Over time, prolonged high cortisol can lead to adrenal gland dysfunction, where the body slows down cortisol production to protect against oxidative stress. This can disrupt the HPA axis (hypothalamic-pituitary-adrenal axis), leading to low cortisol levels and affecting thyroid hormones, estrogen, and progesterone—hormones essential for metabolism and overall health.

Testing cortisol through salivary or urinary methods helps assess adrenal gland function and daily stress patterns. Salivary cortisol testing, like our Diurnal Cortisol Testing Package, measures free cortisol levels. Urinary cortisol testing, such as our Dried Urine Hormone Testing Package, measures cortisol metabolites or breakdown products. Both of these testing methods give valuable insight into your daily cortisol rhythm.

Addressing chronically elevated cortisol through lifestyle and stress management strategies is key to reducing inflammation, restoring hormonal balance, and overcoming weight loss resistance.

Test #5: Free Testosterone

Free testosterone is another key factor in identifying the root causes of weight loss resistance in women. Most testosterone in the blood is inactive, bound to sex hormone-binding globulin (SHBG), while a smaller portion remains free, actively influencing processes in the body.

Testosterone plays a vital role in maintaining bone density, muscle mass, cognitive function, mood, and libido. It also converts into estrogen, which is essential for reproductive health. 

When free testosterone levels are elevated, they can promote insulin resistance and the buildup of visceral fat, or fat around our internal organs. This is often seen in conditions like polycystic ovary syndrome (PCOS), where high testosterone, or other androgens like DHEA, and insulin resistance create a vicious cycle that exacerbates weight gain and metabolic issues.

On the other hand, low free testosterone can also contribute to weight loss resistance by reducing muscle mass. We know that muscle is key for glucose utilization and metabolism. Insufficient testosterone can make it harder to build muscle, therefore more difficult to regulate blood sugar and maintain a healthy weight. Testing free testosterone levels helps identify imbalances that may be impacting metabolism and body composition.

Conclusion

Understanding the root causes of weight loss resistance goes beyond just diet and exercise. Lab testing that is specific and dives deeper than a basic metabolic panel offers valuable insights into key metabolic and hormonal imbalances. Identifying these underlying issues allows for a more targeted approach to weight management, helping to optimize hormone function, reduce inflammation, and improve metabolism. Get started today with our Hormone Testing Packages, or apply for our 1:1 Coaching Program, where we tailor your testing and treatment plan to your unique needs.

Written by Romana Brennan, MS, RD