Within reference range vs optimal blood test results. What you need to know to feel better.

There is a frustrating grey area that I work with in my clinic often, which is the gap between the clients 'within normal range' blood test results from their doctor (but they are still experiencing symptoms) and `optimal’ test results where they are thriving. Just because you have been told that your results are normal, it doesn’t mean that your results are at a level where your symptoms reduce, and you feel better.

What does a `within range’ test result actually mean?

The standard reference ranges are established by laboratories and are based on the statistical analysis of a large population. They typically represent the values where 95% of the "healthy" population falls. This defines a reference range for what is considered normal. So, if you receive a blood test result that is within a normal reference range, it means that the results are within the statistical average.

There are limitations to these reference ranges though, as they may not account for individual variations, such as age, lifestyle, or long-term health risks. Also, the primary aim of these reference ranges is to identify significant deviations with patients that indicate that they may have a disease (e.g. anemia) if their results are significantly lower or higher than the standard reference range. It is possible, though (which is what I see a lot with my clients) to have blood test results within the "normal" reference range, and still have symptoms related to a condition.

What is an optimal reference range?

Optimal ranges focus on achieving the best possible health and energy and minimising future disease risk. They are often based on more recent research that links specific blood marker levels to long-term health outcomes and longevity. Optimal ranges often represent a much narrower and more precise health target.

The benefits of optimal ranges are that they provide a more personalised, preventative approach to help achieve optimal health and disease prevention. They help to identify subtle imbalances that may not be apparent within standard ranges.

When you work with a registered clinical nutritionist (RCN) like myself, or a naturopath or functional medicine doctor, we take a preventative approach to testing. We strive to see optimal test results where you are feeling better and thriving, rather than `within range’ test results where you are considered to be normal but still have symptoms.

The three areas I see this the most are with blood tests completed by your doctor for thyroid function, vitamin B12 and iron studies.

Thyroid function

When your doctor completes a blood test to check your thyroid function, they will mostly only test TSH (thyroid-stimulating hormone) and if there is an abnormality with TSH, then they will test free T4 (thyroxine). 

TSH is a pituitary hormone that stimulates the thyroid gland to produce thyroid hormone when needed.   The standard TSH reference range is 0.4 – 4.0 mIU/L so if your results fall within this reference range then your thyroid will be considered by doctors to be normal.

An optimal TSH ideally needs to be between 0.5 and 2.0 mIU/L for optimum function, anything above 2.5 mIU/L indicates some level of hypothyroidism and lower than 0.5 mIU/L could indicate hyperthyroidism.

The problem is many people have normal TSH levels and still have symptoms of low thyroid function. Unfortunately, in these cases testing just TSH highlights what the pituitary gland is doing, and not the actual function of the thyroid.   If your TSH is lower or higher than the reference range of 0.4 – 4.0 mIU/L , then your doctor will likely test your free T4 (thyroxine) which is used to find out how well your thyroid is functioning.   The standard reference range for free T4 is 9 – 23 pmol/L so if your free T4 result is say 10 or 12 (which is what I see commonly) your thyroid function is considered to be normal.

An optimal Free T4 is 15 – 23 pmol/L so anything within this range shows that your thyroid is functioning well.  So, the ladies I often see with a free T4 of 10 or 12 are still likely to have suboptimal thyroid function and further investigations would be worthwhile.

Testing just Free T4 (thyroxine) as well isn’t really a reliable indicator of thyroid function as T4 is an inactive hormone that needs to be converted to T3 (triiodothyronine) to become active. So, testing Free T3, the active thyroid hormone is going to give a better picture of your thyroid function. 

The standard reference range for Free T3 is 3 – 7 pmol/L and the optimal reference range is 5 – 7 pmol/L. This means that if your result was 3 you would be considered normal, but you may well still have symptoms of low thyroid function such as low energy, fatigue, hair loss, constipation and weight gain.

Unfortunately, it is often challenging to get a Free T3 test from your doctor, unless you push really hard for a full thyroid panel and it is not always easy. This is why so many women have undiagnosed subclinical thyroid problems. Luckily, nowadays, you can request a Free T3 test as part of a full comprehensive thyroid panel in New Zealand and many other countries through a naturopath, nutritionist, or functional medicine practitioner. 

Several factors can impair the conversion of T4 to T3 in the liver. These are aging, inflammation, stress, severe illness or injury, calorie restriction, fasting, poor gut health, an imbalance of gut bacteria, and nutritional deficiencies such as zinc, selenium, vitamin D and iron. If you have concerns that you may have any of these issues, I recommend you work with a nutritionist, naturopath or functional medicine practitioner to get a full thyroid panel done.

Thyroid antibodies

The full comprehensive thyroid panel test also includes TSH, Free T4, Free T3, reverse T3 (more about this shortly) and TPO and Tg thyroid antibodies.  Testing these antibodies are vitally important to test to see if an autoimmune issue such as Hashimoto’s thyroiditis or Grave’s disease is affecting the function of the thyroid gland. The two main antibodies tested are anti-microsomal antibody Ab or thyroid peroxidase (TPOAb) and anti-thyroglobulin antibody (TgAb). Hashimoto’s and Grave’s disease are both autoimmune thyroid conditions, although Hashimoto’s is the most common. The most reliable way to identify autoimmune thyroid is to test for thyroid antibodies. Testing for thyroid antibodies is also important to do if there is a family history of other autoimmune conditions, such as coeliac disease. In cases of both Hashimoto’s and Grave’s disease, the thyroid blood tests may show normal results in the early stages of the disease, but elevated antibodies suggest an immune attack on the thyroid gland. If left untreated, the thyroid blood tests may gradually become abnormal over time.  

The standard reference range for both TPOAb and TgAb thyroid antibodies is less than 35 IU/mL.  So, if you have detectable antibodies of say 32 IU/mL for TPO you are considered normal, but this is in fact showing that there is an autoimmune attack going on in which the immune system is attacking the thyroid gland.

An optimal reference range for thyroid antibodies is less than 2 IU/mL. If your test results show that your antibodies are higher than this, it is important to look at nutritional or supplemental support to help lower your thyroid antibodies over time and increase your sense of wellbeing.

Reverse T3

A comprehensive thyroid panel will also test for reverse T3 (RT3), which is an inactive form of T3. In a normal healthy person, the body converts T4 into both T3 and RT3 and can quickly eliminate RT3. In some situations, the production of RT3 increases as a protective mechanism, which reduces levels of the active T3 in the body. This slows down metabolism and causes hypothyroid symptoms, which is also known as thyroid resistance. 

The key issue with high levels of RT3 is that it will bind to T3 receptor sites in the body, but because it is inactive, it has no activity. So essentially, high RT3 levels can give you symptoms of hypothyroidism, even though your TSH and Free T4 are within the normal range. 

The main causes of high RT3 levels are:

• Stress as cortisol increases the conversion of T4 to reverse T3

• Chronic illness or infection 

• Low-calorie diets

• Inflammation

If you have a high RT3 blood test result, then your focus needs to be on reducing your stress levels in any way you can and making sure you are eating well, not on a restricted low-calorie or too low-carb diet. 

Stress is not just being busy. If you have an infection, gut issue, or food intolerance that is causing inflammation and uncomfortable symptoms, this is stressful for your body as well. These situations can weaken the immune system and can affect your thyroid gland. 

The standard reference range for reverse T3 is 11 – 21ng/dL, although it is rare that your doctor will test for this. An optimal test result is 11 – 18 ng/dL so anything higher than this is considered problematic and may be causing your thyroid symptoms.

Iron

The mineral iron is the leading nutritional deficiency in the world and severe iron deficiency can lead to anemia, which is a condition where the number of red blood cells and their hemoglobin content is not enough to carry oxygen to body cells and tissues.  It is therefore important to optimise iron so that the risk of anemia is reduced.  

Diseases associated with low iron (ferritin) include:

• Anemia

• Fatigue

• Hypothyroidism

• Hair loss

• Inflammatory bowel disease (IBD), coeliac, disease

• Restless legs syndrome

• Insomnia

• Anxiety and depression

• Fibromyalgia

Ferritin is a blood protein that contains iron and testing ferritin shows how much iron your body stores.  The normal reference range is 20 – 450 ng/mL for men and 20 - 380 ng/mL for women.  I often see client who receive test results that are often between 20 – 40 ng/mL and are told their test results are normal and they don’t need to take iron. 

When I was 3 months postpartum with my first child 16 years ago, I was told my ferritin was fine at 23 ng/mL and I didn’t need to take iron, this was despite the fact that I had a massive hemorrhage during his labour and because I had nearly a litre of blood loss, I had to have a blood transfusion. 23 ng/mL was only just above the lowest reference range and was borderline anemic, but the nurse rang me to say my results were normal and I didn’t need to take iron. I couldn’t understand why I was feeling so tired, fatigued and felt like I was running on empty.   

An optimal ferritin range is at least 70 ng/mL so if your results are less than this then you may benefit from additional supplementation.

If your ferritin level comes back as abnormally high but you still feel like your iron levels are low, it could be because of chronic inflammation or an infection, so it is important to consult with a practitioner to determine whether you need an iron supplement.  High ferritin may also be because of the condition hemochromatosis, which is a genetic condition in which the body stores too much iron leading to iron overload which can cause problems with the heart and liver. This is why it is not a good idea to supplement with high doses of iron daily unless you know you need it.

Vitamin B12

Is it estimated that as many as 40% of the population have low plasma B12 levels at a level in which neurological issues begin to manifest. Unfortunately, vitamin B12 levels are not routinely tested in most countries and the reference range of what is considered low (which is 200 pg/mL - 350 pg/mL in most countries) is too low so many people who are tested are considered normal even with clear B12 deficiency symptoms.

An optimal range for vitamin B12 is 500 pg/mL as plasma levels below 500 - 550 pg/mL have been associated with neurological, psychological, and cognitive decline. This is why in countries like Europe and Japan 500 pg/mL this is their low reference range.

Vitamin B12 is an essential nutrient. It works together with folate in the synthesis of DNA and red blood cells; it helps to regulate brain activity and is involved in the production of the myelin sheath around the nerves and the conduction of nerve impulses. It is also important for methylation an important liver detoxification pathway. If B12 levels are low homocysteine levels can be elevated.

The following diseases have been associated with vitamin B12 deficiency:

• Alzheimer’s, dementia, memory loss, multiple sclerosis (MS)

• Depression, anxiety, OCD, bipolar disorder, psychosis

• Cardiovascular disease (due to high homocysteine levels)

• Autism, ADHD, ADD, dyslexia, and other learning and behavioural issues

• Inflammatory bowel disease, coeliac disease

• Infertility and recurrent miscarriage

In the last couple of weeks alone in my clinic I have seen an elderly lady with depression and extreme fatigue, a female with episodes of psychosis on a vegetarian diet, a young man with severe brain fog and auditory hallucinations, and a teenage girl with anxiety and OCD.  What did they have in common? They have all been tested for Vitamin B12 by their GP and their results have come back around 200 pg/mL. This is too low to be considered normal. In New Zealand 200 pg/mL is considered the lower end of the reference range so if you have a result of 201pg/mL then this is considered normal even with clear vitamin B12 deficiency symptoms.  

If you have a blood test result that is less than 500 pg/mL then you will likely benefit from supplementing with vitamin B12. If you are looking to take a B12 supplement look for one that contains sublingual methylcobalamin which is the active coenzyme form of vitamin B12 that is more bioavailable than the common form cyanocobalamin. Sublingual B12 supplements in the form of methylcobalamin are available in most health shops.  

So in summary, if you have had blood tests with your GP and you have been told that your results are within the normal reference range, but you still have symptoms, then ask for a copy of your results.  If your results fall below what is considered optimal (especially for thyroid function, Iron and Vitamin B12) then be assured that there is more that can be done.  Working with a practitioner to aim for optimal test results can improve your energy, vitality, reduce your symptoms and make you feel so much better.

 Need further assistance? Why not book in for a FREE 15-minute consultation via Zoom, a casual space to chat about your situation and how I may be able to help you.