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Low Free T3 and Cognitive Impairment

Explore the link between low free T3 levels and cognitive impairment.
Low Free T3 and Cognitive Impairment
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Cognitive impairment is a broad term that encompasses a range of conditions affecting mental processes, such as memory, attention, and problem-solving abilities. Problems with cognitive functioning can be a result of aging, neurodegenerative diseases such as Alzheimer’s, or other underlying medical conditions. Over the years, researchers have explored various factors that may contribute to cognitive impairment. One area of interest is the relationship between free T3 levels and cognitive function. Free T3 refers to triiodothyronine, a thyroid hormone crucial to brain development and function. This article will explore the connection between free T3 levels, thyroid gland dysfunction, and cognitive impairment, exploring the evidence and potential implications.

Understanding free T3 and its role

Before discussing the relationship between free T3 levels and cognitive impairment, it is important to review the role of free T3 in the body.

Triiodothyronine (T3) is a thyroid hormone that regulates the body’s metabolism, energy production, and growth in various tissues, including the brain. It is the active form of thyroid hormone, meaning it impacts cells in the body. Thyroxine (T4) is the inactive form of thyroid hormone. T3 is produced in two ways: (1) the thyroid gland itself produces some, and (2) the majority of T3 is produced by the conversion of T4 hormone into T3.

T3 exists in two forms: bound, which is T3 attached to a protein, and free T3, which is not attached to anything. The free T3 level measures only the amount of active free T3 in the blood, while the total T3 test measures free and bound T3. T3 tests are used to diagnose thyroid conditions and to monitor treatment for thyroid disease. T3 levels that are low, or that fall in the low-normal end of the normal range, can be a sign of hypothyroidism, and high T3 levels can be a sign of hyperthyroidism.

Thyroid hormones, including free T3, impact brain function significantly. In fact, the brain relies on an adequate supply of thyroid hormones to function optimally. They influence neuronal growth, synaptic plasticity, and neurotransmitter synthesis, all essential for cognitive processes. Thyroid hormones also influence neurological development and function, as well as several neurotransmitter systems, such as serotonin, dopamine, and gamma-aminobutyric acid (GABA). These neurotransmitters are essential for cognitive processes like learning, memory, attention, and executive function.

What is cognitive impairment?

Cognitive impairment refers to a decline in mental abilities or functions necessary for daily life and independent functioning. It can affect various aspects of cognition, including memory, attention, perception, problem-solving, and language skills. The causes of cognitive deterioration can vary, including but not limited to aging, neurological disorders, brain injuries, or certain medical conditions. Understanding cognitive impairment is crucial in identifying and managing the condition effectively.

One of the most common causes of cognitive impairment is aging. As people get older, they may experience changes in cognitive functioning. This is often due to the natural aging process, which can lead to mild cognitive impairment (MCI) or even more severe forms of cognitive decline, such as dementia or Alzheimer’s disease. These conditions can have a significant impact on quality of life and require proper diagnosis and treatment.

Neurological disorders, such as Parkinson’s disease or multiple sclerosis, can also lead to cognitive impairment. These disorders affect the central nervous system and can cause problems with cognition, depressive symptoms, and other physical symptoms. In some cases, cognitive impairment may be an early sign of these diseases, highlighting the importance of early detection and intervention.

Cerebrovascular disease refers to a group of conditions that affect the blood vessels supplying the brain. It involves the disruption of normal flow of blood, oxygen, and nutrients to the brain, which can lead to serious consequences such as stroke or transient ischemic attacks (TIAs). These conditions can lead to cognitive decline due to the damage they cause to the brain. Additionally, the inflammation and scarring that can occur as a result of cerebrovascular disease can also contribute to cognitive decline. 

Brain injuries, such as traumatic brain injury (TBI), can also result in cognitive impairment. These injuries can damage the brain and disrupt normal functioning, leading to various cognitive deficits. Depending on the severity and location of the injury, individuals may experience difficulties with memory, attention, and problem-solving skills. Treatment and rehabilitation programs are essential in aiding recovery and managing cognitive impairment caused by brain injuries.

Certain medical conditions can also contribute to cognitive impairment. Conditions like hypothyroidism, HIV/AIDS, vitamin deficiencies, and metabolic disorders can all affect cognitive functioning.

The symptoms of cognitive impairment can range from mild to severe, and include:

  • Memory impairment
  • Difficulty with recall
  • Difficulty with planning, initiating, and carrying out tasks
  • Trouble focusing, concentrating, and paying attention
  • Depressive symptoms, low mood 
  • Confusion and disorientation
  • Decline in problem-solving and decision-making skills
  • Difficulty with language and communication
  • Disorientation to time and place
  • Poor judgment
  • Difficulty understanding
  • Forgetfulness
  • Missing appointments or social events
  • Losing things often
  • Having more trouble coming up with words than other people of the same age
  • Trouble following a conversation
  • Finding it hard to follow instructions
  • Difficulty finding the way around places you know well

How does free T3 affect cognition?

The exact mechanisms underlying the relationship between free T3 and cognitive impairment are still being investigated. However, several theories exist. One possibility is that lower free T3 levels lead to reduced neuronal energy metabolism, impairing the brain’s ability to function optimally. Another theory suggests that thyroid hormones play a crucial role in the clearance of amyloid-beta, a protein implicated in the development of Alzheimer’s disease. Therefore, decreased free T3 levels may hinder this clearance process, leading to cognitive decline.

Thyroid dysfunction and cognitive impairment

Hypothyroidism, characterized by low levels of thyroid hormones, has long been associated with cognitive impairment. However, the significance of thyroid hormones and the specific role of free T3 levels in cognitive dysfunction are still being investigated.

A number of previous studies have explored the relationship between free T3 levels and cognitive impairment, and identified low free T3 levels as an independent risk factor for cognitive problems.

  • A study published in December 2023, titled “Low levels of free triiodothyronine are associated with risk of cognitive impairment in older euthyroid adults,” discussed the association between low free T3 levels and the risk of cognitive impairment in euthyroid individuals, namely, older adults with normal thyroid function. The study found a significant association between low free T3 levels and an increased risk of cognitive impairment in the study population. Specifically, people with the lowest serum levels of free T3 had a twofold increased risk of cognitive impairment compared to those with the highest levels. The study also found that TSH and free T3 levels were associated with immediate memory. Overall, the researchers observed that decreased free T3 levels were independently linked to a higher likelihood of cognitive impairment, highlighting the potential impact of free T3 on cognitive function in this demographic.
  • A correlational study found significant positive correlations between free T3 levels and processing speed in healthy euthyroid patients with normal thyroid function.
  • A study in BMC Rheumatology showed an association between thyroid status -- specifically serum levels of free T3 -- and memory. Higher free T3 levels positively correlated with immediate memory performance, among other cognitive functions, in patients with systemic lupus erythematosus.
  • A 2022 study published in the journal Diabetes Metabolic Syndrome Obesity found that even within the normal reference ranges, free T3 levels are associated with executive function and memory in Type 2 diabetes patients without diagnosed thyroid diseases.
  • A study in the Egyptian Journal of Internal Medicine found a close correlation between thyroid status and cognitive dysfunction, with serum FT3 levels decreasing in cases of cognitive impairment.
  • One study found that even differences in thyroid hormone levels within the normal range, including free T3, were associated with changes in cognitive functioning.

There’s also evidence that reduced T3 and free T3 levels are linked to Alzheimer’s. A study published in the Iranian Journal of Medical Sciences suggested that a reduced level of T3, even when within the normal range, may be independently associated with cognitive decline in Alzheimer’s patients. A study in the journal Psychoneuroimmunology found that low serum concentration of free T3 is associated with an increased risk of Alzheimer’s disease. And a study published in Alzheimer’s News Today reported that high levels of free T3 are associated with a lower rate of Alzheimer’s disease risk in patients who have subjective or objective mild cognitive impairment.

These studies suggest that free T3 levels can significantly impact cognitive function. Lower levels of free T3 are associated with cognitive impairment or decline, and higher levels may have a protective effect. However, the exact mechanisms behind this relationship are still being explored, and further research is needed.

Factors influencing free T3 levels and cognitive impairment

Several factors can affect free T3 levels in the body. Here are some key factors that influence free T3 levels and, subsequently, cognitive function.

  • Thyroid Disorders: Hypothyroidism is the most common cause of low free T3 levels, which occurs when the thyroid gland does not produce enough thyroid hormones, including free T3.
  • Age: Age can play a role in free T3 levels. Research has shown that free T3 levels tend to decrease with age. This decline may contribute to age-related problems with cognitive functioning. However, it is challenging to determine whether these changes in thyroid hormone levels are the cause – or the consequence – of cognitive deterioration. 
  • Medications: Certain medications can influence free T3 levels. For example, glucocorticoids commonly prescribed to reduce inflammation can inhibit the conversion of T4 to T3, leading to lower free T3 levels. Similarly, medications such as amiodarone and iodine supplements can affect the production and conversion of thyroid hormones.
  • Nutritional Factors: Adequate levels of iodine and selenium are vital for the production and conversion of T4 to T3. Low iodine levels can reduce the synthesis of thyroid hormones, leading to decreased free T3 levels. Similarly, selenium deficiency can impair the activity of enzymes involved in thyroid hormone metabolism.
  • Stress and Illness: Stressful situations and certain illnesses can impact free T3 levels. During periods of physical or emotional stress, the production and conversion of thyroid hormones can be altered, leading to fluctuations in free T3 levels. Additionally, acute and chronic illnesses can affect thyroid function and subsequently impact free T3 levels.
  • Gender: Women generally have higher free T3 levels than men. Hormonal changes during puberty, pregnancy, and menopause can further influence free T3 levels in women.
  • Environmental Factors: Environmental factors, such as exposure to toxins and pollutants, can disrupt thyroid function and influence free T3 levels. Chemicals like perchlorates, nitrates, and polychlorinated biphenyls (PCBs) have been found to interfere with the production and action of thyroid hormones.

How to improve your free t3 levels and potentially protect cognitive functioning

While experts are still studying how free T3 levels affect cognitive processes and function, it makes sense to do everything possible to support optimal free T3 levels and cognitive function. Let’s look at some of the ways to achieve this.

Optimize your thyroid hormone replacement medication

For patients on thyroid medications, regular thyroid testing can measure your free T3 levels. If your levels are low or low-normal, you should discuss whether including some T3 in your thyroid hormone replacement treatment – whether by adding a T3 drug to levothyroxine therapy or switching to a natural desiccated thyroid drug that contains a natural form of T3 – would make sense. The Paloma Health blog has a helpful article on optimizing thyroid levels.

Optimize your nutrition

A healthy, balanced diet is crucial for maintaining optimal thyroid and brain function. Include foods rich in iodine, selenium, and zinc, as these minerals play a vital role in thyroid hormone production. Seafood, dairy products, Brazil nuts, and legumes are excellent sources of these nutrients. Additionally, consuming a diet rich in fruits, vegetables, whole grains, and omega-3 fatty acids may help protect thyroid and brain health and prevent cognitive decline.

Manage stress

Chronic stress can impair thyroid function, decrease free T3 levels, and worsen cognitive function. High cortisol levels, the primary stress hormone, can also disrupt the conversion of T4 into T3. To reduce stress, incorporate stress-management techniques into your daily routine, such as meditation, deep breathing exercises, yoga, or regular physical activity. Find activities that relax and rejuvenate you; a calm mind will promote optimal thyroid and brain function.

Get sufficient sleep

Sleep deprivation can adversely affect thyroid function, hormone production, and brain function. Aim for seven to nine hours of quality sleep each night. Establish a consistent sleep routine, create a relaxing environment for sleep, and avoid stimulating activities before bed. Prioritizing sleep supports hormonal balance and improves cognition and overall well-being.

Exercise regularly

Regular physical activity has been linked to improved thyroid function and brain health and may help prevent or slow cognitive decline. Engaging in moderate-intensity exercises, such as brisk walking, swimming, or cycling, helps regulate hormones and metabolism. Exercise also reduces stress, promotes weight management, and enhances overall health. Aim for at least 30 minutes of exercise most days of the week.

Optimize gut health

The health of your gut plays a significant role in thyroid and brain function. A well-balanced gut microbiome aids in converting inactive T4 hormone into active T3 and supports cognitive health. Evidence even suggests that the resident bacteria in the gastrointestinal tract can influence the brain and behavior, particularly cognitive function. There is increasing support for the role of the gut microbiota in maintaining overall human health and well-being. To support gut health, consume probiotic-rich foods, such as yogurt, sauerkraut, or kefir, and include fiber-rich foods in your diet. Consider adding a high-quality probiotic supplement to your daily routine to support gut health further.

Support with supplements

Certain supplements may assist in improving free T3 levels. Some common supplements that support thyroid function include selenium, iodine, vitamin D, zinc, and iron. It’s important to note that excessive supplementation can have adverse effects, so seeking professional guidance is recommended.

Several supplements have been suggested to help prevent cognitive decline. These include:

  • Ginkgo Biloba: It has been used as a natural remedy to improve memory and cognitive function
  • Vitamins B12 and B9: Deficiencies in these vitamins can cause cognitive impairment, so their supplementation may be beneficial
  • Vitamin E: Some evidence suggests it may slow functional decline in individuals with mild cognitive impairment
  • Omega-3 Fatty Acids: These are good for heart health and may also have benefits for brain health
  • Coenzyme Q10: Coenzyme Q10 is an antioxidant that may help protect brain cells from oxidative damage, which is linked to cognitive decline
  • Alpha Lipoic Acid: Alpha lipoic acid is an antioxidant that has been suggested to help prevent or delay mild cognitive impairment
  • Phosphatidylserine: Phosphatidylserine is a type of fat compound in the brain, and supplementing with it may improve cognitive function and prevent cognitive decline
  • Acetyl-L-Carnitine: Acetyl-L-carnitine is an amino acid that may help improve memory and cognitive function, potentially slowing the progression of Alzheimer’s disease
  • Huperzine-A: Huperzine-A is a substance derived from a plant called Chinese club moss, and it may be effective in improving memory and cognitive function
  • Vinpocetine: Vinpocetine has been suggested to be effective in the management of cognitive impairment and memory loss

Reduce toxic exposures

Toxins in our environment can disrupt thyroid function and hormone production. You can minimize exposure to toxins by choosing organic produce, using natural, chemical-free household cleaning products, and filtering your drinking water. Some specific toxins to avoid include:

  • Heavy Metals: Aluminum, cadmium, and lead, which can induce oxidative stress, inhibit iodide uptake, limit thyroid hormone production, and lead to thyroid enlargement and reduced function.
  • Household Products: BPA, phthalates, and triclosan in items such as plastics, personal care products, and antibacterial soaps  can mimic the structure of thyroid hormones and disrupt thyroid function.
  • Agricultural Agents: Pesticides, herbicides, and fungicides which can negatively impact thyroid hormone production and thyroid health.
  • Industrial Chemicals: Substances found in cleaning products, air fresheners, fire retardants, and water supply, which can act as endocrine disruptors and harm thyroid function.

Get mental stimulation

Research shows that engaging in mentally stimulating activities such as reading, playing games, solving puzzles, learning a new skill or hobby, playing a musical instrument, or taking up a new language can provide mental stimulation, support brain health, and reduce the risk of cognitive impairment.

Interact socially

Social interaction and positive relationships with friends and family have been associated with a significant effect on brain function and less socializing is linked to more depressive symptoms and steeper cognitive decline.

A note from Paloma

While cognitive impairment can be a complex condition with multiple contributing factors, the role of free T3 in brain function is becoming increasingly recognized and demonstrated in research. Understanding the link between low free T3 and cognitive impairment can help you and your healthcare providers take appropriate steps to identify and address potential hormonal imbalances. By doing so, you can potentially protect and improve cognitive function and enhance your overall quality of life with hypothyroidism.

By implementing targeted lifestyle changes to help support your free T3 levels, thyroid health, and brain function, you may be able to reduce your risk of cognitive impairment.

The link between free T3 levels and cognitive impairment is an area of concern for people with hypothyroidism. However, by becoming a Paloma Health member, you’ll benefit from comprehensive hypothyroidism care. Taking a proactive step to manage your thyroid levels can reduce your risk of cognitive impairment. Through personalized treatment plans and ongoing monitoring, Paloma Health offers a supportive and integrated approach to thyroid care, empowering individuals to optimize their thyroid health health. By leveraging the expertise of Paloma Health’s healthcare professionals, you can work towards mitigating the impact of hypothyroidism on not only your cognitive well-being but your overall quality of life.

To stay on top of your free T3 levels and other thyroid function markers, Paloma's at-home test kit allows you to conveniently measure key hormones, including thyroid-stimulating hormone (TSH), free triiodothyronine (free T3), free thyroxine (free T4), and thyroid peroxidase (TPO) antibodies, without the need for an office visit. By regularly monitoring these levels, you can track changes and gain meaningful insights into your thyroid health. This comprehensive approach provides a clear picture of your thyroid function, enabling you to work with healthcare professionals to personalize a plan for optimizing your thyroid levels within the reference range, including free T3. The test is easy to use, and results are typically available within 5 to 7 days, allowing for timely adjustments to your treatment or lifestyle.

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Publishing HH. Protecting against cognitive decline. Harvard Health. Published January 2, 2021.

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Mary Shomon

Patient Advocate

Mary Shomon is an internationally-recognized writer, award-winning patient advocate, health coach, and activist, and the New York Times bestselling author of 15 books on health and wellness, including the Thyroid Diet Revolution and Living Well With Hypothyroidism. On social media, Mary empowers and informs a community of more than a quarter million patients who have thyroid and hormonal health challenges.

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