Multiple sclerosis, Hormones, Neurodegenerative disease, Thyroid hormones

Regulating the Regulators

By Dr. Michaël Friedman

The following excerpt is from Dr. Michaël Friedman’s book There’s No Pill for This: A Naturopathic Doctor’s Personal Prescription for Managing Multiple Sclerosis (Chelsea Green Publishing, November 2020) and is reprinted with permission from the publisher.

Research has established that multiple sclerosis involves inflammation in the brain and damage to the myelin sheath that protects nerve cells. And it’s long been known that hormones play a key role in maintenance of brain and central nervous system (CNS) health. Putting this information together, it becomes clear that in order to effectively treat MS symptoms, it’s important to understand the role of hormones in the body and how to achieve and maintain hormonal balance.

Most hormones are produced in the endocrine system, a system of glands distributed throughout the body. Once produced, hormones enter the bloodstream and travel to their target sites, where they bind to specific receptors and exert some form of influence.

Hormone Production in the Brain, CNS, and Gut

The brain is part of the central nervous system, and it also acts as an endocrine organ. For example, the brain converts one type of hormone secreted by the thyroid gland into a more active form for the body’s use. The brain has receptors for targeted endocrine hormones, and is part of an important feedback loop involving the pituitary gland (which regulates hormone production) and a variety of organs whose function depends upon those hormones. Consequently, the brain has the ability to direct and adjust bodily functions. It does so via production of neurotransmitters such as serotonin and dopamine. The brain and CNS also produce hormones known as neurosteroids. Synthesized from cholesterol, neurosteroids play a role in the myelination of neurons, as well as the growth, differentiation, and maintenance of neurons. (Because of cholesterol’s importance in hormone production, I advise MS patients to think twice about using statins to lower their cholesterol levels. And because the human body manufactures cholesterol from fat, this is also why I advise including a variety of healthy fats in the diet—especially omega-3s.)

Bacteria in the human microbiome also impact hormone production. In fact, gut bacteria produce almost 50 percent of the dopamine used by the body. The microbiome also impacts thyroid hormone conversion and the production of melatonin. This is why I adamantly recommend avoiding processed foods. Many of these may contain chemicals and preservatives that can disrupt hormone balance.

Hormones serve two functions: messaging and the regulation of body systems. In some cases a pair of hormones work in a kind of feedback loop. When this happens, Hormone X acts as a messenger to stimulate or depress an endocrine gland in response to the body’s needs. That gland then releases either more or less of a second hormone, Hormone Y.

When thyroid hormone levels in the body reach normal levels, the brain receives another message through the feedback loop. The brain calls upon the pituitary gland to slow its release of thyroid-stimulating hormone (TSH). The reduction of TSH in the bloodstream signals the thyroid gland to slow the release of thyroid hormone.

When working properly, feedback loops help ensure that cells have the proper amount of necessary hormones at all times, keeping the body in balance. But sometimes those loops can lose their balance, causing too little or too much of a hormone to be released, which can result in damage to cells and tissues. Even worse, a domino effect can occur, triggering imbalances in other hormones. which can lead to other interrelated health problems.

The Impact of Aging on Hormones

As we age, hormone production naturally declines, causing physical and psychological changes in both men and women. The pace at which hormones decline, and thus the rate at which we age, are determined by our genetic makeup, lifestyle, diet choices, exercise levels, weight/BMI, stress level, relationship status, community involvement, and other factors. For example, common life situations such as smoking or gaining excessive weight can cause testosterone production to decline faster.¹ The stress related to job loss or divorce can increase cortisol levels and cause weight gain and damage to neurons. In women, the precipitous drop in estrogen due to age combined with the fact that females tend to have longer life expectancy than males means that women generally experience more cognitive changes with age and have higher rates of Alzheimer’s disease than men.

Many other factors influence the complex aging process, and aging is the result of the accumulation of factors, not a single hormonal change.²

The Role of Thyroid Hormones in MS and Other Neurodegenerative Diseases

Over the short and the long term, hormones can have both positive and negative effects on the health of the brain and the central nervous system. One example is the effect of hormones on neurons in multiple sclerosis.

Although their actions are not well understood, neurosteroid hormones can help to mitigate the severity and the progression of MS. They do so by influencing oligodendrocytes to provide neuroprotection and remyelination that reduces and repairs damage to the myelin sheath.

To date, many of the studies examining the connections between hormones and neurodegenerative disease have focused on Alzheimer’s— which is why I reference studies on Alzheimer’s quite often in my book. Although research into hormones and MS is relatively young, the implications are similar. The following is a brief explanation of thyroid hormones and their therapeutic use for MS.

The thyroid produces two hormones, T3 and T4, that regulate the body’s metabolic rate and other elements of health, including breathing, heart rate, central and peripheral nervous systems, body weight, muscle strength, menstrual cycles, body temperature, and cholesterol levels.

Thyroid hormones also support proper central nervous system function and interact with many facets of the nervous system to help prevent dementia. Maturation of oligodendrocytes and myelination is influenced by thyroid hormone (TH) signaling. Thyroid hormone interacts with acetylcholine, which, as mentioned previously, improves memory and prevents cognitive decline. Low thyroid hormone status can cause insufficient production of acetylcholine. Research has shown that patients with Alzheimer’s disease have diminishing levels of acetylcholine relative to the progression of the disease.³

Triiodothyronine (also called T3) and thyroxine (also called T4) are two hormones that are critical for normal metabolic functioning. Most (about 80 percent) of T3, known as the active thyroid hormone, results from deiodination—the process by which organs such as the liver and kidneys remove one of the four iodine molecules that are part of T4. Some inactive thyroid hormone results from this process as well; that hormone is called reverse T3, or rT3. The thyroid gland produces the other 20 percent of T3 (by combining dietary iodine with the amino acid tyrosine) as well as all of T4.

T3, the active thyroid hormone, promotes nerve growth factor (NGF). (NGF supports nerve growth, proliferation, function, and nerve myelination.) T3 also enhances remyelination by sup- porting oligodendrocyte precursor cells (OPCs). Without adequate thyroid hormone, there is a deficiency of mature, active OPCs and limited ability for myelin repair.⁴

The brain is extremely dependent on thyroid hormone. Low thyroid levels are believed to cause shrinking of the hippocampus, the part of the brain that shifts short-term memories to long-term, enables spatial memory related to navigation, and supports memory and learning. The hippocampus is particularly significant because it is the part of the brain that shows the earliest signs of damage in Alzheimer’s disease (AD) patients. When present in adequate amounts, thyroid hormones may help ward off dementia by hindering a protein that promotes amyloid production and indirectly prevents plaque deposits. On the other hand, deficient thyroid levels may open the floodgates for more amyloid production and consequent damage to the brain.⁵

Adults who develop hypothyroidism can suffer from poor memory, confusion, and difficulty learning new tasks. Fortunately, these symptoms are reversible in adult hypothyroidism, simply by restoring thyroid hormone levels and body temperature.

Thyroid hormone may indirectly contribute to dementia through its influence on the cardiovascular system. Hypothyroidism is a significant risk factor for developing cardiovascular disease. In this condition, blood flow to the brain may become impaired due to a compromised vascular system. Diminished blood flow and the resulting poor delivery of oxygen and nutrients to the brain can contribute to damage in the brain and an increased risk of developing AD.⁶

Thyroid hormone is so crucial to the brain that if there is inadequate thyroid hormone available to a fetus developing in the womb, its brain and neurons will not mature properly, causing irreversible mental deficiencies in the form of cretinism.

A very large clinical trial conducted by Boston University in collaboration with the National Heart, Lung, and Blood Institute known as the Framingham Study collected health data on almost 2,000 people over the course of nearly 13 years to better learn about risk factors for various diseases. It found that for women with non-normal TSH levels (which is an indicator of either elevated or deficient thyroid hormone), there was more than double the risk of developing AD as for women with healthy normal levels.⁷

Therapeutic Use for MS

MS patients are shown to have higher rates of thyroid disorders as compared with healthy peers. One study showed that patients with MS had a significantly higher risk of also having autoimmune thyroid disease, specifically Graves’ disease (hyperthyroidism) and Hashimoto’s disease (hypothyroidism).⁸ I mention this here because individuals with one autoimmune condition are more susceptible to developing others—which could explain the correlation between MS and these types of thyroid disease.

Animal research has shown that daily injections of T3, the active form of thyroid hormone, contributes to remyelination. These studies also show that thyroid hormone supplementation can improve neurological symptoms in animals and improve proliferation and activation of OPC.⁹ At Oregon Health and Science University, thyroid hormone is being studied as a potential MS therapy due to its critical role in protecting myelin and promoting remyelination.

T3 supplementation is not standard of care for MS, but I have found it one of the top three significant therapies in treating my own fatigue and brain fog. When demyelination occurs during an MS attack, the body does produce more rT3, which blocks the active T3 hormone from working. Reverse T3 slows the activity of metabolism in the body and the CNS. It is a normal function to slow metabolic processes during times of fasting, to conserve energy, and also during times of grief. However when the rT3 stays high for the long term, this otherwise healthy slowing process can persist to the point that it leads to chronic disease. It is analogous in this way to inflammation—an appropriate amount of inflammation helps tissues heal, but excess can be damaging. In the case of rT3, overly high levels can contribute to significant, debilitating fatigue. Adding T3 to the body can help take the edge off the fatigue that MS patients experience, especially after an attack, and help the mind become clearer. Interestingly, thyroid hormones stimulate myelination.

Every couple of years, I take 5 mcg of T3 twice a day for a three-month period. This dosage has a beneficial effect for me. I also take a product that I formulated myself called Thyroid Px. This supplement combines iodine, selenium, and thyroid-activating herbs. Over time, my MRI scans have shown some lesions to decrease in size and some to disappear. Although I cannot know for sure, because some types of MS lesions do heal on their own over time, I attribute the size reduction and disappearance of some of my lesions in part to the body’s natural ability to heal itself and in part to the restorative treatments I take.

Michaël Friedman, ND

is a naturopathic physician and founder of the Association for the Advancement of Restorative Medicine. He is cofounder and president of the Restorative Formulations supplement company, and lives in Montpelier, Vermont.

References

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2. Anne Cappola, Qian-Li Xue, and Linda Fried. Multiple Hormonal Deficiencies in Anabolic Hormones Are Found in Frail Older Women: The Women’s Health and Aging Studies. Journals of Gerontology. February 2009; 64A, no. 2: 243–48.

3. Nan Wang et al. Effects of Thyroxin and Donepezil on Hippocampal Acetylcholine Content and Syntaxin-1 and Munc-18 Expression in Adult Rats with Hypothyroidism. Experimental and Therapeutic Medicine. March 2014; 7, no. 3: 529–36.

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Cohort. Journal of Autoimmune Disease. December 2005; 2, no. 1: 9.

9. C. Brian Bai et al. A Mouse Model for Testing Remyelinating Therapies. Experimental Neurology. September 2016; 283, part A: 330–40; Mao Zhang et al., Thyroid Hormone Alleviates Demyelination Induced by Cuprizone through Its Role in Remyelination during the Remission Period. Experimental Biology and Medicine. September 2015; 240, no. 9: 1183–96.