Thyroid Function and Genetics

Gene mapping and treatments to change how our DNA manifests itself is currently one of the biggest areas of medical research. We are afraid of the illnesses suffered by our immediate family members. People routinely test their genetic mapping to determine if their DNA markers indicate they inherited diseases their parents, grandparents, aunts, or uncles had. Following Mendel's Law of Inheritance from Mendel's studies of pea plants in the early 1900s, geneticists thought they could use the same laws to explain human genetics and single-gene human diseases. Mendel's laws explain diseases caused by one gene that runs in families. Humans inherit one allele from their mother and one from their father. Geneticists argue that autosomal recessive single-gene diseases show how diseases skip from generation to generation. If they test their genetic mapping, doctors will often tell people they have the risk of Alzheimer's, ADHD, diabetes, and some cancers, among many other diseases.People are attempting to reduce the risk of having inherited genetic diseases by improving methylation since researchers' animal studies have demonstrated that DNA methylation turns the right genes for proper cell differentiation and embryonic development. The lack of adequate methylation is associated with aging, and diseases are thought to be connected to aging since many studies have shown that abnormal methylation can cause aging-related diseases. The next step would be to discover treatments to rejuvenate methylation.

Many patients tell me they've been diagnosed with MTHFR (Methylene tetrahydrofolate reductase deficiency) deficiency, which would mean they would have a gene even though the enzyme links folate and homocysteine metabolism and is involved in such critical cellular processes as DNA synthesis and DNA methylation. People with homocystinuria can be at risk of neurological disabilities due to the inability to regular amino acids. Homocystinuria causes conditions such as osteoporosis and myopia. Since amino acids are the building blocks of protein, doctors tell people with homocystinuria to eat lowprotein diets, which can only lead to more deficiencies.

The MTHFR gene supposedly reduces the ability to synthesize folate, which is said to impair methylation. Impaired methylation can cause neurological diseases, and it is associated with depression, anxiety, histamine intolerance, some cancers, hormone imbalance, reduced detox ability, infertility, congenital disabilities, fatigue, and low energy.

These symptoms are also associated with hypothyroidism. Hypothyroidism reduces all enzyme activity since hypothyroidism causes a basal metabolic rate, and enzyme catalyzing needs an optimum temperature. Hypothyroidism is associated with the MTHFR C677T variant, which causes the polymorphism associated with reduced methylation because hypothyroidism minimizes the synthesis of all nutrients, including folate and B vitamins. One of the interesting results I've seen in the labs of hypothyroidism is an elevated and out-of-range B12 level. This elevated level of B12 doesn't necessarily mean they are not absorbing B12. I used to have these patients test their unsaturated B12 levels to be sure, and not one had low levels of unsaturated B12 (transcobalamin). The test assesses the amount of transcobalamin necessary to bind with Vitamin B12 in your blood.

Mudd et al. first published the association of MTHFR with the disease and identified a patient with homocystinuria due to a severe enzyme deficiency in 1972. The kind of polymorphism associated with homocystinuria is still rare, but that hasn't stopped genetic researchers from diagnosing MTHFR deficiency in many people and pointing to it as the cause of their health issues.

Folate hadn't even been discovered until 1941, when Mitchel et al. isolated it from spinach leaves. Its discovery created a need. The biochemist Lucy Wills is associated with using folate to prevent Spina Bifida and Anencephaly—the neural tube defects that occur in women who are anemic during pregnancy, yet Dr. Lucy Wills used liver extract to raise the B12 levels of researching macrocytic anemia and pregnancy among poor Muslim women working in textile factories in Mumbai, India. At the time of her research, even though Muslim Indian families ate some meat, they were still 67% vegetarian, especially those who were poor.

Once she returned to England, she worked at a different hospital, continuing to treat pregnant women with macrocytic anemia. She kept careful records of her patients' diets: bread, fish, white meat, sugary milk, vegetables, and fruit. Wills herself stated that she considered the liver extract the best treatment for her patients, as opposed to the Marmite or Brewer's yeast, which contained the subsequently named "Wills Factor." When she returned to England, her work summary stated that she chose the Marmite, or yeast therapy, because it was cheaper.

In 1941, Herschel K. Mitchell, Esmond E. Snell, and Roger J. Williams isolated folate from 4 lbs of spinach. It became a B vitamin called B9. All papers discussing macrocytic anemia indicate B12/ folate deficiency as the cause of neural tube defects, not folate deficiency. Folate was isolated from spinach leaves; hence, the name is derived from the Latin for leaf. But folate isn't necessary. It's B12 that is essential, as demonstrated by Dr. Lucy Wills' research. She said that the vegetable source of B12 in Marmite was less effective than liver extract in raising her patients' B12 levels.

A vegetable source came into use simply because it was cheaper. At the 1991 CDC Conference on "Vitamins, Spina Bifida, and Anencephaly," the CDC declared that women required folic acid before and during early pregnancy to prevent neural tube defects. Nobody needs folate; everyone needs B12.

Since reduced methylation impairs DNA transcription and the switching of genes possibly associated with disease and abnormal cell growth, how does thyroid function fit into this? Active T3 hormone impacts the development of the human brain by gene expression. Hypothyroidism leads to increased or decreased transcription and translation. Transcription is what turns genes on and off. Thyroid hormones regulate gene transcription not only in the fetus but also in adults. T3 hormone regulates gene expression in gluconeogenesis, lipogenesis, insulin signaling, and adenylate cyclase signaling, which modulates signaling to hormones and neurotransmitters, cell proliferation, and apoptosis. Aberrant cell proliferation can cause abnormal tissue growth like cancer. At low thyroid hormone levels, thyroid hormone receptors can repress gene transcription.

Thyroid hormone receptors in the tissue become distorted due to insufficient thyroid hormones. Tumors in the lung, breast, head, neck, renal, uterine, ovarian, and testicular tissue show abnormal thyroid hormone receptor activity. 70% of human liver cancers were found to have mutated thyroid receptors in cells. Low thyroid hormone levels can alter genes and even mutate genes. Because of how it affects genetics, thyroid hormone impacts all biological functions.

The thyroid hormone develops in the fetal brain and body from the mother's placenta until the fetus forms its thyroid. The mother's thyroid hormone grows the fetus but also regulates gene expression, which means the maternal thyroid hormone influences the fetus more than the embryo's genetics. Only after the fetus has a functioning thyroid can the genes from the father be expressed in the child. However, the levels of thyroid hormone the child and eventual adult can produce will continue to impact its genetics— which genes turn on and off, the good and the bad that can bring the risk of disease, from neurological and cognitive disorders to cancer.

In 2018, US-educated Chinese researcher He Jiankui implanted gene-edited embryos into two women. One of the women gave birth to twin girls, and the other to a baby girl. In November of that year, He declared he had modified a gene in several embryos to make them resistant to HIV. He explained that he wanted to spare babies born to couples where the father is HIV positive, but the mother is not at risk of infection. He was not only imprisoned for three years in China but scientists and ethicists criticized him for initiating the possibility of designer babies and risking babies to risks associated with gene editing when there are more effective and safer ways to prevent HIV infections. He is a research technician and has no training in clinical trials.

After He was released from prison, he returned to work in Beijing. In an NPR interview conducted in May 2023, He said he was working on using his CRISPR-gene editing technology to develop a genetic cure for Duchenne muscular dystrophy. This disorder causes muscles to degenerate. He hopes to have a clinical trial in humans ready by 2024. Scientists and lawyers in China are trying to ban He Jiankui from experimenting with humans. Unfortunately, he seems to have some support in the Chinese government because technological supremacy is a nationalist goal.

I mention this story not only because of the possible dangers involved in gene editing but also to underline the fact that scientists are looking in the wrong direction. Thyroid hormones regulate myogenesis. Adequate levels of T3 control the development of muscles and proper growth. Thyroid hormones control not only muscle development but also its integrity. Researchers are already targeting therapies for Duchenne muscular dystrophy using what they've learned from regenerating muscle tissue with T3 signaling in rats. Different kinds of hereditary myopathic disorders are associated with hypothyroidism, as are many genetic disorders involving muscle tissue, such as Dupuytren contracture, and connective tissue, such as Ehlers-Danlos syndrome. This being the case, does it make sense to alter embryos genetically or to ensure pregnant women are not hypothyroid?