hypothyroid

Vitamin C deficiency wreaks havoc on thyroid function

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With an estimated 30 million Americans having some form of thyroid disease, solutions are necessary as impaired thyroid function can lead to other chronic diseases if not treated. Because the thyroid is a hormone-producing gland that regulates the body’s metabolism, it also affects critical body functions.

Keep in mind, the rate at which your body produces energy from oxygen and nutrients can alter the way your heart, brain, muscles, liver, and other body parts work. If they work too fast or slow, you won’t feel well. Therefore, therapy is essential if you want to feel your best.

An important but neglected vitamin for healthy thyroid function

Numerous studies have confirmed the presence of excess oxidative stress and a deteriorated antioxidant defense system in thyroid conditions. In fact, a large experimental study published in the BMC Endocrine Disorders journal reported that all subjects with benign or malignant thyroid disease had low levels of antioxidants, particularly with selenium, zinc, and vitamin C.

While low levels of selenium and zinc were not found in all subjects, low levels of vitamin C were. This confirms an association with vitamin C deficiency and thyroid function. One reason why vitamin C may be deficient in all people with thyroid conditions could be a result of adrenal fatigue.

Physical, mental, and emotional stress takes its toll on the adrenal gland

The adrenal gland contains the highest concentration of vitamin C in the body. In fact, the vitamin plays a crucial role in both the adrenal cortex and adrenal medulla which are responsible for responding to stress.

According to the American Journal of Clinical Nutrition, vitamin C secretion is part of the body’s stress response. Excessive stress, along with the body’s insufficient intake of the vitamin, can create a deficiency that leads to adrenal stress.

Countless studies show chronic adrenal stress disrupts the hypothalamic-pituitary-adrenal (HPA) axis. Because thyroid hormone is directed by the hypothalamus and the pituitary glands, anything that disrupts the HPA axis will affect thyroid function.

With studies proving that vitamin C deficiency is a problem for all people who have a thyroid condition, it’s possible that adrenal fatigue could be the cause. Therefore, it’s imperative to include foods and/or supplements containing vitamin C, especially with extreme or ongoing stress.

How does vitamin C boost thyroid medication delivery

Many people who have been diagnosed with a form of thyroid disease often adopt pharmaceutical medication to regulate their thyroid. However, many patients still exhibit symptoms which indicate the medication may not fully work towards thyroid homeostasis. However, studies are showing that natural antioxidant therapy – such as with vitamin C – can reverse thyroid damage and even help those who don’t see improvement with their prescription medication.

The Journal of Clinical Endocrinology & Metabolism recently studied the effects of vitamin C on the absorption of a synthetic T4 hormone with 31 patients who either had autoimmune thyroiditis or idiopathic hypothyroidism. Prior to the study, all patients were not in good control when taking the synthetic T4. Serum concentrations of T3, T4, and TSH were measured at particular intervals after vitamin C therapy.

All three concentrations were improved while taking vitamin C. TSH decreased in all patients and normalized in nearly 55 percent of them. T4 was higher with 30 of the 31 patients, and T3 was increased with all patients tested. These findings are significant in the role of vitamin C and thyroid function.

Improving thyroid function with vitamin C

Every day is a challenge when it comes to protecting our bodies from damaging chemicals in the food we eat, the water we drink, and the air we breathe. As presented, vitamin C has proven to help prevent adverse effects to health by optimizing thyroid function.

If you suspect or have a thyroid condition, you may want to consider taking a vitamin C supplement. One of the leading experts on treating thyroid disease, the late Dr. John C. Lowe, recommended the highest doses of vitamin C to bowel tolerance for four weeks as therapy.

The supplement should be taken in divided doses throughout the day. Larger amounts taken are less absorbed into the blood. Therefore, you may want to consider 250 to 2,000 milligrams at one time. Absorption rate is 80 to 50 percent respectively.

What’s Behind Brain Fog in Treated Hypothyroidism?

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The phenomenon of brain fog, as described by some patients with hypothyroidism despite treatment, is often associated with fatigue and cognitive symptoms and may be relieved by a variety of pharmacologic and nonpharmacologic approaches, new research suggests.

The findings come from a survey of more than 700 patients with hypothyroidism due to thyroid surgery and/or radioactive iodine therapy (RAI) or Hashimoto’s, who reported having brain fog.

The survey results were presented May 29 at the American Association of Clinical Endocrinology (AACE) Virtual Annual Meeting 2021 by investigators Matthew D. Ettleson, MD, and Ava Raine, of the University of Chicago, Illinois.

Many patients with hypothyroidism continue to experience symptoms despite taking thyroid hormone replacement therapy and having normal thyroid function test results.

These symptoms can include quantifiable cognitive, quality of life, and metabolic abnormalities. However, “some patients also experience vague and difficult to quantify symptoms, which they describe as brain fog,” Raine said.

The brain fog phenomenon has been described with somewhat varying features in several different chronic conditions, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, post-menopausal syndrome, and recently, among people with “long haul” COVID-19 symptoms.

However, brain fog associated with treated hypothyroidism has not been explored in-depth, despite the fact that patients often report it, Raine noted.

Results Will Help Clinicians Assist Patients With Brain Fog

Fatigue was the most prominent brain fog symptom reported in the survey, followed by forgetfulness and difficulty focusing. On the other hand, rest and relaxation were the most reported factors that alleviated symptoms, followed by thyroid hormone adjustment.

“Hopefully these findings will help clinicians to recognize and treat the symptoms of brain fog and shed light on a condition which up until now has not been very well understood,” Ettleson said.

Asked to comment, session moderator Jad G. Sfeir, MD, of the Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “We do see patients complain a lot about this brain fog. The question is how can I help, and what has worked for them in the past?”

“When you have symptoms that are vague, like brain fog, you don’t have a lot of objective tools to [measure] so you can’t really develop a study to see how a certain medication affects the symptoms. Relying on subjective information from patients saying what worked for them and what did not, you can draw a lot of implications to clinical practice.”

The survey results, Sfeir said, “will help direct clinicians to know what type of questions to ask patients based on the survey responses and how to make some recommendations that may help.”

Fatigue, Memory Problems, Difficulty Focusing Characterize Brain Fog

The online survey was distributed to hypothyroidism support groups and through the American Thyroid Association. Of the 5282 respondents with hypothyroidism and symptoms of brain fog, 46% (2453) reported having experienced brain fog symptoms prior to their diagnosis of hypothyroidism.

The population analyzed for the study was the 17% (731) who reported experiencing brain fog weeks to months following a diagnosis of hypothyroidism. Of those, 33% had Hashimoto’s, 21% thyroid surgery, 11% RAI therapy, and 15.6% had both thyroid surgery and RAI.  

Brain fog symptoms were reported as occurring “frequently” by 44.5% and “all the time” by 37.0%. The composite symptom score was 22.9 out of 30.

Fatigue, or lack of energy, was the most commonly named symptom, reported by over 90% of both the thyroid surgery/RAI and Hashimoto’s groups, and as occurring “all the time” by about half in each group. Others reported by at least half of both groups included memory problems, difficulty focusing, sleep problems, and difficulties with decision-making. Other symptoms frequently cited included confusion, mood disturbance, and anxiety.

“Each…domain was reported with some frequency by at least 85% of respondents, regardless of etiology of hypothyroidism, so it really was a high symptom burden that we were seeing, even in those whose symptoms were the least frequent,” Raine noted.

Symptom scores generally correlated with patient satisfaction scores, particularly with those of cognitive signs and difficulty focusing.

Lifting the Fog: What Do Patients Say Helps Them?

The survey asked patients what factors improved or worsened their brain fog symptoms. By far, the most frequent answer was rest/relaxation, endorsed by 58.5%. Another 10.5% listed exercise/outdoor time, but 1.5% said exercise worsened their symptoms.

Unspecified adjustments of thyroid medications were said to improve symptoms for 13.9%. Specific thyroid hormones reported to improve symptoms were liothyronine in 8.8%, desiccated thyroid extract in 3.1%, and levothyroxine in 2.7%. However, another 4.2% said thyroxine worsened their symptoms.

Healthy/nutritious diets were reported to improve symptoms by 6.3%, while consuming gluten, a high-sugar diet, and consuming alcohol were reported to worsen symptoms for 1.3%, 3.2%, and 1.3%, respectively. Caffeine was said to help for 3.1% and to harm by 0.6%.

Small numbers of patients reported improvements in symptoms with vitamins B12 and D, Adderall, or other stimulant medications, antidepressants, naltrexone, sun exposure, and blood glucose stability.

Other factors reported to worsen symptoms included menstruation, infection or other acute illness, pain, and “loud noise.”   

Ettleson pointed out, “For many of these patients [the brain fog] may have nothing to do with their thyroid. We saw a large proportion of patients who said they had symptoms well before they were ever diagnosed with hypothyroidism, and yet many patients have linked these brain fog symptoms to their thyroid.”

Nonetheless, he said, “I think it’s imperative for the clinician to at least engage in these conversations and not just stop when the thyroid function tests are normal. We have many lifestyle suggestions that have emerged from this study that I think physicians can put forward to patients who are dealing with this…early in the process in addition to thyroid hormone adjustment, which may help some patients.”  

Debate Continues on Combination Therapy for Hypothyroidism

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It’s “critically important” for clinicians to recognize that not all patients with hypothyroidism are fully treated with levothyroxine (LT4) and some may need combination treatment with triiodothyronine (LT3) despite normal levels of thyroid stimulating hormone (TSH), according to thyroid expert Antonio C. Bianco, MD, PhD.

Speaking to a crowded room at the recent American Association of Clinical Endocrinology (AACE) Annual Meeting 2022, Bianco summarized the history of thyroid replacement treatment, the emerging data focusing on the subset of patients remaining symptomatic on levothyroxine, and how the clinical guidelines have evolved from stating that LT4 is the one and only treatment to now acknowledging that some patients may need combination therapy.

“Treatment with LT4 will leave residual symptoms in about 10%-20% of the patients. Before planning a thyroid surgery, this issue should be discussed with patients. We used to tell patients that LT4 treatment resolves all symptoms, but this is not true for all. For those…who remain symptomatic while on LT4, physicians should attempt combination therapy,” Bianco told Medscape Medical News.

The acknowledgement, he said, is “critically important because patients are greatly aggravated by the fact that physicians are satisfied with a normal serum TSH and yet they do not feel well. This comes out in every survey we and others have done.” Common residual symptoms include weight gain, fatigue, and “brain fog,” which clinicians sometimes dismiss as psychological, he noted.  

However, Bianco cautioned that before attempting combination therapy, it’s important to make sure that patients don’t have other comorbidities that could explain the residual symptoms, including perimenopause/menopause, obesity, vitamin B deficiency, anemia, or other autoimmune diseases.

Bianco is professor of medicine at the University of Chicago and author of more than 80 publications on the thyroid as well as an upcoming book.

Doctors Follow Guidelines…

Asked for comment, session moderator Alex Tessnow, MD, of the University of Texas Southwestern Medical Center, Southlake, told Medscape Medical News: “I agree with him entirely. I think the biggest challenge we have now is lack of data. It’s amazing how common hypothyroidism is. Almost 20% of women over age 65 have an elevated TSH.”

“Levothyroxine is the number one prescribed drug in the country. And of all those trials, only three have more than one hundred patients in them. That’s how unstudied this topic is. We really need to know more.”

Among the reasons the topic remains controversial, Tessnow said, are that “for years the guidelines said levothyroxine is the first choice. Doctors don’t want to deviate from the guidelines.”

And he noted that some doctors “may be fearful of LT3 being so potent and short-acting and potentially causing cardiac arrhythmias.”

“Levothyroxine is so long-acting it’s easy to give. Often patients have to take LT3 more than once a day on an empty stomach. There’s no combination pill as of now.”

Bianco noted that two investigational slow-release LT3 molecules are currently in the pipeline and could alleviate some of these concerns.

Trials Should Focus on Those Not Doing Well on Levothyroxine Alone

Tessnow and Bianco both noted that most of the studies that have failed to show a benefit of combination LT4+LT3 treatment have included overall populations with hypothyroidism rather than focusing just on those who remain asymptomatic with LT4.

“It is possible that those individuals most likely to benefit from combination therapy may not yet have been included in trials in sufficient numbers in order to provide adequate power for detecting a response,” Bianco said.

Tessnow agreed: “The sheer number of people who are doing fine on levothyroxine are going to cover up the potential benefit the combination would give those who are most symptomatic. We need to focus our studies on those patients”.  

In fact, this research gap was among the conclusions from an expert consensus statement published in March 2021, following a joint conference of the American Thyroid Association (ATA), the British Thyroid Association (BTA), and the European Thyroid Association (ETA). Bianco was one of the statement’s authors.

This “acknowledges that the previous clinical trials were not adequately designed,” says Bianco, adding, “there is a need for new clinical trials.”

Many Patient Reports Document Dissatisfaction With LT4 Treatment

Numerous patient-generated publications have documented residual symptoms with LT4 treatment alone, including higher levels of symptoms on questionnaires, deficits in neurocognitive functioning, impact on psychological well-being, and “brain fog,” as reported by Medscape Medical News and published in December 2021, and notably, a study from Bianco’s group in 2018, which found “prominent dissatisfaction” with their treatment and their physicians.  

“Some changed physicians five to ten times. We concluded there was a significant burden of unsuccessfully resolved symptoms among patients with hypothyroidism,” Bianco said during his talk.

“Some say patient preference isn’t a clinical outcome, but we have to consider it…To not listen to the patient in what they prefer is unfair and just gives them more reason to be mad at us,” he added.

History and Physiology: Why LT4 Is Used But May Not Be Enough for SomeTreatment of hypothyroidism using implantation of a sheep’s entire thyroid gland was first described in 1890, followed by subcutaneous injections of sheep’s thyroid extract. A short time later, thyroid extract by mouth was introduced. In 1965, a study demonstrated efficacy of a 3.5:1 mixture of synthetic LT4 and LT3.The shift to LT4 monotherapy happened in 1970, with a study published in the Journal of Clinical Investigation showing that T4 was converted to T3 in humans, “which all interpreted as ‘no need to use thyroid extract,’ then LT4 became the standard of care,” Bianco said.He then explained the physiologic basis for why some patients may not fare well with LT4 alone.TSH in the normal range doesn’t mean T3 and T4 are normal. “The thyroid is hard-wired to preserve serum T3,” he said.But once the patient develops hypothyroidism, the thyroid no longer responds to TSH, and serum T3 is only maintained via conversion of T4 to T3. Although LT4 is used to normalize serum TSH levels, that occurs before serum T3 is normalized, resulting in lower serum T3 levels and relatively higher serum T4 levels.The lower T3 level with normal serum TSH explains the residual symptoms, Bianco explained.  “Thus, by adding small amounts of LT3 to the regimen with LT4 we can normalize serum TSH but with normal serum T4 and T3 levels,” he said.So why do most patients report feeling fine with LT4 alone? “We do not have the answer to this question. Multiple factors could explain it, including genetics,” he told Medscape Medical News.    

How Can Combination Therapy Be Given Safely?

The 2012 guidance from the ETA provided specific information for how combination therapy should be prescribed by reducing LT4 and replacing a small amount with LT3 in order to keep TSH within normal range.

For example, if the patient is taking 100 µg/day of LT4, drop that to 87.5 µg/day and add 5 µg/day of LT3. Similarly, 200 µg/day of LT4 should be dropped to 175 µg/day and 10 µg/day of LT3 added.

Patients should undergo enhanced follow-up, with measurement of serum T3 at baseline and 3 hours after LT3.

This approach should be avoided in patients with cardiac conditions or concomitant use of other medications that could potentiate the effects.

Indeed, while there has been concern about cardiac effects of LT3, trials following nearly 1000 patients for as long as 1 year have shown that the addition of LT3 only minimally affects serum TSH, heart rate, or blood pressure. Bone turnover markers remained within normal range in two studies.

Another large study published in 2016 also showed no long-term effects of LT3 on cardiovascular disease outcomes or fractures, although there was increased use of antipsychotic medications.  

“Given the new safety data, physicians could be more liberal with this form of therapy as they treat patients with residual symptoms,” he concluded.