The potential dangers of supplements and herbal products marketed for improved thyroid function

Keywords::

• herbal products
• hypothyroidism
• supplements
• T3
• T4
• thyroid function

The trend of using natural products has increased significantly in recent decades in the USA. A national health survey by the CDC in 2007 estimated that Americans spent US $34 billion on herbal supplements, chiropractic visits, meditation and other forms of complementary and alternative medicine, similar to the amount spent on prescription drugs [101].

Recent CDC reports indicate that over 40% of the adult US population used dietary supplements between 1988 and 1994, and the number increased to >50% between 2003 and 2006 [102]. These products have not been under US FDA regulation since the introduction of the Dietary Supplement Health and Education Act in 1994. General perception is that natural products/supplements are by definition safe, when in fact reports indicate that at least some of these products can interact with and/or alter the pharmacology of various prescription drugs. Furthermore, side effects have been reported secondary either to the actual ingredients or contaminants found in these types of preparations. Manufacturers are not required to prove the safety or efficacy of a dietary supplement before it is marketed. Product labels or advertisements are permitted to claim that a particular dietary supplement addresses a nutrient deficiency, supports health or is linked to improvement of a particular body function only if there is research to support the claim. Such a claim must be followed by the words: “This statement has not been evaluated by the US Food and Drug Administration (FDA). This product is not intended to diagnose, treat, cure, or prevent any disease” [103].

A significant percentage of these products target the overweight and obese population, and represent appealing choices as weight-loss aids. As the prevalence of obesity has increased dramatically over the past few decades, popular media has promoted thin figures as desirable; the ‘slimming aid’ industry is seeing an unprecedented growth in sales.

Herbal substances with an effect on thyroid economy

Herbs are plants or plant products, including roots, stems, leaves, flowers, seeds or fruits, valued for their scent, flavor or medicinal properties. They can be marketed and sold in raw form or as extracts. Herbal medicine has been practiced for thousands of years with scarce scientific evidence regarding the safety and efficacy of most herbal products. Basic research over the past few decades demonstrates that several plants have an effect on thyroid economy or thyroid hormone metabolism, although the limited numbers of studies on human subjects have led to contradictory results. Guggulu (the gum resin of Commiphora mukul) is reported to raise the triiodothyronine (T3)/thyroxine (T4) ratio in female mice ">[1,2] and reverse the effects of propylthiouracil in hypothyroid mice by stimulating thyroid function [1].

Radovic et al. demonstrated that xanthohumol (Humulus lupulus) stimulates iodide uptake while in a culture of normal non-transformed rat thyrocytes, possibly by influencing the activity of the sodium iodide symporter, a key protein in thyroid hormone production [3]. This effect actually makes xanthohumol a potential candidate for improving radioactive ablation of the thyroid gland by means of stimulating better radioiodine concentration. Similar effects were observed with forskolin (Coleus forskohlii) in RET/PTC1-expressing thyroid follicular cells [4].

Withania somnifera is credited with anti-aging properties, sedative and anti-inflammatory effects, as well as increased serum T4 but not (T3) levels. It is thought to be a thyroid stimulant, while Bauhinia purpurea bark extract increased both T4 and T3 levels in female mice [5]. A similar effect was observed with Bacopa monnieri (Indian pennywort) extract, which increased both T4 and T3 levels in male mice [6].

Moringa oleifera leaf extract has been observed to decrease the conversion of T4 to T3 in female but not in male adult Swiss rats, therefore increasing the T4/T3 ratio [7], indicating a potential use for therapy of hyperthyroidism. Similar effects were observed with Aegle marmelos extract, which was observed to decrease T3 with an increase in T4 serum concentration in male mice [6].

Even widely used Aloe vera extract has been reported to cause a mild decrease in both T4 and T3 concentrations in male mice [6]. Sea kelp (Ascophyllum nodosum) and bladderwrack (Fucus vesiculosus) are known dietary sources of natural iodine, which, in excess, can be associated with thyroid overactivity.

In addition to herbal products, ground thyroid extract of animal origin was widely used for the treatment of hypothyroidism before the era of synthetic thyroid hormones, and can be found today in some over-the-counter (OTC) preparations found in health food stores, on the internet or by mail order. Animal thyroid gland extract contains a combination of T4 and T3 that can widely vary in amount from batch to batchm and at times with a T3 content that is greater than what the human thyroid directly secretes on a daily basis [8].

Thyroid hormones in nutritional supplements

Numerous natural products marketed today claim that they either contain thyroid extract or substances that have a positive effect on thyroid function or thyroid hormone metabolism, which are also purportedly both safe and beneficial for general health. Researchers have focused on verifying such statements by both analyzing the content of these products and studying their effects on human volunteers.

Csako et al. carried out an in vitro analysis measuring T4 and T3 levels in three generally available natural hormone preparations, and detected apparent T3 content by high-performance liquid chromatography in two out of three of these products [9]. Administration of twice the recommended dose to human volunteers did not lead to clinical consequences; however, the authors recommended against the use of “scientifically unsound and relatively expensive OTC thyroid preparations,” with unproven therapeutic efficacy.

Recently, Kang et al. analyzed the T3 and T4 content in ten OTC products on the market, and found detectable levels of T3 in nine out of ten and T4 in five out of ten samples [10]. Some of these preparations, even taken at the recommended doses, would deliver T3 and/or T4 doses equal to or greater than what may be used on a prescribed basis under the supervision of a health provider.

Dangers associated with the use of natural products containing thyroid hormones as slimming aids

The signs and symptoms of hyperthyroidism are well known to physicians, and include palpitations, tachycardia, heat intolerance, tremors, hyperdefecation and sometimes weight loss; however, these side effects can be subtle and even go unrecognized. Potential long-term complications include, but are not limited to, heart arrhythmias, altered sleep patterns and loss of bone mass. The connection between symptoms and hyperthyroidism may not be always evident, especially when the patient has no personal or family history of thyroid disease and has been previously healthy. Unless specifically asked, patients will not always report the use of such dietary or herbal supplements as they perceive them as being safe.

Several case reports published during recent years point out the consequences of using thyroid-containing OTC products as aids for weight loss. Ohye et al. report 12 cases of thyrotoxicosis associated with the use of two dietary supplements in Japan [11]. They also experimented by administering the drugs to human volunteers, and noticed changes in thyroid hormone levels during the first 24 h following administration. Another case report describes thyrotoxicosis related to the use of W. somnifera [12].

Ma et al. and Bauer et al. describe the cases of two patients aged 38 and 78 years, who developed thyrotoxicosis after ingestion of the OTC dietary supplement tiratricol [13,14]. In the first case, it was used as a slimming aid, and in the second, it was given as a health supplement for ‘mild anemia’. In another case report by Taylor and Czarnowski, a patient presented with clinical signs of hyperthyroidism after taking a European dietary supplement marketed to increase metabolism, and which the patient did not initially report to her physician, assuming that it was safe [15]. In all of these cases, symptoms resolved and thyroid function tests normalized after discontinuation of the preparations in question.

In some cases, the so-called ‘natural preparation’ appears to have been altered by introduction of synthetic pharmacological agents. Poon et al. report three cases of thyrotoxicosis, one of them fatal, after the ingestion of herbal preparations whose compositions turned out to have undeclared animal thyroid tissue as well as synthetic therapeutic substances [16]. Substances containing just T4 or T3 alone should be suspected of being added in the product rather than coming from the actual extract, as the latter would be expected to contain both T4 and T3.

In 2006, a communique from the French health authorities warned against the dangers posed by use of thyroid extracts as slimming aids, referring to examples of hospitalizations and deaths related to cardiac complications from exogenously induced thyrotoxicosis. Their statement clearly indicated the opinion that “thyroid hormones are effective for the treatment of hypothyroidism but have no place in the treatment of obesity” [17].

Conclusion

Although the majority of nutritional supplements available on today's market contain vitamins, minerals, herbs and amino acids and are probably safe, the medical community is in need of studies that evaluate the potential benefits and adverse effects of such products to include any impact on thyroid function. The presence of active thyroid hormone in readily available supplements is of great concern, as the use of thyroid hormone, both T4 and T3, should only be carried out under medical supervision and should be reserved for use in patients with an appropriate indication, specifically confirmed hypothyroidism. We recommend that dietary supplements and herbs should be strictly regulated for hormonal content and that active thyroid hormone should be available only by prescription. In the meantime, healthcare providers should vigilantly screen all their patients for the use of herbal and dietary supplements and appropriately educate their patients on the potential drug interactions and side effects that can be associated with the use of such products.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.