ENP88: Glucocorticoids in Supplements

Summary

Endocrine News Podcast Summary: ENP88 – Glucocorticoids in Supplements

Release Date: August 7, 2024

The Endocrine News Podcast episode titled "ENP88: Glucocorticoids in Supplements", hosted by Aaron Lohr of the Endocrine Society, delves into the hidden dangers of glucocorticoids present in over-the-counter (OTC) arthritis supplements. Featuring an in-depth discussion with Dr. Kevin Way from the Los Angeles General Medical Center USC program, the episode highlights critical research findings, clinical implications, and the urgent need for increased awareness among both patients and healthcare providers.

1. Introduction to the Issue

Aaron Lohr sets the stage by addressing the widespread use of OTC supplements for various health reasons, particularly for managing arthritis pain. However, he raises a significant concern: "some may contain glucocorticoids... which may cause harm" (00:00).

2. The Hidden Threat of Glucocorticoids in Supplements

Dr. Kevin Way elaborates on why the presence of hidden glucocorticoids in supplements is alarming. He explains that “patients take these supplements thinking nothing of it”, unaware of the long-term side effects associated with glucocorticoid use (01:14). These side effects range from adrenal insufficiency symptoms like fatigue and nausea to severe consequences such as liver toxicity, gastrointestinal bleeding, and even death.

Way emphasizes the lack of regulation in the supplement industry: “they are not all FDA regulated... FDA themselves have to issue warnings, but those warnings can become lost in a sea of other information” (02:00). This regulatory gap leaves consumers vulnerable, as illustrated by his observation that many patients remained unaware of the harmful ingredients in popular supplements like Archer King and Artisans.

3. Why Are Glucocorticoids in Supplements?

The conversation shifts to the motivations behind adding glucocorticoids to supplements. Dr. Way points out that “the marketing behind these supplements is very convincing”, promoting them as cures for muscle aches, arthritis pain, osteoporosis, and even bone cancer (03:28). This persuasive marketing leads to widespread dependency, as the supplements interfere with the body's natural steroid equilibrium.

He explains the physiological impact: “when exogenous cortisol... is introduced into the body, this excess steroid amount essentially tells the adrenal gland to shut down in producing steroids” (04:30). Prolonged use results in physical signs of excess cortisol, such as "moon facies," "abdominal striae," and "dorsal cervical fat pad" (05:00). These signs often alert clinicians to the underlying issue of supplement-induced steroid dependency.

4. Dr. Way’s Study on Supplement-Related Adrenal Dysfunction

Dr. Way presents his study, a case series involving 12 patients evaluated for adrenal dysfunction linked to OTC arthritis supplements containing glucocorticoids. The study analyzed symptoms, physical findings, and the necessity for steroid replacement therapy upon discontinuing the supplements.

Key findings include:

• Median Age: 52 years; 33% Female (07:12)
• Common Symptoms Post-Cessation: Nausea, vomiting, fatigue, abdominal pain, and dizziness
• Physical Exam Findings: Moon facies (66%), central adiposity (66%), abdominal striae (50%), dorsal cervical fat pad (33%), and bruising (33%) (08:13)
• Clinical Interventions: Three patients required ICU admission; 11 out of 12 were prescribed glucocorticoid tapering replacements (08:13)

A surprising revelation from the study is the extent of dependency: “most patients who had become dependent... have not yet been able to wean off the taper completely” (09:00). This indicates long-term or potentially permanent adrenal suppression due to prolonged steroid exposure from supplements.

5. Implications for Clinical Care

Dr. Way underscores the critical need for clinician awareness regarding OTC supplements. He advises that “clinicians should make a thorough history of the exact names of the supplements” when patients present with symptoms suggestive of steroid excess (10:53). Additionally, he warns against abrupt discontinuation of supplements, which can precipitate adrenal crises, advocating instead for “a slow taper” of steroid replacement therapy (11:30).

He recounts a case where a patient “was admitted to the ICU for shock” after abruptly stopping supplements, highlighting the life-threatening risks of improper management (12:00). Dr. Way calls for comprehensive patient histories and cautious clinical approaches to managing supplement-induced adrenal dysfunction.

6. Conclusion: Raising Awareness and Ensuring Safety

Aaron Lohr wraps up the discussion by emphasizing the importance of awareness raised by this research. “This is a bit of a wake up call and I hope we were able to raise some awareness of this very important issue” (13:16). Dr. Way echoes this sentiment, expressing hope that his findings will prompt healthcare providers to more diligently inquire about supplement use and better manage the associated health risks.

Key Takeaways

• Hidden Glucocorticoids: Many OTC arthritis supplements contain undisclosed glucocorticoids, posing significant health risks.
• Regulatory Gaps: The lack of stringent FDA regulation on supplements contributes to patient vulnerability and misinformation.
• Clinical Vigilance: Healthcare providers must thoroughly assess supplement use in patients presenting with symptoms of steroid excess or adrenal insufficiency.
• Safe Management: Gradual tapering of steroid replacements is crucial to prevent adrenal crises in affected patients.
• Long-Term Consequences: Prolonged use of glucocorticoid-containing supplements can lead to lasting adrenal suppression and dependency.

This episode serves as a crucial reminder of the potential dangers lurking in seemingly innocuous OTC supplements and the imperative for both patients and healthcare professionals to exercise caution and due diligence.

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Timestamp References:

• 00:00 - Introduction by Aaron Lohr
• 01:14 - Dr. Way on glucocorticoid concerns
• 02:00 - Lack of FDA regulation
• 03:28 - Reasons for glucocorticoids in supplements
• 04:30 - Impact on steroid equilibrium
• 05:00 - Physical signs of excess cortisol
• 07:12 - Study overview by Dr. Way
• 08:13 - Study findings
• 09:00 - Dependency and tapering challenges
• 10:53 - Clinical care implications
• 11:30 - Importance of slow tapering
• 12:00 - Case of ICU admission
• 13:16 - Conclusion and awareness

Transcript

[Aaron Lohr]

Hello, I'm Aaron Lohr and this is the Endocrine News Podcast. Many people take over the counter supplements for a variety of reasons, but it isn't always clear what's in in those supplements. And while they may be intended to help, some may cause harm. Today we'll be talking about the presence of glucocorticoids in some over the counter supplements and why that may be a concern. Joining me today to discuss this issue is Dr. Kevin Way of the Los Angeles General Medical Center USC program. Dr. Way recently presented an abstract at Endo2024 entitled Characterizing the Physiological Side Effects of Over the Counter Arthritis Supplements. Thank you for being here.

[Dr. Kevin Way]

Dr. Wei, thank you so much for having me on your podcast. I greatly appreciate this opportunity to share my research.

[Aaron Lohr]

Now, many people take over the counter health supplements and some may contain glucocorticoids. Why might that be a concern? And how would somebody know if their supplements contain glucocorticoids?

[Dr. Kevin Way]

Yeah, so the reason why glucocorticoids hidden in supplements is such a big concern is because often patients take these supplements thinking nothing of it. Plus it may actually help with their pain. But the longer that they take the supplement, the higher the chance to experience side effects when they try to wean off of them in the future. These side effects can include significant fatigue, nausea, vomiting, dangerously low blood pressure, et cetera, all sequelae from adrenal insufficiency precipitated by the cessation of the supplement containing the steroids. To make matters worse, other serious side effects or prolonged use have also been seen, including liver toxicity, GI bleeding and in serious cases, death. It also does not help that besides glucocorticoids, these supplements also contain other ingredients such as NSAIDs and methocarbamol. All of these substances, when taken long term, especially in a non regulated manner, can lead to serious side effects. And unfortunately, often patients do not know what is in their supplements, especially since they are not all FDA regulated. So often the FDA themselves have to issue warnings, but those warnings can become lost in a sea of other information. This is evident in the fact that so many of the patients I saw had no clue that their supplement contained extra ingredients and had certainly never heard of such FDA warnings. In fact, although some of my patients had been taking supplements like Archer King or Artisans for at least several years by the time I evaluated them, the FDA only recently released their warning about Archer King in 2022. Some sources say the FDA released a warning back in 2012, but I was unable to Verify that using the Internet searches. And in some estimates, leading experts studying the field of of complementary and alternative medicine estimate it to be a multi billion dollar industry. Clearly, supplements are in high demand and this problem will not be going away anytime soon.

[Aaron Lohr]

So if the glucocorticoids have some harm that may be associated with them, why are they in the supplements?

[Dr. Kevin Way]

So the marketing behind these supplements is very convincing. These medications are promoted as being able to help with muscle aches, pain from arthritis, osteoporosis, even bone cancer. Additionally, there exists an entire family of supplements with similar names that all contain secret ingredients such as artraeagyoking, artraking artisans, ortego, mass agere, et cetera, each of which has an unidentified number of different substances in them. Patients essentially take these supplements and unknowingly become dependent on them. And perhaps that is something seen as beneficial to the industry. The reason why patients can become dependent on such supplements can be because of the impact that these supplements can have on glucocorticoid production in the body. Generally, the way that steroid equilibrium works is that the hypothalamus produces cortisol releasing hormone, which acts on the anterior pituitary gland to produce acthe, which then signals to the adrenal gland to produce cortisol, which is analogous to the glucocorticoids found in these supplements. And if adrenal cortisol production increases to an excess state, the pituitary gland naturally stops, signaling the adrenal gland to produce steroids via a negative feedback loop. So we can see how when exogenous cortisol in the form of over the counter arthritis supplements is introduced into the body, this excess steroid amount essentially tells the adrenal gland to shut down in producing steroids. Since there is so much in the body, and with longer term use, patients can start to develop telltale signs that they have been exposed to an excess of cortisol. For example, patients can develop dark purple stretch marks around the abdomen called abdominal striae, or easy bruising throughout their body, or formation of a dorsal cervical fat pad, a concentration of fat buildup surrounding their abdomen and a rounding of their face called moon facies. Sometimes these physical exam findings are what actually tip us off to the fact that patients have been taking these over the counter arthritis supplements. And remember how we were discussing the concept earlier that too much exogenous steroid exposure can cause the adrenal glands to shut down and and go into a deep sleep where the adrenal glands either reduce or stop producing cortisol altogether well. This deep sleep can last for months even after the cessation of exogenous steroid use. That is why patients may develop dependence on the supplements such that when they try to stop taking them they may have the symptoms of adrenal insufficiency, which include feeling weak and lethargic and experiencing nausea, vomiting or abdominal pain. In addition, the arthritis pain for which the patients were taking the supplement may return or worsen, so restarting the supplement would likely resolve these symptoms and thus the patients may think that the supplement is the cure for the symptoms when in reality that supplement was the root cause of their body's steroid dependency in the first place. And to make matters worse, if patients who have been taking these supplements long term abruptly cease taking the medication for whatever reason, that can lead to potentially life threatening side effects of low blood pressure and circulatory collapse leading to eventual death if not treated properly.

[Aaron Lohr]

Your study looks at some real world examples of glucocorticoids in supplements and the problems they may cause. Can you tell us about your study?

[Dr. Kevin Way]

Sure thing. In our study we presented a case series of 12 patients evaluated for iatrogenic adrenal dysfunction, Cushing's syndrome and or adrenal insufficiency associated with taking over the counter arthritis supplements that surreptitiously contained glucocorticoids. These were all patients using over the counter arthritis supplements seen by the Endocrinology Service at the Los Angeles General Medical center during the years of 2022 to 2023. Some of the names of these supplements included Artracain, Artisans and Agile Ray. We evaluated the most common presenting symptoms of adrenal dysfunction as well as the most common physical exam findings related to long term over the counter arthritis supplement use. We also collected data on the percentage of patients who had to be initiated on steroid replacement therapy upon discontinuing the supplement.

[Aaron Lohr]

And what did you find? Did anything in your findings surprise you?

[Dr. Kevin Way]

So in terms of the patient demographics, the median age of people in our study was 52 years old, 33% of them female. All patients had started using the supplements because of joint pain. Median length of use prior to cessation was six months. After supplement cessation, around 42% of patients experienced nausea or vomiting and 42% experiencing fatigue, 33% experiencing abdominal pain and 17% experiencing dizziness and the most common physical exam findings included moon facies at 66%, central adiposity at 66%, abdominal striae at 50%, dorsal cervical fat pad at 33% and bruising also at 33%. Three out of the 12 patients required ICU admission. Cortisol assessment was performed in 11 out of the 12 patients which showed a normal cortisol level in one patient, adrenal insufficiency in three patients and an inequivocal level in seven patients. Of those seven patients, cosyntropin stimulation testing was done on six of them suggesting adrenal insufficiency in four of them, whereas two showed lower but normal response. In total, 11 out of 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis. To date, only 4 out of 11 patients have successfully discontinued steroid replacement. The most surprising results were that most patients who had become dependent on these supplements had to be transitioned to a regulated steroid taper or essentially a plan to replace the supplement with a controlled prescribed dose of prednisone or hydrocortisone to avoid precipitating adrenal insufficiency or crisis for the patient. And even more alarming, most of these patients started on that replacement steroid taper, still have not yet been able to wean off the taper completely. Some likely to need steroids prescribed for life the most likely explanation lies in what we mentioned prior that after a prolonged period of inundating the body with excess steroids, the adrenal glands shut down and stay shut down and can take a long time to awaken again. It is unfortunate to see that these patients who unknowingly bought into this panacea of a drug are suffering from its consequences long term.

[Aaron Lohr]

So how might your findings impact clinical care?

[Dr. Kevin Way]

It is important for clinicians from all departments, whether in endocrinology or primary care or surgery, to be aware of the existence of these supplements and what side effects that they can bring to a patient. In any scenario where there are red flag symptoms of steroid excess such as unexplained weight gain, dorsal cervical fat pad, dark violaceous stretch marks of the abdomen as mentioned prior or or if a patient with a GI bleed states that they are taking a myriad of supplements, then it is crucial to make a thorough history of the exact names of the supplements so as to not miss the possibility that the patient is taking one of those over the counter arthritis supplements. In fact, I still remember one patient I saw who had been taking 14 different supplements, many for pain relief, who presented with severe drug induced liver injury and concern for adrenal insufficiency. Getting that extensive medication history was definitely exhausting it is also important for clinicians to know that if they ever do come across a patient who had been using such supplements for a prolonged period, that they should not jump to discontinuing the supplement immediately because that can also lead to dangerous circumstances such as causing blood pressure to drop suddenly. In fact, several of the patients I have come across that were admitted to the ICU for shock had come from another hospital where a provider there had just told the patient to cold turkey stop taking the supplement and as a result the patient went into adrenal crisis. Therefore, clinicians should know that a slow taper would be the safest, whether that be in the form of consulting endocrinology to come up with a steroid taper regimen or to naturally trial a taper regimen, knowing that many patients may take a long time to be able to tolerate a decreased dose and may not be able to wean off entirely. All in all, physician awareness of such a medication in its management is important to ensuring patient safety and well being. It is my hope that having shared my research, it will lead other clinicians to ask more patients about over the counter arthritis supplement use and to be more equipped to deal with situations and weaning patients off of these supplements.

[Aaron Lohr]

Well, thank you so much for coming on the podcast. This is a bit of a wake up call and I hope we were able to raise some awareness of this very important issue. Thank you again for taking the time and sharing your work with us.

[Dr. Kevin Way]

My pleasure. Thank you so much.

[Endocrine Society Announcer]

That's all for this episode. Before we go, I wanted to let you know about a new and exciting upcoming event from the Endocrine Society Society called the AI in Health Care Virtual Summit. Whether you want to learn more about how AI technologies are redefining diagnostics, treatment planning, and patient outcomes, or you want to explore machine learning, algorithms and predictive analytics, this meeting is for you. It's all online and will take place on November 8th through the 9th. We'll include a link for it in today's episode description. Until next time, thanks for listening.

[Aaron Lohr]

Endocrine News Podcasts are a free service of the Endocrine Society. To learn more or to become a member, visit the society's website at www.endocrine.org.