Supraglan Replaced By Adrenal Harmony Gold: Different Ingredients, Same Empty Promises

Note. Updated with correction Jan. 30, 2013 (see below)

One of the most widely read, and controversial, reviews I have written was for an herbal combination product called Supraglan which was marketed to treat hyperadrenocorticism, also known as Cushing’s Disease (and also its opposite, Addison’s Disease). Essentially, the company made numerous dramatic claims about both the safety and effectiveness of this product without any appropriate scientific evidence to support them. But despite the near miraculous results claimed for this product in testimonials on the company web site (which, of course, prove nothing for reasons I have discussed before), shockingly no scientific evidence has come to light in the two years since I first discussed Supraglan showing that it had any benefit at all. Instead, the company has ceased marketing Supraglan and replaced it with another product, the more soothingly named Adrenal Harmony Gold. The new product comes with equally miraculous testimonials.

But I have to wonder why, if Supraglan was so amazingly safe and effective, the company chose to stop making it rather than pursing the scientific research that would have given it legitimacy, and a much wider market. And why, if Supraglan was so successful, did the company use only one of the ingredients from Supraglan in the new concoction? And if Supraglan didn’t really do all the things claimed for it in those testimonials, why exactly should we believe the same kind of anecdotes for the new product?

What are the Claims?
So how are the claims and the evidence for the new product? Sadly, just as empty and misleading as for Supraglan.

• Promotes healthy skin and coat
• Helps normal hair growth
• Supports normal thirst and urination
• Supports healthy weight, normal appetite
• Supports proper muscle tone

The herbal actions in Adrenal Harmony Gold are: adaptogenic, antioxidant and will support the nervous system. These herbs are particularly suited to supporting the adrenal glands and its functions. “Adaptogens” are a group of herbs considered to nourish and balance the adrenals, helping the body adapt naturally and have normal levels of energy. Antioxidants counter oxidative (free radical) damage that can lead to degeneration.

Together, the ingredients in Adrenal Harmony Gold target the body systems that help to keep the adrenal and anterior pituitary hormones in a healthy and normal balance. They also contribute to the body’s healthy stress response for normally calm moods and sleep.

Adrenal Harmony Gold targets the HPA axis (hypothalamus-pituitary-adrenal) to strengthen the body’s internal feedback mechanisms.

These claims and explanations for the supposed mechanism of action of this product are not supported by scientific evidence. The product is claimed to normalize the symptoms associated with Cushing’s disease, but no plausible scientific explanation for why it should is given. Vague claims like “nourishing” and “supporting” the adrenals are meaningless.

As far as the inclusion of supposed antioxidants, I’ve pointed out before that the hype about antioxidants far exceeds the evidence (c.f. this article also) of any real value, and some evidence has developed showing that they have significant potential risks, including increasing the likelihood of some diseases and interfering with some kinds of medical therapy. So while the potential uses of antioxidants deserve further study, the automatic assumption that they are a good idea is increasingly contradicted by the evidence. In any case, there is no evidence that Cushing’s is caused or exacerbated by oxidative processes or that antioxidants would be beneficial.

The notion of “adaptogens” is also not a concept that is supported by much legitimate scientific theory or research. The idea is that certain herbs can, by some vague mechanisms not yet identified, “restore balance” to any system in the body. This concept has more to do with vitalist spiritual beliefs about health and disease being due to “imbalances” in some vague vital energy than with a scientific understanding of homeostasis.

While herbs undoubtedly contain active chemical ingredients which could possibly have medicinal value, there is no reason to think these medicines are fundamentally different from much better studied conventional medicines. The notion that herbs can act primarily to bring a disease organ system “into balance” regardless of the specific disease the patient is suffering from is pure pseudoscience.

The company web site talks a lot about Cushing’s disease caused by excessive use of steroids. This is a form of the disease which is completely avoidable unless a patient has another medical condition which requires prolonged, relatively high doses of steroids. In these cases, there is no “imbalance,” there is simply an adverse effect to a medication needed for another reason, and as always the risks and benefits of the medication have to be weighed. Cushing’s disease may be better than death from autoimmune disease, for example. And if the steroids are not truly needed, then the Cushing’s disease can be cured simply by gradually taking the patient off of them. The only potential use for herbal therapy here would be to minimize symptoms without addressing the cause, and there is no evidence showing this product can do that.

However, most cases of Cushing’s disease in dogs are caused by a benign tumor in the pituitary gland. The “imbalance” is due to excessive production of a pituitary hormone which, in turn, causes too much steroid production in the adrenal glands. The scientific therapies for this are to take away the pituitary tumor surgically (which is commonly done in humans but which is not usually possible in dogs for anatomical reasons), or to reduce the production of steroids by the adrenal glands. Any herbal therapy that is going to effectively treat this disease will need to be able to reduce the amount of active steroid hormone by some means. It is certainly possible such an herbal therapy may be developed, but if it is effective it will act as a medicine, and like all medicines it will have its side effects and limitations which must be considered along with its benefits. It will not, however, magically make the symptoms go away without actually treating the cause of the disease and without any possible risks.

Finally, a few cases of Cushing’s come from an aggressive cancer in the adrenal gland. This tumor is usually not very responsive to medications and needs to be removed surgically in those cases in which that is possible. Sadly, many of these patients eventually die of this cancer. No “nourishing” or “balancing” of the adrenals or “strengthening of the body’s natural feedback mechanism” is going to help these dogs. And delaying real therapy while messing around with an untested herbal remedy only decreases the chances of a good outcome.

Now could herbal therapies reduce symptoms even if not treating the cause of the disease? It’s possible, but like all other medical claims it should be proven by appropriate research, not wishful thinking and testimonials. The company claims is has “integrated the latest scientific research” with the “time-honored, traditional uses” of herbs to create this product. Let’s see what the science actually says about the ingredients in this product.

The Ingredients and The Science
Here are the ingredients listed for the product (with no specific quantities listed) and some of the statements made about them:

• Fresh Ashwagandha root (Withania somniferum)*: A primary adaptogen in this formula, Ashwagandha assists the adrenal glands directly to respond normally and produce healthy amounts of cortisol. This is a well-known herb for helping      the body’s stress levels and supporting normal, restful sleep.

Coming from the Ayurvedic herbal tradition, this ingredient has the usual thousand-and-one traditional uses, including as a non-specific tonic improving any and every symptom or disease. The plant contains varying amounts of a wide range of chemicals, and there have been some laboratory animal studies (mostly in rodents) indicating these chemicals have a variety of physiological effects. Some studies do suggest the plant can lower steroid hormone levels in rats exposed to chronic stress. This, however, says nothing about the effect on dogs with pituitary tumors or other causes of Cushing’s disease.

There is little research on the use of the herb in humans, and I could find none specifically relating to Cushing’s disease. There is one case report which suggests the herb might raise steroid hormone levels, which would be the opposite of the desired effect in Cushing’s disease. There appear to be no clinical studies on the use of this product in treating dogs with Cushing’s disease.

This summary of the research identifies a lot of interesting preclinical studies suggesting the chemicals in this plant might do interesting things, but it identifies no reliable evidence to support using it to treat Cushing’s disease in dogs.

 

• Holy Basil leaf (Ocimum sanctum): Also called Tulsi, Holy Basil is a gentle adaptogen for supporting the adrenal glands. Of key importance, adaptogens will neither cause the body to relax nor become stimulated, necessarily. Rather, their action is to assist the body to adapt as needed and bring it back into balance. For that reason, adaptogens are used for a variety of reasons when normal adrenal function is desired.

Also common in Ayurvedic medicine, this herb has a very similar profile in terms of the evidence available for it. Lots of pharmacology studies characterizing the chemicals it contains. A moderate number of rodent studies showing physiological effects, including a few that suggest it might ameliorate the effects of chronic noise stress. No clinical trials in humans or dogs suggesting any usefulness in Cushing’s disease.

 

• Fresh Turmeric rhizome (Curcuma longa): One of the best antioxidant herbs      available, Turmeric also supports liver health. Turmeric can be difficult  for the body to absorb. Our extraction method using fresh, organic Turmeric is an extremely potent liquid extract, much stronger than a simple glycerin extraction and captures all of the useful constituents of this herb, including curcumin and other curcuminoids.

Turmeric is one of the most intensively examined herbal agents, with a wide range of proposed uses. With regard to the treatment of Cushing’s disease, I have found no clinical studies in humans or dogs to suggest a benefit. There is one study that found changes in the secretion of steroids by cow adrenal cells in the lab under specific conditions. And there are some of those “chronic stress” studies in rats which suggest some interaction between curcumins and the hypothalamus/pituitary/adrenal (HPA) system. Does this mean these chemicals could be useful as medicines in diseases involving the HPA system? Sure. Does it mean they are safe and effective for treating Cushing’s disease in dogs? Absolutely not.

The National Center for Complementary and Alternative Medicine says:

There is little reliable evidence to support the use of turmeric for any health condition because few clinical trials have been conducted.

Preliminary findings from animal and other laboratory studies suggest that a chemical found in turmeric—called curcumin—may have anti-inflammatory, anticancer, and antioxidant properties, but these findings have not been confirmed in people.

There is even less evidence in dogs. And there have been reports of allergic reactions, liver problems, and other side effects. Any chemical that exerts a substantial effect on the body is going to have unintended effects some of which can be harmful. This is as true for herbal products as for conventional pharmaceuticals.

 

• Bacopa herb (Bacopa monnieri): Bacopa exhibits uses both as an adaptogen and as an antioxidant. It has also been used for stress and is said to generally contribute to healthy moods and cognitive function.

This herb has been studied primarily for effects on anxiety, depression, memory, and other behavioral conditions. There is a fair bit of laboratory rodent research showing effects on stress response, including steroid levels, but again this is quite different from the physiology of Cushing’s disease. This kind of pre-clinical research is not a reliable indicator of whether a medicine will be safe or effective in actual clinical use. I have found no clinical research in humans or in dogs to suggest this herb is appropriate for Cushing’s disease.

 

• Sarsaparilla root (Smilax officinalis): A traditional herb of the south western      United States, Sarsaparilla has a long-standing use for helping the body to normally excrete excess toxic materials through the lymphatic system. It has also been used to support liver function and healthy blood pressure levels.

Claims about “toxins” are a mainstay of alternative theories and treatments of disease, and they are mostly nonsense, the “evil humours” of today’s pseudoscience. Given that the idea of mysterious unnamed “toxins” being involved in Cushig’s disease is nonsense, there is little reason to think this herb would be useful for excreting these toxins. As usual, there are no clinical studies in any species that suggest this is safe and effective as a therapy for patients with Cushing’s disease.

 

• Astragalus root (Astragalus membranaceous): Another popular      “adaptogen”, Astragalus helps the body’s normal ability to adapt to stress. It also contains polysaccharides, constituents that assist the body’s normal immune response to fight off bacteria and viruses.

Again, the claims for the concept of “adaptogens” are not strongly supported by scientific evidence, so this is not a compelling reason to use this herb. And while it is true that patients with Cushing’s disease have impaired immune function, the notion of “boosting the immune system” is about as legitimate as “cleansing toxins” or “protecting against stress.” Vague claims about broad and non-specific health effects, which are uniformly beneficial and never harmful, are a clear warning sign of unscientific and unreliable nonsense. In the absence of any actual clinical studies to suggest this herb is beneficial for Cushing’s patients, these arguments are certainly no reason to use it.

 

• Milk Thistle seed (Silybum marianum): A gentle and effective herb for normal liver function, Milk Thistle assists the liver to metabolize drugs and toxins to be excreted by the body. The liver also plays a role in denaturing some circulating      hormones.

This is one of the few ingredients in this concoction with at least a plausible argument for why it might be useful in patients with Cushing’s disease. There is reasonable evidence that silymarin has protective effects in the liver, and the liver does experience the accumulation of glycogen and other adverse effects of chronically high steroid levels in animals with Cushing’s. However, the evidence for the benefits of milk thistle is generally still weak and mostly concerns toxic and infectious liver disease. There does not appear to be any specific research suggesting a benefit for patients with Cushing’s, so wile the idea is at least plausible, it remains undemonstrated.

 

• Blessed Thistle flower (Cnicus benedictus): Blessed or Holy Thistle has similar uses as Milk Thislte for liver support. Additionally, it has been shown to exhibit      support for the immune system and digestion.

There is generally very little research on the potential medicinal value of this herb, and none I could find on its use for patients with Cushing’s disease. The Natural Medicines Comprehensive Database indicates there is insufficient evidence to draw conclusions about claims for any medicinal use.

 

• Chaste Tree berry (Vitex      agnus-castus): Used for its gentle, tonic action on the anterior pituitary, Vitex is an amphoteric herb, meaning it will help maintain      normal hormonal levels, rather than cause them to go higher or lower. Commonly used for female health matters, Vitex is included in this formula for its affect on the pituitary’s action in adrenal hormone regulation

This is the only one of the ingredients in this product that does appear to have been tested for use in patients with Cushing’s disease. Unfortunately, it didn’t work. Lots of anecdotal reports suggested this herb might have benefits in horses with Cushing’s disease, and uncontrolled evaluation by the manufacturer of a chaste tree berry product seemed supportive of these claims. However, a clinical trial comparing this product to conventional treatment concluded:

Vitex agnus castus Extract,the commercially available form of Vitex agnus castus, did not have a beneficial effect in horses with pituitary pars intermedia hyperplasia (Equine Cushing’s Syndrome).

Whether positive or negative, these results may not be relevant to treatment of Cushing’s in dogs, which involves a very different mechanism than in horses. No studies are available in dogs with Cushing’s.

 

• Prickly Ash bark (Zanthoxylum americanum): Used by many First Nations communities at one time, the bark of the Prickly Ash tree has been termed an      “alternative”, meaning that it will help support normal flow of lymphatic circulation. It also helps maintain normal arterial and capillary circulation.

This herb contains chemicals which have shown some potential antibiotic and antiparasitic properties, though there are no clinical trials of this use. And, almost needless to say at this point, there is absolutely no evidence it is beneficial for dogs with Cushing’s disease. “Supporting normal lymph flow” is not only ridiculously unlikely but not in any obvious way relevant to the needs of patients with Cushing’s disease. And how or why it would maintain normal arterial and capillary circulation (but not venous circulation?), or why this would be relevant for these patients, is also unclear.

Bottom Line
Like Supraglan, this product contains a hodgepodge of herbal ingredients with rationales that are mostly based on traditional use, anecdote, or the findings or in vitro laboratory studies, none of which on their own justify clinical use of any medicine.  Many of the theoretical rationales for the selected ingredients, such as “boosting the immune system” or “excreting toxins” are complete nonsense. There are potentially plausible rationales for the use of a couple ingredients, such as the milk thistle. There is not, however, any clinical trial evidence to support the use of this product for Cushing’s disease in any species. The only ingredient which appears to have been tested for use in patients with Cushing’s disease is the chaste tree berry extract, which failed to show any benefits in a clinical study in horses.

This product will undoubtedly be promoted not only with dubious rationales and a lack of real scientific data showing any benefit, but also with miraculous anecdotes and testimonials supporting its effectiveness. I expect to see passionate, even angry comments from users of the product who are certain, based on their personal experiences, that it works. Apart from all the usual reasons why such uncontrolled observations are not useful in establishing safety and efficacy for any medical therapy, I will point out right from the beginning that the same miraculous testimonials supported the benefits of Supraglan, which many people claimed to have cured their dogs of Cushing’s disease. So why, exactly, did this miraculous product suddenly disappear, replaced by another with almost none of the same ingredients? And why, if the testimonials for Supraglan turned out to be as unreliable as testimonials usually are, should we take those for Adrenal Harmony Gold any more seriously?

** Update Jan. 20, 2013:

Having looked into these products in more detail, it appears that the initial report I found stating Supraglan had been discontinued was inaccurate. Petwellbeing distributed it from 2007 until 2012 and then ceased distributing it and replaced it with Adrenal Harmony Gold. But NHV Natural Pet Products still manufactures Supraglan.

This doesn’t change the substance of this post, since Petwellbeing marketed Supraglan with all the claims and testimonials discussed in the post on that product and then replaced it with a different product containing different ingredients and marketed in the same way. Both products lack sound scientific evidence to support the claims made for them.

The Petwellbeing.com page on Supraglan at the time of the original review can be found HERE.