Page 135 - JSOM Winter 2018

TABLE 1 Selection of “Ingredients” Found in Dietary Supplements structurally similar to testosterone and other anabolic steroids,
That Could Cause Harm and Are Actually Drugs it did not address other “anabolic substances,” such as growth
Methylhexanamine hormone and designer peptides, SARMS, selective estrogen re-
Anabolic steroids Sildenafil analogues
(DMAA) ceptor modulators, and so forth, because these substances are
Selective androgen not “structurally similar” to testosterone and other anabolic
Aromatase inhibitors Tadalafil receptor modulators steroids, As such, SARMS are in the gray area.
Selective estrogen
Sibutramine Modafinil/adrafinil
receptor modulators Importantly, the science to support the anabolic claim of
Growth hormone
Prohormones Tamoxifen SARMS is nonexistent in a healthy population, and although
secretagogues FDA has called out a couple of companies for selling them
DMAA, 1,3-dimethylamylamine. in DSs, the products are still being sold. The US Special Op-
erations Command does have a policy prohibiting the use of
Contaminated products can also be found within categories SARMS and other such substances, but when they are hidden
generally considered safe, such as multivitamin and mineral in DSs, there is no way of knowing. Finally, SARMS and all
products. One such example is a liquid multivitamin and the other ingredients listed in Table 1 are on the World An-
mineral DS that was widely distributed. After the initial case ti-Doping Agency (WADA) list of prohibited substances, so
was recognized, more than 200 additional cases were iden- athletes will be banned from competition if they are found
tified: The product contained 200 times the amount of sele- to be taking any of them. In the military, we currently do not
nium (trace element) on the label and selenium toxicity was test for such substances, in particular steroids, unless there is
noted in all cases. The contamination was accidental, but this cause.
demonstrates the quality of DS products is neither assured nor
uniform. For this reason, we always encourage those who do Another gray area relates to NDIs. Two short examples are
use supplements to only purchase DSs that have been “third- provided. The first relates to a derivative of the hormone de-
party” certified or verified, as discussed later in this article. hydroepiandrosterone (DHEA), which is an allowed DS in the
military but is on the WADA list. Another substance on the
One example is provided of a product claiming to build mus- WADA list is 7-keto DHEA, a relative of DHEA. In 2004, a
cle. An unnamed product was purchased and analyzed on the company submitted a NDIN for 7-keto DHEA and received
basis of a question from the field. On the label were three an Acknowledgement from the FDA; thus, the compound can
ingredients, as shown in Table 2. The recommendation was be present in DSs. The compound 7-keto DHEA is consid-
to take one tablet twice a day; the mass of each tablet was ered a prohormone, but the literature documenting any benefit
0.5g, so the total to be taken was 1g/d. None of the ingredients is limited. However, the safety information submitted to the
on the label was identified in the analysis, but the ingredients FDA must have been sufficient to convince the agency there
noted in Table 2 were found. If any SOF Operator were to take was “reasonable assurance that the ingredient does not pres-
that product, hepatic injury would be likely. Unfortunately, ent a significant or unreasonable risk of illness or injury.”
this is just one of many possible examples.
The next example is related to the DS creatine. Thousands
TABLE 2 One Example of an Adulterated Product Being Marketed of studies demonstrate the safety and efficacy of creatine for
as a Dietary Supplement certain physical tasks; the form used in the studies was cre-
Analysis and atine monohydrate. In 2018, multiple forms of creatine are on
Label: Proprietary Blend: 150mg Daily Dose the market, including creatine ethyl ester HCl. However, an
1-Androstene-3bol,17-one decanoate 1-Androsterone: 10mg/d NDIN was submitted and the company received an Objection,
4-Androstene-3b-ol,17-one ethanthate Androstanedione: 78mg/d which means all products currently being sold with those in-
(25 R)-5alpha-spirostan-2alpha, 3beta, 2-Androsten-17-one: gredients could be considered adulterated. However, the FDA
5alpha-triol-6-OH 63mg/d does not have the resources to go after all the companies sell-
Note: Label ingredients are written as on the actual label. ing products with those ingredients.

Gray Areas The final gray area relates to resource constraints and public
“Gray areas” are defined as gaps in oversight, regulatory health. The FDA warned consumers in 2013 that 1,3-dimeth-
framework, and public confusion. Several examples are pro- ylamylamine (DMAA) was not a legal dietary ingredient and
vided here to make the topic clearer. The major topic areas could cause considerable harm. However, DMAA can still be
relate to “unapproved drugs,” NDIs, and resource constraints. found in multiple DS products in varying amounts; it is either
Table 1 lists various ingredients; some are unapproved drugs named on the label as an ingredient or found in adulterated
or drugs undergoing clinical trials for specific indications. Se- products. The public is the loser here, because problematic in-
lective androgen receptor modulators (SARMs) are the best gredients such as DMAA are being sold and pose a risk, but
example of this. SARMS are found in a wide variety of DSs the FDA does not have sufficient resources to enforce current
with expected “anabolic” actions. Anabolic products include guidance.
testosterone, which is FDA approved for clinical use, and
many other “testosterone-like substances.” Many of the ana- Adverse Events
bolic steroids are regulated by the Designer Anabolic Steroid Over the past 25 years, Servicemembers, including SOF per-
Control Act (DASCA) of 2014, which amended the Act of sonnel, have experienced mild to serious AEs in association
2004 by adding 22 more anabolic steroids to the definition, with taking DSs. Some have died and others have been hospi-
expanding temporary and permanent scheduling authority, talized or suffered serious consequences. 40-47 Hepatic injuries
and establishing new penalties related to false labeling. Al- are not uncommon. 43,45–47 In 2010, Hughes et al. reported on
43
though DASCA did provide authority to control substances 18 SOF Operators who had suspected hepatic dysfunction as
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