Questions to Ask Before Buying Nutritional Supplements

The supplement industry is a vast and lucrative one, with revenues set to approach $300 billion in the coming years [1].

Since the recent COVID-19 pandemic, more than 43% of supplement users are taking more supplements than they did pre-pandemic and more than 50% of adults in the USA are now taking a dietary supplement overall [1,2].

But have you seen the news? Over the last several years, there have been hundreds of stories about adulterated supplements, supplements that don't even have the listed active ingredients in them, supplements that have actual pharmaceuticals in them (like Viagra...yes, Viagra!), and myriad other issues. 

How can you know if the supplements you are taking are safe and effective when (a) the supplement industry is completely unregulated by the FDA and (b) we have the unenviable task of choosing from millions of products and thousands of brands on the market? 

This article will help you navigate. Let's dive in!

First, we'll get into the business of supplement regulation, and then at the end, we'll help you fine-tune your supplement choices!

What is Supplement Quality and Why is it Important? 

As consumers, it is crucially important that the claims on product labels are accurate and supported by research evidence. We need to pay attention to the ingredients and composition of particular products as well as the methods used to harvest and make them. Certain companies apply strict microbiological testing to their products to ensure safety and also provide high-quality technical information on each ingredient that they source. Many do not. 

Key considerations for supplement quality should include the composition and ingredients as the first port of call. Regulation, compliance, and certifications should closely follow, as well as brand reputation and the manufacturing processes used for the product. Brands with a focus on quality will often use pharmaceutical-grade facilities and equipment to manufacture their supplements or will work with third-party manufacturers that adhere to the same ethos or principles.

Product level testing is also an important aspect of supplement quality (see below). Tests for pesticides and other contaminants such as heavy metals, as well as certifications to this effect, demonstrate a high degree of rigor and a commitment to quality.

There are also differences within categories of supplements, as shown by examples like fish oil [9,10]. Often, the quality and composition of these supplements rarely aligns with the label, and in isolated cases, large amounts of soybean oil has been found, which is a true adulteration. Agreement with the label is not the only measure of quality for these supplements though. Analysis of the overall fatty acid composition has noted high amounts of saturated fatty acids in some products, suggestive of an insufficient or non-existent purification process, as well as a safety concern due to the presence of toxic contaminants [11].

What Does "Third-Party Testing" Mean? 

Third-party testing is a process whereby an independent third-party organization performs specific tests that verify the safety of a nutritional supplement. Examples of this from a sports setting include Informed Sport and the NSF Certified for Sport, organizations that test every batch of products before market release and assert that products do not contain substances that are banned in sports, do not have faulty labelling information, and that unsafe and doping-related contaminants are not present [12]. With that said, most products will not undergo third-party testing in any meaningful way simply due to the huge range of products that are available and the costs associated. 

Lack of Oversight in Supplement Manufacturing 

The Dietary Supplement Health and Education Act of 1994 indicates that dietary supplement products must be manufactured free of contamination or adulteration. However, it also allows these products to be sold in the United States without providing proof of their quality to the Food and Drug Administration (FDA) [13]. In fact, it could be said that there is an "innocent until proven guilty" attitude in place, in that the FDA can only remove products from sale if it can prove that they are unsafe.

Supplement manufacturers are also not required to demonstrate clinical efficacy [14]. However, a supplement may not claim to diagnose, treat, cure, or prevent any disease [15,16]. Nevertheless, a study of 443 websites of 8 best-selling herbal products revealed that 81% made one or more health claims, and another study showed that 75% of popular herbal supplement labels contained none of the safety messages about warnings for medical conditions, drug interactions, and side effects.

With such a huge volume of products in the market, there is very little oversight until an instance of harm takes place. Products can be contaminated with microbials, heavy metals, synthetic drugs [17-19], and other substances [13,20]. There have also been instances of fraudulent specification of ingredients on labels [21].

Where possible, consumers should exercise due caution in identifying products and make themselves aware of the potential health risks.

Other Factors at Play When Assessing Supplement Quality

Bioavailability

Let's chat some easy pharmacology. Yes, there is such a thing!

The bioavailability of a particular compound can make or break supplement effectiveness. 

Bioavailability is a term that describes the absorption and utilization of a nutrient. This can be affected by gender, physiological state, and the coexistence of pathological conditions such as liver dysfunction [3]. 

Oral bioavailability of various supplements can vary widely depending on the compound/mixture of compounds along with the route of ingestion. From as little as 10% for NAC (N-acetylcysteine) to almost 100% for methylene blue.

Recent developments in enhancing the bioavailability of dietary supplements have included the use of liposomal technology [4]. The liposome is a phospholipid barrier that encases the active supplement, protecting it from stomach acid and supporting the delivery of the supplement to where it needs to go. This approach, when applied to vitamin C supplements, improved bioavailability by 1.77 times, and demonstrates the benefits of such a delivery method in this context [5].

The buccal troche, although available for many years from compounding pharmacies, was only recently commercialized for mass consumption by Troscriptions. Buccal troches bypass first-pass metabolism in the liver, thus preserving ingredient bioavailability. The troche is placed between your upper cheek and gums and dissolves over 15 to 30 minutes, leveraging the 8 layers of mucosa in this area for efficient absorption. 

Route of Administration

The route of administration (buccal, sublingual, oral, IM, IV, intranasal, etc.) has a huge impact on product effectiveness, and of course, how the fast the effects will be.

IV administration will work the fastest, followed by IM, inhaled, buccal, sublingual, and then oral. 

The key to remember is that some products simply won't work if taken the wrong way. Let's take the neurotransmitter gamma-aminobutyric acid (GABA), for example 

At present, it is thought that orally ingested GABA cannot pass the blood-brain barrier [6]. A potential workaround for this is to consume glutamic acid that can increase brain GABA levels.

Taking GABA as N-nicotinoyl-GABA (GABA attached to a vitamin B3) also dramatically improves blood-brain barrier permeability. You can find this form of GABA in our product Tro Calm for relaxation and the relief of stress/tension.

The takeaway? Choose your route wisely depending on your needs! And do your research to make sure the supplements you are taking are absorbed in the form you are taking them. 

Half-Life

The half-life of a substance is the time it takes for the body to eliminate half of it and is a term that is derived from drug metabolism. Melatonin, for example, has a half-life of 40 to 60 minutes [7,8], and after four or five half-lives is completely eliminated. It is therefore unlikely to remain in the system for the duration of the night, although slow-release formulations are also on the market.

Troscriptions 

Here at Troscriptions, we care deeply about the quality of our products. This is why make sure we have certificates of analysis for all our ingredients, most are pharmaceutical grade with extensive third-party testing (especially our methylene blue), and our troches are made in a GMP-compliant lab under the supervision of a compounding pharmacist with 30 years of experience. 

Long story short: Check your supplement labels, buy from reputable manufacturers, and don't swallow your drugs if there is a troche for it!

References 

[1]        Z. Shi, A. Yan, Dietary Supplements: Are Current Policies Adequate for Promoting Health?, Nutrients. 12 (2020) 3449. https://doi.org/10.3390/nu12113449. 

[2]        P.A. Cohen, S. Bass, Injecting Safety into Supplements - Modernizing the Dietary Supplement Law, N Engl J Med. 381 (2019) 2387–2389. https://doi.org/10.1056/NEJMp1913004. 

[3]        N.F. Krebs, Bioavailability of dietary supplements and impact of physiologic state: infants, children and adolescents, J Nutr. 131 (2001) 1351S–4S. https://doi.org/10.1093/jn/131.4.1351S. 

[4]        M. Daeihamed, S. Dadashzadeh, A. Haeri, M.F. Akhlaghi, Potential of Liposomes for Enhancement of Oral Drug Absorption, Curr Drug Deliv. 14 (2017) 289–303. https://doi.org/10.2174/1567201813666160115125756. 

[5]        S. Gopi, P. Balakrishnan, Evaluation and clinical comparison studies on liposomal and non-liposomal ascorbic acid (vitamin C) and their enhanced bioavailability, J Liposome Res. 31 (2021) 356–364. https://doi.org/10.1080/08982104.2020.1820521. 

[6]        P. Hepsomali, J.A. Groeger, J. Nishihira, A. Scholey, Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review, Front Neurosci. 14 (2020) 923. https://doi.org/10.3389/fnins.2020.00923. 

[7]        M. Emet, H. Ozcan, L. Ozel, M. Yayla, Z. Halici, A. Hacimuftuoglu, A Review of Melatonin, Its Receptors and Drugs, Eurasian J Med. 48 (2016) 135–141. https://doi.org/10.5152/eurasianjmed.2015.0267. 

[8]        L.P.H. Andersen, M.U. Werner, M.M. Rosenkilde, N.G. Harpsøe, H. Fuglsang, J. Rosenberg, I. Gögenur, Pharmacokinetics of oral and intravenous melatonin in healthy volunteers, BMC Pharmacol Toxicol. 17 (2016) 8. https://doi.org/10.1186/s40360-016-0052-2. 

[9]        M. Ahmed, A.A. Moazzami, R. Andersson, J. Pickova, Varying quality of fish oil capsules: fatty acids and tocopherol, Neuro Endocrinol Lett. 32 Suppl 2 (2011) 37–40. 

[10]      A.A. Jairoun, M. Shahwan, S.H. Zyoud, Fish oil supplements, oxidative status, and compliance behaviour: Regulatory challenges and opportunities, PLoS One. 15 (2020) e0244688. https://doi.org/10.1371/journal.pone.0244688. 

[11]      T. Nevigato, M. Masci, R. Caproni, Quality of Fish-Oil-Based Dietary Supplements Available on the Italian Market: A Preliminary Study, Molecules. 26 (2021) 5015. https://doi.org/10.3390/molecules26165015. 

[12]      K.A. Vento, F.C. Wardenaar, Third-Party Testing Nutritional Supplement Knowledge, Attitudes, and Use Among an NCAA I Collegiate Student-Athlete Population, Front Sports Act Living. 2 (2020) 115. https://doi.org/10.3389/fspor.2020.00115. 

[13]      C.M. White, Dietary Supplements Pose Real Dangers to Patients, Ann Pharmacother. 54 (2020) 815–819. https://doi.org/10.1177/1060028019900504. 

[14]      R.L. Bailey, Current regulatory guidelines and resources to support research of dietary supplements in the United States, Crit Rev Food Sci Nutr. 60 (2020) 298–309. https://doi.org/10.1080/10408398.2018.1524364. 

[15]      C.A. Morris, J. Avorn, Internet marketing of herbal products, JAMA. 290 (2003) 1505–1509. https://doi.org/10.1001/jama.290.11.1505. 

[16]      J.E. Gibson, D.A. Taylor, Can claims, misleading information, and manufacturing issues regarding dietary supplements be improved in the United States?, J Pharmacol Exp Ther. 314 (2005) 939–944. https://doi.org/10.1124/jpet.105.085712. 

[17]      C.M. White, Continued Risk of Dietary Supplements Adulterated With Approved and Unapproved Drugs: Assessment of the US Food and Drug Administration’s Tainted Supplements Database 2007 Through 2021, J Clin Pharmacol. 62 (2022) 928–934. https://doi.org/10.1002/jcph.2046. 

[18]      R. Carvajal, Contaminated dietary supplements, N Engl J Med. 362 (2010) 274; author reply 274. https://doi.org/10.1056/NEJMc0911467. 

[19]      J. Tucker, T. Fischer, L. Upjohn, D. Mazzera, M. Kumar, Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings, JAMA Netw Open. 1 (2018) e183337. https://doi.org/10.1001/jamanetworkopen.2018.3337. 

[20]      R.S. Pawar, E. Grundel, Overview of regulation of dietary supplements in the USA and issues of adulteration with phenethylamines (PEAs), Drug Test Anal. 9 (2017) 500–517. https://doi.org/10.1002/dta.1980. 

[21]      K. Rosenberg, Dietary Supplement Labels May Be Inaccurate and Misleading, Am J Nurs. 122 (2022) 56. https://doi.org/10.1097/01.NAJ.0000904100.46205.b5.