This document provides background information on dietary supplement regulation in the United States. The Dietary Supplement Health and Education Act of 1994 established that supplements do not require FDA approval before going to market. This has led to safety concerns as supplements can be sold without testing. The document also discusses a study that found physicians have poor knowledge of supplement regulation. The author then outlines their methods for selecting supplements to research and provide recommendations on, which included a literature review of supplement safety. Key recommendations included whey and casein protein, branched chain amino acids, glutamine, creatine, and beta-alanine as supplements with research supporting their safety and benefits for athletes.

1. Supplements and FDA Regulation:
A User Friendly Guide
By: Zaryab Malik

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Background:
“The Dietary Supplement Health and Education Act (DSHEA) currently defines the term
dietary supplement as a product that is intended to supplement the diet and may contain one or
more dietary ingredients”11. DSHEA was passed in 1994 and helped establish how much
authority the FDA would have over supplement regulation. With its current definition, over
dietary supplements are categorized separately from food and drugs, and must therefore undergo
special rules and regulation. However, as the market expands, it is essential that the laws that
govern these products evolve as well. This act was passed 22 years ago, and it is essential that
additional changes be made since the supplement market has grown from around 4000 to
>85,000 different products as of 201411.
Dietary supplements are classified as such by the information that the manufacturer
provides, either on the label or in accompanying literature1. One a product is established as a

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dietary supplement, it can be sold to the public without FDA approval or premarket evaluation3.
This in turn creates a dangerous cycle because supplements can be put into the market without
any testing or screening, and may lead to potential public health hazards. “Instead, the FDA
relies on post-market surveillance efforts to identify a potential public harm”11, which leaves
them with the burden of collecting enough scientific data to prove harm and remove the product
from the market. Not only is this inefficient and costly, it renders general consumers as test
subjects, because their reactions are key determinants of the overall safety and legitimacy of the
supplement. The general population is unaware of this lack of governmental oversight and
regulation; therefore many turn to their respective physicians, friends and family for education.
However, a recent study conducted in 2006 determined that, “Physician knowledge of dietary
supplement regulation and adverse event reporting is poor”3. The study used a total of 335
physicians that were required to complete a pretest module aimed at supplement knowledge, and
the average score was only 59%. This is an important documentation because it displays a lack
of knowledge not only in the general population, but also amongst medical professionals.
As a moderate athlete and frequent consumer of dietary supplements, this issue sparks
many questions for me. Therefore, the purpose of this project is to review and address commonly
cited concerns with dietary supplements and to create a user-friendly manual that an everyday
consumer can refer to for guidance. My undergraduate training in the Exercise Science program
encompassed various disciplines, but primarily centered on the human body as it relates to
exercise and nutrition. Spending four years in this program has given me the opportunity to hone
in on my skills, and develop a life long foundation in this field. As my undergraduate studies
come to a close, this project has given me a chance to reflect on my overall Exercise Science
experience. This supplement guide is an opportunity to implement the knowledge I have

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acquired in my four years at The George Washington University, and to apply this knowledge
towards formulating a helpful aid for use in the general population. As the dietary supplement
market continues to grow, a project of this nature will have a lasting impact on supplement safety
for the everyday consumer.
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Methods:
1. Selection of Dietary Supplements
Given that there is a wide range of documented supplements available on the market, it
was important to establish parameters for selecting and reviewing dietary supplements. Thus, this
project specifically focused on 1) investigating the history of dietary supplement regulation, 2)
conducting an in-depth literature review to determine the safety of various dietary supplements

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available on the market, and 3) using the literature to compile a list of the safest supplements on
the market.
This project is not intended to provide medical advice, but rather, provides an opportunity
for everyday consumers to have a reliable and easy-to-use reference when deciding whether to
use supplements and in selecting specific supplements that best address their health, goals and
preferences. To narrow the research even more, the search was narrowed down to top
performance picks for athletes. This meant that vitamins, minerals, herbs, and other botanical
supplements were left out. Instead, the research looked at protein, amino acids, performance
enhancers, fat burners, and testosterone support. A majority of the supplements can fit into more
then one of these categories, but for the most part, we will be focusing on their main functions.
2. Comprehensive Literature Review
The majority of the research was conducted via online database searches through the
George Washington University portals. I utilized the SportDiscus and PubMed search engines to
help gather literature on the history and regulation of dietary supplements. The majority of the
collected articles supported one another, and provided an accurate representation of how the
supplement market has grown and been regulated. The majority of the information was pulled
from The American Journal of Clinical Nutrition, New England Journal of Medicine, and the
Clinical Pharmacology and Therapeutics. The specific information on individual supplements
was collected through the NIH’s Dietary Supplement Label Database1, 2 because they provided
comprehensive information on all documented supplements and their individual ingredients. The
site was easy to maneuver through and listed all supplements in alphabetical order along with
brand names and specific ingredients. The supplements that have been gathered for my

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recommendations have been chosen on a basis of most available information and documented
safety.
The style of this research is in the format of a systematic review, because it collected and
analyzed multiple pieces of literature and information. However, it is important to state that this
is in fact not an official systematic review, but the basic principles were utilized in order to
gather concise and agreed upon data. A topic like dietary supplements is most beneficial from
this type of study because there are thousands of supplements on the market and there is not a
consensus study on each individual ingredient. Some supplements are thoroughly researched and
backed by human studies, while others are relatively new and up for debate. For this very reason,
it is important to gather data from multiple sources instead of relying only on scientific literature.
Another major reason for performing research in this manner is because it is quicker and cheaper
then most other methods. It was much more cost efficient to look at preexisting data then
embarking on a completely new study.
Results:
It is important to reiterate that dietary supplements are not tested to the same
extent as food and drug items, and must therefore undergo very different legislation. Since they
are not pre-evaluated, there have been various concerns over safety amongst the general
consumer. In fact, this guide is geared toward the everyday consumer that is looking for aid in
picking safe and reasonable options when trying to choose dietary supplements. Provided below
is a compilation of various adverse effects that may occur when ingesting certain legal
ingredients commonly found in dietary supplements. While these unfavorable consequences are
not linked to specific supplement, this table highlights the importance of ensuring that dietary

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supplements are labeled appropriately and that ingredients are incorporated only in quantities
known to be safe.
Cohen PA. Hazards of Hindsight - MonitoringThe Safetyof Nutritional Supplements. N Engl J Med.2014;370(14):1277-1280.
doi:10.1056/NEJMp1315559.
None of the listed supplements have been approved to diagnose, cure or prevent any
disease and should not be considered on that premise. Each category of recommendation has 2
listed supplements that have been adequately supported by research or have otherwise been on
the market for extended time. Ensuring adequate time on the market is vital because supplements
are regulated by a post market surveillance system. This means that the FDA has had enough
time to monitor and survey the product and take into consideration any reported risks by
consumers.

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Recommendations:
Protein
 Whey Protein- Whey is derived from cow’s milk and has been on the market for quite
some time. It is very fast digesting and provides an abundant source of branched chain
amino acids, which help stimulate protein synthesis. Whey protein supplements are
widely used amongst strength and endurance athletes because they have a very fast rate
of digestion. If used properly alongside a healthy diet and weight lifting program, whey
protein supplementation can support the development of lean body mass. Whey is most
commonly used as a recovery supplement after workouts, but can also be implemented
into various parts of the day to fulfill macronutrient needs. A recent study published
earlier this year, took a look at the effectiveness of whey supplementation as it pertains to
recovery rates in children. Specifically, the study looked at children who suffered from
moderate malnutrition, and how supplementation would aid their recovery rates. The
study concluded, “The proportion of children that recovered from moderate acute
malnutrition (MAM) was significantly higher in the group that received whey ready-to-
use supplementary food (RUSF) than in the group that received soy RUSF”8. The
children who received whey supplementation also demonstrated greater growth markers,
including higher: mean arm circumference, mean height to weight score, and overall
weight gain. Another recent study looked instead at healthy adult patients and the
effectiveness of whey supplementation on building lean mass and strength. Alongside
bouts of physical activity, whey supplementation was found to help increase fat-free
mass, and handgrip strength7. It is important to note that this study supplemented amino
acids and vitamin D alongside whey protein. While this may seem contradicting, most

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whey protein supplements on the market already contain added amino acids in order to
have a complete profile for protein synthesis. Overall, the main takeaway is that whey
protein supplementation has been proven safe and effective for quite some time, and
should be highly considered by anyone looking to make an entrance into the supplement
market.
 Casein Protein- Casein protein also comes from cow’s milk, but makes up about 80% of
that milks profile. Much like whey, casein protein contains all of the essential amino
acids and helps stimulate protein synthesis. A key difference however, is that casein
protein digests much slower and is a longer lasting protein source. Casein is not generally
used post or pre-workout because of how slow the amino acids digest, often settling in
the stomach. Instead, casein can be seen as a helpful meal replacement for nighttime
snacking or times of the day where frequent or adequate meals cannot be acquired.
Taking casein before bed is very helpful because it does not provide a strong surge of
energy. Instead, the slow digestion can help combat the state of fasting your body is in
during sleep and slowly provide protein synthesis and re-synthesis. Another helpful
benefit of casein supplementation is that it helps the consumer stay full and suppresses
appetite because of how long it digests in the stomach. This can be a benefit when trying
to cut weight or build clean muscle mass. Since casein is derived from the same source as
whey, it mirrors its properties and effectiveness very well. In fact, both supplements are
often taken in conjunction because they serve the same purpose but at varying times of
the day. Casein protein is essentially the same as whey in that they both aid protein
synthesis, but casein can be thought of as “long lasting”.

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Amino Acids
 Branched chain amino acids- The three branched chain amino acids, Leucine, Isoleucine
and Valine, are the only amino acids to actually be used by muscles during exercise. This
is very important because they serve various functions for the muscles, both during and
after and exercise bout. The biggest benefit of BCAA’s is that they provide very fast
muscle recovery and can therefore help avoid onset muscle soreness. The main principle
of BCAA’s is that it puts your body in an anabolic environment ready to synthesize
proteins, thus reversing the breakdown effect that exercise puts on your muscles. In other
words, BCAA’s provide greater bioavailability of substrate to improve protein synthesis4.
One study demonstrated the effectiveness of BCAA supplementation on muscle recovery
and reduced soreness. When comparing against a placebo group, “There were significant
group effects showing a reduction in creatine kinase efflux and muscle soreness in the
BCAA group”4. The study implemented 12 randomly assigned men to either the placebo
or BCAA test group, and asked each individual to perform 100-drop jumps. This
damaging exercise was selected to see which group would recover the fastest and most
effectively when all other factors were held consistent. BCAA’s are marketed as a
bodybuilding supplement, but can even be very useful for sprinters and other endurance
athletes that require large amounts of muscle recovery. BCAA’s can be taken before and
after workouts but are generally recommended for after because they are mainly used for
muscle recovery and protein synthesis. Most whey protein supplements have naturally
occurring or added BCAA’s in their ingredient list, so they are generally easy to acquire.
Due to its safety and high degree of benefits for athletes, this supplement makes a great
addition to any nutrition plan.

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 Glutamine- Glutamine is the most common amino acid in your skeletal muscles, and
comprises more then half of it. The main takeaway from glutamine supplementation is
that it helps with protein synthesis and reduces the excessive breakdown of muscles.
Glutamine should be supplemented after intense exercise because it helps with recovery
by restoring strength and stamina within the muscles. Similar to BCAA’s, supplementing
with glutamine allows your body to be placed into an anabolic environment by
encouraging protein synthesis and preventing any further breakdown via intense exercise.
A study from 2009 looked at the effects of glutamine supplementation on skeletal muscle
contractile dysfunction, which was induced by an inflammatory chemical. The idea of the
study was to induce an inflammatory environment similar to what the body experiences
during exercise, and therefore limit the maximal muscle force the subjects could exert.
The glutamine test groups were then introduced to the supplement to see if it would
negate or reduce the effects brought on by inflammation. In conclusion, the glutamine
test group showed viable results and returned full functionality and muscle force to the
subjects. Glutamine supplementation provides an effective, novel, and clinically
applicable means of preserving muscle force during acute inflammation5. Although there
is not much conclusive evidence, glutamine supplementation has been believed to
improve intestinal function and even support immune response. Because the intestinal
tract is lined with smooth muscle, glutamine has shown signs recovery benefit in this
aspect as well. Because it is difficult to keep track of individual ingredients and buy
various separate supplements, the best options are to find products that incorporate all or
some of these recommendations.

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Performance Enhancers
 Creatine- Creatine is a supplement that usually tops consumer’s supplement list because
of its ability to help power through workouts. In general, the body utilizes creatine
kinase, a naturally occurring enzyme, to help breakdown and make use of adenosine
triphosphate (ATP). ATP is thought of as the body’s energy currency and is found in
skeletal muscle, the brain, heart etc. Thus, creatine kinase serves as an energy reservoir
because it helps buffer and regenerate ATP in these important areas. Creatine
supplementation comes into play by introducing your body to an outside creatine source
and creating a creatine rich environment in the body. The idea is that there will be more
creatine readily available for your body to utilize and turn into energy (ATP). Creatine
has a wide range of benefits all stemming from the principle of ATP buffering and
regeneration. The supplement has been shown to increase strength, power and longevity.
Because the creatine users are generally able to pump through workouts at a higher
intensity, they often equate to gaining more muscle mass because they can place their
bodies under strain and tension for larger bouts. A 2006 study looked at all of the varying
benefits of creatine by placing test subjects in a 10-week resistance training program. The
subjects were assigned to either a placebo, creatine, or creatine plus beta-alanine group.
The subjects were assessed for strength power and body composition by performing
bench press, squats, and Wingate tests. When looking at improvements in 1-rep max, the
creatine (C) and creatine plus beta-alanine (CA) groups showed improvements in total
kilograms lifted. When looking at strength comparisons however, the C group showed a
half-fold greater improvement and demonstrated better intensity and overall lifting
strength3. Overall, creatine has various qualities that make it a useful supplement, but it is

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important to understand how it works and what areas can be improved. Creatine can be
taken before or after a bout of exercise because it not only helps power individuals
through workouts, but also has tremendous recovery benefits once the exercise is
completed.
 Beta-Alanine- Beta-alanine is an amino acid that essentially reverses the acidic build up
brought on by exercise, and thus reduces fatigue. Lactic acid build up in the muscles is a
natural process that occurs during weight lifting and high intensity cardio. By taking beta-
alanine, consumers essentially build up natural carnosine, which behaves as a blood and
muscle buffer. Increased levels of beta-alanine equate to increased carnosine and thus
less acid build up. This allows athletes supplementing with beta-alanine to fight off
muscular fatigue and continue through workouts at close to maximal levels. Studies have
shown that beta-alanine is most effective when paired with creatine. The same study
discussed above took a look at how effective this pairing would be when compared to
creatine alone, alongside a placebo group. “The addition of β-alanine to creatine appeared
to enhance training volume more so than supplementing with creatine alone. In addition,
β-alanine supplementation appeared to have the greatest effect on lean tissue accruement
and improvements in body fat composition”3. While the study found creatine to be
effective, it established that a pairing with beta-alanine with have significantly better
results, two-fold to be exact. Once again, beta-alanine isn’t usually market individually,
and is often found with other supplements. Most pre-workout and recovery supplements
often incorporate beta-alanine in small doses for the muscle buffer effect. Supplements

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that pair creatine and beta-alanine together are highly recommended because of their joint
role in reducing fatigue and muscle damage.
Fat Burners
 Caffeine- Caffeine is widely consumed from various foods and products including coffee,
tea, chocolate etc. Pure caffeine can be derived and made available in supplement form to
harness its full benefits, either in pill or powder form. In short, caffeine is a central
nervous system stimulant, and helps the respective user feel more alert and focused.
Strength and endurance athletes can benefit from these effects, because it essentially
makes exercise easier for them. Not only does caffeine supplementation help focus on the
task or exercise at hand, but it also helps your nervous system fire more readily and gives
you optimal control over your muscles via neuromuscular junctions. Caffeine is often
found in various pre-workout and fat-burning supplements due to its varying benefits.
Most fat burning supplements include caffeine because of its ability to free up fatty acids
into the bloodstream. A study published in 1999 looked to investigate whether green tea
extract, by virtue of its high caffeine content, could increase 24-hour energy expenditure
and fat oxidation. 10 healthy men were tested at 3 separate occasions during the day by
breathing into a respiratory chamber. Energy expenditure, respiratory quotient and
urinary excretion of nitrogen were looked at to determine viable results. When compared
to the placebo group, the green tea extract resulted in a significant increase 24-hour
energy expenditure and fat oxidation2. Because of its thermogenic properties, along with
its various uses for focus and alertness, caffeine is a highly recommended supplement.
The benefits of caffeine apply to both the physical and mental aspects of performance and

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should definitely be utilized if seeking an extra edge during exercise. It is important to
note that caffeine often dehydrates the user, so it is recommended to increase daily water
intake if incorporating this supplement. High doses have also shown harmful side effects
like elevated heart rate and dizziness, so it is important not to take more then 200mg in
any one sitting. Caffeine should also be avoided before bed times, because they have a
prolonged half-life in the blood stream and can often cause insomnia.
 Conjugated linoleic acid- Conjugated linoleic acid (CLA) had been discovered for quite
some time, but is relatively new on the supplement scene. Various animal studies have
been conducted in the past and concluded that CLA was very effective in reducing body
fat levels. CLA is itself a special type of fat found in meats, cheese and milk but in very
low quantities. Because they are so hard to obtain through the diet, large quantities of
CLA are derived from sunflower and safflower oil and made into supplement form. In a
recent study, 81 postmenopausal women were subjected to a 16-week intervention which
required them to take either the unidentified placebo or CLA capsule while keeping a
through food record. The extent of the trial was long enough to observe a long-term effect
brought on by CLA supplementation, as opposed to short varying changes that could
possibly be errors. In conclusion, it was found that that the patients who received the
CLA capsules showed a decrease in overall fat mass and a bigger decrease in lower body
fat mass6. This demonstrated a drastic effect brought on by the CLA supplementation
when compared to the placebo group. Studies like this have been replicated under various
different conditions, but it is helpful to know that there are positive studies already out

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there. While CLA could potentially use some more research, its safety and naturally
occurring nature make it a must have supplement with potential weight loss benefits.
Conclusion: Because it is difficult to keep track of individual ingredients and buy various
separate supplements, the best options are to find products that incorporate all or some of these
recommendations. While there are thousands of individualized supplements on the market, these
6 stuck out to me for various reasons. When making this recommendation list, it was important
to do thorough background research on each individual ingredient. By looking for literature on
the safety, effectiveness and availability of various items, I was able to narrow down my top
picks to these select ingredients. These three search criteria were the essential backing of why
these supplements were selected. Although the FDA does not regulate these supplements, there
is enough literature and research to back their effectiveness.
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General References
1. Dietary supplement fact sheets. https://ods.od.nih.gov/factsheets/list-all/.
2. Dietary supplement label database (DSLD).
https://ods.od.nih.gov/Research/Dietary_Supplement_Label_Database.aspx.
3. Ashar B, Rice T, Sisson S. Physicians' understanding of the regulation of dietary supplements.
Archives of internal medicine (1960). 2007;167(9): 966-969.
4. Cermak N, Res P. Protein supplementation augments the adaptive response of skeletal muscle to
resistance-type exercise training: A meta-analysis. Am J Clin Nutr. 2012;96(6):1454; 1454-1464;
1464.
5. Cohen PA. Hazards of Hindsight - Monitoring The Safety of Nutritional Supplements. N Engl J
Med. 2014;370(14):1277-1280. doi:10.1056/NEJMp1315559.
6. Frankos V, Street D, O'Neill R. FDA regulation of dietary supplements and requirements
regarding adverse event reporting. Clin Pharmacol Ther. 2010;87(2): 239-244.
7. Galvan E, Walker D, Simbo S. Acute and chronic safety and efficacy of dose dependent creatine
nitrate supplementation and exercise performance. Journal of the International Society of Sports
Nutrition. 2016;13:12; 12.
8. Kendall K, Moon J, Fairman C. Ingesting a preworkout supplement containing caffeine, creatine,
β-alanine, amino acids, and B vitamins for 28 days is both safe and efficacious in recreationally
active men. Nutrition Research. 2014;34(5): 442-449.
9. Marcus D. A commentary on the american society for clinical pharmacology and therapeutics
position statement on dietary supplement safety and regulation. Clin Pharmacol Ther.
2005;78(2): 114-117.

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10. Posadzki P, Watson L, Ernst E. Contamination and adulteration of herbal medicinal products
(HMPs): An overview of systematic reviews. European Journal of Clinical Pharmacology.
2013;69(3): 295-307.
11. Wallace T. Twenty years of the dietary supplement health and education act--how should dietary
supplements be regulated? J Nutr. 2015;145(8): 1683-1686.
12. Williams M. Dietary supplements and sports performance: Amino acids. Journal of the
International Society of Sports Nutrition. 2005;2(2):1-5. http://dx.doi.org/10.1186/1550-2783-2-
2-63. doi: 10.1186/1550-2783-2-2-63.
Recommendation References
1. Collier SR, Casey DP, Kanaley JA. Growth hormone responses to varying doses of oral
arginine. Growth Horm IGF Res. 2005 Apr;15(2):136-9. Epub 2005 Jan 26.
2. Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J.
Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h
energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999 Dec;70(6):1040-5.
3. Hoffman J, Ratamess N, Kang J, Mangine G, Faigenbaum A, Stout J. Effect of creatine and
beta-alanine supplementation on performance and endocrine responses in strength/power
athletes. Int J Sport Nutr Exerc Metab. 2006 Aug;16(4):430-46.
4. Howatson G, Hoad M, Goodall S, Tallent J, Bell PG, French DN. Exercise-induced muscle
damage is reduced in resistance-trained males by branched chain amino acids: a randomized,
double-blind, placebo controlled study. J Int Soc Sports Nutr. 2012 May 8;9(1):20.
5. Meador BM, Huey KA. Glutamine preserves skeletal muscle force during an inflammatory
insult. Muscle Nerve. 2009 Aug 24. [Epub ahead of print]

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6. Raff M, Tholstrup T, Toubro S, Bruun JM, Lund P, Straarup EM, Christensen R, Sandberg
MB, Mandrup S. Conjugated linoleic acids reduce body fat in healthy postmenopausal
women. J Nutr. 2009 Jul;139(7):1347-52. Epub 2009 Jun 3.
7. Rondanelli M, Klersy C, Terracol G, et al. - Whey protein, amino acids, and vitamin D
supplementation with physical activity increases fat-free mass and strength, functionality,
and quality of life and decreases inflammation in sarcopenic elderly. - The American Journal
of Clinical Nutrition. (- 3):- 830.
8. Stobaugh HC, Ryan KN, Kennedy JA, et al. Including whey protein and whey permeate in
ready-to-use supplementary food improves recovery rates in children with moderate acute
malnutrition: A randomized, double-blind clinical trial. Am J Clin Nutr. 2016;103(3):926