Author: Adrianna Levesque, MD (Senior EM Resident at SAUSHEC, US Army) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Athletes, active adults, and military personnel consume protein drinks with the intent to enhance exercise performance, maximize ability to develop muscle mass, and improve recovery after exercise. However, the decision of which supplements to utilize are based largely on marketing claims instead of available evidence-based medicine. It is questionable as to whether some of these supplements are effective at all. Additionally, some supplements require very specific timing of consumption in conjunction with exercise for best results and others enhance performance in only certain exercise regimens. More importantly, a few of these supplements have been implicated in adverse events requiring hospitalization.1

What are the intended ingredients in your dietary supplements?

Supplements contain several sources of protein, which most commonly are: whey, casein, soy, pea, and rice proteins. Many of these products also contain glutamine, creatine, antioxidants, essential fatty acids, and several minerals such as selenium, zinc, iron and chromium. Additionally, these products may contain caffeine, yohimbine, and synephrine

What are the expected benefits of dietary supplementation?

The estimated consumption of protein supplements in college athletes, recreationally active adults, and active duty military personnel is approximately 20%. Most people who consume protein products assume that they will enhance muscle strength, improve performance, promote health, provide energy, and enhance weight loss.2 The theory is that amino acid intake stimulates uptake into muscle increasing synthesis.3 While scientific evidence does indicate that supplemental protein may confer metabolic advantages to moderately active people during periods of sustained energy deficit, it is likely that the majority of these people who consume a normal diet can meet their dietary protein needs without supplementation.2

One study indicated that supplementation with whey protein and creatine in male subjects increased lean body mass as well as performance on specific exercise measures.4 Another study looked at supplementation with essential fatty acids with and without protein supplementation and demonstrated that the addition of protein supplements after exercising increased the amount of net whole body protein gain. Thus, this study demonstrates that the timing of protein supplement consumption may be the key to benefits gained.5

What are the cons of consuming too many dietary supplements?

Dietary supplements often contain multiple ingredients and are often used as meal replacements. Some of the ingredients in these products may be harmful if ingested in excess. Over a one-year period, the California Poison Control Center reported 275 patients with adverse events related to dietary supplements. Of these, 112 had sympathomimetic symptoms. Eight of those adverse events required hospitalization, three of which were admitted to intensive care units. One death was reported and was due to a stroke in a patient who took multiple caffeine- and yohimbine-containing supplements.6

One of the most common issues seen with dietary supplements is that many of their components do not improve performance or increase weight loss, muscle mass or lean body mass.1,7-9 There is some concern that excessive protein intake may lead to kidney injury; however, in healthy individuals with normal kidney function, there is no solid evidence to support this.10 Some studies have shown hepatotoxicity associated with dietary supplement consumption, however there has been no direct link to specific causative agents within these supplements.

CREATINE

What are the expected benefits of creatine supplementation?Studies suggest that this supplement provides the most benefit in both male and female athletes involved in short stints of high-intensity exercise.12,13 Common sports that seem to benefit from creatine include soccer, football, squash, and lacrosse. The majority of the literature indicates that supplementation with creatine does lead to increased body mass.13 Furthermore, studies show that creatine may be beneficial as a supplement in heart disease, neuromuscular disorders, diabetes, and in people with low bone density.14-16

A loading phase of creatine at 0.07 g/kg of ideal body weight four times per day for 2-3 days followed by a once daily dose of 0.03 g/kg of ideal body weight for maintenance is a regimen that should provide ideal levels of muscle creatine without overusing the supplement. This regimen of creatine should be combined with a high-carbohydrate meal or beverage without high-fructose ingredients.15 There is no literature to suggest that creatine supplementation at recommended dosing negatively affects renal or liver function in healthy individuals.9,13,17

What are the cons of too much creatine consumption?

Research indicates that creatine supplementation is not useful for isometric or endurance exercises.8,9 The most common reported adverse event from creatine supplementation is gastrointestinal distress, including abdominal cramping, nausea, vomiting and diarrhea. There are other anecdotal reports of muscle cramping and water retention, but there is no solid evidence to support these claims.9,13 Studies have shown that if creatine is consumed in higher doses, kidney injury may occur. However, the results of these studies were either rare, or were seen in patients with underlying kidney disease 13,14

GLUTAMINE

What are the expected benefits of glutamine supplementation?

Glutamine is the most abundant amino acid in human muscle and is utilized at high rates by rapidly dividing cells.18 Research shows that glutamine may stimulate muscle development and improve immune function.18,19

What are the cons of too much glutamine consumption?

A study of military police officers showed no difference in exercise strength or endurance with glutamine supplementation.8 Otherwise, there is little concrete evidence of dangers.

OTHER SUPPLEMENTS

What additional ingredients that may be harmful?

The FDA warns that there is “an emerging trend where over-the-counter products, frequently represented as dietary supplements, contain hidden active ingredients that could be harmful. Consumers may unknowingly take products laced with varying quantities of approved prescription drug ingredients, controlled substances, and untested and unstudied pharmaceutically active ingredients”. The FDA notes that these hidden ingredients are increasingly becoming a problem in products promoted for bodybuilding and may be harmful. Note that the FDA does not test all products on the market. 20

In the USA, dietary and protein supplements may contain up to 25% of contaminants. There is a paucity of surveillance and regulation of the contents in these products. 21

Research shows that some protein supplements may contain anabolic steroids that are not declared on the labels. Other contaminants may include dicyandiamide and dihydrotriazenes and stimulants such as caffeine, ephedrine, methylenedioxymetamphetamie and sibutramine , 22,23 The stimulants may also be absent from product labels. 12,

that are not declared on the labels. Other contaminants may include dicyandiamide and dihydrotriazenes and stimulants such as caffeine, ephedrine, , The stimulants may also be absent from product labels. Protein supplements with aim to promote weight loss may contain synephrine . Synephrine has been associated with adverse cardiac events, including hypertension, tachyarrhythmia, variant angina, cardiac arrest, QT prolongation, ventricular fibrillation, myocardial infarction, and sudden death.

. Synephrine has been associated with adverse cardiac events, including hypertension, tachyarrhythmia, variant angina, cardiac arrest, QT prolongation, ventricular fibrillation, myocardial infarction, and sudden death. Selenium has been shown to decrease oxidant stress after exercise in overweight individuals, but it is unclear if this is clinically significant. 24 However, some of the dietary supplements contain selenium for this reason. One particular protein supplement caused several cases of selenium toxicity as it actually contained 200 times the labeled concentration of selenium. This led to 201 cases of selenium toxicity in 10 states, with 1 hospitalization. 25 Symptoms of selenium toxicity include dyspnea, respiratory distress, vomiting, diarrhea, abdominal pain, eye irritation, alopecia, depigmentation and peripheral nerve damage. 26

However, some of the dietary supplements contain selenium for this reason. One particular protein supplement caused several cases of selenium toxicity as it actually contained 200 times the labeled concentration of selenium. This led to 201 cases of selenium toxicity in 10 states, with 1 hospitalization. Symptoms of selenium toxicity include dyspnea, respiratory distress, vomiting, diarrhea, abdominal pain, eye irritation, alopecia, depigmentation and peripheral nerve damage. Interestingly, several studies have demonstrated an association with those who take bodybuilding or performance enhancing substances and high risk behaviors such as anabolic steroid use, heavy drinking, drinking while driving and getting involved in fights. Thus, the reported adverse events associated with these supplements such as hepatotoxicity, heart palpitations, autonomic symptoms and even death may possibly be a result of the combination of supplements and high-risk behaviors.27,28

Of 15 commonly consumed protein drinks (BSNÒ, EASÒ, GNCÒ, Jillian Michaels Pure ProteinÒ, Muscle MilkÒ, Optimum NutritionÒ, Six Star Pro NutritionÒ & Solgar Whey to GoÒ) tested by Consumer Reports, all drinks had at least one or more of the following contaminants: arsenic, cadmium, lead and mercury. Consuming only three servings of these per day may lead to higher than permissible daily exposure allowances. 29,30 Arsenic ranges from 0.6-16.9 mcg/3 servings. Cadmium ranges from 1.6-5.6 mcg/3 servings. Lead ranges from 0.4-13.5 mcg/3 servings. Mercury ranges from 0.2-1.1 mcg/3 servings



Symptoms of heavy metal contaminant toxicities:

Arsenic: headaches, drowsiness, confusion, seizures, encephalopathy, peripheral neuropathy, abdominal pain, nausea, vomiting, diarrhea, anemia, hemolysis, hypotension, generalized weakness, muscle aches, chills, fever, hyperkeratosis, hyperpigmentation, exfoliative dermatitis, cardiomyopathy, renal tubular necrosis, ventricular arrhythmias, intestinal hemorrhage and jaundice.

headaches, drowsiness, confusion, seizures, encephalopathy, peripheral neuropathy, abdominal pain, nausea, vomiting, diarrhea, anemia, hemolysis, hypotension, generalized weakness, muscle aches, chills, fever, hyperkeratosis, hyperpigmentation, exfoliative dermatitis, cardiomyopathy, renal tubular necrosis, ventricular arrhythmias, intestinal hemorrhage and jaundice. Cadmium: vomiting, diarrhea, kidney disease, lung cancer, electrolyte disorders, lactic acidosis and shock.

vomiting, diarrhea, kidney disease, lung cancer, electrolyte disorders, lactic acidosis and shock. Lead: irritability, lethargy, headache, vomiting, abdominal pain, anorexia, constipation, dysarthria, renal injury, hyperproteinemia, pallor, anemia, ataxia, encephalopathy, seizures, papilledema, confusion and hallucinations.

irritability, lethargy, headache, vomiting, abdominal pain, anorexia, constipation, dysarthria, renal injury, hyperproteinemia, pallor, anemia, ataxia, encephalopathy, seizures, papilledema, confusion and hallucinations. Mercury: fatigue, depression, sluggishness, irritability, headaches, dyspnea, respiratory depression, pulmonary edema, pulmonary fibrosis, confusion, ataxia, choreoathetosis, polyneuropathy, seizures, dysarthria, visual impairment, acrodynia, erythema, hyperesthesia, gingivitis, abdominal pain, vomiting and bloody diarrhea.26

Management:

The main treatment of heavy metal poisoning is termination of exposure to the metal .

. Treatment should also be symptomatic and supportive. In cases of cerebral edema, treatment with Mannitol and corticosteroid drugs, along with intracranial monitoring is required. Kidney failure may require hemodialysis.

In some cases, gastric lavage or whole bowel irrigation may be indicated depending on the exposure (acute versus chronic). Activated charcoal will not bind these heavy metals effectively and is therefore not recommended.

bind these heavy metals effectively and is therefore not recommended. Treatment also consists of the use of chelating agents including dimercaprol (BAL), dimercaptopropane sulfonate (DMPS), and succimer (DMSA). 31

including dimercaprol (BAL), dimercaptopropane sulfonate (DMPS), and succimer (DMSA). There is no proven effective therapy for the treatment of cadmium poisoning.26

Conclusions:

When choosing to consume dietary supplements, it is essential to evaluate all of the ingredients on the labeled supplement . In addition, consultation with a nutritionist or physician should be considered prior to starting any supplements.

. In addition, to starting any supplements. It appears that the majority of dietary supplements’ ingredients are not toxic when consumed at the doses recommended on the labels .

. There is mixed evidence as to the benefits of consuming these dietary supplements , however it would appear that the evidence demonstrates some benefit when appropriate timing and amount of creatine supplementation is utilized .

, however it would appear that the evidence demonstrates . Many of the products available may contain contaminants that are not listed on the labels, which may be harmful and cause toxicity when consumed in excessive amounts.

on the labels, which may be harmful and cause toxicity when consumed in excessive amounts. More resources should be utilized to focus attention on the large amount of contaminants in these supplements sold over-the-counter and perhaps more stringent regulation on the companies manufacturing these products.

References / Further Reading

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