Are dietary supplements the ‘’magic bullet’’ for overall health?

Dietary supplements have become very popular worldwide. Globally, over the past 40 years, there has been an observed increase in dietary supplement use from 25% to 70%. Moreover, among all adults from 2007-2008 through 2017-2018, dietary supplement use has increased from 48.4% to 56.1%. While dietary supplements are considered alternative forms of medicine and nutrition primarily used to complement an inadequate diet, promote and maintain overall health, as well as prevent specific diseases, they have nowadays moved consumers away from natural foods and medically approved treatments. This trend of dietary supplement abuse is of public health concern because their excessive, inappropriate, or unsupervised consumption can potentially lead to detrimental health consequences, especially in vulnerable groups with impaired physiological conditions.

Let’s start from the very beginning, though. How a dietary supplement is defined? The term ‘’dietary supplement’’ was described by the U.S. Food and Drug Administration (FDA) as a product purposefully ingested to supplement the diet to achieve a specific health and/or performance benefit. It contains one or more of the following dietary ingredients or their constituents either on their own or in any combination: 

• a) a vitamin (such as multivitamins or individual vitamins like vitamin D),
• b) a mineral (such as calcium, magnesium, and iron),
• c) a herb (such as echinacea) or other botanical (such as caffeine and curcumin),
• d) an amino acid (such as glutamine),
• e) a dietary substance for use by man to supplement the diet by increasing the total dietary intake,
• f) a probiotic or
• g) a concentrate, metabolite, constituent, extract of any ingredient described above. 

Dietary supplements are ingested orally and come in many forms, including tablets, capsules, soft gels, gel caps, powders, bars, gummies, and liquids. Functional foods that are enriched with additional nutrients or components outside their typical nutrient composition (e.g., mineral- and vitamin-fortified), as well as sports foods for targeted use around exercise, providing energy and nutrients in a more convenient form than normal foods  (e.g., sports drinks, gels, bars), are also considered dietary supplements. The most common dietary supplements used are multivitamin-mineral supplements, followed by vitamin D and omega-3 fatty acids.

Dietary supplements are not drugs and, therefore, are not intended to treat, diagnose, or cure diseases. Based on current legislation, dietary supplements must have nutrition information in the form of a Supplement Facts label that includes the serving size, the number of servings per container, a listing of all dietary ingredients in the product, and the amount per serving of those ingredients. They must also be labeled on the front panel as being a dietary supplement and give directions on their safe and appropriate use. Food, Drugs, and Cosmetic Act (FDCA) and Food and Drug Administration (FDA), which are the regulatory agencies under which the dietary supplement industry is liable to, review product labels and other labeling information to ensure products are appropriately labeled and that they don’t include claims that may render the products drugs (e.g., claims to treat, diagnose or cure diseases). They also periodically inspect dietary supplement manufacturing facilities to verify companies meet applicable manufacturing and labeling requirements. If a product is found to be unsafe or doesn’t otherwise comply with the law, these agencies can take action to remove it from the market. However, FDA does not have the authority to approve dietary supplements for safety and effectiveness. In the United States and many other countries, dietary supplements can be marketed without FDA approval and scientific proof of safety or efficacy.

Therefore, the extended use of dietary supplements, not only by athletes, gym attendants, and bodybuilders but by the general public as well, has raised many serious questions about the scientific consensus on the research on dietary supplements, their effectiveness, and safety issues. Although they can contribute to meeting recommended nutrition targets in terms of macro-, micronutrients, and energy, as well as be used for other purposes, including performance enhancement and rapid recovery from injury, they can also potentially lead to excess intakes, thus toxicities and severe subsequent health issues. 

Can consumers know how to avoid excess intakes and their subsequent health concerns? The Institute of Medicine (IOM) has established the Dietary Reference Intakes (DRIs), which are comprised of the Estimated Average Requirements (EAR), the Adequate Intake (AI), the Recommended Dietary Allowances (RDA), and the Tolerable Upper Intake Levels (UL). These DRI categories define the optimal safe levels of nutrients that should be consumed to prevent deficiencies and/or to avoid adverse effects of excess consumption. Supplementation has indeed contributed to increased nutrient intake in the general population and the eradication of several diseases linked to mineral or vitamin deficiencies, such as goiter and scurvy. It has also helped decrease the percentage of people who consume less than the EAR of crucial nutrients. Moreover, dietary supplements are vital for achieving nutrient sufficiency in older people who routinely fail to meet the recommended levels of many vitamins and minerals.

However, many consumers go overboard with supplementation, substituting a healthy, well-balanced diet with them. With increasing dietary supplement use and the availability of more functional foods, the consumption of nutrients above the recommended UL continues to grow. This raises public health concerns since several large clinical trials have demonstrated increased disease incidence and mortality with increased supplement use. For example, excess calcium intake has been linked with a higher rate of hip fractures in older women, an increased incidence of prostate cancer in men, and an increased risk of myocardial infarction. Furthermore, higher total folate intake has been linked with increased incidence of several cancers and higher mortality. The most robust results pertain to the fat-soluble antioxidant vitamins A and E, whose supplementation increased the incidence of lung cancer and the overall mortality risk. The research outcomes regarding supplementation and cancer transfer over to all cancer patients who should be cautioned to avoid certain nutrient supplements whatsoever due to possible interference with therapy. 

Following the trend of other dietary supplements, dietary weight-loss supplements use has increased dramatically over the past twenty years. People generally find dietary modification less demanding than regular exercise, particularly if this modification satisfies the common need for a ‘’magic bullet’’  that is simply taking a dietary supplement for weight loss. Manufacturers of dietary supplements for weight loss tend to promise rapid, easy, and safe weight loss, claims that hit the spot for overweight and obese individuals who are desperate to lose weight. The postulated mechanisms of such dietary supplements effects include: energy expenditure increase, increased satiety, increased fat oxidation, and fat loss, as well as decreased dietary fat absorption. However, most of these supplements have not been subjected to rigorous examination before being licensed; hence, their safety, in terms of adverse side effects and drug interactions, has not yet been sufficiently addressed and is underreported. 

Below, some of the most popular dietary weight-loss supplements and their effects are presented:

β-glucans

They are natural soluble fibers that may increase satiety by extending total gastrointestinal transit time. Cholesterol and glucose-lowering effects have also been reported. However, no significant impact on weight loss has been demonstrated. Reported adverse effects are similar to those of other water-soluble, fermentable fibers and include abdominal discomfort, bloating, diarrhea, and flatulence. 

Caffeine

Higher coffee consumption is associated with a low risk of obesity, metabolic syndrome, and type 2 diabetes. Its proposed mechanism of action is that it suppresses appetite and speeds up metabolism, promoting a fat-burning metabolic state. However, further research is needed to confirm these findings. The FDA and the European Food Safety Authority (EFSA) recommend a caffeine limit for adults between 400-500mg/day. Possible adverse effects include nausea, vomiting, and tachycardia. There also may be possible drug interactions with antiarrhythmics, bronchodilators, and antidepressants.

Capsaicin

It is the major active compound in chili peppers. It has been shown to induce thermogenesis, suppress appetite, and increase satiety, all effects that result in reduced total energy intake and, thus, weight loss. The adverse effects might be gastrointestinal distress, sweating, flushing, and rhinorrhea. Capsaicin compounds can interfere with antihypertensive, antidiabetic, antilipidemic, and anticoagulant drugs. 

Carnitine

It is an essential cofactor in fatty acid metabolism. Studies have shown that supplementing with 1.8-4 g/day led to significantly higher weight loss compared to placebo. However, the effect of carnitine supplementation significantly decreases over time. Side effects such as muscle weakness and seizures are rare and are primarily associated with doses above 4 g/day.

Conjugated linoleic acid (CLA)

It is a naturally occurring omega-6 fatty acid derivative of linoleic acid typically found in dairy and meat products. It potentiates lipolysis and may improve insulin sensitivity in skeletal muscle. The evidence shows a slight difference in fat loss with long-term CLA supplementation in overweight and obese individuals vs. placebo (-1.33kg). CLA appears to be safe. Few adverse effects have been reported, such as abdominal discomfort and pain, constipation, diarrhea, nausea, vomiting, and dyspepsia. 

A healthy diet and physical activity remain the first-line intervention for weight loss, while weight loss dietary supplements should be considered adjuvant. Many of their constituents remain unknown, uncharacterized, or not adequately tested in combination with one another. Considering the lack of clear scientific evidence of their efficacy and safety, habitual consumers should first talk with their healthcare professional. In any case, individuals must not substitute a dietary supplement for a prescription medicine or the variety of foods essential to a healthy diet. 

Many athletes place great emphasis on the use of performance-enhancing dietary supplements. However, only a few of them currently have an adequate level of scientific evidence to suggest that marginal performance gains may be possible. These include caffeine, creatine monohydrate, beta-hydroxy beta-methylbutyrate, nitrates, and possibly beta-alanine.

Caffeine

Caffeine is a stimulant with well-established benefits for athletic performance in endurance-based sports as well as in short-term, and/or repeated sprint tasks. In terms of endurance performance, caffeine has been proposed to promote fat oxidation and inhibit carbohydrate oxidation in skeletal muscle and liver, thereby improving endurance capacity and exercise time to fatigue in endurance-based time trial activities of varying duration (5-150 minutes) across numerous exercise modalities (i.e., cycling, running, rowing, etc.). It can also improve vigilance and alertness as well as reduce the perception of exertion during exercise.  These effects are achieved through a moderate dose of 3-6 mg/kg 30-90 minutes prior to exercise in the form of anhydrous caffeine (i.e., pill or powder form). Higher caffeine doses of 9 mg/kg do not further enhance performance and can result in undesirable side effects, including gastrointestinal distress, nervousness, confusion, restlessness, and disturbed sleep. Conversely, lower caffeine doses (≤3 mg/kg) can still be ergogenic, provided they are combined with a carbohydrate source. 

Creatine monohydrate

Creatine is an amino acid found naturally in human muscle and brain cells and is the most studied dietary supplement for enhancing performance. Creatine loading can acutely boost sports performance, including single and repeated bouts of high-intensity exercise lasting less than 150 seconds. Its most pronounced effects are evident during bouts lasting less than 30 seconds. It can also improve the outcomes of long-term resistance and interval programs, leading to greater gains in muscle mass, hence muscular hypertrophy, strength, and power.  In addition to the well-established performance-enhancing effects, creatine monohydrate also promotes muscle recovery from intense exercise, enhances muscular adaptations to intense exercise, attenuates post-exercise delayed onset muscle soreness (DOMS), and decreases post-exercise inflammation and muscle damage. The protocol for creatine loading includes a loading phase with ~20 g/day divided into four equal daily doses for 5-7 days and a maintenance phase with 3-5 g/day as a single dose for the duration of the supplementation period. No negative health effects are noted with long-term use (up to four years) when appropriate loading protocols are followed. 

Beta-hydroxy beta-methylbutyrate (HMB)

It is the metabolite of the amino acid leucine. It is marketed as an anticatabolic supplement that decreases protein breakdown and increases protein synthesis. However, the anabolic gains in strength, power, and muscle mass, as well as the reductions in muscle damage, are doubtful. It has been demonstrated that a physically active individual who adheres to the current protein recommendations (1.4-2.0 g/kg/d) is not likely to have any extra benefit from HMB supplementation. On the other hand, HMB may be more useful in rehabilitation where there may be periods of extreme inactivity, as studies have shown better preservation of muscle mass in older adults ingesting about 3 g/day (recommended dose) of HMB during ten days of complete bed rest. Therefore, unlike creatine monohydrate, HMB cannot be confidently recommended to athletes, HMB cannot be recommended at this time, as more research is needed.

Nitrates

It is a popular supplement commonly investigated for benefits in prolonged submaximal exercise and high-intensity, intermittent, short-duration efforts, naturally found in high amounts in beets and beetroot juice. It augments exercise performance. Nitrate supplementation has been associated with improvements in exercise time to exhaustion as well as improvements in high-intensity, intermittent, team-sport exercise of 12-40 minutes. Such performance benefits are generally seen within 2-3 hours following a 310-521mg dose and are mainly attributed to improved cardiorespiratory performance at the anaerobic threshold and VO2max. Prolonged periods of intake (> three days) also appear beneficial to performance. They may be an alternative strategy for highly-trained athletes, where performance gains from acute nitrates supplementation appear harder to obtain. Evidence is equivocal for any benefit to exercise lasting less than 12 minutes. The main side effects pertain to gastrointestinal upset issues. Hence, athletes should try nitrate supplementation in training before using it in competition. However, studies are mixed, and it may primarily benefit recreational athletes. 

Beta-alanine

It is an amino acid studied for its potential beneficial effects on sustained high-intensity exercise performance. Daily consumption of ~ 65 mg/kg, ingested via a split-dose regimen (i.e., 0.8-1.6 g every 3-4 hours) over a time frame of 10-12 weeks led to small (~ 0.2-3%) but potentially meaningful performance benefits during both continuous and intermittent exercise tasks of 30s to 10 minutes in duration. Its effectiveness appears harder to obtain in well-trained athletes. In any case, there is a need for further investigation to establish its efficacy in various sport-specific situations. Possible negative side effects include skin rashes and/or transient paresthesia. 

There is also research indicating that some dietary supplements may be valuable in enhancing muscular adaptations to exercise, decreasing DOMS, reducing gastrointestinal problems, enhancing recovery from injury, and mitigating injury severity. These effects are not ergogenic but can influence cellular and tissue health, training resilience, and muscle repair such that athletes can train and/or compete more efficiently with less or without any performance obstructions. These supplements include antioxidants, omega-3 fatty acids, vitamin D, probiotics, and anti-inflammatory supplements, such as curcumin.

Antioxidants

While a healthy diet for athletes should naturally include a variety of antioxidants, extremely high doses from supplements may impair or prevent training adaptations in endurance athletes and are not recommended. Only when an endurance athlete has already peaked in training, and their main goal is timely recovery, a supplement containing various antioxidants such as vitamins C and E, beta-carotene, selenium, and glutathione may help speed recovery. In any case, athletes are recommended to take antioxidant supplements prior to exercise only if recovery is needed within 24 hours. 

Omega-3 polyunsaturated fatty acids

They are essential fatty acids consumed in the diet, mainly through foods such as fatty fish (e.g., sardines, salmon, mackerel) and fish oils. Their supplementation may increase muscle protein synthesis (MPS), lead to cognitive improvements, and also has anti-inflammatory properties, which could play a role in recovery from intense exercise. Concerns about fish oil supplementation include heavy metal contaminants, bleeding, digestive problems, and increased LDL cholesterol. On top of that, no sufficient data indicates that athletes should pursue supplementation instead of having fatty fish in their diet as a source of omega-3. Therefore, a recommendation for frequent fatty fish consumption, including increased omega-3 fatty acids, protein, vitamins, and minerals dietary intake, may be more appropriate for athletes than for fish oil supplementation. 

Vitamin D

Vitamin D insufficiency or deficiency is widespread, and the benefits of supplementation likely improve some aspects of muscle function and increase training adaptations to intense exercise. However, whether vitamin D supplementation is necessary for these beneficial effects likely depends on the athletes’ vitamin D status at the initiation of supplementation. Thus, it is prudent first to identify deficiencies through blood work, consult with a physician, and finally supplement as needed. Indiscriminate high doses of vitamin D for athletes are not advised. 

Probiotics

They are found in fermented foods, such as yogurt, kefir, sourdough bread, etc., or supplements and are live microorganisms intended to maintain or improve the ‘’good’’ bacteria in the body. Athletes prone to gastrointestinal (GIT) problems or traveling to regions with a high risk of gastrointestinal problems may benefit modestly from probiotics supplementation. Moreover, evidence indicates that probiotic supplementation can reduce the incidence, duration, and severity of upper respiratory tract infections (URTI) in athletes. Whether probiotic supplementation can practically improve training or competitive performance by decreasing the negative effects caused by URTI and/or GIT problems is still inconclusive. Therefore, probiotic supplementation should not be routinely recommended in athletes.

Curcumin

It is a substance found naturally in turmeric. Curcumin supplements ingested at a dose of about 5 g/day show promise in reducing markers of muscle damage, DOMS, and/or inflammation in athletes. However, whether these effects can enhance recovery or affect subsequent performance is unknown. 

As with any dietary supplement, there is a risk of contaminants and banned substances in the above supplements, forming not only a safety risk but also a punishment and elimination risk for professional athletes. 

Overall, while dietary supplementation has a clear positive role in overall health due to its imprudent use, it has been associated with toxicities and adverse health outcomes. An ‘’ideal’’ supplement would better serve the public health needs and aid more efficiently in meeting their nutrient needs. However, this would be highly challenging to implement due to the population’s eating patterns and nutrient intake/requirements variability. Therefore, dietary supplementation should be better regulated with stratification of nutrient requirements for different age groups.  It may be time for the regulatory agencies to define and then enforce what percentage of RDAs dietary supplements can provide to complement dietary intake while minimizing excess intake of nutrients. Furthermore, a research priority should be to identify populations with higher nutrient needs and those at risk for adverse health outcomes with increased nutrient intake from dietary supplements. 

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