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Boosting energy, limiting fatigue.jpg

Boosting energy, limiting fatigue

Several dietary ingredients that contribute to energy metabolism or inhibit fatigue are popular in sports nutrition supplements and energy food and drink products.

Insider Takes:

  • Energy metabolism is focused on the molecule ATP, and involves using macronutrients as fuel, and micronutrients as facilitators and regulators of ATP re-synthesis.
  • Protecting ATP from oxidative stress is a secondary approach to energy management, making antioxidants key nutritional ingredients for formulation.
  • Alternative delivery formats and sweeteners are in demand, especially with active consumers, as are clean and transparent labels.


Beyond its popularity with everyday consumers, energy is perennially a hot category for athletes and active people. Energy is a primary driver of the sports nutrition segment—sports energy and hydration drinks are projected to grow about 7.6% through 2022 to surpass US$30 billion, according to the 2019 Nutrition Business Journal Sports Nutrition and Weight Management Report.

Muscles receive energy from the breaking of phosphate bonds of the molecule adenosine triphosphate (ATP). ATP stores energy in its bonds, and muscles store ATP. A limited amount of ATP is stored in muscles and available to fuel intense activity for about 10 seconds, but continued exercise requires restoration or re-synthesis of ATP.

The body makes ATP via phosphorylation, adding phosphates to precursors. Adenine, a purine, and ribose, a pentose sugar, are the backbone of ATP and its precursors. Adenosine monophosphate (AMP) can become adenosine diphosphate (ADP), which can become ATP. When ATP’s phosphate bonds are broken, energy is released, and ATP becomes ADP, which can be further energy-decreased to AMP. AMP-activated protein kinase (AMPK) is the enzymatic regulator of this metabolic process, and ingredients that activate AMPK have grown in popularity as sports nutrition supplements. (See page TK for more on potential performance-enhancing drug testing issues with AMPK activators.)

Stored phosphocreatine in the muscles can be used quickly to restore ADP into ATP, but this again is limited. However, supplemental creatine is a common tool for athletes to increase muscle phosphocreatine stores to extend this fuel source.

For prolonged exercise, the body also uses glucose to synthesize ATP. The body breaks down glucose (glycolysis) in different ways. Anaerobic glycolysis occurs during limited oxygen states, such as in short intense exercise, while aerobic glycolysis kicks in when more oxygen is available from increased breathing from sustained exercise.

Carbohydrates drive glucose production and storage and, thus, are an important source of energy for most athletes. In the absence of adequate carbs, the body can make glucose from protein, a process called gluconeogenesis. This is a key consideration in low-carb diets including keto. However, the focus of keto is metabolizing fats—the body uses peroxidation to synthesize ATP from fat via the Krebs or the citric acid (TCA) cycle—so protein intake should be limited in the keto diet.

Nutritional Energy Boosters

Several dietary ingredients contribute to or amplify energy metabolism, and are popular in sports nutrition supplements, and energy food and drink products.

Exogenous ATP is found in sports nutrition formulations as a salt, often sodium or calcium.

Creatine is commonly found as monohydrate, the most studied form, and hydrochloride, but novel forms include creatine nitrate and buffered creatine for improved bioavailability.

Ribose is a rate-limiting compound in the synthesis of purines and pyrimidines, including ATP. The body’s production of ribose from glucose is slow (Adv Biosci Clin Med. 2018;6(1):1–5), so supplemental ribose is important for supporting or boosting ATP synthesis for athletes and active consumers.

Beta-alanine combines with L-histamine to make carnosine, which buffers hydrogen ions that result from anaerobic glycolysis; when these ions accumulate in the muscles, acidity increases and fatigue is promoted.

L-alanine combined with L-glutamine (as Sustamine, from Kyowa Hakko) may help delay fatigue and improve time-to-exhaustion (J Am Coll Nutr. 2015;34(6):488-96). Glutamine addressing energy and fatigue by increasing glycogen synthesis and removing ammonia from the muscles (Nutrients. 2019;11(4):863). Further, glutamine can be converted to alpha-ketoglutarate, a ketone derivative that helps drive the Krebs/TCA cycle.

Carnitine helps shuttle fatty acids into the mitochondria, where ATP production takes place. These fats can be oxidized to create coenzyme A which is used to make ATP via the Krebs or TCA cycle.

Medium-chain triglycerides (MCTs) can be quickly digested and transported to the muscles for oxidation to drive the Krebs/TCA cycle. MCTs are also oxidized in the liver to make ketone bodies, which can be used to make CoA for energy. Thus, MCTs are popular for keto-focused products.

Beta-hydroxybutyrate (BHB) and acetoacetate are key ketone bodies used by the body for energy in many body tissues. For instance, fatty acid oxidation is limited in the brain, but ketone bodies are readily used by the brain for energy in low glucose conditions, such as ketosis.

Coenzyme Q10 (CoQ10) takes electrons left over from the Krebs/TCA cycle and shuttles them through the electron transport chain. As the electrons move through the chain via redox reactions, a protein gradient is formed; when hydrogen ions move across the gradient, ADP is converted into ATP via chemiosmosis. The electron transport chain and chemiosmosis together are called oxidative phosphorylation, a process that produces more ATP per glucose than any other mechanism.

Magnesium is crucial for ATP activity; ATP must bind with a magnesium ion to be biologically active. This mineral is a cofactor of many important enzymes in ATP synthesis, including creatine kinase in the phosphagen system, pyruvate kinase and others in the glycolytic system, and dehydrogenases in the Krebs/TCA cycle.

Shilajit is an Ayurvedic staple made from a mineral pitch found commonly in the Himalayan mountains. It contains magnesium, phosphorous and other trace minerals.

Ancient peat (plant fossils) is rich in magnesium and other minerals crucial to ATP and energy. In the branded ingredient elevATP (from Futureceuticals), peat is combined with apple extract, which offers the flavonoid quercetin to protect ATP from oxidative stress.

French oak wood (Quercus robur) also contains antioxidant compounds, including tannins (e.g., roburins), which target oxidative stress. Ellagitannins in this botanical can be converted into ellagic acid, which regulates fat oxidation and activates AMPK.

Gynostemma pentaphyllum, also known as jiaogulan (Chinese for “twisting blue plant”), contains antioxidant polysaccharides as well as saponins that activate AMPK to help regulate glucose and fat metabolism.

Glutathione is a potent antioxidant found in plants, animals, fungi and other microorganisms. Glutathione and alanine are key transporters of ammonia—AMP and amino acid breakdown can result in elevated muscle ammonia levels, which impact central fatigue.

Caffeine is a purine alkaloid that inhibits central fatigue by competing with adenosine in the brain. As ATP is broken down to release energy, adenosine accumulates; adenosine binds with corresponding receptors in the brain to signal fatigue. While caffeine’s binding to adenosine receptors delays fatigue signaling, it also stimulates the central nervous system (CNS), increasing heart rate. The body also can respond to increased caffeine binding by creating more adenosine receptors; this means more caffeine is needed over time to create the same stimulant and fatigue-inhibiting response. Caffeine is wildly popular as an energy ingredient and is commonly found in sports nutrition products as either synthetic or natural, including botanical sources such as coffee, tea, guarana, guayasa, kola nut and yerba mate.

Theacrine is another purine alkaloid found in plants like coffee and tea. With a structure similar to caffeine, theacrine offers similar energy benefits but without the unwanted CNS side effects and habituation.

Delivering On Promise

Energy drinks are a popular delivery format in in the sports nutrition market. Nutrition Business Journal (NBJ) reported sports energy and hydration drinks accounted for 66% of the nearly $36 billion sports nutrition market in 2018. While this is a huge share, growth of these drink products has remained steady near 7.5% since 2018 and is expected to hold steady through 2021.

Beverages in the sports nutrition category tend to be either ready-to-drink (RTD), such as the popular Red Bull and Bang (mainstream) and Cellucor C4 (sports market), or ready-to-mix (RTM), which is popular for pre- and post-workout formulation, especially for core sports nutrition users.

Informa Market’s NEXT Concept Lab analyzes more than 1,500 products to determine cultural relevance and purchase intent. Beverages tracked slightly higher than average for both purchase intent (“I would buy it”) and market intent (“I think others will buy it”).

Shots are another increasingly popular energy format, as seen in the 5-Hour Energy success, but shots were slightly low in purchase intent and very low in market intent in the NEXT Concept Lab analysis.

Supplements (pills, capsules, etc.) are still a strong format in sports nutrition, but it is no secret alternative formats are the trend in the mainstream, which is where active consumers are migrating from into the sports market. NBJ reported a 12% increase in non-pill formats between 2013 and 2018, with gummies doubling its, albeit small, share from 6% to 12%.

Gummies, chewables and bars tracked highest in combined purchase and market intent in the NEXT Concept Lab, and “other” formats (lozenge, lollipops, effervescence, etc.) were high in market intent, if a little lower than average in purchase intent. This reflects recent new product launches including Verb energy bites/bars and Olly energy gummies.

While sprays scored low in both areas of the concept lab, Israeli company Matok V’Kal, Ltd. launched Fit4style Energy carbohydrate spray based on the theory that the mere presence of carbs in the mouth can fool the brain into thinking the body has ingested carbs for energy.

Delivering on promises and consumer demands is also a big trend in sports nutrition energy. Holly McHugh of beverage consultant firm Imbibe Inc. noted “clean” energy and transparency are big label trends for energy drinks. These are also in play for RTM and other formats.

The “clean” movement can mean both “free from banned substances,” which includes stimulants and AMPK activators (see page TK), as well as free from artificial or chemical-sounding ingredients. The latter meaning involves use of more natural compounds in short, simpler lists of ingredients.

The sweetener trend is a prime example of clean label and “natural.” The traditional sports nutrition market primarily used artificial sweeteners such as aspartame and sucralose for its energy formulations, but the mainstream trend is toward natural sweeteners such as stevia, monk fruit, honey and agave. While sugar is a valuable carb for energy, the wider trend of reduced sugar intake is somewhat at play in sports nutrition, as formulators use alternative sweeteners to reduce added sugars.

The transparency trend hits sports energy products in two principal ways. First, caffeine sources should be clearly identified and amounts of each source provided. Second, brands should forgo the use of proprietary blends, which often manifest as stimulant blends on energy product labels, and labeling requirements can differ between energy beverages vs. supplements; see page TK for more info.

Overall, the sports energy market is a mainstay with a huge market presence, but standing out is a challenge for brands. Fortunately, a growing list of ingredients can target energy/fatigue from different angles, offering formulators and brands ways to carve out a niche. Further, the many mainstream trends migrating to sports nutrition largely on the backs of migrating active consumers also offer brands an opportunity to deliver on promises while differentiating, especially from legacy brands/formulas.

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