Using Antioxidants to Enhance Athletic Performance
Antioxidant Supplementation- Effects on Exercise and Recovery
Antioxidants - Antioxidant supplementation provides notable benefits for athletic performance during and post-prolonged physical activity. These correlations are significant, reproducible, and robust. A well-studied antioxidant, quercetin, is a flavonol present in various fruits, grains, and vegetables, with elderberries, blueberries, and onions containing the highest concentrations.
In a study on antioxidant supplementation in athletes (MacRae HS, 2006) [1], time trials (TT) involving elite cyclists utilized a randomized, double-blind, cross-over design to assess the impacts of twice-daily antioxidant supplements (AS). These supplements included essential vitamins plus quercetin (FRS) and AS without quercetin (FRS-Q) compared to a baseline TT.
The study revealed a remarkable 9.39% increase with FRS compared to Baseline (P ≤ 0.01). Without additional quercetin (FRS-Q), there was a 5.78% increase in power (P ≤ 0.05), demonstrating the positive effects of a traditional vitamin supplement (FRS-Q). Moreover, the vitamin supplement's effects were heightened by 3.61% due to the additional antioxidant "boost" from quercetin (FRS).
These findings reveal that even elite athletes, performing at peak endurance, had an unmet antioxidant need despite regular vitamin supplementation. The additional antioxidant, quercetin, boosted their performance by an extra 3.61%. This raises questions about the optimal antioxidant dosage: "How much is enough?" and "What level reaches a plateau without further performance enhancement?" Only extensive studies with varied antioxidant dosages can address these questions. Considering the supplements' cost and the potentially high volumes required, practical limitations, beyond the plateau effect, may impact performance enhancement.
Potential Pharmacological Effects of Molecular Antioxidants
A challenge in studying small molecule antioxidants is their potential pharmacological effects, resembling drugs more than nutritional supplements, due to their shape and chemistry interacting with receptors. The oxidized forms of these antioxidants may exert drug-like effects, blurring the distinction from their antioxidant functions. Quercetin exemplifies this dual functionality. Its oxidized derivative, dihydroquercetin or taxifolin, antagonizes adenosine receptors akin to caffeine. While caffeine is considered a performance-enhancing drug, drug-like effects can have drawbacks like jitteriness and overstimulation, affecting performance precision. Combining caffeine-like substances, such as dihydroquercetin, may inadvertently push a well-tuned dose into overdose territory.
Quercetin demonstrates the potential to boost mitochondrial density by activating SIRT1, which, in turn, activates PGC-1α through deacetylation. Studies in mice following quercetin supplementation revealed increased levels of SIRT1, PGC-1α, and mitochondrial DNA, indicating a rise in mitochondria numbers. While these outcomes are promising for performance, the question persists: do these effects stem from pure antioxidant activity or pharmacological receptor interaction? If quercetin's antioxidant action is solely responsible for the increased mitochondria, other antioxidants may offer similar benefits. However, if it involves specific receptor interaction, the advantages might be unique to quercetin.
To unravel the mechanisms behind these effects, researchers employ combined feeding experiments, administering antioxidants with diverse structures to observe if they yield similar outcomes. These studies assess whether the antioxidants work redundantly or synergistically. However, finding a "pure" antioxidant for combination with quercetin is challenging, as many antioxidants may activate receptors with unspecified effects. Despite this complexity, quercetin demonstrates clear antioxidant effects, as confirmed in a study (Boyle SP, 2000) [4]. Increased quercetin levels post-onion consumption correlated with enhanced resistance to DNA strand breakage and reduced oxidative metabolites in urine.
Antioxidants are seldom discussed in terms of their pharmacology, and their path, activities, and fate post-oxidation remain elusive. Currently, research is exploring basic questions about bioavailability, tissue distribution, and the removal of oxidized antioxidants from the body. Limited studies exist on the pharmacological activity of oxidized antioxidants or how they compare to their original forms after strenuous exercise. Given the potential for undesirable effects after oxidation, caution is warranted. Hydrogen gas (H2), known as elemental hydrogen, stands out as a unique antioxidant, neutralizing hydroxyl radicals and producing water. Although challenging to quantify its bioavailability, hydrogen's ability to penetrate all organs and selectively neutralize hydroxyl radicals makes it a valuable research tool.
Figure 1 - The reaction of hydroxyl radicals with hydrogen gas to form water. Reaction occurs only upon collision of H2 and OH• and always forms water (H2O).
Drinking hydrogen-rich water has been shown in numerous studies to decrease oxidative stress. In the following studies, the hydrogen enrichment is accomplished by placing magnesium metal in drinking water, and then drinking the resulting hydrogen-rich water.
Hydrogen has demonstrated effectiveness in countering the oxidative stress induced by radiation therapy. Blood antioxidant status was assessed using two measures: derivatives of reactive oxidative metabolites (dROMs) and biological antioxidant power (BAP). Patients drinking hydrogen-enriched water exhibited a noteworthy decrease in oxidized molecules, as evidenced by a direct measure of dROM levels. Additionally, BAP levels increased, indicating a rise in serum antioxidant capacity (Kang K, 2011). [5].
Strenuous exercise amplifies free radical production, akin to increased emissions during intense car usage. As conditions deviate from optimal, oxygen depletion and rising temperatures heighten oxidation, leading to decreased efficiency. Anaerobic metabolism fails to sustain cellular energy, depleting ATP stores and causing the malfunction of energy-dependent ion pumps. This results in mitochondrial leakage and dysfunction. In a study (Aoki K, 2012) [6] involving high-performing athletes consuming hydrogen-rich water before the test, a significant decrease in blood lactate levels (up to 23%) was observed after 40 minutes of intense exercise compared to controls. This reduction in lactate was coupled with a swifter return to baseline levels after exercise cessation. The hydrogen-rich water also prevented post-exercise decrease of median frequency (MDF) after the initial strenuous exercise. MDF is an indicator of muscle fatigue and is especially important in sports where more than one “sprint” of physical activity is required to give the final outcome of the event.
The Downside of Hydrogen Enriched Water
Hydrogen administration during athletic activity is challenging due to logistical constraints. Its short half-life and high oxidative load limit effectiveness. Drinking hydrogen-saturated water allows prolonged gas release, but the required volume may cause stomach discomfort. In this study, subjects consumed 500ml the night before and 1000ml on the test morning, potentially causing issues before competition.
Loading Prior to Training or Competition
Hydrogen stands out among antioxidants as it doesn't necessitate prior loading, exerting a quick impact on performance when consumed just before an event. However, its effectiveness is maximized when taken close to the activity. In contrast, antioxidants like quercetin require ongoing supplementation throughout training and competition. Athletes must adhere to the regimen to maintain benefits, posing financial strain and compliance challenges, especially when facing the risk of performance decline or withdrawal effects if they miss a dose.
Antioxidants vs. Supplements vs. Drugs- Problems of Tolerance and Withdrawal
Supplement effects tied to receptor-mediated pharmacological interactions often result in tolerance issues, even with faithful adherence to the regimen. Tolerance arises from continuous receptor exposure, leading to down-regulation or up-regulation. Caffeine, a benign receptor antagonist, exhibits tolerance and withdrawal effects. Tolerance demands increased supplement amounts for prior results, forming a delicate balance with withdrawal—revealing opposite effects when the receptor "push" is abruptly withdrawn. Both tolerance and withdrawal pose undesirabilities, making some drugs problematic in the long term despite short-term gains.
Route of Administration
Orally administered supplements, like pills, pose challenges due to interactions with concurrent food intake. Foods and beverages may hinder supplement absorption, as seen with calcium forming insoluble precipitates. Conversely, some substances may accelerate absorption, overwhelming the system. For instance, carbonated drinks, akin to champagne's effects on alcohol absorption, can lead to rapid supplement absorption. Timing and quantity of the carbonated beverage matter, influencing stomach irritation and liver workload. These intricacies highlight potential issues when supplements are taken at the meal's onset.
Taking everything by mouth can be especially difficult when an athlete doesn’t feel hungry or thirsty. Often the anxiety of a performance will make it almost impossible to choke down pills and one bout of vomiting can throw the supplementation regime into disarray. Consuming a large quantity of pills or even hydrogen rich water before an event can be very difficult.
The Problem of Delivery and Waste Removal
When ingested supplements do make it into the blood, the products still have to be delivered to the brain, organs and muscles that need these and will utilize them. The process of absorption into the target tissue and the removal of the spent antioxidant by the venous blood can be a “traffic jam” at times, with a great number of molecules having to move in and out of tissues pushed to their peak of performance.
The route in from the digestive tract to the target organs such as brain and muscles is not a simple one. Once a supplement is liquefied in the stomach, the blood from the intestines that has absorbed the supplement must travel into the portal vein. This blood all goes to the liver, where the liver acts as a barrier for harmful substances that might otherwise cause problems, however, it also causes a considerable delay in the onset of effects and becomes the first user of the antioxidants in the supplement. The liver may consume the lion’s share of the antioxidant supplement, especially for antioxidant molecules that do not have a transporter to take them away. The liver has many enzymes that can change the structure of the drug and this may change its functionality significantly.
https://www.apsubiology.org/anatomy/2020/2020_Exam_Reviews/Exam_1/CH19_Blood_Flow.htm
Figure 2 - The Hepatic Portal Vein and the route of ingested substances into circulation.
Once the antioxidants pass through the liver, they distribute throughout the body in a manner proportional to the blood flow in these areas. Because most antioxidants have either a lipophilic or hydrophilic nature, these partition either into fat or into the body water. This means that the distribution is destined to be uneven, with poor solubility and fleeting effects in target areas as the antioxidants accumulate in the parts of the body that can hold them.
The blood-brain barrier is another problematic impediment to antioxidant distribution. When the destination is the brain, many antioxidants cannot cross and will not remain near the brain. Because the brain has a very high level of energy and oxygen use and is a very dense, hot organ, the antioxidant need can be quite intense. The brain is actually a hot spot for oxidation and is the location where many symptoms of fatigue are the greatest.
https://www.christopherreeve.org/blog/research-news/blood-brain-barrier-the-spinal-cord
Figure 3 - The regulation of migration of antioxidants out of the bloodstream into the brain is much more complex in the brain.
How much do you take at once? How long will it last? Will it leave you hanging? How often will you have to “go”?There is also the question of what quantity of supplement is practical to ingest at one time. Clearly, as endurance events grow longer or more intense, the supplements taken in the beginning of the event are used up before the end. By depending upon ingestion, there is an unfortunate “cliff’s edge” to fall off of as the supplement is used up and its waste products are eliminated into the blood, and then eventually to the bladder. Most people are familiar with the consequences of ingesting caffeine or alcohol; the body eliminates more urine when there are more wastes. This means that some supplements can lead to rapidly filled bladders and result in handicaps such as rapid dehydration and frequent stops.
What is needed- Immediate Effectiveness and Long-Term Efficacy
If an athlete were to have a supplement that isn’t taken orally, the pharmacology and half-life of the supplement would be much simpler and the athlete could get more consistent results. Additionally, topical administration to the target body part would allow much smaller amounts of the supplement to give greater results with less dilution. A more targeted supplement would free the athlete from long pre-event supplementation regimes and would have reduced interactions with food. The result is a much simpler, more normal life for the athlete.
Likewise, if the supplement were to release in response to the athlete’s needs while being lightweight, this would allow the supplementation to occur throughout the event without a need to resupply or drink large quantities of fluid. For events that take place over many hours, an as-needed slow release supplement would change how we view the use of antioxidants to not just enhance performance, but also to reduce the oxidative injury that an athlete must contend with.
The Heliopatch Solution
We have developed a new type of antioxidant supplementation- direct electron donation. This system doesn’t send an antioxidant into the body to deliver an electron. Instead, it connects a potent source of electrons to the skin and these are transmitted into the body creating an electrochemical cell. These naked or free electrons are not like electricity and don’t have a chemical carrier; they flow within the body’s network of electrically conductive paths to the places where the free radicals are made. These electrons are most strongly attracted to potent free radicals such as hydroxyl radicals (OH•). The chemical equation below reveals the chemistry of two half-cell reactions- one happens on the skin surface where metallic magnesium corrodes, while the other happens deep inside the body.
Figure 4 - The reaction of hydroxyl radicals with magnesium metal to form hydroxide and magnesium ions. This reaction does not require direct collisions between the reactants.
The high innate voltage of this electrochemical reaction means that the anodic and cathodic reactions can occur at great distances from one another. Instead of requiring transport of the antioxidant through the bloodstream and adjacent to the free radical, the electrons can flow through tissues using electrically conductive routes that do not depend upon blood. When the free electron encounters the hydroxyl radical (OH•), it creates benign hydroxide (OH-) which increases pH; this alkalization provides a performance-enhancing effect of its own in addition to neutralization of the radical.
Magnesium Ions and Performance
Magnesium ions formed by the reaction can flow into the body and become part of the free magnesium pool. This free magnesium is rapidly exchanged and regulated within a much larger reservoir of magnesium that includes the magnesium in bones, lymph, cells and other tissues. Magnesium is needed in rather large quantities by human metabolism, and a majority of Americans have a dietary intake of magnesium below the RDA (supplements, 2013) [7]. An analysis of data from the National Health and Nutrition Examination Survey (NHANES) of 2005–2006 found that a majority of Americans of all ages ingest less magnesium from food than their respective EARs (Estimated Average Requirement) (Moshfegh A, 2009) [8]. Magnesium overdose is very uncommon and is mild, especially when it is not administered orally, which eliminates the laxative effect. These magnesium ions are nutrients which exert a positive influence on health and performance. This “coproduct” of electron supplementation contrasts with the oxidized forms of small molecule antioxidants, which must be degraded and eliminated from the body.
Hydroxyl Radicals, Hydroxide and the Alkalizing Effect
Hydroxide is considered by many to have positive effects on performance. It is known as an alkalizing effect, and alkaline substances have been used to enhance performance in athletics for many years. When the electrons flow into the person and attack a hydroxyl radical, this increases pH. Most metabolic processes result in acidic output such as CO2 (aerobic) or lactic acid (anaerobic). When you exercise more than your oxygen delivery can keep up with, the body utilizes anaerobic metabolism. A product of this metabolism is pyruvate, which becomes lactic acid; this acidity leads to the burning sensation in the muscle. This lactic acid moves from muscle to the blood, decreasing your blood pH.
Recent studies (Mueller SM, 2013) [9] showed significant performance enhancement where average cycling time-to-exhaustion (Tlim) increased by 23.5% with NaHCO3 supplementation as compared to placebo. These results corroborate the performance enhancing results of ingesting sodium bicarbonate that have been observed since the seventies (Jones NL, 1977) [10]. In horse racing the use of buffering agents is banned, and limits have been set on the concentration of bicarbonate in blood samples taken before races (Amy M Gill, 2015) [11].
In many examples of medical conditions that cause acidosis, the alkalization of the body has beneficial impacts. The use of enough potassium bicarbonate in the diet to neutralize the daily net acid load in postmenopausal women resulted in a significant increase in Insulin-like Growth Factor-1 (IGF-I). Low protein diets lead to a systematic decrease in many factors such as IGF-1; supplementation with bicarbonate increased the levels of IGF-1 from 95.9 ± 31.7 ng/ml to the same levels as the high protein group 136.4 ± 41.3 ng/ml, a statistically significant change of 40.5 ng/ml (Ceglia L, 2009) [12]. IGF-1 has many roles in the body; one well-documented role for this hormone is the anabolic increase in muscle mass (Velloso, 2008) [13].
Bicarbonate supplementation works, but suffers from many of the same drawbacks as other supplements taken orally. Chronic ingestion of bicarbonate may cause intravascular volume expansion with resultant hyporeninemia and hypoaldosteronemia. These are conditions where low levels of renin and aldosterone dysregulate the water/salt balance in the body. Other side effects are gastrointestinal upsets such as vomiting and diarrhea (McNaughton, 1992) [14].
Oral administration of bicarbonate has caused gastric rupture in at least 8 published case reports. Sodium bicarbonate can cause excess CO2 gas release when combined with gastric acid and can lead to gastric rupture which has a mortality rate as high as 65%. (Lazebnik N, 1986) [15].
Clearly, the benefits of alkalizing the blood for athletic performance are significant, but the means employed to produce this effect through oral supplementation can carry some unacceptable risks which are not justified by the increase in performance. If the alkalinity was increased without the production of carbon dioxide, there would be no interference with the body’s normal signaling mechanisms. Likewise, without the evolution of CO2 gas the gruesome prospect of gastric rupture would also be avoided.
Heliopatch generates alkalinity electrochemically rather than through a direct input of an alkaline substance. Converting the dangerous hydroxyl radical (OH•) into hydroxide (OH-) turns the harmful into something beneficial. This is all without oral supplementation, ingestion or the evolution of gaseous CO2.
Works Cited
Aoki K, A. N. (2012). Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes. July 12 2: 12. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395574/
Boyle SP, D. V. (2000). Absorption and DNA protective effects of flavonoid glycosides from an onion meal. Eur J Nutr., Oct;39(5):213-23. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11131368?dopt=Abstract
Ceglia L, S. S.-H. (2009). Potassium Bicarbonate Attenuates the Urinary Nitrogen Excretion That Accompanies an Increase in Dietary Protein and May Promote Calcium Absorption. J Clin Endocrinol Metab., Feb; 94(2): 645–653. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730228/
Davis JM, M. E. (2009). Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol., Apr;296(4):R1071-7. Retrieved from http://ajpregu.physiology.org/content/296/4/R1071.long
Ji XD, M. N. (1996). Interactions of flavonoids and other phytochemicals with adenosine receptors. J Med Chem., Feb 2;39(3):781-8. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8576921
Jones NL, S. J. (1977). Effect of pH on cardiorespiratory and metabolic responses to exercise. J Appl Physiol Respir Environ Exerc Physiol., Dec;43(6):959-64. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24031
Kang K, Y.-N. K.-B. (2011). Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med Gas Res., June 7 1: 11. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3231938/
Lazebnik N, I. A. (1986). Spontaneous rupture of the normal stomach after sodium bicarbonate ingestion. J Clin Gastroenterol., Aug;8(4):454-6. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/3020119
MacRae HS, M. K. (2006). Dietary antioxidant supplementation combined with quercetin improves cycling time trial performance. Int J Sport Nutr Exerc Metab, Aug;16(4):405-19. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17136942
McNaughton, L. R. (1992). Bicarbonate ingestion: effects of dosage on 60 s cycle ergometry. J Sports Sci., Oct;10(5):415-23. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1331493
Mueller SM, G. S. (2013). Multiday acute sodium bicarbonate intake improves endurance capacity and reduces acidosis in men. J Int Soc Sports Nutr., Mar 26;10(1). Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623762/Velloso, C. P. (2008). Regulation of muscle mass by growth hormone and IGF-I. Br J Pharmacol., Jun; 154(3): 557–568. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2439518/
Footnotes
[1]http://www.ncbi.nlm.nih.gov/pubmed/17136942
[2]http://www.ncbi.nlm.nih.gov/pubmed/8576921
[3]http://ajpregu.physiology.org/content/296/4/R1071.long
[4]http://www.ncbi.nlm.nih.gov/pubmed/11131368?dopt=Abstract
[5]http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3231938/
[6]http://www.medicalgasresearch.com/content/2/1/12
[7]https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/
[9]http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623762/
[10]http://www.ncbi.nlm.nih.gov/pubmed/24031
[11]http://www.equiforce.com/bicarbonate-loading-in-horses.aspx
[12]http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730228/
[13]http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2439518/