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Vitamin B12 plays an important role in supplying essential methyl groups for protein and DNA synthesis. Vitamin B12 is bound to the protein in food and hydrochloric acid in the stomach release B12 from protein during digestion. Once released, B12 combines with a substance called instrinsic factor. In humans, Vitamin B12 is required coenzyme for two important enzymes, methionine synthase and methylmalonyl CoA mutase. (3-5)

Methionine synthase, uses the chemical form of the vitamin which has a methyl group attached to the cobalt and is called methylcobalamin. Methionine synthase catalyzes the conversion of homocysteine to methionine via the methionine cycle and regenerates tetrahydrofolate (THF) (3,4).

Unlike the other water-soluble vitamins, vitamin B12 is stored in the liver, primarily in the form of adenosylcobalamin. L-Methylmalonyl CoA mutase requires adenosylcobalamin for the conversion of L-methylmalonyl CoA to succinyl-CoA, an important intermediary in the extraction of energy from proteins and fats. Methylmalonyl CoA mutase, uses a form of vitamin B12 that has a 5’-adeoxyadenosyl moiety attached to the cobalt and is called 5’deoxyadenosylcobalamin, or coenzyme B12.

In nature, there are two other forms of vitamin B12: hydroxycobalamin and aquacobalamin, where hydroxyl and water groups, respectively, are attached to the cobalt. The synthetic form of vitamin B12 found in supplements and fortified foods is cyanocobalamin, which has cyanide attached to the cobalt. These three forms of vitamin B12 are enzymatically activated to the methyl- or deoxyadenosylcobalamins in all mammalian cells. (3, 5).

A double-blind, randomized, placebo-controlled three-arm study of sixty healthy adult women ages 40 - 60 were randomly assigned to one of three groups: a daily oral dose of 250 mg citicoline, 500 mg citicoline, or placebo for 28 days. Participants were evaluated with the Continuous Performance Test II (CPT-II), a measure sensitive to attentional function, during a baseline visit and 28 days after baseline. After 28 days of supplementation, individuals in the 250 mg group made fewer omission (p = 0.04) and commission (p = 0.03) errors compared to those in the placebo group. After 28 days of daily citicoline supplementation, participants who were administered either the 250 mg or the 500 mg citicoline doses showed significantly better ability to produce correct responses on the CPT-II. The study researcher concluded that citicoline may improve attentional performance and may ameliorate attentional deficits.

A separate double-blind, placebo-controlled, three-arm design study investigated the effectiveness of two doses of citicoline (250 and 500 mg/day) or placebo on attention and motor function after 4 weeks of supplementation. 75 healthy adolescent males were given neuropsychological measures assessing motor performance and attention at the beginning and end of the study period to investigate changes in functioning. The study found that citicoline supplementation was associated with improved motor function and attentional abilities in healthy adolescent males in doses of 250-500mg.

Numerous studies have shown that caffeine is known to exert positive effects on cognitive performance such as reaction time, alertness, and sustained attention. Two double-blind, placebo-controlled crossover studies found that moderate levels of caffeine enhanced sustained attention and alertness, decreased feelings of mental fatigue, reduced reaction time, improved performance on attention tasks and increased overall mood ratings.

Nutritional ergogenic acids are “substances that can enhance performance and are either nutrients, metabolic by-products of nutrients, food (plant) extracts, or substances commonly found in foods (e.g. caffeine) that are provided in amounts more concentrated than commonly found in the natural food supply” (2). Furthermore, as a central nervous system stimulant, caffeine may allow a continuation of performance at a higher level by stimulating the brain into a lower level of fatigue (2).

It is widely shown that caffeine can help with endurance-type performance activities. In its position on caffeine and performance, the International Society of Sports Nutrition (ISSN) concludes that caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg/kg body weight). Additionally, caffeine can enhance vigilance during bouts of extended exhaustive exercise, as well as periods of sustained sleep deprivation. Caffeine supplementation has also been shown to be beneficial for high-intensity exercise, sustained maximal endurance exercise and time-trial performance (3).

In 2011, the European Food Safety Authority (EFSA) determined that relationships have been established between caffeine consumption and increased endurance performance and increased endurance capacity at intake levels of at least 3 mg/kg body weight administered at least an hour prior to exercise. The Panel also concluded that caffeine ingestion of at least 4 mg/kg body weight administered at least one our prior to exercise reduced perceived exertion/effort during exercise (4).

Health Canada’s Natural Health Product monograph for caffeine permits the following performance claims at dosages of 100-200 mg (1):

• Helps (temporarily) to relieve fatigue, to promote endurance, and to enhance motor performance

Researchers studying the effect of coffee, which contained approximately 150-200 mg caffeine, on treadmill running time found that individuals taking the caffeinated product had a 4.2 second faster run time, as compared to decaffeinated coffee. Additionally, all subjected achieved significantly faster run speeds following ingestion of caffeinated coffee. Finally, during the sustained high-intensity effort, eight of ten subjects had increased VO2 values (5).

In a randomized, double-blind, placebo controlled study assessing the performance benefits of caffeine on experienced basketball players, researchers found that 3mg/kg body weight of caffeine increased mean jump height, increased the number of body impacts without modifying mean or peak heart rate and also increased the performance index during the game (6).