Athletes and Vitamin Infusions
It all started when...
WHAT THE RESEARCH SHOWS
How do athletes know if they are getting all of their body’s required micronutrient sources from food alone and how many athletes take in a sufficiently balanced, nutrient dense diet?
A study by the National Collegiate Athletic Association (NCAA) paints a clear picture: that a large percentage of athletes aren’t taking in a diet sufficient in recommended micronutrients from food alone found. Males typically fell below the energy intake recommendations of carbohydrates, protein and macronutrients designed specific to athletes needs. The most common micronutrient inadequacies for BOTH genders were folate, vitamin E, and zinc. Additionally, in this study, males were significantly lower in iron, magnesium, potassium, phosphorous, zinc, niacin, vitamin B6, folate, and vitamin A.4
In 2006, Misner analyzed 70 diets from athletes or sedentary subjects who sought to improve the quality of micronutrient intake solely from food choices.2 He found that every one “fell short of the recommended 100% RDA micronutrient level from food alone,” with all subjects presenting between 3 and 15 different micronutrient deficiencies. These studies demonstrate that athletes’ dietary choices do not provide all of the micronutrients necessary to prevent nutrient-deficiency diseases, let alone optimize athletic potential or maximize injury recovery.
According to the ACSM and the IOC, the most common micronutrients found to be lacking in athlete’s diets are iron, zinc, magnesium, calcium, the B vitamins, vitamin D, and antioxidants such as vitamins A, C, E, and selenium.1,5 Furthermore, Misner noted that 100% of the diets examined were deficient in iodine, 95% were deficient in vitamin D, 80% were deficient in zinc, 65% were deficient in vitamin E, and 50% were deficient in calcium.2 As these vitamins and minerals are important coenzymes for many biochemical pathways, it should be of high importance to athletes, coaches, and physicians to address these potential deficiencies in order to prevent injuries and maximize athletic performance.
HOW BEST TO SUPPLEMENT?
The next important question: which route of administration should be used for supplementation – oral or IV? The use of IV therapy may have merit due to the facts that certain vitamins and minerals can compete with each other for absorption when taken orally, and that gastrointestinal (GI) absorption has upper limits. Dr. Dave Arneson, a leader in the field of naturopathic approaches notes “vitamin C absorption is an energy-dependent absorption via ATP and nutritional deficiencies impair the production of ATP, thus inhibiting oral absorption of oral vitamin C. IVs solve this problem and bypass the absorption limitations of the GI system. Unfortunately, research in this area is severely lacking, with only a small handful of studies examining the efficacy of IV versus oral administration of micronutrients. Note however that World Antidoping Agency prohibits Vitamin Infusions as they are considered
Vitamin C is an important micronutrient for athletes due to its role as an antioxidant and its function in collagen synthesis, and is commonly administered intravenously. It is now widely accepted that IV vitamin C (IVC), but not oral vitamin C, produces pharmacologic plasma concentrations, with the ability to produce peak plasma concentrations 25-fold higher than the equivalent oral dose.6 Padayatty et al7 (2004) found that vitamin C plasma concentrations continued to increase with increasing IVC – a phenomenon not seen with oral vitamin C – and resulted in greater than 6-fold higher plasma concentrations, demonstrating the effectiveness of IVC versus oral supplementation of vitamin C (Table 1).
Table 1. Effects of Intravenous Micronutrient Therapy in Humans
Padayatty7; 2004RCT; 17 healthy volunteers
Following vitamin C depletion in a hospital setting, subjects received oral or IV doses in the range of 0.015 to 1.25 g.
Vitamin C from blood samples measured using HPLC with coulometric electrochemical detection
IV administration of vitamin C produced up to 6.6-fold higher peak plasma vitamin C concentrations compared to the same dose administered orally (p<0.001).
Peak plasma vitamin C concentrations appeared to plateau with increasing oral doses, while plasma concentrations continued to increase with increasing IV doses.
Garvican8; 2014RCT; 27 highly-trained distance runners with either low iron status (ferritin <35 µg/L & transferrin saturation <20%, or ferritin <15 µg/L) or sub-optimal iron status (ferritin <65 µg/L)
6 weeks IV iron
6 weeks oral iron
Iron status (blood sample and biochemistry analyzer), Hbmass(carbon monoxide rebreathing method), and VO2max(treadmill test) assessed pre- and post-iron treatment.
Both IV and oral supplementation increased serum ferritin, with IV > oral (417.5 ± 37.2% vs 88.5 ± 29.2%, respectively).
Hbmass and VO2max significantly increased with IV iron, but not oral iron supplementation.
(RCT = randomized controlled trial; IV = intravenous; Hbmass = hemoglobin mass; VO2max = maximum oxygen consumption)
Iron, a common micronutrient deficiency particularly seen in females and endurance athletes among both genders, is another micronutrient that appears to have better results with IV administration. One study8found that IV iron was able to rapidly reverse serum ferritin deficiencies and increase VO2max and hemoglobin mass in iron-deficient distance runners, whereas oral iron supplementation produced a less rapid increase in serum ferritin that was not accompanied by an increase in VO2max or hemoglobin mass (Table 1). These results demonstrate that IV administration of iron is superior to oral administration, not only for removing an athlete’s fatigue, but also for improving their performance.
There is another body of research that examined the potential ergogenic effects of amino acids and their derivatives when administered intravenously. While improving athletic performance is not often considered a focus in naturopathic medicine, IV therapy can be an effective tool for practitioners to deter athletes from the use of illegal performance-enhancing drugs. Potential ergogenic aids discussed in the literature include arginine, ornithine, N-acetylcysteine, and acetyl-L-carnitine.
IV administration of arginine appears to be the most widely studied for its ability to stimulate the pituitary gland to release endogenous growth hormone (GH). In 2002, Chromiak and Antonio9 reviewed 17 sets of data from 11 different randomized controlled trials on the effects of oral and IV arginine on GH release. They concluded that IV infusion of arginine, but not oral consumption, can increase GH release (Table 2). Furthermore, these findings held true when subjects also engaged in exercise, which is known to naturally increase GH. Lastly, gender difference appears to exist in the GH response, with females exhibiting greater increases in GH compared to males.9 It was postulated that the increased GH release with IV infusion may be due to greater serum arginine levels compared to oral consumption.
Table 2. Effects of IV Amino Acids and Derivatives on Athletic Performance
Reference Methods Outcome
Chromiak9; 2002Systematic review; 17 data sets from 11 RCTsGH response examined in:
10 data sets studying oral arginine supplementation (5 with exercise, 5 without)AND
7 data sets studying IV arginine supplementation (1 with exercise, 6 without)Oral with exercise: Four studies found either no increase in exercise-related GH release with amino acid supplementation (which included arginine), or no difference between amino acids + exercise, or placebo + exercise. One study found that 20 g arginine + glutamine decreased exercise-related GH release.
Oral without exercise: One study showed a 2.7-fold increase in plasma GH; another demonstrated an 8-fold increase; and the other 3 studies were not able to detect any increases.
Note: In both studies showing GH increases, subjects consumed both arginine and lysine. No GH increase was observed in the single study that administered oral arginine alone.
IV with exercise: 30 g IV arginine and exercise resulted in a greater increase in GH compared to IV placebo and exercise.
IV without exercise: IV arginine, in doses ranging from 183 mg/kg to 550 mg/kg, resulted in up to a 13-fold increase in GH, except for males receiving the lowest dose (183 mg/kg), who saw no change. Three studies concluded a greater GH response in females compared to males.
Medved10; 2004DBCS; 8 endurance-trained healthy subjects received NAC or placebo before and during 45 min of cycling at 70% VO2max, and then to volitional fatigue at 90% VO2max.IV NAC: loading dose of 125 mg/kg/hr for 15 min, followed by constant infusion of 25 mg/kg/hr beginning 20 min prior to exercise protocol and continuing throughout the duration of exercise
IV saline (control)
NAC, GSH status, and cysteine concentration measured via arterialized venous blood analysis
Skeletal tissue NAC, total GSH, reduced GSH, cysteine and cystine measured via vastus lateralis biopsy
Time to fatigue at 90% VO2max was significantly increased following NAC infusion by 26.3 ± 9.1% vs control group (p<0.05)
Muscle cysteine levels increased above pre-infusion levels following NAC infusion, but were unchanged in the control group (p<0.001).
Both total GSH and reduced GSH were higher in muscle cells in the NAC group vs the control at 45 min and fatigue (p<0.05), suggesting that NAC infusion improved performance by maintaining blood redox status.
Stephens12; 2006RCT; 7 healthy, non-vegetarian young men, mean age 22.4 years
After achieving steady-state hyperinsulinemia (serum insulin 160 mU/L), 5-h IV infusion of 60 mM acetyl-L-carnitine (blood concentration 600 µmol/L)
5-h IV infusion of equal volume saline (control)
Blood carnitine measured via radioenzymatic assay of arterialized venous blood
Muscle carnitine, glycogen, long-chain acyl-CoA, glucose-6-phosphate, and lactate measured via radioenzymatic methods following vastus lateralis biopsy
Skeletal muscle PDC activity assayed from vastus lateralis biopsy and expressed as a rate of acetyl-CoA formation
Intramuscular carnitine levels increased in the treatment group by 15% compared to the control group (p<0.01), and was associated with:
30% decrease in PDC activity (p<0.05);
40% decrease in muscle lactate content (p<0.05);
30% increase in muscle glycogen stores (p<0.01); and
40% increase in long-chain acyl CoA content (p<0.05)
(GH = growth hormone; IV = intravenous; DBCS = double-blind control study; NAC = N-acetylcysteine; GSH = glutathione; VO2max = maximum oxygen consumption; RCT = randomized controlled trial; PDC = pyruvate dehydrogenase complex)
N-acetylcysteine (NAC) is an amino acid derivative shown in research to improve athletic performance, and therefore could be a tool for physicians looking to help athletes legally improve performance. In 2002, Medved et al10 demonstrated that time to exhaustion during an exercise test at 90% VO2max was significantly increased after IV infusion of NAC, compared to a control group (Table 2). As an antioxidant, NAC reduces the harmful effects of reactive oxygen species (ROS) in skeletal muscle (ROS have been linked with muscular fatigue), either through the direct scavenging of ROS and/or by supplying intramuscular cysteine, which results in increased glutathione (GSH) synthesis; GSH is also an endogenous antioxidant within skeletal muscle that functions to minimize the accumulation of ROS.
Lastly, the physiological mechanism for which acetyl-L-carnitine increases intramuscular carnitine (IMC) levels and exerts its ergogenic effects has only recently been discovered in the last decade. Until it was discovered that insulin played an essential role in transporting carnitine into skeletal muscle tissue across a steep concentration gradient, researchers were unable to demonstrate that supplementation led to increased IMC levels.11 Specifically, carnitine plays an essential role in 2 important energy metabolism pathways in skeletal muscle: β-oxidation, and the regulation of the acetyl-CoA/CoASH ratio, which is important in delaying muscular fatigue during intense exercise.12 Stephens et al13 demonstrated an increase in IMC levels following IV infusion of acetyl-L-carnitine in hyperinsulinemic conditions, and concluded that the increase in IMC concentrations inhibited both glycolytic flux (thereby reducing lactate levels) and the oxidation of carbohydrates in the pyruvate dehydrogenase complex, resulting in glucose uptake in skeletal muscle being diverted towards glycogen storage instead of utilization. Furthermore, the decrease in carbohydrate flux was matched by an increase in fat oxidation due to their reciprocal relationship in skeletal muscle.13 This becomes important for athletes when working above 70% VO2max, as the sparing of muscle glycogen, and the consequent upregulation of β-oxidation, delays fatigue and increases exercise performance.12
In regards to body weight maintenance, competitive athletes often have an ideal “competition weight”; they prefer to compete at a slightly lighter weight in an attempt to increase power. One study found that the majority of female athletes, regardless of their sport, had the desire to weigh less. This also held true for males in certain sports (wresting, track and field, and golf), just to a lesser degree. Caloric restriction was the most common strategy for both groups for achieving this weight loss.4 In 2010 the International Olympic Committee (IOC) released a consensus on sports nutrition, stating that “careful selection of nutrient-rich foods to reduce the risk of developing nutrient deficiencies that impair both health and performance is especially important when energy intake is restricted to reduce body and/or fat mass.”5Additionally, calorie deficits tend to increase the number of different micronutrient deficiencies compared to calorie-sufficient diets.2
The aim of this review article is to use current research to challenge the notion that athletes who take in a well-balanced, nutrient-dense diet, and with enough energy to maintain body weight, do not require additional vitamin and mineral supplementation. Our aim is also to promote the idea that IV therapy can be a useful and practical tool for naturopathic physicians, not only to restore optimal micronutrient levels in athletes, but also to serve as an ergogenic aid.
While the field is still in its infancy, there is promising research in support of micronutrient IV administration in comparison to oral consumption. Specifically, research on vitamin C and iron have demonstrated that IV therapy may provide superior results to oral supplementation, which likely is a function of bypassing absorption in the stomach, resulting in pharmacological plasma concentrations. Additionally, research examining IV infusions of arginine has demonstrated superior results compared to oral supplementation for increasing GH secretion from the pituitary gland, thereby acting as an ergogenic aid. N-acetylcysteine has been found to be another IV ergogenic aid due to its ability to minimize ROS accumulation within skeletal muscle, thereby delaying fatigue in athletes. Lastly, IV acetyl-L-carnitine improves performance by sparing muscle glycogen and increasing the need for fat utilization during high-intensity training. Future research should be conducted to identify additional uses of IV therapy in relation to micronutrient status, injury rehabilitation, and performance enhancements.