Creatine supplementation with specific view to exercise/sports performance: an update

ABSTRACT: Creatine is one of the most popular and widely researched natural supplements. The majority of studies have focused on the effects of creatine monohydrate on performance and health; however, many other forms of creatine exist and are commercially available in the sports nutrition/supplement market. Regardless of the form, supplementation with creatine has regularly shown to increase strength, fat free mass, and muscle morphology with concurrent heavy resistance training more than resistance training alone. Creatine may be of benefit in other modes of exercise such as high-intensity sprints or endurance training. However, it appears that the effects of creatine diminish as the length of time spent exercising increases. Even though not all individuals respond similarly to creatine supplementation, it is generally accepted that its supplementation increases creatine storage and promotes a faster regeneration of adenosine triphosphate between high intensity exercises. These improved outcomes will increase performance and promote greater training adaptations. More recent research suggests that creatine supplementation in amounts of 0.1 g/kg of body weight combined with resistance training improves training adaptations at a cellular and sub-cellular level. Finally, although presently ingesting creatine as an oral supplement is considered safe and ethical, the perception of safety cannot be guaranteed, especially when administered for long period of time to different populations (athletes, sedentary, patient, active, young or elderly).     

The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels

Numerous creatine formulations have been developed primarily to maximize creatine absorption. Creatine ethyl ester is alleged to increase creatine bio-availability. This study examined how a seven-week supplementation regimen combined with resistance training affected body composition, muscle mass, muscle strength and power, serum and muscle creatine levels, and serum creatinine levels in 30 non-resistance-trained males. In a double-blind manner, participants were randomly assigned to a maltodextrose placebo (PLA), creatine monohydrate (CRT), or creatine ethyl ester (CEE) group. The supplements were orally ingested at a dose of 0.30 g/kg fat-free body mass (approximately 20 g/day) for five days followed by ingestion at 0.075 g/kg fat free mass (approximately 5 g/day) for 42 days. Results showed significantly higher serum creatine concentrations in PLA (p = 0.007) and CRT (p = 0.005) compared to CEE. Serum creatinine was greater in CEE compared to the PLA (p = 0.001) and CRT (p = 0.001) and increased at days 6, 27, and 48. Total muscle creatine content was significantly higher in CRT (p = 0.026) and CEE (p = 0.041) compared to PLA, with no differences between CRT and CEE. Significant changes over time were observed for body composition, body water, muscle strength and power variables, but no significant differences were observed between groups. In conclusion, when compared to creatine monohydrate, creatine ethyl ester was not as effective at increasing serum and muscle creatine levels or in improving body composition, muscle mass, strength, and power. Therefore, the improvements in these variables can most likely be attributed to the training protocol itself, rather than the supplementation regimen.     

Creatine supplementation enhances muscle force recovery after eccentrically-induced muscle damage in healthy individuals

Background  

Eccentric exercise-induced damage leads to reductions in muscle force, increased soreness, and impaired muscle function. Creatine monohydrate's (Cr) ergogenic potential is well established; however few studies have directly examined the effects of Cr supplementation on recovery after damage. We examined the effects of Cr supplementation on muscle proteins and force recovery after eccentrically-induced muscle damage in healthy individuals.     

The effects of four weeks of creatine supplementation and high-intensity interval training on cardiorespiratory fitness: a randomized controlled trial

Background  

High-intensity interval training has been shown to be a time-efficient way to induce physiological adaptations similar to those of traditional endurance training. Creatine supplementation may enhance high-intensity interval training, leading to even greater physiological adaptations. The purpose of this study was to determine the effects of high-intensity interval training (HIIT) and creatine supplementation on cardiorespiratory fitness and endurance performance (maximal oxygen consumption (VO_2PEAK), time-to-exhaustion (VO_2PEAKTTE), ventilatory threshold (VT), and total work done (TWD)) in college-aged men.     

Effects of creatine loading on electromyographic fatigue threshold during cycle ergometry in college-aged women

The purpose of this study was to examine the effects of 5 days of Creatine (Cr) loading on the electromyographic fatigue threshold (EMG_FT) in college-aged women. Fifteen healthy college-aged women (mean ± SD = 22.3 ± 1.7 yrs) volunteered to participate in this double-blind, placebo-controlled study and were randomly placed into either placebo (PL – 10 g of flavored dextrose powder; n = 8) or creatine (Cr – 5 g di-creatine citrate plus 10 g of flavored dextrose powder; n = 7; Creatine Edge, FSI Nutrition) loading groups. Each group ingested one packet 4 times per day (total of 20 g/day) for 5 days. Prior to and following supplementation, each subject performed a discontinuous incremental cycle ergometer test to determine their EMG_FT value, using bipolar surface electrodes placed on the longitudinal axis of the right vastus lateralis. Subjects completed a total of four, 60 second work bouts (ranging from 100–350 W). The EMG amplitude was averaged over 10 second intervals and plotted over the 60 second work bout. The resulting slopes from each successive work bouts were used to calculate EMG_FT. A two-way ANOVA (group [Cr vs. PL] × time [pre vs. post]) resulted in a significant (p = 0.031) interaction. Furthermore, a dependent samples t-test showed a 14.5% ± 3.5% increase in EMG_FT from pre- to post-supplementation with Cr (p = 0.009), but no change for the PL treatment (-2.2 ± 5.8%; p = 0.732). In addition, a significant increase (1.0 ± 0.34 kg; p = 0.049) in weight (kg) was observed in the Cr group but no change for PL (-0.2 kg ± 0.2 kg). These findings suggest that 5 days of Cr loading in women may be an effective strategy for delaying the onset of neuromuscular fatigue during cycle ergometry.     

Effect of 28 days of creatine ingestion on muscle metabolism and performance of a simulated cycling road race

Purpose

The effects of creatine supplementation on muscle metabolism and exercise performance during a simulated endurance road race was investigated.

Methods

Twelve adult male (27.3 ± 1.0 yr, 178.6 ± 1.4 cm, 78.0 ± 2.5 kg, 8.9 ± 1.1 %fat) endurance-trained (53.3 ± 2.0 ml* kg^-1* min^-1, cycling ~160 km/wk) cyclists completed a simulated road race on a cycle ergometer (Lode), consisting of a two-hour cycling bout at 60% of peak aerobic capacity (VO_2peak) with three 10-second sprints performed at 110% VO_{2 peak} every 15 minutes. Cyclists completed the 2-hr cycling bout before and after dietary creatine monohydrate or placebo supplementation (3 g/day for 28 days). Muscle biopsies were taken at rest and five minutes before the end of the two-hour ride.

Results

There was a 24.5 ± 10.0% increase in resting muscle total creatine and 38.4 ± 23.9% increase in muscle creatine phosphate in the creatine group (P < 0.05). Plasma glucose, blood lactate, and respiratory exchange ratio during the 2-hour ride, as well as VO_{2 peak}, were not affected by creatine supplementation. Submaximal oxygen consumption near the end of the two-hour ride was decreased by approximately 10% by creatine supplementation (P < 0.05). Changes in plasma volume from pre- to post-supplementation were significantly greater in the creatine group (⁺14.0 ± 6.3%) than the placebo group (^-10.4 ± 4.4%; P < 0.05) at 90 minutes of exercise. The time of the final sprint to exhaustion at the end of the 2-hour cycling bout was not affected by creatine supplementation (creatine pre, 64.4 ± 13.5s; creatine post, 88.8 ± 24.6s; placebo pre, 69.0 ± 24.8s; placebo post 92.8 ± 31.2s: creatine vs. placebo not significant). Power output for the final sprint was increased by ~33% in both groups (creatine vs. placebo not significant).

Conclusions

It can be concluded that although creatine supplementation may increase resting muscle total creatine, muscle creatine phosphate, and plasma volume, and may lead to a reduction in oxygen consumption during submaximal exercise, creatine supplementation does not improve sprint performance at the end of endurance cycling exercise.     

The effects of a high dosage of creatine and caffeine supplementation on the lean body mass composition of rats submitted to vertical jumping training

Background  

The influences of creatine and caffeine supplementation associated with power exercise on lean body mass (LBM) composition are not clear. The purpose of this research was to determine whether supplementation with high doses of creatine and caffeine, either solely or combined, affects the LBM composition of rats submitted to vertical jumping training.     

利用薄层层析诊断和优化一水肌酸的合成条件

本文研究了以层析硅胶为固定相、以甲醇-DMF-乙酸乙酯-水体系为流动相的薄层层析对一水肌酸、肌氨酸钠和O-甲基异脲硫酸盐的分离效果,结果表明流动相组成为10∶2∶2∶1时分离效果较佳;用薄层层析方法对不同条件下一水肌酸合成反应液的组分进行检测,发现反应介质的pH值与温度变化幅度对一水肌酸收率的影响较大,设想通过智能控制pH和温度这两个影响因素可提高一水肌酸的收率。     

The effects of training and creatine malate supplementation during preparation period on physical capacity and special fitness in judo contestants

ABSTRACT: BACKGROUND: The purpose of the study was to determine the effect of 6-weeks training and creatine malate supplementation demonstrated in anaerobic capacity and aerobic power and in special judo fitness test performance (Throws in Total and Index in SJFT). METHODS: Ten professional competitors aged 21.2+/-3.3 years and practicing judo for 11+/-4.5 years participated in a typical pre-competition training program. Their height and weight during the first measurement were 1.75+/-0.06 m and 76.09+/-14.85 kg, respectively. Subjects participated in the same training sessions. The contestants have been training for approximately 20 hours a week: 5 days for 2 two-hour-training sessions. They used their usual diets. They were randomly selected to a treatment group who were administered the creatine malate (n=5) whereas the controls were receiving a placebo (n=5). All subjects were tested for anaerobic capacity (the Wingate-test) and aerobic power (the progressive test), and in the SJFT test, pre and post a six-week training during preparation period. We have used double-blind placebo-controlled design. RESULTS: Multifaceted judo training before competition caused a significant (z=2.40, P<0.05) increase in body mass (76.09+/-14.85 kg, Me=70.73 kg vs. 78.52+/-14.53 kg, Me=75.30 kg, P<0.05, n=10). The significant difference (z=2.30, P<0.05) was observed in FM and FMI, but not in percent fat in body mass (PF%). FM and FMI contributed in increased body mass and BMI, repectively (z=2.40, P<0.05). There was observed an increment in anaerobic capacity indices, with particular focus on shortening in time to obtain peak power toPP (3.99+/-0.71, Me=4.20 sec vs. 3.68 +/-0.77, Me=3.78 sec, P<0.05). Diet supplementation with creatine malate did not cause an increase in body mass index higher than in the control group (P>0.05). However, the groups differed in the post-test moment in the fatigue index (FI) (T=48.7+/-5, Me=46.1 vs. C=41.1+/-3, Me=40.4%, Z=1.98, P<0.05), whereas no significant differences were observed between pre- and post-experiment levels of aerobic power (p>0.05). Percent at VO2max at the anaerobic threshold (%VO2max), in the first measurement showed no significant differences between two groups, while in the second measurement statistically significant differences were observed: in T group %VO2max was higher (85.43+/-6.35, Me=85.5% vs. 76.13+/-3.48, Me=75.3%, Z=2.09, P<0.05). In general, a significant differences were observed in pretests and post-test measurement results in SJFT expressed in Throws in Total (pre=26.9+/-2.7, Me=27.5 vs. post=27.9+/-2.4, Me=28.5 throws (z=2.67, P<0.01), but no such changes was found for the index of SJFT. These changes in SJFT were not found to be caused by the supplementation with creatine malate, neither to be reflected in Throws in Total nor in the index of SJFT (post-test measurements comparison, P>0.05). CONCLUSIONS: The multifaceted judo training is conducive to the development of both FM and FMI. Use of supplementation of the diets with creatine malate does not cause an increase in body mass greater than in the control group. Shorter time to obtain peak power (toPP) is conducive to faster execution of rapid planned actions in attack or defense. Pre and post-training aerobic power did not change so it was not supplementation-dependent. Creatine malate did not affect the results in SJFT. There are many determinants of the judo fight results e.g. technical, tactical, physiological and psychological factors, one of them could be supplementation but it cannot be treated as a separate improving factor. The significant improvement in Total Throws in SJFT with the unchanged Index in SJFT suggests better neuromuscular adaptations compared to those occurring in circulatory and respiratory systems. The results obtained during the SJFT test depend not only on energy resources but also on the exercises which improve the technique of performing typical grip-and-throw judo actions, despite the ensuing fatigue. Key words: judo, training effect, creatine malate supplementation, anaerobic capacity, aerobic power, special fitness.     

Sequential Events in the Irreversible Thermal Denaturation of Human Brain-Type Creatine Kinase by Spectroscopic Methods

The non-cooperative or sequential events which occur during protein thermal denaturation are closely correlated with protein folding, stability, and physiological functions. In this research, the sequential events of human brain-type creatine kinase (hBBCK) thermal denaturation were studied by differential scanning calorimetry (DSC), CD, and intrinsic fluorescence spectroscopy. DSC experiments revealed that the thermal denaturation of hBBCK was calorimetrically irreversible. The existence of several endothermic peaks suggested that the denaturation involved stepwise conformational changes, which were further verified by the discrepancy in the transition curves obtained from various spectroscopic probes. During heating, the disruption of the active site structure occurred prior to the secondary and tertiary structural changes. The thermal unfolding and aggregation of hBBCK was found to occur through sequential events. This is quite different from that of muscle-type CK (MMCK). The results herein suggest that BBCK and MMCK undergo quite dissimilar thermal unfolding pathways, although they are highly conserved in the primary and tertiary structures. A minor difference in structure might endow the isoenzymes dissimilar local stabilities in structure, which further contribute to isoenzyme-specific thermal stabilities.     

Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test

Background

Dietary creatine has been largely used as an ergogenic aid to improve strength and athletic performance, especially in short-term and high energy-demanding anaerobic exercise. Recent findings have also suggested a possible antioxidant role for creatine in muscle tissues during exercise. Here we evaluate the effects of a 1-week regimen of 20?g/day creatine supplementation on the plasma antioxidant capacity, free and heme iron content, and uric acid and lipid peroxidation levels of young subjects (23.1?±?5.8?years old) immediately before and 5 and 60?min after the exhaustive Wingate test.

Results

Maximum anaerobic power was improved by acute creatine supplementation (10.5?%), but it was accompanied by a 2.4-fold increase in pro-oxidant free iron ions in the plasma. However, potential iron-driven oxidative insult was adequately counterbalanced by proportional increases in antioxidant ferric-reducing activity in plasma (FRAP), leading to unaltered lipid peroxidation levels. Interestingly, the FRAP index, found to be highly dependent on uric acid levels in the placebo group, also had an additional contribution from other circulating metabolites in creatine-fed subjects.

Conclusions

Our data suggest that acute creatine supplementation improved the anaerobic performance of athletes and limited short-term oxidative insults, since creatine-induced iron overload was efficiently circumvented by acquired FRAP capacity attributed to: overproduction of uric acid in energy-depleted muscles (as an end-product of purine metabolism and a powerful iron chelating agent) and inherent antioxidant activity of creatine.     

Multi-ingredient pre-workout supplements,safety implications,and performance outcomes: a brief review

In recent years, a new class of dietary supplements called multi-ingredient pre-workout supplements (MIPS) has increased in popularity. These supplements are intended to be taken prior to exercise and typically contain a blend of ingredients such as caffeine, creatine, beta-alanine, amino acids, and nitric oxide agents, the combination of which may elicit a synergistic effect on acute exercise performance and subsequent training adaptations compared to single ingredients alone. Therefore, the purpose of this article was to review the theoretical rationale and available scientific evidence assessing the potential ergogenic value of acute and chronic ingestion of MIPS, to address potential safety concerns surrounding MIPS supplementation, and to highlight potential areas for future research. Though direct comparisons between formulations of MIPS or between a MIPS and a single ingredient are challenging and often impossible due to the widespread use of “proprietary blends” that do not disclose specific amounts of ingredients in a given formulation, a substantial body of evidence suggests that the acute pre-exercise consumption of MIPS may positively influence muscular endurance and subjective mood, though mixed results have been reported regarding the acute effect of MIPS on force and power production. The chronic consumption of MIPS in conjunction with a periodized resistance training program appears to augment beneficial changes in body composition through increased lean mass accretion. However, the impact of long-term MIPS supplementation on force production, muscular endurance, aerobic performance, and subjective measures is less clear. MIPS ingestion appears to be relatively safe, though most studies that have assessed the safety of MIPS are relatively short (less than eight weeks) and thus more information is needed regarding the safety of long-term supplementation. As with any dietary supplement, the use of MIPS carries implications for the athlete, as many formulations may intentionally contain banned substances as ingredients or unintentionally as contaminants. We suggest that athletes thoroughly investigate the ingredients present in a given MIPS prior to consumption. In conclusion, it appears that multi-ingredient pre-workout supplements have promise as an ergogenic aid for active individuals, though further information is required regarding long-term efficacy and safety in a wider variety of populations.     

Reduction of Obesity and Insulin Resistance through Dual Targeting of VAT and BAT by a Novel Combination of Metabolic Cofactors

Obesity is an epidemic disease worldwide, characterized by excessive fat accumulation associated with several metabolic perturbations, such as metabolic syndrome, insulin resistance, hypertension, and dyslipidemia. To improve this situation, a specific combination of metabolic cofactors (MC) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) was assessed as a promising treatment in a high-fat diet (HFD) mouse model. Obese animals were distributed into two groups, orally treated with the vehicle (obese + vehicle) or with the combination of metabolic cofactors (obese + MC) for 4 weeks. Body and adipose depots weights; insulin and glucose tolerance tests; indirect calorimetry; and thermography assays were performed at the end of the intervention. Histological analysis of epidydimal white adipose tissue (EWAT) and brown adipose tissue (BAT) was carried out, and the expression of key genes involved in both fat depots was characterized by qPCR. We demonstrated that MC supplementation conferred a moderate reduction of obesity and adiposity, an improvement in serum glucose and lipid metabolic parameters, an important improvement in lipid oxidation, and a decrease in adipocyte hypertrophy. Moreover, MC-treated animals presented increased adipose gene expression in EWAT related to lipolysis and fatty acid oxidation. Furthermore, MC supplementation reduced glucose intolerance and insulin resistance, with an increased expression of the glucose transporter Glut4; and decreased fat accumulation in BAT, raising non-shivering thermogenesis. This treatment based on a specific combination of metabolic cofactors mitigates important pathophysiological characteristics of obesity, representing a promising clinical approach to this metabolic disease.     

Sex-Based Impact of Creatine Supplementation on Depressive Symptoms,Brain Serotonin and SSRI Efficacy in an Animal Model of Treatment-Resistant Depression

Background: Rates of major depressive disorder (MDD) increase with living at altitude. In our model, rats housed at moderate altitude (in hypobaric hypoxia) exhibit increased depression-like behavior, altered brain serotonin and a lack of antidepressant response to most selective serotonin reuptake inhibitors (SSRIs). A forebrain deficit in the bioenergetic marker creatine is noted in people living at altitude or with MDD. Methods: Rats housed at 4500 ft were given dietary creatine monohydrate (CRMH, 4% w/w, 5 weeks) vs. un-supplemented diet, and impact on depression-like behavior, brain bioenergetics, serotonin and SSRI efficacy assessed. Results: CRMH significantly improved brain creatine in a sex-based manner. At altitude, CRMH increased serotonin levels in the female prefrontal cortex and striatum but reduced male striatal and hippocampal serotonin. Dietary CRMH was antidepressant in the forced swim test and anti-anhedonic in the sucrose preference test in only females at altitude, with motor behavior unchanged. CRMH improved fluoxetine efficacy (20 mg/kg) in only males at altitude: CRMH + SSRI significantly improved male striatal creatine and serotonin vs. CRMH alone. Conclusions: Dietary CRMH exhibits sex-based efficacy in resolving altitude-related deficits in brain biomarkers, depression-like behavior and SSRI efficacy, and may be effective clinically for SSRI-resistant depression at altitude. This is the first study to link CRMH treatment to improving brain serotonin.     

Polyphenols and Sunburn

Polyphenols are antioxidant molecules found in many foods such as green tea, chocolate, grape seeds, and wine. Polyphenols have antioxidant, anti-inflammatory, and antineoplastic properties. Growing evidence suggests that polyphenols may be used for the prevention of sunburns as polyphenols decrease the damaging effects of ultraviolet A (UVA) and ultraviolet B (UVB) radiation on the skin. This review was conducted to examine the evidence for use of topically and orally ingested polyphenols in prevention of sunburns. The PubMed database was searched for studies that examined polyphenols and its effects on sunburns. Of the 27 studies found, 15 met the inclusion criteria. Seven studies were conducted on human subjects and eight on animals (mice and rats). Eleven studies evaluated the effects of topical polyphenols, two studies examined ingested polyphenols, and two studies examined both topical and ingested polyphenols. Polyphenol sources included the following plant origins: green tea, white tea, cocoa, Romanian propolis (RP), Calluna vulgaris (Cv), grape seeds, honeybush, and Lepidium meyenii (maca). Eight studies examined green tea. Overall, based on the studies, there is evidence that polyphenols in both oral and topical form may provide protection from UV damage and sunburn, and thus are beneficial to skin health. However, current studies are limited and further research is necessary to evaluate the efficacy, mechanism of action, and potential side effects of various forms and concentrations of polyphenols.     

Tierische Fette in Backwaren

Animal Fats in Bakery Products In the bakery industry fats play an important role as baking agent and frying medium. Animal fats are employed in this field due to their taste convenience in handling fatty doughs made with them, and due to the crispyness and freshness of the baked goods prepared with these fats. However, due to changes in the manufacture of baked goods and consumer desires, the use of animal fats in bakery products has declined considerably. In this respect the occurrence of free fatty acids in freshly rendered animal fats has the most undesirable impact. It is shown that the decline in the use of animal fats is possibly related to the problems involved in their recovery, freshness and stability. Examples are given showing the alterations of lard during frying. Products of such alterations of fats are ingested with the baked good. Possible deteriorations of the quality of such goods are explained. The quality of baked goods could be improved by using refined animal fats.     

Regulation of the Fructose Transporter Gene Slc2a5 Expression by Glucose in Cultured Microglial Cells

Microglia play a role in the regulation of metabolism and pathogenesis of obesity. Microglial activity is altered in response to changes in diet and the body’s metabolic state. Solute carrier family 2 member 5 (Slc2a5) that encodes glucose transporter 5 (GLUT5) is a fructose transporter primarily expressed in microglia within the central nervous system. However, little is known about the nutritional regulation of Slc2a5 expression in microglia and its role in the regulation of metabolism. The present study aimed to address the hypothesis that nutrients affect microglial activity by altering the expression of glucose transporter genes. Murine microglial cell line SIM-A9 cells and primary microglia from mouse brain were exposed to different concentrations of glucose and levels of microglial activation markers and glucose transporter genes were measured. High concentration of glucose increased levels of the immediate-early gene product c-Fos, a marker of cell activation, Slc2a5 mRNA, and pro-inflammatory cytokine genes in microglial cells in a time-dependent manner, while fructose failed to cause these changes. Glucose-induced changes in pro-inflammatory gene expression were partially attenuated in SIM-A9 cells treated with the GLUT5 inhibitor. These findings suggest that an increase in local glucose availability leads to the activation of microglia by controlling their carbohydrate sensing mechanism through both GLUT5-dependent and –independent mechanisms.     

Incorporation of alpha-linolenic acid and linoleic acid into human respiratory epithelial cell lines

Animal and human studies designed to examine the effects of α-linolenic acid (ALA) and linoleic acid (LA) supplementation on the fatty acid composition of plasma and tissues have demonstrated a marked difference in incorporation into phospholipids of these 18-carbon precursors of the long-chain polyunsaturates. Whereas tissue phospholipid levels are linearly related to dietary ALA and LA, the levels of tissue LA can be 10-fold higher than tissue ALA even when dietary levels are equivalent. There is some dispute whether this disparity is due to ALA being more rapidly metabolized to its products or substantially oxidized by the liver, or whether LA but not ALA is readily incorporated into cellular phospholipids. We examined the level of incorporation of polyunsaturated fatty acids into human respiratory epithelial cell lines (A549, 16HBE) by determining the dose-dependent incorporation of ALA and LA as free fatty acid (5–150 μg FFA/mL). Cell membrane phospholipid ALA and LA were both increased up to ∼20–30% total fatty acids, with a concomitant decrease predominantly in monounsaturated membrane fatty acids, before significant toxicity was observed (50 μg/mL). Our data support the concept that rather than any inherent inability by human cells to incorporate ALA into membrane phospholipids, the lack of ALA content in human and animal tissues in vivo is due to the rapid metabolism or oxidation of this fatty acid in the liver.