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Medium-chain fatty acids: Evidence for incorporation into chylomicron triqlycerides in humans
Abstract
The purpose of this study was to evaluate the fatty acid composition of chylomicron triglycerides isolated from subjects fed liquid-formula diets containing 40% of total energy as medium- (C8:0 and C10:0) or long-chain (C16-C18) triglycerides (MCT, LCT) for 6 d. Medium-chain fatty acids (MCFA) comprised 8% of total chylomicron triglyceride fatty acids after the first MCT meal. After 6 d of continued MCT feeding, chylomicron triglyceride MCFA content increased to 13%. When subjects were fed the LCT (soybean oil) diet, C16:0, C18:1, and C18:2 comprised nearly 90% of the chylomicron triglyceride fatty acids. The mass of triglyceride transported in chylomicrons isolated from subjects fed the MCT diet was approximately 20% of that found when subjects consumed the LCT diet. We conclude that although total triglyceride production during MCT ingestion is low, the chylomicron triglycerides that are synthesized contain significant amounts of MCFA.
... 126,127 Individuals with FCS are allowed to consume MCTs because these fatty acids are absorbed almost entirely via the portal circulation, being minimally incorporated into chylomicrons. 128,129 It is important to note that lauric acid (C12:0) is considered a long-chain fatty acid that is transported mainly via chylomicrons, being transported via the portal circulation only when its storage capacity in this lipoprotein is exceeded. 129,130 Therefore, it is essential to carefully observe the fatty acid composition of the product, which should preferably contain no or minimal concentrations of lauric acid to prevent an increase in chylomicron concentrations. ...
... 128,129 It is important to note that lauric acid (C12:0) is considered a long-chain fatty acid that is transported mainly via chylomicrons, being transported via the portal circulation only when its storage capacity in this lipoprotein is exceeded. 129,130 Therefore, it is essential to carefully observe the fatty acid composition of the product, which should preferably contain no or minimal concentrations of lauric acid to prevent an increase in chylomicron concentrations. ...
... In addition, MCTs can be recommended to achieve optimal energy intake, according to tolerance, because they are minimally transported by chylomicrons. 128,129 The introduction of solid foods such as vegetables, fruits, and lean meats (e.g., fish, skinless chicken breast, lean beef), and grains should follow the recommendations of national and international pediatric societies, limiting dietary fat intake to 10% of daily TEI. ...
... 126,127 Individuals with FCS are allowed to consume MCTs because these fatty acids are absorbed almost entirely via the portal circulation, being minimally incorporated into chylomicrons. 128,129 It is important to note that lauric acid (C12:0) is considered a long-chain fatty acid that is transported mainly via chylomicrons, being transported via the portal circulation only when its storage capacity in this lipoprotein is exceeded. 129,130 Therefore, it is essential to carefully observe the fatty acid composition of the product, which should preferably contain no or minimal concentrations of lauric acid to prevent an increase in chylomicron concentrations. ...
... 128,129 It is important to note that lauric acid (C12:0) is considered a long-chain fatty acid that is transported mainly via chylomicrons, being transported via the portal circulation only when its storage capacity in this lipoprotein is exceeded. 129,130 Therefore, it is essential to carefully observe the fatty acid composition of the product, which should preferably contain no or minimal concentrations of lauric acid to prevent an increase in chylomicron concentrations. ...
... In addition, MCTs can be recommended to achieve optimal energy intake, according to tolerance, because they are minimally transported by chylomicrons. 128,129 The introduction of solid foods such as vegetables, fruits, and lean meats (e.g., fish, skinless chicken breast, lean beef), and grains should follow the recommendations of national and international pediatric societies, limiting dietary fat intake to 10% of daily TEI. ...
... This is because most of the lauric acid in the diet (70-75%) is absorbed via chylomicrons, similar to a LCFA (Denke and Grundv, 1992). In comparison, approximately 95% of other MCFAs are absorbed straight into the portal vein (Swift et al., 1990). Therefore, depending on whether the chemical nature or the physiological properties are examined, lauric acid can be categorized as a MCFA or a LCFA. ...
... Despite the potential benefits of MCFAs for weight reduction, the current study's findings do not support this hypothesis. This might be because, when metabolic functions are considered, lauric acid, which has also been classified as an LCFA is first transported into the lymphatic and peripheral systems (Denke and Grundv, 1992), while 95% of MCFAs are taken directly to the liver (Swift et al., 1990), causing rapid oxidation of MCFA than LCFA. As a consequence, our anthropometric measurement results showing no significant weight loss confirms that the biological function of both palm and coconut oil may be attributable to LCFAs. ...
... These fatty acids in various proportions may lead to differences in drug loading into chylomicrons. Previously published works reported that MCT appears in human chylomicrons after oral administration of MCT [265]. Indeed, the current study has also shown that MCT were detected in the chylomicron samples after administration of coconut oil (Table 5-2). ...
Lipid-based formulations play a significant role in oral delivery of lipophilic drugs. Previous studies have shown that natural sesame oil promotes the intestinal lymphatic transport and oral bioavailability of highly lipophilic drug cannabidiol (CBD). However, both lymphatic transport and systemic bioavailability were also associated with considerable variability. The first aim of this thesis was to test the hypothesis that pre-digested lipid formulations (oleic acid, linoleic acid, oleic acid with 2-oleoylglycerol, oleic acid with 2-oleoylglycerol and oleic acid with glycerol) could reduce variability and increase the extent of the intestinal lymphatic transport and oral bioavailability of CBD. In vivo studies in rats showed that pre-digested or purified triglyceride did not improve the lymphatic transport and bioavailability of CBD in comparison to sesame oil. Moreover, the results suggest that both the absorption of lipids and the absorption of co-administered CBD were more efficient following administration of natural sesame oil vehicle compared with pre-digested lipids or purified trioleate. However, this natural oil-based formulation also leads to considerable variability in absorption of CBD [1]. Therefore, the second approach in this thesis was to test the performance of lipid-based formulations with the addition of medium-chain triglyceride (MCT) or surfactants to the sesame oil vehicle in vitro and in vivo using CBD as a model drug. The in vitro lipolysis has shown that addition of the MCT leads to a higher distribution of CBD into the micellar phase. Further addition of surfactants to MCT-containing formulations did not improve distribution of the drug into the micellar phase. In vivo, formulations containing MCT led to lower or similar concentrations of CBD in serum, lymph and mesenteric lymph nodes (MLN), but with reduced variability. MCT improves the emulsification and micellar solubilisation of CBD, but surfactants did not facilitate further the rate and extent of lipolysis. Even though addition of MCT reduces the variability, the in vivo performance for the extent of both lymphatic transport and systemic bioavailability remains superior with a pure natural oil vehicle [2]. These results lead to the hypothesis that differences in composition of vegetable oils lead to differences in promotion of intestinal lymphatic transport of lipophilic drugs. Therefore, the differences in composition of sesame, sunflower, peanut, soybean, olive and coconut oils and their corresponding role as vehicles in promoting CBD lymphatic targeting and bioavailability were investigated in this thesis. The comparative analysis suggested that the fatty acids profile of vegetable oils is overall similar to the fatty acids profile in the corresponding chylomicrons in rat lymph. However, arachidonic acid (C20:4), was introduced to chylomicrons from endogenous nondietary sources in all cases. Overall, fatty acid composition of natural vegetable oils vehicles affected the intestinal lymphatic transport and bioavailability of CBD following oral administration in this work. Olive oil led to the highest concentration of CBD in the lymphatic system and systemic circulation and low variability in comparison to other natural vegetable oils following oral administration in rats. The natural rapeseed oil bodies also used as lipid-based vehicles to facilitate CBD oral bioavailability and lymphatic transport in this thesis. The oral bioavailability of CBD was 1.7-fold higher in oil bodies-based formulation than rapeseed oil-based formulation in rats. This finding indicates that oil bodies could potentially to improve lipophilic drug systemic exposure and lymphatic targeting in comparison to simple oils, and their other pharmaceutical properties as a drug delivery carrier needs to be further investigated. Overall in this thesis, olive oil and oil bodies are preferred lipid vehicles for improving intestinal lymphatic transport and bioavailability of co-administered CBD following oral administration.
... Intestinal lymphatic transport of absorbed nutraceuticals Nearly 90% of LCFAs and a small number of MCFAs are assembled into TAGs in the epithelium cells, which then form the hydrophobic core of colloidal lipoproteins (chylomicrons) that are released into the intestinal lymph ( Figure 5) (Porter et al., 2007;Swift et al., 1990). This process involves a collaboration between the ER and Golgi, and involves lipoproteins, such as apolipoprotein B48 (apoB48), apolipoprotein AI (apoAI), and apolipoprotein AIV (apoAIV) (Abumrad & Davidson, 2012;Hussain, 2014;Hussain et al., 2012). ...
Increasing awareness of the health benefits of specific constituents in fruits, vegetables, cereals, and other whole foods has sparked a broader interest in the potential health benefits of nutraceuticals. Many nutraceuticals are hydrophobic substances, which means they must be encapsulated in colloidal delivery systems. Oil‐in‐water emulsions are one of the most widely used delivery systems for improving the bioavailability and bioactivity of these nutraceuticals. The composition and structure of emulsions can be designed to improve the water dispersibility, physicochemical stability, and bioavailability of the encapsulated nutraceuticals. The nature of the emulsion used influences the interfacial area and properties of the nutraceutical‐loaded oil droplets in the gastrointestinal tract, which influences their digestion, as well as the bioaccessibility, metabolism, and absorption of the nutraceuticals. In this article, we review recent in vitro and in vivo studies on the utilization of emulsions to improve the bioavailability of nutraceuticals. The findings from this review should facilitate the design of more efficacious nutraceutical‐loaded emulsions with increased bioactivity.
Although numerous studies indicate that formula-fed infants are more prone to obesity than breastfed ones, the underlying reasons have not been fully elucidated. This study aimed to determine the impact of human milk fat substitutes (HMFS) on the lipid metabolism of first-weaned Sprague Dawley rats. The findings revealed that administering HMFS did not affect the body weight of the rats (control: 298.38 ± 26.73 g, OPO (1,3-dioleic acid-2-palmitoyl triglyceride): 287.82 ± 19.85 g and HMFS: 302.31 ± 19.21 g), but it significantly decreased their body fat content (control: 28.70 ± 1.17 cm3, OPO: 22.51 ± 1.10 cm3 and HMFS: 14.90 ± 0.95 cm3) (p < 0.05). Lipidome analysis revealed that glycerophospholipid was the primary differentiating lipid present in the liver of HMFS-fed rats. The abundance of Bacteroides significantly increased in the intestine of HMFS-fed rats (p < 0.05), and their short-chain fatty acid (SCFA) content significantly increased (p < 0.05). The multi-omics correlation analysis established the "Bacteroidetes-SCFAs-Glycerophospholipid pathway" as a potential mechanism by which administering HMFS affects body fat buildup in first-weaned rats. Additionally, it was found that HMFS administration significantly promoted lipid metabolism in the rat liver at both the gene and protein levels (p < 0.05). These findings serve to underscore the nutritional benefits of HMFS for infants.
Background:
The current lack of effective drug therapies for Alzheimer's disease (AD) has prompted researchers to seek alternative nutritional therapies, such as medium chain triglycerides (MCTs). However, results are inconclusive.
Objective:
This systematic review and meta-analysis aims to summarize current evidence on the effect of MCT on cognitive function in patients with mild cognitive impairment (MCI) or AD.
Methods:
A systematic search was conducted up until December 16, 2022, to identify human interventions reporting the effects of MCT on cognitive functioning of MCI or AD patients. 995 non-duplicated publications were identified, of which nine (n = 10 studies) met the inclusion criteria.
Results:
Meta-analysis showed cognitive improvements in general (SMD = 0.64; 95% CI [0.05, 1.24]), but not in memory, language, and attention domains after oral MCT administration, compared to placebo. The effect of MCT was greater among APOEɛ4 (-) subjects than APOEɛ4 (+) subjects (SMD = 1.87; 95% CI [0.35, 3.40]).
Conclusion:
This review provides some evidence that treatment with MCT could improve general cognitive function in APOEɛ4 (-) cognitive impaired patients. Better characterized clinical studies are warranted before making a definitive conclusion on the use of MCT for MCI and AD management.
Background:
Approximately 84% of fatty acids contained in coconut oil (CO) are saturated fatty acids (SFA), and approximately 47% of the SFA are lauric acid with 12 carbon atoms. Lauric acid carbon chain length is intermediate between medium and long chain fatty acids. We examined how CO acts on lipid-related substances in the blood to determine whether its properties were similar to medium-chain fatty acids (MCFA) or long-chain fatty acids (LCFA).
Methods:
This is a randomized controlled single-blind crossover study. 15 females were enrolled, using three test meals containing 30-g each of three different oils: CO (CO-meal), medium-chain triacylglycerol-oil (MCT-meal), and long-chain triacylglycerol-oil (LCT-meal). Blood samples were collected at fasted baseline and every 2 h for 8 h after the intake of each test meal.
Results:
Repeated measure analysis of variance (ANOVA) of the ketone bodies and triglyceride (TG) showed an interaction between time and the test meal (P < 0.01 and P < 0.001, respectively). In subsequent Tukey's honestly significant difference (HSD) test of the ketone bodies, statistically significant differences were observed between the CO-meal and the LCT-meal (P < 0.05) 83.8 (95% CI, 14.7,153.0) and between the MCT-meal and the LCT-meal (P < 0.05) 79.2 (95% CI, 10.0,148.4). The incremental area under the curve (iAUC) and maximum increase in very low-density lipoprotein cholesterol (VLDL-C) and intermediate-density lipoprotein cholesterol (IDL-C) were the lowest for CO-meal intakes.
Conclusions:
The characteristics of lauric acid contained in coconut oil, including the kinetics of β-oxidation and effects on blood TG, were very similar to those of MCFA. Moreover, regarding the iAUC and peak increment, VLDL-C and IDL-C were the lowest with the CO-meal. These results suggest that the intake of CO after fasting does not increase the TG, VLDL-C, and IDL-C, and may help prevent dyslipidemia. This trial was registered at UMIN as UMIN000019959.
This study sought to improve the biological fate of β-carotene obtained from spinach, using in vitro digestion, in situ single-pass intestinal perfusion, and in vivo approaches, to investigate the effects of excipient emulsions with medium- (MCT) and long-chain triglyceride (LCT) as a vehicle for improved health benefits of β-carotene. Results showed that the bioavailability and bioactivity of β-carotene were both significantly higher in the excipient emulsions relative to those without the emulsions. This was especially true when LCT was used as the vehicle. These results were confirmed by bioaccessibility, duodenal absorption, and in vivo absorption and metabolism. Furthermore, animal feeding studies revealed that LCT may have the potential to promote triglyceride and apo-B48 reconstitution and secretion. This suggested that LCT may facilitate the entry of carotenoids into circulation via the lymphatic pathway. These results highlight the importance of the optimization of excipient foods to improve the efficacy of lipophilic carotenoid.
Although natural sesame oil has been shown to facilitate the lymphatic delivery and oral bioavailability of the highly lipophilic drug cannabidiol (CBD), considerable variability remains an unresolved challenge. Vegetable oils differ substantially in composition, which could lead to differences in promotion of intestinal lymphatic transport of lipophilic drugs. Therefore, the differences in composition of sesame, sunflower, peanut, soybean, olive and coconut oils and their corresponding role as vehicles in promoting CBD lymphatic targeting and bioavailability were investigated in this study. The comparative analysis suggests that the fatty acids profile of vegetable oils is overall similar to the fatty acids profile in the corresponding chylomicrons in rat lymph. However, arachidonic acid (C20:4), was introduced to chylomicrons from endogenous nondietary sources. Overall, fatty acid composition of natural vegetable oils vehicles affected the intestinal lymphatic transport and bioavailability of CBD following oral administration in this work. Olive oil led to the highest concentration of CBD in the lymphatic system and in the systemic circulation in comparison to the other natural vegetable oils following oral administration in rats.
Although medium chain triglyceride (MCT) is less calorically dense than long chain triglyceride (LCT), it produces a greater thermic effect following ingestion. We hypothesized that the previously observed high rate of thermogenesis produced by MCT overfeeding was due to hepatic de novo synthesis of long chain fatty acids (LCFA) from the excess medium chain fatty acids (MCFA). To study this, we compared the effects of overfeeding MCT- and LCT-containing diets on blood lipid profiles. Ten in-patient, nonobese males were overfed (150% of estimated energy requirements) two formula diets for 6 days each, in a randomized crossover design. Diets differed only in the composition of the fat and contained either 40% of energy as MCT or LCT (soybean oil). The major differences between diets in the resulting pattern of blood lipids were: 1) a reduction in fasting serum total cholesterol concentrations with the LCT, but not the MCT diet; and 2) a threefold increase in fasting serum triglyceride concentrations with MCT, but not LCT, diet. Moreover, 10% of the fasting triglyceride fatty acids were medium chain and 40% were 16:0 with the MCT diet. This compared to 1% and 20% for medium chain and 16:0, respectively, with the LCT diet. In addition, there were increases in 16:1, 18:0, and 18:1 in the triglycerides during MCT feeding. The changes in fatty acids in triglycerides with MCT feeding are consistent with the hypothesis that excess dietary MCT cause a significant increase in the hepatic synthesis of these fatty acids from MCFA through de novo synthesis and/or chain elongation and desaturation. These processes could account for the higher rate of postprandial thermogenesis with MCT as compared to LCT.
We describe a new method of studying the thermic response to dietary fuels that involves continuous infusion of a liquid formula diet through a thin nasogastric tube. The data show that the steady inflow of dietary fuel is accompanied by a relatively constant level of energy expenditure, the magnitude of which depends on the rate of fuel inflow. An increase in the rate of fuel infusion above that required for caloric maintenance leads to a rise in energy expenditure. We also give examples, based on preliminary observations, of how the technique can be used to more precisely quantify energy metabolism. The technique may prove useful in the studying efficiency of energy utilization and in examining the extent to which individuals differ in energy efficiency.
Lipid decomposition studies in frozen fish have led to the development of a simple and rapid method for the extraction and purification of lipids from biological materials. The entire procedure can be carried out in approximately 10 minutes; it is efficient, reproducible, and free from deleterious manipulations. The wet tissue is homogenized with a mixture of chloroform and methanol in such proportions that a miscible system is formed with the water in the tissue. Dilution with chloroform and water separates the homogenate into two layers, the chloroform layer containing all the lipids and the methanolic layer containing all the non-lipids. A purified lipid extract is obtained merely by isolating the chloroform layer. The method has been applied to fish muscle and may easily be adapted to use with other tissues.
Nutrition support has played a major role in the treatment of chylothorax, both to prevent malnutrition and to minimize chyle production and flow. This report evaluates chyle composition in a patient with chylothorax who was placed on a low-fat diet, medium-chain triglyceride diet, and total parenteral nutrition in sequence. Both triglyceride content and volume of chyle declined, but drainage persisted, ultimately requiring thoracic duct ligation. The chyle triglyceride while on total parenteral nutrition, which presumably originates from both the intestine and plasma, contained more long-chain unsaturated fatty acids than the circulating serum triglyceride. Of particular interest was the detection of an appreciable amount of medium-chain fatty acids in the chyle triglyceride, constituting 20% of the triglyceride fatty acids when an enteral formulation with medium-chain triglyceride as a sole fat source was administered. The finding of almost threefold more decanoic acid (C10:0) than octanoic acid (C8:0), despite the presence of considerably more octanoic acid in the original diet, suggests that trioctanoin may be a preferable medium-chain triglyceride substrate for the nonsurgical treatment of chylothorax.
Three siblings with familial hyperchylomicronemia (dietary fat-induced lipemia) and two subjects with "carbohydrate-accentuated" lipemia were studied during periods of strictly controlled diets. Corn oil, coconut oil, mixed, naturally occurring dietary fats, and medium chain triglycerides (MCT) consisting of 98 per cent C8 and C10 fatty acids, were fed in amounts contributing 40 per cent to 70 per cent of calories. In the siblings with hyperchylomicronemia (due to prolonged retention, of chylomicrons in the blood beacuse of a defective lipoprotein lipase system), marked reduction in serum triglyceride levels occurred when MCT was the sole source of dietary fat. Simultaneously with the reduction in serum triglyceride levels, there was an increase, both relative and absolute, in the amount of very low-density lipid (d < 1.006 Gm. per milliliter) circulating as Sf 20 to 400 lipoproteins rather than as chylomicron (Sf > 5,000) lipid. When a fat-free diet was provided two of the siblings with hyperchylomicronemia, serum triglyceride levels were as low as, or lower than, those observed when MCT was the sole source of fat. The data provide additional evidence that the hyperglyceridemia in these subjects is due to excessive chylomicronemia, and that C8 and C10 fatty acids are not utilized for chylomicron triglyceride synthesis in the intestine to any appreciable degree. The feeding of formula diets containing MCT as the sole source of fat to the subjects with dietary carbohydrate-accentuated lipemia did not lower serum triglyceride levels, in comparison with corn oil or coconut oil. Lower serum triglyceride levels were observed when these subjects were fed diets in which 70 per cent rather than 40 per cent of the calories came from fat, regardless of the nature of the fat. MCT appeared less effective than corn oil or coconut oil in this respect. Serum cholesterol levels varied with triglyceride levels and were lowest when the sole source of dictary fat was corn oil.
A review of the literature on the medical and nutritional use of medium-chain triglycerides (MCTs) since 1970 is presented with additional discussions on the various modifications and applications of the MCTs in the synthesis of certain structured lipids. The metabolism of MCTs in the liver and extrahepatic tissues is discussed along with further documentation of the use of MCTs in malabsorption and hyperlipidemia cases. Recent applications of MCTs and modified MCTs in hyperalimentation, deficiency in the carnitine system, epilepsy, obesity, and other special areas of application are cited. The use of medium-chain monodiglycerides for dissolving cholesterol gallstones is presented. The contraindications for the use of MCTs in ketosis, acidosis, and cirrhosis are also discussed. Suggestions for use of MCTs in a variety of medical and nutritional applications are presented.
Low density lipoproteins and the triglyceride-rich lipoproteins of human serum each contain proteins of high molecular weight termed apolipoprotein B, which have previously been thought to be identical. We have isolated four species of apolipoprotein B with unique molecular weights and amino acid compositions. We have assigned numerical designations to these species in a centile system based upon their relative apparent Mr in NaDodSO4. One which we term B-100, with an apparent Mr of 549,000 +/- 7650 (SD) determined by NaDodSO4 gel electrophoresis, predominates in low density and very low density lipoproteins and is also present in chylomicrons from thoracic duct lymph or from plasma. Substantial amounts of two large proteins designated B-74 (apparent Mr 407,000 +/- 5790) and B-26 (apparent Mr 144,500 +/- 8970), which appear to be complementary fragments or constituents of the B-100 protein, are found in the low density lipoproteins of many individuals. A distinct protein, B-48, with an apparent Mr of 264,000 +/- 8150 is a major and constant constituent of chylomicrons from thoracic duct lymph or from plasma.