Effectiveness of a Novel ω-3 Krill Oil Agent in Patients With Severe Hypertriglyceridemia

Mozaffarian, Dariush; Maki, Kevin C.; Bays, Harold; Aguilera, Fernando; Gould, Glenn; Hegele, Robert A.; Moriarty, Patrick M.; Robinson, Jennifer G.; Shi, Peilin; Tur, Josefina F.; Lapointe, Jean-François; Aziz, Sarya; Lemieux, Pierre; Hao, Tong; Mirza, Lubna; Kipp, Gaylon; Jarrett, Wentworth; Little, Raymond; Mariano, Hipolito; Nagajothi, Nagapradeep; Bender, Kevin J.; Everhart, None Brian; Rahman, Syed T.; Usdan, Lisa; Larsen, David A.; McGettigan, John; Faiyaz, Roohi; Foucauld, J.; Higgins, Calvin; Chalhoub, Fadi; Freeman, William K.; Corse, Steven; Miller, Stephen D.; Malanakar, Amol; Reschak, Michael; Jain, Mahendra; Ghazi, Adline; Daboul, Nizar; Hegedosh, Natalia; McKenzie, Mark; Raikhel, Marina; Dodd, John H.; Dunn, Leonard; Jannach, Stephan; Sojka, S; Sherman, H; Diener, James; Horowitz, Barry; Shaw, Marian; Pharr, Walter; Lentx, John David; Hanabergh, Enrique; Miller, Randall S.; Patron, Andres; Agaiby, John; Feldman, Michael; Ledesma, Gilbert; Bermudez, Lidia Rosa; Jetty, Preetham; Debs-Perez, Giselle; Loya, Aslam; Butuk, David; Cullen, Amy; Recknor, Chris; Lynn, Lon; Connery, Lisa; Ylisastigui, Pedro; Huling, Randall; Portilla, Marianela De La; Cruz, Humberto; Sotolongo, Roberto; Dor, Isaac; Ebran-Gonzalez, Raul; Lederman, Samuel; Benitez, Omar; Cain, James C.; Awasty, Vivek; Martinez, Cindy; Hernandez, Ramon; Dao, Michael; Terrelonge, Antonio; Jackson, Jennifer; Busch, Robert S.; Trenche, Sameul Mujica; Barbel-Johnson, Kim; Ince, Carlos; Garcia, Bernard; Grossman, Colby; Cornett, George Mitchell; Latif, Faisal; Al-Karadsheh, Amer; Koilpillai, Robinson; Alvarez-Moreno, Jorge; Preston, Krista; Wright, David C.; Eck, J W Martijn van; Fussell, Suzanne; Reyna, Javier; Solano, Royce Keith; Raoof, Joseph; Park, Jean; Williams, Hayes; Miller, Alan B.; Remler, Robert; Trevino, Miguel; Harper, Charles R.; Gordon, Connor; Iglesias, Nayvis; Makam, Sashi; Jordan, Staci; Shah, Suresh D.; Griffin, Carl; Gardner, Donald J.; Aguiar, Oricel; Rama, Bhola N.; Zepeda, Luis; French, William J.; Braddock, Matthew; Boscia, Joseph; Galvez, Oscar; Rankin, Bruce; Straubing, Stephen; Hurley, Cathy; Rosenfeld, Jack; Hogan, E. M.; Risser, None Joseph; Willis, John; Andrawis, Nabil S.; Ahmed, Khalid; Bertolet, Barry D.; Guido, Giancarlo; Erb, David; Chaykin, Louis; Greenwald, James H.; Barlow, Christin; Dever, Michael; Santander, Jorge; O'Mahony, John B.; Aggarwal, Naresh; Frechette, Andre; Dzongowski, Peter; Henein, Sam; O’Keefe, Dennis D.; Ransom, Thomas; Datta, Sudip; Saunders, Kevin O.; Girard, Ginette; Gaudet, Daniel; Castrezana, Laura Castro; Alvarez, Israel Olvera; Ruiz, Alberto Esteban Bazzoni; Antonio, Guillermo; Gamba, Marco Antonio Alcocer; Eduardo, Carlos; Mijangos, Jose Hector Sanchez; Quintero, Martha Ofelia Pereda; Ramos, Carlos

doi:10.1001/jamanetworkopen.2021.41898

Cited by 17 publications

(11 citation statements)

References 26 publications

(50 reference statements)

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“…Interestingly, the serum apo-B content was not changed between the groups, suggesting that the quality of HDL and LDL might not be changed. More recently, the consumption of omega-3 krill oil (4 g/d) for 26 weeks resulted in a decrease in the TG, but no significant improvement in HDL-C [ 50 ]. Therefore, despite the conflicting data, it can be concluded that the consumption of omega-3 did not increase the serum HDL-C in both long-term and short-term consumptions.…”

Section: Change In Hdl-c Quantity During One’s Lifetimementioning

confidence: 99%

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

Cho

2022

IJMS

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The quantity of high-density lipoproteins (HDL) is represented as the serum HDL-C concentration (mg/dL), while the HDL quality manifests as the diverse features of protein and lipid content, extent of oxidation, and extent of glycation. The HDL functionality represents several performance metrics of HDL, such as antioxidant, anti-inflammatory, and cholesterol efflux activities. The quantity and quality of HDL can change during one’s lifetime, depending on infection, disease, and lifestyle, such as dietary habits, exercise, and smoking. The quantity of HDL can change according to age and gender, such as puberty, middle-aged symptoms, climacteric, and the menopause. HDL-C can decrease during disease states, such as acute infection, chronic inflammation, and autoimmune disease, while it can be increased by regular aerobic exercise and healthy food consumption. Generally, high HDL-C at the normal level is associated with good HDL quality and functionality. Nevertheless, high HDL quantity is not always accompanied by good HDL quality or functionality. The HDL quality concerns the morphology of the HDL, such as particle size, shape, and number. The HDL quality also depends on the composition of the HDL, such as apolipoproteins (apoA-I, apoA-II, apoC-III, serum amyloid A, and α-synuclein), cholesterol, and triglyceride. The HDL quality is also associated with the extent of HDL modification, such as glycation and oxidation, resulting in the multimerization of apoA-I, and the aggregation leads to amyloidogenesis. The HDL quality frequently determines the HDL functionality, which depends on the attached antioxidant enzyme activity, such as the paraoxonase and cholesterol efflux activity. Conventional HDL functionality is regression, the removal of cholesterol from atherosclerotic lesions, and the removal of oxidized species in low-density lipoproteins (LDL). Recently, HDL functionality was reported to expand the removal of β-amyloid plaque and inhibit α-synuclein aggregation in the brain to attenuate Alzheimer’s disease and Parkinson’s disease, respectively. More recently, HDL functionality has been associated with the susceptibility and recovery ability of coronavirus disease 2019 (COVID-19) by inhibiting the activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The appearance of dysfunctional HDL is frequently associated with many acute infectious diseases and chronic aging-related diseases. An HDL can be a suitable biomarker to diagnose many diseases and their progression by monitoring the changes in its quantity and quality in terms of the antioxidant and anti-inflammatory abilities. An HDL can be a protein drug used for the removal of plaque and as a delivery vehicle for non-soluble drugs and genes. A dysfunctional HDL has poor HDL quality, such as a lower apoA-I content, lower antioxidant ability, smaller size, and ambiguous shape. The current review analyzes the recent advances in HDL quantity, quality, and functionality, depending on the health and disease state during one’s lifetime.

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Section: Change In Hdl-c Quantity During One’s Lifetimementioning

confidence: 99%

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

Cho

2022

IJMS

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“…In 2004, Bunea et al demonstrated that administration of krill oil 1–3 g/day reduced the levels of total cholesterol, triglycerides, and LDL in patients with hypercholesterolemia, compared with levels produced by fish oil and a placebo [ 14 ]. Moreover, Parolini et al reported that dietary supplementation of krill oil reduced VLDL and IDL/LDL-cholesterol levels in apoE-deficient mice [ 15 ], and Mozaffarian et al found that a krill-oil-derived ω-3 formulation reduced TG levels in patients with severe hypertriglyceridemia [ 19 ]. Accordingly, we observed the factors involved in cholesterol synthesis in the liver to investigate the mechanism of the antihypercholesterolemic effects of krill oil.…”

Section: Discussionmentioning

confidence: 99%

Krill Oil Inhibits Cholesterol Synthesis and Stimulated Cholesterol Excretion in Hypercholesterolemic Rats

et al. 2022

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The present study aimed to investigate the antihypercholesterolemic effects of krill oil supplementation in high-cholesterol diet-induced hypercholesterolemic rats, and the mechanisms underlying these effects. Rats were divided into five groups: normal control, control (high-cholesterol diet), krill oil 100 mg/kg b.w. (high-cholesterol diet with Krill oil 100 mg/kg b.w.), and krill oil 200 mg/kg b.w. (high-cholesterol diet with Krill oil 200 mg/kg b.w.). After 12 weeks, the rats were sacrificed to observe the effects of krill oil on cholesterol synthesis and excretion. We found that krill oil supplementation suppressed total triglycerides, total cholesterol, and LDL-cholesterol levels, as well as HMG-CoA reductase activity. It stimulated AMPK phosphorylation, LDL receptor and ACAT2 expression in the liver, and the fecal output of cholesterol. Furthermore, it decreased the levels of P-selectin, sVCAM-1, and NO, as well as aortic wall thickness, demonstrating its role in the prevention of atherosclerosis. Thus, we suggest that krill oil supplementation can reduce LDL-cholesterol levels in the blood during hypercholesterolemia by stimulating the uptake of LDL-cholesterol into tissue and cholesterol excretion, as well as inhibition of cholesterol synthesis.

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“…The treatment of F-HTG focuses on the reduction of low-density lipoprotein (LDL) cholesterol levels, followed by management of non–high-density lipoprotein cholesterol levels; this can be achieved by changes in lifestyle and dietary modifications [ 126 ] or by the administration of statins such as Atorvastatin, Lovastatin, Fluvastatin, Pravastatin Rosuvastatin and Simvastatin [ 127 ]. Fibrates [ 128 ], Niacin [ 129 ] and Fish oil [ 126 , 130 , 131 ], The development of alternatives to statins, which include Evinacumab, the angiotensin-like 2 monoclonal antibody [ 132 ], which has shown adequate safety in trials [ 133 ]. The resurgence of approval for monoclonal antibody treatments for rare disorders [ 134 ] and gene therapy in animal models [ 135 ] will set the direction for the advancement of therapeutics for the management of this emerging disorder.…”

Section: Familial Hypertriglyceridemiamentioning

confidence: 99%

Current Understanding on the Genetic Basis of Key Metabolic Disorders: A Review

Rodrigues

Yong

Bhuiyan

et al. 2022

Biology

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Advances in data acquisition via high resolution genomic, transcriptomic, proteomic and metabolomic platforms have driven the discovery of the underlying factors associated with metabolic disorders (MD) and led to interventions that target the underlying genetic causes as well as lifestyle changes and dietary regulation. The review focuses on fourteen of the most widely studied inherited MD, which are familial hypercholesterolemia, Gaucher disease, Hunter syndrome, Krabbe disease, Maple syrup urine disease, Metachromatic leukodystrophy, Mitochondrial encephalopathy lactic acidosis stroke-like episodes (MELAS), Niemann-Pick disease, Phenylketonuria (PKU), Porphyria, Tay-Sachs disease, Wilson’s disease, Familial hypertriglyceridemia (F-HTG) and Galactosemia based on genome wide association studies, epigenetic factors, transcript regulation, post-translational genetic modifications and biomarker discovery through metabolomic studies. We will delve into the current approaches being undertaken to analyze metadata using bioinformatic approaches and the emerging interventions using genome editing platforms as applied to animal models.

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Effectiveness of a Novel ω-3 Krill Oil Agent in Patients With Severe Hypertriglyceridemia

Cited by 17 publications

References 26 publications

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

Krill Oil Inhibits Cholesterol Synthesis and Stimulated Cholesterol Excretion in Hypercholesterolemic Rats

Current Understanding on the Genetic Basis of Key Metabolic Disorders: A Review

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