MaxSimil and Vitamin K2: Determining Their Bioavailability

NCT03897660 | Completed

• 1 other identifier: MaxSimil and vitamin K2
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The benefits of a diet enriched with omega-3 fatty acids are multiple and confirmed by several clinical studies. Supplementation with vitamin K, a fat-soluble vitamin, can increase or maintain bone density in postmenopausal women and reduce the risk of fracture. In addition, some studies show that vitamin K may promote the absorption of omega-3 fatty acids. Fish oil, rich in omega-3, is one of the world's favorite forms of omega-3 supplements. However, many people suffer from gastrointestinal discomfort when ingesting fish oil capsules. To minimize these discomforts and improve plasmatic omega-3 bioavailability, Neptune Wellness Solutions has developed a patented formulation of fish oil called MaxSimil®, where omega-3s are in the monoglyceride (MAG) form, a predigested omega-3 form. This formulation has been tested in humans in a double-blind controlled-randomized pharmacokinetic (PK) pilot study with crossover design. PK is defined as a monitoring of omega-3 levels in the blood by frequent blood sampling over a period of 24 hours following the ingestion of a single dose of omega-3. The results obtained showed that MaxSimil® omega-3s are 3 times more absorbed in the blood than the comparison formulation, a source of omega-3 in the ethyl ester (EE) form. Although this first study confirms a greater bioavailability of MaxSimil®, a complementary PK study is necessary to confirm these results and to correct an important methodological bias. In fact, the pilot study did not include a comparator group where omega-3s were in the triglyceride (TG) form, the most widely omega-3 form currently consumed, but rather use an EE form, which have lower bioavailability than TG form. This may therefore have biased the study from the point of view of the comparator and thus give the impression that the comparator had been deliberately chosen to be less bioavailable than the MaxSimil®. In order to confirm the superiority of MaxSimil® (omega-3 MAG form), both in terms of bioavailability and incidence of side effects, the aim of this study is to redo a PK study using this time two comparators, the two main forms of omega-3 currently used (TG and EE forms), as well as a supplementation with vitamin K2 (a form of vitamin K). Our hypothesis is that MaxSimil® will be associated with a better omega-3 bioavailability and a lower incidence of side effects than the other two forms (TG and EE), and possibly also with a better vitamin K bioavailability.

Conditions

Healthy

Keywords

Omega-3 fatty acids; Vitamin K2; Bioavailability; Side effects; Monoacylglyderols

Outcome Measures

Primary Outcomes (4)

• Determine the bioavailability of omega-3 and vitamin K2 according to the forms ethyl ester (EE), triglycerides (TG) and MaxSimil® (monoglycerides, MAG): Calculating the area under the curve (AUC) 0-24h as the first parameter of the PK

  Plasma omega-3 (DHA and EPA) levels will be measured by gas phase chromatography while plasma vitamin K2 level will be measured by high-performance liquid chromatography (HPLC), each being performed randomly blindly. After GC and HPLC analyzes, area under the curve (AUC) 0-24 hours will be calculated, as the first parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

  Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. GC and HPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours post-treatment.

• Determine the bioavailability of omega-3 and vitamin K2 according to the forms ethyl ester (EE), triglycerides (TG) and MaxSimil® (monoglycerides, MAG): Calculating the AUC 0-6h (absorption study) as the second parameter of the PK

  Plasma Omega-3 (DHA and EPA) will be measured by gas phase chromatography while plasma vitamin K2 will be measured by high-performance liquid chromatography (HPLC), each being performed randomly blindly. After GC and HPLC analyzes, AUC 0-6 hours (absorption study) will be calculated, as the second parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

  Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. GC and HPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours post-treatment.

• Determine the bioavailability of omega-3 and vitamin K2 according to the forms ethyl ester (EE), triglycerides (TG) and MaxSimil® (monoglycerides, MAG): Calculating the maximum concentration as the third parameter of the PK

  Plasma Omega-3 (DHA and EPA) will be measured by gas phase chromatography while plasma vitamin K2 will be measured by high-performance liquid chromatography (HPLC), each being performed randomly blindly. After GC and HPLC analyzes, maximum concentration will be calculated, as the third parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

  Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. GC and HPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours post-treatment.

• Determine the bioavailability of omega-3 and vitamin K2 according to the forms ethyl ester (EE), triglycerides (TG) and MaxSimil® (monoglycerides, MAG): Calculating the time when the maximum concentration is reached, as the fourth parameter of the PK

  Plasma Omega-3 (DHA and EPA) will be measured by gas phase chromatography while plasma vitamin K2 will be measured by high-performance liquid chromatography (HPLC), each being performed randomly blindly. After GC and HPLC analyzes, time when the maximum concentration is reached will be calculated, as the fourth parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

  Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. GC and HPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours post-treatment.

Secondary Outcomes (1)

• To determine the incidence of side effects (including gastrointestinal discomfort) of these same three forms of omega-3 fatty acid supplements

  A questionnaire will document the side effects felt by participants during the omega-3 supplement taking day.

Study Arms (3)

TG form of omega-3

ACTIVE COMPARATOR

The participant will arrive fasted at he research center. After installing a cathether and drawing 5 mL of blood, the participants will be given one of the active comparator or the treatment. The choice of the treatment/comparator will be random. In this arm, the participant will receive the omega-3 fatty acidsesterified in a reconstitute triglyceride form as a unique dose of 1.5 g EPA + DHA in TG form + 45 mg vitamin K2.The participant will consume this unique dose with a standardized breakfast. There will thereafter be blood sample collection over 24 h to evaluate the level of omega-3 fatty acids in the plasma and a side effect questionnaire will be administered to monitor side effects.

Dietary Supplement: Omega-3 + vitamin K2 (TG form of omega-3)

EE form of omega-3

ACTIVE COMPARATOR

The participant will arrive fasted at he research center. After installing a cathether and drawing 5 mL of blood, the participants will be given one of the active comparator or the treatment. The choice of the treatment/comparator will be random. In this arm, the participant will receive the omega-3 fatty acids in ethyl esters form as a unique dose of 1.5 g EPA + DHA in TG form + 45 mg vitamin K2.The participant will consume this unique dose with a standardized breakfast. There will thereafter be blood sample collection over 24 h to evaluate the level of omega-3 fatty acids in the plasma and a side effect questionnaire will be administered to monitor side effects.

Dietary Supplement: Omega-3 + vitamin K2 (EE form of omega-3)

MaxSimil (MAG form of omega-3)

EXPERIMENTAL

The participant will arrive fasted at he research center. After installing a cathether and drawing 5 mL of blood, the participants will be given one of the active comparator or the treatment. The choice of the treatment/comparator will be random. In this arm, the participant will receive the omega-3 fatty acids in MaxSimil® form as a unique dose of 1.5 g EPA + DHA in TG form + 45 mg vitamin K2.The participant will consume this unique dose with a standardized breakfast. There will thereafter be blood sample collection over 24 h to evaluate the level of omega-3 fatty acids in the plasma and a side effect questionnaire will be administered to monitor side effects.

Dietary Supplement: Omega-3 + vitamin K2 [MaxSimil (MAG form of omega-3)]

Interventions

Omega-3 + vitamin K2 (TG form of omega-3) DIETARY_SUPPLEMENT

The intervention is a randomized double bond cross over design testing the pharmacokinetics of a monoglyceride formulation compared to a triglyceride and an ethyl ester form. Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. Blood samples will be collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours. Each participant will perform all three treatments, with a minimum of 6 days between treatments. A questionnaire will document the side effects felt by participants during the omega-3 supplement taking day.

TG form of omega-3

Omega-3 + vitamin K2 (EE form of omega-3) DIETARY_SUPPLEMENT

The intervention is a randomized double bond cross over design testing the pharmacokinetics of a monoglyceride formulation compared to a triglyceride and an ethyl ester form. Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. Blood samples will be collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours. Each participant will perform all three treatments, with a minimum of 6 days between treatments. A questionnaire will document the side effects felt by participants during the omega-3 supplement taking day.

EE form of omega-3

Omega-3 + vitamin K2 [MaxSimil (MAG form of omega-3)] DIETARY_SUPPLEMENT

The intervention is a randomized double blind cross over design testing the pharmacokinetics of a monoglyceride formulation compared to a triglyceride and an ethyl ester form. Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. Blood samples will be collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours. Each participant will perform all three treatments, with a minimum of 6 days between treatments. At each blood draw time points, a questionnaire will be administered to the particpant to monitor if they experiencec side effects with the dietary supplement they ingested in the morning.

MaxSimil (MAG form of omega-3)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18-65 years (inclusive)
• Body mass index between 18.5 and 29.9 kg / m² (inclusive) at the pre-selection visit
• Normal to moderately elevated lipidemia (total cholesterol ≤ 240 mg / dl, LDL ≤ 160 mg / dl, TG ≤ 199 mg / dl)
• Women of childbearing potential should use an approved method of contraception for the duration of the study so that they do not become pregnant during the study

You may not qualify if:

• Menopause or pre-menopause with amenorrhea\> 6 months
• Tobacco
• Malnutrition (assessed by albumin, hemoglobin and blood lipid levels)
• DHA plasma levels greater than 3% or people consuming omega-3 fatty acid supplements for more than one month
• History of current or past alcohol and / or drug abuse
• Parkinson's disease
• Down syndrome
• Cardiac event or recent major surgery (6 months)
• Current or past performance athlete
• Systemic disease: vasculitis, Systemic Lupus Erythematosus (SLE), sarcoidosis, cancer (unless in remission for more than 5 years and without cerebral involvement), uncompensated hypothyroidism (unless stabilized on treatment for more than 3 months), vitamin deficiency B12 not supplemented and / or complicated (unless stabilized on treatment for more than 3 months), diabetes, severe renal insufficiency
• Abnormal blood pressure and / or liver, renal or thyroid function; these conditions will not exclude a patient if he has been stabilized on treatment for at least 3 months and there has been no recent change in the medication.
• Known psychiatric history: schizophrenia, psychotic disorders, major affective disorders (bipolar disorder and major depression \<5 years), panic disorder, Obsessive Compulsive Disorder (OCD)
• Epilepsy, cerebral trauma with loss of consciousness, subarachnoid hemorrhage
• Not available to perform the 3 different treatments
• Medication affecting fat absorption (i.e., Orlistat, Alli, etc.), which interferes with omega-3 fatty acids uptake (i.e., anticoagulants) or which affects lipid metabolism (i.e., all types of drug for decrease cholesterol or triglycerides)

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Samuel Fortin, SFC pharma and associate professor UQAR: collaborator

Study Sites (1)

Melanie Plourde

Sherbrooke, Quebec, J1H4C4, Canada

Location

Related Publications (1)

• Chevalier L, Vachon A, Plourde M. Pharmacokinetics of Supplemental Omega-3 Fatty Acids Esterified in Monoglycerides, Ethyl Esters, or Triglycerides in Adults in a Randomized Crossover Trial. J Nutr. 2021 May 11;151(5):1111-1118. doi: 10.1093/jn/nxaa458.

  PMID: 33564872 DERIVED

MeSH Terms

Interventions

Docosahexaenoic Acids; Vitamin K 2

Intervention Hierarchy (Ancestors)

Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils; Vitamin K; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds

Study Officials

• Mélanie Plourde, PhD

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Neither the participant nor the research nurse will know the administration order of the different treatments administered. All plasma samples collected during the research project will be anonymized i.e. it will not be possible to identify the participant by his name since a number will be assigned to him. The code key linking the participant's name to his number will be stored, with access restricted to those designated by the principal investigator. The data file is also protected by a password.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor, Department of medicine, Geriatric service

Model Details: Double-blind controlled-randomized pharmacokinetic (PK) pilot study with crossover design (10 men and 10 women), with a minimum of 6 days between treatments

Study Record Dates

• First Submitted: February 27, 2019
• First Posted: April 1, 2019
• Study Start: March 29, 2019
• Primary Completion: November 23, 2019
• Study Completion: March 31, 2020
• Last Updated: August 27, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)