Pharmacokinetic Study on Three Formulations of Curcumin With Different Carriers
Pharmacokinetic Study on Three Formulations of Curcumin With Different Carriers
Curcumin is a molecule soluble in fat. It has multiple health benefits. Indeed, it has
 anti-inflammatory and anti-oxidant properties. Curcumin could play a role in preventing
 diseases such as cancer, inflammatory, cardiovascular and neurodegenerative diseases. Omega-3
 fatty acids are also important for good health, as they have positive effects on the
 cardiovascular and neurological systems. However, curcumin is poorly absorbed by the body
 when provided in supplements. In order to improve curcumin's absorption, a natural health
 product that combines curcumin and omega-3 fatty acids has been developped. The goal of this
 project is therefore to determine the absorption of curcumin when administered in combination
 with omega-3 fatty acids esterified in monoacylglycerol (MAG). This combination will be
 compared with a curcumin extract alone or in rice oil. A pharmacokinetic study will be
 carried out for each of the formulations. Pharmacokinetics (PK) is defined as monitoring the
 blood concentrations of curcumin over a 24-hour period after taking one of the three
 different supplements.
15 men and 15 women in good health conditions will be recruited for this project. The study
 has a randomized double-blinded crossover design with three treatments that include an equal
 dosage of curcumin as follows :

 -  400 mg of curcumin extract,

 -  400 mg of curcumin in rice oil,

 -  400 mg of curcumin extract + 1.5 g omega-3 in MAG form.

 For each of the above listed products, a natural product number (NPN) was requested to Health
 Canada and these number are currently pending.

 Each participant will consume each of the three treatments in a random order with a minimum
 of 7 days washout phase between both treatments. Blood samples will be collected at time 0,
 1, 2, 3, 4, 5, 6, 8, 10, and 24h (10 blood samples per participant per treatment) after
 taking the single dose intake. A questionnaire will allow documenting side effects throughout
 the study period. The analyses will be performed by ultra-high-performance liquid
 chromatography couples to a quadrupole mass spectrometer (UPLC/MS/MS). Samples will be
 analyzed in a blinded manner such that the student and research assistant will be blinded
 from the type of treatment and the time point they are analyzing. After performing all the
 analyses, sample identification will be decoded and pharmacokinetic data of the curcuminoids
 in each of the treatments will be plotted on a plasma concentration vs time curve. The
 parameters below will be calculated:

 -  Area under the curve (AUC) 0-24h (bioavailability);

 -  Area under the curve (AUC) 0-6h (absorption);

 -  Maximum concentration (Cmax);

 -  Time to reach the maximum concentration (Tmax);

 -  Half-life (if available).
Inclusion Criteria:

 -  Men or women between 18 and 50 years old (inclusive).

 -  Body mass index between 18,5 and 34,9 at the selection visit (inclusive).

 -  Normal to moderately high lipidemia (total cholesterol ≤ 240 mg / dl; LDL ≤ 160 mg /
 dl; Triglyceride ≤ 199 mg / dl).

 -  Women of child bearing potential must accept to use an effective contraceptive method
 for the duration of the study.

 Exclusion Criteria:

 -  Allergy to fish or seafood.

 -  Special diet like a vegetarian or vegan diet.

 -  Tobacco.

 -  History of current or past alcohol and / or drug abuse.

 -  Current or past performance athlete.

 -  Malnutrition (assessed by albumin, hemoglobin and blood lipid levels).

 -  People consuming omega 3 fatty acid or curcumin supplements for more than 6 months.

 -  Medication affecting fat absorption (ie, Orlistat, Alli, etc.).

 -  Medication which interferes with the metabolization of the medication (ie,
 anticoagulants like coumadin or warfarin, aspirin is not an exclusion criterion
 (Watson et al, 2009))

 -  Medication which affects lipid metabolism (ie, all types of drugs to lower cholesterol
 or triglycerides).

 -  Medication which curcumin interacts with : angiotensin II blockers (losartan,
 valsartan), β-blockers (talinolol, celiprolol), calcium channels blockers
 (nifedipine), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG CoA) reductase
 inhibitors (rosuvastatin), antineoplastic agents (docetaxel, etoposide, tamoxifen,
 everolimus, sirolimus), antibiotics (norfloxacin), antidepressant (midazolam),
 sulfonamides (sulfasalazine), antidiabetics (gliclazide).

 -  Pregnant women or nursing women.

 -  Menopause or pre-menopause with amenorrhea > 6 months.

 -  Systemic disease: vasculitis, Lupus Erythrocyte Disseminated (SLE), sarcoidosis,
 cancer (except if in remission for more than 10 years and without cerebral
 involvement), uncompensated hypothyroidism, vitamin B12 deficiency not supplemented
 and / or complicated, diabetes, severe renal insufficiency.

 -  Abnormal liver, kidney or thyroid function; these conditions will not exclude a
 patient if he / she has been stabilized on treatment for at least 3 months and there
 has been no recent change in his / her medication.

 -  Cardiac event or recent major surgery (<6 months).

 -  History of thrombosis or haemorrhagic diathesis.

 -  Malabsorption disease such as pancreatitis, Crohn's disease or has had bariatric
 surgery.

 -  Neurodegenerative disease (Parkinson disease).

 -  Genetic disorder (Down syndrome).

 -  Known psychiatric history: schizophrenia, psychotic disorders, major affective
 disorder (bipolar disorder and major depression <5 years), panic disorder, Compulsive
 Obsessive Compulsive Disorder (OCD).

 -  Neurological disorder (Epilepsy, cerebral trauma with loss of consciousness,
 subarachnoid hemorrhage).

 -  Person who has donated blood or had significant blood loss in the 30 days prior to the
 start of the study.

 -  Not available to perform the 3 treatments.