Clinical Research Directory

Targeting Risk Factors for Diabetes in Subjects With Normal Blood Cholesterol Using Omega-3 Fatty Acids

Every 3 minutes a new case of diabetes is diagnosed in Canada, mostly type 2 diabetes (T2D) increasing the risk for heart disease. T2D and heart disease share many common risk factors such as aging, obesity and unhealthy lifestyle. Paradoxically however, while lowering blood LDL, commonly known as "bad cholesterol", is protective against heart disease, research over the past 10 years have shown that the lower is blood LDL, the higher is the chance of developing T2D. This phenomena is happening whether blood LDL is lowered by a common drug against heart disease called Statins, or by being born with certain variations in genes, some of which are very common (\~80% of people have them). To date, it is unclear why lowering blood LDL is associated with higher risk for diabetes, and whether this can be treated naturally with certain nutrients. Investigators believe that lowering blood LDL by forcing LDL entry into the body tissue through their receptors promotes T2D. This is because investigators have shown that LDL entry into human fat tissue induces fat tissue dysfunction, which would promote T2D especially in subjects with excess weight. On the other hand, investigators have shown that omega-3 fatty acids (omega-3) can directly treat the same defects induced by LDL entry into fat tissue. Omega-3 is a unique type of fat that is found mostly in fish oil. Thus the objectives of this clinical trial to be conducted in 48 subjects with normal blood LDL are to explore if: 1. Subjects with higher LDL receptors and LDL entry into fat tissue have higher risk factors for T2D compared to subjects with lower LDL receptors and LDL entry into fat tissue 2. 6-month supplementation of omega-3 from fish oil can treat subjects with higher LDL receptors and LDL entry into fat tissue reducing their risk for T2D. This study will thus explore and attempt to treat a new risk factor for T2D using an inexpensive and widely accessible nutraceutical, which would aid in preventing T2D in humans.

ALA-enriched Nutrition for Prevention of Cognitive Decline in APOE4 Older Adults

This randomized, double-blind, placebo-controlled pilot trial will evaluate the effects of alpha-linolenic acid (ALA) supplementation on cognitive function, blood-brain barrier integrity, and brain vascular health in older adults with mild cognitive impairment and APOE4 genotype. By targeting the endogenous synthesis of docosahexaenoic acid (DHA) through ALA supplementation, the investigators aim to overcome the limitations of direct DHA supplementation, particularly in APOE4 carriers who exhibit low brain DHA levels and impaired blood-brain barrier function. This innovative approach offers a safe, cost-effective, and easily implementable therapeutic strategy for older adults at high risk for Alzheimer's dementia, especially APOE4 carriers, addressing a critical need given the limited cognitive benefits and significant adverse events of current amyloid-clearing drugs in this population.

Evaluation of the Nutritional Status of Omega-3 Fatty Acids and the Possible Influences of Dietary Patterns and Different Socioeconomic Factors, in a Spanish Population Over 60 Years of Age

The long-chain polyunsaturated fatty acids (PUFA) of the n-3 or omega-3 series and, in particular, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both derived from the essential fatty acid alpha-linolenic acid, are part of all cell membranes and from them derive numerous compounds such as prostaglandins, thromboxanes, leukotrienes, resolvins, protectins and maresins that play numerous biological roles, most notably in the control of body homeostasis, blood coagulation and inflammation. The omega-3 index is a biomarker that reflects the nutritional status of n-3 PUFA, as well as cardiometabolic risk and cardiovascular health. This index is determined as the sum of the percentages in weight of EPA and DHA over the total of fatty acids present in the erythrocyte membranes. Previous studies carried out in Spain, such as ANIBES, indicate that in adults, and especially in those over 60 years of age, the intake of n-3 PUFA is well below the international recommendations, which is directly related to a low intake of fish, since both EPA and DHA are abundant in oily fish. However, in Spain, the nutritional status of omega-3 PUFA and their possible association with a higher prevalence of cardiometabolic risk is unknown, as well as the relationships with food intake and the cultural and socioeconomic status of the population. Therefore, the main objective of the present study is to evaluate the omega-3 index in the Spanish population over 60 years of age and to establish whether there are differences by sex, as well as in the different Spanish communities. In addition, we will study the possible associations between the omega-3 index and food intake, particularly of fish and omega-3 PUFA-rich supplements, as well as their possible associations with cardiometabolic risk indicators and cultural and socioeconomic conditions of the population. Determination of the omega-3 index usually requires an invasive venous blood collection followed by processing for separation of erythrocytes and extraction and methylation of their membrane lipids followed by chromatographic analysis. But fatty acids can also be determined on whole blood using less invasive methods, such as obtaining drops of blood with a lancet and depositing them on chromatographic paper impregnated with an antioxidant (dried spots). All this makes sampling much easier, although the result of the omega-3 index has to be corrected because it is affected by the lipid composition present in the plasma. For this reason, this project aims to carry out a validation study between the results of the fatty acid profile obtained in erythrocytes and in whole blood in the Spanish population (medamediantedried spots). In short, the results obtained will be used to calculate regression lines that allow us to evaluate the omega-3 index in erythrocytes in the adult Spanish population from different regions of Spain by means of a minimally invasive methodology. For this purpose, 800 participants aged 60 years or more will be recruited from different regions of Spain, randomized by age and sex for each region; at least 100 of the total number of participants should be frequent consumers of omega-3 supplements; if this figure is not obtained, an active search will be carried out until this number is reached (booster). All of them will be interviewed to complete different questionnaires on cultural and socioeconomic status, history of metabolic disease and cardiovascular health, and questionnaires on frequency of consumption and food intake reminders as established by the European Union. With the help of health personnel from different pharmacies and in mutual agreement with the General Council of Pharmaceutical Associations of Spain, a whole blood sample will be taken by lancet, which will be used to quantify the omega-3 index. For the validation study it will be necessary to obtain whole venous blood extracted by venipuncture from a subsample of 200 participants. This sample will be processed and will be used to determine the fatty acid profile in whole blood and in erythrocytes, which will be related by means of multiple linear and bivariate regression models with the fatty acid profile obtained in the dried spots. Cardiometabolic risk markers will also be determined in these 200 subjects, which will be used to establish relationships with the calculated omega-3 status.