Research lab
Current projects 

Areas of Focus Include:

1. Understanding the relationship between the cardiovascular system and the immune system

2. Nutritional interventions to mitigate immune dysfunction related to obesity, insulin resistance and type 2 diabetes

3. Phosphatidylcholine and dairy fat counteracting the immune dysfunction associated with obesity

4. Diet quality in chronic kidney diseases as it relates to potassium and phosphorous metabolism

Research Highlights:

1. We were the first to demonstrate that individuals with obesity and type 2 diabetes (T2D) have an impaired T cell response after challenge compared with metabolically healthy individuals with obesity.

2. We demonstrated that not only the amount but the forms of choline in the maternal diet during lactation influences the immune system of the dams and suckled offspring.

3. We published a systematic review and book chapter on the effect of egg consumption on cardiovascular disease (CVD) risk factors in individuals with or at risk of T2D.

4. We demonstrated that a dietary supply of docosahexaenoic acid (DHA) early in life is essential for the immune system development and the establishment of oral tolerance.

5. We were the first to document the mechanisms underlying the low-density lipoprotein-cholesterol (LDL-C) lowering properties of the MedDiet in high-risk men with metabolic syndrome.

6. We recently demonstrated that consuming a higher proportion of lipid soluble forms of choline (i.e. PC) can counteract some of the obesity-related immune dysfunction in a pre-clinical model of obesity.

7. Low-fat dairy appears to improve the obesity-related immune dysfunction to a greater extent than regular fat dairy.

Research Summary:

The immune system regulates inflammation, and plays a role in the pathogenesis of chronic diseases. Obesity and hyperglycemia increase inflammation and the risk of infection. However, little is known about the immune dysfunction related to obesity. Dr. Richard’s research program will support the establishment of clinical evidence-based nutritional recommendations for the management of obesity-related immune dysfunction. Her research aims first at understanding the independent contributions of diet and hyperglycemia in modulating immune function in obesity and secondly at developing dietary approaches (dietary pattern, food or supplement) that precisely mitigate obesity-related immune dysfunction. Identifying specific immune functions (markers to target), independent of diet, that are impaired in different health conditions (e.g., obesity, prediabetes or T2D) is crucial to determine targeted and personalized approaches to precisely improve immune function in each health condition. The second part of her program will provide evidence to support food-based recommendations (ex. Phosphatidylcholine) that are directed at precisely improving obesity-related immune dysfunction. This is important since weight loss, although known to improve inflammation and the immune system, has resulted in little long-term success. Therefore, there is an urgent need to identify other effective strategies for the management of obesity co-morbidities.

KETO-IM STUDY

Low-carbohydrate diets, including ketogenic diet (KETO) are gaining interest as a treatment for type 2 diabetes because they are believed to help manage blood sugar and weight. However, KETO is often high in saturated fats. Compared with a traditional KETO, we want to test the feasibility of substituting healthier fats such as canola oil to improve cardiovascular risk factors.

Canola oil is low in saturated fat. Therefore, utilizing canola oil in a KETO diet may improve its health benefits in people with high risk of / living with type 2 diabetes. The purpose of our study is to investigate the health beneficial effects of a healthy KETO diet supplemented with Canola oil, compared to a traditional Keto Diet and low-fat diet in adults at high risk of type 2 diabetes. 

Objectives: 

1. To assess the effects on CVD risk factors. Comparisons among groups at 3 and 6 months of intervention on the main risk factors for CVD including plasma cholesterol, TG, ApoB100, glucose, insulin and HbA1C will be conducted.

2. To assess the effects on systemic inflammation and immune function.

3. To document the safety of and adherence to interventions.

Participants will be randomized to one of these three diets and will receive nutrition counselling during 6 months:

1. KETO supplemented with Canola oil (KETO-Can; high in Monounsaturated fatty acids and omega-3).

2. KETO supplemented with butter, coconut and palm oil (KETO-Sat; high in saturated fatty acids).

3. LFD supplemented with whole grains and other low-fat foods (Low-fat diet).

Utilization of 3 groups in the Randomized Controlled Trial will allow us to establish whether either KETO-Can or KETO-Sat elicit better glycemic, lipid and inflammatory outcomes compared with standard recommendations (i.e. diets lower in fat) and will allow a direct comparison between fat sources in the 2 KETO diets. Moreover, by monitoring ketosis and collecting multiple dietary records, we will be able to understand participant compliance with the diets and detailed nutrition intake.

Clinical trials registration: NCT05681468

To learn more about this study or find out if you are eligible: https://sites.google.com/ualberta.ca/ketoim-study

UNDERSTANDING THE HEALTH EFFECT OF A BIOACTIVE PEPTIDE FROM EGG: A PILOT STUDY

Bioactive peptides derived from food proteins show vast potential for improving human health, in addition to providing nutritional value. One of such promising peptides is a short tripeptide IRW (made of three amino acids, isoleucine-arginine-tryptophan), the first discovered peptide that can activate ACE2 (angiotensin converting enzyme 2) in preclinical models. ACE2 is best known as the entry receptor of some coronaviruses, including the pandemic’s SARS-CoV-2, while the primary role of ACE2 is to provide protection on the cardiometabolic system. Therefore, activation of ACE2 is a novel strategy to mitigate cardiometabolic diseases. Our decade-long collaborative research on IRW has established a large body of knowledge about IRW’s health effects on hypertension, type-2 diabetes (T2D)/insulin resistance (IR), oxidation, and inflammation. To translate the knowledge for human applications, it is essential to investigate the bioavailability and efficacy of bioactive peptide IRW in egg white hydrolysate in humans.

IRW is derived from ovotransferrin, which accounts for ~12% of total egg white protein. IRW can only be released by a combination of thermolysin and pepsin (2 enzymes). If only thermolysin is applied, a pentapeptide IRWCT is formed; however, as pepsin is naturally secreted in the stomach, we will prepare egg white hydrolysate using only one enzyme, thermolysin. We expect that IRW will be released in vivo by the gastrically secreted pepsin. 

This is the first study to attempt to translate the health beneficial effect observed in pre-clinical models into human applications. Development of a functional food containing IRW could provide a dietary-strategy for the mitigation of IR/T2D and hypertension if our hypothesis is confirmed.

BUTTERMILK STUDY

Obesity is associated with an increased risk of infection due to an impaired immune system. Dairy is highly unique due to its nutrient density and provides many essential macro- and micronutrients, including choline. Although dairy products are high in choline in general, buttermilk, the co-product of butter making, is one of the richest sources of milk fat globule membrane (MFGM)-derived polar lipids comprised of lipid soluble forms of choline i.e. phosphatidylcholine and sphingomyelin. In contrast, evidence now suggests that dairy products are either neutral or beneficial for many risk factors including inflammation. Moreover, our group has recently demonstrated that the forms of choline derived from buttermilk have a beneficial effect on the immune system during both the lactation and early developmental periods (see past studies below). Despite this, no studies have specifically examined how buttermilk-derived polar lipids can improve obesity-related immune dysfunction. 

The main objective of this research project is to test the hypothesis that lipid-soluble forms of choline from buttermilk can precisely counteract the immune dysfunction observed in obesity. This project will focus on the importance of consuming buttermilk as a whole and its derived polar lipids on inflammation and the immune system. Outcomes from this study will provide essential mechanistic evidence of buttermilk and dairy fat's nutritional and health benefits to improve the immune system. Finally, this research project has the potential to support dietary guidelines to recommend regular dairy consumption to meet the daily requirement of choline intake to prevent obesity-related immune dysfunction.

INVESTIGATING THE EFFECT OF PHOSPHATIDYLCHOLINE AT COUNTERACTING OBESITY INDUCED IMMUNE DYSFUNCTION

Phosphatidylcholine (PC) is a lipid-soluble form of choline that is present in both animal (egg yolks, dairy, beef) and plant (soy) sources. PC is an integral phospholipid in cell membranes, and also plays a role in maintaining the mucosal layer of the gastrointestinal tract. Thus, dietary PC may support immune function by supporting immune cell membrane composition and the intestinal barrier. 

Using an animal model, we explored the following 3 objectives:

1. To investigate the effect of feeding a diet containing 100% egg-PC on the development of obesity-related T cell dysfunction.

2. To determine the dose response of feeding egg-PC on T cell function in obesity.

3. To compare the efficacy of feeding soy-PC vs. egg-PC on T cell function in obesity.

This study has implications for the general public by providing evidence of the health benefits of PC containing foods such as eggs and soy. Further, this study has implications for research as most rodent research diets provide choline solely in the form of water-soluble free choline and thus may not confer optimal effects on immune function. 

THE ROLE OF DIETARY CHOLINE ON THE IMMUNE SYSTEM THROUGH DIFFERENT LIFE STAGES

Choline is an essential nutrient that can be found in the diet as water- (i.e., free choline (FC)) and lipid-soluble (i.e., phosphatidylcholine (PC) and sphingomyelin (SM)) forms. Previous studies have demonstrated that choline is needed for optimal maternal immune function and the immune system development in offspring with the most benefits being observed when choline was provided as PC in rodents. Yet, this is not representative of the choline forms distribution in a human diet. Despite evidence suggesting a greater impact of PC on immune responses when compared to FC, little is known about the role of SM, another important dietary form of choline, on the immune system. In rodents, feeding dietary PC has been shown to enhance T cell function by increasing the production of Th1 cytokines (i.e. IFN-γ and TNF-α) and IL-2 (a proliferation marker) upon stimulation.

 A series of experiments were conducted to determine the impact of feeding diets high in SM and/or PC using buttermilk on immune responses of lactating dams and local and peripheral immune systems development in their offspring. We observed that the forms of choline in the maternal diet were able to modulate the proportion of choline forms in breastmilk during the lactation period. Feeding lactating dams a diet high in SM and PC (34-36% each) improved T cell response by increasing the ex vivo production of IL-2, TNF-α, and IFN-γ by splenocytes. In addition, when dams were fed diets containing a high proportion of lipid-soluble forms (at least 50%) T cell responses were enhanced in both suckled and weaned pups where a higher production of IL-2 TNF-α, and IFN-γ by splenocytes was observed. Similarly, in mesenteric lymph nodes (MLN) of weaned pups, the lipid-soluble forms of choline positively modulated T cell responses in the gut by increasing IL-2, TNF-α, and IFN-γ production. Moreover, upon dietary antigen stimulation, there was a lower production of IL-2, TNF-α, and IL-6 and a higher production of IL-10 by immune cells from both the spleen and MLN in weaned pups, suggesting that the lipid-soluble forms of choline could potentially favor the development of oral tolerance (i.e. lower the risk of allergies).