Spices in the postprandial metabolic regulation of healthy humans : An integrated physiological and omics approach

Sammanfattning: Metabolic syndrome (MetS) is a consequence of obesity and defined as cluster of at least three out of five criteria covering insulin resistance/glucose intolerance, abdominal obesity, hypertension, low HDL-c and elevated TG levels. Imbalance between energy intake and expenditure is known to alter normal physiological function in many aspects, and leads to obesity, which in the long run may turn into type 2 diabetes (T2D) and ultimately cardiovascular disease (CVD). Looking at our everyday meal patterns (breakfast, lunch, dinner and snacks in between), we are constantly being challenged by foods that vary in macronutrient composition. In association with meal patterns, it is well established that the postprandial (occurring a meal) response is importantly associated with cardiovascular risk factors. Exaggerated response in the postprandial glucose and TG levels are known to provoke an atherogenic milieu. Diet and lifestyle interventions are key to alleviating obesity prior to the onset of CVD. Several strategies have been suggested to be beneficial, including the consumption of fibre-rich and whole grains foods, increasing fruit and vegetable intake, lowering fat and processed meat intake, reducing high sugar foods and salt as well as avoiding saturated and trans-fatty acids consumption, features that are also part of current Nordic Nutrition Recommendations. Plants, including spices are rich in various bioactive compounds owing pleiotropic health-associated benefits. Many studies have shown that diverse bioactives might beneficially influence several aspects of human metabolism by improving appetite regulation mediated by gut hormones or through their interaction with transient receptor potential (TRP) channels, inhibiting alpha-amylase and alpha-glucosidase leading to reduced glucose absorption, affecting lipid metabolism by influencing lipid-associated enzymes as well as modulating the transcription factors of genes associated with metabolic processes. Although in a small amount, spices are one the most commonly consumed plant products, often in the form of sauces. Despite extensive investigation on certain spices such as turmeric and cinnamon, evidences for their beneficial effects in humans are limited, particularly in the postprandial setting and therefore need to be explored. In a meal study performed within this dissertation, spices such as turmeric and cinnamon formulated as beverages, significantly improved early postprandial glycemia when consumed prior to white wheat bread (WWB) as a meal challenge. Not only that, improved appetite modulation was also achieved by turmeric- and star anise-based beverages, with the gut hormone peptide tyrosine-tyrosine (PYY) being increased after turmeric-based beverage. Another study included in this dissertation also showed that a black pepper-based beverage improved overall appetite regulation, but the mechanism behind this response might not be related to gut hormones release. Given prominence to the favourable effect of turmeric on glucose and appetite regulation from the earlier study, another study included in this dissertation showed that turmeric-based beverages significantly improved lipid and and oxidative stress markers when consumed prior to medium (MF) or high fat (HF) meals. Furthermore, another study using spice blend included in a high fat meal (HF-Spices) was compared to high fat meal (HF) alone as control. Relative to HF, HF-Spices showed a profound effect in reducing postprandial insulin and increasing insulin sensitivity as well as increasing high density lipoprotein cholesterol (HDL-c). In addition, appetite sensations were also modulated after HF-Spices relative to HF. To a certain extent, cardiometabolic risk markers and appetite sensations were differently affected by gender and metabolic status (i.e. body mass index), which clearly marks the importance of inter-individual variability and supports the concept of personalized nutrition in nutritional research and interventions.Bile acids are known to facilitate lipid digestion and absorption, and are important players in lipid and glucose metabolisms. Turmeric-based beverage consumed prior to MF or HF was shown to modulate the circulating bile acid profiles in postprandial setting, turning it into a possible healthier one.A transcriptomic array covering more than 47000 genes involved in human metabolism revealed possible underlying mechanisms involved in the different responses observed after the intervention. In a study covered within this dissertation, mixed spices included in a high fat meal profoundly dampened inflammatory response indicated by a lower inflammation-associated gene expression of peripheral blood mononuclear cells (PBMCs), such as interleukin (IL)-8, tumour necrosis factor alpha (TNF-alpha) and prostaglandin-endoperoxide synthase (PTGS)2. The enriched differentially expressed genes were related with pathways and processes involved in inflammation, apoptosis, lipid metabolism and cell adhesion associated with early atherosclerosis process. Furthermore, HF-Spices also appeared to promote cholesterol efflux, possibly mediated by the increase of ATP-binding cassette transporter (ABCA)1 expression in PBMCs accompanied by increased HDL-c levels relative to HF.In conclusion, this dissertation brings novel findings and sheds light on the beneficial effect of spices on the human metabolism. This offers new evidence for advocating the inclusion of bioactive-rich spices in meals in order to mitigate the alteration of cardiometabolic risk-associated markers induced by the diet.