4. Discussion
DISEASE, OXIDATIVE STRESS
The human body is exposed to a lifetime variety of xenobiotics that need to be properly recognized, metabolized, and excreted to preserve and maintain health. Ubiquitous sources of xenobiotics include natural foods and drink products that are routinely digested and detoxified, as well as byproducts of their cellular metabolism that can build up over time and become harmful [The bulk of tissue detoxification reactions occur in the liver and the gastrointestinal tract, with the kidneys, lungs, lymphatics, and skin tissues contributing to the different aspects of this process. Central to this process is adequate nutritional support for the activity of phase I (activation) [This randomized controlled study showed that a whole food, multi-ingredient nutritional intervention was well tolerated for 4 weeks with good palatability. The intervention showed no effect on general physiological outcomes, such as weight, BMI, blood pressure, and heart rate, in healthy volunteers, and did not affect the baseline values of the metabolic, lipid, and inflammatory panels. The main advantage of the tested intervention was the series of whole food ingredients used in its formulation. A mixture of pea protein, pumpkin seed protein, and oat flour was designed to deliver good levels of amino acids relevant to the detoxification reactions, including arginine (1300 mg), glycine (600 mg), isoleucine (850 mg), leucine (1600 mg), methionine (300 mg), and valine (900 mg) per serving. The total sugars (1 g) and total fats (5 g) were kept low using a mixture of flax meal, oat flour, and buckwheat flour. A series of functional ingredients was also selected to support the activity of the detoxification enzymes, including beets reported to activate glutathione S-transferase [The study also demonstrated that measurable biological effects on the total plasma antioxidant activity and oxidative stress in PBMCs can be achieved in healthy participants at intervention doses that are well tolerated. These findings correlated with increases in SOD and GST activities in the absence of the overall levels of reduced glutathione (GSH) or the GSH:GSSG ratio in the participating healthy volunteers. While multiple studies demonstrate the challenge associated with the maintenance of an endogenous glutathione pool, owing to a multitude of factors, including age and physiological and pathological conditions [The current study also demonstrated high variability in hepatic detoxification (phase I D-glucaric acid, phase II mercapturic acids) and urine porphyrin profiles. The explanation for this intersubject variability is not obvious, however; individual responses to plant foods often depend on individual genetic polymorphisms and gender, as shown previously for GST enzymes [While this study offers novel insights into a whole food, nutritional intervention and its potential application to detoxification and antioxidant support, it does have notable limitations. We enrolled healthy volunteers, and it remains to be determined whether these findings apply generally to diverse patient populations with pre-existing disease states and metabolic pathologies. The majority of subjects were females, and this may limit our understanding of the effects of this supplementation in a male population. Furthermore, small but significant changes in BMI observed in the control population may be attributed to the placebo-like effects of the educational session and may be further explored in the future. This will be critical in determining the beneficial potential of the whole food, multi-ingredient supplementation in subsequent clinical studies in specific patient populations. In summary, this study both reports the successful development of a whole food, multi-ingredient nutritional intervention and demonstrates that its oral administration for 4 weeks improves the total plasma antioxidant activity and oxidative stress in PBMCs, in part, by increasing phase II detoxification and antioxidant enzyme activity, such as SOD and GSTs, in healthy participants. These effects were observed in the absence of apparent clinical side effects and changes in the laboratory biomarkers. Our work highlights the feasibility of translating the whole food, multi-ingredient supplementation and positions it as a novel formulation capable of supporting the body’s endogenous detoxification pathways. These results also present a strong case for incorporating functional biomarkers and guided education into personalized metabolic detoxification programs. 