Foods 2020 , 9 , 1147
14of 19
The rice NPN was manufactured and assayed in vitro using di ff erentiated THP1 macrophages stimulated with LPS. We showed that rice NPN could inhibit TNF- α secretion in a dose-dependent manner, with no e ff ect on cell viability, indicating the e ff ect was not due to cell viability issues. We further characterized the NPN to identify the bioactive component peptides contained therein. Their presence was confirmed using MS and activity was confirmed using LPS stimulated THP1 cells. Rice NPN was then administered to aged volunteers (NCT04450979). Plasma cytokines, glucose tolerance and changes in LDL / HDL concentrations were determined as well as changes in physical performance tests. Administration of rice NPN to an inflammaging population lead to significantly decreased plasma concentrations of TNF- α as well as significant benefits on glucose tolerance and changes in LDL and HDL cholesterol concentrations. These benefits correlated with increased performance in a standard physical battery test and gains in lower limb strength, as measured by a significant improvement in a chair stand test. Inflammaging is a process whereby our immune system changes with age, rather than a disease. However, as we age, many diseases can develop, and this is thought to be due to this changing immune system and the associated state of low-grade chronic inflammation. With this in mind, we conducted a pilot human study in an “inflammaging” population, i.e., elderly but otherwise healthy. The primary endpoint of this study was to assess digestive discomfort, measured using a subjective self-reporting mechanism. As such, this part of the trial did not meet significance. While it is disappointing that the primary endpoint was not achieved, it is unsurprising given the subjective nature of the readout. However, analysis of objectively measured secondary readouts showed clear benefits on the ability to carry out physical challenges that correlated with a decrease in serum circulating TNF- α , aswell as other health benefits such as improved glucose control, a decrease in serum LDL concentration and an increase in HDL concentration. We observed a significant association between the change in TNF- α and the absolute start values of TNF- α at visit 2 ( p < 0.001), the higher the start value the larger the decrease in TNF- α . This possibly indicated that rice NPN was e ff ective when cytokine concentrations were elevated and not as e ff ective when circulating TNF- α concentrations were low. For example, 44% of subjects that initially displayed serum concentrations higher than 10 pg / mL showed concentrations lower than 10 pg / mL after four weeks of supplementation. This was compared to no e ff ect observed in the placebo. The significant di ff erence between treatment and control observed at week four decreased in intensity at week 8. This suggested that the rice NPN dose used was high and could be significantly lowered to decrease circulating TNF- α in a more transient way over a longer period of time under the current regimen or that the current dose could be maintained but administered less frequently, these observations will be factored in for any future trial design, such as reduced dosage (5 g / day) and intermittent dosing. Mobility has been shown to be a key determinant of health and quality of life among the elderly [50–53] and inflammaging has been shown to significantly accelerate morbidity and mortality [54]. Lack of physical activity has been shown to decrease cognitive function, reduce independence, and increase the risk of fractures, falls, and death [55–61]. The consumption of rice NPN for 12 weeks without additional exercise or other specific dietary alterations resulted in the improvement of lower body muscle strength and significant improvement in mobility performance as measured by the clinically relevant chair stand and SPPB. SPPB has been used as a predictive tool for disability, nursing home admission, and a gradient of risk for mortality [41]. The changes observed were not due to any increased protein intake from the rice NPN as the muscle mass was not significantly di ff erent between placebo and rice NPN group. Subjects also carried out their normal day to day activities without additional exercise, indicating the e ff ect is due to supplementation with NPN alone. There was no clear e ff ect on the hand grip test taken to measure upper body strength, but this test has been shown to be a less sensitive measurement for testing intervention compared to the lower limb tests [34]. To the best of our knowledge, this represents the first time that a functional protein ingredient demonstrated inhibitory e ff ects against TNF- α in a placebo-controlled setting. We note that the maximal di ff erence over placebo for rice NPN was seen at week 4, where the greatest e ff ect is attained.
Powered by FlippingBook